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Sample records for normal adult tissue

  1. Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues.

    Directory of Open Access Journals (Sweden)

    Xiaoli Zhang

    Full Text Available The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1 and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes.

  2. Normal CT characteristics of the thymus in adults

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    Simanovsky, Natalia, E-mail: natalias@hadassah.org.il [Department of Medical Imaging, Hadassah - Hebrew University Medical Center, Jerusalem (Israel); Hiller, Nurith; Loubashevsky, Natali; Rozovsky, Katya [Department of Medical Imaging, Hadassah - Hebrew University Medical Center, Jerusalem (Israel)

    2012-11-15

    Background: The thymus changes with age. Its shape and the proportion of solid tissue and fat vary between individuals, yet there is no comprehensive work describing the size and morphology of the normal thymus on CT. As a result, many adults with some preserved soft tissue in the thymus may undergo extensive work-up to exclude mediastinal tumor. Our aim was to quantify CT characteristics of the normal thymus in an adult population. Methods: CT chest scans of 194 trauma patients aged 14-78 years (mean 52.6 years), were retrospectively reviewed. The density, volume, shape and predominant side of the thymus were recorded for 56 patients in whom some solid tissue was preserved. Statistical analysis of these characteristics according to the patient age and gender was performed. Results: Thymic density and volume decreased progressively with age. No solid tissue component was seen in the thymus in patients older than 54 years. In the majority of patients, the thymus had an arrowhead shape, with middle position. However, great variability in thymic shape and border were noted. There was a highly significant relationship between density and patient age (p < 0.0001). Conclusion: We hope that our work will help in the definition of normal thymic CT parameters in adults, help to prevent unnecessary and expensive imaging procedures, and reduce patient exposure to ionizing radiation.

  3. Normal CT characteristics of the thymus in adults

    International Nuclear Information System (INIS)

    Simanovsky, Natalia; Hiller, Nurith; Loubashevsky, Natali; Rozovsky, Katya

    2012-01-01

    Background: The thymus changes with age. Its shape and the proportion of solid tissue and fat vary between individuals, yet there is no comprehensive work describing the size and morphology of the normal thymus on CT. As a result, many adults with some preserved soft tissue in the thymus may undergo extensive work-up to exclude mediastinal tumor. Our aim was to quantify CT characteristics of the normal thymus in an adult population. Methods: CT chest scans of 194 trauma patients aged 14–78 years (mean 52.6 years), were retrospectively reviewed. The density, volume, shape and predominant side of the thymus were recorded for 56 patients in whom some solid tissue was preserved. Statistical analysis of these characteristics according to the patient age and gender was performed. Results: Thymic density and volume decreased progressively with age. No solid tissue component was seen in the thymus in patients older than 54 years. In the majority of patients, the thymus had an arrowhead shape, with middle position. However, great variability in thymic shape and border were noted. There was a highly significant relationship between density and patient age (p < 0.0001). Conclusion: We hope that our work will help in the definition of normal thymic CT parameters in adults, help to prevent unnecessary and expensive imaging procedures, and reduce patient exposure to ionizing radiation.

  4. Abdominal Adipose Tissue was Associated with Glomerular Hyperfiltration among Non- Diabetic and Normotensive Adults with a Normal Body Mass Index.

    Directory of Open Access Journals (Sweden)

    Jeonghwan Lee

    Full Text Available Glomerular hyperfiltration is recognized as an early marker of progressive kidney dysfunction in the obese population. This study aimed to identify the relationship between glomerular hyperfiltration and body fat distribution measured by computed tomography (CT in healthy Korean adults. The study population included individuals aged 20-64 years who went a routine health check-up including an abdominal CT scan. We selected 4,378 individuals without diabetes and hypertension. Glomerular filtration rate was estimated using the CKD-EPI equation, and glomerular hyperfiltration was defined as the highest quintile of glomerular filtration rate. Abdominal adipose tissue areas were measured at the level of the umbilicus using a 16-detector CT scanner, and the cross-sectional area was calculated using Rapidia 2.8 CT software. The prevalence of glomerular hyperfiltration increased significantly according to the subcutaneous adipose tissue area in men (OR = 1.74 (1.16-2.61, P for trend 0.016, for the comparisons of lowest vs. highest quartile and visceral adipose tissue area in women (OR = 2.34 (1.46-3.75, P for trend < 0.001 in multivariate analysis. After stratification by body mass index (normal < 23 kg/m2, overweight ≥ 23 kg/m2, male subjects with greater subcutaneous adipose tissue, even those in the normal BMI group, had a higher prevalence of glomerular hyperfiltration (OR = 2.11 (1.17-3.80, P for trend = 0.009. Among women, the significance of visceral adipose tissue area on glomerular hyperfiltration resulted from the normal BMI group (OR = 2.14 (1.31-3.49, P for trend = 0.002. After menopause, the odds ratio of the association of glomerular hyperfiltration with subcutaneous abdominal adipose tissue increased (OR = 2.96 (1.21-7.25, P for trend = 0.013. Subcutaneous adipose tissue areas and visceral adipose tissue areas are positively associated with glomerular hyperfiltration in healthy Korean adult men and women, respectively. In post

  5. The expression of Egfl7 in human normal tissues and epithelial tumors.

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    Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

    2013-04-23

    To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

  6. Neutron RBE for normal tissues

    International Nuclear Information System (INIS)

    Field, S.B.; Hornsey, S.

    1979-01-01

    RBE for various normal tissues is considered as a function of neutron dose per fraction. Results from a variety of centres are reviewed. It is shown that RBE is dependent on neutron energy and is tissue dependent, but is not specially high for the more critical tissues or for damage occurring late after irradiation. (author)

  7. Oxygen delivery in irradiated normal tissue

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    Kiani, M.F.; Ansari, R. [Univ. of Tennessee Health Science Center, Memphis, TN (United States). School of Biomedical Engineering; Gaber, M.W. [St. Jude Children' s Research Hospital, Memphis, TN (United States)

    2003-03-01

    Ionizing radiation exposure significantly alters the structure and function of microvascular networks, which regulate delivery of oxygen to tissue. In this study we use a hamster cremaster muscle model to study changes in microvascular network parameters and use a mathematical model to study the effects of these observed structural and microhemodynamic changes in microvascular networks on oxygen delivery to the tissue. Our experimental observations indicate that in microvascular networks while some parameters are significantly affected by irradiation (e.g. red blood cell (RBC) transit time), others remain at the control level (e.g. RBC path length) up to 180 days post-irradiation. The results from our mathematical model indicate that tissue oxygenation patterns are significantly different in irradiated normal tissue as compared to age-matched controls and the differences are apparent as early as 3 days post irradiation. However, oxygen delivery to irradiated tissue was not found to be significantly different from age matched controls at any time between 7 days to 6 months post-irradiation. These findings indicate that microvascular late effects in irradiated normal tissue may be due to factors other than compromised tissue oxygenation. (author)

  8. Radiogenomics: predicting clinical normal tissue radiosensitivity

    DEFF Research Database (Denmark)

    Alsner, Jan

    2006-01-01

    Studies on the genetic basis of normal tissue radiosensitivity, or  'radiogenomics', aims at predicting clinical radiosensitivity and optimize treatment from individual genetic profiles. Several studies have now reported links between variations in certain genes related to the biological response...... to radiation injury and risk of normal tissue morbidity in cancer patients treated with radiotherapy. However, after these initial association studies including few genes, we are still far from being able to predict clinical radiosensitivity on an individual level. Recent data from our own studies on risk...

  9. MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

    International Nuclear Information System (INIS)

    Constine, L; Hodgson, D; Bentzen, S

    2014-01-01

    With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-response data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for

  10. MO-D-BRF-01: Pediatric Treatment Planning II: The PENTEC Report On Normal Tissue Complications

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    Constine, L; Hodgson, D; Bentzen, S [University of Maryland, Baltimore, MD (United States)

    2014-06-15

    With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy may cause debilitating or even fatal ‘late effects’ that are critical to understand, mitigate, or prevent. QUANTEC identified the uncertainties relating to side-effects of adult treatments, but this is more complicated for children in whom a mosaic of tissues develops at different rates and temporal sequences. Childhood cancer survivors have long life expectancy and may develop treatmentinduced secondary cancers and severe organ/tissue injury decades after treatment. Collaborative long-term observational studies and clinical research programs for survivors of pediatric and adolescent cancer provide some dose-response data for follow-up periods exceeding 40 years. Data analysis is challenging due to the influence of both therapeutic and developmental variables. PENTEC is a group of radiation oncologists, pediatric oncologists, subsepcialty physicians, medical physicists, biomathematic modelers/statisticians, and epidemiologists charged with conducting a critical synthesis of existing literature aiming to: critically analyze radiation dose-volume effects on normal tissue tolerances as a function of age/development in pediatric cancer patients in order to inform treatment planning and improve outcomes for survivors; describe relevant physics issues specific to pediatric radiotherapy; propose dose-volumeoutcome reporting standards to improve the knowledge base to inform future treatment guidelines. PENTEC has developed guidelines for systematic literature reviews, data extraction tolls and data analysis. This education session will discuss:1. Special considerations for normal tissue radiation response of children/adolescents, e.g. the interplay between development and radiotherapy effects.2. Epidemiology of organ/tissue injuries and secondary cancers.3. Exploration of dose-response differences between children and adults4. Methodology for

  11. A compendium of canine normal tissue gene expression.

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    Joseph Briggs

    Full Text Available BACKGROUND: Our understanding of disease is increasingly informed by changes in gene expression between normal and abnormal tissues. The release of the canine genome sequence in 2005 provided an opportunity to better understand human health and disease using the dog as clinically relevant model. Accordingly, we now present the first genome-wide, canine normal tissue gene expression compendium with corresponding human cross-species analysis. METHODOLOGY/PRINCIPAL FINDINGS: The Affymetrix platform was utilized to catalogue gene expression signatures of 10 normal canine tissues including: liver, kidney, heart, lung, cerebrum, lymph node, spleen, jejunum, pancreas and skeletal muscle. The quality of the database was assessed in several ways. Organ defining gene sets were identified for each tissue and functional enrichment analysis revealed themes consistent with known physio-anatomic functions for each organ. In addition, a comparison of orthologous gene expression between matched canine and human normal tissues uncovered remarkable similarity. To demonstrate the utility of this dataset, novel canine gene annotations were established based on comparative analysis of dog and human tissue selective gene expression and manual curation of canine probeset mapping. Public access, using infrastructure identical to that currently in use for human normal tissues, has been established and allows for additional comparisons across species. CONCLUSIONS/SIGNIFICANCE: These data advance our understanding of the canine genome through a comprehensive analysis of gene expression in a diverse set of tissues, contributing to improved functional annotation that has been lacking. Importantly, it will be used to inform future studies of disease in the dog as a model for human translational research and provides a novel resource to the community at large.

  12. DNA-repair, cell killing and normal tissue damage

    International Nuclear Information System (INIS)

    Dahm-Daphi, J.; Dikomey, E.; Brammer, I.

    1998-01-01

    Background: Side effects of radiotherapy in normal tissue is determined by a variety of factors of which cellular and genetic contributions are described here. Material and methods: Review. Results: Normal tissue damage after irradiation is largely due to loss of cellular proliferative capacity. This can be due to mitotic cell death, apoptosis, or terminal differentiation. Dead or differentiated cells release cytokines which additionally modulate the tissue response. DNA damage, in particular non-reparable or misrepaired double-strand breaks are considered the basic lesion leading to G1-arrest and ultimately to cell inactivation. Conclusion: Evidence for genetic bases of normal tissue response, cell killing and DNA-repair capacity is presented. However, a direct link of all 3 endpoints has not yet been proved directly. (orig.) [de

  13. Normal tissue dose-effect models in biological dose optimisation

    International Nuclear Information System (INIS)

    Alber, M.

    2008-01-01

    Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

  14. Radiation-induced normal tissue damage: implications for radiotherapy

    International Nuclear Information System (INIS)

    Prasanna, Pataje G.

    2014-01-01

    Radiotherapy is an important treatment modality for many malignancies, either alone or as a part of combined modality treatment. However, despite technological advances in physical treatment delivery, patients suffer adverse effects from radiation therapy due to normal tissue damage. These side effects may be acute, occurring during or within weeks after therapy, or intermediate to late, occurring months to years after therapy. Minimizing normal tissue damage from radiotherapy will allow enhancement of tumor killing and improve tumor control and patients quality of life. Understanding mechanisms through which radiation toxicity develops in normal tissue will facilitate the development of next generation radiation effect modulators. Translation of these agents to the clinic will also require an understanding of the impact of these protectors and mitigators on tumor radiation response. In addition, normal tissues vary in radiobiologically important ways, including organ sensitivity to radiation, cellular turnover rate, and differences in mechanisms of injury manifestation and damage response. Therefore, successful development of radiation modulators may require multiple approaches to address organ/site-specific needs. These may include treatments that modify cellular damage and death processes, inflammation, alteration of normal flora, wound healing, tissue regeneration and others, specifically to counter cancer site-specific adverse effects. Further, an understanding of mechanisms of normal tissue damage will allow development of predictive biomarkers; however harmonization of such assays is critical. This is a necessary step towards patient-specific treatment customization. Examples of important adverse effects of radiotherapy either alone or in conjunction with chemotherapy, and important limitations in the current approaches of using radioprotectors for improving therapeutic outcome will be highlighted. (author)

  15. Telomere length in normal and neoplastic canine tissues.

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    Cadile, Casey D; Kitchell, Barbara E; Newman, Rebecca G; Biller, Barbara J; Hetler, Elizabeth R

    2007-12-01

    To determine the mean telomere restriction fragment (TRF) length in normal and neoplastic canine tissues. 57 solid-tissue tumor specimens collected from client-owned dogs, 40 samples of normal tissue collected from 12 clinically normal dogs, and blood samples collected from 4 healthy blood donor dogs. Tumor specimens were collected from client-owned dogs during diagnostic or therapeutic procedures at the University of Illinois Veterinary Medical Teaching Hospital, whereas 40 normal tissue samples were collected from 12 control dogs. Telomere restriction fragment length was determined by use of an assay kit. A histologic diagnosis was provided for each tumor by personnel at the Veterinary Diagnostic Laboratory at the University of Illinois. Mean of the mean TRF length for 44 normal samples was 19.0 kilobases (kb; range, 15.4 to 21.4 kb), and the mean of the mean TRF length for 57 malignant tumors was 19.0 kb (range, 12.9 to 23.5 kb). Although the mean of the mean TRF length for tumors and normal tissues was identical, tumor samples had more variability in TRF length. Telomerase, which represents the main mechanism by which cancer cells achieve immortality, is an attractive therapeutic target. The ability to measure telomere length is crucial to monitoring the efficacy of telomerase inhibition. In contrast to many other mammalian species, the length of canine telomeres and the rate of telomeric DNA loss are similar to those reported in humans, making dogs a compelling choice for use in the study of human anti-telomerase strategies.

  16. Pathologic evaluation of normal and perfused term placental tissue

    DEFF Research Database (Denmark)

    Maroun, Lisa Leth; Mathiesen, Line; Hedegaard, Morten

    2014-01-01

    This study reports for the 1st time the incidence and interobserver variation of morphologic findings in a series of 34 term placentas from pregnancies with normal outcome used for perfusion studies. Histologic evaluation of placental tissue is challenging, especially when it comes to defining...... "normal tissue" versus "pathologic lesions." A scoring system for registration of abnormal morphologic findings was developed. Light microscopic examination was performed independently by 2 pathologists, and interobserver variation was analyzed. Findings in normal and perfused tissue were compared...... and selected findings were tested against success parameters from the perfusions. Finally, the criteria for frequent lesions with fair to poor interobserver variation in the nonperfused tissue were revised and reanalyzed. In the perfused tissue, the perfusion artefact "trophoblastic vacuolization," which...

  17. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues.

    Science.gov (United States)

    Foldager, Casper Bindzus; Toh, Wei Seong; Gomoll, Andreas H; Olsen, Bjørn Reino; Spector, Myron

    2014-04-01

    The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti-collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional roles of these 2 extracellular matrix proteins

  18. Distribution of Basement Membrane Molecules, Laminin and Collagen Type IV, in Normal and Degenerated Cartilage Tissues

    Science.gov (United States)

    Toh, Wei Seong; Gomoll, Andreas H.; Olsen, Bjørn Reino; Spector, Myron

    2014-01-01

    Objective: The objective of the present study was to investigate the presence and distribution of 2 basement membrane (BM) molecules, laminin and collagen type IV, in healthy and degenerative cartilage tissues. Design: Normal and degenerated tissues were obtained from goats and humans, including articular knee cartilage, the intervertebral disc, and meniscus. Normal tissue was also obtained from patella-tibial enthesis in goats. Immunohistochemical analysis was performed using anti-laminin and anti–collagen type IV antibodies. Human and goat skin were used as positive controls. The percentage of cells displaying the pericellular presence of the protein was graded semiquantitatively. Results: When present, laminin and collagen type IV were exclusively found in the pericellular matrix, and in a discrete layer on the articulating surface of normal articular cartilage. In normal articular (hyaline) cartilage in the human and goat, the proteins were found co-localized pericellularly. In contrast, in human osteoarthritic articular cartilage, collagen type IV but not laminin was found in the pericellular region. Nonpathological fibrocartilaginous tissues from the goat, including the menisci and the enthesis, were also positive for both laminin and collagen type IV pericellularly. In degenerated fibrocartilage, including intervertebral disc, as in degenerated hyaline cartilage only collagen type IV was found pericellularly around chondrocytes but with less intense staining than in non-degenerated tissue. In calcified cartilage, some cells were positive for laminin but not type IV collagen. Conclusions: We report differences in expression of the BM molecules, laminin and collagen type IV, in normal and degenerative cartilaginous tissues from adult humans and goats. In degenerative tissues laminin is depleted from the pericellular matrix before collagen type IV. The findings may inform future studies of the processes underlying cartilage degeneration and the functional

  19. Radiobiology in clinical radiation therapy - Part III: Normal tissue damage

    International Nuclear Information System (INIS)

    Travis, Elizabeth L.

    1996-01-01

    Objective: This is the third part of a course designed for residents in radiation oncology preparing for their boards. This part of the course will focus on the mechanisms underlying damage in normal tissues. Although conventional wisdom long held that killing and depletion of a critical cell(s) in a tissue was responsible for the later expression of damage, histopathologic changes in normal tissue can now be explained and better understood in terms of the new molecular biology. The concept that depletion of a single cell type is responsible for the observed histopathologic changes in normal tissues has been replaced by the hypothesis that damage results from the interaction of many different cell systems, including epithelial, endothelial, macrophages and fibroblasts, via the production of specific autocrine, paracrine and endocrine growth factors. A portion of this course will discuss the clinical and experimental data on the production and interaction of those cytokines and cell systems considered to be critical to tissue damage. It had long been suggested that interindividual differences in radiation-induced normal tissue damage was genetically regulated, at least in part. Both clinical and experimental data supported this hypothesis but it is the recent advances in human and mouse molecular genetics which have provided the tools to dissect out the genetic component of normal tissue damage. These data will be presented and related to the potential to develop genetic markers to identify sensitive individuals. The impact on clinical outcome of the ability to identify prospectively sensitive patients will be discussed. Clinically it is well-accepted that the volume of tissue irradiated is a critical factor in determining tissue damage. A profusion of mathematical models for estimating dose-volume relationships in a number of organs have been published recently despite the fact that little data are available to support these models. This course will review the

  20. Comparison of soft-tissue orbital morphometry in attractive and normal Italian subjects.

    Science.gov (United States)

    Sforza, Chiarella; Dolci, Claudia; Grandi, Gaia; Tartaglia, Gianluca M; Laino, Alberto; Ferrario, Virgilio F

    2015-01-01

    To identify esthetic characteristics of the orbital soft tissues of attractive Italian adult women and men. Three-dimensional computerized digitizers were used to collect the coordinates of facial landmarks in 199 healthy, normal subjects aged 18 to 30 years (71 women, 128 men; mean age, 22 years) and in 126 coetaneous attractive subjects (92 women, 34 men; mean age, 20 years) selected during beauty competitions. From the landmarks, six linear distances, two ratios, six angles, and two areas were calculated. Attractive subjects were compared with normal ones by computing z-scores. Intercanthal width was reduced while eye fissure lengths were increased in both genders. Orbital heights (os-or) were increased only in attractive women, with a significant gender-related difference. The inclinations of the eye fissure were increased in attractive subjects, while the inclinations of the orbit were reduced. For several of the analyzed measurements, similar patterns of z-scores were observed for attractive men and women (r  =  .883). Attractive women and men had several specific esthetic characteristics in their orbital soft tissues; esthetic reference values can be used to determine optimal goals in surgical treatment.

  1. Immunolocalization of transforming growth factor alpha in normal human tissues

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

  2. Measurement of human normal tissue and tumour responses

    International Nuclear Information System (INIS)

    Ross, G.; Yarnold, J.R.

    1988-01-01

    The scarcity of quantitative measures of normal tissue damage and tumour response in patients undergoing radiotherapy is an obstacle to the clinical evaluation of new treatment strategies. Retrospective studies of complications in critical normal tissues taught important lessons in the past concerning the potential dangers of hypofractionation. However, it is unethical to use serious complications as planned end-points in prospective studies. This paper reviews the desirable characteristics of clinical end-points required to compare alternative treatments employing radiotherapy, with emphasis on simple scales applied by clinicians or even the patients themselves

  3. Extravascular transport in normal and tumor tissues.

    Science.gov (United States)

    Jain, R K; Gerlowski, L E

    1986-01-01

    The transport characteristics of the normal and tumor tissue extravascular space provide the basis for the determination of the optimal dosage and schedule regimes of various pharmacological agents in detection and treatment of cancer. In order for the drug to reach the cellular space where most therapeutic action takes place, several transport steps must first occur: (1) tissue perfusion; (2) permeation across the capillary wall; (3) transport through interstitial space; and (4) transport across the cell membrane. Any of these steps including intracellular events such as metabolism can be the rate-limiting step to uptake of the drug, and these rate-limiting steps may be different in normal and tumor tissues. This review examines these transport limitations, first from an experimental point of view and then from a modeling point of view. Various types of experimental tumor models which have been used in animals to represent human tumors are discussed. Then, mathematical models of extravascular transport are discussed from the prespective of two approaches: compartmental and distributed. Compartmental models lump one or more sections of a tissue or body into a "compartment" to describe the time course of disposition of a substance. These models contain "effective" parameters which represent the entire compartment. Distributed models consider the structural and morphological aspects of the tissue to determine the transport properties of that tissue. These distributed models describe both the temporal and spatial distribution of a substance in tissues. Each of these modeling techniques is described in detail with applications for cancer detection and treatment in mind.

  4. Computer modeling the boron compound factor in normal brain tissue

    International Nuclear Information System (INIS)

    Gavin, P.R.; Huiskamp, R.; Wheeler, F.J.; Griebenow, M.L.

    1993-01-01

    The macroscopic distribution of borocaptate sodium (Na 2 B 12 H 11 SH or BSH) in normal tissues has been determined and can be accurately predicted from the blood concentration. The compound para-borono-phenylalanine (p-BPA) has also been studied in dogs and normal tissue distribution has been determined. The total physical dose required to reach a biological isoeffect appears to increase directly as the proportion of boron capture dose increases. This effect, together with knowledge of the macrodistribution, led to estimates of the influence of the microdistribution of the BSH compound. This paper reports a computer model that was used to predict the compound factor for BSH and p-BPA and, hence, the equivalent radiation in normal tissues. The compound factor would need to be calculated for other compounds with different distributions. This information is needed to design appropriate normal tissue tolerance studies for different organ systems and/or different boron compounds

  5. A Cancer-Indicative microRNA Pattern in Normal Prostate Tissue

    Directory of Open Access Journals (Sweden)

    Thorsten Schlomm

    2013-03-01

    Full Text Available We analyzed the levels of selected micro-RNAs in normal prostate tissue to assess their potential to indicate tumor foci elsewhere in the prostate. Histologically normal prostate tissue samples from 31 prostate cancer patients and two cancer negative control groups with either unsuspicious or elevated prostate specific antigen (PSA levels (14 and 17 individuals, respectively were analyzed. Based on the expression analysis of 157 microRNAs in a pool of prostate tissue samples and information from data bases/literature, we selected eight microRNAs for quantification by real-time polymerase chain reactions (RT-PCRs. Selected miRNAs were analyzed in histologically tumor-free biopsy samples from patients and healthy controls. We identified seven microRNAs (miR-124a, miR-146a & b, miR-185, miR-16 and let-7a & b, which displayed significant differential expression in normal prostate tissue from men with prostate cancer compared to both cancer negative control groups. Four microRNAs (miR-185, miR-16 and let-7a and let-7b remained to significantly discriminate normal tissues from prostate cancer patients from those of the cancer negative control group with elevated PSA levels. The transcript levels of these microRNAs were highly indicative for the presence of cancer in the prostates, independently of the PSA level. Our results suggest a microRNA-pattern in histologically normal prostate tissue, indicating prostate cancer elsewhere in the organ.

  6. Differentiating cancerous from normal breast tissue by redox imaging

    Science.gov (United States)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2015-02-01

    Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (pcancerous tissues than in the normal ones (pcancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

  7. Effect of anti-sclerostin therapy and osteogenesis imperfecta on tissue-level properties in growing and adult mice while controlling for tissue age.

    Science.gov (United States)

    Sinder, Benjamin P; Lloyd, William R; Salemi, Joseph D; Marini, Joan C; Caird, Michelle S; Morris, Michael D; Kozloff, Kenneth M

    2016-03-01

    Bone composition and biomechanics at the tissue-level are important contributors to whole bone strength. Sclerostin antibody (Scl-Ab) is a candidate anabolic therapy for the treatment of osteoporosis that increases bone formation, bone mass, and bone strength in animal studies, but its effect on bone quality at the tissue-level has received little attention. Pre-clinical studies of Scl-Ab have recently expanded to include diseases with altered collagen and material properties such as osteogenesis imperfecta (OI). The purpose of this study was to investigate the role of Scl-Ab on bone quality by determining bone material composition and tissue-level mechanical properties in normal wild type (WT) tissue, as well as mice with a typical OI Gly➔Cys mutation (Brtl/+) in type I collagen. Rapidly growing (3-week-old) and adult (6-month-old) WT and Brtl/+ mice were treated for 5weeks with Scl-Ab. Fluorescent guided tissue-level bone composition analysis (Raman spectroscopy) and biomechanical testing (nanoindentation) were performed at multiple tissue ages. Scl-Ab increased mineral to matrix in adult WT and Brtl/+ at tissue ages of 2-4wks. However, no treatment related changes were observed in mineral to matrix levels at mid-cortex, and elastic modulus was not altered by Scl-Ab at any tissue age. Increased mineral-to-matrix was phenotypically observed in adult Brtl/+ OI mice (at tissue ages>3wks) and rapidly growing Brtl/+ (at tissue ages>4wks) mice compared to WT. At identical tissue ages defined by fluorescent labels, adult mice had generally lower mineral to matrix ratios and a greater elastic modulus than rapidly growing mice, demonstrating that bone matrix quality can be influenced by animal age and tissue age alike. In summary, these data suggest that Scl-Ab alters the matrix chemistry of newly formed bone while not affecting the elastic modulus, induces similar changes between Brtl/+ and WT mice, and provides new insight into the interaction between tissue age and

  8. T lymphocytes and normal tissue responses to radiation

    International Nuclear Information System (INIS)

    Schaue, Dörthe; McBride, William H.

    2012-01-01

    There is compelling evidence that lymphocytes are a recurring feature in radiation damaged normal tissues, but assessing their functional significance has proven difficult. Contradictory roles have been postulated in both tissue pathogenesis and protection, although these are not necessarily mutually exclusive as the immune system can display what may seem to be opposing faces at any one time. While the exact role of T lymphocytes in irradiated normal tissue responses may still be obscure, their accumulation after tissue damage suggests they may be critical targets for radiotherapeutic intervention and worthy of further study. This is accentuated by recent findings that pathologically damaged “self,” such as occurs after exposure to ionizing radiation, can generate danger signals with the ability to activate pathways similar to those that activate adoptive immunity to pathogens. In addition, the demonstration of T cell subsets with their recognition radars tuned to “self” moieties has revolutionized our ideas on how all immune responses are controlled and regulated. New concepts of autoimmunity have resulted based on the dissociation of immune functions between different subsets of immune cells. It is becoming axiomatic that the immune system has the power to regulate radiation-induced tissue damage, from failure of regeneration to fibrosis, to acute and chronic late effects, and even to carcinogenesis. Our understanding of the interplay between T lymphocytes and radiation-damaged tissue may still be rudimentary but this is a good time to re-examine their potential roles, their radiobiological and microenvironmental influences, and the possibilities for therapeutic manipulation. This review will discuss the yin and yang of T cell responses within the context of radiation exposures, how they might drive or protect against normal tissue side effects and what we may be able do about it.

  9. Role of endothelium in radiation-induced normal tissue damages

    International Nuclear Information System (INIS)

    Milliat, F.

    2007-05-01

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  10. Human normal tissue reactions in radiotherapy

    International Nuclear Information System (INIS)

    Taniike, Keiko

    1990-01-01

    Acute and late normal tissue reactions in radiotherapy have not been considered to be major problems with conventional fractionation. But they may cause certain problems when newer schedules such as hyperfractionation or accelerated fractionation are used. In opposing parallel radiotherapy, the dose fractionation of skin or subcutaneous connective tissue are different between in one portal and two portals daily. So we examined acute skin erythema and late connective tissue fibrosis in the two groups (one and two portals) of the patients with uterus cancer. Acute skin erythema and late connective tissue fibrosis were slightly stronger in case of one portal daily. In relation to the anatomical site of skin, acute skin erythema was stronger at the buttocks than the lower abdomen, but late fibrosis was reverse to that. So the degree of acute skin erythema did not predict the degree of late connective tissue fibrosis. The number of Time Dose Fractionation Factor could roughly estimate the degree of erythema and fibrosis. Late fibrosis in 36 fractions increased with an increase of abdominal thickness, but acute erythema did not. (author)

  11. Mast cell distribution in normal adult skin

    NARCIS (Netherlands)

    A.S. Janssens (Artiena Soe); R. Heide (Rogier); J.C. den Hollander (Jan); P.G.M. Mulder (P. G M); B. Tank (Bhupendra); A.P. Oranje (Arnold)

    2005-01-01

    markdownabstract__AIMS:__ To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. __METHODS:__ Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults.

  12. Analytical formulae in fractionated irradiation of normal tissue

    International Nuclear Information System (INIS)

    Kozubek, S.

    1982-01-01

    The new conception of the modeling of the cell tissue kinetics after fractionated irradiation is proposed. The formulae given earlier are compared with experimental data on various normal tissues and further adjustments are considered. The tissues are shown to exhibit several general patterns of behaviour. The repopulation, if it takes place, seems to start after some time, independently of fractionation in first approximation and can be treated as simple autogenesis. The results are compared with the commonly used NSD conception and the well-known Cohen cell tissue kinetic model

  13. Roentgenographic studies of Korean adults profile with normal occlusion

    Energy Technology Data Exchange (ETDEWEB)

    Park, Tae Won [College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1972-11-15

    A roentgraphic cephalometric study was made on the soft and hard tissue profile of Korean adults. The subject consisted of 52 males and 54 females from 17 to 22 years of age and with normal occlusion and acceptable profile. Twenty one landmarks were plotted and two oriented lines named SnH line and SnV line were drawn on the tracings of all cephalograms. The means and the standard deviations from the subjects were calculated in each measuring category and the means were compared with those of male and female samples. The results were obtained as follow: 1. In depth and height, individual variations and sex differences of the lower facial profile were larger than the upper face. 2. The sex differences of upper facial profile were larger in height than depth. 3. The individual variations and sex differences of the top of nose were the smallest in all measuring points. 4. The thickness of the soft tissue of upper face and upper lip in male sample were larger than those of female, but the same matter were not found in mental region.

  14. Comparative study of radiosensitivity of normal and regenerating tissues

    International Nuclear Information System (INIS)

    Samokhvalova, H.S.; Popova, M.F.

    1983-01-01

    A comparative study of radiosensitivity of cells of normal and regenerating tissues of bone marrow and spleen has demonstrated that single exposure to X-rays produces a lesser damaging effect on regenerating tissues than on normal ones. The data obtained indicate that the increase in radioresistance of the organism during active regeneration of the haemopoietic organs is due not merely to the increase in the dividing cell pool of these organs but also to qualitative changes in their functional state

  15. Effects of pions on normal tissues

    International Nuclear Information System (INIS)

    Tokita, N.

    1981-01-01

    Verification of the uniform biological effectiveness of pion beams of various dimensions produced at LAMPF has been made using cultured mammalian cells and mouse jejunum. Normal tissue radiobiology studies at LAMPF are reviewed with regard to biological beam characterization for the therapy program and the current status of acute and late effect studies on rodents

  16. Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

    DEFF Research Database (Denmark)

    Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

    2014-01-01

    to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers......, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis...... and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further...

  17. DNA Double-Strand Break Rejoining in Complex Normal Tissues

    International Nuclear Information System (INIS)

    Ruebe, Claudia E.; Dong, Xiaorong; Kuehne, Martin; Fricke, Andreas; Kaestner, Lars; Lipp, Peter; Ruebe, Christian

    2008-01-01

    Purpose: The clinical radiation responses of different organs vary widely and likely depend on the intrinsic radiosensitivities of their different cell populations. Double-strand breaks (DSBs) are the most deleterious form of DNA damage induced by ionizing radiation, and the cells' capacity to rejoin radiation-induced DSBs is known to affect their intrinsic radiosensitivity. To date, only little is known about the induction and processing of radiation-induced DSBs in complex normal tissues. Using an in vivo model with repair-proficient mice, the highly sensitive γH2AX immunofluorescence was established to investigate whether differences in DSB rejoining could account for the substantial differences in clinical radiosensitivity observed among normal tissues. Methods and Materials: After whole body irradiation of C57BL/6 mice (0.1, 0.5, 1.0, and 2.0 Gy), the formation and rejoining of DSBs was analyzed by enumerating γH2AX foci in various organs representative of both early-responding (small intestine) and late-responding (lung, brain, heart, kidney) tissues. Results: The linear dose correlation observed in all analyzed tissues indicated that γH2AX immunofluorescence allows for the accurate quantification of DSBs in complex organs. Strikingly, the various normal tissues exhibited identical kinetics for γH2AX foci loss, despite their clearly different clinical radiation responses. Conclusion: The identical kinetics of DSB rejoining measured in different organs suggest that tissue-specific differences in radiation responses are independent of DSB rejoining. This finding emphasizes the fundamental role of DSB repair in maintaining genomic integrity, thereby contributing to cellular viability and functionality and, thus, tissue homeostasis

  18. β class II tubulin predominates in normal and tumor breast tissues

    International Nuclear Information System (INIS)

    Dozier, James H; Hiser, Laree; Davis, Jennifer A; Thomas, Nancy Stubbs; Tucci, Michelle A; Benghuzzi, Hamed A; Frankfurter, Anthony; Correia, John J; Lobert, Sharon

    2003-01-01

    Antimitotic chemotherapeutic agents target tubulin, the major protein in mitotic spindles. Tubulin isotype composition is thought to be both diagnostic of tumor progression and a determinant of the cellular response to chemotherapy. This implies that there is a difference in isotype composition between normal and tumor tissues. To determine whether such a difference occurs in breast tissues, total tubulin was fractionated from lysates of paired normal and tumor breast tissues, and the amounts of β-tubulin classes I + IV, II, and III were measured by competitive enzyme-linked immunosorbent assay (ELISA). Only primary tumor tissues, before chemotherapy, were examined. Her2/neu protein amplification occurs in about 30% of breast tumors and is considered a marker for poor prognosis. To gain insight into whether tubulin isotype levels might be correlated with prognosis, ELISAs were used to quantify Her2/neu protein levels in these tissues. β-Tubulin isotype distributions in normal and tumor breast tissues were similar. The most abundant β-tubulin isotypes in these tissues were β-tubulin classes II and I + IV. Her2/neu levels in tumor tissues were 5–30-fold those in normal tissues, although there was no correlation between the Her2/neu biomarker and tubulin isotype levels. These results suggest that tubulin isotype levels, alone or in combination with Her2/neu protein levels, might not be diagnostic of tumorigenesis in breast cancer. However, the presence of a broad distribution of these tubulin isotypes (for example, 40–75% β-tubulin class II) in breast tissue, in conjunction with other factors, might still be relevant to disease progression and cellular response to antimitotic drugs

  19. Late effects of normal tissues (lent) scoring system: the soma scale

    International Nuclear Information System (INIS)

    Mornex, F.; Pavy, J.J.; Denekamp, J.

    1997-01-01

    Radiation tolerance of normal tissues remains the limiting factor for delivering tumoricidal dose. The late toxicity of normal tissues is the most critical element of an irradiation: somatic, functional and structural alterations occur during the actual treatment itself, but late effects manifest months to years after acute effects heal, and may progress with time. The optimal therapeutic ratio ultimately requires not only complete tumor clearance, but also minimal residual injury to surrounding vital normal tissues. The disparity between the intensity of acute and late effects and the inability to predict the eventual manifestation of late normal tissue injury has made radiation oncologists recognize the importance of careful patient follow-up. There is so far no uniform toxicity scoring system to compare several clinical studies in the absence of a 'common toxicity language'. This justifies the need to establish a precise evaluation system for the analysis of late effects of radiation on normal tissues. The SOMA/LENT scoring system results from an international collaboration. European Organization Treatment of Cancer (EORTC) and Radiation Therapy Oncology Group (RTOG) have created subcommittees with the aim of addressing the question of standardized toxic effects criteria. This effort appeared as a necessity to standardize and improve the data recording, to then describe and evaluate uniform toxicity at regular time intervals. The current proposed scale is not yet validated, and should be used cautiously. (authors)

  20. Pathway-specific differences between tumor cell lines and normal and tumor tissue cells

    Directory of Open Access Journals (Sweden)

    Tozeren Aydin

    2006-11-01

    Full Text Available Abstract Background Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue. Methods This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM. Results Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs, and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways. Conclusion Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative

  1. Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms.

    Science.gov (United States)

    Svingen, T; Jørgensen, A; Rajpert-De Meyts, E

    2014-08-01

    The measurement of gene expression levels in cells and tissues typically depends on a suitable point of reference for inferring biological relevance. For quantitative (or real-time) RT-PCR assays, the method of choice is often to normalize gene expression data to an endogenous gene that is stably expressed across the samples analysed: a so-called normalizing or housekeeping gene. Although this is a valid strategy, the identification of stable normalizing genes has proved challenging and a gene showing stable expression across all cells or tissues is unlikely to exist. Therefore, it is necessary to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further recommend that such studies should be accompanied by additional assessment of histology and cellularity of each sample. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Activin receptor subunits in normal and dysfunctional adult human testis

    DEFF Research Database (Denmark)

    Dias, V; Meachem, S; Rajpert-De Meyts, E

    2008-01-01

    The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.......The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown....

  3. Comparison of effective atomic numbers of the cancerous and normal kidney tissue

    International Nuclear Information System (INIS)

    Manjunatha, H.C.

    2015-01-01

    The effective atomic number (Z eff ) and electron density (N e ) of normal kidney and cancerous kidney have been computed for total and partial photon interactions by computing the molecular, atomic, and electronic cross section in the wide energy range of 1 keV-100 GeV using WinXCOM. The mean Z eff and N e of normal kidney and cancerous kidney in the various energy ranges and for total and partial photon interactions are tabulated. The variation of effective N e with energy is shown graphically for all photon interactions. In addition to this computer tomography (CT), numbers of normal kidney and cancerous kidney for photon interaction and energy absorption is also computed. The role of Z eff in the dual-energy dividing radiography is also discussed. The values of Z eff and N e for cancerous kidney are higher than normal kidney. This is due to the levels of elements K, Ca, Fe, Ni, and Se are lower and those of the elements Ti, Co, Zn, As, and Cd are higher in the cancer tissue of kidney than those observed in the normal tissue. The soft tissue and cancerous tissue are very similar, but their atomic number differs. The cancerous tissue exhibits a higher Z eff than the normal tissue. This fact helps in the dual-energy dividing radiography which enables to improve the diagnosis of the kidney cancer. Hence, the computed values may be useful in the diagnosis of the kidney cancer. CT numbers for normal kidney are higher than cancerous kidney. (author)

  4. Changes in tissue morphology and collagen composition during the repair of cortical bone in the adult chicken.

    Science.gov (United States)

    Glimcher, M J; Shapiro, F; Ellis, R D; Eyre, D R

    1980-09-01

    An animal model was developed to study the histology and collagen chemistry of healing cortical bone. A hole was cut through the cortex of the mid-shaft of the humerus of the adult chicken, which allowed for repair at a mechanically stable site. After one to two weeks the collagen of the repair tissue, which consisted principally of woven bone, contained almost three times as much hydroxylysine as the collagen of normal adult bone and thus resembled the collagen of embryonic long bones. By eight weeks, when lamellar one predominated, the hydroxylysine content had fallen to normal levels. Type I was the major genetic type of collagen present throughout. No type-II collagen, characteristic of cartilage, was detected; this was consistent with the histological findings. The results established that hydroxylysine-rich type-I collagen can be made by osteoblasts of adult animals as well as by those of embryos and early postnates. In order to understand the biological characteristics of fracture healing, it is vital to study not only the macroscopic organization of the repair tissue but also the chemical properties of its molecular components. The strength of healing fractured bone, and indeed of normal bone, depends largely on the properties of the structural protein collagen. To date, it is not known whether the collagen in healing fractures is the same as that in normal bone, or whether it has distinct chemical features that may suit it for bone repair.

  5. MRI characterization of brown adipose tissue in obese and normal-weight children

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Schoeneman, Samantha E. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Medical Imaging, 225 E. Chicago Ave., Box 9, Chicago, IL (United States); Zhang, Huiyuan [John H. Stroger, Jr. Hospital of Cook County, Collaborative Research Unit, Chicago, IL (United States); Kwon, Soyang [Ann and Robert H. Lurie Children' s Hospital of Chicago, Stanley Manne Children' s Research Institute, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States); Josefson, Jami L. [Ann and Robert H. Lurie Children' s Hospital of Chicago, Division of Endocrinology, Chicago, IL (United States); Northwestern University, Department of Pediatrics, Feinberg School of Medicine, Chicago, IL (United States)

    2015-10-15

    Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

  6. MRI characterization of brown adipose tissue in obese and normal-weight children

    International Nuclear Information System (INIS)

    Deng, Jie; Rigsby, Cynthia K.; Shore, Richard M.; Schoeneman, Samantha E.; Zhang, Huiyuan; Kwon, Soyang; Josefson, Jami L.

    2015-01-01

    Brown adipose tissue (BAT) is identified in mammals as an adaptive thermogenic organ for modulation of energy expenditure and heat generation. Human BAT may be primarily composed of brown-in-white (BRITE) adipocytes and stimulation of BRITE may serve as a potential target for obesity interventions. Current imaging studies of BAT detection and characterization have been mainly limited to PET/CT. MRI is an emerging application for BAT characterization in healthy children. To exploit Dixon and diffusion-weighted MRI methods to characterize cervical-supraclavicular BAT/BRITE properties in normal-weight and obese children while accounting for pubertal status. Twenty-eight healthy children (9-15 years old) with a normal or obese body mass index participated. MRI exams were performed to characterize supraclavicular adipose tissues by measuring tissue fat percentage, T2*, tissue water mobility, and microvasculature properties. We used multivariate linear regression models to compare tissue properties between normal-weight and obese groups while accounting for pubertal status. MRI measurements of BAT/BRITE tissues in obese children showed higher fat percentage (P < 0.0001), higher T2* (P < 0.0001), and lower diffusion coefficient (P = 0.015) compared with normal-weight children. Pubertal status was a significant covariate for the T2* measurement, with higher T2* (P = 0.0087) in pubertal children compared to prepubertal children. Perfusion measurements varied by pubertal status. Compared to normal-weight children, obese prepubertal children had lower perfusion fraction (P = 0.003) and pseudo-perfusion coefficient (P = 0.048); however, obese pubertal children had higher perfusion fraction (P = 0.02) and pseudo-perfusion coefficient (P = 0.028). This study utilized chemical-shift Dixon MRI and diffusion-weighted MRI methods to characterize supraclavicular BAT/BRITE tissue properties. The multi-parametric evaluation revealed evidence of morphological differences in brown

  7. Radiosensitization effects of nicotinamide on malignant and normal mouse tissue

    International Nuclear Information System (INIS)

    Jonsson, G.G.; Kjellen, E.; Pero, R.W.; Cameron, R.

    1985-01-01

    Inhibitors of the chromatin-associated enzyme adenosine diphosphate ribosyltransferase have been found to inhibit DNA strand rejoining and to potentiate lethality of DNA-damaging agents both in vivo and in vitro. The authors have in this work examined the radiosensitizing potential of one such inhibitor, nicotinamide, on tumor tissue by using transplanted C3H mouse mammary adenocarcinomas and on normal tissue in a tail-stunting experiment using BALB/cA mice. The data indicate a radiosensitizing effect of nicotinamide on tumor cells as well as on normal tissue. The data indicate a possible role of adenosine diphosphate ribosyltransferase inhibitors as a sensitizing agent in the radiotherapy of malignant tumors

  8. Potential clinical impact of normal-tissue intrinsic radiosensitivity testing

    International Nuclear Information System (INIS)

    Bentzen, Soeren M.

    1997-01-01

    A critical appraisal is given of the possible benefit from a reliable pre-treatment knowledge of individual normal-tissue sensitivity to radiotherapy. The considerations are in part, but not exclusively, based on the recent experience with in vitro colony-forming assays of the surviving fraction at 2 Gy, the SF 2 . Three strategies are reviewed: (1) to screen for rare cases with extreme radiosensitivity, so-called over-reactors, and treat these with reduced total dose, (2) to identify the sensitive tail of the distribution of 'normal' radiosensitivities, refer these patients to other treatment, and to escalate the dose to the remaining patients, or (3) to individualize dose prescriptions based on individual radiosensitivity, i.e. treating to isoeffect rather than to a specific dose-fractionation schedule. It is shown that these strategies will have a small, if any, impact on routine radiotherapy. Screening for over-reactors is hampered by the low prevalence of these among otherwise un-selected patients that leads to a low positive predictive value of in vitro radiosensitivity assays. It is argued, that this problem may persist even if the noise on current assays could be reduced to (the unrealistic value of) zero, simply because of the large biological variation in SF 2 . Removing the sensitive tail of the patient population, will only have a minor effect on the dose that could be delivered to the remaining patients, because of the sigmoid shape of empirical dose-response relationships. Finally, individualizing dose prescriptions based exclusively on information from a normal-tissue radiosensitivity assay, leads to a nearly symmetrical distribution of dose-changes that would produce a very small gain, or even a loss, of tumor control probability if implemented in the clinic. From a theoretical point of view, other strategies could be devised and some of these are considered in this review. Right now the most promising clinical use of in vitro radiosensitivity

  9. Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

    Science.gov (United States)

    Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  10. Differentiation in boron distribution in adult male and female rats' normal brain: A BNCT approach

    International Nuclear Information System (INIS)

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Baghban Khojasteh, Nasrin

    2012-01-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. - Highlights: ► Boron distribution in male and female rats' normal brain was studied in this research. ► Coronal sections of animal tissue samples were irradiated with thermal neutrons. ► Alpha and Lithium tracks were counted using alpha autoradiography. ► Different boron concentration was seen in brain sections of male and female rats. ► The highest boron concentration was seen in 4 h after boron compound injection.

  11. Normal tissue complication probability (NTCP), the clinician,s perspective

    International Nuclear Information System (INIS)

    Yeoh, E.K.

    2011-01-01

    Full text: 3D radiation treatment planning has enabled dose distributions to be related to the volume of normal tissues irradiated. The dose volume histograms thus derived have been utilized to set NTCP dose constraints to facilitate optimization of treatment planning. However, it is not widely appreciated that a number of important variables other than DYH's which determine NTCP in the individual patient. These variables will be discussed under the headings of patient and treatment related as well as tumour related factors. Patient related factors include age, co-morbidities such as connective tissue disease and diabetes mellitus, previous tissue/organ damage, tissue architectural organization (parallel or serial), regional tissue/organ and individual tissue/organ radiosensitivities as well as the development of severe acute toxicity. Treatment related variables which need to be considered include dose per fraction (if not the conventional 1.8012.00 Gy/fraction, particularly for IMRT), number of fractions and total dose, dose rate (particularly if combined with brachytherapy) and concurrent chemotherapy or other biological dose modifiers. Tumour related factors which impact on NTCP include infiltration of normal tissue/organ usually at presentation leading to compromised function but also with recurrent disease after radiation therapy as well as variable tumour radiosensitivities between and within tumour types. Whilst evaluation of DYH data is a useful guide in the choice of treatment plan, the current state of knowledge requires the clinician to make an educated judgement based on a consideration of the other factors.

  12. Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

    Science.gov (United States)

    Li, Li; Xie, Wengming; Li, Hui

    2012-12-01

    The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

  13. Statistical validation of normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; van t Veld, Aart; Langendijk, Johannes A.; Schilstra, Cornelis

    2012-01-01

    PURPOSE: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: A penalized regression method, LASSO (least absolute shrinkage

  14. Iso-effect tables and therapeutic ratios for epidermoid cancer and normal tissue stroma

    International Nuclear Information System (INIS)

    Cohen, L.; Creditor, M.

    1983-01-01

    Available literature on radiation injury to normal tissue stroma and ablation of epidermoid carcinoma was surveyed. Computer programs (RAD3 and RAD1) were then used to derive cell kinetic parameters and generate iso-effect tables for the relevant tissues. The two tables provide a set of limiting doses for tolerance of normal connective tissue (16% risk of injury) and for ablation of epidermoid cancer (16% risk of recurrence) covering a wide range of treatment schedules. Calculating the ratios of normal tissue tolerance to tumor control doses for each treatment scheme provides an array of therapeutic ratios, from which appropriate treatment schemes can be selected

  15. Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

    Science.gov (United States)

    Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

    1998-01-01

    The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

  16. Evaluation of normal tissue responses to high-LET radiations

    International Nuclear Information System (INIS)

    Halnan, K.E.

    1979-01-01

    Clinical results presented have been analysed to evaluate normal tissue responses to high-LET radiations. Damage to brain, spinal cord, gut, skin, connective tissue and bone has occurred. A high RBE is probable for brain and possible for spinal cord and gut but other reasons for damage are also discussed. A net gain seems likely. Random controlled trials are advocated. (author)

  17. MRI appearance of radiation-induced changes of normal cervical tissues

    International Nuclear Information System (INIS)

    Noemayr, A.; Lell, M.; Bautz, W.; Sweeney, R.; Lukas, P.

    2001-01-01

    Irradiation causes specific MRI changes in anatomic morphology and signal intensity. To avoid misinterpretation, it is important to consider the potential radiation changes of normal tissue in MRI. The aim of this study was to describe the detected radiation effects on normal cervical tissues in MRI. Pretreatment and posttreatment MRI of 52 patients with primary neck tumors were evaluated retrospectively. The MR imaging was performed before initiating radiotherapy and at the end of the treatment period. Patients underwent follow-up studies within 24 months after the end of irradiation. Edema was the main radiation-induced effect. It was detected in the epiglottis, larynx, pharynx wall, retro- and parapharyngeal space, salivary glands, muscles, and subcutaneous tissue. In some cases the bone marrow of the mandible showed edema, due to osteonecrosis. We additionally detected fluid accumulation in the mastoid cells. Radiation caused volume reduction of the parotid gland, thickening of the pharynx wall, and fatty degeneration of bone marrow. Magnetic resonance imaging is an excellent method of depicting radiation-induced changes of normal tissue. Especially T2-weighted sequences allow the detection of even slight edema. It is important to be aware of the most common radiation-induced changes in MRI and to take them into account when assessing an examination. (orig.)

  18. Quantitative analysis of DNA methylation at all human imprinted regions reveals preservation of epigenetic stability in adult somatic tissue

    Directory of Open Access Journals (Sweden)

    Woodfine Kathryn

    2011-01-01

    Full Text Available Abstract Background Genes subject to genomic imprinting are mono-allelically expressed in a parent-of-origin dependent manner. Each imprinted locus has at least one differentially methylated region (DMR which has allele specific DNA methylation and contributes to imprinted gene expression. Once DMRs are established, they are potentially able to withstand normal genome reprogramming events that occur during cell differentiation and germ-line DMRs are stably maintained throughout development. These DMRs, in addition to being either maternally or paternally methylated, have differences in whether methylation was acquired in the germ-line or post fertilization and are present in a variety of genomic locations with different Cytosine-phosphate guanine (CpG densities and CTCF binding capacities. We therefore examined the stability of maintenance of DNA methylation imprints and determined the normal baseline DNA methylation levels in several adult tissues for all imprinted genes. In order to do this, we first developed and validated 50 highly specific, quantitative DNA methylation pyrosequencing assays for the known DMRs associated with human imprinted genes. Results Remarkable stability of the DNA methylation imprint was observed in all germ-line DMRs and paternally methylated somatic DMRs (which maintained average methylation levels of between 35% - 65% in all somatic tissues, independent of gene expression. Maternally methylated somatic DMRs were found to have more variation with tissue specific methylation patterns. Most DMRs, however, showed some intra-individual variability for DNA methylation levels in peripheral blood, suggesting that more than one DMR needs to be examined in order to get an overall impression of the epigenetic stability in a tissue. The plasticity of DNA methylation at imprinted genes was examined in a panel of normal and cancer cell lines. All cell lines showed changes in DNA methylation, especially at the paternal germ

  19. Raman spectroscopy of normal oral buccal mucosa tissues: study on intact and incised biopsies

    Science.gov (United States)

    Deshmukh, Atul; Singh, S. P.; Chaturvedi, Pankaj; Krishna, C. Murali

    2011-12-01

    Oral squamous cell carcinoma is one of among the top 10 malignancies. Optical spectroscopy, including Raman, is being actively pursued as alternative/adjunct for cancer diagnosis. Earlier studies have demonstrated the feasibility of classifying normal, premalignant, and malignant oral ex vivo tissues. Spectral features showed predominance of lipids and proteins in normal and cancer conditions, respectively, which were attributed to membrane lipids and surface proteins. In view of recent developments in deep tissue Raman spectroscopy, we have recorded Raman spectra from superior and inferior surfaces of 10 normal oral tissues on intact, as well as incised, biopsies after separation of epithelium from connective tissue. Spectral variations and similarities among different groups were explored by unsupervised (principal component analysis) and supervised (linear discriminant analysis, factorial discriminant analysis) methodologies. Clusters of spectra from superior and inferior surfaces of intact tissues show a high overlap; whereas spectra from separated epithelium and connective tissue sections yielded clear clusters, though they also overlap on clusters of intact tissues. Spectra of all four groups of normal tissues gave exclusive clusters when tested against malignant spectra. Thus, this study demonstrates that spectra recorded from the superior surface of an intact tissue may have contributions from deeper layers but has no bearing from the classification of a malignant tissues point of view.

  20. Tumor and normal tissue responses to fractioned non-uniform dose delivery

    Energy Technology Data Exchange (ETDEWEB)

    Kaellman, P; Aegren, A; Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

    1996-08-01

    The volume dependence of the radiation response of a tumor is straight forward to quantify because it depends primarily on the eradication of all its clonogenic cells. A tumor therefore has a parallel organization as any surviving clonogen in principle can repopulate the tumor. The difficulty with the response of the tumor is instead to know the density and sensitivity distribution of the most resistant clonogenic cells. The increase in the 50% tumor control dose and the decrease in the maximum normalized slope of the dose response relation, {gamma}, in presence of small compartments of resistant tumor cells have therefore been quantified to describe their influence on the dose response relation. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of the differentiated and clonogenic cells that in addition may have a complex structural and functional organization. The volume dependence of the dose response relation of normal tissues is therefore described here by the relative seriality, s, of the infrastructure of the organ. The model can also be generalized to describe the response of heterogeneous tissues to non uniform dose distributions. The new model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose response relation and the volume dependence of the isoeffect dose. The response of tumors and normal tissues are quantified for arbitrary dose fractionations using the linear quadratic cell survival parameters {alpha} and {beta}. The parameters of the dose response relation are derived both for a constant dose per fraction and a constant number of dose fractions, thus in the latter case accounting also for non uniform dose delivery. (author). 26 refs, 4 figs.

  1. High and Low LET Radiation Differentially Induce Normal Tissue Damage Signals

    International Nuclear Information System (INIS)

    Niemantsverdriet, Maarten; Goethem, Marc-Jan van; Bron, Reinier; Hogewerf, Wytse; Brandenburg, Sytze; Langendijk, Johannes A.; Luijk, Peter van; Coppes, Robert P.

    2012-01-01

    Purpose: Radiotherapy using high linear energy transfer (LET) radiation is aimed at efficiently killing tumor cells while minimizing dose (biological effective) to normal tissues to prevent toxicity. It is well established that high LET radiation results in lower cell survival per absorbed dose than low LET radiation. However, whether various mechanisms involved in the development of normal tissue damage may be regulated differentially is not known. Therefore the aim of this study was to investigate whether two actions related to normal tissue toxicity, p53-induced apoptosis and expression of the profibrotic gene PAI-1 (plasminogen activator inhibitor 1), are differentially induced by high and low LET radiation. Methods and Materials: Cells were irradiated with high LET carbon ions or low LET photons. Cell survival assays were performed, profibrotic PAI-1 expression was monitored by quantitative polymerase chain reaction, and apoptosis was assayed by annexin V staining. Activation of p53 by phosphorylation at serine 315 and serine 37 was monitored by Western blotting. Transfections of plasmids expressing p53 mutated at serines 315 and 37 were used to test the requirement of these residues for apoptosis and expression of PAI-1. Results: As expected, cell survival was lower and induction of apoptosis was higher in high -LET irradiated cells. Interestingly, induction of the profibrotic PAI-1 gene was similar with high and low LET radiation. In agreement with this finding, phosphorylation of p53 at serine 315 involved in PAI-1 expression was similar with high and low LET radiation, whereas phosphorylation of p53 at serine 37, involved in apoptosis induction, was much higher after high LET irradiation. Conclusions: Our results indicate that diverse mechanisms involved in the development of normal tissue damage may be differentially affected by high and low LET radiation. This may have consequences for the development and manifestation of normal tissue damage.

  2. Dosimetric precision requirements and quantities for characterizing the response of tumors and normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

    1996-08-01

    Based on simple radiobiological models the effect of the distribution of absorbed dose in therapy beams on the radiation response of tumor and normal tissue volumes are investigated. Under the assumption that the dose variation in the treated volume is small it is shown that the response of the tissue to radiation is determined mainly by the mean dose to the tumor or normal tissue volume in question. Quantitative expressions are also given for the increased probability of normal tissue complications and the decreased probability of tumor control as a function of increasing dose variations around the mean dose level to these tissues. When the dose variations are large the minimum tumor dose (to cm{sup 3} size volumes) will generally be better related to tumor control and the highest dose to significant portions of normal tissue correlates best to complications. In order not to lose more than one out of 20 curable patients (95% of highest possible treatment outcome) the required accuracy in the dose distribution delivered to the target volume should be 2.5% (1{sigma}) for a mean dose response gradient {gamma} in the range 2 - 3. For more steeply responding tumors and normal tissues even stricter requirements may be desirable. (author). 15 refs, 6 figs.

  3. Differentiation in boron distribution in adult male and female rats' normal brain: A BNCT approach

    Energy Technology Data Exchange (ETDEWEB)

    Goodarzi, Samereh, E-mail: samere.g@gmail.com [Department of Nuclear Engineering, Science and Research Branch, Islamic Azad University, PO Box 19395-1943, Tehran (Iran, Islamic Republic of); Pazirandeh, Ali, E-mail: paziran@yahoo.com [Department of Nuclear Engineering, Science and Research Branch, Islamic Azad University, PO Box 19395-1943, Tehran (Iran, Islamic Republic of); Jameie, Seyed Behnamedin, E-mail: behnamjameie@tums.ac.ir [Basic Science Department, Faculty of Allied Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Baghban Khojasteh, Nasrin, E-mail: khojasteh_n@yahoo.com [Department of Nuclear Engineering, Science and Research Branch, Islamic Azad University, PO Box 19395-1943, Tehran (Iran, Islamic Republic of)

    2012-06-15

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. - Highlights: Black-Right-Pointing-Pointer Boron distribution in male and female rats' normal brain was studied in this research. Black-Right-Pointing-Pointer Coronal sections of animal tissue samples were irradiated with thermal neutrons. Black-Right-Pointing-Pointer Alpha and Lithium tracks were counted using alpha autoradiography. Black-Right-Pointing-Pointer Different boron concentration was seen in brain sections of male and female rats. Black-Right-Pointing-Pointer The highest boron concentration was seen in 4 h after boron compound injection.

  4. Optical redox imaging indices discriminate human breast cancer from normal tissues

    Science.gov (United States)

    Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

    2016-01-01

    Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (predox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (predox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

  5. Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

    International Nuclear Information System (INIS)

    Badylak, S.F.; Babbs, C.F.

    1984-01-01

    The sequential morphologic alterations in normal skeletal muscle in rats, Walker 256 tumors in rats, and transmissible venereal tumors (TVT) in dogs following microwave-induced hyperthermia (43 0 C and 45 0 for 20 minutes) were studied by light and electron microscopy. Normal muscle and Walker 256 tumors showed vascular damage at 5 minutes post-heating (PH), followed by suppuration and thrombosis at 6 and 48 hours PH, and by regeneration and repair at 7 days PH. Endothelial damage and parenchymal degeneration were present 5 minutes PH. Progressive ischemic injury occurred for at least 48 hours PH. Two hyperthermia treatments, separated by a 30 or 60 minute cooling interval, were applied to rats implanted with Walker 256 tumors. Increased selective heating of tumor tissue versus surrounding normal tissue, and increased intratumoral temperatures were found during the second hyperthermia treatment. Canine TVTs were resistant to hyperthermia damage. These results characterized the sequential morphologic alterations following hyperthermia treatment and showed that: 1) vascular damage contributed to the immediate and latent cytotoxic effects of hyperthermia, 2) selective heating occurred in the neoplastic tissue disrupted by prior heat treatment, and 3) not all neoplasms are responsive to hyperthermia treatment

  6. No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial.

    Science.gov (United States)

    Kuzma, Jessica N; Cromer, Gail; Hagman, Derek K; Breymeyer, Kara L; Roth, Christian L; Foster-Schubert, Karen E; Holte, Sarah E; Weigle, David S; Kratz, Mario

    2016-08-01

    Sugar-sweetened beverage (SSB) consumption and low-grade chronic inflammation are both independently associated with type 2 diabetes and cardiovascular disease. Fructose, a major component of SSBs, may acutely trigger inflammation, which may be one link between SSB consumption and cardiometabolic disease. We sought to determine whether beverages sweetened with fructose, high-fructose corn syrup (HFCS), and glucose differentially influence systemic inflammation [fasting plasma C-reactive protein and interleukin-6 (IL-6) as primary endpoints] acutely and before major changes in body weight. Secondary endpoints included adipose tissue inflammation, intestinal permeability, and plasma fetuin-A as potential mechanistic links between fructose intake and low-grade inflammation. We conducted a randomized, controlled, double-blind, crossover design dietary intervention (the Diet and Systemic Inflammation Study) in 24 normal-weight to obese adults without fructose malabsorption. Participants drank 4 servings/d of fructose-, glucose-, or HFCS-sweetened beverages accounting for 25% of estimated calorie requirements while consuming a standardized diet ad libitum for three 8-d periods. Subjects consumed 116% of their estimated calorie requirement while drinking the beverages with no difference in total energy intake or body weight between groups as reported previously. Fasting plasma concentrations of C-reactive protein and IL-6 did not differ significantly at the end of the 3 diet periods. We did not detect a consistent differential effect of the diets on measures of adipose tissue inflammation except for adiponectin gene expression in adipose tissue (P = 0.005), which was lowest after the glucose phase. We also did not detect consistent evidence of a differential impact of these sugars on measures of intestinal permeability (lactulose:mannitol test, plasma zonulin, and plasma lipopolysaccharide-binding protein). Excessive amounts of fructose, HFCS, and glucose from SSBs

  7. Lovastatin attenuates ionizing radiation-induced normal tissue damage in vivo

    International Nuclear Information System (INIS)

    Ostrau, Christian; Huelsenbeck, Johannes; Herzog, Melanie; Schad, Arno; Torzewski, Michael; Lackner, Karl J.; Fritz, Gerhard

    2009-01-01

    Background and purpose: HMG-CoA-reductase inhibitors (statins) are widely used lipid-lowering drugs. Moreover, they have pleiotropic effects on cellular stress responses, proliferation and apoptosis in vitro. Here, we investigated whether lovastatin attenuates acute and subchronic ionizing radiation-induced normal tissue toxicity in vivo. Materials and methods: Four hours to 24 h after total body irradiation (6 Gy) of Balb/c mice, acute pro-inflammatory and pro-fibrotic responses were analyzed. To comprise subchronic radiation toxicity, mice were irradiated twice with 2.5 Gy and analyses were performed 3 weeks after the first radiation treatment. Molecular markers of inflammation and fibrosis as well as organ toxicities were measured. Results: Lovastatin attenuated IR-induced activation of NF-κB, mRNA expression of cell adhesion molecules and mRNA expression of pro-inflammatory and pro-fibrotic marker genes (i.e. TNFα, IL-6, TGFβ, CTGF, and type I and type III collagen) in a tissue- and time-dependent manner. γH2AX phosphorylation stimulated by IR was not affected by lovastatin, indicating that the statin has no major impact on the induction of DNA damage in vivo. Radiation-induced thrombopenia was significantly alleviated by lovastatin. Conclusions: Lovastatin inhibits both acute and subchronic IR-induced pro-inflammatory and pro-fibrotic responses and cell death in normal tissue in vivo. Therefore, lovastatin might be useful for selectively attenuating acute and subchronic normal tissue damage caused by radiotherapy.

  8. Modification of the biologic dose to normal tissue by daily fraction

    Energy Technology Data Exchange (ETDEWEB)

    Wollin, M; Kagan, A R [Southern California Permanente Medical Group, Los Angeles Calif. (USA). Dep. of Radiation Therapy

    1976-12-01

    A method to predict normal tissue injury is proposed that includes high daily doses and unusual times successfully by calculating a new value called BIR (Biologic Index of Reaction). BIR and NSD were calculated for various normal tissue reactions. With the aid of statistical correlation techniques it is found that the BIR model is better than the NSD model in predicting radiation myelopathy and vocal edema and as good as NSD IN PREDICTING RIB FRACTURE/ Neither model predicts pericardial effusion. In no case were the results of BIR inferior to those of NSD.

  9. Mast cell distribution in normal adult skin.

    Science.gov (United States)

    Janssens, A S; Heide, R; den Hollander, J C; Mulder, P G M; Tank, B; Oranje, A P

    2005-03-01

    To investigate mast cell distribution in normal adult skin to provide a reference range for comparison with mastocytosis. Mast cells (MCs) were counted in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders in adults. There was an uneven distribution of MCs in different body sites using the anti-tryptase monoclonal antibody technique. Numbers of MCs on the trunk, upper arm, and upper leg were similar, but were significantly different from those found on the lower leg and forearm. Two distinct groups were formed--proximal and distal. There were 77.0 MCs/mm2 at proximal body sites and 108.2 MCs/mm2 at distal sites. Adjusted for the adjacent diagnosis and age, this difference was consistent. The numbers of MCs in uninvolved skin adjacent to basal cell carcinomas and other dermatological disorders were not different from those in the control group. Differences in the numbers of MCs between the distal and the proximal body sites must be considered when MCs are counted for a reliable diagnosis of mastocytosis. A pilot study in patients with mastocytosis underlined the variation in the numbers of MCs in mastocytosis and normal skin, but showed a considerable overlap. The observed numbers of MCs in adults cannot be extrapolated to children. MC numbers varied significantly between proximal and distal body sites and these differences must be considered when MCs are counted for a reliable diagnosis of mastocytosis. There was a considerable overlap between the numbers of MCs in mastocytosis and normal skin.

  10. Differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance

    Directory of Open Access Journals (Sweden)

    Ben-Zhou Feng

    2016-04-01

    Full Text Available Objective: To study the differential expression of GPR30 in preeclampsia placenta tissue and normal placenta tissue and its clinical significance. Methods: Preeclampsia placenta tissue and normal placenta tissue were collected and GPR30 expression levels were detected; human umbilical vein endothelial cells were cultured and processed with GRP30 inhibitor and GRP30 agonist combined with hypoxia-reoxygenation respectively, and cell apoptosis as well as pro-angiogenesis molecule and apoptosis molecule contents were detected. Results: mRNA content and protein content of GRP30 in preeclampsia placenta tissue were significantly lower than those in normal placenta tissue; apoptosis rate of G15 group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of H/R group was significantly higher than that of control group, VEGF and bFGF contents in supernatant were significantly lower than those of control group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly higher than those of control group; apoptosis rate of G1 group was significantly lower than that of H/R group, VEGF and bFGF contents in supernatant were significantly higher than those of H/R group, and mRNA contents of Bax, Caspase-3 and Caspase-9 in cells were significantly lower than those of H/R group. Conclusions: Low expression of GPR30 in placenta tissue is closely associated with the occurrence of preeclampsia, enhancing GPR function can reduce endothelial cell apoptosis and increase the contents of pro-angiogenesis factors, and it has endothelial protection effect.

  11. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L. [Dept.of Radiation Oncology, Henry Ford Health System, Detroit (United States)

    2014-09-15

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

  12. Mechanisms of radiation-induced normal tissue toxicity and implications for future clinical trials

    International Nuclear Information System (INIS)

    Kim, Jae Ho; Jenrow, Kenneth A.; Brown, Stephen L.

    2014-01-01

    To summarize current knowledge regarding mechanisms of radiation-induced normal tissue injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity-modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Injury to critical normal tissues and organs, however, poses substantial risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. The principal pathogenesis is initiated by depletion of tissue stem cells and progenitor cells and damage to vascular endothelial microvessels. Emerging concepts of radiation-induced normal tissue toxicity suggest that the recovery and repopulation of stromal stem cells remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure. Better understanding the mechanisms mediating interactions among excessive generation of reactive oxygen species, production of pro-inflammatory cytokines and activated macrophages, and role of bone marrow-derived progenitor and stem cells may provide novel insight on the pathogenesis of radiation-induced injury of tissues. Further understanding the molecular signaling pathways of cytokines and chemokines would reveal novel targets for protecting or mitigating radiation injury of tissues and organs.

  13. No differential effect of beverages sweetened with fructose, high-fructose corn syrup, or glucose on systemic or adipose tissue inflammation in normal-weight to obese adults: a randomized controlled trial1

    Science.gov (United States)

    Cromer, Gail; Breymeyer, Kara L; Roth, Christian L; Weigle, David S

    2016-01-01

    Background: Sugar-sweetened beverage (SSB) consumption and low-grade chronic inflammation are both independently associated with type 2 diabetes and cardiovascular disease. Fructose, a major component of SSBs, may acutely trigger inflammation, which may be one link between SSB consumption and cardiometabolic disease. Objective: We sought to determine whether beverages sweetened with fructose, high-fructose corn syrup (HFCS), and glucose differentially influence systemic inflammation [fasting plasma C-reactive protein and interleukin-6 (IL-6) as primary endpoints] acutely and before major changes in body weight. Secondary endpoints included adipose tissue inflammation, intestinal permeability, and plasma fetuin-A as potential mechanistic links between fructose intake and low-grade inflammation. Design: We conducted a randomized, controlled, double-blind, crossover design dietary intervention (the Diet and Systemic Inflammation Study) in 24 normal-weight to obese adults without fructose malabsorption. Participants drank 4 servings/d of fructose-, glucose-, or HFCS-sweetened beverages accounting for 25% of estimated calorie requirements while consuming a standardized diet ad libitum for three 8-d periods. Results: Subjects consumed 116% of their estimated calorie requirement while drinking the beverages with no difference in total energy intake or body weight between groups as reported previously. Fasting plasma concentrations of C-reactive protein and IL-6 did not differ significantly at the end of the 3 diet periods. We did not detect a consistent differential effect of the diets on measures of adipose tissue inflammation except for adiponectin gene expression in adipose tissue (P = 0.005), which was lowest after the glucose phase. We also did not detect consistent evidence of a differential impact of these sugars on measures of intestinal permeability (lactulose:mannitol test, plasma zonulin, and plasma lipopolysaccharide-binding protein). Conclusion: Excessive

  14. Comparison of Tissue Stiffness Using Shear Wave Elastography in Men with Normal Testicular Tissue, Testicular Microlithiasis and Testicular Cancer

    DEFF Research Database (Denmark)

    Pedersen, Malene Roland; Møller, Henrik; Osther, Palle Jørn Sloth

    2017-01-01

    Objectives: To compare elastography measurements in men with normal testicular tissue, testicular microlithiasis and testicular cancer. Methods: A total of 248 consecutive patients were included. All men provided written informed consent. Testicular stiffness was assessed using shear wave...... elastography (SWE). Three SWE velocity measurements were assessed in each testicle. The patients were divided into three groups; men with normal testicular tissue (n=130), men with testicular microlithiasis (n=99) and men with testicular cancer (n=19). Results: We found a higher mean velocity in the group...... of patients with testicular cancer (1.92 m/s (95% CI 1.82-2.03)) compared to both the group with normal tissue (0.76 m/s (95% CI: 0.75-0.78)) (ptesticular microlithiasis 0.79 m/s (95% CI: 0.77-0.81) (ptesticular microlithiasis increased stiffness...

  15. Calculation of neutron kerma in tissues

    International Nuclear Information System (INIS)

    Vega C, H.R.; Manzanares A, E.

    2004-01-01

    Neutron kerma of normal and tumor tissues has been calculated using the tissues elemental concentration. A program developed in Math cad contains the kerma factors of C, H, O, N, Na, Mg, P, S, Cl, K, etc. that are in normal and tumor human tissues. Having the elemental composition of any human tissue the neutron kerma can be calculated. The program was tested using the elemental composition of tumor tissues such as sarcoma, melanoma, carcinoma and adenoid cystic, also neutron kerma for adipose and muscle tissue for normal adult was calculated. The results are in agreement with those published in literature. The neutron kerma for water was also calculated because in some dosimetric calculations water is used to describe normal and tumor tissues. From this comparison was found that at larger energies kerma factors are approximately the same, but energies less than 100 eV the differences are large. (Author)

  16. Radiation Dose Estimates in Indian Adults in Normal and Pathological Conditions due to 99Tcm-Labelled Radiopharmaceuticals

    International Nuclear Information System (INIS)

    Tyagi, K.; Jain, S.C.; Jain, P.C.

    2001-01-01

    ICRP Publications 53, 62 and 80 give organ dose coefficients and effective doses to ICRP Reference Man and Child from established nuclear medicine procedures. However, an average Indian adult differs significantly from the ICRP Reference Man as regards anatomical, physiological and metabolic characteristics, and is also considered to have different tissue weighting factors (called here risk factors). The masses of total body and most organs are significantly lower for the Indian adult than for his ICRP counterpart (e.g. body mass 52 and 70 kg respectively). Similarly, the risk factors are lower by 20-30% for 8 out of the 13 organs and 30-60% higher for 3 organs. In the present study, available anatomical data of Indians and their risk factors have been utilised to estimate the radiation doses from administration of commonly used 99 Tc m -labelled radiopharmaceuticals under normal and certain pathological conditions. The following pathological conditions have been considered for phosphates/phosphonates - high bone uptake and severely impaired kidney function; IDA - parenchymal liver disease, occlusion of cystic duct, and occlusion of bile duct; DTPA - abnormal renal function; large colloids - early to intermediate diffuse parenchymal liver disease, intermediate to advanced parenchymal liver disease; small colloids - early to intermediate parenchymal liver disease, intermediate to advanced parenchymal liver disease; and MAG3 - abnormal renal function, acute unilateral renal blockage. The estimated 'effective doses' to Indian adults are 14-21% greater than the ICRP value from administration of the same activity of radiopharmaceutical under normal physiological conditions based on anatomical considerations alone, because of the smaller organ masses for the Indian; for some pathological conditions the effective doses are 11-22% more. When tissue risk factors are considered in addition to anatomical considerations, the estimated effective doses are still found to be

  17. Trace elemental correlation study in malignant and normal breast tissue by PIXE technique

    International Nuclear Information System (INIS)

    Raju, G.J. Naga; Sarita, P.; Kumar, M. Ravi; Murty, G.A.V. Ramana; Reddy, B. Seetharami; Lakshminarayana, S.; Vijayan, V.; Lakshmi, P.V.B. Rama; Gavarasana, Satyanarayana; Reddy, S. Bhuloka

    2006-01-01

    Particle induced X-ray emission technique was used to study the variations in trace elemental concentrations between normal and malignant human breast tissue specimens and to understand the effects of altered homeostasis of these elements in the etiology of breast cancer. A 3 MeV proton beam was used to excite the biological samples of normal and malignant breast tissues. The elements Cl, K, Ca, Ti, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Br, Rb and Sr were identified and their relative concentrations were estimated. Almost all the elements were found to be elevated (p < 0.05, Wilcoxon signed-ranks test) in the cancerous tissues when compared with normal tissues. The excess levels of trace elements observed in the cancerous breast tissues could either be a cause or a consequence of breast cancer. Regarding their role in the initiation or promotion of breast cancer, one possible interpretation is that the elevated levels of Cu, Fe and Cr could have led to the formation of free radicals or other reactive oxygen species (ROS) that adversely affect DNA thereby causing breast cancer, which is mainly attributed to genetic abnormalities. Moreover, since Cu and Fe are required for angiogenesis, elevated concentrations of these elements are likely to promote breast cancer by increasing the blood supply for tumor growth. On the other hand elevated concentrations of elements in breast cancer tissues might also be a consequence of the cancer. This can be understood in terms of the biochemical and histological differences between normal and cancerous breast tissues. Tumors, characterized by unregulated multiplication of cells, need an ever-increasing supply of essential nutrients including trace elements. This probably results in an increased vascularity of malignant tissues, which in turn leads to enhancement of elemental concentrations in tumors

  18. SU-E-T-168: Evaluation of Normal Tissue Damage in Head and Neck Cancer Treatments

    International Nuclear Information System (INIS)

    Ai, H; Zhang, H

    2014-01-01

    Purpose: To evaluate normal tissue toxicity in patients with head and neck cancer by calculating average survival fraction (SF) and equivalent uniform dose (EUD) for normal tissue cells. Methods: 20 patients with head and neck cancer were included in this study. IMRT plans were generated using EclipseTM treatment planning system by dosimetrist following clinical radiotherapy treatment guidelines. The average SF for three different normal tissue cells of each concerned structure can be calculated from dose spectrum acquired from differential dose volume histogram (DVH) using linear quadratic model. The three types of normal tissues include radiosensitive, moderately radiosensitive and radio-resistant that represents 70%, 50% and 30% survival fractions, respectively, for a 2-Gy open field. Finally, EUDs for three types of normal tissue of each structure were calculated from average SF. Results: The EUDs of the brainstem, spinal cord, parotid glands, brachial plexus and etc were calculated. Our analysis indicated that the brainstem can absorb as much as 14.3% of prescription dose to the tumor if the cell line is radiosensitive. In addition, as much as 16.1% and 18.3% of prescription dose were absorbed by the brainstem for moderately radiosensitive and radio-resistant cells, respectively. For the spinal cord, the EUDs reached up to 27.6%, 35.0% and 42.9% of prescribed dose for the three types of radiosensitivities respectively. Three types of normal cells for parotid glands can get up to 65.6%, 71.2% and 78.4% of prescription dose, respectively. The maximum EUDs of brachial plexsus were calculated as 75.4%, 76.4% and 76.7% of prescription for three types of normal cell lines. Conclusion: The results indicated that EUD can be used to quantify and evaluate the radiation damage to surrounding normal tissues. Large variation of normal tissue EUDs may come from variation of target volumes and radiation beam orientations among the patients

  19. Adipose Tissues Characteristics of Normal, Obesity, and Type 2 Diabetes in Uygurs Population

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2015-01-01

    Full Text Available Our results showed that, at the same BMI level, Uygurs have greater WHR values, abdominal visceral fat content, and diabetes risks than Kazaks. In addition, values of HDL-C in Uygur subjects were lower than those in Kazak subjects, and values of creatinine, uric acid, diastolic blood pressure, blood glucose, and fructosamine in Uygur male subjects were lower than those in Kazak male subjects. In contrast, systolic blood pressure values in Uygur subjects were greater than those in Kazak subjects, and blood glucose values were greater in Uygur female subjects than in Kazak female subjects. Additionally, in Uygurs, visceral adipose tissue expression levels of TBX1 and TCF21 were greater in obesity group than in normal and T2DM groups and lower in T2DM group than in normal group (P<0.01. The visceral adipose tissue expression levels of APN in normal group was greater than those in obesity and T2DM groups, and visceral adipose tissue expression levels of TNF-α and MCP-1 in normal group were lower than those in obesity and T2DM groups (P<0.01. In conclusion, T2DM in Uygurs was mainly associated with not only distribution of adipose tissue in body, but also change in metabolic activity and adipocytokines secretion of adipose tissue.

  20. Radioprotection of normal tissues in tumor-bearing mice by troxerutin

    International Nuclear Information System (INIS)

    Maurya, D.K.; Salvi, V.P.; Krishnan Nair, C.K.

    2004-01-01

    The flavanoid derivative troxerutin, used clinically for treating venous disorders, protected biomembranes and cellular DNA against the deleterious effects of γ-radiation. The peroxidation of lipids (measured as thiobarbituric acid-reacting substances, or TBARS) in rat liver microsomal and mitochondrial membranes resulting from γ-irradiation up to doses of 500 Gy in vitro was prevented by 0.2 mM troxerutin. The administration of troxerutin (175 mg/kg body weight) to tumor-bearing mice by intraperitoneal (ip) one hour prior to 4 Gy whole-body γ-irradiation significantly decreased the radiation-induced peroxidation of lipids in tissues such as liver and spleen, but there was no reduction of lipid peroxidation in tumor. The effect of troxerutin in γ-radiation-induced DNA strand breaks in different tissues of tumor-bearing mice was studied by comet assay. The administration of troxerutin to tumor-bearing animals protected cellular DNA against radiation-induced strand breaks. This was evidenced from decreases in comet tail length, tail moment, and percent of DNA in the tails in cells of normal tissues such as blood leukocytes and bone marrow, and these parameters were not altered in cells of fibrosarcoma tumor. The results revealed that troxerutin could preferentially protect normal tissues against radiation-induced damages in tumor-bearing animals. (author)

  1. Diffusion tensor trace mapping in normal adult brain using single-shot EPI technique: A methodological study of the aging brain

    International Nuclear Information System (INIS)

    Chen, Z.G.; Hindmarsh, T.; Li, T.Q.

    2001-01-01

    Purpose: To quantify age-related changes of the average diffusion coefficient value in normal adult brain using orientation-independent diffusion tensor trace mapping and to address the methodological influences on diffusion quantification. Material and Methods: Fifty-four normal subjects (aged 20-79 years) were studied on a 1.5-T whole-body MR medical unit using a diffusion-weighted single-shot echo-planar imaging technique. Orientation-independent diffusion tensor trace maps were constructed for each subject using diffusion-weighted MR measurements in four different directions using a tetrahedral gradient combination pattern. The global average (including cerebral spinal fluid) and the tissue average of diffusion coefficients in adult brains were determined by analyzing the diffusion coefficient distribution histogram for the entire brain. Methodological influences on the measured diffusion coefficient were also investigated by comparing the results obtained using different experimental settings. Results: Both global and tissue averages of the diffusion coefficient are significantly correlated with age (p<0.03). The global average of the diffusion coefficient increases 3% per decade after the age of 40, whereas the increase in the tissue average of diffusion coefficient is about 1% per decade. Experimental settings for self-diffusion measurements, such as data acquisition methods and number of b-values, can slightly influence the statistical distribution histogram of the diffusion tensor trace and its average value. Conclusion: Increased average diffusion coefficient in adult brains with aging are consistent with findings regarding structural changes in the brain that have been associated with aging. The study also demonstrates that it is desirable to use the same experimental parameters for diffusion coefficient quantification when comparing between different subjects and groups of interest

  2. Position and width of normal adult optic chiasm as measured in coronal MRI

    International Nuclear Information System (INIS)

    Kim, Myung Soon; Park, Jin Sook

    1994-01-01

    To evaluate the position and transverse dimension of the adult optic chiasm in normal Korean adult. The authors analysed 3D coronal volume images (TR/TE=30/13, flip angle=30 .deg. ) of 136 normal adult subjects without known visual abnormality. All MRI examinations were performed using a 0.5T system. MRI was reviewed retrospectively to determine the position (horizontal and tilted) of the potic chiosm and the transverse dimension of the optic chiasm was measured. Seventy- five (55%) of the 136 normal subjects had horizontal position, and sixty-one (45%) had tilted position. Thirty- eight (62%) of 61 with tilted position showed higher position on the right side, and twenty-three (38%) showed higher position on the side. The average transverse dimension(mean SD) was 15.2 ± 0.7mm in men and 14.6 ± 1.0mm in women. The difference of transverse dimension between men and women was statistically significant. Tilted position of the adult optic chiasm on coronal MRI was seen in approximately half of normal adults. The average of transverse dimension of normal optic chiasm was 15mm

  3. Epimorphic regeneration approach to tissue replacement in adult mammals

    Science.gov (United States)

    Urodeles and fetal mammals are capable of impressive epimorphic regeneration in a variety of tissues, whereas the typical default response to injury in adult mammals consists of inflammation and scar tissue formation. One component of epimorphic regeneration is the recruitment of resident progenitor...

  4. Radiologic study of patellofemoral congruence in normal adults

    International Nuclear Information System (INIS)

    Diedrichs, L.C.

    1986-01-01

    In order to establish the normal position of the patella, in relation to the intercondilar sulcus, we have evaluated 72 adults patients, making use of the FICAT view in axial radiographys at 30 0 : a simple and accurate technique adopted to measure the congrunce angle in the detection of sub-luxation of the patella. The value of +9 0 was used as the normal pattern for the maximal lateral position of the patella in the intercondilar sulcus. (Author) [pt

  5. Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

    Science.gov (United States)

    Hoffmann, Aswin L; Nahum, Alan E

    2013-10-07

    The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

  6. Comparison of normal adult and children brain SPECT imaging using statistical parametric mapping(SPM)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung Hoon; Yoon, Seok Nam; Joh, Chul Woo; Lee, Dong Soo [Ajou University School of Medicine, Suwon (Korea, Republic of); Lee, Jae Sung [Seoul national University College of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    This study compared rCBF pattern in normal adult and normal children using statistical parametric mapping (SPM). The purpose of this study was to determine distribution pattern not seen visual analysis in both groups. Tc-99m ECD brain SPECT was performed in 12 normal adults (M:F=11:1, average age 35 year old) and 6 normal control children (M:F=4:2, 10.5{+-}3.1y) who visited psychiatry clinic to evaluate ADHD. Their brain SPECT revealed normal rCBF pattern in visual analysis and they were diagnosed clinically normal. Using SPM method, we compared normal adult group's SPECT images with those of 6 normal children subjects and measured the extent of the area with significant hypoperfusion and hyperperfusion (p<0.001, extent threshold=16). The areas of both angnlar gyrus, both postcentral gyrus, both superior frontal gyrus, and both superior parietal lobe showed significant hyperperfusion in normal adult group compared with normal children group. The areas of left amygdala gyrus, brain stem, both cerebellum, left globus pallidus, both hippocampal formations, both parahippocampal gyrus, both thalamus, both uncus, both lateral and medial occipitotemporal gyrus revealed significantly hyperperfusion in the children. These results demonstrated that SPM can say more precise anatomical area difference not seen visual analysis.

  7. Comparison of normal adult and children brain SPECT imaging using statistical parametric mapping(SPM)

    International Nuclear Information System (INIS)

    Lee, Myoung Hoon; Yoon, Seok Nam; Joh, Chul Woo; Lee, Dong Soo; Lee, Jae Sung

    2002-01-01

    This study compared rCBF pattern in normal adult and normal children using statistical parametric mapping (SPM). The purpose of this study was to determine distribution pattern not seen visual analysis in both groups. Tc-99m ECD brain SPECT was performed in 12 normal adults (M:F=11:1, average age 35 year old) and 6 normal control children (M:F=4:2, 10.5±3.1y) who visited psychiatry clinic to evaluate ADHD. Their brain SPECT revealed normal rCBF pattern in visual analysis and they were diagnosed clinically normal. Using SPM method, we compared normal adult group's SPECT images with those of 6 normal children subjects and measured the extent of the area with significant hypoperfusion and hyperperfusion (p<0.001, extent threshold=16). The areas of both angnlar gyrus, both postcentral gyrus, both superior frontal gyrus, and both superior parietal lobe showed significant hyperperfusion in normal adult group compared with normal children group. The areas of left amygdala gyrus, brain stem, both cerebellum, left globus pallidus, both hippocampal formations, both parahippocampal gyrus, both thalamus, both uncus, both lateral and medial occipitotemporal gyrus revealed significantly hyperperfusion in the children. These results demonstrated that SPM can say more precise anatomical area difference not seen visual analysis

  8. Compton scattering spectrum as a source of information of normal and neoplastic breast tissues' composition

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, 14040-901 Sao Paulo (Brazil)

    2012-07-15

    In this work we measured X-ray scatter spectra from normal and neoplastic breast tissues using photon energy of 17.44 keV and a scattering angle of 90 Degree-Sign , in order to study the shape (FWHM) of the Compton peaks. The obtained results for FWHM were discussed in terms of composition and histological characteristics of each tissue type. The statistical analysis shows that the distribution of FWHM of normal adipose breast tissue clearly differs from all other investigated tissues. Comparison between experimental values of FWHM and effective atomic number revealed a strong correlation between them, showing that the FWHM values can be used to provide information about elemental composition of the tissues. - Highlights: Black-Right-Pointing-Pointer X-ray scatter spectra from normal and neoplastic breast tissues were measured. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak was related with elemental composition and characteristics of each tissue type. Black-Right-Pointing-Pointer A statistical hypothesis test showed clear differences between normal and neoplastic breast tissues. Black-Right-Pointing-Pointer There is a strong correlation between experimental values of FWHM and effective atomic number. Black-Right-Pointing-Pointer Shape (FWHM) of Compton peak can be used to provide information about elemental composition of the tissues.

  9. Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer

    International Nuclear Information System (INIS)

    Ananthanarayanan, Vijayalakshmi; Deaton, Ryan J; Yang, Ximing J; Pins, Michael R; Gann, Peter H

    2006-01-01

    Molecular markers identifying alterations in proliferation and apoptotic pathways could be particularly important in characterizing high-risk normal or pre-neoplastic tissue. We evaluated the following markers: Ki67, Minichromosome Maintenance Protein-2 (Mcm-2), activated caspase-3 (a-casp3) and Bcl-2 to determine if they showed differential expression across progressive degrees of intraepithelial neoplasia and cancer in the prostate. To identify field effects, we also evaluated whether high-risk expression patterns in normal tissue were more common in prostates containing cancer compared to those without cancer (supernormal), and in histologically normal glands adjacent to a cancer focus as opposed to equivalent glands that were more distant. The aforementioned markers were studied in 13 radical prostatectomy (RP) and 6 cystoprostatectomy (CP) specimens. Tissue compartments representing normal, low grade prostatic intraepithelial neoplasia (LGPIN), high grade prostatic intraepithelial neoplasia (HGPIN), as well as different grades of cancer were mapped on H&E slides and adjacent sections were analyzed using immunohistochemistry. Normal glands within 1 mm distance of a tumor focus and glands beyond 5 mm were considered 'near' and 'far', respectively. Randomly selected nuclei and 40 × fields were scored by a single observer; basal and luminal epithelial layers were scored separately. Both Ki-67 and Mcm-2 showed an upward trend from normal tissue through HGPIN and cancer with a shift in proliferation from basal to luminal compartment. Activated caspase-3 showed a significant decrease in HGPIN and cancer compartments. Supernormal glands had significantly lower proliferation indices and higher a-casp3 expression compared to normal glands. 'Near' normal glands had higher Mcm-2 indices compared to 'far' glands; however, they also had higher a-casp3 expression. Bcl-2, which varied minimally in normal tissue, did not show any trend

  10. Psychosocial Functioning of Adult Epileptic and MS Patients and Adult Normal Controls on the WPSI.

    Science.gov (United States)

    Tan, Siang-Yang

    1986-01-01

    Psychosocial functioning of adult epileptic outpatients as assessed by the Washington Psychosocial Seizure Inventory (WPSI) was compared to that of adult multiple sclerosis (MS) outpatients and normal subjects. When only valid WPSI profiles were considered, the only significant finding was that the epilepsy group and the MS group had more…

  11. Pattern of somatostatin receptors expression in normal and bladder cancer tissue samples.

    Science.gov (United States)

    Karavitakis, Markos; Msaouel, Pavlos; Michalopoulos, Vassilis; Koutsilieris, Michael

    2014-06-01

    Known risks factors for bladder cancer progression and recurrence are limited regarding their prognostic ability. Therefore identification of molecular determinants of disease progression could provide with more specific prognostic information and could be translated into new approaches for biomarker development. In the present study we evaluated, the expression patterns of somatostatin receptors 1-5 (SSTRs) in normal and tumor bladder tissues. The expression of SSTR1-5 was characterized in 45 normal and bladder cancer tissue samples using reverse transcriptase-polymerase chain reaction (RT-PCR). SSTR1 was expressed in 24 samples, SSTR2 in 15, SSTR3 in 23, SSTR4 in 16 and SSTR5 in all but one sample. Bladder cancer tissue samples expressed lower levels of SSTR3. Co-expression of SSTRs was associated with superficial disease. Our results demonstrate, for the first time, that there is expression of SSTR in normal and bladder cancer urothelium. Further studies are required to evaluate the prognostic and therapeutic significance of these findings. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Radioprotection of normal tissues of the mouse by hypoxic breathing

    International Nuclear Information System (INIS)

    Stevens, G.N.; Joiner, B.; Denekamp, J.

    1989-01-01

    Hypoxic breathing during irradiation has been advocated as a therapeutic modality, to increase the efficacy of radiotherapy. In this form of treatment, the total and daily X-ray dose is increased by a factor of 1.25, on the assumption that all normal tissues in the beam will be protected to a similar extent by breathing gas containing a reduced oxygen concentration (usually 10%). To test this concept, we have determined the effect of varying the inspired oxygen tension on the radiosensitivity of 3 normal tissues in the mouse (kidney, jejunum and skin), and have compared these results with data from the literature for mouse lung. Reduction of the inspired oxygen tension from 21% (air) to 7-8% led to much greater radioprotection of skin (protection factor 1.37) than of lung (1.09). Protection factors for jejunum and kidney were 1.16 and 1.36 respectively. The results show that the extent of radioprotection afforded by hypoxic breathing is tissue dependent, and that great care must be taken clinically in choosing the increased radiation dose to be used in conjunction with hypoxic breathing

  13. Normal tissue complication probability for salivary glands

    International Nuclear Information System (INIS)

    Rana, B.S.

    2008-01-01

    The purpose of radiotherapy is to make a profitable balance between the morbidity (due to side effects of radiation) and cure of malignancy. To achieve this, one needs to know the relation between NTCP (normal tissue complication probability) and various treatment variables of a schedule viz. daily dose, duration of treatment, total dose and fractionation along with tissue conditions. Prospective studies require that a large number of patients be treated with varied schedule parameters and a statistically acceptable number of patients develop complications so that a true relation between NTCP and a particular variable is established. In this study Salivary Glands Complications have been considered. The cases treated in 60 Co teletherapy machine during the period 1994 to 2002 were analyzed and the clinicians judgement in ascertaining the end points was the only means of observations. The only end points were early and late xerestomia which were considered for NTCP evaluations for a period of 5 years

  14. Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

    International Nuclear Information System (INIS)

    Zhao, Q L; Guo, Z Y; Wei, H J; Guo, X; Zhong, H Q; Li, L Q; Si, J L; Yang, H Q; Xie, S S; Wu, G Y; Li, X Y

    2011-01-01

    We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10 -5 cm/s in normal esophagus and (2.45±0.06)×10 -5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G

  15. Quantifying glucose permeability and enhanced light penetration in ex vivo human normal and cancerous esophagus tissues with optical coherence tomography

    Science.gov (United States)

    Zhao, Q. L.; Si, J. L.; Guo, Z. Y.; Wei, H. J.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Li, X. Y.; Guo, X.; Zhong, H. Q.; Li, L. Q.

    2011-01-01

    We report our pilot results on quantification of glucose (G) diffusion permeability in human normal esophagus and ESCC tissues in vitro by using OCT technique. The permeability coefficient of 40% aqueous solution of G was found to be (1.74±0.04)×10-5 cm/s in normal esophagus and (2.45±0.06)×10-5 cm/s in ESCC tissues. The results from this study indicate that ESCC tissues had a higher permeability coefficient compared to normal esophageal tissues, and the light penetration depths gradually increase with the increase of applied topically with G time for the normal esophageal and ESCC tissues. The results indicate that the permeability coefficient of G in cancer tissues was 1.41-fold than that in normal tissues, and the light penetration depth for the ESCC tissues is significantly smaller than that of normal esophagus tissues in the same time range. These results demonstrate that the optical clearing of normal and cancer esophagus tissues are improved after application of G.

  16. Radiotherapy- and chemotherapy-induced normal tissue damage. The role of cytokines and adhesion molecules

    International Nuclear Information System (INIS)

    Plevova, P.

    2002-01-01

    Background. Ionising radiation and cytostatic agents used in cancer therapy exert damaging effects on normal tissues and induce a complex response at the cellular and molecular levels. Cytokines and adhesion molecules are involved in this response. Methods. Published data on the given topic have been reviewed. Results and conclusions. Various cytokines and adhesion molecules, including tumor necrosis factor α, interleukins- 1,-2,-4, and -6, interferon γ, granulocyte macrophage- and macrophage- colony stimulating factors, transforming growth factor β, platelet-derived growth factor, insulin-like growth factor I, fibroblast and epidermal growth factors, platelet-activating factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E- and P-selectins are involved in the response of normal tissues to ionizing radiation- and chemotherapy- induced normal tissues damage and are co-responsible for some side effects of these treatment modalities, including fever, anorexia and fatigue, suppression of hematopoiesis, both acute and late local tissue response. (author)

  17. [Quantification of acetabular coverage in normal adult].

    Science.gov (United States)

    Lin, R M; Yang, C Y; Yu, C Y; Yang, C R; Chang, G L; Chou, Y L

    1991-03-01

    Quantification of acetabular coverage is important and can be expressed by superimposition of cartilage tracings on the maximum cross-sectional area of the femoral head. A practical Autolisp program on PC AutoCAD has been developed by us to quantify the acetabular coverage through numerical expression of the images of computed tomography. Thirty adults (60 hips) with normal center-edge angle and acetabular index in plain X ray were randomly selected for serial drops. These slices were prepared with a fixed coordination and in continuous sections of 5 mm in thickness. The contours of the cartilage of each section were digitized into a PC computer and processed by AutoCAD programs to quantify and characterize the acetabular coverage of normal and dysplastic adult hips. We found that a total coverage ratio of greater than 80%, an anterior coverage ratio of greater than 75% and a posterior coverage ratio of greater than 80% can be categorized in a normal group. Polar edge distance is a good indicator for the evaluation of preoperative and postoperative coverage conditions. For standardization and evaluation of acetabular coverage, the most suitable parameters are the total coverage ratio, anterior coverage ratio, posterior coverage ratio and polar edge distance. However, medial coverage and lateral coverage ratios are indispensable in cases of dysplastic hip because variations between them are so great that acetabuloplasty may be impossible. This program can also be used to classify precisely the type of dysplastic hip.

  18. SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D [M.D. Anderson Cancer Center, Houston, TX (United States)

    2015-06-15

    Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted.

  19. SU-E-J-212: MR Diffusion Tensor Imaging for Assessment of Tumor and Normal Brain Tissue Responses of Juvenile Pilocytic Astrocytoma Treated by Proton Therapy

    International Nuclear Information System (INIS)

    Hou, P; Park, P; Li, H; Zhu, X; Mahajan, A; Grosshans, D

    2015-01-01

    Purpose: Diffusion tensor imaging (DTI) can measure molecular mobility at the cellular level, quantified by the apparent diffusion coefficient (ADC). DTI may also reveal axonal fiber directional information in the white matter, quantified by the fractional anisotropy (FA). Juvenile pilocytic astrocytoma (JPA) is a rare brain tumor that occurs in children and young adults. Proton therapy (PT) is increasingly used in the treatment of pediatric brain tumors including JPA. However, the response of both tumors and normal tissues to PT is currently under investigation. We report tumor and normal brain tissue responses for a pediatric case of JPA treated with PT assessed using DTI. Methods: A ten year old male with JPA of the left thalamus received passive scattered PT to a dose of 50.4 Gy (RBE) in 28 fractions. Post PT, the patient has been followed up in seven years. At each follow up, MRI imaging including DTI was performed to assess response. MR images were registered to the treatment planning CT and the GTV mapped onto each MRI. The GTV contour was then mirrored to the right side of brain through the patient’s middle line to represent normal brain tissue. ADC and FA were measured within the ROIs. Results: Proton therapy can completely spare contra lateral brain while the target volume received full prescribed dose. From a series of MRI ADC images before and after PT at different follow ups, the enhancement corresponding to GTV had nearly disappeared more than 2 years after PT. Both ADC and FA demonstrate that contralateral normal brain tissue were not affect by PT and the tumor volume reverted to normal ADC and FA values. Conclusion: DTI allowed quantitative evaluation of tumor and normal brain tissue responses to PT. Further study in a larger cohort is warranted

  20. Cell-surface glycoproteins of human sarcomas: differential expression in normal and malignant tissues and cultured cells

    International Nuclear Information System (INIS)

    Rettig, W.F.; Garin-Chesa, P.; Beresford, H.R.; Oettgen, H.F.; Melamed, M.R.; Old, L.J.

    1988-01-01

    Normal differentiation and malignant transformation of human cells are characterized by specific changes in surface antigen phenotype. In the present study, the authors have defined six cell-surface antigens of human sarcomas and normal mesenchymal cells, by using mixed hemadsorption assays and immunochemical methods for the analysis of cultured cells and immunohistochemical staining for the analysis of normal tissues and > 200 tumor specimens. Differential patterns of F19, F24, G171, G253, S5, and Thy-1 antigen expression were found to characterize (i) subsets of cultured sarcoma cell lines, (ii) cultured fibroblasts derived from various organs, (iii) normal resting and activated mesenchymal tissues, and (iv) sarcoma and nonmesenchymal tumor tissues. These results provide a basic surface antigenic map for cultured mesenchymal cells and mesenchymal tissues and permit the classification of human sarcomas according to their antigenic phenotypes

  1. The adult brain tissue response to hollow fiber membranes of varying surface architecture with or without cotransplanted cells

    Science.gov (United States)

    Zhang, Ning

    A variety of biomaterials have been chronically implanted into the central nervous system (CNS) for repair or therapeutic purposes. Regardless of the application, chronic implantation of materials into the CNS induces injury and elicits a wound healing response, eventually leading to the formation of a dense extracellular matrix (ECM)-rich scar tissue that is associated with the segregation of implanted materials from the surrounding normal tissue. Often this reaction results in impaired performance of indwelling CNS devices. In order to enhance the performance of biomaterial-based implantable devices in the CNS, this thesis investigated whether adult brain tissue response to implanted biomaterials could be manipulated by changing biomaterial surface properties or further by utilizing the biology of co-transplanted cells. Specifically, the adult rat brain tissue response to chronically implanted poly(acrylonitrile-vinylchloride) (PAN-PVC) hollow fiber membranes (HFMs) of varying surface architecture were examined temporally at 2, 4, and 12 weeks postimplantation. Significant differences were discovered in the brain tissue response to the PAN-PVC HFMs of varying surface architecture at 4 and 12 weeks. To extend this work, whether the soluble factors derived from a co-transplanted cellular component further affect the brain tissue response to an implanted HFM in a significant way was critically exploited. The cells used were astrocytes, whose ability to influence scar formation process following CNS injury by physical contact with the host tissue had been documented in the literature. Data indicated for the first time that astrocyte-derived soluble factors ameliorate the adult brain tissue reactivity toward HFM implants in an age-dependent manner. While immature astrocytes secreted soluble factors that suppressed the brain tissue reactivity around the implants, mature astrocytes secreted factors that enhanced the gliotic response. These findings prove the feasibility

  2. Correlation study of trace metals in malignant and normal breast tissues by AAS technique

    International Nuclear Information System (INIS)

    Rahman, S.

    2012-01-01

    The study reports the application of atomic absorption spectrophotometry (AAS) for quantification of Fe, Cu and Zn in forty one formalin-fixed biopsy breast carcinoma tissue and adjoining fifteen normal tissue samples. These tissues samples were of category two breast carcinoma patients and of normal subjects. The qualitative comparison between the elements levels measured in the two types of specimens suggests significant elevation of these metals in the histopathological samples of carcinoma tissue. The samples were collected from women aged 19-51 years. Most of the patients belong to urban areas of Pakistan and middle to high socioeconomic status with the exception of few. Findings of study depicts that these elements have an important role in the initiation and development of carcinoma as consistent pattern of elevation for Fe, Cu and Zn was observed. The results showed the excessive accumulation of Fe (166.9 mg/L) in tissue samples of breast carcinoma patients (p < 0.01) than that in normal tissues samples (23.5 mg/L). In order to validate our method of analysis certified reference material Muscle Tissue Lyophilised (IAEA) MA-M-2/TM was analyzed for Fe, Cu and Zn. Determined concentrations were in good agreement with certified levels. The concentration distribution of trace elements Cu, Zn and Fe measured in the malignant tissues were found to be higher when compared to benign tissues, indicating the involvement of these metals in the breast malignancy. Results also indicate that excess iron may play a role in breast carcinogenesis. (Orig./A.B.)

  3. Utility of Normal Tissue-to-Tumor {alpha}/{beta} Ratio When Evaluating Isodoses of Isoeffective Radiation Therapy Treatment Plans

    Energy Technology Data Exchange (ETDEWEB)

    Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri (United States); Jin Jianyue [Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan (United States); Chang, Albert J. [Department of Radiation Oncology, University of California, San Francisco, California (United States); Ten Haken, Randall K. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)

    2013-01-01

    Purpose: To achieve a better understanding of the effect of the number of fractions on normal tissue sparing for equivalent tumor control in radiation therapy plans by using equivalent biologically effective dose (BED) isoeffect calculations. Methods and Materials: The simple linear quadratic (LQ) model was assumed to be valid up to 10 Gy per fraction. Using the model, we formulated a well-known mathematical equality for the tumor prescription dose and probed and solved a second mathematical problem for normal tissue isoeffect. That is, for a given arbitrary relative isodose distribution (treatment plan in percentages), 2 isoeffective tumor treatment regimens (N fractions of the dose D and n fractions of the dose d) were denoted, which resulted in the same BED (corresponding to 100% prescription isodose). Given these situations, the LQ model was further exploited to mathematically establish a unique relative isodose level, z (%), for the same arbitrary treatment plan, where the BED to normal tissues was also isoeffective for both fractionation regimens. Results: For the previously stated problem, the relative isodose level z (%), where the BEDs to the normal tissue were also equal, was defined by the normal tissue {alpha}/{beta} ratio divided by the tumor {alpha}/{beta} times 100%. Fewer fractions offers a therapeutic advantage for those portions of the normal tissue located outside the isodose surface, z, whereas more fractions offer a therapeutic advantage for those portions of the normal tissue within the isodose surface, z. Conclusions: Relative isodose-based treatment plan evaluations may be useful for comparing isoeffective tumor regimens in terms of normal tissue effects. Regions of tissues that would benefit from hypofractionation or standard fractionation can be identified.

  4. Genetic markers for prediction of normal tissue toxicity after radiotherapy

    DEFF Research Database (Denmark)

    Alsner, Jan; Andreassen, Christian Nicolaj; Overgaard, Jens

    2008-01-01

    During the last decade, a number of studies have supported the hypothesis that there is an important genetic component to the observed interpatient variability in normal tissue toxicity after radiotherapy. This review summarizes the candidate gene association studies published so far on the risk...

  5. EPR study of the reactions of tumour and normal tissues under ionizing radiation

    International Nuclear Information System (INIS)

    Rikhireva, G.T.; Pulatova, M.K.; Turganov, M.M.; Pal'mina, N.P.; Burlakova, E.B.

    1978-01-01

    Data on the EPR spectrum characteristics of irradiated tissues of tumour-free animals and animals with tumour are presented. Mice of the Csub(3)Hsub(A) line were used in the experiments. Hepatoma was subcutaneously transplanted with the suspension of tumour tissue reduced to fragments. Animals were killed in 6-8 days after transplantation and in the case of tumour-free animals liver was immediately isolated while in the case of animals with tumour isolated were liver and tumour. Tissues cut with scissors were frozen in liquid nitrogen. Tissue samples were exposed to 60 Co at 1 Mrad dose and -196 deg C. On the base of the data it has been concluded: firstly, there are differences between the EPR spectra of normal and tumour tissue samples irradiated at -196 deg C. Asymmetryc signal with Δ H=Ge and g=2.0005 (''tumour signal'') is typical only for the EPR spectra of tumour and liver tissues of the animal with tumour. Thus, in the -author's opinion, irradiation use turns out to be useful for detecting the difference between the normal and tumour tissues. Secondly, ''tumour signal'' intensity changes after ionol incorporation into animal organism, used as a modificator of tissue sensitivity to the irradiation effect

  6. Accumulation of DNA Double-Strand Breaks in Normal Tissues After Fractionated Irradiation

    International Nuclear Information System (INIS)

    Ruebe, Claudia E.; Fricke, Andreas; Wendorf, Juliane; Stuetzel, Annika; Kuehne, Martin; Ong, Mei Fang; Lipp, Peter; Ruebe, Christian

    2010-01-01

    Purpose: There is increasing evidence that genetic factors regulating the recognition and/or repair of DNA double-strand breaks (DSBs) are responsible for differences in radiosensitivity among patients. Genetically defined DSB repair capacities are supposed to determine patients' individual susceptibility to develop adverse normal tissue reactions after radiotherapy. In a preclinical murine model, we analyzed the impact of different DSB repair capacities on the cumulative DNA damage in normal tissues during the course of fractionated irradiation. Material and Methods: Different strains of mice with defined genetic backgrounds (SCID -/- homozygous, ATM -/- homozygous, ATM +/- heterozygous, and ATM +/+ wild-type mice) were subjected to single (2 Gy) or fractionated irradiation (5 x 2 Gy). By enumerating γH2AX foci, the formation and rejoining of DSBs were analyzed in organs representative of both early-responding (small intestine) and late-responding tissues (lung, kidney, and heart). Results: In repair-deficient SCID -/- and ATM -/- homozygous mice, large proportions of radiation-induced DSBs remained unrepaired after each fraction, leading to the pronounced accumulation of residual DNA damage after fractionated irradiation, similarly visible in early- and late-responding tissues. The slight DSB repair impairment of ATM +/- heterozygous mice was not detectable after single-dose irradiation but resulted in a significant increase in unrepaired DSBs during the fractionated irradiation scheme. Conclusions: Radiation-induced DSBs accumulate similarly in acute- and late-responding tissues during fractionated irradiation, whereas the whole extent of residual DNA damage depends decisively on the underlying genetically defined DSB repair capacity. Moreover, our data indicate that even minor impairments in DSB repair lead to exceeding DNA damage accumulation during fractionated irradiation and thus may have a significant impact on normal tissue responses in clinical

  7. The effect of irradiation on function in self-renewing normal tissues with differing proliferative organisation

    International Nuclear Information System (INIS)

    Wheldon, T.E.; Michalowski, A.S.

    1982-01-01

    The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as ''hierarchical'' (like haemopoietic tissues) or as ''flexible'' (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the ''flexible'' or ''F-type'' category display a variety of novel radiobiological properties, different from those of the more familiar ''hierarchical'' or ''H-type'' tissues. The ''F-type'' responses are strongly influenced by radiation-sterilised (''doomed'') cells, and is is suggested that the role of ''doomed'' cells has been undervalued relative to that of clonogenic survivors. Since ''F-type'' tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy. (author)

  8. Prodrugs designed to discriminate pathological (tumour) and physiological (normal tissue) hypoxia

    International Nuclear Information System (INIS)

    Wilson, W.R.; Patterson, A.V.

    2003-01-01

    There is now abundant evidence that hypoxic contributes to treatment failure in radiation therapy. As a target for therapeutic intervention, hypoxia is especially attractive because it is a common feature of most human tumours and therefore a potential 'pan target' across many tumour types. However, attempts to exploit hypoxia face the problem that oxygen concentrations in some normal tissues are also heterogeneous and that O 2 distributions in tumours and normal tissues overlap. Simply adjusting the K value (O 2 concentration for 50% inhibition of activation) does not provide a satisfactory solution. Bioreductive drugs like tirapazamine with high K values are activated significantly in several normal tissues, while nitro compounds and quinones with low K values spare the hypoxic tumour cells at 'intermediate' O 2 tensions (1-10 mM O 2 ) which are considered to be major contributors to tumour radioresistance. A potential strategy for overcoming this dilemma is to design prodrugs that are activated only at very low K values, but give relatively stable cytotoxic metabolites capable of diffusing to cells at higher O 2 concentrations. This approach redefines the therapeutic target as cells adjacent to zones of pathological hypoxia ( 2 ), providing discrimination from physiological hypoxia in normal tissues. Detecting bioreductive prodrugs capable of providing bystander killing of this kind is not straightforward. We have adapted a multicellular layer (MCL) co-culture model for quantifying bystander effects in GDEPT (Wilson et al., Cancer Res., 62: 1425-1432, 2002), and have used this to measure bystander effects of hypoxia-activated prodrugs. This model uses differences in metabolic activation of bioreductive drugs between A459 cell lines with low and high cytochrome P450 reductase activity, rather than O 2 gradients, to effect localised prodrug activation. It shows that TPZ and the nitroimidazole RSU-1069 have little or no bystander effect, but that dinitrobenzamide

  9. Pathology, physiologic parameters, tissue contaminants, and tissue thiamine in morbid and healthy central Florida adult American alligators (Alligator mississippiensis)

    Science.gov (United States)

    Honeyfield, D.C.; Ross, J.P.; Carbonneau, D.A.; Terrell, S.P.; Woodward, A.R.; Schoeb, T.R.; Perceval, H.F.; Hinterkopf, J.P.

    2008-01-01

    An investigation of adult alligator (Alligator mississippiensis) mortalities in Lake Griffin, central Florida, was conducted from 1998-2004. Alligator mortality was highest in the months of April and May and annual death count peaked in 2000. Bacterial pathogens, heavy metals, and pesticides were not linked with the mortalities. Blood chemistry did not point to any clinical diagnosis, although differences between impaired and normal animals were noted. Captured alligators with signs of neurologic impairment displayed unresponsive and uncoordinated behavior. Three of 21 impaired Lake Griffin alligators were found to have neural lesions characteristic of thiamine deficiency in the telencephalon, particularly the dorsal ventricular ridge. In some cases, lesions were found in the thalamus, and parts of the midbrain. Liver and muscle tissue concentrations of thiamine (vitamin B"1) were lowest in impaired Lake Griffin alligators when compared to unimpaired alligators or to alligators from Lake Woodruff. The consumption of thiaminase-positive gizzard shad (Dorosoma cepedianum) is thought to have been the cause of the low tissue thiamine and resulting mortalities. ?? Wildlife Disease Association 2008.

  10. Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.

    Science.gov (United States)

    Robinson, Paulette M; Smith, Tyler S; Patel, Dilan; Dave, Meera; Lewin, Alfred S; Pi, Liya; Scott, Edward W; Tuli, Sonal S; Schultz, Gregory S

    2012-12-13

    Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is up-regulated by TGF-β and mediates most key fibrotic actions of TGF-β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. This study addresses the role of proteolytic processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-β, normal ocular tissues and wounded corneas. Proteolytic processing of CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas were examined by Western blot. The identity of a 21-kDa band was determined by tandem mass spectrometry, and possible alternative splice variants of CTGF were assessed by 5' Rapid Amplification of cDNA Ends (RACE). HCF stimulated by TGF-β contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13 kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of CTGF that contained the middle "hinge" region of CTGF. Fragmentation of recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and trace amounts of 38-kDa CTGF, although no alternative transcripts were detected. All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer ablated rat corneas, peaking on day 11. Proteolytic processing of 38-kDa CTGF occurs during corneal wound healing, which may have important implications in regulation of corneal scar formation.

  11. Stem Cell Therapy to Reduce Radiation-Induced Normal Tissue Damage

    NARCIS (Netherlands)

    Coppes, Rob P.; van der Goot, Annemieke; Lombaert, Isabelle M. A.

    Normal tissue damage after radiotherapy is still a major problem in cancer treatment. Stem cell therapy may provide a means to reduce radiation-induced side effects and improve the quality of life of patients. This review discusses the current status in stem cell research with respect to their

  12. Responses of some normal tissues to low doses of γ-radiation

    International Nuclear Information System (INIS)

    Withers, H.R.

    1975-01-01

    The response of four normal tissues to low doses of γ-radiation was measured in mice using three indirect methods. The survival curves for cells of the tissues studied (colon, jejunum, testis and haemoleucopoietic system) may be exponential over an uncertain dose range (from zero to between 100 to 230 rad), the slope being about one third of that in the high-dose region. Some of the uncertainties in the data probably reflect variations in age-density distribution. (author)

  13. Normal isometric strength of rotator cuff muscles in adults

    OpenAIRE

    Chezar, A.; Berkovitch, Y.; Haddad, M.; Keren, Y.; Soudry, M.; Rosenberg, N.

    2013-01-01

    Objectives The most prevalent disorders of the shoulder are related to the muscles of rotator cuff. In order to develop a mechanical method for the evaluation of the rotator cuff muscles, we created a database of isometric force generation by the rotator cuff muscles in normal adult population. We hypothesised the existence of variations according to age, gender and dominancy of limb. Methods A total of 400 healthy adult volunteers were tested, classified into groups of 50 men and women for e...

  14. Discriminant analysis of normal and malignant breast tissue based upon INAA investigation of elemental concentration

    International Nuclear Information System (INIS)

    Kwanhoong Ng; Senghuat Ong; Bradley, D.A.; Laimeng Looi

    1997-01-01

    Discriminant analysis of six trace element concentrations measured by instrumental neutron activation analysis (INAA) in 26 paired-samples of malignant and histologically normal human breast tissues shows the technique to be a potentially valuable clinical tool for making malignant-normal classification. Nonparametric discriminant analysis is performed for the data obtained. Linear and quadratic discriminant analyses are also carried out for comparison. For this data set a formal analysis shows that the elements which may be useful in distinguishing between malignant and normal tissues are Ca, Rb and Br, providing correct classification for 24 out of 26 normal samples and 22 out of 26 malignant samples. (Author)

  15. Review of RBE values of 15 MeV neutrons for effects on normal tissues

    NARCIS (Netherlands)

    Broerse, J.J.

    1974-01-01

    Values of the relative biological effectiveness (RBE) of fast neutrons for effect on normal tissue depend not only on the neutron energy and the dose, but also on the type of tissue irradiated. Values of the RBE of 15 MeV neutrons are reviewed for rapidly proliferating rodent tissue, such as mouse

  16. Options and pitfalls of normal tissues complication probability models

    International Nuclear Information System (INIS)

    Dorr, Wolfgang

    2011-01-01

    Full text: Technological improvements in the physical administration of radiotherapy have led to increasing conformation of the treatment volume (TV) with the planning target volume (PTV) and of the irradiated volume (IV) with the TV. In this process of improvement of the physical quality of radiotherapy, the total volumes of organs at risk exposed to significant doses have significantly decreased, resulting in increased inhomogeneities in the dose distributions within these organs. This has resulted in a need to identify and quantify volume effects in different normal tissues. Today, irradiated volume today must be considered a 6t h 'R' of radiotherapy, in addition to the 5 'Rs' defined by Withers and Steel in the mid/end 1980 s. The current status of knowledge of these volume effects has recently been summarized for many organs and tissues by the QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) initiative [Int. J. Radiat. Oncol. BioI. Phys. 76 (3) Suppl., 2010]. However, the concept of using dose-volume histogram parameters as a basis for dose constraints, even without applying any models for normal tissue complication probabilities (NTCP), is based on (some) assumptions that are not met in clinical routine treatment planning. First, and most important, dose-volume histogram (DVH) parameters are usually derived from a single, 'snap-shot' CT-scan, without considering physiological (urinary bladder, intestine) or radiation induced (edema, patient weight loss) changes during radiotherapy. Also, individual variations, or different institutional strategies of delineating organs at risk are rarely considered. Moreover, the reduction of the 3-dimentional dose distribution into a '2dimensl' DVH parameter implies that the localization of the dose within an organ is irrelevant-there are ample examples that this assumption is not justified. Routinely used dose constraints also do not take into account that the residual function of an organ may be

  17. Radiobiology of normal tissue. Scientific advances and perspectives; Strahlenbiologie der Normalgewebe. Wissenschaftliche Fortschritte und Perspektiven

    Energy Technology Data Exchange (ETDEWEB)

    Doerr, W. [Medizinische Univ. Wien (Austria). Universitaetsklinik fuer Strahlentherapie; Medizinische Univ. Wien (Austria). Universitaetsklinik fuer Radioonkologie; Medizinische Univ. Wien (Austria). Christian Doppler Labor fuer Medizinische Strahlenforschung fuer die Radioonkologie; Herskind, C. [Universitaetsmedizin Mannheim, Heidelberg Univ., Mannheim (Germany). Labor fuer Zellulaere und Molekulare Radioonkologie

    2012-11-15

    Radiotherapy involves always the exposure of normal tissue, resulting in an excepted risk of complications. The side effect rate is therefore the compromise between optimized tumor doses and the side effect minimization. The report covers the issues target cell hypothesis and the consequences, new aspect of the pathogenesis of normal issue reactions and strategies of targeted reduction of normal tissue effects. The complexity of the radiobiological processes, the specificity and action mechanisms, the mutual interactions of chemical and radiological processes require further coordinated radiobiological research in the future.

  18. Quantitation of two endogenous lactose-inhibitable lectins in embryonic and adult chicken tissues

    International Nuclear Information System (INIS)

    Beyer, E.C.; Barondes, S.H.

    1982-01-01

    Two lactose-binding lectins from chicken tissues, chicken-lactose-lectin-I (CLL-I) and chicken-lactose-lectin-II (CLL-II) were quantified with a radioimmunoassay in extracts of a number of developing and adult chicken tissues. Both lectins could be measured in the same extract without separation, because they showed no significant immunological cross- reactivity. Many embryonic and adult tissues, including brain, heart, intestine, kidney, liver, lung, muscle, pancreas, and spleen, contained one or both lectins, although their concentrations differed markedly. For example, embryonic muscle, the richest source of CLL-I contained only traces of CLL-II whereas embryonic kidney, a very rich source of CLL-II contained substantial CLL-I. In both muscle and kidney, lectin levels in adulthood were much lower than in the embryonic state. In contrast, CLL-I in liver and CLL-II in intestine were 10-fold to 30-fold more concentrated in the adult than in the 15-d embryo. CLL-I and CLL-II from several tissues were purified by affinity chromatography and their identity in the various tissues was confirmed by polyacrylamide gel electrophoresis, isoelectric focusing, and peptide mapping. The results suggest that these lectins might have different functions in the many developing and adult tissues in which they are found

  19. Mathematical model of normal tissue injury in telegammatherapy

    International Nuclear Information System (INIS)

    Belov, S.A.; Lyass, F.M.; Mamin, R.G.; Minakova, E.I.; Raevskaya, S.A.

    1983-01-01

    A model of normal tissue injury as a result of exposure to ionizing radiation is based on an assumption that the degree of tissue injury is determined by the degree of destruction by certain critical cells. The dependence of the number of lethal injuriies on a single dose is expressed by a trinomial - linear and quadratic parts and a constant, obtained as a result of the processing of experimental data. Quantitative correlations have been obtained for the skin and brain. They have been tested using clinical and experimental material. The results of the testing point out to the absence of time dependence on a single up to 6-week irradiation cources. Correlation with an irradiation field has been obtained for the skin. A conclusion has been made that the concept of isoefficacy of irradiation cources is conditional. Spatial-time fractionation is a promising direction in the development of radiation therapy

  20. Variation in normal and tumor tissue sensitivity of mice to ionizing radiation-induced DNA strand breaks in vivo

    International Nuclear Information System (INIS)

    Meyn, R.E.; Jenkins, W.T.

    1983-01-01

    The efficiency of DNA strand break formation in normal and tumor tissues of mice was measured using the technique of alkaline elution coupled with a microfluorometric determination of DNA. This methodology allowed measurement of the DNA strand breaks produced in tissues irradiated in vivo with doses of radiation comparable to those used in radiotherapy (i.e., 1.0 gray) without the necessity for the cells to be dividing and incorporating radioactive precursors to label the DNA. The results showed that substantial differences existed among various tissues in terms of the amount of DNA strand break damage produced for a given dose of radiation. Of the normal tissues, the most breaks were produced in bone marrow and the least were produced in gut. Furthermore, strand break production was relatively inefficient in the tumor compared to the normal tissues. The efficiency of DNA strand break formation measured in the cells from the tissues irradiated in vitro was much more uniform and considerably greater than that measured in vivo, suggesting that the normal tissues in the animal may be radiobiologically hypoxic

  1. Mathematical models of tumour and normal tissue response

    International Nuclear Information System (INIS)

    Jones, B.; Dale, R.G.; Charing Cross Group of Hospitals, London

    1999-01-01

    The historical application of mathematics in the natural sciences and in radiotherapy is compared. The various forms of mathematical models and their limitations are discussed. The Linear Quadratic (LQ) model can be modified to include (i) radiobiological parameter changes that occur during fractionated radiotherapy, (ii) situations such as focal forms of radiotherapy, (iii) normal tissue responses, and (iv) to allow for the process of optimization. The inclusion of a variable cell loss factor in the LQ model repopulation term produces a more flexible clonogenic doubling time, which can simulate the phenomenon of 'accelerated repopulation'. Differential calculus can be applied to the LQ model after elimination of the fraction number integers. The optimum dose per fraction (maximum cell kill relative to a given normal tissue fractionation sensitivity) is then estimated from the clonogen doubling times and the radiosensitivity parameters (or α/β ratios). Economic treatment optimization is described. Tumour volume studies during or following teletherapy are used to optimize brachytherapy. The radiation responses of both individual tumours and tumour populations (by random sampling 'Monte-Carlo' techniques from statistical ranges of radiobiological and physical parameters) can be estimated. Computerized preclinical trials can be used to guide choice of dose fractionation scheduling in clinical trials. The potential impact of gene and other biological therapies on the results of radical radiotherapy are testable. New and experimentally testable hypotheses are generated from limited clinical data by exploratory modelling exercises. (orig.)

  2. Experimental studies on interactions of radiation and cancer chemotherapeutic drugs in normal tissues and a solid tumour

    International Nuclear Information System (INIS)

    Maase, H. van der

    1986-01-01

    The interactions of radiation and seven cancer chemotherapeutic drugs have been investigated in four normal tissues and in a solid C 3 H mouse mammary carcinoma in vivo. The investigated drugs were adriamycin (ADM), bleomycin (BLM), cyclophosphamide (CTX), 5-fluorouracil (5-FU), methotrexate (MTX), mitomycin C (MM-C) and cis-diamminedichloroplatinum(II) (cis-DDP). The drugs enhanced the radiation response in most cases. However, signs of radioprotection was observed for CTX in skin and for MTX in haemopoietic tissue. The interval and the sequence of the two treatment modalities were of utmost importance for the normal tissue reactions. In general, the most serious interactions occurred when drugs were administered simultaneously with or a few hours before radiation. The radiation-modifying effect of the drugs deviated from this pattern in the haemopoietic tissue as the radiation response was most enhanced on drug administration 1-3 days after radiation. Enhancement of the radiation response was generally less pronounced in the tumour model than in the normal tissues. The combined drug-radiation effect was apparently less time-dependent in the tumour than in the normal tissues. (Auth.)

  3. Elemental concentration analysis in PCa, BPH and normal prostate tissues using SR-TXRF

    International Nuclear Information System (INIS)

    Leitao, Roberta G.; Anjos, Marcelino J.; Canellas, Catarine G.L.; Lopes, Ricardo T.

    2009-01-01

    Prostate cancer (PCa) is one of the main causes of illness and death all over the world. In Brazil, prostate cancer currently represents the second most prevalent malignant neoplasia in men, representing 21% of all cancer cases. Benign Prostate Hyperplasia (BPH) is an illness prevailing in men above the age of 50, close to 90% after the age of 80. The prostate presents a high zinc concentration, about 10-fold higher than any other body tissue. In this work, samples of human prostate tissues with cancer (PCa), BPH and normal tissue were analyzed utilizing the total reflection X-ray fluorescence spectroscopy using synchrotron radiation technique (SRTXRF) to investigate the differences in the elemental concentrations in these tissues. SR-TXRF analyses were performed at the X-Ray fluorescence beamline at Brazilian National Synchrotron Light Laboratory (LNLS), in Campinas, Sao Paulo. It was possible to determine the concentrations of the following elements: P, S, K, Ca, Fe, Cu, Zn, Br and Rb. By using Mann-Whitney U test it was observed that almost all elements presented concentrations with significant differences α = 0.05) between the groups studied. The elements and groups were: S, K, Ca, Fe, Zn, Br and Rb (PCa X Normal); S, Fe, Zn and Br (PCa X BPH); K, Ca, Fe, Zn, Br and Rb (BPH X Normal). (author)

  4. Trace element determinations in brain tissues from normal and clinically demented individuals

    International Nuclear Information System (INIS)

    Saiki, Mitiko; Genezini, Frederico A.; Leite, Renata E.P.; Grinberg, Lea T.; Ferretti, Renata E.L.; Suemoto, Claudia; Pasqualucci, Carlos A.; Jacob-Filho, Wilson

    2013-01-01

    Studies on trace element levels in human brains under normal and pathological conditions have indicated a possible correlation between some trace element concentrations and neurodegenerative diseases. In this study, analysis of brain tissues was carried out to investigate if there are any differences in elemental concentrations between brain tissues from a normal population above 50 years of age presenting Clinical Dementia Rating (CDR) equal to zero (CDR=0) and that cognitively affected population ( CDR=3). The tissues were dissected, ground, freeze-dried and then analyzed by instrumental neutron activation analysis. Samples and elemental standards were irradiated in a neutron flux at the IEA-R1 nuclear research reactor for Br, Fe, K, Na, Rb, Se and Zn determinations. The induced gamma ray activities were measured using a hyperpure Ge detector coupled to a gamma ray spectrometer. The one-way ANOVA test (p< 0.05) was used to compare the results. All the elements determined in the hippocampus brain region presented differences between the groups presenting CDR=0 and CDR=3. In the case of frontal region only the elements Na, Rb and Zn showed differences between these two groups. These findings proved the correlation between elemental levels present in brain tissues neurodegenerative diseases. Biological standard reference materials SRM 1566b Oyster Tissue and SRM 1577b Bovine Liver analyzed for quality control indicated good accuracy and precision of the results. (author)

  5. Pelvic Normal Tissue Contouring Guidelines for Radiation Therapy: A Radiation Therapy Oncology Group Consensus Panel Atlas

    Energy Technology Data Exchange (ETDEWEB)

    Gay, Hiram A., E-mail: hgay@radonc.wustl.edu [Washington University School of Medicine, St Louis, MO (United States); Barthold, H. Joseph [Commonwealth Hematology and Oncology, Weymouth, MA (United States); Beth Israel Deaconess Medical Center, Boston, MA (Israel); O' Meara, Elizabeth [Radiation Therapy Oncology Group, Philadelphia, PA (United States); Bosch, Walter R. [Washington University School of Medicine, St Louis, MO (United States); El Naqa, Issam [Department of Radiation Oncology, McGill University Health Center, Montreal, Quebec (Canada); Al-Lozi, Rawan [Washington University School of Medicine, St Louis, MO (United States); Rosenthal, Seth A. [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); Lawton, Colleen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI (United States); Lee, W. Robert [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Sandler, Howard [Cedars-Sinai Medical Center, Los Angeles, CA (United States); Zietman, Anthony [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Myerson, Robert [Washington University School of Medicine, St Louis, MO (United States); Dawson, Laura A. [Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, Ontario (Canada); Willett, Christopher [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Kachnic, Lisa A. [Department of Radiation Oncology, Boston Medical Center, Boston University School of Medicine, Boston, MA (United States); Jhingran, Anuja [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Portelance, Lorraine [University of Miami, Miami, FL (United States); Ryu, Janice [Radiation Oncology Centers, Radiological Associates of Sacramento, Sacramento, CA (United States); and others

    2012-07-01

    Purpose: To define a male and female pelvic normal tissue contouring atlas for Radiation Therapy Oncology Group (RTOG) trials. Methods and Materials: One male pelvis computed tomography (CT) data set and one female pelvis CT data set were shared via the Image-Guided Therapy QA Center. A total of 16 radiation oncologists participated. The following organs at risk were contoured in both CT sets: anus, anorectum, rectum (gastrointestinal and genitourinary definitions), bowel NOS (not otherwise specified), small bowel, large bowel, and proximal femurs. The following were contoured in the male set only: bladder, prostate, seminal vesicles, and penile bulb. The following were contoured in the female set only: uterus, cervix, and ovaries. A computer program used the binomial distribution to generate 95% group consensus contours. These contours and definitions were then reviewed by the group and modified. Results: The panel achieved consensus definitions for pelvic normal tissue contouring in RTOG trials with these standardized names: Rectum, AnoRectum, SmallBowel, Colon, BowelBag, Bladder, UteroCervix, Adnexa{sub R}, Adnexa{sub L}, Prostate, SeminalVesc, PenileBulb, Femur{sub R}, and Femur{sub L}. Two additional normal structures whose purpose is to serve as targets in anal and rectal cancer were defined: AnoRectumSig and Mesorectum. Detailed target volume contouring guidelines and images are discussed. Conclusions: Consensus guidelines for pelvic normal tissue contouring were reached and are available as a CT image atlas on the RTOG Web site. This will allow uniformity in defining normal tissues for clinical trials delivering pelvic radiation and will facilitate future normal tissue complication research.

  6. Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

    Science.gov (United States)

    Samani, Abbas; Zubovits, Judit; Plewes, Donald

    2007-03-01

    Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

  7. Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

    International Nuclear Information System (INIS)

    Samani, Abbas; Zubovits, Judit; Plewes, Donald

    2007-01-01

    Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed

  8. Elastic moduli of normal and pathological human breast tissues: an inversion-technique-based investigation of 169 samples

    Energy Technology Data Exchange (ETDEWEB)

    Samani, Abbas [Department of Medical Biophysics/Electrical and Computer Engineering, University of Western Ontario, Medical Sciences Building, London, Ontario, N6A 5C1 (Canada); Zubovits, Judit [Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 (Canada); Plewes, Donald [Department of Medical Biophysics, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5 (Canada)

    2007-03-21

    Understanding and quantifying the mechanical properties of breast tissues has been a subject of interest for the past two decades. This has been motivated in part by interest in modelling soft tissue response for surgery planning and virtual-reality-based surgical training. Interpreting elastography images for diagnostic purposes also requires a sound understanding of normal and pathological tissue mechanical properties. Reliable data on tissue elastic properties are very limited and those which are available tend to be inconsistent, in part as a result of measurement methodology. We have developed specialized techniques to measure tissue elasticity of breast normal tissues and tumour specimens and applied them to 169 fresh ex vivo breast tissue samples including fat and fibroglandular tissue as well as a range of benign and malignant breast tumour types. Results show that, under small deformation conditions, the elastic modulus of normal breast fat and fibroglandular tissues are similar while fibroadenomas were approximately twice the stiffness. Fibrocystic disease and malignant tumours exhibited a 3-6-fold increased stiffness with high-grade invasive ductal carcinoma exhibiting up to a 13-fold increase in stiffness compared to fibrogalndular tissue. A statistical analysis showed that differences between the elastic modulus of the majority of those tissues were statistically significant. Implications for the specificity advantages of elastography are reviewed.

  9. A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries.

    Science.gov (United States)

    Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

    2007-05-21

    The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at the University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties.

  10. A large-scale study of the ultrawideband microwave dielectric properties of normal breast tissue obtained from reduction surgeries

    International Nuclear Information System (INIS)

    Lazebnik, Mariya; McCartney, Leah; Popovic, Dijana; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Magliocco, Anthony; Booske, John H; Okoniewski, Michal; Hagness, Susan C

    2007-01-01

    The efficacy of emerging microwave breast cancer detection and treatment techniques will depend, in part, on the dielectric properties of normal breast tissue. However, knowledge of these properties at microwave frequencies has been limited due to gaps and discrepancies in previously reported small-scale studies. To address these issues, we experimentally characterized the wideband microwave-frequency dielectric properties of a large number of normal breast tissue samples obtained from breast reduction surgeries at University of Wisconsin and University of Calgary hospitals. The dielectric spectroscopy measurements were conducted from 0.5 to 20 GHz using a precision open-ended coaxial probe. The tissue composition within the probe's sensing region was quantified in terms of percentages of adipose, fibroconnective and glandular tissues. We fit a one-pole Cole-Cole model to the complex permittivity data set obtained for each sample and determined median Cole-Cole parameters for three groups of normal breast tissues, categorized by adipose tissue content (0-30%, 31-84% and 85-100%). Our analysis of the dielectric properties data for 354 tissue samples reveals that there is a large variation in the dielectric properties of normal breast tissue due to substantial tissue heterogeneity. We observed no statistically significant difference between the within-patient and between-patient variability in the dielectric properties

  11. Enhancer of the rudimentary gene homologue (ERH expression pattern in sporadic human breast cancer and normal breast tissue

    Directory of Open Access Journals (Sweden)

    Knüchel Ruth

    2008-05-01

    Full Text Available Abstract Background The human gene ERH (Enhancer of the Rudimentary gene Homologue has previously been identified by in silico analysis of four million ESTs as a gene differentially expressed in breast cancer. The biological function of ERH protein has not been fully elucidated, however functions in cell cycle progression, pyrimidine metabolism a possible interaction with p21(Cip1/Waf1 via the Ciz1 zinc finger protein have been suggested. The aim of the present study was a systematic characterization of ERH expression in human breast cancer in order to evaluate possible clinical applications of this molecule. Methods The expression pattern of ERH was analyzed using multiple tissue northern blots (MTN on a panel of 16 normal human tissues and two sets of malignant/normal breast and ovarian tissue samples. ERH expression was further analyzed in breast cancer and normal breast tissues and in tumorigenic as well as non-tumorigenic breast cancer cell lines, using quantitative RT-PCR and non-radioisotopic in situ hybridization (ISH. Results Among normal human tissues, ERH expression was most abundant in testis, heart, ovary, prostate, and liver. In the two MTN sets of malignant/normal breast and ovarian tissue,ERH was clearly more abundantly expressed in all tumours than in normal tissue samples. Quantitative RT-PCR analyses showed that ERH expression was significantly more abundant in tumorigenic than in non-tumorigenic breast cancer cell lines (4.5-fold; p = 0.05, two-tailed Mann-Whitney U-test; the same trend was noted in a set of 25 primary invasive breast cancers and 16 normal breast tissue samples (2.5-fold; p = 0.1. These findings were further confirmed by non-radioisotopic ISH in human breast cancer and normal breast tissue. Conclusion ERH expression is clearly up-regulated in malignant as compared with benign breast cells both in primary human breast cancer and in cell models of breast cancer. Since similar results were obtained for ovarian

  12. Normal tissue tolerance to external beam radiation therapy: Adult bone

    International Nuclear Information System (INIS)

    Sargos, P.; Mamou, N.; Dejean, C.; Henriques de Figueiredo, B.; Kantor, G.; Huchet, A.; Italiano, A.

    2010-01-01

    Radiation tolerance for bone tissue has been mostly evaluated with regard to bone fracture. Main circumstances are mandibula osteoradionecrosis, hip and costal fracture, and patent or radiologic fractures in the treated volume. After radiation therapy of bone metastasis, the analysis of related radiation fracture is difficult to individualize from a pathologic fracture. Frequency of clinical fracture is less than 5% in the large series or cohorts and is probably under-evaluated for the asymptomatic lesions. Women older than 50 years and with osteoporosis are probably the main population at risk. Dose-effect relations are difficult to qualify in older series. Recent models evaluating radiations toxicity on diaphysa suggest an important risk after 60 Gy, for high dose-fraction and for a large volume. (authors)

  13. Comparative study of rabbit VX2 hepatic implantation tumor and normal liver tissue on magnetic resonance perfusion weighted imaging

    International Nuclear Information System (INIS)

    Jiao Zimei; Wang Xizhen; Wang Bin; Liu Feng; Li Haiqing; Sun Yequan; Dong Peng

    2012-01-01

    Objective: To investigate the value of magnetic resonance (MR) perfusion weighted imaging (PWI) in evaluating the blood perfusion of tumor by analyzing the features and indexes of PWI on rabbit VX2 hepatic implantation tumor and normal liver tissue. Methods: Twenty-four New Zealand White rabbits with VX2 carcinoma were established under direct surgical vision embedding tumor tissue. MR examination was performed at 21 days after the tumor implantation. The signal intensity -time curve of hepatic tumor and normal liver tissue were obtained. Mean time to enhance (MTE), negative enhancement integral (NEI), time to minimum (TM), maximum slope of decrease (MSD) and maximum slope of increase (MSI) were measured. Results: MTE, NEI, TM, MSD, and MSI of the normal liver tissue were 208.341±2.226 ms, 78.334±8.152, 24.059±1.927 ms, 38.221±2.443, and 15.389±2.526, respectively. MTE, NEI, TM, MSD, and MSI of the tumor tissue were 175.437±4.182 ms, 123.203±19.455, 17.061±1.834 ms, 125.740±4.842, and 67.832±2.882, respectively. The MTE and TM of tumor were shorter than those of normal hepatic tissue (P<0.05). NEI, MSD, and MSI of tumor were higher than those of normal hepatic tissue (P<0.05). Conclusion: PWI can distinguish the normal liver tissue from the tumor tissue, which is helpful in evaluating blood perfusion of different hepatic tissues. (authors)

  14. YAP expression in normal and neoplastic breast tissue: an immunohistochemical study.

    Science.gov (United States)

    Jaramillo-Rodríguez, Yolanda; Cerda-Flores, Ricardo M; Ruiz-Ramos, Ruben; López-Márquez, Francisco C; Calderón-Garcidueñas, Ana Laura

    2014-04-01

    Yes-associated protein (YAP) is a transcriptional factor involved in normal cell proliferation, apoptosis and carcinogenesis; however, its contribution to breast cancer (BC) is still controversial. We undertook this study to compare the expression of YAP by immunohistochemistry (IHC) in normal breast tissue of women without breast cancer (BC) (controls), non-neoplastic breast tissue in women with cancer (internal controls) and in four different subtypes of invasive ductal carcinoma. There were 17 controls and 105 tumor cases (53 luminal A, 15 luminal B, 20 overexpression of HER2 and 17 triple negative cases) studied by IHC. Statistical analysis included χ(2) for linear trend (Extended Mantel-Haenszel). There were 40% of internal controls that showed expression of YAP in myoepithelial cells, whereas in controls expression was 100%. In controls, 3/17 (17.6%) showed cytoplasmic staining in luminal cells. There was a significant difference in nuclear expression between the ductal BC subtypes. Luminal A had 4% of positive cases with <10% of cells affected in each case; in contrast, there were 17-20% of positive cases in the other groups with 50% or more of stained cells. YAP expression in stromal cells was not observed in controls or in triple-negative cases, and luminal B pattern had the highest YAP nuclear expression (20%). YAP showed decreased expression in tumor cells compared with normal breast tissue. These findings are consistent with a role of YAP as a suppressor gene in BC and show differences in YAP expression in different patterns of ductal BC. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  15. Differential Expression of Cytochrome P450 Enzymes in Normal and Tumor Tissues from Childhood Rhabdomyosarcoma

    Science.gov (United States)

    Molina-Ortiz, Dora; Camacho-Carranza, Rafael; González-Zamora, José Francisco; Shalkow-Kalincovstein, Jaime; Cárdenas-Cardós, Rocío; Ností-Palacios, Rosario; Vences-Mejía, Araceli

    2014-01-01

    Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs. PMID:24699256

  16. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  17. Safety of disclosing amyloid status in cognitively normal older adults.

    Science.gov (United States)

    Burns, Jeffrey M; Johnson, David K; Liebmann, Edward P; Bothwell, Rebecca J; Morris, Jill K; Vidoni, Eric D

    2017-09-01

    Disclosing amyloid status to cognitively normal individuals remains controversial given our lack of understanding the test's clinical significance and unknown psychological risk. We assessed the effect of amyloid status disclosure on anxiety and depression before disclosure, at disclosure, and 6 weeks and 6 months postdisclosure and test-related distress after disclosure. Clinicians disclosed amyloid status to 97 cognitively normal older adults (27 had elevated cerebral amyloid). There was no difference in depressive symptoms across groups over time. There was a significant group by time interaction in anxiety, although post hoc analyses revealed no group differences at any time point, suggesting a minimal nonsustained increase in anxiety symptoms immediately postdisclosure in the elevated group. Slight but measureable increases in test-related distress were present after disclosure and were related to greater baseline levels of anxiety and depression. Disclosing amyloid imaging results to cognitively normal adults in the clinical research setting with pre- and postdisclosure counseling has a low risk of psychological harm. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  18. Local stem cell depletion model for normal tissue damage

    International Nuclear Information System (INIS)

    Yaes, R.J.; Keland, A.

    1987-01-01

    The hypothesis that radiation causes normal tissue damage by completely depleting local regions of tissue of viable stem cells leads to a simple mathematical model for such damage. In organs like skin and spinal cord where destruction of a small volume of tissue leads to a clinically apparent complication, the complication probability is expressed as a function of dose, volume and stem cell number by a simple triple negative exponential function analogous to the double exponential function of Munro and Gilbert for tumor control. The steep dose response curves for radiation myelitis that are obtained with our model are compared with the experimental data for radiation myelitis in laboratory rats. The model can be generalized to include other types or organs, high LET radiation, fractionated courses of radiation, and cases where an organ with a heterogeneous stem cell population receives an inhomogeneous dose of radiation. In principle it would thus be possible to determine the probability of tumor control and of damage to any organ within the radiation field if the dose distribution in three dimensional space within a patient is known

  19. Sonographic Measurement of Normal Splenic Length in Korean Adults

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Sang Bum; Cheon, Byung Kook; Kim, Jong Min; Oh, Kyung Seoung; Jung, Gyoo Sik; Huh, Jin Do; Joh, Young Duk [Kosin University College of Medicine, Busan (Korea, Republic of)

    1996-12-15

    To establish upper limit of normal splenic length of Korean adults on ultrasonography and to determice the degree of interobserver and intraobserver variation. Ultrasonographic scans were performed to measure the maximum length of spleen in 105 of 150 adults selected by convenience sampling. Remained 45 cases with any conditions that could alter splenic size were excluded from this study. The maximum length of spleen was measured and correlated with body surface area, patient height, weight, age and sex. In 31 of the 105 adults we evaluated the interobserver and intraobserver variations in sonographic measurements of splenic length obtained by three radiologists in blind fashion. The mean splenic length in 105 adults was 8.56cm ({+-} 0.95). The splenic length positively correlated with body surface area, patient height and weight (P <0.001), and negatively correlated with patient age (P < 0.01). Male spleen (8.87 cm {+-} 1.07) was longer than female spleen (8.35 cm {+-} 0.81) (P < 0.05). The following guidelines are proposed for the upper limit of normal splenic length at different groups of body surface area: no longer than 10 cm at 1.20{approx}1.59 m{sup 2}, 11 cm at1.60{approx}1.79 m{sup 2}, and 12 cm at 1.80{approx}1.99 m{sup 2}. The mean interobserver variation between any two radiologists ranged from 0.32 cm ({+-} 0.29) to 0.39 cm ({+-} 0.33) and interobserver variations were within 1 cm in 96%. The mean intraobserver variations were within 0.5 cm in 91%. The splenic length closely correlated with body surface area, patient height, weight and age. Particularly the upper limit of normal splenic length changed according to body surface area. Interobserver variation about 1 cm and intraobserver variation about 0.5 cm should be considered in the measurement of the splenic length on ultrasonography

  20. Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

    Directory of Open Access Journals (Sweden)

    Emara Marwan

    2010-09-01

    Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

  1. Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite Allograft Transplantation

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-2-0042 TITLE: Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite...2017 2. REPORT TYPE Annual 3. DATES COVERED 30 Sep 2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Adult Tissue-Derived Stem Cells and Tolerance Induction...Distribution Unlimited 13. SUPPLEMENTARY NOTES The utilization of adult derived adipose stem cells administration in composite tissue transplantation

  2. Tumor control and normal tissue toxicity: The two faces of radiotherapy

    NARCIS (Netherlands)

    van Oorschot, B.

    2016-01-01

    This thesis discusses the two contrasting sides of radiotherapy: tumor control and normal tissue toxicity. On one hand, radiation treatment aims to target the tumor with the highest possible radiation dose, inducing as much lethal DNA damage as possible. On the other hand however, escalation of the

  3. A simple method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation

    International Nuclear Information System (INIS)

    Begnozzi, L.; Gentile, F.P.; Di Nallo, A.M.; Chiatti, L.; Zicari, C.; Consorti, R.; Benassi, M.

    1994-01-01

    Since volumetric dose distributions are available with 3-dimensional radiotherapy treatment planning they can be used in statistical evaluation of response to radiation. This report presents a method to calculate the influence of dose inhomogeneity and fractionation in normal tissue complication probability evaluation. The mathematical expression for the calculation of normal tissue complication probability has been derived combining the Lyman model with the histogram reduction method of Kutcher et al. and using the normalized total dose (NTD) instead of the total dose. The fitting of published tolerance data, in case of homogeneous or partial brain irradiation, has been considered. For the same total or partial volume homogeneous irradiation of the brain, curves of normal tissue complication probability have been calculated with fraction size of 1.5 Gy and of 3 Gy instead of 2 Gy, to show the influence of fraction size. The influence of dose distribution inhomogeneity and α/β value has also been simulated: Considering α/β=1.6 Gy or α/β=4.1 Gy for kidney clinical nephritis, the calculated curves of normal tissue complication probability are shown. Combining NTD calculations and histogram reduction techniques, normal tissue complication probability can be estimated taking into account the most relevant contributing factors, including the volume effect. (orig.) [de

  4. The influence of dose fractionation and dose rate on normal tissue responses

    International Nuclear Information System (INIS)

    Barendsen, G.W.

    1982-01-01

    An analysis of responses of a variety of normal tissues in animals to fractionated irradiations has been made with the aim of developing a formalism for the prediction of tolerance doses as a function of the dose per fraction and the overall treatment time. An important feature of the formalism is that it is directly based on radiological insights and therefore provides a logical concept to account for the diversity of tissue responses. (Auth.)

  5. CURED I - LENT. Late effects of cancer treatment on normal tissues

    International Nuclear Information System (INIS)

    Rubin, P.; Okunieff, P.; Constine, L.S.; Rochester Univ. School of Medicine and Dentistry, Rochester, NY; Marks, L.B.

    2008-01-01

    The search for the most favorable therapeutic ratio - at which ablation of cancer is achieved while normal tissues are conserved - has been modern radiation oncology's equivalent of the quest for the Holy Grail. Our awareness of the late effects of radiation grew during the past century as new modalities were introduced. Heightened normal tissue reactions accompanied the higher rates of cancer ablation achieved by escalation of radiation doses, accelerated fractionated radiotherapy, and aggressive concurrent chemotherapy and radiation regimens. This volume is based on the LENT V NCI-sponsored meeting held in May 2004 and the CURED I conference held in 2006. Written by experts in the field, it addresses a number of critical topics relating to late effects, such as mechanisms of injury, the role of screening, options for interventions, second malignancies, and prevention. It is hoped that it will assist the reader in understanding how to prevent and treat the long-term side-effects of irradiation. (orig.)

  6. Static and dynamic postural control in low-vision and normal-vision adults.

    Science.gov (United States)

    Tomomitsu, Mônica S V; Alonso, Angelica Castilho; Morimoto, Eurica; Bobbio, Tatiana G; Greve, Julia M D

    2013-04-01

    This study aimed to evaluate the influence of reduced visual information on postural control by comparing low-vision and normal-vision adults in static and dynamic conditions. Twenty-five low-vision subjects and twenty-five normal sighted adults were evaluated for static and dynamic balance using four protocols: 1) the Modified Clinical Test of Sensory Interaction on Balance on firm and foam surfaces with eyes opened and closed; 2) Unilateral Stance with eyes opened and closed; 3) Tandem Walk; and 4) Step Up/Over. The results showed that the low-vision group presented greater body sway compared with the normal vision during balance on a foam surface (p≤0.001), the Unilateral Stance test for both limbs (p≤0.001), and the Tandem Walk test. The low-vision group showed greater step width (p≤0.001) and slower gait speed (p≤0.004). In the Step Up/Over task, low-vision participants were more cautious in stepping up (right p≤0.005 and left p≤0.009) and in executing the movement (p≤0.001). These findings suggest that visual feedback is crucial for determining balance, especially for dynamic tasks and on foam surfaces. Low-vision individuals had worse postural stability than normal-vision adults in terms of dynamic tests and balance on foam surfaces.

  7. 68Ga-DOTATOC PET/CT and somatostatin receptor (sst1-sst5) expression in normal human tissue: correlation of sst2 mRNA and SUVmax

    International Nuclear Information System (INIS)

    Boy, Christian; Poeppel, Thorsten D.; Jentzen, Walter; Brandau, Wolfgang; Bockisch, Andreas; Heusner, Till A.; Antoch, Gerald; Redmann-Bischofs, Anja; Unger, Nicole; Mann, Klaus; Petersenn, Stephan

    2011-01-01

    By targeting somatostatin receptors (sst) radiopeptides have been established for both diagnosis and therapy. For physiologically normal human tissues the study provides a normative database of maximum standardized uptake value (SUV max ) and sst mRNA. A total of 120 patients were subjected to diagnostic 68 Ga-DOTATOC positron emission tomography (PET)/CT (age range 19-83 years). SUV max values were measured in physiologically normal tissues defined by normal morphology, absence of surgical intervention and absence of metastatic spread during clinical follow-up. Expression of sst subtypes (sst1-sst5) was measured independently in pooled adult normal human tissue by real-time reverse transcriptase polymerase chain reaction (RT-PCR). SUV max revealed a region-specific pattern (e.g., mean ± SD, spleen 31.1 ± 10.9, kidney 16.9 ± 5.3, liver 12.8 ± 3.6, stomach 7.0 ± 3.1, head of pancreas 6.2 ± 2.3, small bowel 4.8 ± 1.8, thyroid 4.7 ± 2.2, bone 3.9 ± 1.3, large bowel 2.9 ± 0.8, muscle 2.1 ± 0.5, parotid gland 1.9 ± 0.6, axillary lymph node 0.8 ± 0.3 and lung 0.7 ± 0.3). SUV max was age independent. Gender differences were evident within the thyroid (female/male: 3.7 ± 1.6/5.5 ± 2.4, p max values exclusively correlated with sst2 expression (r = 0.846, p max with the expression of the other four subtypes. In normal human tissues 68 Ga-DOTATOC imaging has been related to the expression of sst2 at the level of mRNA. The novel normative database may improve diagnostics, monitoring and therapy of sst-expressing tumours or inflammation on a molecular basis. (orig.)

  8. Injury Response of Resected Human Brain Tissue In Vitro

    NARCIS (Netherlands)

    Verwer, Ronald W. H.; Sluiter, Arja A.; Balesar, Rawien A.; Baaijen, Johannes C.; de Witt Hamer, Philip C.; Speijer, Dave; Li, Yichen; Swaab, Dick F.

    2015-01-01

    Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by

  9. Computed tomography of the normal feline nasal cavity and paranasal sinuses

    International Nuclear Information System (INIS)

    Losonsky, J.M.; Abbott, L.C.; Kuriashkin, I.V.

    1997-01-01

    Computed tomography (CT) images of the feline nasal cavity and paranasal sinuses were acquired from normal adult cats, Good resolution and anatomic detail were obtained from the CT images using soft tissue formatting. A description of normal feline nasal cavity and paranasal sinus anatomy using CT is presented

  10. Effect of different BNCT protocols on DNA synthesis in precancerous and normal tissues in an experimental model of oral cancer

    International Nuclear Information System (INIS)

    Heber, Elisa M.; Aromando, Romina; Trivillin, Veronica A.; Itoiz, Maria E.; Kreimann, Erica L.; Schwint, Amanda E.; Nigg, David W.

    2006-01-01

    We previously reported the therapeutic success of different BNCT protocols in the treatment of oral cancer, employing the hamster cheek pouch model. The aim of the present study was to evaluate the effect of these BNCT protocols on DNA synthesis in precancerous and normal tissue in this model and assess the potential lag in the development of second primary tumors in precancerous tissue. The data are relevant to potential control of field cancerized tissue and tolerance of normal tissue. We evaluated DNA synthesis in precancerous and normal pouch tissue 1-30 days post-BNCT mediated by BPA, GB-10 or BPA + GB-10 employing incorporation of bromo-deoxyuridine as an end-point. The BNCT-induced potential lag in the development of second primary tumors in precancerous tissue was monitored. A drastic, statistically significant reduction in DNA synthesis occurred in pacancerous tissue as early as 1 day post-BNCT and was sustained at virtually all time points until 30 days post-BNCT for all protocols. The histological categories evaluated individually within precancerous tissue (dysplasia, hyperplasia and NUMF [no unusual microscopic features]) responded similarly. DNA synthesis in normal tissue treated with BNCT oscillated around the very low pre-treatment values. A BNCT-induced lag in the development of second primary tumors was observed. BNCT induced a drastic fall in DNA synthesis in precancerous tissue that would be associated to the observed lag in the development of second primary tumors. The minimum variations in DNA synthesis in BNCT-treated normal tissue would correlate with the absence of normal tissue radiotoxicity. The present data would contribute to optimize therapeutic efficacy in the treatment of field-cancerized areas. (author)

  11. SU-F-J-174: A Series of Computational Human Phantoms in DICOM-RT Format for Normal Tissue Dose Reconstruction in Epidemiological Studies

    International Nuclear Information System (INIS)

    Pyakuryal, A; Moroz, B; Lee, C; Pelletier, C; Jung, J; Lee, C

    2016-01-01

    Purpose: Epidemiological studies of second cancer risk in radiotherapy patients often require individualized dose estimates of normal tissues. Prior to 3D conformal radiation therapy planning, patient anatomy information was mostly limited to 2D radiological images or not even available. Generic patient CT images are often used in commercial radiotherapy treatment planning system (TPS) to reconstruct normal tissue doses. The objective of the current work was to develop a series of reference size computational human phantoms in DICOM-RT format for direct use in dose reconstruction in TPS. Methods: Contours of 93 organs and tissues were extracted from a series of pediatric and adult hybrid computational human phantoms (newborn, 1-, 5-, 10-, 15-year-old, and adult males and females) using Rhinoceros software. A MATLAB script was created to convert the contours into the DICOM-RT structure format. The simulated CT images with the resolution of 1×1×3 mm3 were also generated from the binary phantom format and coupled with the DICOM-structure files. Accurate volumes of the organs were drawn in the format using precise delineation of the contours in converted format. Due to complex geometry of organs, higher resolution (1×1×1 mm3) was found to be more efficient in the conversion of newborn and 1-year-old phantoms. Results: Contour sets were efficiently converted into DICOM-RT structures in relatively short time (about 30 minutes for each phantom). A good agreement was observed in the volumes between the original phantoms and the converted contours for large organs (NRMSD<1.0%) and small organs (NRMSD<7.7%). Conclusion: A comprehensive series of computational human phantoms in DICOM-RT format was created to support epidemiological studies of second cancer risks in radiotherapy patients. We confirmed the DICOM-RT phantoms were successfully imported into the TPS programs of major vendors.

  12. SU-F-J-174: A Series of Computational Human Phantoms in DICOM-RT Format for Normal Tissue Dose Reconstruction in Epidemiological Studies

    Energy Technology Data Exchange (ETDEWEB)

    Pyakuryal, A; Moroz, B [National Cancer Institute, National Institutes of Health, Rockville, MD (United States); Lee, C [University of Michigan, Ann Arbor, MI (United States); Pelletier, C; Jung, J [East Carolina University Greenville, NC (United States); Lee, C [National Cancer Institute, Rockville, MD (United States)

    2016-06-15

    Purpose: Epidemiological studies of second cancer risk in radiotherapy patients often require individualized dose estimates of normal tissues. Prior to 3D conformal radiation therapy planning, patient anatomy information was mostly limited to 2D radiological images or not even available. Generic patient CT images are often used in commercial radiotherapy treatment planning system (TPS) to reconstruct normal tissue doses. The objective of the current work was to develop a series of reference size computational human phantoms in DICOM-RT format for direct use in dose reconstruction in TPS. Methods: Contours of 93 organs and tissues were extracted from a series of pediatric and adult hybrid computational human phantoms (newborn, 1-, 5-, 10-, 15-year-old, and adult males and females) using Rhinoceros software. A MATLAB script was created to convert the contours into the DICOM-RT structure format. The simulated CT images with the resolution of 1×1×3 mm3 were also generated from the binary phantom format and coupled with the DICOM-structure files. Accurate volumes of the organs were drawn in the format using precise delineation of the contours in converted format. Due to complex geometry of organs, higher resolution (1×1×1 mm3) was found to be more efficient in the conversion of newborn and 1-year-old phantoms. Results: Contour sets were efficiently converted into DICOM-RT structures in relatively short time (about 30 minutes for each phantom). A good agreement was observed in the volumes between the original phantoms and the converted contours for large organs (NRMSD<1.0%) and small organs (NRMSD<7.7%). Conclusion: A comprehensive series of computational human phantoms in DICOM-RT format was created to support epidemiological studies of second cancer risks in radiotherapy patients. We confirmed the DICOM-RT phantoms were successfully imported into the TPS programs of major vendors.

  13. Lewis x is highly expressed in normal tissues: a comparative immunohistochemical study and literature revision.

    Science.gov (United States)

    Croce, María V; Isla-Larrain, Marina; Rabassa, Martín E; Demichelis, Sandra; Colussi, Andrea G; Crespo, Marina; Lacunza, Ezequiel; Segal-Eiras, Amada

    2007-01-01

    An immunohistochemical analysis was employed to determine the expression of carbohydrate antigens associated to mucins in normal epithelia. Tissue samples were obtained as biopsies from normal breast (18), colon (35) and oral cavity mucosa (8). The following carbohydrate epitopes were studied: sialyl-Lewis x, Lewis x, Lewis y, Tn hapten, sialyl-Tn and Thomsen-Friedenreich antigen. Mucins were also studied employing antibodies against MUC1, MUC2, MUC4, MUC5AC, MUC6 and also normal colonic glycolipid. Statistical analysis was performed and Kendall correlations were obtained. Lewis x showed an apical pattern mainly at plasma membrane, although cytoplasmic staining was also found in most samples. TF, Tn and sTn haptens were detected in few specimens, while sLewis x was found in oral mucosa and breast tissue. Also, normal breast expressed MUC1 at a high percentage, whereas MUC4 was observed in a small number of samples. Colon specimens mainly expressed MUC2 and MUC1, while most oral mucosa samples expressed MUC4 and MUC1. A positive correlation between MUC1VNTR and TF epitope (r=0.396) was found in breast samples, while in colon specimens MUC2 and colonic glycolipid versus Lewis x were statistically significantly correlated (r=0.28 and r=0.29, respectively). As a conclusion, a defined carbohydrate epitope expression is not exclusive of normal tissue or a determined localization, and it is possible to assume that different glycoproteins and glycolipids may be carriers of carbohydrate antigens depending on the tissue localization considered.

  14. Analysis of RF exposure in the head tissues of children and adults

    International Nuclear Information System (INIS)

    Wiart, J; Hadjem, A; Wong, M F; Bloch, I

    2008-01-01

    This paper analyzes the radio frequencies (RF) exposure in the head tissues of children using a cellular handset or RF sources (a dipole and a generic handset) at 900, 1800, 2100 and 2400 MHz. Based on magnetic resonance imaging, child head models have been developed. The maximum specific absorption rate (SAR) over 10 g in the head has been analyzed in seven child and six adult heterogeneous head models. The influence of the variability in the same age class is carried out using models based on a morphing technique. The SAR over 1 g in specific tissues has also been assessed in the different types of child and adult head models. Comparisons are performed but nevertheless need to be confirmed since they have been derived from data sets of limited size. The simulations that have been performed show that the differences between the maximum SAR over 10 g estimated in the head models of the adults and the ones of the children are small compared to the standard deviations. But they indicate that the maximum SAR in 1 g of peripheral brain tissues of the child models aged between 5 and 8 years is about two times higher than in adult models. This difference is not observed for the child models of children above 8 years old: the maximum SAR in 1 g of peripheral brain tissues is about the same as the one in adult models. Such differences can be explained by the lower thicknesses of pinna, skin and skull of the younger child models

  15. Angular photogrammetric soft tissue facial profile analysis of Bangladeshi young adults

    Directory of Open Access Journals (Sweden)

    Lubna Akter

    2017-01-01

    Full Text Available Introduction: Angular photogrammetric soft tissue facial profile analysis provides a permanent record for the actual appearance of a person, which would also serve to establish an ideal esthetic treatment goal. The aim of the present study was to evaluate the average angular variables that define the soft tissue facial profile of a Bangladeshi sample. Materials and Methods: This cross-sectional study was carried out at Department of Orthodontics and Dentofacial Orthopedics of Dhaka Dental College and Hospital, Bangladesh, from July to December 2015. Soft tissue facial profiles of 200 participants (100 males and 100 females between 18 and 25 years of age, with a dental Class I occlusal relationship and harmonious soft tissue profile, were selected by convenience sampling among students, doctors, and patients of Dhaka Dental College. Standardized photographs of 200 samples were taken in the natural head position. The photographic records were analyzed with the software for Windows, Microsoft Visio 2007, Standard Edition. All data were analyzed through standard methods using Statistical Package for the Statistical Package for Social Science Software (SPSS Version-20, IBM Corp, USA. Results: The average angular measurements for nasofrontal, total facial angle, facial angle, upper lip angle, projection of lower lip to chin, and mentolabial angle were wider in females. The mean value for nose tip angle, nasolabial angle, nasomental angle, and projection of upper lip to chin angle was higher in males compared to females. Nasofrontal angle (G-N-Nd (P = 0.000 and mentolabial angle (Li-Sm-Pg (P = 0.001 showed statistically significant differences. The greatest variability was found for mentolabial angle. Conclusion: The study of angular photogrammetric soft tissue facial profile analysis of Bangladeshi young adults contributes to the establishment of standardized normal values for the population. This study provides data which can be used in treatment

  16. Studies by radioiodination of normal adult, fetal and leukemic cell membranes

    Energy Technology Data Exchange (ETDEWEB)

    Kannourakis, G; Cauchi, M N [Department of Pathology and Immunology, Monash Medical School, Melbourne, Australia

    1978-01-01

    A comparison was made between cord blood lymphocytes, normal adult lymphocytes and leukemic cells after membrane iodination with lactoperoxidase. A double-labeling technique using lactoperoxidase iodination with /sup 125/I and /sup 131/I followed by analysis on polyacrylamide gel electrophoresis revealed a number of membrane differences between leukemic, normal and fetal cells. There was a reduction in the 70,000 molecular weight component in cord blood cells compared to adult lymphocytes, and an increase in membrane peptides with molecular weights of 35,000, 20,000, 9,000 and 4,000. Although smaller molecular weight peptides were also present in chronic lymphatic leukemia as well as acute myeloid leukemia, these were shown to be distinct from fetal type membrane components.

  17. Adverse event reporting and developments in radiation biology after normal tissue injury: International Atomic Energy Agency consultation

    International Nuclear Information System (INIS)

    Chen Yuhchyau; Trotti, Andy; Coleman, C. Norman; Machtay, Mitchell; Mirimanoff, Rene O.; Hay, John; O'Brien, Peter C.; El-Gueddari, Brahim; Salvajoli, Joao V.; Jeremic, Branislav

    2006-01-01

    Purpose: Recent research has enhanced our understanding of radiation injury at the molecular-cellular and tissue levels; significant strides have occurred in standardization of adverse event reporting in clinical trials. In response, the International Atomic Energy Agency, through its Division of Human Health and its section for Applied Radiation Biology and Radiotherapy, organized a consultation meeting in Atlanta (October 2, 2004) to discuss developments in radiobiology, normal tissue reactions, and adverse event reporting. Methods and Materials: Representatives from cooperative groups of African Radiation Oncology Group, Curriculo Radioterapeutica Ibero Latino Americana, European Organization for Research and Treatment of Cancer, National Cancer Institute of Canada Clinical Trials Group, Radiation Therapy Oncology Group, and Trans-Tasman Radiation Oncology Group held the meeting discussion. Results: Representatives of major radiotherapy groups/organizations and prominent leaders in radiotherapy discussed current understanding of normal tissue radiobiologic effects, the design and implementation of future clinical and translational projects for normal tissue injury, and the standardization of adverse-event reporting worldwide. Conclusions: The consensus was to adopt NCI comprehensive adverse event reporting terminology and grading system (CTCAE v3.0) as the new standard for all cooperative group trials. Future plans included the implementation of coordinated research projects focusing on normal tissue biomarkers and data collection methods

  18. Changes in regional blood flow of normal and tumor tissues following hyperthermia and combined X-ray irradiation

    International Nuclear Information System (INIS)

    Suga, Kazuyoshi

    1986-01-01

    Hyperthermia and X-ray irradiation were given to Ehrlich tumors, which were induced in the ventrum of the right hind foot of ICR mice, and to the normal tissues. Their effects on regional blood flow were examined using Xe-133 local clearance method. Blood flow of the normal tissues remained unchanged by heating at 41 deg C for 30 minutes, and increased by heating at 43 deg C and 45 deg C for 30 minutes. On the contrary, blood flow of the tumors decreased with an increase in temperature. When hypertermia (43 deg C for 30 minutes) was combined with irradiation of 30 Gy, decrease in blood flow of the tumors was greater than the normal tissues at 24 hours. Blood flow of the tumors depended on tumor size. The decreased amount of blood flow by hyperthermia was more for tumors > 250 mm 3 than tumors 3 . Blood flow ratios of tumor to normal tissues were also smaller in tumors > 250 mm 3 than tumors 3 . In the case of tumors 3 , blood flow tended to return to normal at 3 hr after heating at 43 deg C for 30 min. However, this was not seen in tumors > 250 mm 3 . (Namekawa, K.)

  19. Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

    International Nuclear Information System (INIS)

    Curtis, Carol D; Thorngren, Daniel L; Nardulli, Ann M

    2010-01-01

    During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue. We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells

  20. Repair in normal tissues and the possible relevance to radiotherapy

    International Nuclear Information System (INIS)

    Field, S.B.; Hornsey, S.

    1977-01-01

    Between each fraction in radiotherapy, there is repair and recovery of both normal and neoplastic tissues. Several different types of repair have been identified. Some relate specifically to the effect of changing the number of fractions and others to the overall treatment time. Each will be discussed and particular attention will be paid to slow repair phenomena which have recently been the subject of much interest. (orig.) [de

  1. Evaluation of cyclooxygenase protein expression in traumatized versus normal tissues from eastern box turtles (Terrapene carolina carolina).

    Science.gov (United States)

    Royal, Lillian W; Lascelles, B Duncan X; Lewbart, Gregory A; Correa, Maria T; Jones, Samuel L

    2012-06-01

    This pilot study was designed to determine whether cyclooxygenase (COX)-1, COX-2, or both are expressed in normal turtle tissues and whether level of expression changes when tissue becomes inflamed. Five eastern box turtles, Terrapene carolina carolina, that either died or were euthanatized due to disease or injuries were used for this work. Tissues were obtained from the five turtles. Western blot analysis was used to evaluate tissues for COX-1 and COX-2 proteins. Densiometric analysis was used to compare Western blot bands within each turtle. COX-1 and COX-2 were found in the liver, kidney, grossly normal muscle, and grossly traumatized (inflamed) muscle of all study turtles. In all cases, COX-1 and COX-2 proteins were increased in traumatized muscle over grossly normal nontraumatized muscle. The highest levels of COX-1 and COX-2 proteins were found in kidney and liver. There was no statistical difference between the amount of COX-1 protein in liver and kidney, but traumatized muscle compared with grossly normal muscle had significantly greater COX-1 but not COX 2 protein concentrations. There was no statistical difference between the amount of COX-2 protein in liver and kidney. Traumatized muscle expressed nonstatistically significant greater amounts of COX-2 compared with grossly normal muscle. COX-1 and COX-2 proteins are expressed in turtle tissues, and both isoforms are upregulated during inflammation of muscle tissue. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) that block both COX isoforms might be more efficacious than COX-2-selective drugs. This work suggests that NSAIDs should be evaluated for potential liver and kidney toxicity in turtles.

  2. Normal breast tissue DNA methylation differences at regulatory elements are associated with the cancer risk factor age.

    Science.gov (United States)

    Johnson, Kevin C; Houseman, E Andres; King, Jessica E; Christensen, Brock C

    2017-07-10

    The underlying biological mechanisms through which epidemiologically defined breast cancer risk factors contribute to disease risk remain poorly understood. Identification of the molecular changes associated with cancer risk factors in normal tissues may aid in determining the earliest events of carcinogenesis and informing cancer prevention strategies. Here we investigated the impact cancer risk factors have on the normal breast epigenome by analyzing DNA methylation genome-wide (Infinium 450 K array) in cancer-free women from the Susan G. Komen Tissue Bank (n = 100). We tested the relation of established breast cancer risk factors, age, body mass index, parity, and family history of disease, with DNA methylation adjusting for potential variation in cell-type proportions. We identified 787 cytosine-guanine dinucleotide (CpG) sites that demonstrated significant associations (Q value breast cancer risk factors. Age-related DNA methylation changes are primarily increases in methylation enriched at breast epithelial cell enhancer regions (P = 7.1E-20), and binding sites of chromatin remodelers (MYC and CTCF). We validated the age-related associations in two independent populations, using normal breast tissue samples (n = 18) and samples of normal tissue adjacent to tumor tissue (n = 97). The genomic regions classified as age-related were more likely to be regions altered in both pre-invasive (n = 40, P = 3.0E-03) and invasive breast tumors (n = 731, P = 1.1E-13). DNA methylation changes with age occur at regulatory regions, and are further exacerbated in cancer, suggesting that age influences breast cancer risk in part through its contribution to epigenetic dysregulation in normal breast tissue.

  3. Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

    Science.gov (United States)

    McDonald, Robert J; McDonald, Jennifer S; Kallmes, David F; Jentoft, Mark E; Paolini, Michael A; Murray, David L; Williamson, Eric E; Eckel, Laurence J

    2017-11-01

    Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings

  4. Metabolomic Evidence for a Field Effect in Histologically Normal and Metaplastic Tissues in Patients with Esophageal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Michelle A.C. Reed

    2017-03-01

    Full Text Available Patients with Barrett's esophagus (BO are at increased risk of developing esophageal adenocarcinoma (EAC. Most Barrett's patients, however, do not develop EAC, and there is a need for markers that can identify those most at risk. This study aimed to see if a metabolic signature associated with the development of EAC existed. For this, tissue extracts from patients with EAC, BO, and normal esophagus were analyzed using 1H nuclear magnetic resonance. Where possible, adjacent histologically normal tissues were sampled in those with EAC and BO. The study included 46 patients with EAC, 7 patients with BO, and 68 controls who underwent endoscopy for dyspeptic symptoms with normal appearances. Within the cancer cohort, 9 patients had nonneoplastic Barrett's adjacent to the cancer suitable for biopsy. It was possible to distinguish between histologically normal, BO, and EAC tissue in EAC patients [area under the receiver operator curve (AUROC 1.00, 0.86, and 0.91] and between histologically benign BO in the presence and absence of EAC (AUROC 0.79. In both these cases, sample numbers limited the power of the models. Comparison of histologically normal tissue proximal to EAC versus that from controls (AUROC 1.00 suggests a strong field effect which may develop prior to overt EAC and hence be useful for identifying patients at high risk of developing EAC. Excellent sensitivity and specificity were found for this model to distinguish histologically normal squamous esophageal mucosa in EAC patients and healthy controls, with 8 metabolites being very significantly altered. This may have potential diagnostic value if a molecular signature can detect tissue from which neoplasms subsequently arise.

  5. Brown adipose tissue in young adults who were born preterm or small for gestational age.

    Science.gov (United States)

    Kistner, Anna; Rydén, Henric; Anderstam, Björn; Hellström, Ann; Skorpil, Mikael

    2018-06-27

    Brown adipose tissue (BAT) is present and functions to dissipate energy as heat in young adults and can be assessed using magnetic resonance imaging (MRI) to estimate the voxel fat fraction, i.e. proton density fat fraction (PDFF). It is hypothesized that subjects born preterm or small for gestational age (SGA) may exhibit disrupted BAT formation coupled to metabolic factors. Our purpose was to assess the presence of BAT in young adults born extremely preterm or SGA in comparison with controls. We studied 30 healthy subjects (median age, 21 years): 10 born extremely preterm, 10 full term but SGA and 10 full term with a normal birth weight (controls). We utilized an MRI technique combining multiple scans to enable smaller echo spacing and an advanced fat-water separation method applying graph cuts to estimate B0 inhomogeneity. We measured supraclavicular/cervical PDFF, R2*, fat volume, insulin-like growth factor 1, glucagon, thyroid stimulating hormone and the BAT-associated hormones fibroblast growth factor 21 and irisin. The groups did not significantly differ in supraclavicular/cervical PDFF, R2*, fat volume or hormone levels. The mean supraclavicular/cervical PDFF was equivalent between the groups (range 75-77%). Young adults born extremely preterm or SGA show BAT development similar to those born full term at a normal birth weight. Thus, the increased risk of cardiovascular and metabolic disorders in these groups is not due to the absence of BAT, although our results do not exclude possible BAT involvement in this scenario. Larger studies are needed to understand these relationships.

  6. The effect of customized beam shaping on normal tissue complications in radiation therapy of parotid gland tumors

    International Nuclear Information System (INIS)

    Keus, R.; Boer, R. de; Lebesque, J.; Noach, P.

    1991-01-01

    The impact of customized beam shaping was studied for 5 patients with parotid tumors treated with a paired wedged field technique. For each patient 2 plans were generated. The standard plan had unblocked portals with field sizes defined by the largest target contour found in any CT slice. In the 2nd plan customized beam's view (BEV) designed blocks were added to both beams. The differences in those distributions between the 2 types of plans were evaluated using dose-volume histograms (DVH). As expected, the dose distribution within the target volume showed no difference. However, a considerable sparing of normal tissue was observed for the plans with customized blocks. The volume of un-necessary exposed normal tissue that received more than 90 percent of the prescribed dose, was reduced by a factor of about 4: from 165 to 44 percent on an average, if the volume is expressed as a percentage of the target volume in each patient. In particular, the homolateral mandible showed a mean decrease of 21 percent of integral dose when blocks were used. Normal tissue complication probabilities (NTCP) were calculated. For a tumor dose of 70 Gy, the average bone necrosis probability was reduced from 8.4 percent (no blocks) to 4.1. percent (blocks). For other normal tissues such as nervous tissue, other soft tissues and bones a substantial reduction of integral dose was found for al patients when individual blocks were used. (author). 10 refs.; 4 figs.; 2 tabs

  7. A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

    Energy Technology Data Exchange (ETDEWEB)

    Lazebnik, Mariya [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Popovic, Dijana [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); McCartney, Leah [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); Watkins, Cynthia B [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Lindstrom, Mary J [Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI (United States); Harter, Josephine [Department of Pathology, University of Wisconsin, Madison, WI (United States); Sewall, Sarah [Department of Pathology, University of Wisconsin, Madison, WI (United States); Ogilvie, Travis [Department of Pathology, University of Calgary, Calgary, AB (Canada); Magliocco, Anthony [Department of Pathology, University of Calgary, Calgary, AB (Canada); Breslin, Tara M [Department of Surgery, University of Wisconsin, Madison, WI (United States); Temple, Walley [Department of Surgery and Oncology, University of Calgary, Calgary, AB (Canada); Mew, Daphne [Department of Surgery and Oncology, University of Calgary, Calgary, AB (Canada); Booske, John H [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States); Okoniewski, Michal [Department of Electrical and Computer Engineering, University of Calgary, Calgary, AB (Canada); Hagness, Susan C [Department of Electrical and Computer Engineering, University of Wisconsin, Madison, WI (United States)

    2007-10-21

    The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

  8. A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

    Science.gov (United States)

    Lazebnik, Mariya; Popovic, Dijana; McCartney, Leah; Watkins, Cynthia B.; Lindstrom, Mary J.; Harter, Josephine; Sewall, Sarah; Ogilvie, Travis; Magliocco, Anthony; Breslin, Tara M.; Temple, Walley; Mew, Daphne; Booske, John H.; Okoniewski, Michal; Hagness, Susan C.

    2007-10-01

    The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%.

  9. A large-scale study of the ultrawideband microwave dielectric properties of normal, benign and malignant breast tissues obtained from cancer surgeries

    International Nuclear Information System (INIS)

    Lazebnik, Mariya; Popovic, Dijana; McCartney, Leah; Watkins, Cynthia B; Lindstrom, Mary J; Harter, Josephine; Sewall, Sarah; Ogilvie, Travis; Magliocco, Anthony; Breslin, Tara M; Temple, Walley; Mew, Daphne; Booske, John H; Okoniewski, Michal; Hagness, Susan C

    2007-01-01

    The development of microwave breast cancer detection and treatment techniques has been driven by reports of substantial contrast in the dielectric properties of malignant and normal breast tissues. However, definitive knowledge of the dielectric properties of normal and diseased breast tissues at microwave frequencies has been limited by gaps and discrepancies across previously published studies. To address these issues, we conducted a large-scale study to experimentally determine the ultrawideband microwave dielectric properties of a variety of normal, malignant and benign breast tissues, measured from 0.5 to 20 GHz using a precision open-ended coaxial probe. Previously, we reported the dielectric properties of normal breast tissue samples obtained from reduction surgeries. Here, we report the dielectric properties of normal (adipose, glandular and fibroconnective), malignant (invasive and non-invasive ductal and lobular carcinomas) and benign (fibroadenomas and cysts) breast tissue samples obtained from cancer surgeries. We fit a one-pole Cole-Cole model to the complex permittivity data set of each characterized sample. Our analyses show that the contrast in the microwave-frequency dielectric properties between malignant and normal adipose-dominated tissues in the breast is considerable, as large as 10:1, while the contrast in the microwave-frequency dielectric properties between malignant and normal glandular/fibroconnective tissues in the breast is no more than about 10%

  10. Altered expression of estrogen receptor-α variant messenger RNAs between adjacent normal breast and breast tumor tissues

    International Nuclear Information System (INIS)

    Leygue, Etienne; Dotzlaw, Helmut; Watson, Peter H; Murphy, Leigh C

    2000-01-01

    Using semiquantitative reverse transcription-polymerase chain reaction assays, we investigated the expression of variant messenger RNAs relative to wild-type estrogen receptor (ER)-α messenger RNA in normal breast tissues and their adjacent matched breast tumor tissues. Higher ER variant truncated after sequences encoding exon 2 of the wild-type ER-α (ERC4) messenger RNA and a lower exon 3 deleted ER-α variant (ERD3) messenger RNA relative expression in the tumor compartment were observed in the ER-positive/PR-positive and the ER-positive subsets, respectively. A significantly higher relative expression of exon 5 deleted ER-α varient (ERD5) messenger RNA was observed in tumor components overall. These data demonstrate that changes in the relative expression of ER-α variant messenger RNAs occur between adjacent normal and neoplastic breast tissues. We suggest that these changes might be involved in the mechanisms that underlie breast tumorigenesis. Estrogen receptor (ER)-α and ER-β are believed to mediate the action of estradiol in target tissues. Several ER-α and ER-β variant messenger RNAs have been identified in both normal and neoplastic human tissues. Most of these variants contain a deletion of one or more exons of the wild-type (WT) ER messenger RNAs. The putative proteins that are encoded by these variant messenger RNAs would therefore be missing some functional domains of the WT receptors, and might interfere with WT-ER signaling pathways. The detection of ER-α variants in both normal and neoplastic human breast tissues raised the question of their possible role in breast tumorigenesis. We have previously reported an increased relative expression of exon 5 deleted ER-α variant (ERD5) messenger RNA and of another ER-α variant truncated of all sequences following the exon 2 of the WT ER-α (ERC4) messenger RNA in breast tumor samples versus independent normal breast tissues. In contrast, a decreased relative expression of exon 3 deleted ER

  11. Radiosensitization In Vivo by Histone Deacetylase Inhibition with No Increase in Early Normal Tissue Radiation Toxicity.

    Science.gov (United States)

    Groselj, Blaz; Ruan, Jia-Ling; Scott, Helen; Gorrill, Jessica; Nicholson, Judith; Kelly, Jacqueline; Anbalagan, Selvakumar; Thompson, James; Stratford, Michael R L; Jevons, Sarah J; Hammond, Ester M; Scudamore, Cheryl L; Kerr, Martin; Kiltie, Anne E

    2018-02-01

    As the population ages, more elderly patients require radiotherapy-based treatment for their pelvic malignancies, including muscle-invasive bladder cancer, as they are unfit for major surgery. Therefore, there is an urgent need to find radiosensitizing agents minimally toxic to normal tissues, including bowel and bladder, for such patients. We developed methods to determine normal tissue toxicity severity in intestine and bladder in vivo , using novel radiotherapy techniques on a small animal radiation research platform (SARRP). The effects of panobinostat on in vivo tumor growth delay were evaluated using subcutaneous xenografts in athymic nude mice. Panobinostat concentration levels in xenografts, plasma, and normal tissues were measured in CD1-nude mice. CD1-nude mice were treated with drug/irradiation combinations to assess acute normal tissue effects in small intestine using the intestinal crypt assay, and later effects in small and large intestine at 11 weeks by stool assessment and at 12 weeks by histologic examination. In vitro effects of panobinostat were assessed by qPCR and of panobinostat, TMP195, and mocetinostat by clonogenic assay, and Western blot analysis. Panobinostat resulted in growth delay in RT112 bladder cancer xenografts but did not significantly increase acute (3.75 days) or 12 weeks' normal tissue radiation toxicity. Radiosensitization by panobinostat was effective in hypoxic bladder cancer cells and associated with class I HDAC inhibition, and protein downregulation of HDAC2 and MRE11. Pan-HDAC inhibition is a promising strategy for radiosensitization, but more selective agents may be more useful radiosensitizers clinically, resulting in fewer systemic side effects. Mol Cancer Ther; 17(2); 381-92. ©2017 AACR See all articles in this MCT Focus section, "Developmental Therapeutics in Radiation Oncology." ©2017 American Association for Cancer Research.

  12. Simulation study of pO2 distribution in induced tumour masses and normal tissues within a microcirculation environment.

    Science.gov (United States)

    Li, Mao; Li, Yan; Wen, Peng Paul

    2014-01-01

    The biological microenvironment is interrupted when tumour masses are introduced because of the strong competition for oxygen. During the period of avascular growth of tumours, capillaries that existed play a crucial role in supplying oxygen to both tumourous and healthy cells. Due to limitations of oxygen supply from capillaries, healthy cells have to compete for oxygen with tumourous cells. In this study, an improved Krogh's cylinder model which is more realistic than the previously reported assumption that oxygen is homogeneously distributed in a microenvironment, is proposed to describe the process of the oxygen diffusion from a capillary to its surrounding environment. The capillary wall permeability is also taken into account. The simulation study is conducted and the results show that when tumour masses are implanted at the upstream part of a capillary and followed by normal tissues, the whole normal tissues suffer from hypoxia. In contrast, when normal tissues are ahead of tumour masses, their pO2 is sufficient. In both situations, the pO2 in the whole normal tissues drops significantly due to the axial diffusion at the interface of normal tissues and tumourous cells. As the existence of the axial oxygen diffusion cannot supply the whole tumour masses, only these tumourous cells that are near the interface can be partially supplied, and have a small chance to survive.

  13. Influence of nanoparticles accumulation on optical properties of human normal and cancerous liver tissue in vitro estimated by OCT

    International Nuclear Information System (INIS)

    Zhou, Fang; Wei, Huajiang; Guo, Zhouyi; Ye, Xiangping; Hu, Kun; Wu, Guoyong; Yang, Hongqin; Xie, Shusen; He, Yonghong

    2015-01-01

    In this work, the potential use of nanoparticles as contrast agents by using spectral domain optical coherence tomography (SD-OCT) in liver tissue was demonstrated. Gold nanoparticles (average size of 25 and 70 nm), were studied in human normal and cancerous liver tissues in vitro, respectively. Each sample was monitored with SD-OCT functional imaging for 240 min. Continuous OCT monitoring showed that, after application of gold nanoparticles, the OCT signal intensities of normal liver and cancerous liver tissue both increase with time, and the larger nanoparticles tend to produce a greater signal enhancement in the same type of tissue. The results show that the values of attenuation coefficients have significant differences between normal liver tissue and cancerous liver tissue. In addition, 25 nm gold nanoparticles allow higher penetration depth than 70 nm gold nanoparticles in liver tissues. (paper)

  14. Chemical modification of conventional cancer radiotherapy. Tumor sensitization combined with normal tissue protection

    International Nuclear Information System (INIS)

    Kagiya, Tsutomu

    2006-01-01

    Nitrotriazole radiosensitizer, Sanazole (AK-2123, N-(2'-methoxyethyl)-2-(3''-nitro-1''-triazolyl) acetamide) developed by Kyoto University group was studied by 18 groups of 7 countries on fundamental aspects and clinical studies by 30 groups of 12 countries, and reported its effects on tumor sensitization of conventional cancer radiotherapy. On the other hand, the glucosides of vitamin C (Ascorbic acid glucoside, (AsAG) and water soluble derivative of vitamin-E (α-tocopherol glucoside, TMG) developed by Kyoto University group were studied fundamentally by 4 groups of 4 countries and clinically by 2 groups of 2 countries, and reported their effects on normal tissue protection in cancer treatments. These two studies of tumor sensitization and normal tissue protection were proposed as an advanced strategy of conventional cancer radiotherapy. (author)

  15. The use of normal tissue complication probability to predict radiation hepatitis

    International Nuclear Information System (INIS)

    Keum, Ki Chang; Seong, Jin Sil; Suh, Chang Ok; Lee, Sang Wook; Chung, Eun Ji; Shin, Hyun Soo; Kim, Gwi Eon

    2000-01-01

    Although it has been known that the tolerance of the liver to external beam irradiation depends on the irradiated volume and dose, few data exist which quantify this dependence. However, recently, with the development of three dimensional (3-D) treatment planning, have the tools to quantify the relationships between dose, volume, and normal tissue complications become available. The objective of this study is to investigate the relationships between normal tissue complication probability (NTCP) and the risk of radiation hepatitis for patients who received variant dose partial liver irradiation. From March 1992 to December 1994, 10 patients with hepatoma and 10 patients with bile duct cancer were included in this study. Eighteen patients had normal hepatic function, but 2 patients (prothrombin time 73%, 68%) had mild liver cirrhosis before irradiation. Radiation therapy was delivered with 10MV linear accelerator, 180-200 cGy fraction per day. The total dose ranged from 3,960 cGy to 6,000 cGy (median dose 5,040 cGy). The normal tissue complication probability was calculated by using Lyman's model. Radiation hepatitis was defined as the development of anicteric elevation of alkaline phosphatase of at least two fold and non-malignant ascites in the absence of documented progressive. The calculated NTCP ranged from 0.001 to 0.840 (median 0.05). Three of the 20 patients developed radiation hepatitis. The NTCP of the patients with radiation hepatitis were 0.390, 0.528, 0.844 (median: O.58±0.23), but that of the patients without radiation hepatitis ranged from 0.001 to 0.308 (median: 0.09±0.09). When the NTCP was calculated by using the volume factor of 0.32, a radiation hepatitis was observed only in patients with the NTCP value more than 0.39. By contrast, clinical results of evolving radiation hepatitis were not well correlated with NTCP value calculated when the volume factor of 0.69 was applied. On the basis of these observations, volume factor of 0.32 was more

  16. Hole Burning Imaging Studies of Cancerous and Analogous Normal Ovarian Tissues Utilizing Organelle Specific Dyes

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Satoshi [Iowa State Univ., Ames, IA (United States)

    2004-01-01

    Presented in this dissertation is the successful demonstration that nonphotochemical hole burning (NPWB) imaging can be used to study in vitro tissue cellular systems for discerning differences in cellular ultrastructures due to cancer development. This has been accomplished with the surgically removed cancerous ovarian and analogous normal peritoneal tissues from the same patient and the application of a fluorescent mitochondrion specific dye, Molecular Probe MitoFluor Far Red 680 (MF680), commonly known as rhodamine 800, that has been proven to exhibit efficient NPHB. From the results presented in Chapters 4 and 5 , and Appendix B, the following conclusions were made: (1) fluorescence excitation spectra of MF680 and confocal microscopy images of thin sliced tissues incubated with MF680 confirm the site-specificity of the probe molecules in the cellular systems. (2) Tunneling parameters, {lambda}{sub 0} and σΛ, as well as the standard hole burning parameters (namely, γ and S), have been determined for the tissue samples by hole growth kinetics (HGK) analyses. Unlike the preliminary cultured cell studies, these parameters have not shown the ability to distinguish tissue cellular matrices surrounding the chromophores. (3) Effects of an external electric (Stark) field on the nonphotochemical holes have been used to determine the changes in permanent dipole moment (fΔμ) for MF680 in tissue samples when burn laser polarization is parallel to the Stark field. Differences are detected between fΔμs in the two tissue samples, with the cancerous tissue exhibiting a more pronounced change (1.35-fold increase) in permanent dipole moment change relative to the normal analogs. It is speculated that the difference may be related to differences in mitochondrial membrane potentials in these tissue samples. (4) In the HGK mode, hole burning imaging (HBI) of cells adhered to coverslips and cooled to liquid helium temperatures in the complete absence of

  17. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    International Nuclear Information System (INIS)

    Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

    2012-01-01

    Highlights: ► Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. ► Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. ► Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. ► Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P 0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors.

  18. Basement membrane chondroitin sulfate proteoglycans: localization in adult rat tissues

    DEFF Research Database (Denmark)

    McCarthy, K J; Couchman, J R

    1990-01-01

    Heparan sulfate proteoglycans have been described as the major proteoglycan component of basement membranes. However, previous investigators have also provided evidence for the presence of chondroitin sulfate glycosaminoglycan in these structures. Recently we described the production...... and characterization of core protein-specific monoclonal antibodies (MAb) against a chondroitin sulfate proteoglycan (CSPG) present in Reichert's membrane, a transient extra-embryonic structure of rodents. This CSPG was also demonstrated to be present in adult rat kidney. We report here the tissue distribution...... of epitopes recognized by these MAb. The ubiquitous presence of these epitopes in the basement membranes of nearly all adult rat tissues demonstrates that at least one CSPG is a constituent of most basement membranes, and by virtue of its unique distribution is distinct from other chondroitin and dermatan...

  19. Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

    Science.gov (United States)

    Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

    2016-02-01

    Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

  20. Esophageal Clearance Patterns in Normal Older Adults as Documented with Videofluoroscopic Esophagram

    Directory of Open Access Journals (Sweden)

    Janice Jou

    2009-01-01

    Full Text Available Normal esophageal bolus transport in asymptomatic healthy older adults has not been well defined, potentially leading to ambiguity in differentiating esophageal swallowing patterns of dysphagic and healthy individuals. This pilot study of 24 young (45–64 years and old (65+years men and women was designed to assess radiographic esophageal bolus movement patterns in healthy adults using videofluoroscopic recording. Healthy, asymptomatic adults underwent videofluoroscopic esophagram to evaluate for the presence of ineffective esophageal clearance, namely, intraesophageal stasis and intraesophageal reflux. Intraesophageal stasis and intraesophageal reflux were visualized radiographically in these normal subjects. Intraesophageal stasis occurred significantly more frequently with semisolid (96% compared with liquid (16% barium, suggesting that a variety of barium consistencies, as opposed to only the traditional fluids, would better define the spectrum of esophageal transport. Intraesophageal reflux was observed more frequently in older males than in their younger counterparts. The rates of intraesophageal stasis and intraesophageal reflux were potentially high given that successive bolus presentations were spaced 10 seconds apart. These findings suggest a need for a more comprehensive definition regarding the range of normal esophageal bolus transport to (a prevent misdiagnosis of dysphagia and (b to enhance generalization to functional eating, which involves solid foods in addition to liquids.

  1. Fatty acid and lipidomic data in normal and tumor colon tissues of rats fed diets with and without fish oil

    Directory of Open Access Journals (Sweden)

    Zora Djuric

    2017-08-01

    Full Text Available Data is provided to show the detailed fatty acid and lipidomic composition of normal and tumor rat colon tissues. Rats were fed either a Western fat diet or a fish oil diet, and half the rats from each diet group were treated with chemical carcinogens that induce colon cancer (azoxymethane and dextran sodium sulfate. The data show total fatty acid profiles of sera and of all the colon tissues, namely normal tissue from control rats and both normal and tumor tissues from carcinogen-treated rats, as obtained by gas chromatography with mass spectral detection. Data from lipidomic analyses of a representative subset of the colon tissue samples is also shown in heat maps generated from hierarchical cluster analysis. These data display the utility lipidomic analyses to enhance the interpretation of dietary feeding studies aimed at cancer prevention and support the findings published in the companion paper (Effects of fish oil supplementation on prostaglandins in normal and tumor colon tissue: modulation by the lipogenic phenotype of colon tumors, Djuric et al., 2017 [1].

  2. N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Eiko; Mishima, Michiaki; Kawakami, Kenzo; Sakai, Naoki; Sugiura, Naoharu; Kuno, Kenshi [Kyoto Univ. (Japan). Dept. of Clinical Physiology; Taniguchi, Takashi [Kyoto Pharmaceutical Univ. (Japan). Dept. of Neurobiology

    1993-04-01

    N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (K[sub d]) values of 53[+-]2 and 4687[+-]124 nM and maximum binding capacity (Bmax) values of 7[+-]1 and 133[+-]27 pmol/mg protein (n=5) respectively. The IC[sub 50] values of various amines were as follows: IMP, 9x10[sup -5] M; propranolol, 5x10[sup -4] M; haloperidol, 6x10[sup -4] M; ketamine, 9x10[sup -3] M; dopamine, 1x10[sup -2] M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with K[sub d] values of 54[+-]2 and 5277[+-]652 nM and Bmax values of 7[+-]1 and 103[+-]21 pmol/mg protein (n=3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue. (orig.).

  3. [FTIR study on the normal and cancerous stomach tissues].

    Science.gov (United States)

    Tong, Y; Lin, Y

    2001-06-01

    Tissues of cancerous and corresponding normal stomach were studied by FTIR technique. The results showed that there are obvious differences between FTIR spectra of them in spectral parameters such as frequency, intensity and band shape etc. The changes involving the phosphate symmetric stretching nu s, PO2- and asymmetric stretching nu as, PO2- modes, the CH3 and CH2 groups stretching (nu s, CH2, nu as, CH3) and bending (delta CH2) modes and the C-O stretching nu C-O mode were discussed. In addition, the changes of structure of hydrogen-bonding of nucleic acid and cell proteins and the packing and the conformational structure of the membrance lipids were analysed further. The average wavenumber of band of nu s, PO2- shifted from 1,080.92 cm-1 to 1,085.93 cm-1 and that of nu as, PO2- shifted from 1,239.64 cm-1 to 1,238.73 cm-1 which indicated that the degree of hydrogen-bonding formed by oxygen atom of the phosphodiester groups of nucleic acids was increased. The average wavenumber of band of delta CH2 of membrance lipids shifted from 1,455.23 cm-1 to 1,457.37 cm-1 that suggested that the conformational structure of the methylene chains of membrance lipids is more disordered than in normal tissues. The shift of band of nu C-O of cell proteins from 1,166.08 cm-1 to 1,166.58 cm-1 indicated that the hydrogen-bond of cell proteins become weaker.

  4. Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis

    Directory of Open Access Journals (Sweden)

    Ana Paula Cleto Marolla

    2016-01-01

    Conclusions: The expression of HA was found to be slightly lower in tumor tissue than in colorectal non-neoplastic mucosa, although this difference was not statistically significant. This finding probably influenced the lower expression of HA in tumor tissue than in colorectal non-neoplastic mucosa. Compared to normal tissues, HA levels are significantly increased in the tumor tissues unless they exhibit lymph node metastasis. Otherwise, the expression of HA in tumor tissue did not correlated with the other clinicopathological parameters.

  5. The Effect of the Alcoholic Extract of Walnut on the Testis Tissue of Adult Male Rats

    Directory of Open Access Journals (Sweden)

    M Abedinzade

    2012-08-01

    Methods: In the present experimental study, forty adult male Wistar rats weighing 250-300 grams were divided into five groups. The control group did not receive any treatment. Normal saline was intraperitoneally injected to the control group. Experimental groups received three different doses of alcoholic extract of walnut: 10, 20 and 50 mg/ kg intraperitoneally/daily, respectively. The testes were removed from the abdomen and the tissue sections were studied. The gathered data were analyzed using One-way Analysis of variance and Tukey's range test. Results: Results indicated that walnut extract affect the development and maintenance of spermatogenesis to its final stages, and increased the number of sperms and interstitial cells in the testis. Alcoholic extract of walnut during the test instrument did not have much impact on the structure of the sperm tube tissue. Conclusion: The alcoholic extract of walnut led to the increased activity of the testis and interstitial cells, followed by an increase in sperm cells and reproductive activity of male rats.

  6. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Antoniassi, M.; Conceicao, A.L.C. [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica-Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto-Universidade de Sao Paulo, Ribeirao Preto, Sao Paulo (Brazil)

    2012-07-15

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: Black-Right-Pointing-Pointer Electron density of normal and neoplastic breast tissues was measured using Compton scattering. Black-Right-Pointing-Pointer Monochromatic synchrotron radiation was used to obtain the Compton scattering data. Black-Right-Pointing-Pointer The area of Compton peaks was used to determine the electron densities of samples. Black-Right-Pointing-Pointer Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. Black-Right-Pointing-Pointer Comparison with previous results showed differences smaller than 4%.

  7. Study of electron densities of normal and neoplastic human breast tissues by Compton scattering using synchrotron radiation

    International Nuclear Information System (INIS)

    Antoniassi, M.; Conceição, A.L.C.; Poletti, M.E.

    2012-01-01

    Electron densities of 33 samples of normal (adipose and fibroglangular) and neoplastic (benign and malignant) human breast tissues were determined through Compton scattering data using a monochromatic synchrotron radiation source and an energy dispersive detector. The area of Compton peaks was used to determine the electron densities of the samples. Adipose tissue exhibits the lowest values of electron density whereas malignant tissue the highest. The relationship with their histology was discussed. Comparison with previous results showed differences smaller than 4%. - Highlights: ► Electron density of normal and neoplastic breast tissues was measured using Compton scattering. ► Monochromatic synchrotron radiation was used to obtain the Compton scattering data. ► The area of Compton peaks was used to determine the electron densities of samples. ► Adipose tissue shows the lowest electron density values whereas the malignant tissue the highest. ► Comparison with previous results showed differences smaller than 4%.

  8. Reaffirming normal: the high risk of pathologizing healthy adults when interpreting the MMPI-2-RF.

    Science.gov (United States)

    Odland, Anthony P; Lammy, Andrew B; Perle, Jonathan G; Martin, Phillip K; Grote, Christopher L

    2015-01-01

    Monte Carlo simulations were utilized to determine the proportion of the normal population expected to have scale elevations on the MMPI-2-RF when multiple scores are interpreted. Results showed that when all 40 MMPI-2-RF scales are simultaneously considered, approximately 70% of normal adults are likely to have at least one scale elevation at or above 65 T, and as many as 20% will have five or more elevated scales. When the Restructured Clinical (RC) Scales are under consideration, 34% of normal adults have at least one elevated score. Interpretation of the Specific Problem Scales and Personality Psychopathology Five Scales--Revised also yielded higher than expected rates of significant scores, with as many as one in four normal adults possibly being miscategorized as having features of a personality disorder by the latter scales. These findings are consistent with the growing literature on rates of apparently abnormal scores in the normal population due to multiple score interpretation. Findings are discussed in relation to clinical assessment, as well as in response to recent work suggesting that the MMPI-2-RF's multiscale composition does not contribute to high rates of elevated scores.

  9. Normal weight obesity among young adults in Trinidad and Tobago: prevalence and associated factors.

    Science.gov (United States)

    Ramsaran, Cherrita; Maharaj, Rohan G

    2017-04-01

    Patients with normal weight obesity (NWO) have a normal body mass index (BMI) but elevated body fat percentage (BF%), thereby increasing their risk of cardiovascular and metabolic disorders. The purpose of this research was to determine the prevalence of NWO and its associated factors in a sample of young adults in Trinidad and Tobago (T&T). A cross sectional study involving a convenience non-voluntary sample of participants with a normal BMI of 18.5-24.9 kg/m2 was conducted. The following information was collected: history, basic anthropometric measurements, including BF% via the Tanita Ironman Body Composition Analyzer (BC554), physical examination and basic blood investigations. Participants were divided into two groups; normal BF% (young adult population was found to have NWO. Long-term studies are recommended to study the full implications of these findings.

  10. Mineral density volume gradients in normal and diseased human tissues.

    Directory of Open Access Journals (Sweden)

    Sabra I Djomehri

    Full Text Available Clinical computed tomography provides a single mineral density (MD value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca to phosphorus (P and Ca to zinc (Zn elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males contained significant mineral density variations (enamel: 2820-3095 mg/cc, bone: 570-1415 mg/cc, cementum: 1240-1340 mg/cc, dentin: 1480-1590 mg/cc, cementum affected by periodontitis: 1100-1220 mg/cc, hypomineralized carious dentin: 345-1450 mg/cc, hypermineralized carious dentin: 1815-2740 mg/cc, and dental calculus: 1290-1770 mg/cc. A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49, hypomineralized dentin (0.32-0.46, cementum (1.51, and bone (1.68 were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765 and in cementum (595-990, highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations.

  11. Mineral Density Volume Gradients in Normal and Diseased Human Tissues

    Science.gov (United States)

    Djomehri, Sabra I.; Candell, Susan; Case, Thomas; Browning, Alyssa; Marshall, Grayson W.; Yun, Wenbing; Lau, S. H.; Webb, Samuel; Ho, Sunita P.

    2015-01-01

    Clinical computed tomography provides a single mineral density (MD) value for heterogeneous calcified tissues containing early and late stage pathologic formations. The novel aspect of this study is that, it extends current quantitative methods of mapping mineral density gradients to three dimensions, discretizes early and late mineralized stages, identifies elemental distribution in discretized volumes, and correlates measured MD with respective calcium (Ca) to phosphorus (P) and Ca to zinc (Zn) elemental ratios. To accomplish this, MD variations identified using polychromatic radiation from a high resolution micro-computed tomography (micro-CT) benchtop unit were correlated with elemental mapping obtained from a microprobe X-ray fluorescence (XRF) using synchrotron monochromatic radiation. Digital segmentation of tomograms from normal and diseased tissues (N=5 per group; 40-60 year old males) contained significant mineral density variations (enamel: 2820-3095mg/cc, bone: 570-1415mg/cc, cementum: 1240-1340mg/cc, dentin: 1480-1590mg/cc, cementum affected by periodontitis: 1100-1220mg/cc, hypomineralized carious dentin: 345-1450mg/cc, hypermineralized carious dentin: 1815-2740mg/cc, and dental calculus: 1290-1770mg/cc). A plausible linear correlation between segmented MD volumes and elemental ratios within these volumes was established, and Ca/P ratios for dentin (1.49), hypomineralized dentin (0.32-0.46), cementum (1.51), and bone (1.68) were observed. Furthermore, varying Ca/Zn ratios were distinguished in adapted compared to normal tissues, such as in bone (855-2765) and in cementum (595-990), highlighting Zn as an influential element in prompting observed adaptive properties. Hence, results provide insights on mineral density gradients with elemental concentrations and elemental footprints that in turn could aid in elucidating mechanistic processes for pathologic formations. PMID:25856386

  12. Validation of putative reference genes for normalization of Q-RT-PCR data from paraffin-embedded lymphoid tissue

    DEFF Research Database (Denmark)

    Green, Tina Marie; de Stricker, Karin; Møller, Michael Boe

    2009-01-01

    Normalization of quantitative reverse transcription-PCR (Q-RT-PCR) data to appropriate tissue-specific reference genes is an essential part of interpreting the results. This study aimed to determine the most appropriate reference genes for normalizing gene expressions in lymphatic tissue...... was 0.93 (Pnormalization with the appropriate reference genes. Thus, we show that formalin-fixed, paraffin-embedded lymphoid samples are suitable for Q-RT-PCR when using thoroughly validated reference genes....

  13. Alteration of Diastereoisomeric and Enantiomeric Profiles of Hexabromocyclododecanes (HBCDs) in Adult Chicken Tissues, Eggs, and Hatchling Chickens.

    Science.gov (United States)

    Zheng, Xiaobo; Qiao, Lin; Sun, Runxia; Luo, Xiaojun; Zheng, Jing; Xie, Qilai; Sun, Yuxin; Mai, Bixian

    2017-05-16

    The concentrations and enantiomer fractions (EFs) of α-, β-, and γ-hexabromocyclododecanes (HBCDs) were measured in chicken diet sources (soil and chicken feed), home-raised adult chicken (Gallus domesticus) tissues, eggs during incubation, and hatchling chicken tissues. HBCD concentrations were not detected-0.69 ng/g dry weight (dw) and 25.6-48.4 ng/g dw in chicken feed and soil, respectively. HBCDs were detected in all adult chicken tissues, except the brain, at median levels of 13.1-44.0 ng/g lipid weight (lw). The proportions of α-HBCD in total HBCDs increased from 51% in soil to more than 87% in adult chicken tissues. The accumulation ratios (ARs) of α-HBCD from diet to adult chicken tissues were 4.27 for liver, 11.2 for fat, and 7.64-12.9 for other tissues, respectively. The AR and carry-over rate (COR) of α-HBCD from diet to eggs were 22.4 and 0.226, respectively. The concentrations of α-HBCD in hatchling chicken liver (median: 35.4 ng/g lw) were significantly lower than those in hatchling chicken pectoral muscle (median: 130 ng/g lw). The EFs of α-HBCD decreased from soil to adult chicken tissues and from eggs to hatchling chicken liver. Meanwhile, the EFs of γ-HBCD increased from soil to adult chicken tissues. These results indicate the preferential enrichment of (-)-α-HBCD and (+)-γ-HBCD in chickens. The alteration of diastereoisomeric and enantiomeric patterns of HBCDs might be influenced by the different absorption and elimination rates of the six HBCD enantiomers as well as variations in HBCD metabolism in chickens.

  14. SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

    International Nuclear Information System (INIS)

    Zhang, Q; Lei, Y; Zheng, D; Zhu, X; Wahl, A; Lin, C; Zhou, S; Zhen, W

    2015-01-01

    Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness were created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing

  15. Bowman Capsule Volume and Related Factors in Adults With Normal Renal Function

    Directory of Open Access Journals (Sweden)

    Takaya Sasaki

    2018-03-01

    Conclusion: In the normal adult kidney, there may be an optimal BV to GV ratio for maintaining effective filtration in a variety of clinical situations, including advanced age, obesity, and hypertension.

  16. Human papillomavirus in normal conjunctival tissue and in conjunctival papilloma: types and frequencies in a large series.

    Science.gov (United States)

    Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia; Norrild, Bodil; Prause, Jan Ulrik; Vinding, Troels; Heegaard, Steffen

    2007-08-01

    To examine conjunctival papilloma and normal conjunctival tissue for the presence of human papillomavirus (HPV). Archival paraffin wax-embedded tissue from 165 conjunctival papillomas and from 20 histological normal conjunctival biopsy specimens was analysed for the presence of HPV by PCR. Specimens considered HPV positive using consensus primers, but with a negative or uncertain PCR result using type-specific HPV probes, were analysed with DNA sequencing. HPV was present in 86 of 106 (81%) beta-globin-positive papillomas. HPV type 6 was positive in 80 cases, HPV type 11 was identified in 5 cases and HPV type 45 was present in a single papilloma. All the 20 normal conjunctival biopsy specimens were beta-globin positive and HPV negative. There is a strong association between HPV and conjunctival papilloma. The study presents the largest material of conjunctival papilloma investigated for HPV and the first investigation of HPV in normal conjunctival tissue. HPV types 6 and 11 are the most common HPV types in conjunctival papilloma. This also is the first report of HPV type 45 in conjunctival papilloma.

  17. Statistical validation of normal tissue complication probability models.

    Science.gov (United States)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Van't Veld, Aart A; Langendijk, Johannes A; Schilstra, Cornelis

    2012-09-01

    To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Statistical Validation of Normal Tissue Complication Probability Models

    Energy Technology Data Exchange (ETDEWEB)

    Xu Chengjian, E-mail: c.j.xu@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der; Veld, Aart A. van' t; Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schilstra, Cornelis [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Radiotherapy Institute Friesland, Leeuwarden (Netherlands)

    2012-09-01

    Purpose: To investigate the applicability and value of double cross-validation and permutation tests as established statistical approaches in the validation of normal tissue complication probability (NTCP) models. Methods and Materials: A penalized regression method, LASSO (least absolute shrinkage and selection operator), was used to build NTCP models for xerostomia after radiation therapy treatment of head-and-neck cancer. Model assessment was based on the likelihood function and the area under the receiver operating characteristic curve. Results: Repeated double cross-validation showed the uncertainty and instability of the NTCP models and indicated that the statistical significance of model performance can be obtained by permutation testing. Conclusion: Repeated double cross-validation and permutation tests are recommended to validate NTCP models before clinical use.

  19. Motivation to Address Self-Reported Hearing Problems in Adults with Normal Hearing Thresholds

    Science.gov (United States)

    Alicea, Carly C. M.; Doherty, Karen A.

    2017-01-01

    Purpose: The purpose of this study was to compare the motivation to change in relation to hearing problems in adults with normal hearing thresholds but who report hearing problems and that of adults with a mild-to-moderate sensorineural hearing loss. Factors related to their motivation were also assessed. Method: The motivation to change in…

  20. An automatic method to discriminate malignant masses from normal tissue in digital mammograms

    International Nuclear Information System (INIS)

    Brake, Guido M. te; Karssemeijer, Nico; Hendriks, Jan H.C.L.

    2000-01-01

    Specificity levels of automatic mass detection methods in mammography are generally rather low, because suspicious looking normal tissue is often hard to discriminate from real malignant masses. In this work a number of features were defined that are related to image characteristics that radiologists use to discriminate real lesions from normal tissue. An artificial neural network was used to map the computed features to a measure of suspiciousness for each region that was found suspicious by a mass detection method. Two data sets were used to test the method. The first set of 72 malignant cases (132 films) was a consecutive series taken from the Nijmegen screening programme, 208 normal films were added to improve the estimation of the specificity of the method. The second set was part of the new DDSM data set from the University of South Florida. A total of 193 cases (772 films) with 372 annotated malignancies was used. The measure of suspiciousness that was computed using the image characteristics was successful in discriminating tumours from false positive detections. Approximately 75% of all cancers were detected in at least one view at a specificity level of 0.1 false positive per image. (author)

  1. Assessment of various hilar measurements on PA chest of Korean normal adults

    International Nuclear Information System (INIS)

    Ro, Hee Jeong; Kim, Hyun; Kang, Si Won; Park, Seog Hee; Bahk, Yong Whee

    1990-01-01

    Appreciation of the normal position of the hila is essential in screening and diagnosis of the diseases of the chest. Many authors assessed the hilar position in normal adults using PA chest roentgenograms. However there have been no previous publication regarding consolidated assessment of various measurements. The authors carried out the present study to evaluate various hilar measurements including hilar points, hilar distances, difference between both hilar heights, hilar height ratio, and the relationship between the level of the clavicle and hila on the 500 normal PA chest roentgenograms

  2. Azacytidine and miR156 promote rooting in adult but not in juvenile Arabidopsis tissues.

    Science.gov (United States)

    Massoumi, Mehdi; Krens, Frans A; Visser, Richard G F; De Klerk, Geert-Jan M

    2017-01-01

    Poor adventitious root (AR) formation is a major obstacle in micropropagation and conventional vegetative propagation of many crops. It is affected by many endogenous and exogenous factors. With respect to endogenous factors, the phase change from juvenile to adult has a major influence on AR formation and rooting is usually much reduced or even fully inhibited in adult tissues. It has been reported that the phase change is characterized by an increase in DNA-methylation and a decrease in the expression of microRNA156 (miR156). In this paper, we examined the effect of azacytidine (AzaC) and miR156 on AR formation in adult and juvenile Arabidopsis tissues. To identify the ontogenetic state researchers have used flowering or leaf morphology. We have used the rootability which allows - in contrast with both other characteristics- to examine the ontogenetic state at the cellular level. Overexpression of miR156 promoted only the rooting of adult tissues indicating that the phase change-associated loss in tissues' competence to develop ARs is also under the control of miR156. Azacytidine inhibits DNA methylation during DNA replication. Azacytidine treatment also promoted AR formation in nonjuvenile tissues but had no or little effect in juvenile tissues. Its addition during seedling growth (by which all tissues become hypomethylated) or during the rooting treatment (by which only those cells become hypomethylated that are generated after taking the explant) are both effective in the promotion of rooting. An AzaC treatment may be useful in tissue culture for crops that are recalcitrant to root. Copyright © 2016 Elsevier GmbH. All rights reserved.

  3. On radiation damage to normal tissues and its treatment. Pt. 2

    International Nuclear Information System (INIS)

    Michalowski, A.S.

    1994-01-01

    In addition to transiently inhibiting cell cycle progression and sterilizing those cells capable of proliferation, irradiation disturbs the homeostasis effected by endogenous mediators of intercellular communication (humoral component of tissue response to radiation). Changes in the mediator levels may modulate radiation effects either by a assisting a return to normality (e.g., through a rise in H-type cell lineage-specific growth factors) or by aggravating the damage. The latter mode is illustrated with reports on changes in eicosanoid levels after irradiation and on results of empirical treatment of radiation injuries with anti-inflammatory drugs. Prodromal, acute and chronic effects of radiation are accompanied by excessive production of eicosanoids (prostaglandins, prostacyclin, thromboxanes and leukotrienes). These endogenous mediators of inflammatory reactions may be responsible for the vasodilatation, vasoconstriction, increased microvascular permeability, thrombosis and chemotaxis observed after radiation exposure. Glucocorticoids inhibit eicosanoid synthesis primarily by interfering with phospholipase A 2 whilst non-steroidal anti-inflammatory drugs prevent prostaglandin/thromboxane synthesis by inhibiting cycloxygenase. When administered after irradiation on empirical grounds, drugs belonging to both groups tend to attenuate a range of prodomal, acute and chronic effects of radiation in man and animals. Taken together, these two sets of observations are highly suggestive of a contribution of humoral factors to the adverse responses of normal tissues and organs to radiation. A full account of radiation damage should therefore consist of complementary descriptions of cellular and humoral events. Further studies on anti-inflammatory drug treatment of radiation damage to normal organs are justified and desirable. (orig.)

  4. Extracranial soft-tissue swelling: a normal postmortem radiographic finding or a sign of trauma?

    International Nuclear Information System (INIS)

    Strouse, P.J.; Caplan, M.; Owings, C.L.

    1998-01-01

    Objective. To determine if extracranial soft-tissue swelling is an expected postmortem finding or a sign of trauma. Materials and methods. Extracranial soft-tissue thickness was measured at 5 standardized locations on postmortem skull films obtained of 18 infants with no evidence of trauma on autopsy. The same measurements were performed on the skull films of 100 living children, all less than 3 years old and without clinical history of trauma. Results. Extracranial soft tissues measured only slightly greater in the postmortem group than on films of living children; however, the difference did achieve statistical significance. Conclusion. Minimal extracranial soft-tissue swelling is a normal finding on a postmortem skeletal survey. The presence of substantial or asymmetric extracranial soft-tissue swelling should be viewed with suspicion for trauma. (orig.)

  5. Extracranial soft-tissue swelling: a normal postmortem radiographic finding or a sign of trauma?

    Energy Technology Data Exchange (ETDEWEB)

    Strouse, P.J. [Section of Pediatric Radiology, University of Michigan Medical Center, Ann Arbor (United States); Caplan, M. [Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan (United States); Owings, C.L. [Department of Pediatrics and Communicable Diseases, C. S. Mott Children`s Hospital, Ann Arbor, Michigan (United States)

    1998-08-01

    Objective. To determine if extracranial soft-tissue swelling is an expected postmortem finding or a sign of trauma. Materials and methods. Extracranial soft-tissue thickness was measured at 5 standardized locations on postmortem skull films obtained of 18 infants with no evidence of trauma on autopsy. The same measurements were performed on the skull films of 100 living children, all less than 3 years old and without clinical history of trauma. Results. Extracranial soft tissues measured only slightly greater in the postmortem group than on films of living children; however, the difference did achieve statistical significance. Conclusion. Minimal extracranial soft-tissue swelling is a normal finding on a postmortem skeletal survey. The presence of substantial or asymmetric extracranial soft-tissue swelling should be viewed with suspicion for trauma. (orig.) With 2 tabs., 5 refs.

  6. A general native-state method for determination of proliferation capacity of human normal and tumor tissues in vitro

    International Nuclear Information System (INIS)

    Hoffman, R.M.; Connors, K.M.; Meerson-Monosov, A.Z.; Herrera, H.; Price, J.H.

    1989-01-01

    An important need in cancer research and treatment is a physiological means in vitro by which to assess the proliferation capacity of human tumors and corresponding normal tissue for comparison. The authors have recently developed a native-state, three-dimensional, gel-supported primary culture system that allows every type of human cancer to grow in vitro at more than 90% frequency, with maintenance of tissue architecture, tumor-stromal interaction, and differentiated functions. Here they demonstrate that the native-state culture system allows proliferation indices to be determined for all solid cancer types explanted directly from surgery into long-term culture. Normal tissues also proliferate readily in this system. The degree of resolution of measurement of cell proliferation by histological autoradiography within the cultured tissues is greatly enhanced with the use of epi-illumination polarization microscopy. The histological status of the cultured tissues can be assessed simultaneously with the proliferation status. Carcinomas generally have areas of high epithelial proliferation with quiescent stromal cells. Sarcomas have high proliferation of cells of mesenchymal organ. Normal tissues can also proliferate at high rates. An image analysis system has been developed to automate proliferation determination. The high-resolution physiological means described here to measure the proliferation capacity of tissues will be important in further understanding of the deregulation of cell proliferation in cancer as well as in cancer prognosis and treatment

  7. Association between individual fat depots and cardio-metabolic traits in normal- and overweight children, adolescents and adults.

    Science.gov (United States)

    Hübers, M; Geisler, C; Plachta-Danielzik, S; Müller, M J

    2017-05-08

    To determine age-related associations between fat mass (FM), regional fat depots and cardiometabolic traits in normal- and overweight children, adolescents and adults. Detailed body composition (regional subcutaneous and visceral adipose tissue; SAT, VAT) by whole-body magnetic resonance imaging (MRI), FM and fat-free mass by air-displacement plethysmography, systolic and diastolic blood pressure (SBP, DBP), triglycerides (TG), high-density lipoprotein cholesterol (HDL), plasma glucose and plasma insulin were measured in 433 subjects (BMI: 23.6 (21.0-27.7); 151 children and adolescents, aged 6-18 years, 150 young adults, aged 18-30 years and 132 adults, aged 30-60 years). Data were derived from pooled data of the 'Reference Center for Body Composition' in Kiel, Germany. Insulin resistance was determined by the homeostatic model assessment of insulin resistance (HOMA-IR). Partial correlations and multivariate linear regression analyses were used to evaluate the associations between body composition and cardiometabolic traits. A descriptive approach was used to demonstrate age-dependent differences in associations between body fat depots and insulin resistance, independent of BMI. FM, SAT, and VAT increased from childhood to adulthood with low VAT in children and adolescents. When compared to children, TG was higher in adults. HDL and DBP did not differ between age groups. Insulin resistance was highest in male adolescents and female young adults. Associations between body fat depots and cardiometabolic traits were seen after puberty with no associations in pre- and intrapubertal children. When compared to FM, SAT and VAT had the strongest association with insulin resistance in adults. This association was independent of BMI. Associations between individual body fat depots and most cardiometabolic traits became evident after puberty only. The strongest associations were observed between insulin resistance and abdominal fat in adults. The impact of VAT was independent

  8. Improving normal tissue complication probability models: the need to adopt a "data-pooling" culture.

    Science.gov (United States)

    Deasy, Joseph O; Bentzen, Søren M; Jackson, Andrew; Ten Haken, Randall K; Yorke, Ellen D; Constine, Louis S; Sharma, Ashish; Marks, Lawrence B

    2010-03-01

    Clinical studies of the dependence of normal tissue response on dose-volume factors are often confusingly inconsistent, as the QUANTEC reviews demonstrate. A key opportunity to accelerate progress is to begin storing high-quality datasets in repositories. Using available technology, multiple repositories could be conveniently queried, without divulging protected health information, to identify relevant sources of data for further analysis. After obtaining institutional approvals, data could then be pooled, greatly enhancing the capability to construct predictive models that are more widely applicable and better powered to accurately identify key predictive factors (whether dosimetric, image-based, clinical, socioeconomic, or biological). Data pooling has already been carried out effectively in a few normal tissue complication probability studies and should become a common strategy. Copyright 2010 Elsevier Inc. All rights reserved.

  9. Silver nanoparticle based surface enhanced Raman scattering spectroscopy of diabetic and normal rat pancreatic tissue under near-infrared laser excitation

    International Nuclear Information System (INIS)

    Huang, H; Shi, H; Chen, W; Yu, Y; Lin, D; Xu, Q; Feng, S; Lin, J; Huang, Z; Li, Y; Chen, R

    2013-01-01

    This paper presents the use of high spatial resolution silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) from rat pancreatic tissue to obtain biochrmical information about the tissue. A high quality SERS signal from a mixture of pancreatic tissues and silver nanoparticles can be obtained within 10 s using a Renishaw micro-Raman system. Prominent SERS bands of pancreatic tissue were assigned to known molecular vibrations, such as the vibrations of DNA bases, RNA bases, proteins and lipids. Different tissue structures of diabetic and normal rat pancreatic tissues have characteristic features in SERS spectra. This exploratory study demonstrated great potential for using SERS imaging to distinguish diabetic and normal pancreatic tissues on frozen sections without using dye labeling of functionalized binding sites. (letter)

  10. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

    Science.gov (United States)

    Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

    2011-01-01

    Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

  11. Strategies for homeostatic stem cell self-renewal in adult tissues

    NARCIS (Netherlands)

    Simons, B.D.; Clevers, H.

    2011-01-01

    In adult tissues, an exquisite balance exists between stem cell proliferation and the generation of differentiated offspring. Classically, it has been argued that this balance is obtained at the level of a single stem cell, which divides strictly into a new stem cell and a progenitor. However,

  12. Normal isometric strength of rotatorcuff muscles in adults.

    Science.gov (United States)

    Chezar, A; Berkovitch, Y; Haddad, M; Keren, Y; Soudry, M; Rosenberg, N

    2013-01-01

    The most prevalent disorders of the shoulder are related to the muscles of rotator cuff. In order to develop a mechanical method for the evaluation of the rotator cuff muscles, we created a database of isometric force generation by the rotator cuff muscles in normal adult population. We hypothesised the existence of variations according to age, gender and dominancy of limb. A total of 400 healthy adult volunteers were tested, classified into groups of 50 men and women for each decade of life. Maximal isometric force was measured at standardised positions for supraspinatus, infraspinatus and subscapularis muscles in both shoulders in every person. Torque of the force was calculated and normalised to lean body mass. The profiles of mean torque-time curves for each age and gender group were compared. Our data showed that men gradually gained maximal strength in the fifth decade, and showed decreased strength in the sixth. In women the maximal strength was gained in the fourth decade with gradual decline to the sixth decade of life. The dominant arm was stronger in most of the tested groups. The torque profiles of the rotator cuff muscles in men at all ages were significantly higher than that in women. We found previously unrecognised variations of rotator cuff muscles' isometric strength according to age, gender and dominancy in a normal population. The presented data may serve as a basis for the future studies for identification of the abnormal patterns of muscle isometric strength in patients with pathology of the rotator cuff muscles. Cite this article: Bone Joint Res 2013;2:214-19.

  13. Expression of Apoptosis Inducing-Ligands, TRAIL and Fas-L in Hydatid Cyst Germinal Layer and Normal Tissue

    Directory of Open Access Journals (Sweden)

    Adel Spotin

    2012-04-01

    Full Text Available Background & objectives: Hydaticosis is a zoonotic helminthic disease of human and other intermediated hosts in which larval stages of the tapeworm Echinococcus granulosu transfect human. The liver and lung are the host tissues for the hydatid cyst . It is unknown which mechanisms are involved in infertility of the cyst and suppression of the fertile cyst. This study was aimed to evaluate the expression of the apoptosis inducing-ligands such as TRAIL and Fas-L in germinal layer of the cyst and human normal tissue surrounding the cyst that is one of the unknown host innate immunity mechanisms against the hydatid cyst.   Methods: In this study, four isolated hydatid cysts were used which had been diagnosed in patients by radiography and parasitological examination in Mashhad Ghaem hospital. Furthermore, the germinal layer of the cyst and accompanied normal peripheral tissues were separated by scalpel in sterile conditions. After homogenization, expression of TRAIL and Fas-L genes were studied by semi-quantitive RT-PCR method.   Results: The TRAIL and Fas-L showed significant higher level expression in germinal layer of infertile cyst than the fertile cyst and host normal tissues.   Conclusion: The host tissue-induced apoptosis of germinal layer of the fertile cysts is probably one of the infertility mechanism in patients with hydaticosis

  14. A study of several normal values of Korean healthy adults on chest roentgenograms

    Energy Technology Data Exchange (ETDEWEB)

    Rhee, Byung Chull [Choong Nam University College of Medicine, Taejeon (Korea, Republic of)

    1975-06-15

    Determination of several normal values were carried out healthy 1805 cases of Korean adults, 1436 cases of male and 369 cases of female, by the drawing and calculation on chest roentgenograms. In many instances, the change of normal values provides an important clinical values, and often is decisive to evaluate the diagnosis, treatment and prognosis of pulmonary, cardiac and mediastinal disease.

  15. Morphology and epidermal thickness of normal skin imaged by optical coherence tomography

    DEFF Research Database (Denmark)

    Mogensen, Mette; Morsy, Hanan A.; Thrane, Lars

    2008-01-01

    colour. Methods: OCT imaging is based on infrared light reflection/backscatter from tissue. PS-OCT detects birefringence of tissue. Imaging was performed in 12 skin regions. ET was calculated from the OCT images. Results: Normal skin has a layered structure. Layering is less pronounced in adults......Background: Optical coherence tomography (OCT) is an optical imaging technology with a potential in the non-invasive diagnosis of skin cancer. To identify skin pathologies using OCT, it is of prime importance to establish baseline morphological features of normal skin. Aims: The aim of this study...... is to describe normal skin morphology using OCT and polarization-sensitive OCT (PS-OCT), which is a way of representing birefringent tissue such as collagen in OCT images. Anatomical locations in 20 healthy volunteers were imaged, and epidermal thickness (ET) was measured and compared to age, gender and skin...

  16. CT and MRI Findings of Soft Tissue Adult Fibrosarcoma in Extremities

    Directory of Open Access Journals (Sweden)

    Hexiang Wang

    2018-01-01

    Full Text Available Objective. To characterize and evaluate CT and MRI features of extremity soft tissue adult fibrosarcoma. Methods. CT and MRI images from 10 adult patients with pathologically proven fibrosarcomas were retrospectively analyzed with regard to tumor location, size, number, shape, margins, attenuation, signal intensity, and enhancement patterns on MR images. Additionally, the relationships between lesions, deep fascia, and change in adjacent bones were also assessed. Results. Nineteen tumor lesions in 10 patients were selected for this study. Eighteen lesions were lobulated and one was oval in shape. Most cases were located under the deep fascia, including seven cases that had a nodular lump adjacent to the deep fascia and one case that had broken lesion through the deep fascia. On CT, the adult fibrosarcomas mostly showed iso-attenuated soft tissue masses (n=6. On MRI, all the cases (n=9 displayed low signal on T1-weighted imaging (T1WI and heterogeneous low and high intensity signals on T2-weighted imaging (T2WI, with band-like areas of low signal on both T1WI and T2WI. On contrast-enhanced MRI images, three cases showed heterogeneous peripheral enhancement and one case demonstrated a spoke-wheel-like enhancement. Eight cases showed muscle edema signals in the peritumoral muscle and one case involved adjacent bone. Conclusion. CT and MR imaging have respective advantages in diagnosing adult fibrosarcoma. Combined application of CT and MR is recommended for patients with suspected adult fibrosarcoma.

  17. Radionuclide investigation of the blood flow in tumor and normal rat tissues in induced hyperglycemia

    International Nuclear Information System (INIS)

    Istomin, Yu.P.; Shitikov, B.D.; Markova, L.V.

    1991-01-01

    Radionuclide angiography was performed in rats with transplantable tumors. Induced hyperglycemia was shown to result in blood flow inhibition in tumor and normal tissues of tumor-bearing rats. Some differences were revealed in a degree of reversibility of blood flow disorders in tissues of the above strains. The results obtained confirmed the advisability of radiation therapy at the height of a decrease in tumor blood

  18. Estrogen receptor alpha localization in the testes of men with normal spermatogenesis Estrogen receptor alpha localization in the testes of men with normal spermatogenesis

    Directory of Open Access Journals (Sweden)

    Eliza Filipiak

    2012-10-01

    Full Text Available It is known that estrogens act on the male reproductive tract by binding to estrogen receptors (ER a and
    b. However, studies on ER localization in the human testis are discordant. The aim of this study was to investigate
    the localization of ERa in the testes of adult men with normal spermatogenesis. Semen analysis of ten adult men
    revealed azoospermia. FSH, LH and testosterone serum concentrations were within normal values, and the volume
    of the testes was normal, hence obstructive azoospermia was suspected. The tissues from testicular surgical
    biopsies were fixed in Bouin’s fluid and embedded in paraffin. Assessments of the seminiferous epithelium (scoring
    10 to –1, the number of Leydig cells (scoring 1 to 5, the areal fraction of intertubular space (IS, measurements
    of seminiferous tubule diameter, and the thickness of the tubular wall, were performed on microscopic
    sections. Immunohistochemical staining was applied with monoclonal antibodies against ERa. The mean spermatogenesis
    score was 10 points; IS — 30.6 ± 8.1%; seminiferous tubule diameter — 193.9 ± 19.4 μm; thickness of
    tubular wall — 7.44 ± 1.1 μm; number of Leydig cells — 1.6 ± 1.1 points. Immunohistochemical staining showed
    the localization of ERa to be in the Sertoli and Leydig cell cytoplasm, while ERa was absent in germ cells. The
    results of testicular tissue analysis confirmed its normal structure and normal, full spermatogenesis. The presence
    of ERa in Sertoli and Leydig cells in normal human testis demonstrated in this study suggests that estrogens may
    affect testicular function.It is known that estrogens act on the male reproductive tract by binding to estrogen receptors (ER a and
    b. However, studies on ER localization in the human testis are discordant. The aim of this study was to investigate
    the localization of ERa in the testes of adult men with normal spermatogenesis. Semen

  19. [Human brown adipose tissue].

    Science.gov (United States)

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  20. Thermal coagulation-induced changes of the optical properties of normal and adenomatous human colon tissues in vitro in the spectral range 400-1100 nm

    International Nuclear Information System (INIS)

    Ao Huilan; Xing Da; Wei Huajiang; Gu Huaimin; Wu Guoyong; Lu Jianjun

    2008-01-01

    The absorption coefficients, the reduced scattering coefficients and the optical penetration depths for native and coagulated human normal and adenomatous colon tissues in vitro were determined over the range of 400-1100 nm using a spectrophotometer with an internal integrating sphere system, and the inverse adding-doubling method was applied to calculate the tissue optical properties from diffuse reflectance and total transmittance measurements. The experimental results showed that in the range of 400-1100 nm there were larger absorption coefficients (P < 0.01) and smaller reduced scattering coefficients (P < 0.01) for adenomatous colon tissues than for normal colon tissues, and there were smaller optical penetration depths for adenomatous colon tissues than for normal colon tissues, especially in the near-infrared wavelength. Thermal coagulation induced significant increase of the absorption coefficients and reduced scattering coefficients for the normal and adenomatous colon tissues, and significantly reduced decrease of the optical penetration depths for the normal and adenomatous colon tissues. The smaller optical penetration depth for coagulated adenomatous colon tissues is a disadvantage for laser-induced thermotherapy (LITT) and photodynamic therapy (PDT). It is necessary to adjust the application parameters of lasers to achieve optimal therapy

  1. Dichotic and dichoptic digit perception in normal adults.

    Science.gov (United States)

    Lawfield, Angela; McFarland, Dennis J; Cacace, Anthony T

    2011-06-01

    Verbally based dichotic-listening experiments and reproduction-mediated response-selection strategies have been used for over four decades to study perceptual/cognitive aspects of auditory information processing and make inferences about hemispheric asymmetries and language lateralization in the brain. Test procedures using dichotic digits have also been used to assess for disorders of auditory processing. However, with this application, limitations exist and paradigms need to be developed to improve specificity of the diagnosis. Use of matched tasks in multiple sensory modalities is a logical approach to address this issue. Herein, we use dichotic listening and dichoptic viewing of visually presented digits for making this comparison. To evaluate methodological issues involved in using matched tasks of dichotic listening and dichoptic viewing in normal adults. A multivariate assessment of the effects of modality (auditory vs. visual), digit-span length (1-3 pairs), response selection (recognition vs. reproduction), and ear/visual hemifield of presentation (left vs. right) on dichotic and dichoptic digit perception. Thirty adults (12 males, 18 females) ranging in age from 18 to 30 yr with normal hearing sensitivity and normal or corrected-to-normal visual acuity. A computerized, custom-designed program was used for all data collection and analysis. A four-way repeated measures analysis of variance (ANOVA) evaluated the effects of modality, digit-span length, response selection, and ear/visual field of presentation. The ANOVA revealed that performances on dichotic listening and dichoptic viewing tasks were dependent on complex interactions between modality, digit-span length, response selection, and ear/visual hemifield of presentation. Correlation analysis suggested a common effect on overall accuracy of performance but isolated only an auditory factor for a laterality index. The variables used in this experiment affected performances in the auditory modality to a

  2. Elemental analysis of the frontal lobe of 'normal' brain tissue and that affected by Alzheimer's disease

    International Nuclear Information System (INIS)

    Stedman, J.D.; Spyrou, N.M.

    1997-01-01

    'Normal' brain tissue and brain tissue affected by Alzheimer's disease has been taken from the frontal lobe of both hemispheres and their elemental compositions in terms of major, minor and trace elements compared. Brain samples were obtained from the MRC Alzheimer's Disease Brain Bank, London. 25 samples were taken from 18 individuals (5 males and 13 females) of mean age 79.9 ± 7.3 years with pathologically confirmed Alzheimer's disease and 26 samples from 15 individuals (8 males and 7 females) of mean age 71.8 ± 13.0 years with no pathological sings of Alzheimer's disease ('normals'). The elemental concentration of the samples were determined by the techniques of Rutherford backscattering (RBS) analysis, particle induced X-ray emission (PIXE) analysis and instrumental neutron activation analysis (INAA). Na, Mg, Al, Cl, K, Sc, Fe, Zn, Se, Br, Rb and Cs were detected by INAA and significant differences in concentrations were found between concentrations in normal and Alzheimer tissue for the elements. Na, Cl, K, Se, Br and Rb, P, S, Cl, K, Ca, Fe, Zn and Cd were detected by PIXE analysis and significant differences found for the elements P, S, Cl, K and Ca. (author)

  3. Age and Gender Effects on Wideband Absorbance in Adults with Normal Outer and Middle Ear Function

    Science.gov (United States)

    Mazlan, Rafidah; Kei, Joseph; Ya, Cheng Li; Yusof, Wan Nur Hanim Mohd; Saim, Lokman; Zhao, Fei

    2015-01-01

    Purpose: This study examined the effects of age and gender on wideband energy absorbance in adults with normal middle ear function. Method: Forty young adults (14 men, 26 women, aged 20-38 years), 31 middle-aged adults (16 men, 15 women, aged 42-64 years), and 30 older adults (20 men, 10 women, aged 65-82 years) were assessed. Energy absorbance…

  4. Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

    Science.gov (United States)

    Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

    2013-07-01

    Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

  5. The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage

    Directory of Open Access Journals (Sweden)

    Arpita Chatterjee

    2018-01-01

    Full Text Available Radiation therapy is commonly used for prostate cancer treatment; however, normal tissues can be damaged from the reactive oxygen species (ROS produced by radiation. In separate reports, we and others have shown that manganese porphyrins (MnPs, ROS scavengers, protect normal cells from radiation-induced damage but inhibit prostate cancer cell growth. However, there have been no studies demonstrating that MnPs protect normal tissues, while inhibiting tumor growth in the same model. LNCaP or PC3 cells were orthotopically implanted into athymic mice and treated with radiation (2 Gy, for 5 consecutive days in the presence or absence of MnPs. With radiation, MnPs enhanced overall life expectancy and significantly decreased the average tumor volume, as compared to the radiated alone group. MnPs enhanced lipid oxidation in tumor cells but reduced oxidative damage to normal prostate tissue adjacent to the prostate tumor in combination with radiation. Mechanistically, MnPs behave as pro-oxidants or antioxidants depending on the level of oxidative stress inside the treated cell. We found that MnPs act as pro-oxidants in prostate cancer cells, while in normal cells and tissues the MnPs act as antioxidants. For the first time, in the same in vivo model, this study reveals that MnPs enhance the tumoricidal effect of radiation and reduce oxidative damage to normal prostate tissue adjacent to the prostate tumor in the presence of radiation. This study suggests that MnPs are effective radio-protectors for radiation-mediated prostate cancer treatment.

  6. Cerebral Blood Flow and Amyloid-β Interact to Affect Memory Performance in Cognitively Normal Older Adults

    Directory of Open Access Journals (Sweden)

    Katherine J. Bangen

    2017-06-01

    Full Text Available Cerebral blood flow (CBF alterations and amyloid-β (Aβ accumulation have been independently linked to cognitive deficits in older adults at risk for dementia. Less is known about how CBF and Aβ may interact to affect cognition in cognitively normal older adults. Therefore, we examined potential statistical interactions between CBF and Aβ status in regions typically affected in Alzheimer’s disease (AD within a sample of older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI study. Sixty-two cognitively normal participants (mean age = 72 years underwent neuroimaging and memory testing. Arterial spin labeling magnetic resonance imaging was used to quantify CBF and florbetapir PET amyloid imaging was used to measure Aβ deposition. Aβ status (i.e., positivity versus negativity was determined based on established cutoffs (Landau et al., 2013. The Rey Auditory Verbal Learning Test was used to assess memory. Linear regression models adjusted for age, education, and sex, demonstrated significant interactions between CBF and Aβ status on memory performance. Among Aβ positive older adults, there were significant negative associations between higher CBF in hippocampus, posterior cingulate, and precuneus and poorer memory performance. In contrast, among Aβ negative older adults, there were no significant associations between CBF and cognition. Our findings extend previous CBF studies of dementia risk by reporting interactions between Aβ status and CBF on memory performance in a sample of well-characterized, cognitively normal older adults. Results suggest that differential CBF-cognition associations can be identified in healthy, asymptomatic Aβ positive older adults relative to Aβ negative individuals. Associations between higherCBF and poorer memory among Aβ positive older adults may reflect a cellular and/or vascular compensatory response to pathologic processes whereby higher CBF is needed to maintain normal memory

  7. Immunohistochemical Expression of FXR1 in Canine Normal Tissues and Melanomas.

    Science.gov (United States)

    Nordio, Laura; Marques, Andreia T; Lecchi, Cristina; Luciano, Alberto M; Stefanello, Damiano; Giudice, Chiara

    2018-04-01

    Fragile X mental retardation-related protein 1 (FXR1) is a cytoplasmic RNA-binding protein highly conserved among vertebrates. It has been studied for its role in muscle development, inflammation, and tumorigenesis, being related, for example, to metastasizing behavior in human and canine uveal melanoma. Anti-FXR1 antibodies have never been validated in the canine species. To investigate FXR1 expression in canine melanocytic tumors, the present study tested two commercially available polyclonal anti-human FXR1 antibodies, raised in goat and rabbit, respectively. The cross-reactivity of the anti-FXR1 antibodies was assessed by Western blot analysis, and the protein was localized by IHC in a set of normal canine tissues and in canine melanocytic tumors (10 uveal and 10 oral). Western blot results demonstrated that the antibody raised in rabbit specifically recognized the canine FXR1, while the antibody raised in goat did not cross-react with this canine protein. FXR1 protein was immunodetected using rabbit anti-FXR1 antibody, in canine normal tissues with different levels of intensity and distribution. It was also detected in 10/10 uveal and 9/10 oral melanocytic tumors. The present study validated for the first time the use of anti-FXR1 antibody in dogs and highlighted different FXR1 protein expression in canine melanocytic tumors, the significance of which is undergoing further investigations.

  8. In vivo P-31 MR spectroscopic studies of liver in normal adults and cirrhotic patients

    International Nuclear Information System (INIS)

    Ban, N.; Moriyasu, F.; Tamada, T.

    1986-01-01

    The author performed in vivo P-31 MR spectroscopic studies of normal and diseased human liver using an experimental 2.0-T whole-body MR imager. Then normal adults and ten cirrhotic patients in the fasting state were studied. Spatially localized in vivo P-31 MR spectra of human liver were obtained in combination with the use of a surface coil and gradient magnetic field. Six spectral peaks were observed in both groups and were assigned, from left to right, to phosphomonoester, inorganic phosphate, phosophodiester, γ-ATP, α-ATP, and β-ATP, on the basis of the chemical shifts. There were no definite differences between the spectral patterns of normal adults and those of cirrhotic patients in the fasting state

  9. The use of biological isodoses ''IsobioGy 2'' for evaluation of tumour and normal tissues response for fractionated irradiation

    International Nuclear Information System (INIS)

    Maciejewski, B.; Skolyszewski, J.; Majewski, S.; Lobodziec, W.; Jedynak, T.; Slosarek, K.

    1988-01-01

    Divergences between physical and biological dose distributions were analysed using linear quadratic model. It was found that small variations in physical dose distribution and differences in normal tissue sensitivity for change in dose per fraction, expressed by a α/β value, can cause a high difference between physical and biological doses. This difference significantly increases when one field instead of two fields is daily treated. If there is no enough separation between treated fields, the biological dose may dramatically increase. The use of biological ''isobioGy 2'' isodoses, instead of physical isodoses, can provide an important information on biological effect in tumour or normal tissue and may diminish the risk of giving too high dose to normal tissue and too low dose to the tumour. 6 figs., 13 refs. (author)

  10. Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, Carsten [University of Bonn, Department of Radiology, Bonn (Germany); Pieper, Claus Christian; Wilhelm, Kai E.; Schild, Hans Heinz [University of Bonn, Department of Radiology, Bonn (Germany); Ezziddin, Samer; Ahmadzadehfar, Hojjat [University of Bonn, Department of Nuclear Medicine, Bonn (Germany)

    2014-02-15

    To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with {sup 90}Y microspheres. Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept {sup registered} S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and {sup 99m}Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with {sup 18}F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization. Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. {sup 99m}Tc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded. Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases. (orig.)

  11. Feasibility of temporary protective embolization of normal liver tissue using degradable starch microspheres during radioembolization of liver tumours

    International Nuclear Information System (INIS)

    Meyer, Carsten; Pieper, Claus Christian; Wilhelm, Kai E.; Schild, Hans Heinz; Ezziddin, Samer; Ahmadzadehfar, Hojjat

    2014-01-01

    To describe a new approach to protect nontarget healthy liver tissue using degradable starch microspheres (DSM) as a short-term embolizate during radioembolization of liver tumours with 90 Y microspheres. Between December 2011 and July 2012 radioembolization was performed in 54 patients. Five of these patients (three women, two men; mean age 67 years) underwent protective temporary embolization using DSM (EmboCept registered S) of normal liver tissue that could not be excluded from the area treated by radioembolization through catheter repositioning. Clinical symptoms, laboratory findings, preinterventional imaging, and 99m Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up imaging with 18 F-FDG PET/CT and MRI, were evaluated in relation to the technical and clinical success of the protective embolization. Temporary embolization of arteries supplying normal liver tissue using DSM was technically successful in all five patients. 99m Tc-MAA SPECT/CT performed in the first two patients after DSM injection showed no increased pulmonary shunting compared to the MAA test injection without DSM. Bremsstrahlung SPECT/CT after radioembolization demonstrated satisfactory irradiation of the tumour and successful protection of normal liver tissue. There were only mild hepatotoxic effects (grade 1) on laboratory follow-up examinations, and no adverse events associated with DSM embolization or radioembolization were recorded. Temporary embolization with DSM before radioembolization is feasible and can effectively protect areas of normal liver tissue from irradiation and avoid permanent embolization if other methods such as catheter repositioning are not possible due to the location of the metastases. (orig.)

  12. Variability of individual normal tissue radiation sensitivity. An international empirical evaluation of endogenous and exogenous

    International Nuclear Information System (INIS)

    Zimmermann, J.S.; Kumpf, L.; Kimmig, B.

    1998-01-01

    Background: The variability of normal-tissue response is of major concern for radiation therapy. Multiple endogenous and exogenous factors are qualitatively known to alter the acute and late tissue response. Which of them are regarded most important by the European radiation oncologists and what is, empirically, their quantitative influence on the acute or late tissue tolerance? Methods: In August 1997, we sent a questionnaire to 255 European radiation oncology departments. Among others, the questionnaire asked for endogenous and exogenous factors modifying the tissue response to radiation therapy and their quantitative influence on the acute and late radiation morbidity (TD5/5). Fifty-five questionnaires (21.5%) were answered. Results: Empirically, the most important endogenous factors to modify the acute tissue tolerance are (a) metabolic/other diseases with macro- or microangiopathia (17 answers [a]/32% mean decrease of tissue tolerance), (b) collagen diseases (9 a/37%) and (c) immune diseases (5 a/53%). As endogenous response modifiers for the TD5/5 are recognized (a) metabolic or other diseases leading to marcro- or microangiopathia (15 a/31%), (b) collagen diseases (11 a/38%) and (c) immune diseases (2 a/50%). Inflammations from any reason are assumed to alter the acute tissue tolerance by (6 a/26%) and the TD5/5 by (10 a/24%). Exogenous modifiers of the acute tissue response mentioned are (a) smoking (34 a/44%), (b) alcohol (23 a/45%), (c) nutrition/diets (16 a/45%), (d) hygiene (9 a/26%) and (e) medical therapies (10 a/37%). Exogenous factors assumed to influence the TD5/5 are (a) smoking (22 a/40%), (b) alcohol (15 a/38%), (c) nutrition/diets (9 a/48%), (d) hygiene (5 a/34%) and (e) medical therapies (10 a/30%). Conclusions: Exogenous factors are regarded more important by number and extent on the acute and late tissue response than endogenous modifiers. Both may have an important influence on the individual expression of normal tissue response. (orig

  13. The effect of setup uncertainty on normal tissue sparing with IMRT for head-and-neck cancer

    International Nuclear Information System (INIS)

    Manning, Matthew A.; Wu Quiwen; Cardinale, Robert M.; Mohan, Radhe; Lauve, Andrew D.; Kavanagh, Brian D.; Morris, Monica M.; Schmidt-Ullrich, Rupert K.

    2001-01-01

    Purpose: Intensity-modulated radiotherapy (IMRT) is being evaluated in the management of head-and-neck cancers at several institutions, and a Radiation Therapy Oncology Group study of its utility in parotid sparing is under development. There is an inherent risk that the sharper dose gradients generated by IMRT amplify the potentially detrimental impact of setup uncertainty. The International Commission on Radiation Units and Measurements Report 62 (ICRU-62) defined planning organ-at-risk volume (PRV) to account for positional uncertainties for normal tissues. The purpose of this study is to quantify the dosimetric effect of employing PRV for the parotid gland and to evaluate the use of PRV on normal-tissue sparing in the setting of small clinical setup errors. Methods and Materials: The optimized nine-beam IMRT plans for three head-and-neck cancer patients participating in an institutional review board approved parotid-sparing protocol were used as reference plans. A second optimized plan was generated for each patient by adding a PRV of 5 mm for the contralateral parotid gland. The effect of these additions on the quality of the plans was quantified, in terms of both target coverage and normal-tissue sparing. To test the value of PRV in a worst-case scenario, systematic translational setup uncertainties were simulated by shifting the treatment isocenter 5 mm superiorly, inferiorly, left, right, anteriorly, and posteriorly, without altering optimized beam profiles. At each shifted isocenter, dose distributions were recalculated, producing a total of six shifted plans without PRV and six shifted plans with PRV for each patient. The effect of setup uncertainty on parotid sparing and the value of PRV in compensating for the uncertainty were evaluated. Results: The addition of the PRV and reoptimization did not significantly affect the dose to gross tumor volume, spinal cord, or brainstem. In contrast, without any shift, the PRV did increase parotid sparing and reduce

  14. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Shan Liu

    2016-06-01

    Full Text Available Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous. The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells, early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium, using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration, timing for cell therapy (immediate vs. a few days after injury, single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  15. Expression and relevant research of MGMT and XRCC1 gene in differentgrades of brain glioma and normal brain tissues

    Institute of Scientific and Technical Information of China (English)

    Ya-Fei Zhang

    2015-01-01

    Objective: To explore and analyze expression and relevant research of MGMT and XRCC1 gene in different grades of brain glioma and normal brain tissues. Methods: 52 cases of patients with brain glioma treated in our hospital from December 2013 to December 2014, and 50 cases of normal brain-tissue patients with intracranial hypertension were selected, and proceeding test to the surgical resection of brain tissue of the above patients to determine its MGMT and XRCC1 protein content, sequentially to record the expression of MGMT and XRCC1 of both groups. Grading of tumors to brain glioma after operation was carried out, and the expression of MGMT and XRCC1 gene in brain tissues of different patients was analyzed and compared;finally the contingency tables of X2 test was used to analyze the correlation of XRCC1and MGMT. Results:Positive rate of MGMT expression in normal brain tissue was 2%,while positive rate of MGMT expression in brain glioma was 46.2%,which was obviously higher than that in normal brain tissues (χ2=26.85, P0.05), which had no statistical significance. There were 12 cases of patients whose MGMT protein expression was positive and XRCC1 protein expression was positive; there were 18 cases of patients whose MGMT protein expression was negative and XRCC1 protein expression was negative. Contingency tables of X2 test was used to analyze the correlation of XRCC1 and MGMT, which indicated that the expression of XRCCI and MGMT in brain glioma had no correlation (r=0.9%, P=0.353), relevancy of both was r=0.9%. Conclusions: Positive rate of the expression of MGMT and XRCC1 in brain glioma was obviously higher than that in normal brain tissues, but the distribution of different grades of brain glioma had no obvious difference, and MGMT and XRCC1 expression had no obvious correlation, which needed further research.

  16. Characterization of adenoviral transduction profile in prostate cancer cells and normal prostate tissue.

    Science.gov (United States)

    Ai, Jianzhong; Tai, Phillip W L; Lu, Yi; Li, Jia; Ma, Hong; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

    2017-09-01

    Prostate diseases are common in males worldwide with high morbidity. Gene therapy is an attractive therapeutic strategy for prostate diseases, however, it is currently underdeveloped. As well known, adeno virus (Ad) is the most widely used gene therapy vector. The aims of this study are to explore transduction efficiency of Ad in prostate cancer cells and normal prostate tissue, thus further providing guidance for future prostate pathophysiological studies and therapeutic development of prostate diseases. We produced Ad expressing enhanced green fluorescence protein (EGFP), and characterized the transduction efficiency of Ad in both human and mouse prostate cancer cell lines in vitro, as well as prostate tumor xenograft, and wild-type mouse prostate tissue in vivo. Ad transduction efficiency was determined by EGFP fluorescence using microscopy and flow cytometry. Cell type-specific transduction was examined by immunofluorescence staining of cell markers. Our data showed that Ad efficiently transduced human and mouse prostate cancer cells in vitro in a dose dependent manner. Following intratumoral and intraprostate injection, Ad could efficiently transduce prostate tumor xenograft and the major prostatic cell types in vivo, respectively. Our findings suggest that Ad can efficiently transduce prostate tumor cells in vitro as well as xenograft and normal prostate tissue in vivo, and further indicate that Ad could be a potentially powerful toolbox for future gene therapy of prostate diseases. © 2017 Wiley Periodicals, Inc.

  17. [Morphology of basement membrane and associated matrix proteins in normal and pathological tissues].

    Science.gov (United States)

    Nerlich, A

    1995-01-01

    Basement membranes (BM) are specialized structures of the extracellular matrix. Their composition is of particular importance for the maintenance of normal morphological and functional properties of a multitude of organs and tissue systems and it is thus required for regular homeostasis of body function. Generally, they possess three main functions, i.e. participation in the maintenance of tissue structure, control of fluid and substrate exchange, and regulation of cell growth and differentiation. BMs are made up by various components which are in part specifically localized within the BM zone, or which represent ubiquitous matrix constituents with specific quantitative and/or qualitative differences in their localization. On the basis of a thorough immunohistochemical analysis of normal and diseased tissues, we provide here a concept of "functional morphology/pathomorphology" of the different BM components analyzed: 1.) The ubiquitous BM-constituent collagen IV primarily stabilizes the BM-zone and thus represents the "backbone" of the BM providing mechanical strength. Its loss leads to cystic tissue transformation as it is evidenced from the analysis of polycystic nephropathies. Thus, in other cystic tissue transformations a similar formal pathogenesis may be present. 2.) The specific localization of collagen VII as the main structural component of anchoring fibrils underlines the mechanical anchoring function of this collagenous protein. Defects in this protein lead to hereditary epidermolysis. The rapid re-occurrence of epidermal collagen VII during normal human wound healing indicates a quick reconstitution of the mechanical tensile strength of healing wounds. 3.) The BM-specific heparan sulfate proteoglycan (HSPG, Perlecan) with its highly negative anionic charge can be assumed to exert filter control. This assumption is corroborated by the localizatory findings of a preferential deposition of HSPG in endothelial and particularly in glomerular BM. Similarly

  18. Analysis of the genetic phylogeny of multifocal prostate cancer identifies multiple independent clonal expansions in neoplastic and morphologically normal prostate tissue.

    Science.gov (United States)

    Cooper, Colin S; Eeles, Rosalind; Wedge, David C; Van Loo, Peter; Gundem, Gunes; Alexandrov, Ludmil B; Kremeyer, Barbara; Butler, Adam; Lynch, Andrew G; Camacho, Niedzica; Massie, Charlie E; Kay, Jonathan; Luxton, Hayley J; Edwards, Sandra; Kote-Jarai, ZSofia; Dennis, Nening; Merson, Sue; Leongamornlert, Daniel; Zamora, Jorge; Corbishley, Cathy; Thomas, Sarah; Nik-Zainal, Serena; O'Meara, Sarah; Matthews, Lucy; Clark, Jeremy; Hurst, Rachel; Mithen, Richard; Bristow, Robert G; Boutros, Paul C; Fraser, Michael; Cooke, Susanna; Raine, Keiran; Jones, David; Menzies, Andrew; Stebbings, Lucy; Hinton, Jon; Teague, Jon; McLaren, Stuart; Mudie, Laura; Hardy, Claire; Anderson, Elizabeth; Joseph, Olivia; Goody, Victoria; Robinson, Ben; Maddison, Mark; Gamble, Stephen; Greenman, Christopher; Berney, Dan; Hazell, Steven; Livni, Naomi; Fisher, Cyril; Ogden, Christopher; Kumar, Pardeep; Thompson, Alan; Woodhouse, Christopher; Nicol, David; Mayer, Erik; Dudderidge, Tim; Shah, Nimish C; Gnanapragasam, Vincent; Voet, Thierry; Campbell, Peter; Futreal, Andrew; Easton, Douglas; Warren, Anne Y; Foster, Christopher S; Stratton, Michael R; Whitaker, Hayley C; McDermott, Ultan; Brewer, Daniel S; Neal, David E

    2015-04-01

    Genome-wide DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer, reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of ongoing abnormal mutational processes, consistent with field effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing, as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissues or between different ERG lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.

  19. Pharmacokinetics and tissue distribution of five active ingredients of Eucommiae cortex in normal and ovariectomized mice by UHPLC-MS/MS.

    Science.gov (United States)

    An, Jing; Hu, Fangdi; Wang, Changhong; Zhang, Zijia; Yang, Li; Wang, Zhengtao

    2016-09-01

    1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic. 2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice. 3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC0-∞ and Cmax. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state.

  20. Quantitative radiation dose-response relationships for normal tissues in man - I. Gustatory tissues response during photon and neutron radiotherapy

    International Nuclear Information System (INIS)

    Mossman, K.L.

    1982-01-01

    Quantitative radiation dose-response curves for normal gustatory tissue in man were studied. Taste function, expressed as taste loss, was evaluated in 84 patients who were given either photon or neutron radiotherapy for tumors in the head and neck region. Patients were treated to average tumor doses of 6600 cGy (photon) or 2200 cGy intervals for photon patients and 320-cGy intervals for neutron patients during radiotherapy. The dose-response curves for photons and neutrons were analyzed by fitting a four-parameter logistic equation to the data. Photon and neutron curves differed principally in their relative position along the dose axis. Comparison of the dose-response curves were made by determination of RBE. At 320 cGy, the lowest neutron dose at which taste measurements were made, RBE = 5.7. If this RBE is correct, then the therapeutic gain factor may be equal to or less than 1, indicating no biological advantage in using neutrons over photons for this normal tissue. These studies suggest measurements of taste function and evaluation of dose-response relationships may also be useful in quantitatively evaluating the efficacy of chemical modifiers of radiation response such as hypoxic cell radiosensitizers and radioprotectors

  1. A distinct regulatory region of the Bmp5 locus activates gene expression following adult bone fracture or soft tissue injury.

    Science.gov (United States)

    Guenther, Catherine A; Wang, Zhen; Li, Emma; Tran, Misha C; Logan, Catriona Y; Nusse, Roel; Pantalena-Filho, Luiz; Yang, George P; Kingsley, David M

    2015-08-01

    Bone morphogenetic proteins (BMPs) are key signaling molecules required for normal development of bones and other tissues. Previous studies have shown that null mutations in the mouse Bmp5 gene alter the size, shape and number of multiple bone and cartilage structures during development. Bmp5 mutations also delay healing of rib fractures in adult mutants, suggesting that the same signals used to pattern embryonic bone and cartilage are also reused during skeletal regeneration and repair. Despite intense interest in BMPs as agents for stimulating bone formation in clinical applications, little is known about the regulatory elements that control developmental or injury-induced BMP expression. To compare the DNA sequences that activate gene expression during embryonic bone formation and following acute injuries in adult animals, we assayed regions surrounding the Bmp5 gene for their ability to stimulate lacZ reporter gene expression in transgenic mice. Multiple genomic fragments, distributed across the Bmp5 locus, collectively coordinate expression in discrete anatomic domains during normal development, including in embryonic ribs. In contrast, a distinct regulatory region activated expression following rib fracture in adult animals. The same injury control region triggered gene expression in mesenchymal cells following tibia fracture, in migrating keratinocytes following dorsal skin wounding, and in regenerating epithelial cells following lung injury. The Bmp5 gene thus contains an "injury response" control region that is distinct from embryonic enhancers, and that is activated by multiple types of injury in adult animals. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Talker Differences in Clear and Conversational Speech: Perceived Sentence Clarity for Young Adults with Normal Hearing and Older Adults with Hearing Loss

    Science.gov (United States)

    Ferguson, Sarah Hargus; Morgan, Shae D.

    2018-01-01

    Purpose: The purpose of this study is to examine talker differences for subjectively rated speech clarity in clear versus conversational speech, to determine whether ratings differ for young adults with normal hearing (YNH listeners) and older adults with hearing impairment (OHI listeners), and to explore effects of certain talker characteristics…

  3. Seeing the Talker's Face Improves Free Recall of Speech for Young Adults with Normal Hearing but Not Older Adults with Hearing Loss

    Science.gov (United States)

    Rudner, Mary; Mishra, Sushmit; Stenfelt, Stefan; Lunner, Thomas; Rönnberg, Jerker

    2016-01-01

    Purpose: Seeing the talker's face improves speech understanding in noise, possibly releasing resources for cognitive processing. We investigated whether it improves free recall of spoken two-digit numbers. Method: Twenty younger adults with normal hearing and 24 older adults with hearing loss listened to and subsequently recalled lists of 13…

  4. An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues.

    Science.gov (United States)

    Saraco, Nora; Nesi-Franca, Suzana; Sainz, Romina; Marino, Roxana; Marques-Pereira, Rosana; La Pastina, Julia; Perez Garrido, Natalia; Sandrini, Romolo; Rivarola, Marco Aurelio; de Lacerda, Luiz; Belgorosky, Alicia

    2015-01-01

    Splicing CYP19 gene variants causing aromatase deficiency in 46,XX disorder of sexual development (DSD) patients have been reported in a few cases. A misbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast development but an incomplete sex maturation progress. The aim of this study was to functionally characterize a novel CYP19A1 intronic homozygote mutation (IVS9+5G>A) in a 46,XX DSD girl presenting spontaneous breast development and primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. Genomic DNA analysis, splicing prediction programs, splicing assays, and in vitro protein expression and enzyme activity analyses were carried out. CYP19A1 mRNA expression in human steroidogenic tissues was also studied. A novel IVS9+5G>A homozygote mutation was found. In silico analysis predicts the disappearance of the splicing donor site in intron 9, confirmed by patient peripheral leukocyte cP450arom and in vitro studies. Protein analysis showed a shorter and inactive protein. The intron 9 transcript variant was also found in human steroidogenic tissues. The mutation IVS9+5G>A generates a splicing variant that includes intron 9 which is also present in normal human steroidogenic tissues, suggesting that a misbalance between normal and aberrant splicing variants might occur in target tissues, explaining the clinical phenotype in the affected patient. © 2015 S. Karger AG, Basel.

  5. Differentiation of prostate cancer from normal prostate tissue in an animal model: conventional MRI and dynamic contrast-enhanced MRI

    International Nuclear Information System (INIS)

    Gemeinhardt, O.; Prochnow, D.; Taupitz, M.; Hamm, B.; Beyersdorff, D.; Luedemann, L.; Abramjuk, C.

    2005-01-01

    Purpose: to differentiate orthotopically implanted prostate cancer from normal prostate tissue using magnetic resonance imaging (MRI) and Gd-DTPA-BMA-enhanced dynamic MRI in the rat model. Material and methods: tumors were induced in 15 rats by orthotopic implantation of G subline Dunning rat prostatic tumor cells. MRI was performed 56 to 60 days after tumor cell implantation using T1-weighted spin-echo, T2-weighted turbo SE sequences, and a 2D FLASH sequence for the contrast medium based dynamic study. The interstitial leakage volume, normalized permeability and the permeability surface area product of tumor and healthy prostate were determined quantitatively using a pharmacokinetic model. The results were confirmed by histologic examination. Results: axial T2-weighted TSE images depicted low-intensity areas suspicious for tumor in all 15 animals. The mean tumor volume was 46.5 mm3. In the dynamic study, the suspicious areas in all animals displayed faster and more pronounced signal enhancement than surrounding prostate tissue. The interstitial volume and the permeability surface area product of the tumors increased significantly by 420% (p<0.001) and 424% (p<0.001), respectively, compared to normal prostate tissue, while no significant difference was seen for normalized permeability alone. Conclusion: the results of the present study demonstrate that quantitative analysis of contrast-enhanced dynamic MRI data enables differentiation of small, slowly growing orthotopic prostate cancer from normal prostate tissue in the rat model. (orig.)

  6. The claudin gene family: expression in normal and neoplastic tissues

    International Nuclear Information System (INIS)

    Hewitt, Kyle J; Agarwal, Rachana; Morin, Patrice J

    2006-01-01

    The claudin (CLDN) genes encode a family of proteins important in tight junction formation and function. Recently, it has become apparent that CLDN gene expression is frequently altered in several human cancers. However, the exact patterns of CLDN expression in various cancers is unknown, as only a limited number of CLDN genes have been investigated in a few tumors. We identified all the human CLDN genes from Genbank and we used the large public SAGE database to ascertain the gene expression of all 21 CLDN in 266 normal and neoplastic tissues. Using real-time RT-PCR, we also surveyed a subset of 13 CLDN genes in 24 normal and 24 neoplastic tissues. We show that claudins represent a family of highly related proteins, with claudin-16, and -23 being the most different from the others. From in silico analysis and RT-PCR data, we find that most claudin genes appear decreased in cancer, while CLDN3, CLDN4, and CLDN7 are elevated in several malignancies such as those originating from the pancreas, bladder, thyroid, fallopian tubes, ovary, stomach, colon, breast, uterus, and the prostate. Interestingly, CLDN5 is highly expressed in vascular endothelial cells, providing a possible target for antiangiogenic therapy. CLDN18 might represent a biomarker for gastric cancer. Our study confirms previously known CLDN gene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that express CLDN3 and CLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4

  7. ALERT. Adverse late effects of cancer treatment. Vol. 2. Normal tissue specific sites and systems

    Energy Technology Data Exchange (ETDEWEB)

    Rubin, Philip; Constine, Louis S. [Univ. Rochester Medical Center, NY (United States). Dept. of Radiation Oncology; Marks, Lawrence B. (ed.) [Univ. North Carolina and Lineberger, Comprehensive Cancer Center, Chapel Hill, NC (United States). Dept. of Radiation Oncology

    2014-09-01

    Comprehensively documents potential late effects in all the normal tissue sites in the human body. Considers in detail the detection, diagnosis, management and prevention of effects and discusses prognostic outcomes. Clearly presents radiation risk factors and interactions with chemotherapy effects. Provides the most current evidence-based medicine for cancer care survivorship guidelines. The literature on the late effects of cancer treatment is widely scattered in different journals since all major organ systems are affected and management is based on a variety of medical and surgical treatments. The aim of ALERT - Adverse Late Effects of Cancer Treatment is to offer a coherent multidisciplinary approach to the care of cancer survivors. The central paradigm is that cytotoxic multimodal therapy results in a perpetual cascade of events that affects each major organ system differently and is expressed continually over time. Essentially, radiation and chemotherapy are intense biologic modifiers that allow for cancer cure and cancer survivorship but accelerate senescence of normal tissues and increase the incidence of age-related diseases and second malignant tumors. Volume 2 of this two-volume work comprehensively documents potential late effects in all the normal tissue anatomic sites in the human body. The detection, diagnosis, management and prevention of effects are all considered in detail, and prognostic outcomes are discussed. Radiation risk factors and interactions with chemotherapy effects are clearly presented. The text is accompanied by numerous supportive illustrations and tables.

  8. Cutoff Values of Serum Carcinoembryonic Antigen (CEA) in Normal Korean Adults and Factors Influencing Serum CEA Level

    International Nuclear Information System (INIS)

    Kim, Jong Soon; Kim, Sun Wook; Chung, June Key; Lee, Dong Soo

    1994-01-01

    Carcinoembryonic Antigen is one of most frequently checked tumor markers in cancer management. We performed statistical analysis with serum CEA data of 2626 persons who received regular health examination and were thought to be free of active disease to determine the cutoff values of serum CEA level in normal Korean adults and to study the factors influencing serum CEA levels in normal subjects. 1) The cutoff values of serum CEA in normal Korean adults in general were 9.28 ng/ml for men, 5.90 ng/ml for women. 2) Serum CEA level was influenced by age, present smoking history, sex, and abnormal findings in chest X ray. 3) Serum CEA level had no correlation with the history of amount of alcohol consumption or obesity. 4) Cutoff values of serum CEA in normal Korean adults were tabulated according to age, sex, and smoking history. Serum CEA level was influenced by age, sex, present smoking history and abnormal findings in chest X ray and cutoff values of serum CEA were tabulated according to age, sex, and smoking history.

  9. Further proof of the plasticity of adult stem cells and their role in tissue repair

    OpenAIRE

    Prockop, Darwin J.

    2003-01-01

    In this issue, De Bari et al. (2003) present elegant data to counter the recent claims that adult stem cells have a limited plasticity. Further, they provide evidence that adult stem cells can seek out damaged tissues and repair them.

  10. Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

    Directory of Open Access Journals (Sweden)

    Cindy J.M. Loomans

    2018-03-01

    Full Text Available Summary: Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi, express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC, and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+ cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhi cells formed INS+ cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential. : In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. These organoids harbor a subpopulation of ALDHhi cells that display proliferative capacity and can differentiate to an endocrine fate. Keywords: pancreas, organoid, human, ALDH, endocrine differentiation, beta cells, insulin, progenitor, fetal, diabetes

  11. Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

    Science.gov (United States)

    Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

    2017-01-01

    Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

  12. Apparent diffusion coefficient of breast cancer and normal fibroglandular tissue in diffusion-weighted imaging: the effects of menstrual cycle and menopausal status.

    Science.gov (United States)

    Kim, Jin You; Suh, Hie Bum; Kang, Hyun Jung; Shin, Jong Ki; Choo, Ki Seok; Nam, Kyung Jin; Lee, Seok Won; Jung, Young Lae; Bae, Young Tae

    2016-05-01

    The purpose of this study was to investigate prospectively whether the apparent diffusion coefficients (ADCs) of both breast cancer and normal fibroglandular tissue vary with the menstrual cycle and menopausal status. Institutional review board approval was obtained, and informed consent was obtained from each participant. Fifty-seven women (29 premenopausal, 28 postmenopausal) with newly diagnosed breast cancer underwent diffusion-weighted imaging twice (interval 12-20 days) before surgery. Two radiologists independently measured ADC of breast cancer and normal contralateral breast tissue, and we quantified the differences according to the phases of menstrual cycle and menopausal status. With normal fibroglandular tissue, ADC was significantly lower in postmenopausal than in premenopausal women (P = 0.035). In premenopausal women, ADC did not differ significantly between proliferative and secretory phases in either breast cancer or normal fibroglandular tissue (P = 0.969 and P = 0.519, respectively). In postmenopausal women, no significant differences were found between ADCs measured at different time intervals in either breast cancer or normal fibroglandular tissue (P = 0.948 and P = 0.961, respectively). The within-subject variability of the ADC measurements was quantified using the coefficient of variation (CV) and was small: the mean CVs of tumor ADC were 2.90 % (premenopausal) and 3.43 % (postmenopausal), and those of fibroglandular tissue ADC were 4.37 % (premenopausal) and 2.55 % (postmenopausal). Both intra- and interobserver agreements were excellent for ADC measurements, with intraclass correlation coefficients in the range of 0.834-0.974. In conclusion, the measured ADCs of breast cancer and normal fibroglandular tissue were not affected significantly by menstrual cycle, and the measurements were highly reproducible both within and between observers.

  13. The Protective Effects of Vitamins C and E on The Oxidative Stress Induced by Sodium Metabisulfite on The Kidney Tissue in Adult Rats

    Directory of Open Access Journals (Sweden)

    Abdolnabi Peyravi

    2016-09-01

    Full Text Available Background & Objective: Sodium metabisulfite which is used as a food preservative in the food industry, has adverse effects on body organs such as kidney and body grouth rate. In this research we have studied the protective effect of Vitamin C and E as antioxidants, on the kidney tissue damage after the consumption of Sodium metabisulfite. Materials & methods: Forty-eight Adult male Wistar rats of 150-200 grams were divided into 6 groups of 8 each. Rats in the experimental groups received Sodium metabisulfite (520 mg / kg body weight by gavage feeding for 30 consecutive days. Also during this period, the experimental groups 2 and 3 received a daily dose of 100 mg / kg vitamins C and E, Respectively. The experimental group 4 received 50 mg / kg vitamin C plus 50 mg / kg of vitamin E by the same root. Control group received only normal diet and water. The placebo received vehicle (drug solvent as well as normal diet and water. At the end of the exprimental period the body growth rate was measured between the groups. The histhopatological examination was performed on the kidney tissue sections. by light microscope Results: The results showed sodium metabisulfite in daily dietary could lead to the kidney tissue damage and reduced body weight in rats (p <0.05. However, vitamins C and E can reduce the kidney tissue damage and allow a normal growth weight (p <0.05. Conclusion: With this study we could conclude that the antioxidant effect of that vitamins C and E have a protective effect on renal damage induced by sodium metabisulfite consumption

  14. 2-deoxyglucose tissue levels and insulin levels following tolazamide dosing in normal and obese mice

    International Nuclear Information System (INIS)

    Skillman, C.A.; Fletcher, H.P.

    1986-01-01

    The effect of tolazamide (TZ), a sulfonylurea, on 14 C-2-deoxyglucose ( 14 C-2DG) tissue distribution and insulin levels of normal and obese mice was investigated using an in vivo physiological method. Acute doses of TZ (50 mg/kg ip) increased 14 C-2DG levels in gastrocnemius muscle and retroperitoneal fat and produced a transient elevation of insulin which most likely accounts for the increased 14 C-2DG levels in muscle and fat. The results demonstrate that the in vivo 14 C-2DG method produced results consistent with known actions of sulfonylureas on in vitro hexose assimilation in muscle and fat. Subchronic treatment (7 days) with TZ 50 mg/kg ip twice daily did not result in increased insulin-stimulated 14 C-2DG tissue levels in normal mice when compared to saline treated controls. However, insulin levels were lower in mice treated subchronically with TZ compared to saline controls suggesting an enhancement of insulin action. Viable yellow obese mice represent a model of maturity onset obesity presenting with insulin resistance. The insulin resistance of this obese strain appears to reside in the fat tissue as assessed by comparing 14 C-2DG tissue levels of obese mice with lean littermate controls. Subchronic TZ treatment had no effect on 14 C-2DG uptake in fat or muscle tissue of viable yellow obese mice and did not alter their plasma insulin levels. It appears that genetically obese viable mice may be resistant to subchronic treatment with TZ. (author)

  15. Human BLCAP transcript: new editing events in normal and cancerous tissues.

    Science.gov (United States)

    Galeano, Federica; Leroy, Anne; Rossetti, Claudia; Gromova, Irina; Gautier, Philippe; Keegan, Liam P; Massimi, Luca; Di Rocco, Concezio; O'Connell, Mary A; Gallo, Angela

    2010-07-01

    Bladder cancer-associated protein (BLCAP) is a highly conserved protein among species, and it is considered a novel candidate tumor suppressor gene originally identified from human bladder carcinoma. However, little is known about the regulation or the function of this protein. Here, we show that the human BLCAP transcript undergoes multiple A-to-I editing events. Some of the new editing events alter the highly conserved amino terminus of the protein creating alternative protein isoforms by changing the genetically coded amino acids. We found that both ADAR1 and ADAR2-editing enzymes cooperate to edit this transcript and that different tissues displayed distinctive ratios of edited and unedited BLCAP transcripts. Moreover, we observed a general decrease in BLCAP-editing level in astrocytomas, bladder cancer and colorectal cancer when compared with the related normal tissues. The newly identified editing events, found to be downregulated in cancers, could be useful for future studies as a diagnostic tool to distinguish malignancies or epigenetic changes in different tumors.

  16. Identification of the boundary between normal breast tissue and invasive ductal carcinoma during breast-conserving surgery using multiphoton microscopy

    Science.gov (United States)

    Deng, Tongxin; Nie, Yuting; Lian, Yuane; Wu, Yan; Fu, Fangmeng; Wang, Chuan; Zhuo, Shuangmu; Chen, Jianxin

    2014-11-01

    Breast-conserving surgery has become an important way of surgical treatment for breast cancer worldwide nowadays. Multiphoton microscopy (MPM) has the ability to noninvasively visualize tissue architectures at the cellular level using intrinsic fluorescent molecules in biological tissues without the need for fluorescent dye. In this study, MPM is used to image the microstructures of terminal duct lobular unit (TDLU), invasive ductal carcinoma and the boundary region between normal and cancerous breast tissues. Our study demonstrates that MPM has the ability to not only reveal the morphological changes of the cuboidal epithelium, basement membrane and interlobular stroma but also identify the boundary between normal breast tissue and invasive ductal carcinoma, which correspond well to the Hematoxylin and Eosin (H and E) images. Predictably, MPM can monitor surgical margins in real time and provide considerable accuracy for resection of breast cancerous tissues intraoperatively. With the development of miniature, real-time MPM imaging technology, MPM should have great application prospects during breast-conserving surgery.

  17. Hypothyroidism after primary radiotherapy for head and neck squamous cell carcinoma: Normal tissue complication probability modeling with latent time correction

    DEFF Research Database (Denmark)

    Rønjom, Marianne Feen; Brink, Carsten; Bentzen, Søren

    2013-01-01

    To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors.......To develop a normal tissue complication probability (NTCP) model of radiation-induced biochemical hypothyroidism (HT) after primary radiotherapy for head and neck squamous cell carcinoma (HNSCC) with adjustment for latency and clinical risk factors....

  18. Effects of warm ischemic time on gene expression profiling in colorectal cancer tissues and normal mucosa.

    Directory of Open Access Journals (Sweden)

    Valeria Musella

    Full Text Available BACKGROUND: Genome-wide gene expression analyses of tumors are a powerful tool to identify gene signatures associated with biologically and clinically relevant characteristics and for several tumor types are under clinical validation by prospective trials. However, handling and processing of clinical specimens may significantly affect the molecular data obtained from their analysis. We studied the effects of tissue handling time on gene expression in human normal and tumor colon tissues undergoing routine surgical procedures. METHODS: RNA extracted from specimens of 15 patients at four time points (for a total of 180 samples after surgery was analyzed for gene expression on high-density oligonucleotide microarrays. A mixed-effects model was used to identify probes with different expression means across the four different time points. The p-values of the model were adjusted with the Bonferroni method. RESULTS: Thirty-two probe sets associated with tissue handling time in the tumor specimens, and thirty-one in the normal tissues, were identified. Most genes exhibited moderate changes in expression over the time points analyzed; however four of them were oncogenes, and two confirmed the effect of tissue handling by independent validation. CONCLUSIONS: Our results suggest that a critical time point for tissue handling in colon seems to be 60 minutes at room temperature. Although the number of time-dependent genes we identified was low, the three genes that already showed changes at this time point in tumor samples were all oncogenes, hence recommending standardization of tissue-handling protocols and effort to reduce the time from specimen removal to snap freezing accounting for warm ischemia in this tumor type.

  19. The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

    International Nuclear Information System (INIS)

    Lawton, P.A.

    1995-01-01

    Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author)

  20. The measurement of intrinsic cellular radiosensitivity in human tumours and normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Lawton, P.A.

    1995-12-31

    Human tumour and normal cell radiosensitivity are thought to be important factors determining the response of tumour and normal tissues to radiotherapy, respectively. Clonogenic assays are the standard method for measuring radiosensitivity but they are of limited applicability for clinical use with fresh human tumours. The main aim of this work was to evaluate the Adhesive Tumour Cell Culture System (ATCCS), as a method for measuring the radiosensitivity of human tumours. A soft agar clonogenic assay, the modified Courtenay-Mills assay, was used as a standard to compare with the ATCCS. The demonstration that fibroblast contamination could occur with both assay methods led to the investigation of a new technique for removing unwanted fibroblasts from tumour cell suspensions and to the use of a multiwell assay for measuring fibroblast radiosensitivity. (author).

  1. Comparisons of Soft Tissue Thickness Measurements in Adult Patients With Various Vertical Patterns

    Directory of Open Access Journals (Sweden)

    Neslihan Seyhan Cezairli

    2017-08-01

    Full Text Available Objective: The purposes of this study were to evaluate to study soft tissue facial profile among the different vertical patterns using the Holdaway analysis and the soft tissue thickness measurements. Materials and Methods: The study sample consisted of 90 patients divided into 3 groups: low angle group (30 patients; mean age, 20.38±3.76 years, normal angle group (30 patients; mean age, 19.36±2.83 years and high angle group (30 patients; mean age, 19.44±2.14 years. The study sample, comprised a total of 90 patients (54 women and 36 men divided into low-angle, normal-angle and high angle groups based on vertical growth pattern using the SN/GoGn angle (high-angle group >37°; low-angle group <27°; and control group or normal angle group 27-37°. Facial soft-tissue thickness and Holdaway measurements were analyzed on each radiograph with Image J programme. One-way analysis of variance and post-hoc test (Tukey were used to compare Holdaway measurements and soft tissue thicknesses among the three groups. Results: Significant differences among vertical patterns were observed for the ‘gnathion’, ‘menton’, ‘stomion’ and ‘inferior sulcus to H line’ when both genders were combined. These measurements were thinner in the high-angle group. Significant differences among vertical patterns were observed for ‘gnathion’ and ‘lower lip to H line’ in women; for ‘stomion’ and ‘nose prominence’ in men when examined separately. Conclusion: Facial soft tissue measurements except some for in high angle group were thinner than in low angle group. All soft tissue measurements were greater except for gnathion in low angle group in men than in women.

  2. Large animal normal tissue tolerance with boron neutron capture.

    Science.gov (United States)

    Gavin, P R; Kraft, S L; DeHaan, C E; Swartz, C D; Griebenow, M L

    1994-03-30

    Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA2B12H11SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood.

  3. Large animal normal tissue tolerance with boron neutron capture

    International Nuclear Information System (INIS)

    Gavin, P.R.; Swartz, C.D.; Kraft, S.L.; Briebenow, M.L.; DeHaan, C.E.

    1994-01-01

    Normal tissue tolerance of boron neutron capture irradiation using borocaptate sodium (NA 2 B 12 H 11 SH) in an epithermal neutron beam was studied. Large retriever-type dogs were used and the irradiations were performed by single dose, 5 x 10 dorsal portal. Fourteen dogs were irradiated with the epithermal neutron beam alone and 35 dogs were irradiated following intravenous administration of borocaptate sodium. Total body irradiation effect could be seen from the decreased leukocytes and platelets following irradiation. Most values returned to normal within 40 days postirradiation. Severe dermal necrosis occurred in animals given 15 Gy epithermal neutrons alone and in animals irradiated to a total peak physical dose greater than 64 Gy in animals following borocaptate sodium infusion. Lethal brain necrosis was seen in animals receiving between 27 and 39 Gy. Lethal brain necrosis occurred at 22-36 weeks postirradiation. A total peak physical dose of approximately 27 Gy and blood-boron concentrations of 25-50 ppm resulted in abnormal magnetic resonance imaging results in 6 months postexamination. Seven of eight of these animals remained normal and the lesions were not detected at the 12-month postirradiation examination. The bimodal therapy presents a complex challenge in attempting to achieve dose response assays. The resultant total radiation dose is a composite of low and high LET components. The short track length of the boron fission fragments and the geometric effect of the vessels causes much of the intravascular dose to miss the presumed critical target of the endothelial cells. The results indicate a large dose-sparing effect from the boron capture reactions within the blood. 23 refs., 6 figs., 2 tabs

  4. Sonographic determination of normal spleen size in an adult African population

    Energy Technology Data Exchange (ETDEWEB)

    Mustapha, Zainab; Tahir, Abdulrahman [Department of Radiology, University of Maiduguri Teaching Hospital, Maiduguri, Borno State (Nigeria); Tukur, Maisaratu [Department of Human Physiology, University of Maiduguri, Maiduguri, Borno State (Nigeria); Bukar, Mohammed [Department of Obstetrics and Gynaecology, University of Maiduguri Teaching Hospital, Maiduguri, Borno State (Nigeria); Lee, Wai-Kit, E-mail: leewk33@hotmail.co [Department of Medical Imaging, St. Vincent' s Hospital, University of Melbourne, 41 Victoria Parade, Fitzroy, Victoria 3065 (Australia)

    2010-07-15

    Objective: The purpose of this study was to determine the normal range of spleen size in an adult African population, and compare the findings to published data to determine any correlation with ethnicity. Materials and methods: Three hundred and seventy-four African adults without conditions that can affect the spleen or splenic abnormalities were evaluated with ultrasonography. Spleen length, width and thickness were measured and spleen volume calculated. Spleen size was correlated with age, gender, height, weight, and body mass index. Results: The mean spleen volume was 120 cm{sup 3}. Spleen volume correlated with spleen width (r = 0.85), thickness (r = 0.83) and length (r = 0.80). Men had a larger mean spleen volume than women. No correlation was found between spleen volume and age, weight, height, or body mass index. Conclusion: Mean spleen volume in African adults is smaller than data from Western sources, and cannot be explained by difference in body habitus.

  5. Antiandrogenic actions of medroxyprogesterone acetate on epithelial cells within normal human breast tissues cultured ex vivo.

    Science.gov (United States)

    Ochnik, Aleksandra M; Moore, Nicole L; Jankovic-Karasoulos, Tanja; Bianco-Miotto, Tina; Ryan, Natalie K; Thomas, Mervyn R; Birrell, Stephen N; Butler, Lisa M; Tilley, Wayne D; Hickey, Theresa E

    2014-01-01

    Medroxyprogesterone acetate (MPA), a component of combined estrogen-progestin therapy (EPT), has been associated with increased breast cancer risk in EPT users. MPA can bind to the androgen receptor (AR), and AR signaling inhibits cell growth in breast tissues. Therefore, the aim of this study was to investigate the potential of MPA to disrupt AR signaling in an ex vivo culture model of normal human breast tissue. Histologically normal breast tissues from women undergoing breast surgical operation were cultured in the presence or in the absence of the native AR ligand 5α-dihydrotestosterone (DHT), MPA, or the AR antagonist bicalutamide. Ki67, bromodeoxyuridine, B-cell CLL/lymphoma 2 (BCL2), AR, estrogen receptor α, and progesterone receptor were detected by immunohistochemistry. DHT inhibited the proliferation of breast epithelial cells in an AR-dependent manner within tissues from postmenopausal women, and MPA significantly antagonized this androgenic effect. These hormonal responses were not commonly observed in cultured tissues from premenopausal women. In tissues from postmenopausal women, DHT either induced or repressed BCL2 expression, and the antiandrogenic effect of MPA on BCL2 was variable. MPA significantly opposed the positive effect of DHT on AR stabilization, but these hormones had no significant effect on estrogen receptor α or progesterone receptor levels. In a subset of postmenopausal women, MPA exerts an antiandrogenic effect on breast epithelial cells that is associated with increased proliferation and destabilization of AR protein. This activity may contribute mechanistically to the increased risk of breast cancer in women taking MPA-containing EPT.

  6. Heads and tails of endoderm development and adult tissue homeostasis in zebrafish

    NARCIS (Netherlands)

    Faro, A.

    2010-01-01

    The regulatory signaling pathways crucial during embryonic development seem to play key roles in adult tissues homeostasis and are often deregulated in pathological conditions. The Wnt pathway plays a pivotal role in orchestrating cell fate decisions during embryonic development, organogenesis, and

  7. CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis

    International Nuclear Information System (INIS)

    Liu Fugeng; Wei Jiahu; Pan Jishu; Zhou Cheng; Chen Qihang; Yu Jingying; Wu Guogeng; Xu Xianhao

    2006-01-01

    Objective: To evaluate the CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis (MG). Methods: The CT findings of thymus area of 134 adult patients with lymphofollicular thymic hyperplasia in MG were reviewed, all of them with surgically and histologically proven diagnosis, and compared with the CT findings of 165 normal subjects. Results: In the group of patient, CT showed enlargement of thymus in 31 patients, 5 patients had nodule or mass ( 3 cm) and 9 patients (6.7%) had normal size thymus with soft-tissue density, it can considered with thymic hyperplasia. The spotty or streak shadow showed in other patients, though it could not be certain diagnosed as thymic hyperplasia, but could not be except it. The thymus area tissue complete replacement by fatty density were not found in patient group. The CT findings of patients had marked difference when compared with group of normal subjects (P<0.01), except the spotty or streak shadows. Conclusion: CT scan is an important method in diagnosing thymic lymphofollicular hyperplasia of MG in adult. (authors)

  8. Pesquisa da prevalência do papilomavírus humano em amostras de tecido endometrial normal e com carcinoma pela técnica de PCR Search for human papillomavirus in samples of normal endometrial tissue and tissue with carcinoma by the PCR technique

    Directory of Open Access Journals (Sweden)

    Edison Natal Fedrizzi

    2004-05-01

    tissue, and tissue with endometrial carcinoma of women submitted to surgical treatment (hysterectomy, or between endometrial carcinoma and benign disease, through the PCR technique. METHODS: this is an observational control-case study where 100 women (50 with endometrial carcinoma and 50 with normal endometrial tissue were analyzed for the detection of HPV DNA in samples of endometrial tissue kept in paraffin blocks by the PCR technique. The cases of endometrial carcinoma with uncertain primary site of the lesion as well as the cases with previous or current history of pre-neoplasic lesions or carcinoma of the lower genital tract were excluded. Variables as age, smoking habit, endometrial trophism, squamous differentiation and degree of tumor differentiation were also evaluated. RESULTS: the estimated relative risk of the presence of HPV in the endometrial carcinoma and in the normal endometrial tissue was the same. HPV was detected in 8% of the cases of carcinoma and 10% in the normal endometrial tissue. In spite of HPV having been 3.5 times more detected in women with smoking habit in the group without carcinoma, there was no statistical difference. The presence of HPV was also not correlated with the women's age, endometrial trophism, squamous differentiation and degree of tumor differentiation. The HPV types 16 (5 cases and 18 (4 cases were the viruses most frequently found both in the normal endometrial tissue or in the tissue with carcinoma. No oncogenic low risk virus was detected in the samples. CONCLUSION: The same proportion of HPV is present in the endometrial tissue of women with endometrial cancer and with normal endometrium. It could not be demonstrated a possible correlation of DNA of HPV with the development of endometrial carcinoma.

  9. Determination and correlation of spatial distribution of trace elements in normal and neoplastic breast tissues evaluated by μ-XRF

    International Nuclear Information System (INIS)

    Silva, M.P.; Oliveira, M.A.; Poletti, M.E.

    2012-01-01

    Full text: Some trace elements, naturally present in breast tissues, participate in a large number of biological processes, which include among others, activation or inhibition of enzymatic reactions and changes on cell membranes permeability, suggesting that these elements may influence carcinogenic processes. Thus, knowledge of the amounts of these elements and their spatial distribution in normal and neoplastic tissues may help in understanding the role of these elements in the carcinogenic process and tumor progression of breast cancers. Concentrations of trace elements like Ca, Fe, Cu and Zn, previously studied at LNLS using TXRF and conventional XRF, were elevated in neoplastic breast tissues compared to normal tissues. In this study we determined the spatial distribution of these elements in normal and neoplastic breast tissues using μ-XRF technique. We analyzed 22 samples of normal and neoplastic breast tissues (malignant and benign) obtained from paraffin blocks available for study at the Department of Pathology HC-FMRP/USP. From the blocks, a small fraction of material was removed and subjected to histological sections of 60 μm thick made with a microtome. The slices where placed in holder samples and covered with ultralen film. Tissue samples were irradiated with a white beam of synchrotron radiation. The samples were positioned at 45 degrees with respect to the incident beam on a table with 3 freedom degrees (x, y and z), allowing independent positioning of the sample in these directions. The white beam was collimated by a 20 μm microcapillary and samples were fully scanned. At each step, a spectrum was detected for 10 s. The fluorescence emitted by elements present in the sample was detected by a Si (Li) detector with 165 eV at 5.9 keV energy resolution, placed at 90 deg with respect to the incident beam. Results reveal that trace elements Ca-Zn and Fe-Cu could to be correlated in malignant breast tissues. Quantitative results, achieved by Spearman

  10. Pluripotency Genes and Their Functions in the Normal and Aberrant Breast and Brain

    Directory of Open Access Journals (Sweden)

    Tracy Seymour

    2015-11-01

    Full Text Available Pluripotent stem cells (PSCs attracted considerable interest with the successful isolation of embryonic stem cells (ESCs from the inner cell mass of murine, primate and human embryos. Whilst it was initially thought that the only PSCs were ESCs, in more recent years cells with similar properties have been isolated from organs of the adult, including the breast and brain. Adult PSCs in these organs have been suggested to be remnants of embryonic development that facilitate normal tissue homeostasis during repair and regeneration. They share certain characteristics with ESCs, such as an inherent capacity to self-renew and differentiate into cells of the three germ layers, properties that are regulated by master pluripotency transcription factors (TFs OCT4 (octamer-binding transcription factor 4, SOX2 (sex determining region Y-box 2, and homeobox protein NANOG. Aberrant expression of these TFs can be oncogenic resulting in heterogeneous tumours fueled by cancer stem cells (CSC, which are resistant to conventional treatments and are associated with tumour recurrence post-treatment. Further to enriching our understanding of the role of pluripotency TFs in normal tissue function, research now aims to develop optimized isolation and propagation methods for normal adult PSCs and CSCs for the purposes of regenerative medicine, developmental biology, and disease modeling aimed at targeted personalised cancer therapies.

  11. The effects of familiarity and complexity on appraisal of complex songs by cochlear implant recipients and normal hearing adults.

    Science.gov (United States)

    Gfeller, Kate; Christ, Aaron; Knutson, John; Witt, Shelley; Mehr, Maureen

    2003-01-01

    The purposes of this study were (a) to develop a test of complex song appraisal that would be suitable for use with adults who use a cochlear implant (assistive hearing device) and (b) to compare the appraisal ratings (liking) of complex songs by adults who use cochlear implants (n = 66) with a comparison group of adults with normal hearing (n = 36). The article describes the development of a computerized test for appraisal, with emphasis on its theoretical basis and the process for item selection of naturalistic stimuli. The appraisal test was administered to the 2 groups to determine the effects of prior song familiarity and subjective complexity on complex song appraisal. Comparison of the 2 groups indicates that the implant users rate 2 of 3 musical genres (country western, pop) as significantly more complex than do normal hearing adults, and give significantly less positive ratings to classical music than do normal hearing adults. Appraisal responses of implant recipients were examined in relation to hearing history, age, performance on speech perception and cognitive tests, and musical background.

  12. Collecting and Storing Tissue, Blood, and Bone Marrow Samples From Patients With Rhabdomyosarcoma or Other Soft Tissue Sarcoma

    Science.gov (United States)

    2017-12-11

    Adult Rhabdomyosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Chordoma; Desmoid Tumor; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Previously Untreated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  13. Stem cell therapy for the treatment of radiation-induced normal tissue damage

    International Nuclear Information System (INIS)

    Chapel, A.; Benderitter, M.; Gourmelon, P.; Lataillade, J.J.; Gorin, N.C.

    2013-01-01

    Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumour. In Europe, per year, 1.5 million patients undergo external radiotherapy. Acute adverse effect concern 80% of patients. The late adverse effect of radiotherapy concern 5 to 10% of them, which could be life threatening. Eradication of these manifestations is crucial. The French Institute of Radioprotection and Nuclear Safety (IRSN) contribute to understand effect of radiation on healthy tissue. IRSN is strongly implicated in the field of regeneration of healthy tissue after radiotherapy or radiological accident and in the clinical use of cell therapy in the treatment of irradiated patients. Our first success in cell therapy was the correction of deficient hematopoiesis in two patients. The intravenous injection of Mesenchymal Stem Cells (MSC) has restored bone marrow micro-environment after total body irradiation necessary to sustain hematopoiesis. Cutaneous radiation reactions play an important role in radiation accidents, but also as a limitation in radiotherapy and radio-oncology. We have evidenced for the first time, the efficiency of MSC therapy in the context of acute cutaneous and muscle damage following irradiation in five patients. Concerning the medical management of gastrointestinal disorder after irradiation, we have demonstrated the promising approach of the MSC treatment. We have shown that MSC migrate to damaged tissues and restore gut functions after radiation damage. The evaluation of stem cell therapy combining different sources of adult stem cells is under investigation

  14. Genomic instability: potential contributions to tumour and normal tissue response, and second tumours, after radiotherapy

    International Nuclear Information System (INIS)

    Hendry, Jolyon H.

    2001-01-01

    Purpose: Induced genomic instability generally refers to a type of damage which is transmissible down cell generations, and which results in a persistently enhanced frequency of de novo mutations, chromosomal abnormalities or lethality in a significant fraction of the descendant cell population. The potential contribution of induced genomic instability to tumour and normal tissue response, and second tumours, after radiotherapy, is explored. Results: The phenomenon of spontaneous genomic instability is well known in some rare genetic diseases (e.g. Gorlin's syndrome), and there is evidence in such cases that it can lead to a greater propensity for carcinogenesis (with shortened latency) which is enhanced after irradiation. It is unclear what role induced genomic instability plays in the response of normal individuals, but persistent chromosomal instability has been detected in vivo in lymphocytes and keratinocytes from irradiated normal individuals. Such induced genomic instability might play some role in tumour response in a subset of tumours with specific defects in damage response genes, but again its contribution to radiocurability in the majority of cancer patients is unclear. In normal tissues, genomic instability induced in wild-type cells leading to delayed cell death might contribute to more severe or prolonged early reactions as a consequence of increased cell loss, a longer time required for recovery, and greater residual injury. In tumours, induced genomic instability reflected in delayed reductions in clonogenic capacity might contribute to the radiosensitivity of primary tumours, and also to a lower incidence, longer latency and slower growth rate of recurrences and metastases. Conclusions: The evidence which is reviewed shows that there is little information at present to support these propositions, but what exists is consistent with their expectations. Also, it is not yet clear to what extent mutations associated with genomic instability

  15. Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

    Science.gov (United States)

    Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Gullu Amuran, Gokce; Ozmen, Tolga; Gulluoglu, Bahadır M; Kaya, Handan; Ozer, Ayse

    2017-09-01

    Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. Telomeres were shorter in tumor tissues compared to controls (Pbreast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association. © 2016 Wiley Periodicals, Inc.

  16. Binding of (/sup 3/H) progesterone to normal and neoplastic tissue samples from tumour bearing breasts

    Energy Technology Data Exchange (ETDEWEB)

    Pollow, K; Sinnecker, R; Schmidt-Gollwitzer, M; Boquoi, E; Pollow, B [Institut fuer Molekularbiologie und Biochemie, Frauenklinik Charlottenburg der Freien Universitat, Berlin (G.F.R.)

    1977-01-01

    Macromolecular components of normal human mammary cytosol (obtained from 'non-malignant tissue samples' from cancer bearing breasts) which bind (/sup 3/H)progesterone in vitro were characterized by sucrose gradient centrifugation, gel filtration on Agarose, ion exchange chromatography, isoelectric focusing, competition studies and kinetic parameters. The size of the cytoplasmic binding components vary with the concentration of KCl. In the absence of KCl, the major components are characterized by sedimentation coefficients of about 4 S and 8 S. In solutions containing 0.3M KCl, the cytoplasmic components sediment at 4 S in sucrose gradient. The corticosteroid-binding component of normal human mammary cytosol both sediment at about the same rate in the presence of 0.3M KCl and chromatograph as a single component on Agarose. The isoelectric point of the progesterone-binding component of normal human mammary cytosol was located around pH 5.0. The progesterone-binding component was more thermo-labile than serum CBG. CBG was inactivated at temperatures above 45 deg C but temperature above 20 deg C destroyed specific progesterone receptor binding. Progesterone receptor concentrations in normal mammary cytosol of premenopausal women depended on the menstrual cycle. The binding of progesterone was highest around the time of ovulation. In breast tumor tissue samples the progesterone receptor concentration was lower than in the normal mammary cytosol (obtained in each case from the same tumor-bearing breast). In 5 out of 37 breast tumor samples progesterone binding activity could not be detected.

  17. Comparison of incidences of normal tissue complications with tumor response in a phase III trial comparing heat plus radiation to radiation alone

    International Nuclear Information System (INIS)

    Dewhirst, M.W.; Sim, D.A.; Grochowski, K.J.

    1984-01-01

    The success of hyperthermia (/sup Δ/) as an adjuvant to radiation (XRT) will depend on whether the increase in tumor control is greater than that for normal tissue reactions. One hundred and thirty dogs and cats were stratified by histology and randomized to receive XRT (460 rads per fraction, two fractions per week, for eight fractions) or /sup Δ/ + XRT (30 min. at 44 +-2 0 C; one fraction per week, four fractions; immediately prior to XRT). Heat induced changes in tumor and normal tissue responses were made by comparing ratios of incidence for /sup Δ/ + XRT and XRT alone (TRR; Thermal Relative Risk). Change in tumor response duration was calculated from statistical analysis of response duration curves (RRR; Relative Relapse Rate). Heat increased early normal tissue reactions (moist desquamation and mucositis by a factor of 1.08. Tumor complete response, by comparison, was significantly improved (TRR = 2.12, p < .001). Late skin fibrosis was also increased (TRR = 1.51), but the prolongation in tumor response was greater (RRR 1.85). The degree of thermal enhancement for all tissues was dependent on the minimum temperature achieved on the first treatment, but the values for tumor were consistently greater than those achieved for normal tissues

  18. Normal Values of Tissue-Muscle Perfusion Indexes of Lower Limbs Obtained with a Scintigraphic Method.

    Science.gov (United States)

    Manevska, Nevena; Stojanoski, Sinisa; Pop Gjorceva, Daniela; Todorovska, Lidija; Miladinova, Daniela; Zafirova, Beti

    2017-09-01

    Introduction Muscle perfusion is a physiologic process that can undergo quantitative assessment and thus define the range of normal values of perfusion indexes and perfusion reserve. The investigation of the microcirculation has a crucial role in determining the muscle perfusion. Materials and method The study included 30 examinees, 24-74 years of age, without a history of confirmed peripheral artery disease and all had normal findings on Doppler ultrasonography and pedo-brachial index of lower extremity (PBI). 99mTc-MIBI tissue muscle perfusion scintigraphy of lower limbs evaluates tissue perfusion in resting condition "rest study" and after workload "stress study", through quantitative parameters: Inter-extremity index (for both studies), left thigh/right thigh (LT/RT) left calf/right calf (LC/RC) and perfusion reserve (PR) for both thighs and calves. Results In our investigated group we assessed the normal values of quantitative parameters of perfusion indexes. Indexes ranged for LT/RT in rest study 0.91-1.05, in stress study 0.92-1.04. LC/RC in rest 0.93-1.07 and in stress study 0.93-1.09. The examinees older than 50 years had insignificantly lower perfusion reserve of these parameters compared with those younger than 50, LC (p=0.98), and RC (p=0.6). Conclusion This non-invasive scintigraphic method allows in individuals without peripheral artery disease to determine the range of normal values of muscle perfusion at rest and stress condition and to clinically implement them in evaluation of patients with peripheral artery disease for differentiating patients with normal from those with impaired lower limbs circulation.

  19. SU-D-18A-04: Quantifying the Ability of Tumor Tracking to Spare Normal Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Burger, A; Buzurovic, I; Hurwitz, M; Williams, C; Lewis, J [Brigham and Women' s Hospital, Dana-Farber Cancer Center, Harvard Medical Sc, Boston, MA (United States); Mishra, P [Varian Medical Systems, Palo Alto, CA (United States); Seco, J [Mass General Hospital, Harvard Medical, Boston, MA (United States)

    2014-06-01

    Purpose: Tumor tracking allows for smaller tissue volumes to be treated, potentially reducing normal tissue damage. However, tumor tracking is a more complex treatment and has little benefit in some scenarios. Here we quantify the benefit of tumor tracking for a range of patients by estimating the dose of radiation to organs at risk and the normal tissue complication probability (NTCP) for both standard and tracking treatment plans. This comparison is performed using both patient 4DCT data and extended Cardiac-Torso (XCAT) digital phantoms. Methods: We use 4DCT data for 10 patients. Additionally, we generate digital phantoms with motion derived from measured patient long tumor trajectories to compare standard and tracking treatment plans. The standard treatment is based on the average intensity projection (AIP) of 4DCT images taken over a breath cycle. The tracking treatment is based on doses calculated on images representing the anatomy at each time point. It is assumed that there are no errors in tracking the target. The NTCP values are calculated based on RTOG guidelines. Results: The mean reduction in the mean dose delivered was 5.5% to the lungs (from 7.3 Gy to 6.9 Gy) and 4.0% to the heart (from 12.5 Gy to 12.0 Gy). The mean reduction in the max dose delivered was 13% to the spinal cord (from 27.6 Gy to 24.0 Gy), 2.5% to the carina (from 31.7 Gy to 30.9 Gy), and 15% to the esophagus (from 69.6 Gy to 58.9 Gy). The mean reduction in the probability of 2nd degree radiation pneumonitis (RP) was 8.7% (3.1% to 2.8%) and the mean reduction in the effective volume was 6.8% (10.8% to 10.2%). Conclusions: Tumor tracking has the potential to reduce irradiation of organs at risk, and consequentially reduce the normal tissue complication probability. The benefits vary based on the clinical scenario. This study is supported by Varian Medical Systems, Inc.

  20. Nonlinear optical microscopy for histology of fresh normal and cancerous pancreatic tissues.

    Directory of Open Access Journals (Sweden)

    Wenyan Hu

    Full Text Available BACKGROUND: Pancreatic cancer is a lethal disease with a 5-year survival rate of only 1-5%. The acceleration of intraoperative histological examination would be beneficial for better management of pancreatic cancer, suggesting an improved survival. Nonlinear optical methods based on two-photon excited fluorescence (TPEF and second harmonic generation (SHG of intrinsic optical biomarkers show the ability to visualize the morphology of fresh tissues associated with histology, which is promising for real-time intraoperative evaluation of pancreatic cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to investigate whether the nonlinear optical imaging methods have the ability to characterize pancreatic histology at cellular resolution, we studied different types of pancreatic tissues by using label-free TPEF and SHG. Compared with other routine methods for the preparation of specimens, fresh tissues without processing were found to be most suitable for nonlinear optical imaging of pancreatic tissues. The detailed morphology of the normal rat pancreas was observed and related with the standard histological images. Comparatively speaking, the preliminary images of a small number of chemical-induced pancreatic cancer tissues showed visible neoplastic differences in the morphology of cells and extracellular matrix. The subcutaneous pancreatic tumor xenografts were further observed using the nonlinear optical microscopy, showing that most cells are leucocytes at 5 days after implantation, the tumor cells begin to proliferate at 10 days after implantation, and the extracellular collagen fibers become disordered as the xenografts grow. CONCLUSIONS/SIGNIFICANCE: In this study, nonlinear optical imaging was used to characterize the morphological details of fresh pancreatic tissues for the first time. We demonstrate that it is possible to provide real-time histological evaluation of pancreatic cancer by the nonlinear optical methods, which present an

  1. Impact of statistical learning methods on the predictive power of multivariate normal tissue complication probability models

    NARCIS (Netherlands)

    Xu, Cheng-Jian; van der Schaaf, Arjen; Schilstra, Cornelis; Langendijk, Johannes A.; van t Veld, Aart A.

    2012-01-01

    PURPOSE: To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. METHODS AND MATERIALS: In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator

  2. Recognition of "real-world" musical excerpts by cochlear implant recipients and normal-hearing adults.

    Science.gov (United States)

    Gfeller, Kate; Olszewski, Carol; Rychener, Marly; Sena, Kimberly; Knutson, John F; Witt, Shelley; Macpherson, Beth

    2005-06-01

    The purposes of this study were (a) to compare recognition of "real-world" music excerpts by postlingually deafened adults using cochlear implants and normal-hearing adults; (b) to compare the performance of cochlear implant recipients using different devices and processing strategies; and (c) to examine the variability among implant recipients in recognition of musical selections in relation to performance on speech perception tests, performance on cognitive tests, and demographic variables. Seventy-nine cochlear implant users and 30 normal-hearing adults were tested on open-set recognition of systematically selected excerpts from musical recordings heard in real life. The recognition accuracy of the two groups was compared for three musical genre: classical, country, and pop. Recognition accuracy was correlated with speech recognition scores, cognitive measures, and demographic measures, including musical background. Cochlear implant recipients were significantly less accurate in recognition of previously familiar (known before hearing loss) musical excerpts than normal-hearing adults (p genre. Implant recipients were most accurate in the recognition of country items and least accurate in the recognition of classical items. There were no significant differences among implant recipients due to implant type (Nucleus, Clarion, or Ineraid), or programming strategy (SPEAK, CIS, or ACE). For cochlear implant recipients, correlations between melody recognition and other measures were moderate to weak in strength; those with statistically significant correlations included age at time of testing (negatively correlated), performance on selected speech perception tests, and the amount of focused music listening following implantation. Current-day cochlear implants are not effective in transmitting several key structural features (i.e., pitch, harmony, timbral blends) of music essential to open-set recognition of well-known musical selections. Consequently, implant

  3. Estrogen receptor alpha localization in the testes of men with normal spermatogenesis.

    Science.gov (United States)

    Filipiak, Eliza; Suliborska, Dagmara; Laszczynska, Maria; Walczak-Jedrzejowska, Renata; Oszukowska, Elzbieta; Marchlewska, Katarzyna; Kula, Krzysztof; Slowikowska-Hilczer, Jolanta

    2013-10-08

    It is known that estrogens act on the male reproductive tract by binding to estrogen receptors (ER) α and β. However, studies on ER localization in the human testis are discordant. The aim of this study was to investigate the localization of ERα in the testes of adult men with normal spermatogenesis. Semen analysis of ten adult men revealed azoospermia. FSH, LH and testosterone serum concentrations were within normal values, and the volume of the testes was normal, hence obstructive azoospermia was suspected. The tissues from testicular surgical biopsies were fixed in Bouin's fluid and embedded in paraffin. Assessments of the seminiferous epithelium (scoring 10 to -1), the number of Leydig cells (scoring 1 to 5), the areal fraction of intertubular space (IS), measurements of seminiferous tubule diameter, and the thickness of the tubular wall, were performed on microscopic sections. Immunohistochemical staining was applied with monoclonal antibodies against ERα. The mean spermatogenesis score was 10 points; IS - 30.6 ± 8.1%; seminiferous tubule diameter - 193.9 ± 19.4 μm; thickness of tubular wall - 7.44 ± 1.1 μm; number of Leydig cells - 1.6 ± 1.1 points. Immunohistochemical staining showed the localization of ERα to be in the Sertoli and Leydig cell cytoplasm, while ERα was absent in germ cells. The results of testicular tissue analysis confirmed its normal structure and normal, full spermatogenesis. The presence of ERα in Sertoli and Leydig cells in normal human testis demonstrated in this study suggests that estrogens may affect testicular function.

  4. Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

    Energy Technology Data Exchange (ETDEWEB)

    Milliat, F

    2007-05-15

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  5. The composition of engineered cartilage at the time of implantation determines the likelihood of regenerating tissue with a normal collagen architecture.

    Science.gov (United States)

    Nagel, Thomas; Kelly, Daniel J

    2013-04-01

    The biomechanical functionality of articular cartilage is derived from both its biochemical composition and the architecture of the collagen network. Failure to replicate this normal Benninghoff architecture in regenerating articular cartilage may in turn predispose the tissue to failure. In this article, the influence of the maturity (or functionality) of a tissue-engineered construct at the time of implantation into a tibial chondral defect on the likelihood of recapitulating a normal Benninghoff architecture was investigated using a computational model featuring a collagen remodeling algorithm. Such a normal tissue architecture was predicted to form in the intact tibial plateau due to the interplay between the depth-dependent extracellular matrix properties, foremost swelling pressures, and external mechanical loading. In the presence of even small empty defects in the articular surface, the collagen architecture in the surrounding cartilage was predicted to deviate significantly from the native state, indicating a possible predisposition for osteoarthritic changes. These negative alterations were alleviated by the implantation of tissue-engineered cartilage, where a mature implant was predicted to result in the formation of a more native-like collagen architecture than immature implants. The results of this study highlight the importance of cartilage graft functionality to maintain and/or re-establish joint function and suggest that engineering a tissue with a native depth-dependent composition may facilitate the establishment of a normal Benninghoff collagen architecture after implantation into load-bearing defects.

  6. The normal tissue sparing obtained with simultaneous treatment of pelvic lymph nodes and bladder using intensity-modulated radiotherapy

    International Nuclear Information System (INIS)

    Soendergaard, Jimmi; Hoeyer, Morten; Wright, Pauliina; Grau, Cai; Muren, Ludvig Paul; Petersen, Joergen B.

    2009-01-01

    We have implemented an intensity-modulated radiotherapy (IMRT) protocol for simultaneous irradiation of bladder and lymph nodes. In this report, doses to normal tissue from IMRT and our previous conformal sequential boost technique are compared. Material and methods. Sixteen patients with urinary bladder cancer were treated using a six-field dynamic IMRT beam arrangement delivering 60 Gy to the bladder and 48 Gy to the pelvic lymph nodes. Dose-volume histogram (DVH) parameters for relevant normal tissues (bowel, bowel cavity, rectum and femoral heads) for the IMRT plans were compared with corresponding DVHs from our previous conformal sequential boost technique. Calculations of the generalized Equivalent Uniform Dose (gEUD) were performed for the bowel, with a reference volume of 200 cm 3 and a volume effect parameter k = 4, as well as for the rectum, using k = 12. Acute gastrointestinal (GI) and genitourinary (GU) RTOG toxicity was recorded. Results. Statistical significant normal tissue sparing was obtained by IMRT. For the bowel, a significant reduction was obtained at all dose levels between 20 and 50 Gy (p 3 at 50 Gy, while the gEUD was reduced from 58 to 53 Gy (p 3 at 50 Gy. The rectum gEUD was reduced from 55 to 53 Gy (p < 0.05). For the femoral heads, IMRT reduced the maximum dose as well as the volumes above all dose levels. The rate of acute peak Grade 2 GI RTOG complications was 38% after IMRT. Conclusion. IMRT to the urinary bladder and elective lymph nodes result in considerable normal tissue sparing compared to conformal sequential boost technique. This has paved the way for further studies combining IMRT with image-guided radiotherapy (IGRT) in bladder cancer

  7. Gender Dependence in Mouth Opening Dimensions in Normal Adult Malaysians Population

    OpenAIRE

    Shaari, Ramizu; Hwa, Teoh Eng; Rahman, Shaifulizan Abdul

    2011-01-01

    While measurement of mouth opening is an important clinica examination in diagnosis and management of oral disease, data on non-Western populations are limited. This study was therefore conducted to determine the range of mouth opening in normal Malaysian male and female adults. A total of 34 dental students of Universiti Sains Malaysia (USM) were chosen randomly and their maximum mouth opening was measured after being asked to open their mouth sufficiently to accommodate three fingers. Measu...

  8. DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing.

    Science.gov (United States)

    Rübe, Claudia E; Grudzenski, Saskia; Kühne, Martin; Dong, Xiaorong; Rief, Nicole; Löbrich, Markus; Rübe, Christian

    2008-10-15

    Radiotherapy is an effective cancer treatment, but a few patients suffer severe radiation toxicities in neighboring normal tissues. There is increasing evidence that the variable susceptibility to radiation toxicities is caused by the individual genetic predisposition, by subtle mutations, or polymorphisms in genes involved in cellular responses to ionizing radiation. Double-strand breaks (DSB) are the most deleterious form of radiation-induced DNA damage, and DSB repair deficiencies lead to pronounced radiosensitivity. Using a preclinical mouse model, the highly sensitive gammaH2AX-foci approach was tested to verify even subtle, genetically determined DSB repair deficiencies known to be associated with increased normal tissue radiosensitivity. By enumerating gammaH2AX-foci in blood lymphocytes and normal tissues (brain, lung, heart, and intestine), the induction and repair of DSBs after irradiation with therapeutic doses (0.1-2 Gy) was investigated in repair-proficient and repair-deficient mouse strains in vivo and blood samples irradiated ex vivo. gammaH2AX-foci analysis allowed to verify the different DSB repair deficiencies; even slight impairments caused by single polymorphisms were detected similarly in both blood lymphocytes and solid tissues, indicating that DSB repair measured in lymphocytes is valid for different and complex organs. Moreover, gammaH2AX-foci analysis of blood samples irradiated ex vivo was found to reflect repair kinetics measured in vivo and, thus, give reliable information about the individual DSB repair capacity. gammaH2AX analysis of blood and tissue samples allows to detect even minor genetically defined DSB repair deficiencies, affecting normal tissue radiosensitivity. Future studies will have to evaluate the clinical potential to identify patients more susceptible to radiation toxicities before radiotherapy.

  9. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    Energy Technology Data Exchange (ETDEWEB)

    Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  10. Self-rated driving habits among older adults with clinically-defined mild cognitive impairment, clinically-defined dementia, and normal cognition.

    Science.gov (United States)

    O'Connor, Melissa L; Edwards, Jerri D; Bannon, Yvonne

    2013-12-01

    Older adults with clinically-defined dementia may report reducing their driving more than cognitively normal controls. However, it is unclear how these groups compare to individuals with clinically-defined mild cognitive impairment (MCI) in terms of driving behaviors. The current study investigated self-reported driving habits among adults age 60 and older with clinical MCI (n=41), clinical mild dementia (n=40), and normal cognition (n=43). Participants reported their driving status, driving frequency (days per week), and how often they avoided accessing the community, making left turns, driving at night, driving in unfamiliar areas, driving on high-traffic roads, and driving in bad weather. After adjusting for education, a MANCOVA revealed that participants with MCI and dementia avoided unfamiliar areas and high-traffic roads significantly more than normal participants. Participants with dementia also avoided left turns and accessing the community more than those with normal cognition and MCI (pdriving variables did not significantly differ between groups. Thus, older adults with clinically-defined MCI, as well as those with dementia, avoided some complex driving situations more than cognitively intact adults. However, all diagnostic groups had similar rates of driving cessation and frequency. Future research should examine the safety implications of such findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Longitudinal Changes in Segmental Aortic Stiffness Determined by Cardiac Magnetic Resonance in Children and Young Adults With Connective Tissue Disorders (the Marfan, Loeys-Dietz, and Ehlers-Danlos Syndromes, and Nonspecific Connective Tissue Disorders).

    Science.gov (United States)

    Merlocco, Anthony; Lacro, Ronald V; Gauvreau, Kimberlee; Rabideau, Nicole; Singh, Michael N; Prakash, Ashwin

    2017-10-01

    Aortic stiffness measured by cardiac magnetic resonance (CMR) in connective tissue disorder (CTD) patients has been previously shown to be abnormal and to be associated with adverse aortic outcomes. The rate of increase in aortic stiffness with normal aging has been previously described. However, longitudinal changes in aortic stiffness have not been characterized in CTD patients. We examined longitudinal changes in CMR-derived aortic stiffness in children and young adults with CTDs. A retrospective analysis of 50 children and young adults (median age, 20 years; range, 0.2 to 49; 40% age, whereas the β stiffness index increased at all aortic segments. The average rates of decline in distensibility (x10 -3  mm Hg -1 per 10-year increase in age) were 0.7, 1.3, and 1 at the AoR, ascending aorta, and descending aorta, respectively. The rates of decline in distensibility were not associated with the rates of AoR dilation or surgical AoR replacement. In conclusion, on serial CMR measurements in children and young adults with CTDs, aortic stiffness progressively increased with age, with rates of change only slightly higher than those previously reported in healthy adults. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Digital ranges of motion: normal values in young adults.

    Science.gov (United States)

    Mallon, W J; Brown, H R; Nunley, J A

    1991-09-01

    Analysis of the range of motion of fingers was done in young (eighteen to thirty-five year old) adult volunteers with no history of previous injury to their hands. The data show that there are slight differences between the individual digits. Notably, metacarpophalangeal flexion and total active motion increase linearly in proceeding from the index to the small finger. There were also minor differences in comparing sexes. Women have greater extension at the metacarpophalangeal joint in both active and passive motion and have a greater total active motion at all digits as a result. A significant tenodesis effect was found at the distal interphalangeal joint in normal subjects. No differences were found that could be attributable to handedness.

  13. Comparison of normal tissue pharmacokinetics with 111In/9Y monoclonal antibody m170 for breast and prostate cancer

    International Nuclear Information System (INIS)

    Lehmann, Joerg; DeNardo, Gerald L.; Yuan, Aina; Shen Sui; O'Donnell, Robert T.; Richman, Carol M.; De Nardo, Sally J.

    2006-01-01

    Purpose: Radioactivity deposition in normal tissues limits the dose deliverable by radiopharmaceuticals (RP) in radioimmunotherapy (RIT). This study investigated the absorbed radiation dose in normal tissues for prostate cancer patients in comparison to breast cancer patients for 2 RPs using the monoclonal antibody (MAb) m170. Methods and Materials: 111 In-DOTA-glycylglycylglycyl-L-p-isothiocyanatophenylalanine amide (GGGF)-m170 and 111 In-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA) 2-iminothiolane (2IT)-m170, representing the same MAb and chelate with and without a cleavable linkage, were studied in 13 breast cancer and 26 prostate cancer patients. Dosimetry for 9 Y was calculated using 111 In MAb pharmacokinetics from the initial imaging study for each patient, using reference man- and patient-specific masses. Results: The reference man-specific radiation doses (cGy/MBq) were not significantly different for the breast and the prostate cancer patients for both RPs in all but one tissue-RP combination (liver, DOTA-2IT). The patient-specific doses had differences between the groups most of which can be related to weight differences. Conclusions: Similar normal tissue doses were calculated for two groups of patients having different cancers and genders. This similarity combined with continued careful analysis of the imaging data might allow the use of higher starting doses in early phase RIT studies

  14. Dynamic contrast-enhanced magnetic resonance imaging: a non-invasive method to evaluate significant differences between malignant and normal tissue

    International Nuclear Information System (INIS)

    Rudisch, Ansgar; Kremser, Christian; Judmaier, Werner; Zunterer, Hildegard; DeVries, Alexander F.

    2005-01-01

    Purpose: An ever recurring challenge in diagnostic radiology is the differentiation between non-malignant and malignant tissue. Based on evidence that microcirculation of normal, non-malignant tissue differs from that of malignant tissue, the goal of this study was to assess the reliability of dynamic contrast-enhanced Magnetic Resonance Imaging (dcMRI) for differentiating these two entities. Materials and methods: DcMRI data of rectum carcinoma and gluteus maximus muscles were acquired in 41 patients. Using an fast T1-mapping sequence on a 1.5-T whole body scanner, T1-maps were dynamically retrieved before, during and after constant rate i.v. infusion of a contrast medium (CM). On the basis of the acquired data sets, PI-values were calculated on a pixel-by-pixel basis. The relevance of spatial heterogeneities of microcirculation was investigated by relative frequency histograms of the PI-values. Results: A statistically significant difference between malignant and normal tissue was found for the mean PI-value (P < 0.001; 8.95 ml/min/100 g ± 2.45 versus 3.56 ml/min/100 g ± 1.20). Additionally relative frequency distributions of PI-values with equal class intervals of 2.5 ml/min/100 g revealed significant differences between the histograms of muscles and rectum carcinoma. Conclusion: We could show that microcirculation differences between malignant and normal, non-malignant tissue can be reliably assessed by non-invasive dcMRI. Therefore, dcMRI holds great promise in the aid of cancer assessment, especially in patients where biopsy is contraindicated

  15. Transplantation of Normal Adipose Tissue Improves Blood Flow and Reduces Inflammation in High Fat Fed Mice With Hindlimb Ischemia

    Directory of Open Access Journals (Sweden)

    Liyuan Chen

    2018-03-01

    Full Text Available Background: Fat deposition is associated with peripheral arterial disease. Adipose tissue has recently been implicated in vascular remodeling and angiogenic activity. We hypothesized that the transplantation of adipose tissues from normal mice improves blood flow perfusion and neovascularization in high-fat diet fed mice.Methods: After 14 weeks of high-fat diet (HFD-fed mice, unilateral hind limb ischemia was performed. Subcutaneous white adipose tissue (WAT and brown adipose tissue (BAT fat pads were harvested from normal EGFP mice, and subcutaneously transplanted over the region of the adductor muscles of HFD mice. Blood flow was measured using Laser Doppler Scanner. Vascular density, macrophages infiltration, and macrophage polarization were examined by RT-qPCR, and immunohistochemistry.Results: We found that the transplantation of WAT derived from normal mice improved functional blood flow in HFD-fed mice compared to mice transplanted with BAT and sham-treated mice. WAT transplantation increased the recruitment of pericytes associated with nascent blood vessels, but did not affect capillary formation. Furthermore, transplantation of WAT ameliorated HFD-induced insulin resistance, M2 macrophage predominance and the release of arteriogenic factors in ischemic muscles. Mice receiving WAT also displayed a marked reduction in several proinflammatory cytokines. In contrast, mice transplanted with BAT were glucose intolerant and demonstrated increased IL-6 levels in ischemic muscles.Conclusion: These results indicate that transplantation of adipose tissue elicits improvements in blood perfusion and beneficial effects on systemic glucose homeostasis and could be a promising therapeutic option for the treatment of diabetic peripheral arterial disease.

  16. Attitudes of Overweight and Normal Weight Adults Regarding Exercise at a Health Club

    Science.gov (United States)

    Miller, Wayne C.; Miller, Todd A.

    2010-01-01

    Objective: To compare attitudes of overweight (OW) and normal weight (NW) adults regarding health club exercise. Design: A 46-item survey (23 pairs of attitude/value statements) measured attitudes toward exercising at a health club 30 minutes, twice a week, for a month. Setting: Survey posted on surveymonkey.com. Respondents (men = 730, women =…

  17. Non-invasive characterization of normal and pathological tissues through dynamic infrared imaging in the hamster cheek pouch oral cancer model

    Science.gov (United States)

    Herrera, María. S.; Monti Hughes, Andrea; Salva, Natalia; Padra, Claudio; Schwint, Amanda; Santa Cruz, Gustavo A.

    2017-05-01

    Biomedical infrared thermography, a non-invasive and functional imaging method, provides information on the normal and abnormal status and response of tissues in terms of spatial and temporal variations in body infrared radiance. It is especially attractive in cancer research due to the hypervascular and hypermetabolic activity of solid tumors. Moreover, healthy tissues like skin or mucosa exposed to radiation can be examined since inflammation, changes in water content, exudation, desquamation, erosion and necrosis, between others, are factors that modify their thermal properties. In this work we performed Dynamic Infrared Imaging (DIRI) to contribute to the understanding and evaluation of normal tissue, tumor and precancerous tissue response and radiotoxicity in an in vivo model, the hamster cheek pouch, exposed to Boron Neutron Capture Therapy. In this study, we particularly focused on the observation of temperature changes under forced transient conditions associated with mass moisture transfer in the tissue-air interface, in each tissue with or without treatment. We proposed a simple mathematical procedure that considerers the heat transfer from tissue to ambient through convection and evaporation to model the transient (exponential decay o recover) thermal study. The data was fitted to determined the characteristic decay and recovery time constants of the temperature as a function of time. Also this model allowed to explore the mass flux of moisture, as a degree of evaporation occurring on the tissue surface. Tissue thermal responses under provocation tests could be used as a non-invasive method to characterize tissue physiology.

  18. Increased PDGFRα Activation Disrupts Connective Tissue Development and Drives Systemic Fibrosis

    OpenAIRE

    Olson, Lorin E.; Soriano, Philippe

    2009-01-01

    PDGF signaling regulates the development of mesenchymal cell types in the embryo and in the adult, but the role of receptor activation in tissue homeostasis has not been investigated. We have generated conditional knockin mice with mutations in PDGFRα that drive increased kinase activity under the control of the endogenous PDGFRα promoter. In embryos, increased PDGFRα signaling leads to hyperplasia of stromal fibroblasts that disturbs normal smooth muscle tissue in radially patterned organs. ...

  19. Role of plasminogen activator inhibitor type-1 in radiation-induced normal tissues injury

    International Nuclear Information System (INIS)

    Abderrahmani, R.

    2010-01-01

    Radiotherapy is an essential tool for cancer treatment, but there is a balance between benefits and risks related to the use of ionizing radiation: the objective is to deliver a maximum dose to the tumour to destroy or to sterilize it while protecting surrounding normal tissues. Radio-induced damages to normal tissues are therefore a limiting factor when increasing the dose delivered to the tumour. One of the objectives of this research thesis is to bring to the fore a relationship between the initiation of lesions and the development of late damages, more particularly in the intestine, and to identify the involved molecular actors and their inter-connectivity. After a first part presenting ionizing radiation, describing biological effects of ionizing radiation and their use in radiotherapy, presenting the intestine and the endothelium and discussing the intestine radio-sensitivity, discussing the radio-induced intestine damages and radiotherapy-induced complications, and presenting the plasminogen activator inhibitor (PAI-1) and its behaviour in presence of ionizing radiation, two articles are reproduced. The first one addresses the effect of a pharmacological inhibition and of genetic deficiency in PAI-1 on the evolution of radio-induced intestine lesions. The second one discusses the fact that radio-induced PAI-1-related death of endothelial cells determines the severity of early radio-induced intestine lesions

  20. Identification of Reference Genes for Normalizing Quantitative Real-Time PCR in Urechis unicinctus

    Science.gov (United States)

    Bai, Yajiao; Zhou, Di; Wei, Maokai; Xie, Yueyang; Gao, Beibei; Qin, Zhenkui; Zhang, Zhifeng

    2018-06-01

    The reverse transcription quantitative real-time PCR (RT-qPCR) has become one of the most important techniques of studying gene expression. A set of valid reference genes are essential for the accurate normalization of data. In this study, five candidate genes were analyzed with geNorm, NormFinder, BestKeeper and ΔCt methods to identify the genes stably expressed in echiuran Urechis unicinctus, an important commercial marine benthic worm, under abiotic (sulfide stress) and normal (adult tissues, embryos and larvae at different development stages) conditions. The comprehensive results indicated that the expression of TBP was the most stable at sulfide stress and in developmental process, while the expression of EF- 1- α was the most stable at sulfide stress and in various tissues. TBP and EF- 1- α were recommended as a suitable reference gene combination to accurately normalize the expression of target genes at sulfide stress; and EF- 1- α, TBP and TUB were considered as a potential reference gene combination for normalizing the expression of target genes in different tissues. No suitable gene combination was obtained among these five candidate genes for normalizing the expression of target genes for developmental process of U. unicinctus. Our results provided a valuable support for quantifying gene expression using RT-qPCR in U. unicinctus.

  1. A study on normal value of eyeball protrusion in Korean adult using CT

    International Nuclear Information System (INIS)

    Song, Chi Sung; Chang, Kee Hyun

    1984-01-01

    CT may be valuably used in determination of proptosis. Normal value of eyeball protrusion was measured in normal Koreans using CT. Among 86 Koreans, 26 have normal both eyes, but 60 have one normal eye with one abnormal eye (chiefly, proptosis and and eyeball tumor). The results of 112 eyes are as follows: Absolute measurement of 'a', that is, the distance between cornea and IZL (interzygomatic line) is 16.0±3.4 mm in male (for 63 eye), 15.7±4.0 mm in female for 49 eyes. Ratio of 'a' over 'A' (A-P diameter of eyeball) is 57±12% is male (for 63 eye), 57±14% in female (for 49 eye) Discrepancy of eyeball protrusion between both eyes is 0.67±1.5 mm (for 26 adults). Practically, normal range of eyeball prtotrusion ('a') is 12.6 mm < male < 19.4 mm, 11.7 mm < female < 19.7 mm. 'a/A' ratio over 70% and over 2mm discrepancy between both eyes are also suggested as genuine exophthalmos

  2. Exposure to a Highly Caloric Palatable Diet during the Perinatal Period Affects the Expression of the Endogenous Cannabinoid System in the Brain, Liver and Adipose Tissue of Adult Rat Offspring.

    Directory of Open Access Journals (Sweden)

    María Teresa Ramírez-López

    Full Text Available Recent studies have linked gestational exposure to highly caloric diets with a disrupted endogenous cannabinoid system (ECS. In the present study, we have extended these studies by analyzing the impact of the exposure to a palatable diet during gestation and lactation on a the adult expression of endocannabinoid-related behaviors, b the metabolic profile of adult offspring and c the mRNA expression of the signaling machinery of the ECS in the hypothalamus, the liver and the adipose tissue of adult offspring of both sexes. Exposure to a palatable diet resulted in a sex-dimorphic and perinatal diet specific feeding behaviors, including the differential response to the inhibitory effects of the cannabinoid receptor inverse agonist AM251, b features of metabolic syndrome including increased adiposity, hyperleptinemia, hypertriglyceridemia and hypercholesterolemia and c tissue and sex-specific changes in the expression of both CB1 and CB2 receptors and in that of the endocannabinoid-degrading enzymes FAAH and MAGL, being the adipose tissue the most affected organ analyzed. Since the effects were observed in adult animals that were weaned while consuming a normal diet, the present results indicate that the ECS is one of the targets of maternal programming of the offspring energy expenditure. These results clearly indicate that the maternal diet has long-term effects on the development of pups through multiple alterations of signaling homeostatic pathways that include the ECS. The potential relevance of these alterations for the current obesity epidemic is discussed.

  3. Tissue-specific increases in 11beta-hydroxysteroid dehydrogenase type 1 in normal weight postmenopausal women.

    Directory of Open Access Journals (Sweden)

    Therése Andersson

    Full Text Available With age and menopause there is a shift in adipose distribution from gluteo-femoral to abdominal depots in women. Associated with this redistribution of fat are increased risks of type 2 diabetes and cardiovascular disease. Glucocorticoids influence body composition, and 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1 which converts inert cortisone to active cortisol is a putative key mediator of metabolic complications in obesity. Increased 11betaHSD1 in adipose tissue may contribute to postmenopausal central obesity. We hypothesized that tissue-specific 11betaHSD1 gene expression and activity are up-regulated in the older, postmenopausal women compared to young, premenopausal women. Twenty-three pre- and 23 postmenopausal, healthy, normal weight women were recruited. The participants underwent a urine collection, a subcutaneous adipose tissue biopsy and the hepatic 11betaHSD1 activity was estimated by the serum cortisol response after an oral dose of cortisone. Urinary (5alpha-tetrahydrocortisol+5beta-tetrahydrocortisol/tetrahydrocortisone ratios were higher in postmenopausal women versus premenopausal women in luteal phase (P<0.05, indicating an increased whole-body 11betaHSD1 activity. Postmenopausal women had higher 11betaHSD1 gene expression in subcutaneous fat (P<0.05. Hepatic first pass conversion of oral cortisone to cortisol was also increased in postmenopausal women versus premenopausal women in follicular phase of the menstrual cycle (P<0.01, at 30 min post cortisone ingestion, suggesting higher hepatic 11betaHSD1 activity. In conclusion, our results indicate that postmenopausal normal weight women have increased 11betaHSD1 activity in adipose tissue and liver. This may contribute to metabolic dysfunctions with menopause and ageing in women.

  4. HPV-Induced Field Cancerisation: Transformation of Adult Tissue Stem Cell Into Cancer Stem Cell.

    Science.gov (United States)

    Olivero, Carlotta; Lanfredini, Simone; Borgogna, Cinzia; Gariglio, Marisa; Patel, Girish K

    2018-01-01

    Field cancerisation was originally described as a basis for multiple head and neck squamous cell carcinoma (HNSCC) and is a pre-malignant phenomenon that is frequently attributable to oncogenic human papillomavirus (HPV) infection. Our work on β-HPV-induced cutaneous squamous cell carcinomas identified a novel Lrig1+ hair follicle junctional zone keratinocyte stem cell population as the basis for field cancerisation. Herein, we describe the ability for HPV to infect adult tissue stem cells in order to establish persistent infection and induce their proliferation and displacement resulting in field cancerisation. By review of the HPV literature, we reveal how this mechanism is conserved as the basis of field cancerisation across many tissues. New insights have identified the capacity for HPV early region genes to dysregulate adult tissue stem cell self-renewal pathways ensuring that the expanded population preserve its stem cell characteristics beyond the stem cell niche. HPV-infected cells acquire additional transforming mutations that can give rise to intraepithelial neoplasia (IEN), from environmental factors such as sunlight or tobacco induced mutations in skin and oral cavity, respectively. With establishment of IEN, HPV viral replication is sacrificed with loss of the episome, and the tissue is predisposed to multiple cancer stem cell-driven carcinomas.

  5. Evaluation of Specific Metabolic Rates of Major Organs and Tissues: Comparison Between Nonobese and Obese Women

    OpenAIRE

    Wang, ZiMian; Ying, Zhiliang; Bosy-Westphal, Anja; Zhang, Junyi; Heller, Martin; Later, Wiebke; Heymsfield, Steven B.; Müller, Manfred J.

    2011-01-01

    Elia (1992) identified the specific resting metabolic rates (Ki) of major organs and tissues in young adults with normal weight: 200 for liver, 240 for brain, 440 for heart and kidneys, 13 for skeletal muscle, 4.5 for adipose tissue and 12 for residual mass (all units in kcal/kg per day). The aim of the present study was to assess the applicability of Elia’s Ki values for obese adults. A sample of young women (n = 80) was divided into two groups, nonobese (BMI

  6. Role of endothelium in radiation-induced normal tissue damages; Role de l'endothelium dans les dommages radio-induits aux tissus sains

    Energy Technology Data Exchange (ETDEWEB)

    Milliat, F

    2007-05-15

    More than half of cancers are treated with radiation therapy alone or in combination with surgery and/or chemotherapy. The goal of radiation therapy is to deliver enough ionising radiation to destroy cancer cells without exceeding the level that the surrounding healthy cells can tolerate. Unfortunately, radiation-induced normal tissue injury is still a dose limiting factor in the treatment of cancer with radiotherapy. The knowledge of normal tissue radiobiology is needed to determine molecular mechanisms involved in normal tissue pathogenic pathways in order to identify therapeutic targets and develop strategies to prevent and /or reduce side effects of radiation therapy. The endothelium is known to play a critical role in radiation-induced injury. Our work shows that endothelial cells promote vascular smooth muscle cell proliferation, migration and fibro-genic phenotype after irradiation. Moreover, we demonstrate for the first time the importance of PAI-1 in radiation-induced normal tissue damage suggesting that PAI-1 may represent a molecular target to limit injury following radiotherapy. We describe a new role for the TGF-b/Smad pathway in the pathogenesis of radiation-induced damages. TGF-b/Smad pathway is involved in the fibro-genic phenotype of VSMC induced by irradiated EC as well as in the radiation-induced PAI-1 expression in endothelial cells. (author)

  7. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    Science.gov (United States)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  8. Cell-based and biomaterial approaches to connective tissue repair

    Science.gov (United States)

    Stalling, Simone Suzette

    Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in

  9. Mammary stem cell and macrophage markers are enriched in normal tissue adjacent to inflammatory breast cancer.

    Science.gov (United States)

    Reddy, Jay P; Atkinson, Rachel L; Larson, Richard; Burks, Jared K; Smith, Daniel; Debeb, Bisrat G; Ruffell, Brian; Creighton, Chad J; Bambhroliya, Arvind; Reuben, James M; Van Laere, Steven J; Krishnamurthy, Savitri; Symmans, William F; Brewster, Abenaa M; Woodward, Wendy A

    2018-06-01

    We hypothesized that breast tissue not involved by tumor in inflammatory breast cancer (IBC) patients contains intrinsic differences, including increased mammary stem cells and macrophage infiltration, which may promote the IBC phenotype. Normal breast parenchyma ≥ 5 cm away from primary tumors was obtained from mastectomy specimens. This included an initial cohort of 8 IBC patients and 60 non-IBC patients followed by a validation cohort of 19 IBC patients and 25 non-IBC patients. Samples were immunostained for either CD44 + CD49f + CD133/2 + mammary stem cell markers or the CD68 macrophage marker and correlated with IBC status. Quantitation of positive cells was determined using inForm software from PerkinElmer. We also examined the association between IBC status and previously published tumorigenic stem cell and IBC tumor signatures in the validation cohort samples. 8 of 8 IBC samples expressed isolated CD44 + CD49f + CD133/2 + stem cell marked cells in the initial cohort as opposed to 0/60 non-IBC samples (p = 0.001). Similarly, the median number of CD44 + CD49f + CD133/2 + cells was significantly higher in the IBC validation cohort as opposed to the non-IBC validation cohort (25.7 vs. 14.2, p = 0.007). 7 of 8 IBC samples expressed CD68 + histologically confirmed macrophages in initial cohort as opposed to 12/48 non-IBC samples (p = 0.001). In the validation cohort, the median number of CD68 + cells in IBC was 3.7 versus 1.0 in the non-IBC cohort (p = 0.06). IBC normal tissue was positively associated with a tumorigenic stem cell signature (p = 0.02) and with a 79-gene IBC signature (p stem cell signature and IBC-specific tumor signature. Collectively, these data suggest that IBC normal tissue differs from non-IBC tissue. Whether these changes occur before the tumor develops or is induced by tumor warrants further investigation.

  10. DNA double strand break repair pathway plays a significant role in determining the radiotherapy induced normal tissue toxicity among head-and-neck and breast cancer

    International Nuclear Information System (INIS)

    Sadashiva, Satish Rao Bola; Mumbrekar, Kamalesh Dattaram; Venkatesh, Goutham Hassan; Fernandes, Donald Jerard; Bejadi, Vadhiraja Manjunath; Kapaettu, Satyamoorthy

    2014-01-01

    The ability to predict individual risk of radiotherapy induced normal tissue complications prior to the therapy may give an opportunity to personalize the treatment aiming improved therapeutic effect and quality of life. Therefore, predicting the risk of developing acute reactions before the initiation of radiation therapy may serve as a potential biomarker. DNA double-strand break (DSB) induction and its repair kinetics in lymphocytes of Head-and-Neck (n = 183) and Breast cancer (n = 132) patients undergoing chemoradiation or radiation therapy alone were analyzed by performing γ-H2AX foci, neutral comet and a modified neutral filter elution assay. Candidate radioresponsive genes like DNA repair, antioxidant pathway, profibrotic cytokine genes were screened for the common variants for their association with normal tissue toxicity outcome. Patients were stratified as non-over responders (NOR) and over responders (OR) based on their Radiation Therapy Oncology Group grading for normal tissue adverse reactions. Our results suggest that DSB repair plays a major role in the development of normal tissue adverse reactions in H and N and Breast cancer patients. The cellular (γ-H2AX analysis) and SNP analysis may have the potential to be developed into a clinically useful predictive assay for identifying the normal tissue over reactors

  11. Hypoxyradiotherapy: lack of experimental evidence for a preferential radioprotective effect on normal versus tumor tissue as shown by direct oxygenation measurements in experimental sarcomas

    International Nuclear Information System (INIS)

    Kelleher, Debra K.; Thews, Oliver; Vaupel, Peter

    1997-01-01

    Aim: In order to investigate possible pathophysiological mechanisms underlying the postulated preferential protective effect of hypoxia on normal tissue during radiotherapy, the impact of acute respiratory hypoxia (8.2% O 2 + 91.8% N 2 ) on tissue oxygenation was assessed. Methods: Tumor and normal tissue oxygenation was directly determined using O 2 -sensitive electrodes in two experimental rat tumors (DS and Yoshida sarcomas) and in the normal subcutis of the hind foot dorsum. Results: During respiratory hypoxia, arterial blood O 2 tension (pO 2 ), oxyhemoglobin saturation and mean arterial blood pressure decreased. Changes in the arterial blood gas status were accompanied by a reflex hyperventilation leading to hypocapnia and respiratory alkalosis. In the subcutis, tissue oxygenation worsened during acute hypoxia, with decreases in the mean and median pO 2 . Significant increases in the hypoxic fractions were, however, not seen. In tumor tissues, oxygenation also worsened upon hypoxic hypoxia with significant decreases in the mean and median pO 2 and increases in the size of the hypoxic fractions for both sarcomas. Conclusion: These results suggest that during respiratory hypoxia, radiobiologically relevant reductions in the oxygenation (and a subsequent selective radioprotection) of normal tissue may not be achieved. In addition, in the tumor models studied, a worsening of tumor oxygenation was seen which could result in an increased radioresistance

  12. Incorporation of tritiated thymidine and uridine in normal and endopolyploid nuclei of differentiated tissue

    International Nuclear Information System (INIS)

    Bansal, Y.K.; Sen, Sumitra

    1987-01-01

    Rate of replication and transcription between normal and giant endopolyploid nuclei of differentiated tissue of Hordeum vulgare L. (2n=14) roots and Phlox drummondii Hook. (2n=14) and Zea mays L. (2n=20) endosperms were studied by labelling experiments with tritiated thymidine and uridine. The incorporation of thymidine and uridine was identical in both diploid and giant endopolyploid nuclei of the roots of H. vulgare. The endosperm cells of P. drummondii and Z. mays, however, exhibit markedly different labelling pattern in normal (i.e. triploid) and endopolyploid nuclei where both replication and transcription were rather high. The nutritive function of the endosperm is probably responsible for this high degree of activity. (author). 14 refs., 10 figs., 3 tables

  13. Comparison of radiosensitivity between tumor and normal tissue in terms of cell population kinetics

    International Nuclear Information System (INIS)

    Sugahara, Tsutomu; Utsumi, Hiroshi

    1975-01-01

    Puck and Marcus in 1956 established the in vitro colony formation of mammalian cells and demonstrated a dose-survival curve of mammalian cells well fitted to the target theory. Since then almost all of the work on the radiosensitivity of malignant and normal cells has been based on the reproductive integrity of cells. However, in the author's laboratory, a recent work was done on the effect of ionizing radiation on the differentiative trait, using clonal cell cultures developed by Coon (1966) in chick embryonic cartilage cells. This work demonstrated clearly that the differentiative trait is more radiosensitive than is reproduction. Based on this finding a new compartment model is proposed for a cell renewal system which demonstrates the difference between normal and malignant tissue. (author)

  14. Radiation-induced soft-tissue and bone sarcoma

    International Nuclear Information System (INIS)

    Kim, J.H.; Chu, F.C.; Woodard, H.Q.; Melamed, R.; Huvos, A.; Cantin, J.

    1978-01-01

    From the records of Memorial Hospital of the past 50 years, 47 cases with an established diagnosis of radiation-induced sarcoma were identified and divided into two groups: the first included 20 cases of soft-tissue sarcoma arising from irradiated tissues, and the second comprised 27 cases of bone sarcoma arising from normal bones in the irradiated field. Medians for the latent periods from irradiation to diagnosis of bone and soft-tissue sarcoma were 11 and 12, years, respectively. In bone sarcomas, the latent period was longer after larger radiation doses and children appeared to be more susceptible to cancer induction than adults. Criteria for establishing the diagnosis of radiation-induced sarcoma and the magnitude of the risk of bone sarcoma are discussed

  15. Comparison of SUVs normalized by lean body mass determined by CT with those normalized by lean body mass estimated by predictive equations in normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Woo Hyoung; Kim, Chang Guhn; Kim, Dae Weung [Wonkwang Univ. School of Medicine, Iksan (Korea, Republic of)

    2012-09-15

    Standardized uptake values (SUVs)normalized by lean body mass (LBM)determined by CT were compared with those normalized by LBM estimated using predictive equations (PEs)in normal liver, spleen, and aorta using {sup 18}F FDG PET/CT. Fluorine 18 fluorodeoxyglucose (F FDG)positron emission tomography/computed tomography (PET/CT)was conducted on 453 patients. LBM determined by CT was defined in 3 ways (LBM{sup CT1}-3). Five PEs were used for comparison (LBM{sup PE1}-5). Tissue SUV normalized by LBM (SUL) was calculated using LBM from each method (SUL{sup CT1}-3, SUL{sup PE1}-5). Agreement between methods was assessed by Bland Altman analysis. Percentage difference and percentage error were also calculated. For all liver SUL{sup CTS} vs. liver SUL{sup PES} except liver SUL{sup PE3}, the range of biases, SDs of percentage difference and percentage errors were -0.17-0.24 SUL, 6.15-10.17%, and 25.07-38.91%, respectively. For liver SUL{sup CTs} vs. liver SUL{sup PE3}, the corresponding figures were 0.47-0.69 SUL, 10.90-11.25%, and 50.85-51.55%, respectively, showing the largest percentage errors and positive biases. Irrespective of magnitudes of the biases, large percentage errors of 25.07-51.55% were observed between liver SUL{sup CT1}-3 and liver SUL{sup PE1}-5. The results of spleen and aorta SUL{sup CTs} and SUL{sup PEs} comparison were almost identical to those for liver. The present study demonstrated substantial errors in individual SUL{sup PEs} compared with SUL{sup CTs} as a reference value. Normalization of SUV by LBM determined by CT rather than PEs may be a useful approach to reduce errors in individual SUL{sup PEs}.

  16. Comparison of SUVs normalized by lean body mass determined by CT with those normalized by lean body mass estimated by predictive equations in normal tissues

    International Nuclear Information System (INIS)

    Kim, Woo Hyoung; Kim, Chang Guhn; Kim, Dae Weung

    2012-01-01

    Standardized uptake values (SUVs)normalized by lean body mass (LBM)determined by CT were compared with those normalized by LBM estimated using predictive equations (PEs)in normal liver, spleen, and aorta using 18 F FDG PET/CT. Fluorine 18 fluorodeoxyglucose (F FDG)positron emission tomography/computed tomography (PET/CT)was conducted on 453 patients. LBM determined by CT was defined in 3 ways (LBM CT1 -3). Five PEs were used for comparison (LBM PE1 -5). Tissue SUV normalized by LBM (SUL) was calculated using LBM from each method (SUL CT1 -3, SUL PE1 -5). Agreement between methods was assessed by Bland Altman analysis. Percentage difference and percentage error were also calculated. For all liver SUL CTS vs. liver SUL PES except liver SUL PE3 , the range of biases, SDs of percentage difference and percentage errors were -0.17-0.24 SUL, 6.15-10.17%, and 25.07-38.91%, respectively. For liver SUL CTs vs. liver SUL PE3 , the corresponding figures were 0.47-0.69 SUL, 10.90-11.25%, and 50.85-51.55%, respectively, showing the largest percentage errors and positive biases. Irrespective of magnitudes of the biases, large percentage errors of 25.07-51.55% were observed between liver SUL CT1 -3 and liver SUL PE1 -5. The results of spleen and aorta SUL CTs and SUL PEs comparison were almost identical to those for liver. The present study demonstrated substantial errors in individual SUL PEs compared with SUL CTs as a reference value. Normalization of SUV by LBM determined by CT rather than PEs may be a useful approach to reduce errors in individual SUL PEs

  17. Classification of mass and normal breast tissue: A convolution neural network classifier with spatial domain and texture images

    International Nuclear Information System (INIS)

    Sahiner, B.; Chan, H.P.; Petrick, N.; Helvie, M.A.; Adler, D.D.; Goodsitt, M.M.; Wei, D.

    1996-01-01

    The authors investigated the classification of regions of interest (ROI's) on mammograms as either mass or normal tissue using a convolution neural network (CNN). A CNN is a back-propagation neural network with two-dimensional (2-D) weight kernels that operate on images. A generalized, fast and stable implementation of the CNN was developed. The input images to the CNN were obtained form the ROI's using two techniques. The first technique employed averaging and subsampling. The second technique employed texture feature extraction methods applied to small subregions inside the ROI. Features computed over different subregions were arranged as texture images, which were subsequently used as CNN inputs. The effects of CNN architecture and texture feature parameters on classification accuracy were studied. Receiver operating characteristic (ROC) methodology was used to evaluate the classification accuracy. A data set consisting of 168 ROI's containing biopsy-proven masses and 504 ROI's containing normal breast tissue was extracted from 168 mammograms by radiologists experienced in mammography. This data set was used for training and testing the CNN. With the best combination of CNN architecture and texture feature parameters, the area under the test ROC curve reached 0.87, which corresponded to a true-positive fraction of 90% at a false positive fraction of 31%. The results demonstrate the feasibility of using a CNN for classification of masses and normal tissue on mammograms

  18. The presence and absence of lymphatic vessels in the adult human intervertebral disc: relation to disc pathology

    International Nuclear Information System (INIS)

    Kliskey, Karolina; Williams, Kelly; Yu, J.; Urban, Jill; Athanasou, Nick; Jackson, David

    2009-01-01

    Although the normal adult human intervertebral disc is considered to be avascular, vascularised cellular fibrous tissue can be found in pathological conditions involving the disc such as disc herniation. Whether lymphatics vessels form a component of this reparative tissue is not known as the presence or absence of lymphatics in herniated and normal disc tissue is not known. We examined spinal tissues and discectomy specimens for the presence of lymphatics. The examination used immunohistochemistry to identify the specific lymphatic endothelial cell markers, podoplanin and LYVE1. Lymphatic vessels were not found in the nucleus pulposus or annulus fibrosus of intact, non-herniated lumbar and thoracic discs but were present in the surrounding ligaments. Ingrowth of fibrous tissue was seen in 73% of herniated disc specimens of which 36% contained LYVE1+/podoplanin + lymphatic vessels. Lymphatic vessels were not seen in the sacrum and coccyx or biopsies of four sacrococcygeal chordomas, but they were noted in surrounding extra-osseous fat and fibrous tissue at the edge of the infiltrating tumour. Our findings indicate that lymphatic vessels are not present in the normal adult intervertebral disc but that, when there is extrusion of disc material into surrounding soft tissue, there is ingrowth of reparative fibrous tissue containing lymphatic vessels. Our findings also indicate that chordoma, a tumour of notochordal origin, spreads to regional lymph nodes via lymphatics in para-spinal soft tissues. (orig.)

  19. Flow-regulated versus differential pressure-regulated shunt valves for adult patients with normal pressure hydrocephalus

    DEFF Research Database (Denmark)

    Ziebell, Morten; Wetterslev, Jørn; Tisell, Magnus

    2013-01-01

    Since 1965 many ventriculo-peritoneal shunt systems have been inserted worldwide to treat hydrocephalus. The most frequent indication in adults is normal pressure hydrocephalus (NPH), a condition that can be difficult to diagnose precisely. Surgical intervention with flow-regulated and differential...

  20. Psychiatric and psychosocial problems in adults with normal-intelligence autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Herbrecht Evelyn

    2009-06-01

    Full Text Available Abstract Background Individuals with autism spectrum disorders (ASDs often display symptoms from other diagnostic categories. Studies of clinical and psychosocial outcome in adult patients with ASDs without concomitant intellectual disability are few. The objective of this paper is to describe the clinical psychiatric presentation and important outcome measures of a large group of normal-intelligence adult patients with ASDs. Methods Autistic symptomatology according to the DSM-IV-criteria and the Gillberg & Gillberg research criteria, patterns of comorbid psychopathology and psychosocial outcome were assessed in 122 consecutively referred adults with normal intelligence ASDs. The subjects consisted of 5 patients with autistic disorder (AD, 67 with Asperger's disorder (AS and 50 with pervasive developmental disorder not otherwise specified (PDD NOS. This study group consists of subjects pooled from two studies with highly similar protocols, all seen on an outpatient basis by one of three clinicians. Results Core autistic symptoms were highly prevalent in all ASD subgroups. Though AD subjects had the most pervasive problems, restrictions in non-verbal communication were common across all three subgroups and, contrary to current DSM criteria, so were verbal communication deficits. Lifetime psychiatric axis I comorbidity was very common, most notably mood and anxiety disorders, but also ADHD and psychotic disorders. The frequency of these diagnoses did not differ between the ASD subgroups or between males and females. Antisocial personality disorder and substance abuse were more common in the PDD NOS group. Of all subjects, few led an independent life and very few had ever had a long-term relationship. Female subjects more often reported having been bullied at school than male subjects. Conclusion ASDs are clinical syndromes characterized by impaired social interaction and non-verbal communication in adulthood as well as in childhood. They also

  1. Reirradiation of normal tissues: Preclinical radiobiological data; Reirradiation des tissus sains: donnees radiobiologiques precliniques

    Energy Technology Data Exchange (ETDEWEB)

    Bourgier, C.; Vozenin, M.C.; Deutsch, E. [Departement de radiotherapie et laboratoire Upres EA2710, institut Gustave-Roussy, 94 - Villejuif (France)

    2010-10-15

    Reirradiation represent an unfrequent particular clinical situation. The risk/benefit ratio assessment must be taken into account, considering both clinical and dosimetric aspects. There is a relatively limited amount of preclinical data available to date and clinicians should cautiously perform re-irradiations in selected indications. This review summarizes the experimental data available on reirradiation of normal tissues, the consequences on early and late toxicities as well as the intrinsic limitations of these models. (authors)

  2. Sensory-motor relationships in speech production in post-lingually deaf cochlear-implanted adults and normal-hearing seniors: Evidence from phonetic convergence and speech imitation.

    Science.gov (United States)

    Scarbel, Lucie; Beautemps, Denis; Schwartz, Jean-Luc; Sato, Marc

    2017-07-01

    Speech communication can be viewed as an interactive process involving a functional coupling between sensory and motor systems. One striking example comes from phonetic convergence, when speakers automatically tend to mimic their interlocutor's speech during communicative interaction. The goal of this study was to investigate sensory-motor linkage in speech production in postlingually deaf cochlear implanted participants and normal hearing elderly adults through phonetic convergence and imitation. To this aim, two vowel production tasks, with or without instruction to imitate an acoustic vowel, were proposed to three groups of young adults with normal hearing, elderly adults with normal hearing and post-lingually deaf cochlear-implanted patients. Measure of the deviation of each participant's f 0 from their own mean f 0 was measured to evaluate the ability to converge to each acoustic target. showed that cochlear-implanted participants have the ability to converge to an acoustic target, both intentionally and unintentionally, albeit with a lower degree than young and elderly participants with normal hearing. By providing evidence for phonetic convergence and speech imitation, these results suggest that, as in young adults, perceptuo-motor relationships are efficient in elderly adults with normal hearing and that cochlear-implanted adults recovered significant perceptuo-motor abilities following cochlear implantation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Identification of molecular mechanisms of radiation-induced vascular damage in normal tissues using microarray analyses

    International Nuclear Information System (INIS)

    Kruse, J.J.C.M.; Te Poele, J.A.M.; Russell, N.S.; Boersma, L.J.; Stewart, F.A.

    2003-01-01

    Radiation-induced telangiectasia, characterized by thin-walled dilated blood vessels, can be a serious late complication in patients that have been previously treated for cancer. It might cause cosmetic problems when occurring in the skin, and excessive bleeding requiring surgery when occurring in rectal mucosa. The mechanisms underlying the development of radiation-induced telangiectasia are unclear. The aim of the present study is to determine whether microarrays are useful for studying mechanisms of radiation-induced telangiectasia. The second aim is to test the hypotheses that telangiectasia is characterized by a final common pathway in different tissues. Microarray experiments were performed using amplified RNA from (sham)irradiated mouse tissues (kidney, rectum) at different intervals (1-30 weeks) after irradiation. After normalization procedures, the differentially expressed genes were identified. Control/repeat experiments were done to confirm that the observations were not artifacts of the array procedure. The mouse kidney experiments showed significant upregulation of 31 and 42 genes and downregulation of 9 and 4 genes at 10 and 20 weeks after irradiation, respectively. Irradiated mouse rectum has 278 upregulated and 537 downregulated genes at 10 weeks and 86 upregulated and 29 downregulated genes at 20 weeks. During the development of telangiectasia, 19 upregulated genes and 5 downregulated genes were common to both tissues. Upregulation of Jagged-1, known to play a role in angiogenesis, is particularly interesting in the context of radiation-induced telangiectasia. Microarrays are affective discovery tools to identify novel genes of interest, which may be involved in radiation-induced normal tissue injury. Using information from control arrays (particularly straight color, color reverse and self-self experiments) allowed for a more accurate and reproducible identification of differentially expressed genes than the selection of an arbitrary 2-fold change

  4. Elemental composition of 'normal' and Alzheimer brain tissue by INA and PIXE analyses

    International Nuclear Information System (INIS)

    Stedman, J.D.; Spyrou, N.M.

    1997-01-01

    Instrumental methods based on the nuclear and atomic properties of the elements have been used for many years to determine elemental concentrations in a variety of materials for biomedical, industrial and environmental applications. These methods offer high sensitivity for accurate trace element measurements, suffer few interfering or competing effects. Present no blank problems and are convenient for both research and routine analyses. The present article describes the use of two trace element techniques. Firstly the use of activation of stable nuclei irradiated by neutrons in the core of a low power research reactor as a means of detection of elements through the resulting gamma-rays emitted. Secondly, the observations of the interactions of energetic ion beams with the material in order to identify elemental species. Over recent years there has been some interest in determining the elemental composition of 'normal' and Alzheimer affected brain tissue, however literature findings are inconsistent. Possible reasons for discrepancies need to be identified for further progress to be made. Here, post-mortem tissue samples, provided by the Alzheimer's Disease Brain Bank, Institute of Psychiatry, London, were taken from the frontal, occipital, parietal and temporal lobes of both hemispheres of brains from 13 'normal' and 19 Alzheimer subjects. The elemental composition of the samples was determined using the analytical techniques of INAA (instrumental neutron activation analysis), RBS (Rutherford back-scattering) and PIXE (particle induced x-ray emission). The principal findings are summarised here. (author)

  5. Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

    Science.gov (United States)

    Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

    2015-10-10

    Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Comparison of multiple assays for detecting human antibodies directed against antigens on normal and malignant tissue culture cells

    International Nuclear Information System (INIS)

    Rosenberg, S.A.; Schwarz, S.; Anding, H.; Hyatt, C.; Williams, G.M.; Johns Hopkins Univ., Baltimore, Md.

    1977-01-01

    Four separate assays of human antibody reactivity to four separate normal and malignant human tissue culture cells lines from two patients have been evaluated using a single highly-reactive allogeneic serum. The visual end-point cytolysis assay and the chromium-51 release assay were equally sensitive in measuring complement mediated antibody cytotoxicity and both were far more sensitive than a trypan blue dye exclusion assay. The assay of antibody reactivity by hemadsorption technique was about 10 times more sensitive than any of the cytotoxicity assays. This latter assay measures only IgG antibody however. These assays showed that cell lines from different patients may differ greatly in 'reactivity' to an allogeneic serum and emphasized the importance of utilizing tumor and normal cells from the same patient when using tissue culture cells to search for tumor specific reactivity. These observations emphasize the importance of utilizing multiple assays against paired normal and malignant cells from the same patient to be certain of the specificity and magnitude of the measured antibody

  7. Clinical evaluation of normal tissue toxicity induced by ionizing radiation in cases of laryngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ramos, Adriano de Paula; Marques, Gustavo Inacio de Gomes; Soares, Renata da Bastos Ascenco; Dourado, Juliana Castro Dourado [Pontificia Universidade Catolica de Goias (PUCGO), Goiania, GO (Brazil). Dept. of Medicine; Mendonca, Yuri de Abreu, E-mail: renata.soares@pucgoias.edu.br [Goias Association Against Cancer, Goiania, GO (Brazil). Lab. of Radiobiology and Oncogenetics

    2012-07-01

    Laryngeal cancer is the second most frequent head and neck cancer in the Brazilian male population. For treatment, radiotherapy combined with chemotherapy is now used in substitution for total laryngectomy, becoming the standard treatment for advanced larynx cancer cases, with the aim of organ preservation. However, this method needs assessment of the side effects caused to normal tissue and organ functionality after treatment and the relation of these clinical factors to the individual characteristics of patients. Thus, the clinical characteristics of 229 patients with laryngeal cancer treated with radiotherapy were evaluated by medical records analysis in relation to normal tissue radiosensibility. Significant relations between smoking (p = 0.018) and combined chemoradiotherapy assistance (p = 0.03) were identified with high frequency of treatment suspension cases. The application of combined chemoradiotherapy also resulted in a higher incidence of oral mucositis (p = 0.04), xerostomia (p = 0.001) and treatment side effects to GIT (p = 0.04). Advanced clinical staging was associated with worse prognosis (p = 0.002) and a higher occurrence of treatment failure (p < 0.001). Radiotherapy was also less effective depending on the primary tumor location (p = 0.001). (author)

  8. Gene expression profile of the cartilage tissue spontaneously regenerated in vivo by using a novel double-network gel: Comparisons with the normal articular cartilage

    Directory of Open Access Journals (Sweden)

    Kurokawa Takayuki

    2011-09-01

    Full Text Available Abstract Background We have recently found a phenomenon that spontaneous regeneration of a hyaline cartilage-like tissue can be induced in a large osteochondral defect by implanting a double-network (DN hydrogel plug, which was composed of poly-(2-Acrylamido-2-methylpropanesulfonic acid and poly-(N, N'-Dimetyl acrylamide, at the bottom of the defect. The purpose of this study was to clarify gene expression profile of the regenerated tissue in comparison with that of the normal articular cartilage. Methods We created a cylindrical osteochondral defect in the rabbit femoral grooves. Then, we implanted the DN gel plug at the bottom of the defect. At 2 and 4 weeks after surgery, the regenerated tissue was analyzed using DNA microarray and immunohistochemical examinations. Results The gene expression profiles of the regenerated tissues were macroscopically similar to the normal cartilage, but showed some minor differences. The expression degree of COL2A1, COL1A2, COL10A1, DCN, FMOD, SPARC, FLOD2, CHAD, CTGF, and COMP genes was greater in the regenerated tissue than in the normal cartilage. The top 30 genes that expressed 5 times or more in the regenerated tissue as compared with the normal cartilage included type-2 collagen, type-10 collagen, FN, vimentin, COMP, EF1alpha, TFCP2, and GAPDH genes. Conclusions The tissue regenerated by using the DN gel was genetically similar but not completely identical to articular cartilage. The genetic data shown in this study are useful for future studies to identify specific genes involved in spontaneous cartilage regeneration.

  9. Assessment of the mandibular symphysis of Caucasian Brazilian adults with well-balanced faces and normal occlusion: the influence of gender and facial type

    Directory of Open Access Journals (Sweden)

    Karine Evangelista Martins Arruda

    2012-06-01

    Full Text Available OBJECTIVE: This study aimed to establish cephalometric reference values for mandibular symphysis in adults. Dentoalveolar, skeletal and soft tissue variables were measured considering the influence of gender and facial type. METHODS: The sample consisted of sixty cephalometric radiographs of white Brazilian adult patients, with a mean age of 27 years and 6 months, who had not undergone orthodontic treatment and who presented well-balanced faces and normal occlusion. The sample was standardized according to gender (30 males and 30 females and facial type (20 were dolichofacial, 20 mesofacial and 20 brachyfacial. RESULTS: The results showed that male and female symphyses are similar, except for symphyseal height, which was greater in males. In terms of facial type, the dolichofacial group presented narrower symphysis in dentoalveolar and basal areas, with a more accentuated lingual dentoalveolar inclination. CONCLUSION: The brachyfacial group showed broader symphysis in the dentoalveolar and basal areas and a greater buccal dentoalveolar inclination. The projection of the chin was 6.67 mm below the subnasal vertical line and there was no significant difference between the genders or facial types.

  10. Normal patterns of 18F-FDG appendiceal uptake in children

    Energy Technology Data Exchange (ETDEWEB)

    Reavey, Hamilton E. [Emory University, Department of Radiology and Imaging Sciences, Division of Nuclear Medicine Molecular Imaging, Atlanta, GA (United States); Alazraki, Adina L.; Simoneaux, Stephen F. [Emory University, Department of Radiology and Imaging Sciences, Division of Pediatric Imaging, Children' s Healthcare of Atlanta at Egleston, Atlanta, GA (United States)

    2014-04-15

    Prior to interpreting PET/CT, it is crucial to understand the normal biodistribution of fluorodeoxyglucose (FDG). It is also important to realize that the normal biodistribution can vary between adults and children. Although many studies have defined normal patterns of pediatric FDG uptake in structures like the thymus, brown fat and bone marrow, patterns of normal pediatric bowel activity, specifically uptake within the appendix, have not been well described. Active lymphoid tissue has increased FDG uptake when compared with inactive tissue. Since children have more active lymphoid tissue than adults, and because the appendix contains aggregated lymphoid tissue, we postulated that appendiceal uptake may be increased in pediatric patients. To define the normal level of appendiceal FDG activity in children by evaluating a series of consecutive FDG PET/CT scans performed for other indications. After obtaining IRB approval, we retrospectively reviewed 128 consecutive whole-body pediatric FDG PET/CT examinations obtained for a variety of clinical indications. CT scans on which the appendix could not be visualized were excluded from analysis. CT scans on which the appendix could be visualized were evaluated for underlying appendiceal pathology. Studies with appendiceal or periappendiceal pathology by CT criteria were excluded. A region of interest (ROI) was placed over a portion of each appendix and appendiceal maximum standardized uptake value (SUVmax) was calculated. If an adjacent loop of bowel activity interfered with accurate measurements of the appendix SUVmax, the scan was excluded from the analysis. A chart review was performed on patients with elevated appendiceal SUVmax values to ensure that the patients did not have clinical symptomatology suggestive of acute appendicitis. When the appendix or a portion of the appendix could be visualized and accurately measured, the SUVmax was determined. SUVmax of the appendix was compared to the SUVmax of normal liver and

  11. Radiation therapy and late reactions in normal tissues

    International Nuclear Information System (INIS)

    Aoyama, Takashi; Kuroda, Yasumasa

    1998-01-01

    Recent developments in cancer therapy have made us increasingly aware that the quality of life of a patient is as valuable as other benefits received from therapy. This awareness leads to an emphasis on organ and/or function preservation in the course of therapy. In line with this new thinking, greater consideration is placed on radiation therapy as an appropriate modality of cancer therapy. Possible complications in normal tissues, especially those of late reaction type after the therapy must be overcome. This review, therefore, focuses on recent progress of studies on mechanisms of the complications of the late reaction type. An observation of a clinical case concerning a late reaction of spinal cord (radiation myelopathy) and surveys of experimental studies on the mechanisms of late reactions (including radiation pneumonitis and lung fibrosis, and radiation response of vascular endothelial cells) provide a hypothesis that apoptosis through the pathway starting with radiation-induced sphingomyelin hydrolysis may play an important role in causing a variety of late reactions. This insight is based on the fact that radiation also activates protein kinase C which appears to block apoptosis. The mechanisms of late reactions, therefore, may involve a balance between radiation-induced apoptotic death and its down regulation by suppressor mechanisms through protein kinase C. (author)

  12. Normal liver tissue sparing by intensity-modulated proton stereotactic body radiotherapy for solitary liver tumours

    International Nuclear Information System (INIS)

    Petersen, Joergen B. B.; Hansen, Anders T.; Lassen, Yasmin; Grau, Cai; Hoeyer, Morten; Muren, Ludvig P.

    2011-01-01

    Background. Stereotactic body radiotherapy (SBRT) is often the preferred treatment for the advanced liver tumours which owing to tumour distribution, size and multi-focality are out of range of surgical resection or radiofrequency ablation. However, only a minority of patients with liver tumours may be candidates for conventional SBRT because of the limited radiation tolerance of normal liver, intestine and other normal tissues. Due to the favourable depth-dose characteristics of protons, intensity-modulated proton therapy (IMPT) may be a superior alternative to photon-based SBRT. The purpose of this treatment planning study was therefore to investigate the potential sparing of normal liver by IMPT compared to photon-based intensity-modulated radiotherapy (IMRT) for solitary liver tumours. Material and methods. Ten patients with solitary liver metastasis treated at our institution with multi-field SBRT were retrospectively re-planned with IMRT and proton pencil beam scanning techniques. For the proton plans, two to three coplanar fields were used in contrast to five to six coplanar and non-coplanar photon fields. The same planning objectives were used for both techniques. A risk adapted dose prescription to the PTV surface of 12.5-16.75 Gy x 3 was used. Results. The spared liver volume for IMPT was higher compared to IMRT in all 10 patients. At the highest prescription dose level, the median liver volume receiving less than 15 Gy was 1411 cm 3 for IMPT and 955 cm 3 for IMRT (p D 15 Gy > 700 cm 3 constraint. For the D mean = 15 Gy constraint, nine of 10 cases could be treated at the highest dose level using IMPT whereas with IMRT, only two cases met this constraint at the highest dose level and six at the lowest dose level. Conclusion. A considerable sparing of normal liver tissue can be obtained using proton-based SBRT for solitary liver tumours

  13. B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue

    OpenAIRE

    Carlsen, H S; Baekkevold, E S; Johansen, F-E; Haraldsen, G; Brandtzaeg, P

    2002-01-01

    Background and aims: In mice, the B lymphocyte chemoattractant (BLC) CXC chemokine ligand 13 (CXCL13) is sufficient to induce a series of events leading to the formation of organised lymphoid tissue. Its receptor, CXCR5, is required for normal development of secondary lymphoid tissue. However, the human counterpart, B cell attracting chemokine 1 (BCA-1) has only been detected in the stomach and appendix and not in other parts of normal or diseased gut. Hence to elucidate the potential role of...

  14. Quantification of Estrogen Receptor Expression in Normal Breast Tissue in Postmenopausal Women With Breast Cancer and Association With Tumor Subtypes.

    Science.gov (United States)

    Gulbahce, H Evin; Blair, Cindy K; Sweeney, Carol; Salama, Mohamed E

    2017-09-01

    Estrogen exposure is important in the pathogenesis of breast cancer and is a contributing risk factor. In this study we quantified estrogen receptor (ER) alpha expression in normal breast epithelium (NBR) in women with breast cancer and correlated it with breast cancer subtypes. Tissue microarrays were constructed from 204 breast cancer patients for whom normal breast tissue away from tumor was available. Slides stained with ER were scanned and expression in normal terminal duct lobular epithelium was quantitated using computer-assisted image analysis. ER expression in normal terminal duct lobular epithelium of postmenopausal women with breast cancer was significantly associated with estrogen and triple (estrogen, progesterone receptors, and HER2) negative phenotypes. Also increased age at diagnosis was significantly associated with ER expression in NBR. ER positivity in normal epithelium did not vary by tumor size, lymph node status, tumor grade, or stage. On the basis of quantitative image analysis, we confirm that ER expression in NBR increases with age in women with breast cancer, and report for the first time, a significant association between ER expression in NBR with ER-negative and triple-negative cancers in postmenopausal women.

  15. Novel Molecular Markers of Malignancy in Histologically Normal and Benign Breast

    Directory of Open Access Journals (Sweden)

    Aejaz Nasir

    2011-01-01

    Full Text Available To detect the molecular changes of malignancy in histologically normal breast (HNB tissues, we recently developed a novel 117-gene-malignancy-signature. Here we report validation of our leading malignancy-risk-genes, topoisomerase-2-alpha (TOP2A, minichromosome-maintenance-protein-2 (MCM2 and “budding-uninhibited-by-benzimidazoles-1-homolog-beta” (BUB1B at the protein level. Using our 117-gene malignancy-signature, we classified 18 fresh-frozen HNB tissues from 18 adult female breast cancer patients into HNB-tissues with low-grade (HNB-LGMA; =9 and high-grade molecular abnormality (HNB-HGMA; =9. Archival sections of additional HNB tissues from these patients, and invasive ductal carcinoma (IDC tissues from six other patients were immunostained for these biomarkers. TOP2A/MCM2 expression was assessed as staining index (% and BUB1B expression as H-scores (0–300. Increasing TOP2A, MCM2, and BUB1B protein expression from HNB-LGMA to HNB-HGMA tissues to IDCs validated our microarray-based molecular classification of HNB tissues by immunohistochemistry. We also demonstrated an increasing expression of TOP2A protein on an independent test set of HNB/benign/reductionmammoplasties, atypical-ductal-hyperplasia with and without synchronous breast cancer, DCIS and IDC tissues using a custom tissue microarray (TMA. In conclusion, TOP2A, MCM2, and BUB1B proteins are potential molecular biomarkers of malignancy in histologically normal and benign breast tissues. Larger-scale clinical validation studies are needed to further evaluate the clinical utility of these molecular biomarkers.

  16. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States); Roeske, John C., E-mail: jroeske@lumc.edu [Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois (United States)

    2012-08-01

    Purpose: To implement the 'plan-do-check-act' (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues ('gold' contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes {>=}8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose

  17. A System for Continual Quality Improvement of Normal Tissue Delineation for Radiation Therapy Treatment Planning

    International Nuclear Information System (INIS)

    Breunig, Jennifer; Hernandez, Sophy; Lin, Jeffrey; Alsager, Stacy; Dumstorf, Christine; Price, Jennifer; Steber, Jennifer; Garza, Richard; Nagda, Suneel; Melian, Edward; Emami, Bahman; Roeske, John C.

    2012-01-01

    Purpose: To implement the “plan-do-check-act” (PDCA) cycle for the continual quality improvement of normal tissue contours used for radiation therapy treatment planning. Methods and Materials: The CT scans of patients treated for tumors of the brain, head and neck, thorax, pancreas and prostate were selected for this study. For each scan, a radiation oncologist and a diagnostic radiologist, outlined the normal tissues (“gold” contours) using Radiation Therapy Oncology Group (RTOG) guidelines. A total of 30 organs were delineated. Independently, 5 board-certified dosimetrists and 1 trainee then outlined the same organs. Metrics used to compare the agreement between the dosimetrists' contours and the gold contours included the Dice Similarity Coefficient (DSC), and a penalty function using distance to agreement. Based on these scores, dosimetrists were re-trained on those organs in which they did not receive a passing score, and they were subsequently re-tested. Results: Passing scores were achieved on 19 of 30 organs evaluated. These scores were correlated to organ volume. For organ volumes <8 cc, the average DSC was 0.61 vs organ volumes ≥8 cc, for which the average DSC was 0.91 (P=.005). Normal tissues that had the lowest scores included the lenses, optic nerves, chiasm, cochlea, and esophagus. Of the 11 organs that were considered for re-testing, 10 showed improvement in the average score, and statistically significant improvement was noted in more than half of these organs after education and re-assessment. Conclusions: The results of this study indicate the feasibility of applying the PDCA cycle to assess competence in the delineation of individual organs, and to identify areas for improvement. With testing, guidance, and re-evaluation, contouring consistency can be obtained across multiple dosimetrists. Our expectation is that continual quality improvement using the PDCA approach will ensure more accurate treatments and dose assessment in

  18. Somatomedin-C/insulin-like growth factor-I and Insulin-like growth factor-II mRNAs in rate fetal and adult tissues

    International Nuclear Information System (INIS)

    Lund, P.K.; Moats-Staats, B.M.; Hynes, M.A.; Simmons, J.G.; Jansen, M.; D'ercole, A.J.; Van Wyk, J.J.

    1986-01-01

    Somatomedin-C or insulin-like growth factor I (Sm-C/IGF-I) and insulin-like growth factor II (IGF-II) have been implicated in the regulation of fetal growth and development. In the present study 32 P-labeled complementary DNA probes encoding human and mouse Sm-C/IGF-I and human IGF-II were used in Northern blot hybridizations to analyze rat Sm-C/IGF-I and IGF-II mRNAs in poly(A + ) RNAs from intestine, liver, lung, and brain of adult rats and fetal rats between day 14 and 17 of gestation. In fetal rats, all four tissues contained a major mRNA of 1.7 kilobase (kb) that hybridized with the human Sm-C/IGF-I cDNA and mRNAs of 7.5, 4.7, 1.7, and 1.2 kb that hybridized with the mouse Sm-C/IGF-I cDNA. Adult rat intestine, liver, and lung also contained these mRNAs but Sm-C/IGF-I mRNAs were not detected in adult rat brain. These findings provide direct support for prior observations that multiple tissues in the fetus synthesize immunoreactive Sm-C/IGF-I and imply a role for Sm-C/IGF-I in fetal development as well as postnatally. Multiple IGF-II mRNAs of estimated sizes 4.7, 3.9, 2.2, 1.75, and 1.2 kb were observed in fetal rat intestine, liver, lung, and brain. The 4.7- and 3.9-kb mRNAs were the major hybridizing IGF-II mRNAs in all fetal tissues. Higher abundance of IGF-II mRNAs in rat fetal tissues compared with adult tissues supports prior hypotheses, based on serum IGF-II concentrations, that IGF-II is predominantly a fetal somatomedin. IGF-II mRNAs are present, however, in some poly(A + ) RNAs from adult rat tissues. The brain was the only tissue in the adult rat where the 4.7- and 3.9-kb IGF-II mRNAs were consistently detected. These findings suggest that a role for IGF-II in the adult rat, particularly in the central nervous system, cannot be excluded

  19. Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients

    NARCIS (Netherlands)

    Mulder, Renée L.; Paulides, Marios; Langer, Thorsten; Kremer, Leontien C. M.; van Dalen, Elvira C.

    2010-01-01

    BACKGROUND: Alkylating agents, such as cyclophosphamide and ifosfamide, play a major role in the improved survival of children and young adults with bone and soft tissue sarcoma. However, there is still controversy as to their comparative anti-tumour efficacy and possible adverse effects.

  20. A rare presentation of patent ductus arteriosus in an adult patient with normal pulmonary hypertension and limb edema

    Directory of Open Access Journals (Sweden)

    Bahram Pishgoo

    2014-09-01

    Full Text Available BACKGROUND: Patent ductus arteriosus (PDA at childhood is one of the five major and frequent congenital abnormalities, but it can be rarely seen in adults. Pulmonary hypertension (PHTN and other presentations such as heart failure and edema are the identified complications of longstanding PDA, but adult case with no permanent heart symptoms and PHTN was rare. We reported a rare case of with an obvious PDA and normal pulmonary pressure. CASE REPORT: A 61-year-old woman presented with dyspnea (New York Heart Association class 2, chest pain, and lower limb edema. Echocardiogram showed; normal left ventricular chamber size and function, normal size of both atria. Furthermore, an obvious PDA (diameter = 6-7 mm connecting the aortic arch to the pulmonary artery was reported in echocardiography. No lung congestion and evidence for PHTN was reported by computed tomographic angiography [Pulmonary capillary wedge pressure (PCWP = 30 mmHg]. The patient was treated with antihypertensive drugs and after 1 and 3 months follow-up, edema and other symptoms were resolved. CONCLUSION: Finally, we conclude that PDA in adulthood can present with nonspecific cardiovascular symptoms, and it seems that PHTN is not a fixed echocardiographic finding in these patients.   Keywords: Adults, Edema, Patent Ductus Arteriosus eri, Pulmonary Hypertension  Normal 0 false false false EN-US X-NONE AR-SA

  1. Calculation of normal tissue complication probability and dose-volume histogram reduction schemes for tissues with a critical element architecture

    International Nuclear Information System (INIS)

    Niemierko, Andrzej; Goitein, Michael

    1991-01-01

    The authors investigate a model of normal tissue complication probability for tissues that may be represented by a critical element architecture. They derive formulas for complication probability that apply to both a partial volume irradiation and to an arbitrary inhomogeneous dose distribution. The dose-volume isoeffect relationship which is a consequence of a critical element architecture is discussed and compared to the empirical power law relationship. A dose-volume histogram reduction scheme for a 'pure' critical element model is derived. In addition, a point-based algorithm which does not require precomputation of a dose-volume histogram is derived. The existing published dose-volume histogram reduction algorithms are analyzed. The authors show that the existing algorithms, developed empirically without an explicit biophysical model, have a close relationship to the critical element model at low levels of complication probability. However, it is also showed that they have aspects which are not compatible with a critical element model and the authors propose a modification to one of them to circumvent its restriction to low complication probabilities. (author). 26 refs.; 7 figs

  2. Negative psychosocial and heavy physical workloads associated with musculoskeletal pain interfering with normal life in older adults: cross-sectional analysis.

    Science.gov (United States)

    Lilje, Stina C; Skillgate, Eva; Anderberg, Peter; Berglund, Johan

    2015-07-01

    Pain is one of the most frequent reasons for seeking health care, and is thus a public health problem. Although there is a progressive increase in pain and impaired physical function with age, few studies are performed on older adults. The aim of this study was to investigate if there are associations between musculoskeletal pain interfering with normal life in older adults and physical and psychosocial workloads through life. The association of heavy physical workload and negative psychosocial workload and musculoskeletal pain interfering with normal life (SF 12) was analyzed by multiple logistic regression. The model was adjusted for eight background covariates: age, gender, growing-up environment, educational level, if living alone or not, obesity, smoking, and leisure physical activity. Negative psychosocial and heavy physical workloads were independently associated with musculoskeletal pain interfering with normal life (adjusted OR: 4.44, 95% CI: 2.84-6.92), and (adjusted OR: 1.88, 95% CI: 1.20-2.93), respectively. The background covariates female gender and higher education were also associated with musculoskeletal pain interfering with normal life, and physical leisure activity was inversely associated. The findings suggest that negative psychosocial and heavy physical workloads are strongly associated with musculoskeletal pain interfering with normal life in older adults. © 2015 the Nordic Societies of Public Health.

  3. Influence of low-energy laser radiation on normal skin and certain tumor tissues

    Energy Technology Data Exchange (ETDEWEB)

    Pletnev, S.D.; Karpenko, O.M.

    For some years, the authors' Institute has studied the influence of various types of low-energy laser radiation on normal tissue and the growth of tumors. Radiation at 3 and 30 J/cm/sup 2/ causes an increase in biological activity of various cell elements, manifested as an increase in mitotic activity of the cells in the basal layer of the epidermis, conglomeration of chromatin in the cell nuclei and an increase in degranulation of fat cells in the process of their migration to the reticular layer. Also noted was an increase in content of fibroblastic and lymphohistocytic elements in the dermis, as well as an increase in collagenization of connective tissue. It was found that irradiation of the skin by helium-neon, cadmium-helium and nitrogen lasers before and after grafting of the cells of various tumors modifies the course of the tumor process. This effect is apparently related to the fact that systematic irradiation results in changes creating a favorable background for survival and proliferation of tumor cells in the skin tissue medium. The changes facilitate an increase in survival and growth of both pigmented and nonpigmented tumors. Low power radiation stimulates the activity of the cells or cell structures; medium power stimulates their activity; high power suppresses activity.

  4. Sarcoglycans in the normal and pathological breast tissue of humans: an immunohistochemical and molecular study.

    Science.gov (United States)

    Arco, Alba; Favaloro, Angelo; Gioffrè, Mara; Santoro, Giuseppe; Speciale, Francesco; Vermiglio, Giovanna; Cutroneo, Giuseppina

    2012-01-01

    The sarcoglycan complex, consisting of α-, β-, γ-, δ- and ε-sarcoglycans, is a multimember transmembrane system providing a mechanosignaling connection from the cytoskeleton to the extracellular matrix. Whereas the expression of α- and γ-sarcoglycan is restricted to striated muscle, other sarcoglycans are widely expressed. Although many studies have investigated sarcoglycans in all muscle types, insufficient data are available on the distribution of the sarcoglycan complex in nonmuscle tissue. On this basis, we used immunohistochemical and RT-PCR techniques to study preliminarily the sarcoglycans in normal glandular breast tissue (which has never been studied in the literature on these proteins) to verify the effective wider distribution of this complex. Moreover, to understand the role of sarcoglycans, we also tested samples obtained from patients affected by fibrocystic mastopathy and breast fibroadenoma. Our data showed, for the first time, that all sarcoglycans are always detectable in all normal samples both in epithelial and myoepithelial cells; in pathological breast tissue, all sarcoglycans appeared severely reduced. These data demonstrated that all sarcoglycans, not only β-, δ-, and ε-sarcoglycans, have a wider distribution, implying a new unknown role for these proteins. Moreover, in breast diseases, sarcoglycans containing cadherin domain homologs could provoke a loss of strong adhesion between epithelial cells, permitting and facilitating the degeneration of these benign breast tumors into malignant tumors. Consequently, sarcoglycans could play an important and intriguing role in many breast diseases and in particular in tumor progression from benign to malignant. Copyright © 2011 S. Karger AG, Basel.

  5. Impact of margin on tumour and normal tissue dosimetry in patients treated with IMRT using an endorectal balloon for prostate immobilization

    International Nuclear Information System (INIS)

    Ahmad, S.

    2004-01-01

    Full text: In treatment of prostate cancer with IMRT (Intensity Modulated Radiation Therapy), clinical target volume margin is determined by organ motion and set-up error. However, the margin width that achieves the desired dose escalation while minimizing normal tissue exposure is dependent upon the patient immobilization and/or organ localization techniques. In this study, we compare the impact of margin width on the dosimetry of tumour and normal tissues using the endorectal balloon for prostate immobilization. IMRT plans were generated for ten patients using margin widths of 0, 3, 5, 8 and 10 mm. Patients had a planning CT scan in the prone position with an endorectal balloon filled with 100 cc of air for prostate immobilization. The Corvus version 3.0.11 was used for treatment planning. The dose for the prostate and seminal vesicles was 70 Gy in 2 Gy per fractions, prescribed at the 83% isodose line. Dose restrictions to normal tissues were as follows: 33% of bladder was allowed to receive above 65 Gy, 15% of rectum above 68 Gy and 10% of femurs above 45 Gy. Analysis of Variance was used to compare the target and normal tissue doses. Tumour control probability and normal tissue complication probability calculations are currently being performed and will be presented. The mean doses ranged from 73.93 to 75.31 Gy for the prostate and from 73.71 to 75.31 Gy for the seminal vesicles. A 10 mm margin produced significantly lower mean doses compared to 0 or 5 mm for both targets (prostate p 0.062). For bladder and rectum the mean doses ranged from 18.49 to 22.30 Gy (p=0.605) and from 29.34 to 31.33 Gy (p=0.135), respectively, while the percent rectal volumes above 68 Gy were significantly higher for margins of 5, 8 and 10 mm (p<0.006) ranging from 10.72% to 15.81%. Mean doses to the femurs and pelvis were significantly higher for 8 and 10 mm margins, ranging from 20.9 to 29.39 Gy for femurs (p<0.015) and from 15.05 to 19.98 Gy for pelvis (p<0.0005). Also the percent

  6. Human Colors-The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

    Science.gov (United States)

    Piña-Oviedo, Sergio; Ortiz-Hidalgo, Carlos; Ayala, Alberto G

    2017-03-01

    - Colors are important to all living organisms because they are crucial for camouflage and protection, metabolism, sexual behavior, and communication. Human organs obviously have color, but the underlying biologic processes that dictate the specific colors of organs and tissues are not completely understood. A literature search on the determinants of color in human organs yielded scant information. - To address 2 specific questions: (1) why do human organs have color, and (2) what gives normal and pathologic tissues their distinctive colors? - Endogenous colors are the result of complex biochemical reactions that produce biologic pigments: red-brown cytochromes and porphyrins (blood, liver, spleen, kidneys, striated muscle), brown-black melanins (skin, appendages, brain nuclei), dark-brown lipochromes (aging organs), and colors that result from tissue structure (tendons, aponeurosis, muscles). Yellow-orange carotenes that deposit in lipid-rich tissues are only produced by plants and are acquired from the diet. However, there is lack of information about the cause of color in other organs, such as the gray and white matter, neuroendocrine organs, and white tissues (epithelia, soft tissues). Neoplastic tissues usually retain the color of their nonneoplastic counterpart. - Most available information on the function of pigments comes from studies in plants, microorganisms, cephalopods, and vertebrates, not humans. Biologic pigments have antioxidant and cytoprotective properties and should be considered as potential future therapies for disease and cancer. We discuss the bioproducts that may be responsible for organ coloration and invite pathologists and pathology residents to look at a "routine grossing day" with a different perspective.

  7. Speech Recognition in Real-Life Background Noise by Young and Middle-Aged Adults with Normal Hearing

    OpenAIRE

    Lee, Ji Young; Lee, Jin Tae; Heo, Hye Jeong; Choi, Chul-Hee; Choi, Seong Hee; Lee, Kyungjae

    2015-01-01

    Background and Objectives People usually converse in real-life background noise. They experience more difficulty understanding speech in noise than in a quiet environment. The present study investigated how speech recognition in real-life background noise is affected by the type of noise, signal-to-noise ratio (SNR), and age. Subjects and Methods Eighteen young adults and fifteen middle-aged adults with normal hearing participated in the present study. Three types of noise [subway noise, vacu...

  8. Changes in radiation dose with variations in human anatomy: larger and smaller normal-stature adults.

    Science.gov (United States)

    Marine, Patrick M; Stabin, Michael G; Fernald, Michael J; Brill, Aaron B

    2010-05-01

    A systematic evaluation has been performed to study how specific absorbed fractions (SAFs) vary with changes in adult body size, for persons of different size but normal body stature. A review of the literature was performed to evaluate how individual organ sizes vary with changes in total body weight of normal-stature individuals. On the basis of this literature review, changes were made to our easily deformable reference adult male and female total-body models. Monte Carlo simulations of radiation transport were performed; SAFs for photons were generated for 10th, 25th, 75th, and 90th percentile adults; and comparisons were made to the reference (50th) percentile SAF values. Differences in SAFs for organs irradiating themselves were between 0.5% and 1.0%/kg difference in body weight, from 15% to 30% overall, for organs within the trunk. Differences in SAFs for organs outside the trunk were not greater than the uncertainties in the data and will not be important enough to change calculated doses. For organs irradiating other organs within the trunk, differences were significant, between 0.3% and 1.1%/kg, or about 8%-33% overall. The differences are interesting and can be used to estimate how different patients' dosimetry might vary from values reported in standard dose tables.

  9. Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas

    International Nuclear Information System (INIS)

    Haakensen, Vilde D; Børresen-Dale, Anne-Lise; Helland, Åslaug; Bjøro, Trine; Lüders, Torben; Riis, Margit; Bukholm, Ida K; Kristensen, Vessela N; Troester, Melissa A; Homen, Marit M; Ursin, Giske

    2011-01-01

    High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol. We compared whole genome expression data of breast tissue samples with serum hormone levels using data from 79 healthy women and 64 breast cancer patients. Significance analysis of microarrays (SAM) was used to identify differentially expressed genes and multivariate linear regression was used to identify independent associations. Six genes (SCGB3A1, RSPO1, TLN2, SLITRK4, DCLK1, PTGS1) were found differentially expressed according to serum estradiol levels (FDR = 0). Three of these independently predicted estradiol levels in a multivariate model, as SCGB3A1 (HIN1) and TLN2 were up-regulated and PTGS1 (COX1) was down-regulated in breast samples from women with high serum estradiol. Serum estradiol, but none of the differentially expressed genes were significantly associated with mammographic density, another strong breast cancer risk factor. In breast carcinomas, expression of GREB1 and AREG was associated with serum estradiol in all cancers and in the subgroup of estrogen receptor positive cases. We have identified genes associated with serum estradiol levels in normal breast tissue and in breast carcinomas. SCGB3A1 is a suggested tumor suppressor gene that inhibits cell growth and invasion and is methylated and down-regulated in many epithelial cancers. Our findings indicate this gene as an important inhibitor of breast cell proliferation in healthy women with high estradiol levels. In the breast, this gene is expressed in luminal cells only and is methylated in non-BRCA-related breast cancers. The possibility of a carcinogenic contribution of silencing of this gene for luminal, but not basal-like cancers should be further explored. PTGS1 induces prostaglandin E2 (PGE2) production which in turn stimulates aromatase expression and hence increases the

  10. Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

    Science.gov (United States)

    Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

    1993-06-01

    The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

  11. Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients

    NARCIS (Netherlands)

    Mulder, Renée L.; Paulides, Marios; Langer, Thorsten; Kremer, Leontien C. M.; van Dalen, Elvira C.

    2012-01-01

    Background Alkylating agents, such as cyclophosphamide and ifosfamide, play a major role in the improved survival of children and young adults with bone and soft tissue sarcoma. However, there is still controversy as to their comparative anti-tumour efficacy and possible adverse effects. This is an

  12. Cyclophosphamide versus ifosfamide for paediatric and young adult bone and soft tissue sarcoma patients

    NARCIS (Netherlands)

    Mulder, Renée L.; Paulides, Marios; Langer, Thorsten; Kremer, Leontien C. M.; van Dalen, Elvira C.

    2015-01-01

    Alkylating agents, such as cyclophosphamide and ifosfamide, play a major role in the improved survival of children and young adults with bone and soft tissue sarcoma. However, there is still controversy as to their comparative anti-tumour efficacy and possible adverse effects. This is the second

  13. Growing into obesity: patterns of height growth in those who become normal weight, overweight, or obese as young adults.

    Science.gov (United States)

    Stovitz, Steven D; Demerath, Ellen W; Hannan, Peter J; Lytle, Leslie A; Himes, John H

    2011-01-01

    To study whether patterns of height growth differ by adult obesity status, and determine the contribution of subcutaneous fatness as an explanatory variable for any differences. A multicenter, prospective longitudinal cohort assessed in 3rd grade (8.8 years), 5th grade (11.1 years), 8th grade (14.1 years), and 12th grade (18.3 years). Exposures were young adult obesity status classified by CDC adult BMI categories at 12th grade. Skinfolds were measured in third, fifth, and eighth grades. Outcome was mean height (cm) at the four measurements using repeated-measures ANCOVA for young adult obesity status, and height increments between grades by adult obesity status in sequential models including initial height and, secondarily, initial skinfolds. Adjusted for age, and race/ethnicity, young adult obesity status explained a small, but statistically significant amount of height growth among both females and males within each of the three intervals. Compared with normal weight young adults, overweight or obese young adults stood taller in childhood, but had relatively less growth in height throughout the teenage years. There was no association between adult height and weight status. Skinfolds explained only a small amount of the height patterns in the three weight groups. Childhood and adolescent height growth patterns differ between those who become young adults who are normal weight and those who become overweight or obese. Since differences in fatness explain only a small amount of these height growth patterns, research is needed to identify other determinants. Copyright © 2011 Wiley-Liss, Inc.

  14. Tremor severity and age: a cross-sectional, population-based study of 2,524 young and midlife normal adults.

    Science.gov (United States)

    Louis, Elan D; Hafeman, Danella; Parvez, Faruque; Liu, Xinhua; Alcalay, Roy N; Islam, Tariqul; Ahmed, Alauddin; Siddique, Abu Bakar; Patwary, Tazul Islam; Melkonian, Stephanie; Argos, Maria; Levy, Diane; Ahsan, Habibul

    2011-07-01

    Mild action tremor occurs in most normal people. Yet this tremor mainly has been studied within the context of advanced age rather than among the vast bulk of adults who are not elderly. Whether this tremor worsens during young and middle age is unknown. Using cross-sectional data from a large population-based study of young and midlife normal adults (age range, 18-60 years), we assessed whether increasing age is associated with more severe action tremor. Two thousand five hundred and twenty-four adults in Araihazar, Bangladesh, drew an Archimedes spiral with each hand. Tremor in spirals was rated (0-3) by a blinded neurologist, and a spiral score (range, 0-6) was assigned. Spiral score was correlated with age (r = 0.06, P = .004). With each advancing decade, the spiral score increased (P = .002) so that the spiral score in participants in the highest age group (age 60) was approximately twice that of participants in the youngest age group (age 18-19); P = .003. In the regression model that adjusted for potential confounders (sex, cigarettes, medications, asthma inhalers, and tea and betel nut use), spiral score was associated with age (P = .0045). In this cross-sectional, population-based study of more than 2500 young and midlife normal adults, there was a clear association between age and tremor severity. Although the magnitude of the correlation coefficient was modest, tremor severity was higher with each passing decade. These data suggest that age-dependent increase in tremor amplitude is not restricted to older people but occurs in all adult age groups. Copyright © 2011 Movement Disorder Society.

  15. Nucleotide excision repair genes are expressed at low levels and are not detectably inducible in Caenorhabditis elegans somatic tissues, but their function is required for normal adult life after UVC exposure

    International Nuclear Information System (INIS)

    Boyd, Windy A.; Crocker, Tracey L.; Rodriguez, Ana M.; Leung, Maxwell C.K.; Wade Lehmann, D.; Freedman, Jonathan H.; Van Houten, Ben; Meyer, Joel N.

    2010-01-01

    We performed experiments to characterize the inducibility of nucleotide excision repair (NER) in Caenorhabditis elegans, and to examine global gene expression in NER-deficient and -proficient strains as well as germline vs. somatic tissues, with and without genotoxic stress. We also carried out experiments to elucidate the importance of NER in the adult life of C. elegans under genotoxin-stressed and control conditions. Adult lifespan was not detectably different between wild-type and NER-deficient xpa-1 nematodes under control conditions. However, exposure to 6 J/m 2 /day of ultraviolet C radiation (UVC) decreased lifespan in xpa-1 nematodes more than a dose of 100 J/m 2 /day in wild-type. Similar differential sensitivities were observed for adult size and feeding. Remarkably, global gene expression was nearly identical in young adult wild-type and xpa-1 nematodes, both in control conditions and 3 h after exposure to 50 J/m 2 UVC. Neither NER genes nor repair activity were detectably inducible in young adults that lacked germ cells and developing embryos (glp-1 strain). However, expression levels of dozens of NER and other DNA damage response genes were much (5-30-fold) lower in adults lacking germ cells and developing embryos, suggesting that somatic and post-mitotic cells have a much lower DNA repair ability. Finally, we describe a refinement of our DNA damage assay that allows damage measurement in single nematodes.

  16. Nucleotide excision repair genes are expressed at low levels and are not detectably inducible in Caenorhabditis elegans somatic tissues, but their function is required for normal adult life after UVC exposure

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, Windy A. [Biomolecular Screening Branch, National Toxicology Program, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC (United States); Crocker, Tracey L. [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Rodriguez, Ana M. [Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC (United States); Leung, Maxwell C.K. [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States); Wade Lehmann, D. [Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC (United States); Freedman, Jonathan H. [Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC (United States); Van Houten, Ben [Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC (United States); Meyer, Joel N., E-mail: joel.meyer@duke.edu [Nicholas School of the Environment, Duke University, Durham, NC 27708 (United States)

    2010-01-05

    We performed experiments to characterize the inducibility of nucleotide excision repair (NER) in Caenorhabditis elegans, and to examine global gene expression in NER-deficient and -proficient strains as well as germline vs. somatic tissues, with and without genotoxic stress. We also carried out experiments to elucidate the importance of NER in the adult life of C. elegans under genotoxin-stressed and control conditions. Adult lifespan was not detectably different between wild-type and NER-deficient xpa-1 nematodes under control conditions. However, exposure to 6 J/m{sup 2}/day of ultraviolet C radiation (UVC) decreased lifespan in xpa-1 nematodes more than a dose of 100 J/m{sup 2}/day in wild-type. Similar differential sensitivities were observed for adult size and feeding. Remarkably, global gene expression was nearly identical in young adult wild-type and xpa-1 nematodes, both in control conditions and 3 h after exposure to 50 J/m{sup 2} UVC. Neither NER genes nor repair activity were detectably inducible in young adults that lacked germ cells and developing embryos (glp-1 strain). However, expression levels of dozens of NER and other DNA damage response genes were much (5-30-fold) lower in adults lacking germ cells and developing embryos, suggesting that somatic and post-mitotic cells have a much lower DNA repair ability. Finally, we describe a refinement of our DNA damage assay that allows damage measurement in single nematodes.

  17. Therapy-induced effects in normal tissue; Therapieinduzierte Effekte am Normalgewebe

    Energy Technology Data Exchange (ETDEWEB)

    Kaick, G. van; Delorme, S. [Deutsches Krebsforschungszentrum (DKFZ), Abteilung E010 - Radiologie, Heidelberg (Germany)

    2008-09-15

    More than 50% of cancer patients survive for more than 5 years, owing to modern and effective treatment. Therefore, long-term sequelae of treatment are more frequently seen than in the past. Such effects on normal tissue may both mimic and obscure tumor recurrences. Besides the direct consequences of surgery, tissue damage due to radiation or chemotherapy frequently cause problems in differential diagnosis. Among the numerous sequelae of radiotherapy, the most prominent are disturbance of the blood-brain barrier, radiation pneumonitis, osteodystrophy and osteoradionecrosis, fatty changes of bone marrow, or increased radiodensity of breast parenchyma. Chemotherapy may cause, e.g., diffuse abnormalities of white matter, pneumonitis and lung fibrosis, cardiomyopathy, or diffuse and patchy changes in bone marrow signals in MRI. The most devastating long-term complications are secondary cancers and leukemia induced by both radiotherapy and chemotherapy. (orig.) [German] Mehr als 50% der Tumorpatienten ueberleben dank moderner Therapie laenger als 5 Jahre, sodass die Spaetfolgen am gesunden Gewebe haeufiger und genauer erfasst werden. Diese koennen Tumorrezidive sowohl verschleiern als auch vortaeuschen. Neben den unmittelbaren Folgen operativer Eingriffe sind Auswirkungen der Chemo- und Strahlentherapie ein haeufiges differenzialdiagnostisches Problem. Wichtige Folgen einer Strahlentherapie sind z. B. Blut-Hirn-Schranken-Stoerungen, Strahlenpneumonitis, Osteodystrophie und -radionekrose, Verfettung des blutbildenden Knochenmarks oder Parenchymverdichtungen der Brust. Chemotherapie kann u. a. zur Leukenzephalopathie, Pneumonitis und Lungenfibrose, Kardiomyopathie sowie zu diffusen und fleckfoermigen Signalaenderungen des Knochenmarks in der MRT fuehren. Die schwerstwiegende Spaetkomplikation ist die Induktion solider Zweittumoren und Leukaemien sowohl nach Strahlen- als auch Chemotherapie. (orig.)

  18. Isolation and characterization of adult human liver progenitors from ischemic liver tissue derived from therapeutic hepatectomies.

    Science.gov (United States)

    Stachelscheid, Harald; Urbaniak, Thomas; Ring, Alexander; Spengler, Berlind; Gerlach, Jörg C; Zeilinger, Katrin

    2009-07-01

    Recent evidence suggests that progenitor cells in adult tissues and embryonic stem cells share a high resistance to hypoxia and ischemic stress. To study the ischemic resistance of adult liver progenitors, we characterized remaining viable cells in human liver tissue after cold ischemic treatment for 24-168 h, applied to the tissue before cell isolation. In vitro cultures of isolated cells showed a rapid decline of the number of different cell types with increasing ischemia length. After all ischemic periods, liver progenitor-like cells could be observed. The comparably small cells exhibited a low cytoplasm-to-nucleus ratio, formed densely packed colonies, and showed a hepatobiliary marker profile. The cells expressed epithelial cell adhesion molecule, epithelial-specific (CK8/18) and biliary-specific (CK7/19) cytokeratins, albumin, alpha-1-antitrypsin, cytochrome-P450 enzymes, as well as weak levels of hepatocyte nuclear factor-4 and gamma-glutamyl transferase, but not alpha-fetoprotein or Thy-1. In vitro survival and expansion was facilitated by coculture with mouse embryonic fibroblasts. Hepatic progenitor-like cells exhibit a high resistance to ischemic stress and can be isolated from human liver tissue after up to 7 days of ischemia. Ischemic liver tissue from various sources, thought to be unsuitable for cell isolation, may be considered as a prospective source of hepatic progenitor cells.

  19. Expression of IL-18, IL-18 Binding Protein, and IL-18 Receptor by Normal and Cancerous Human Ovarian Tissues: Possible Implication of IL-18 in the Pathogenesis of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Liat Medina

    2014-01-01

    Full Text Available Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were significantly higher in cancerous ovarian tissues (P=0.0007, IL-18BP levels were significantly higher in normal ovarian tissues (P=0.04, and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P=0.036. Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P=0.025, while there was no difference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

  20. Differentiating the two main histologic categories of fibroadenoma tissue from normal breast tissue by using multiphoton microscopy.

    Science.gov (United States)

    Nie, Y T; Wu, Y; Fu, F M; Lian, Y E; Zhuo, S M; Wang, C; Chen, J X

    2015-04-01

    Multiphoton microscopy has become a novel biological imaging technique that allows cellular and subcellular microstructure imaging based on two-photon excited fluorescence and second harmonic generation. In this work, we used multiphoton microscopy to obtain the high-contrast images of human normal breast tissue and two main histologic types of fibroadenoma (intracanalicular, pericanalicular). Moreover, quantitative image analysis was performed to characterize the changes of collagen morphology (collagen content, collagen orientation). The results show that multiphoton microscopy combined with quantitative method has the ability to identify the characteristics of fibroadenoma including changes of the duct architecture and collagen morphology in stroma. With the advancement of multiphoton microscopy, we believe that the technique has great potential to be a real-time histopathological diagnostic tool for intraoperative detection of fibroadenoma in the future. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

  1. Fluid Distribution Pattern in Adult-Onset Congenital, Idiopathic, and Secondary Normal-Pressure Hydrocephalus: Implications for Clinical Care.

    Science.gov (United States)

    Yamada, Shigeki; Ishikawa, Masatsune; Yamamoto, Kazuo

    2017-01-01

    In spite of growing evidence of idiopathic normal-pressure hydrocephalus (NPH), a viewpoint about clinical care for idiopathic NPH is still controversial. A continuous divergence of viewpoints might be due to confusing classifications of idiopathic and adult-onset congenital NPH. To elucidate the classification of NPH, we propose that adult-onset congenital NPH should be explicitly distinguished from idiopathic and secondary NPH. On the basis of conventional CT scan or MRI, idiopathic NPH was defined as narrow sulci at the high convexity in concurrent with enlargement of the ventricles, basal cistern and Sylvian fissure, whereas adult-onset congenital NPH was defined as huge ventricles without high-convexity tightness. We compared clinical characteristics and cerebrospinal fluid distribution among 85 patients diagnosed with idiopathic NPH, 17 patients with secondary NPH, and 7 patients with adult-onset congenital NPH. All patients underwent 3-T MRI examinations and tap-tests. The volumes of ventricles and subarachnoid spaces were measured using a 3D workstation based on T2-weighted 3D sequences. The mean intracranial volume for the patients with adult-onset congenital NPH was almost 100 mL larger than the volumes for patients with idiopathic and secondary NPH. Compared with the patients with idiopathic or secondary NPH, patients with adult-onset congenital NPH exhibited larger ventricles but normal sized subarachnoid spaces. The mean volume ratio of the high-convexity subarachnoid space was significantly less in idiopathic NPH than in adult-onset congenital NPH, whereas the mean volume ratio of the basal cistern and Sylvian fissure in idiopathic NPH was >2 times larger than that in adult-onset congenital NPH. The symptoms of gait disturbance, cognitive impairment, and urinary incontinence in patients with adult-onset congenital NPH tended to progress more slowly compared to their progress in patients with idiopathic NPH. Cerebrospinal fluid distributions and

  2. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    International Nuclear Information System (INIS)

    Bujak, Emil; Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah; Neri, Dario

    2014-01-01

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  3. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Bujak, Emil [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland); Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah [Philochem AG, Libernstrasse 3, CH-8112 Otelfingen (Switzerland); Neri, Dario, E-mail: neri@pharma.ethz.ch [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland)

    2014-09-10

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  4. SU-D-16A-01: A Novel Method to Estimate Normal Tissue Dose for Radiotherapy Patients to Support Epidemiologic Studies of Second Cancer Risk

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C [University of Michigan, Ann Arbor, MI (United States); Jung, J; Pelletier, C [East Carolina University, Greenville, NC (United States); Kim, J [University of Pittsburgh Medical Center, Pittsburgh, PA (United States); Lee, C [National Cancer Institute, Bethesda, MD (United States)

    2014-06-01

    Purpose: Patient cohort of second cancer study often involves radiotherapy patients with no radiological images available: We developed methods to construct a realistic surrogate anatomy by using computational human phantoms. We tested this phantom images both in a commercial treatment planning system (Eclipse) and a custom Monte Carlo (MC) transport code. Methods: We used a reference adult male phantom defined by International Commission on Radiological Protection (ICRP). The hybrid phantom which was originally developed in Non-Uniform Rational B-Spline (NURBS) and polygon mesh format was converted into more common medical imaging format. Electron density was calculated from the material composition of the organs and tissues and then converted into DICOM format. The DICOM images were imported into the Eclipse system for treatment planning, and then the resulting DICOM-RT files were imported into the MC code for MC-based dose calculation. Normal tissue doses were calculation in Eclipse and MC code for an illustrative prostate treatment case and compared to each other. Results: DICOM images were generated from the adult male reference phantom. Densities and volumes of selected organs between the original phantom and ones represented within Eclipse showed good agreements, less than 0.6%. Mean dose from Eclipse and MC code match less than 7%, whereas maximum and minimum doses were different up to 45%. Conclusion: The methods established in this study will be useful for the reconstruction of organ dose to support epidemiological studies of second cancer in cancer survivors treated by radiotherapy. We also work on implementing body size-dependent computational phantoms to better represent patient's anatomy when the height and weight of patients are available.

  5. Up-regulation of ALG-2 in hepatomas and lung cancer tissue

    DEFF Research Database (Denmark)

    la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

    2003-01-01

    , a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...... using Western blot analysis and immunohistochemistry. Western blot analysis of 15 different adult mouse tissues demonstrated that ALG-2 is ubiquitously expressed. We found that ALG-2 was more than threefold overexpressed in rat liver hepatoma compared to normal rat liver using Western blot analysis...

  6. Protons Offer Reduced Normal-Tissue Exposure for Patients Receiving Postoperative Radiotherapy for Resected Pancreatic Head Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, Romaine C., E-mail: rnichols@floridaproton.org [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Huh, Soon N. [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Prado, Karl L.; Yi, Byong Y.; Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States); Ho, Meng W.; Hoppe, Bradford S.; Mendenhall, Nancy P.; Li, Zuofeng [University of Florida Proton Therapy Institute, Jacksonsville, FL (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland, Baltimore, MD (United States)

    2012-05-01

    Purpose: To determine the potential role for adjuvant proton-based radiotherapy (PT) for resected pancreatic head cancer. Methods and Materials: Between June 2008 and November 2008, 8 consecutive patients with resected pancreatic head cancers underwent optimized intensity-modulated radiotherapy (IMRT) treatment planning. IMRT plans used between 10 and 18 fields and delivered 45 Gy to the initial planning target volume (PTV) and a 5.4 Gy boost to a reduced PTV. PTVs were defined according to the Radiation Therapy Oncology Group 9704 radiotherapy guidelines. Ninety-five percent of PTVs received 100% of the target dose and 100% of the PTVs received 95% of the target dose. Normal tissue constraints were as follows: right kidney V18 Gy to <70%; left kidney V18 Gy to <30%; small bowel/stomach V20 Gy to <50%, V45 Gy to <15%, V50 Gy to <10%, and V54 Gy to <5%; liver V30 Gy to <60%; and spinal cord maximum to 46 Gy. Optimized two- to three-field three-dimensional conformal proton plans were retrospectively generated on the same patients. The team generating the proton plans was blinded to the dose distributions achieved by the IMRT plans. The IMRT and proton plans were then compared. A Wilcoxon paired t-test was performed to compare various dosimetric points between the two plans for each patient. Results: All proton plans met all normal tissue constraints and were isoeffective with the corresponding IMRT plans in terms of PTV coverage. The proton plans offered significantly reduced normal-tissue exposure over the IMRT plans with respect to the following: median small bowel V20 Gy, 15.4% with protons versus 47.0% with IMRT (p = 0.0156); median gastric V20 Gy, 2.3% with protons versus 20.0% with IMRT (p = 0.0313); and median right kidney V18 Gy, 27.3% with protons versus 50.5% with IMRT (p = 0.0156). Conclusions: By reducing small bowel and stomach exposure, protons have the potential to reduce the acute and late toxicities of postoperative chemoradiation in this setting.

  7. On Predicting lung cancer subtypes using ‘omic’ data from tumor and tumor-adjacent histologically-normal tissue

    International Nuclear Information System (INIS)

    Pineda, Arturo López; Ogoe, Henry Ato; Balasubramanian, Jeya Balaji; Rangel Escareño, Claudia; Visweswaran, Shyam; Herman, James Gordon; Gopalakrishnan, Vanathi

    2016-01-01

    Adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the most prevalent histological types among lung cancers. Distinguishing between these subtypes is critically important because they have different implications for prognosis and treatment. Normally, histopathological analyses are used to distinguish between the two, where the tissue samples are collected based on small endoscopic samples or needle aspirations. However, the lack of cell architecture in these small tissue samples hampers the process of distinguishing between the two subtypes. Molecular profiling can also be used to discriminate between the two lung cancer subtypes, on condition that the biopsy is composed of at least 50 % of tumor cells. However, for some cases, the tissue composition of a biopsy might be a mix of tumor and tumor-adjacent histologically normal tissue (TAHN). When this happens, a new biopsy is required, with associated cost, risks and discomfort to the patient. To avoid this problem, we hypothesize that a computational method can distinguish between lung cancer subtypes given tumor and TAHN tissue. Using publicly available datasets for gene expression and DNA methylation, we applied four classification tasks, depending on the possible combinations of tumor and TAHN tissue. First, we used a feature selector (ReliefF/Limma) to select relevant variables, which were then used to build a simple naïve Bayes classification model. Then, we evaluated the classification performance of our models by measuring the area under the receiver operating characteristic curve (AUC). Finally, we analyzed the relevance of the selected genes using hierarchical clustering and IPA® software for gene functional analysis. All Bayesian models achieved high classification performance (AUC > 0.94), which were confirmed by hierarchical cluster analysis. From the genes selected, 25 (93 %) were found to be related to cancer (19 were associated with ADC or SCC), confirming the biological relevance of our

  8. THE PRESENCE OF ENDOGENOUS PYROGEN IN NORMAL RABBIT TISSUES.

    Science.gov (United States)

    SNELL, E S; ATKINS, E

    1965-06-01

    Saline extracts of homogenized, uninfected, rabbit tissues produced febrile responses when injected intravenously into rabbits. Extracts of muscle, lung, and heart evoked fevers that were similar to those induced by leucocyte pyrogen; extracts of spleen, liver, and kidney caused more sustained fevers. The minimal pyrogenic dose appeared to be between 1.5 and 3 gm wet weight of tissue. Evidence is presented that neither Gram-negative bacterial endotoxin nor polymorphonuclear leucocytes (circulating or sequestered in the tissues) can be implicated as the source of pyrogen in tissue extracts. It seems likely, therefore, that a pyrogenic material of truly endogenous origin is widely distributed in tissues. Tissue pyrogen appears to be a large molecule which is relatively resistant to treatment with acid but not with alkali. Possible pathological roles for this endogenous agent (or agents) are briefly indicated.

  9. Activity of pyrimidine degradation enzymes in normal tissues

    NARCIS (Netherlands)

    van Kuilenburg, A. B. P.; van Lenthe, H.; van Gennip, A. H.

    2006-01-01

    In this study, we measured the activity of dihydropyrimidine dehydrogenase (DPD), dihydropyrimidinase (DHP) and beta-ureidopropionase (beta-UP), using radiolabeled substrates, in 16 different tissues obtained at autopsy from a single patient. The activity of DPD could be detected in all tissues

  10. Reflectance spectrometry of normal and bruised human skins: experiments and modeling

    International Nuclear Information System (INIS)

    Kim, Oleg; Alber, Mark; McMurdy, John; Lines, Collin; Crawford, Gregory; Duffy, Susan

    2012-01-01

    A stochastic photon transport model in multilayer skin tissue combined with reflectance spectroscopy measurements is used to study normal and bruised skins. The model is shown to provide a very good approximation to both normal and bruised real skin tissues by comparing experimental and simulated reflectance spectra. The sensitivity analysis of the skin reflectance spectrum to variations of skin layer thicknesses, blood oxygenation parameter and concentrations of main chromophores is performed to optimize model parameters. The reflectance spectrum of a developed bruise in a healthy adult is simulated, and the concentrations of bilirubin, blood volume fraction and blood oxygenation parameter are determined for different times as the bruise progresses. It is shown that bilirubin and blood volume fraction reach their peak values at 80 and 55 h after contusion, respectively, and the oxygenation parameter is lower than its normal value during 80 h after contusion occurred. The obtained time correlations of chromophore concentrations in developing contusions are shown to be consistent with previous studies. The developed model uses a detailed seven-layer skin approximation for contusion and allows one to obtain more biologically relevant results than those obtained with previous models using one- to three-layer skin approximations. A combination of modeling with spectroscopy measurements provides a new tool for detailed biomedical studies of human skin tissue and for age determination of contusions. (paper)

  11. Transcriptional profiling differences for articular cartilage and repair tissue in equine joint surface lesions

    Directory of Open Access Journals (Sweden)

    Stromberg Arnold J

    2009-09-01

    Full Text Available Abstract Background Full-thickness articular cartilage lesions that reach to the subchondral bone yet are restricted to the chondral compartment usually fill with a fibrocartilage-like repair tissue which is structurally and biomechanically compromised relative to normal articular cartilage. The objective of this study was to evaluate transcriptional differences between chondrocytes of normal articular cartilage and repair tissue cells four months post-microfracture. Methods Bilateral one-cm2 full-thickness defects were made in the articular surface of both distal femurs of four adult horses followed by subchondral microfracture. Four months postoperatively, repair tissue from the lesion site and grossly normal articular cartilage from within the same femorotibial joint were collected. Total RNA was isolated from the tissue samples, linearly amplified, and applied to a 9,413-probe set equine-specific cDNA microarray. Eight paired comparisons matched by limb and horse were made with a dye-swap experimental design with validation by histological analyses and quantitative real-time polymerase chain reaction (RT-qPCR. Results Statistical analyses revealed 3,327 (35.3% differentially expressed probe sets. Expression of biomarkers typically associated with normal articular cartilage and fibrocartilage repair tissue corroborate earlier studies. Other changes in gene expression previously unassociated with cartilage repair were also revealed and validated by RT-qPCR. Conclusion The magnitude of divergence in transcriptional profiles between normal chondrocytes and the cells that populate repair tissue reveal substantial functional differences between these two cell populations. At the four-month postoperative time point, the relative deficiency within repair tissue of gene transcripts which typically define articular cartilage indicate that while cells occupying the lesion might be of mesenchymal origin, they have not recapitulated differentiation to

  12. Hard and soft tissue correlations in facial profiles: a canonical correlation study

    Directory of Open Access Journals (Sweden)

    Shamlan MA

    2015-01-01

    Full Text Available Manal A Shamlan,1 Abdullah M Aldrees2 1Faculty of Dentistry, King Abdulaziz University, Jeddah, 2Division of Orthodontics, Department of Pediatric Dentistry and Orthodontics, College of Dentistry, King Saud University, Riyadh, Saudi Arabia Background: The purpose of this study was to analyze the relationship between facial hard and soft tissues in normal Saudi individuals by studying the canonical correlation between specific hard tissue landmarks and their corresponding soft tissue landmarks. Methods: A retrospective, cross-sectional study was designed, with a sample size of 60 Saudi adults (30 males and 30 females who had a class I skeletal and dental relationship and normal occlusion. Lateral cephalometric radiographs of the study sample were investigated using a series of 29 linear and angular measurements of hard and soft tissue features. The measurements were calculated electronically using Dolphin® software, and the data were analyzed using canonical correlation. Results: Eighty-four percent of the variation in the soft tissue was explained by the variation in hard tissue. Conclusion: The position of the upper and lower incisors and inclination of the lower incisors influence upper lip length and lower lip position. The inclination of the upper incisors is associated with lower lip length. Keywords: facial profile, hard tissue, soft tissue, canonical correlation

  13. Radiosensitization of tumors and normal tissues by combined treatment with misonidazole and heat

    International Nuclear Information System (INIS)

    Hofer, K.G.; MacKinnon, A.R.; Schubert, A.L.; Lehr, J.E.; Grimmett, E.V.

    1981-01-01

    Combination treatment of mice with misonidazole (0.5 mg/g body wt.) and hyperthermia (41.5/sup o/C for 45 mins.) produced dramatic radiosensitization in hypoxic BP-8 murine sarcoma cells. The dose modifying factor (DMF: 4.3) was such that hypoxic BP-8 cells subjected to combination therapy became more radiosensitive than untreated, fully oxygenated cell populations. In contrast, radiosensitization by combination treatment was comparatively minor or completely absent in normal body tissues such as skin (DMF: 1.57), intestine (DMF: 1.0), and bone marrow (DMF: 1.0). These results suggest that simultaneous administration of misonidazole and hyperthermia may prove an effective adjuvant to conventional clinical radiation therapy

  14. Differentiation between chronic hepatitis and normal liver of grayscale ultrasound tissue quantification using adobe photoshop(5.0)

    International Nuclear Information System (INIS)

    Choi, Jong Cheol; Oh, Jong Young; Lim, Jong Uk; Nam, Kyung Jin

    2001-01-01

    To evaluate whether was any difference in the brightness of echogenicity on gray scale ultrasound imaging between the liver with chronic hepatitis and the normal liver using Adobe photoshop 5.0 Seventy-five patients with pathologically proven chronic hepatitis and twenty normal volunteers were included in this study. Adobe photoshop 5.0 histogram was used to measure the brightness of image. The measured brightness of the liver was divided by the brightness of the kidney, and the radio was calculated and compared between patients with chronic hepatitis and the normal control groups. In addition, the degree of fibrosis was also evaluated. The difference in brightness between the normal liver and live with chronic hepatitis was statistically significant, but no statistically significant difference was observed between the brightness of the liver and the degree of fibrosis in the liver. Tissue echo quantification using Adobe Photoshop 5.0 may be a helpful diagnostic methods for the patients with chronic hepatitis.

  15. [Relationship between the Mandarin acceptable noise level and the personality traits in normal hearing adults].

    Science.gov (United States)

    Wu, Dan; Chen, Jian-yong; Wang, Shuo; Zhang, Man-hua; Chen, Jing; Li, Yu-ling; Zhang, Hua

    2013-03-01

    To evaluate the relationship between the Mandarin acceptable noise level (ANL) and the personality trait for normal-hearing adults. Eighty-five Mandarin speakers, aged from 21 to 27, participated in this study. ANL materials and the Eysenck Personality Questionnaire (EPQ) questionnaire were used to test the acceptable noise level and the personality trait for normal-hearing subjects. SPSS 17.0 was used to analyze the results. ANL were (7.8 ± 2.9) dB in normal hearing participants. The P and N scores in EPQ were significantly correlated with ANL (r = 0.284 and 0.318, P 0.05). Listeners with higher ANL were more likely to be eccentric, hostile, aggressive, and instabe, no ANL differences were found in listeners who were different in introvert-extravert or lying.

  16. Correlation of in vitro lymphocyte radiosensitivity and gene expression with late normal tissue reactions following curative radiotherapy for breast cancer

    International Nuclear Information System (INIS)

    Finnon, Paul; Kabacik, Sylwia; MacKay, Alan; Raffy, Claudine; A’Hern, Roger; Owen, Roger; Badie, Christophe; Yarnold, John; Bouffler, Simon

    2012-01-01

    Background and purpose: Identification of mechanisms of late normal tissue responses to curative radiotherapy that discriminate individuals with marked or mild responses would aid response prediction. This study aimed to identify differences in gene expression, apoptosis, residual DNA double strand breaks and chromosomal damage after in vitro irradiation of lymphocytes in a series of patients with marked (31 cases) or mild (28 controls) late adverse reaction to adjuvant breast radiotherapy. Materials and methods: Gene expression arrays, residual γH2AX, apoptosis, G2 chromosomal radiosensitivity and G0 micronucleus assay were used to compare case and control lymphocyte radiation responses. Results: Five hundred and thirty genes were up-regulated and 819 down-regulated by ionising radiation. Irradiated samples were identified with an overall cross-validated error rate of 3.4%. Prediction analyses to classify cases and controls using unirradiated (0 Gy), irradiated (4 Gy) or radiation response (4–0 Gy) expression profiles correctly identified samples with, respectively, 25%, 22% or 18.5% error rates. Significant inter-sample variation was observed for all cellular endpoints but cases and controls could not be distinguished. Conclusions: Variation in lymphocyte radiosensitivity does not necessarily correlate with normal tissue response to radiotherapy. Gene expression analysis can predict of radiation exposure and may in the future help prediction of normal tissue radiosensitivity.

  17. A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues

    Science.gov (United States)

    Yu, Yen-Rei A.; O’Koren, Emily G.; Hotten, Danielle F.; Kan, Matthew J.; Kopin, David; Nelson, Erik R.; Que, Loretta; Gunn, Michael D.

    2016-01-01

    Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that is both comprehensive and widely applicable has not been described. We developed a protocol for the flow cytometric analysis of non-lymphoid tissues, including methods of tissue preparation, a 10-fluorochrome panel for cell staining, and a standardized gating strategy, that allows the simultaneous identification and quantification of all major immune cell types in a variety of normal and inflamed non-lymphoid tissues. We demonstrate that our basic protocol minimizes cell loss, reliably distinguishes macrophages from dendritic cells (DC), and identifies all major granulocytic and mononuclear phagocytic cell types. This protocol is able to accurately quantify 11 distinct immune cell types, including T cells, B cells, NK cells, neutrophils, eosinophils, inflammatory monocytes, resident monocytes, alveolar macrophages, resident/interstitial macrophages, CD11b- DC, and CD11b+ DC, in normal lung, heart, liver, kidney, intestine, skin, eyes, and mammary gland. We also characterized the expression patterns of several commonly used myeloid and macrophage markers. This basic protocol can be expanded to identify additional cell types such as mast cells, basophils, and plasmacytoid DC, or perform detailed phenotyping of specific cell types. In examining models of primary and metastatic mammary tumors, this protocol allowed the identification of several distinct tumor associated macrophage phenotypes, the appearance of which was highly specific to individual tumor cell lines. This protocol provides a valuable tool to examine immune cell repertoires and follow immune responses in a wide variety of tissues and experimental conditions. PMID:26938654

  18. Increase in circulating holotranscobalamin after oral administration of cyanocobalamin or hydroxocobalamin in healthy adults with low and normal cobalamin status

    DEFF Research Database (Denmark)

    Greibe, Eva; Mahalle, Namita; Bhide, Vijayshri

    2017-01-01

    PURPOSE: To investigate the absorption of synthetic cyanocobalamin and natural occurring hydroxocobalamin in populations with low and normal cobalamin (vitamin B12) status. METHODS: We included adults with low (n = 59) and normal (n = 42) cobalamin status and measured the change in serum holotran...

  19. Exploring the Factor Structure of Financial Capacity in Cognitively Normal and Impaired Older Adults.

    Science.gov (United States)

    Gerstenecker, Adam; Triebel, Kristen; Eakin, Amanda; Martin, Roy; Marson, Daniel

    2018-01-01

    To investigate the factor structure of financial capacity using a direct-performance measure of financial skills (The Financial Capacity Instrument [FCI]) as a proxy for the financial capacity construct. The study sample was composed of 440 older adults who represented the cognitive spectrum from normal cognitive aging to mild cognitive impairment (MCI) to mild dementia: 179 healthy older adults, 149 participants with MCI, and 112 participants with mild Alzheimer's dementia (AD). Both Velicer's Minimum Average Partial test and Horn's parallel analysis supported a four-factor solution which accounted for 46% of variance. The four extracted factors were interpreted as: (1) Basic Monetary Knowledge and Calculation Skills, (2) Financial Judgment, (3) Financial Conceptual Knowledge, and (4) Financial Procedural Knowledge. The study findings represent an important first step in empirically articulating the financial capacity construct in aging. The four identified factors can guide both clinical practice and future instrument utilization and development. Cognitively impaired older adults with MCI and mild AD dementia are likely to show financial changes in one or more of the four identified financial factors. Clinicians working with older adults should routinely examine for potential changes in these four areas of financial function.

  20. Amyloid burden and incident depressive symptoms in cognitively normal older adults.

    Science.gov (United States)

    Harrington, Karra D; Gould, Emma; Lim, Yen Ying; Ames, David; Pietrzak, Robert H; Rembach, Alan; Rainey-Smith, Stephanie; Martins, Ralph N; Salvado, Olivier; Villemagne, Victor L; Rowe, Christopher C; Masters, Colin L; Maruff, Paul

    2017-04-01

    Several studies have reported that non-demented older adults with clinical depression show changes in amyloid-β (Aβ) levels in blood, cerebrospinal fluid and on neuroimaging that are consistent with those observed in patients with Alzheimer's disease. These findings suggest that Aβ may be one of the mechanisms underlying the relation between the two conditions. We sought to determine the relation between elevated cerebral Aβ and the presence of depression across a 54-month prospective observation period. Cognitively normal older adults from the Australian Imaging Biomarkers and Lifestyle study who were not depressed and had undergone a positron emission tomography scan to classify them as either high Aβ (n = 81) or low Aβ (n = 278) participated. Depressive symptoms were assessed using the Geriatric Depression Scale - Short Form at 18-month intervals over 54 months. Whilst there was no difference in probable depression between groups at baseline, incidence was 4.5 (95% confidence interval [CI] 1.3-16.4) times greater within the high Aβ group (9%) than the low Aβ group (2%) by the 54-month assessment. Results of this study suggest that elevated Aβ levels are associated with a 4.5-fold increased likelihood of developing clinically significant depressive symptoms on follow-up in preclinical Alzheimer's disease. This underscores the importance of assessing, monitoring and treating depressive symptoms in older adults with elevated Aβ. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Canine tumor and normal tissue response to heat and radiation

    International Nuclear Information System (INIS)

    Gillette, E.L.; McChesney, S.L.

    1985-01-01

    Oral squamous cell carcinomas of dogs were treated with either irradiation alone or combined with hyperthermia. Tumor control was assessed as no evidence of disease one year following treatment. Dogs were randomized to variable radiation doses which were given in ten fractions three times a week for three weeks. Heat was given three hours after the first and third radiation dose each week for seven treatments. The attempt was made to achieve a minimum tumor temperature of 42 0 C for thirty minutes with a maximum normal tissue temperature of 40 0 C. It was usually possible to selectively heat tumors. The TCD 50 for irradiation alone was about 400 rads greater than for heat plus irradiation. The dose response curve for heat plus radiation was much steeper than for radiation alone indicating less heterogeneity of tumor response. That also implies a much greater effectiveness of radiation combined with heat at higher tumor control probabilities. Early necrosis caused by heating healed with conservative management. No increase in late radiation necrosis was observed

  2. Acute and late effects of multimodal therapy on normal tissues

    International Nuclear Information System (INIS)

    Phillips, T.L.; Fu, K.K.

    1977-01-01

    The increasing use of combined radiation, chemotherapy, and surgery has led to an increased incidence of acute and late complications. The complications are, in general, similar to those seen with each modality alone, but occur with increased incidence. Enhanced effects of combined radiation and surgery are modest in number and consist primarily of problems with wound healing and fibrosis, as well as late gastrointestinal damage. Combinations of radiotherapy and chemotherapy have shown a greater degree of enhanced acute and late reactions. Drugs, such as actinomycin-D and Adriamycin, are particularly dangerous if the marked enhancement of radiation effects caused by the drugs in almost all organs is not appreciated and the radiation dose not adjusted accordingly. Proper selection of drugs can lead to enhanced local control by radiotherapy and/or surgery, as well as eradication of microscopic distant metastases, without increased normal tissue injury. Late induction of malignancy can occur with either radiation or chemotherapy alone and, in some cases, this appears to be enhanced when they are combined

  3. ERP C250 shows the elderly (cognitively normal, Alzheimer's disease) store more stimuli in short-term memory than Young Adults do.

    Science.gov (United States)

    Chapman, Robert M; Gardner, Margaret N; Mapstone, Mark; Klorman, Rafael; Porsteinsson, Anton P; Dupree, Haley M; Antonsdottir, Inga M; Kamalyan, Lily

    2016-06-01

    To determine how aging and dementia affect the brain's initial storing of task-relevant and irrelevant information in short-term memory. We used brain Event-Related Potentials (ERPs) to measure short-term memory storage (ERP component C250) in 36 Young Adults, 36 Normal Elderly, and 36 early-stage AD subjects. Participants performed the Number-Letter task, a cognitive paradigm requiring memory storage of a first relevant stimulus to compare it with a second stimulus. In Young Adults, C250 was more positive for the first task-relevant stimulus compared to all other stimuli. C250 in Normal Elderly and AD subjects was roughly the same to relevant and irrelevant stimuli in Intratrial Parts 1-3 but not 4. The AD group had lower C250 to relevant stimuli in part 1. Both normal aging and dementia cause less differentiation of relevant from irrelevant information in initial storage. There was a large aging effect involving differences in the pattern of C250 responses of the Young Adult versus the Normal Elderly/AD groups. Also, a potential dementia effect was obtained. C250 is a candidate tool for measuring short-term memory performance on a biological level, as well as a potential marker for memory changes due to normal aging and dementia. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  4. Suberoylanilide hydroxamic acid affects γH2AX expression in osteosarcoma, atypical teratoid rhabdoid tumor and normal tissue cell lines after irradiation

    International Nuclear Information System (INIS)

    Blattmann, C.; Oertel, S.; Thiemann, M.; Weber, K.J.; Schmezer, P.; Zelezny, O.; Lopez Perez, R.; Kulozik, A.E.; Debus, J.; Ehemann, V.

    2012-01-01

    Osteosarcoma and atypical teratoid rhabdoid tumors are tumor entities with varying response to common standard therapy protocols. Histone acetylation affects chromatin structure and gene expression which are considered to influence radiation sensitivity. The aim of this study was to investigate the effect of the combination therapy with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and irradiation on atypical teratoid rhabdoid tumors and osteosarcoma compared to normal tissue cell lines. Clonogenic assay was used to determine cell survival. DNA double-strand breaks (DSB) were examined by pulsed-field electrophoresis (PFGE) as well as by γH2AX immunostaining involving flow cytometry, fluorescence microscopy, and immunoblot analysis. SAHA lead to an increased radiosensitivity in tumor but not in normal tissue cell lines. γH2AX expression as an indicator for DSB was significantly increased when SAHA was applied 24 h before irradiation to the sarcoma cell cultures. In contrast, γH2AX expression in the normal tissue cell lines was significantly reduced when irradiation was combined with SAHA. Analysis of initial DNA fragmentation and fragment rejoining by PFGE, however, did not reveal differences in response to the SAHA pretreatment for either cell type. SAHA increases radiosensitivity in tumor but not normal tissue cell lines. The increased H2AX phosphorylation status of the SAHA-treated tumor cells post irradiation likely reflects its delayed dephosphorylation within the DNA damage signal decay rather than chromatin acetylation-dependent differences in the overall efficacy of DSB induction and rejoining. The results support the hypothesis that combining SAHA with irradiation may provide a promising strategy in the treatment of solid tumors. (orig.)

  5. The anabolic activity of bone tissue, suppressed by disuse, is normalized by brief exposure to extremely low-magnitude mechanical stimuli

    Science.gov (United States)

    Rubin, C.; Xu, G.; Judex, S.

    2001-01-01

    It is generally believed that mechanical signals must be large in order to be anabolic to bone tissue. Recent evidence indicates, however, that extremely low-magnitude (bone formation if induced at a high frequency. We examined the ability of extremely low-magnitude, high-frequency mechanical signals to restore anabolic bone cell activity inhibited by disuse. Adult female rats were randomly assigned to six groups: baseline control, age-matched control, mechanically stimulated for 10 min/day, disuse (hind limb suspension), disuse interrupted by 10 min/day of weight bearing, and disuse interrupted by 10 min/day of mechanical stimulation. After a 28 day protocol, bone formation rates (BFR) in the proximal tibia of mechanically stimulated rats increased compared with age-matched control (+97%). Disuse alone reduced BFR (-92%), a suppression only slightly curbed when disuse was interrupted by 10 min of weight bearing (-61%). In contrast, disuse interrupted by 10 min per day of low-level mechanical intervention normalized BFR to values seen in age-matched controls. This work indicates that this noninvasive, extremely low-level stimulus may provide an effective biomechanical intervention for the bone loss that plagues long-term space flight, bed rest, or immobilization caused by paralysis.

  6. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides.

    Directory of Open Access Journals (Sweden)

    Caghan Kizil

    Full Text Available Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI, RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs and identified two- polyR and Trans - that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael's addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues.

  7. In-vivo tissue uptake and retention of Sn-117m(4+)DTPA in a human subject with metastatic bone pain and in normal mice

    International Nuclear Information System (INIS)

    Swailem, Fayez M.; Krishnamurthy, Gerbail T.; Srivastava, Suresh C.; Aguirre, Maria L.; Ellerson, Dawn L.; Walsh, T. Kent; Simpson, Laura

    1998-01-01

    Organ and tissue uptake and retention of Sn-117m(4+)DTPA were studied in a human subject treated for metastatic bone pain, and the results were compared with the biodistribution studies in five normal mice. The explanted organs from a patient who received a therapy dose of 18.6 mCi (688.2 MBq) Sn-117m(4+)DTPA and who died 47 days later were imaged with a γ-camera, and tissue samples were counted and also autoradiographed. Bone, muscle, liver, fat, lungs, kidneys, spleen, heart and pancreas tissue samples were assayed in a well counter for radioactivity. Regions of interest were drawn over bone and major organs to calculate and quantify clearance times using three in vivo Sn-117m(4+)DTPA whole-body scintigrams acquired at 1, 24 and 168 h after injection. Five normal mice injected with the same batch of Sn-117m(4+)DTPA as used for the human subject were sacrificed at 24 h, and tissue samples were collected and assayed for radioactivity for comparison with the human data. For the human subject, whole-body retention at 47 days postinjection was 81% of the injected dose, and the rest (19%) was excreted in urine. Of the whole-body retained activity at 47 days, 82.4% was in bone, 7.8% in the muscle and 1.5% in the liver, and the rest was distributed among other tissues. γ-Ray scintigrams and electron autoradiographs of coronal slices of the thoracolumbar vertebral body showed heterogenous metastatic involvement with normal bone between metastatic lesions. There was nonuniform distribution of radioactivity even within a single vertebral body, indicating normal bone between metastatic lesions. Lesion-to-nonlesion ratios ranged from 3 to 5. However, the osteoid-to-marrow cavity deposition ratio, from the microautoradiographs, was 11:1. The peak uptake in the human bone was seen at 137 h with no biological clearance. Soft tissues showed peak uptake at 1 h and exhibited three compartmental clearance components. Whole-body retention in normal mice was 38.7% of the injected

  8. Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics.

    Directory of Open Access Journals (Sweden)

    Maryna Perepelyuk

    Full Text Available Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G' and G" and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver.

  9. High-risk human papilloma virus in archival tissues of oral pathosis and normal oral mucosa

    Directory of Open Access Journals (Sweden)

    Raghu Dhanapal

    2015-01-01

    Full Text Available Objectives: Oral cancer ranks third among all cancers in the Indian population. Human papilloma virus (HPV plays a significant role in oral carcinogenesis. Population-based subtype variations are present in the HPV prevalence. This study gives an emphasis on the parameters to be considered in formalin fixed paraffin embedded tissues for polymerase chain reaction (PCR-based research work. Materials and Methods: Cross-sectional study on archival paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC, epithelial dysplasia, and normal oral mucosa surrounding impacted tooth was amplified by PCR for the E6 gene of HPV type 16 and E1 gene of HPV type 18. Results: HPV 18 was positive in three OSCC cases. There was no statistically significant association of the positivity of HPV with the age, gender or habit. The HPV positive patients had a tobacco habit and were of a younger age group. Conclusion: The presence of HPV in carcinomatous tissue highlights the possible role of HPV in carcinogenesis and archival paraffin embedded tissue specimen can be used for this analysis. Recent studies on genomic analyses have highlighted that the HPV positive tumors are a separate subgroup based on genomic sequencing. The results of a larger retrospective study will help further in our understanding of the role of HPV in carcinogenesis, this study could form the baseline for such follow-up studies.

  10. High-risk human papilloma virus in archival tissues of oral pathosis and normal oral mucosa.

    Science.gov (United States)

    Dhanapal, Raghu; Ranganathan, K; Kondaiah, Paturu; Devi, R Uma; Joshua, Elizabeth; Saraswathi, T R

    2015-01-01

    Oral cancer ranks third among all cancers in the Indian population. Human papilloma virus (HPV) plays a significant role in oral carcinogenesis. Population-based subtype variations are present in the HPV prevalence. This study gives an emphasis on the parameters to be considered in formalin fixed paraffin embedded tissues for polymerase chain reaction (PCR)-based research work. Cross-sectional study on archival paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC), epithelial dysplasia, and normal oral mucosa surrounding impacted tooth was amplified by PCR for the E6 gene of HPV type 16 and E1 gene of HPV type 18. HPV 18 was positive in three OSCC cases. There was no statistically significant association of the positivity of HPV with the age, gender or habit. The HPV positive patients had a tobacco habit and were of a younger age group. The presence of HPV in carcinomatous tissue highlights the possible role of HPV in carcinogenesis and archival paraffin embedded tissue specimen can be used for this analysis. Recent studies on genomic analyses have highlighted that the HPV positive tumors are a separate subgroup based on genomic sequencing. The results of a larger retrospective study will help further in our understanding of the role of HPV in carcinogenesis, this study could form the baseline for such follow-up studies.

  11. Relaxation time of normal breast tissues. Changes with age and variations during the menstrual cycle

    International Nuclear Information System (INIS)

    Dean, K.I.; Majurin, M.L.; Komu, M.

    1994-01-01

    The influence of age on the relaxation times of normal breast parenchyma and its surrounding fatty tissue were evaluated, and the variations during a normal menstrual cycle were analyzed using an ultra low field 0.02 T imager. Thirty-nine healthy volunteers aged 21 to 59 years were examined to determine T1 and T2 relaxation times, and 8 of these volunteers were studied once weekly during one menstrual cycle. The only significant trend was an increase in the T2 of breast parenchyma with increasing age. During the menstrual cycle there was a slight but insignificant (p=0.10) increase in T1 of the breast parenchyma values during the latter half of the menstrual cycle, and a corresponding increase in T2 values between the 2nd and 3rd weeks of the menstrual cycle, which was significant. (orig.)

  12. Relaxation time of normal breast tissues. Changes with age and variations during the menstrual cycle

    Energy Technology Data Exchange (ETDEWEB)

    Dean, K.I. (University Central Hospital, Turku (Finland). Dept. of Diagnostic Radiology); Majurin, M.L. (University Central Hospital, Turku (Finland). Dept. of Diagnostic Radiology); Komu, M. (University Central Hospital, Turku (Finland). Dept. of Diagnostic Radiology)

    1994-05-01

    The influence of age on the relaxation times of normal breast parenchyma and its surrounding fatty tissue were evaluated, and the variations during a normal menstrual cycle were analyzed using an ultra low field 0.02 T imager. Thirty-nine healthy volunteers aged 21 to 59 years were examined to determine T1 and T2 relaxation times, and 8 of these volunteers were studied once weekly during one menstrual cycle. The only significant trend was an increase in the T2 of breast parenchyma with increasing age. During the menstrual cycle there was a slight but insignificant (p=0.10) increase in T1 of the breast parenchyma values during the latter half of the menstrual cycle, and a corresponding increase in T2 values between the 2nd and 3rd weeks of the menstrual cycle, which was significant. (orig.).

  13. Segmentation and labeling of the ventricular system in normal pressure hydrocephalus using patch-based tissue classification and multi-atlas labeling

    Science.gov (United States)

    Ellingsen, Lotta M.; Roy, Snehashis; Carass, Aaron; Blitz, Ari M.; Pham, Dzung L.; Prince, Jerry L.

    2016-03-01

    Normal pressure hydrocephalus (NPH) affects older adults and is thought to be caused by obstruction of the normal flow of cerebrospinal fluid (CSF). NPH typically presents with cognitive impairment, gait dysfunction, and urinary incontinence, and may account for more than five percent of all cases of dementia. Unlike most other causes of dementia, NPH can potentially be treated and the neurological dysfunction reversed by shunt surgery or endoscopic third ventriculostomy (ETV), which drain excess CSF. However, a major diagnostic challenge remains to robustly identify shunt-responsive NPH patients from patients with enlarged ventricles due to other neurodegenerative diseases. Currently, radiologists grade the severity of NPH by detailed examination and measurement of the ventricles based on stacks of 2D magnetic resonance images (MRIs). Here we propose a new method to automatically segment and label different compartments of the ventricles in NPH patients from MRIs. While this task has been achieved in healthy subjects, the ventricles in NPH are both enlarged and deformed, causing current algorithms to fail. Here we combine a patch-based tissue classification method with a registration-based multi-atlas labeling method to generate a novel algorithm that labels the lateral, third, and fourth ventricles in subjects with ventriculomegaly. The method is also applicable to other neurodegenerative diseases such as Alzheimer's disease; a condition considered in the differential diagnosis of NPH. Comparison with state of the art segmentation techniques demonstrate substantial improvements in labeling the enlarged ventricles, indicating that this strategy may be a viable option for the diagnosis and characterization of NPH.

  14. of the stomach (ID 345), neutralisation of gastric acid (ID 345), contribution to normal formation of collagen and connective tissue (ID 287, 288, 333, 334, 335, 1405, 1652, 1718, 1719, 1945), maintenance of normal bone (ID 287, 335, 1652, 1718, 1945), maintenance of normal joints (ID 1405, 1652, 1945

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to silicon and protection against aluminium accumulation in the brain, cardiovascular health, forming a protective coat on the mucous membrane of the stomach, neutralisation of gastric acid, contribution to normal formation of collagen and connective tissue, maintenance of normal bone...

  15. Discrimination of prostate cancer from normal peripheral zone and central gland tissue by using dynamic contrast-enhanced MR imaging

    NARCIS (Netherlands)

    Engelbrecht, Marc R.; Huisman, Henkjan J.; Laheij, Robert J. F.; Jager, Gerrit J.; van Leenders, Geert J. L. H.; Hulsbergen-van de Kaa, Christina A.; de La Rosette, Jean J. M. C. H.; Blickman, Johan G.; Barentsz, Jelle O.

    2003-01-01

    PURPOSE: To evaluate which parameters of dynamic magnetic resonance (MR) imaging and T2 relaxation rate would result in optimal discrimination of prostatic carcinoma from normal peripheral zone (PZ) and central gland (CG) tissues and to correlate these parameters with tumor stage, Gleason score,

  16. Comparison between β-thalassemia minor and normal individuals using the Wechsler Adult Intelligence Scale.

    Science.gov (United States)

    Zangiabadi, Nasser; Yarahmadi, Fahimeh; Darekordi, Ali; Shabani, Mohammad; Dadgar, Mehrak Memaran

    2013-01-01

    The present study aimed at investigating and comparing patients suffering from β-thalassemia (β-thal) minor with normal individuals in regard to their performances in the short version of the Wechsler Adult Intelligence Scale (WAIS) test. Patients with β-thal minor are carriers of β-thal genes. They have mild microcytic and hypochromic anemia and are usually asymptomatic. In this cross-sectional study, a total of 60 individuals were divided into two equal groups of β-thal minor and normal subjects; they were then studied by the WAIS subscales. The mean performance scores of the normal group in the subtests of arithmetic and vocabulary (p <0.01) and picture completion (p <0.05) were higher than those of the thalassemia group. The mean performance score and ability of the normal group on the verbal scale was higher in comparison to the thalassemia group (p <0.05), while on the non verbal scale, there was no significant difference between the two groups. It can be concluded that β-thal minor negatively influences verbal fluency, reasoning and conceptualization, and sequencing tasks, perceptual skill, prediction of social situations and abstract thinking.

  17. Is NAA reduction in normal contralateral cerebral tissue in stroke patients dependent on underlying risk factors?

    Science.gov (United States)

    Walker, P M; Ben Salem, D; Giroud, M; Brunotte, F

    2006-05-01

    This retrospective study investigated the dependence of N-acetyl aspartate (NAA) ratios on risk factors for cerebral vasculopathy such as sex, age, hypertension, diabetes mellitus, carotid stenosis, and dyslipidaemia, which may have affected brain vessels and induced metabolic brain abnormalities prior to stroke. We hypothesise that in stroke patients metabolic alterations in the apparently normal contralateral brain are dependent on the presence or not of such risk factors. Fifty nine patients (31 male, 28 female: 58.8+/-16.1 years old) with cortical middle cerebral artery (MCA) territory infarction were included. Long echo time chemical shift imaging spectroscopy was carried out on a Siemens 1.5 T Magnetom Vision scanner using a multi-voxel PRESS technique. Metabolite ratios (NAA/choline, NAA/creatine, lactate/choline, etc) were studied using uni- and multivariate analyses with respect to common risk factors. The influence of age, stroke lesion size, and time since stroke was studied using a linear regression approach. Age, sex, and hypertension all appeared to individually influence metabolite ratios, although only hypertension was significant after multivariate analysis. In both basal ganglia and periventricular white matter regions in apparently normal contralateral brain, the NAA/choline ratio was significantly lower in hypertensive (1.37+/-0.16 and 1.50+/-0.19, respectively) than in normotensive patients (1.72+/-0.19 and 1.85+/-0.15, respectively). Regarding MCA infarction, contralateral tissue remote from the lesion behaves abnormally in the presence of hypertension, the NAA ratios in hypertensive patients being significantly lower. These data suggest that hypertension may compromise the use of contralateral tissue data as a reference for comparison with ischaemic tissue.

  18. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    Science.gov (United States)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; hide

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  19. Effect of virtual reality exercise using the nintendo wii fit on muscle activities of the trunk and lower extremities of normal adults.

    Science.gov (United States)

    Park, Jungseo; Lee, Daehee; Lee, Sangyong

    2014-02-01

    [Purpose] The present study aimed to determine the effect of virtual reality exercise using the Nintendo Wii Fit on the muscle activities of the trunk and lower extremities of normal adults. [Subjects] The subjects of the study were 24 normal adults who were divided into a virtual reality exercise group (VREG, n=12) and a stable surface exercise group (SEG, n=12). [Methods] The exercises of the VREG using the Nintendo Wii Fit and the SEG using a stable surface were conducted three times a week for six weeks. Electromyography was used to measure the muscle activities of the tibialis anterior (TA), medial gastrocnemius (MG), erector spinae (ES), and rectus abdominal (RA) muscles. [Results] VREG showed significant within group differences in TA and MG muscle activities, while the SEG showed a significant difference in the muscle activity of the MG. [Conclusion] Virtual reality exercise using the Nintendo Wii Fit was an effective intervention for the muscle activities of the TA and MG of normal adults.

  20. Adult opossums (Didelphis virginiana) demonstrate near normal locomotion after spinal cord transection as neonates.

    Science.gov (United States)

    Wang, X M; Basso, D M; Terman, J R; Bresnahan, J C; Martin, G F

    1998-05-01

    When the thoracic spinal cord of the North American opossum (Didelphis virginiana) is transected on postnatal day (PD) 5, the site of injury becomes bridged by histologically recognizable spinal cord and axons which form major long tracts grow through the lesion. In the present study we asked whether opossums lesioned on PD5 have normal use of the hindlimbs as adults and, if so, whether that use is dependent upon axons which grow through the lesion site. The thoracic spinal cord was transected on PD5 and 6 months later, hindlimb function was evaluated using the Basso, Beattie, and Bresnahan (BBB) locomotor scale. All animals supported their weight with the hindlimbs and used their hindlimbs normally during overground locomotion. In some cases, the spinal cord was retransected at the original lesion site or just caudal to it 6 months after the original transection and paralysis of the hindlimbs ensued. Surprisingly, however, these animals gradually recovered some ability to support their weight and to step with the hindlimbs. Similar recovery was not seen in animals transected only as adults. In order to verify that descending axons which grew through the lesion during development were still present in the adult animal, opossums subjected to transection of the thoracic cord on PD5 were reoperated and Fast blue was injected several segments caudal to the lesion. In all cases, neurons were labeled rostral to the lesion in each of the spinal and supraspinal nuclei labeled by comparable injections in unlesioned, age-matched controls. The results of orthograde tracing studies indicated that axons which grew through the lesion innervated areas that were appropriate for them. Copyright 1998 Academic Press.

  1. SU-F-T-150: Comparing Normal Tissue Irradiated Volumes for Proton Vs. Photon Treatment Plans On Lung Patients

    Energy Technology Data Exchange (ETDEWEB)

    Liu, A; Mohan, R; Liao, Z [UT MD Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: The aim of this work is to compare the “irradiated volume” (IRV) of normal tissues receiving 5, 20, 50, 80 and 90% or higher of the prescription dose with passively scattered proton therapy (PSPT) vs. IMRT of lung cancer patients. The overall goal of this research is to understand the factors affecting outcomes of a randomized PSPT vs. IMRT lung trial. Methods: Thirteen lung cancer patients, selected randomly, were analyzed. Each patient had PSPT and IMRT 74 Gy (RBE) plans meeting the same normal tissue constraints generated. IRVs were created for pairs of IMRT and PSPT plans on each patient. The volume of iGTV, (respiratory motion-incorporated GTV) was subtracted from each IRV to create normal tissue irradiated volume IRVNT. The average of IRVNT DVHs over all patients was also calculated for both modalities and inter-compared as were the selected dose-volume indices. Probability (p value) curves were calculated based on the Wilcoxon matched-paired signed-rank test to determine the dose regions where the statistically significant differences existed. Results: As expected, the average 5, 20 and 50% IRVNT’s for PSPT was found to be significantly smaller than for IMRT (p < 0.001, 0.01, and 0.001 respectively). However, the average 90% IRVNT for PSPT was greater than for IMRT (p = 0.003) presumably due to larger penumbra of protons and the long range of protons in lower density media. The 80% IRVNT for PSPT was also larger but not statistically distinguishable (p = .224). Conclusion: PSPT modality has smaller irradiated volume at lower doses, but larger volume at high doses. A larger cohort of lung patients will be analyzed in the future and IRVNT of patients treated with PSPT and IMRT will be compared to determine if the irradiated volumes (the magnitude of “dose bath”) correlate with outcomes.

  2. mRNA Quantification of NIPBL Isoforms A and B in Adult and Fetal Human Tissues, and a Potentially Pathological Variant Affecting Only Isoform A in Two Patients with Cornelia de Lange Syndrome

    Directory of Open Access Journals (Sweden)

    Beatriz Puisac

    2017-02-01

    Full Text Available Cornelia de Lange syndrome (CdLS is a congenital developmental disorder characterized by craniofacial dysmorphia, growth retardation, limb malformations, and intellectual disability. Approximately 60% of patients with CdLS carry a recognizable pathological variant in the NIPBL gene, of which two isoforms, A and B, have been identified, and which only differ in the C-terminal segment. In this work, we describe the distribution pattern of the isoforms A and B mRNAs in tissues of adult and fetal origin, by qPCR (quantitative polymerase chain reaction. Our results show a higher gene expression of the isoform A, even though both seem to have the same tissue distribution. Interestingly, the expression in fetal tissues is higher than that of adults, especially in brain and skeletal muscle. Curiously, the study of fibroblasts of two siblings with a mild CdLS phenotype and a pathological variant specific of the isoform A of NIPBL (c.8387A > G; P.Tyr2796Cys, showed a similar reduction in both isoforms, and a normal sensitivity to DNA damage. Overall, these results suggest that the position of the pathological variant at the 3´ end of the NIPBL gene affecting only isoform A, is likely to be the cause of the atypical mild phenotype of the two brothers.

  3. Fibrochondrogenic potential of synoviocytes from osteoarthritic and normal joints cultured as tensioned bioscaffolds for meniscal tissue engineering in dogs

    Directory of Open Access Journals (Sweden)

    Jennifer J. Warnock

    2014-09-01

    Full Text Available Meniscal tears are a common cause of stifle lameness in dogs. Use of autologous synoviocytes from the affected stifle is an attractive cell source for tissue engineering replacement fibrocartilage. However, the diseased state of these cells may impede in vitro fibrocartilage formation. Synoviocytes from 12 osteoarthritic (“oaTSB” and 6 normal joints (“nTSB” were cultured as tensioned bioscaffolds and compared for their ability to synthesize fibrocartilage sheets. Gene expression of collagens type I and II were higher and expression of interleukin-6 was lower in oaTSB versus nTSB. Compared with nTSB, oaTSB had more glycosaminoglycan and alpha smooth muscle staining and less collagen I and II staining on histologic analysis, whereas collagen and glycosaminoglycan quantities were similar. In conclusion, osteoarthritic joint—origin synoviocytes can produce extracellular matrix components of meniscal fibrocartilage at similar levels to normal joint—origin synoviocytes, which makes them a potential cell source for canine meniscal tissue engineering.

  4. The influences of silent cerebral infarction and hypertension on brain atrophy in normal adults

    International Nuclear Information System (INIS)

    Zhefeng, Quan; Bokura, Hirokazu; Iijima, Kenichi; Oguro, Hiroaki; Yamaguchi, Shuhei

    2008-01-01

    We studied the influences of silent brain infarction (SBI) and hypertension on brain atrophy and its longitudinal progression in healthy adults. MRI scans were performed on 109 neurologically normal adults (mean age, 58.6±5.8 years), with follow-up at an average of 4.9 years later. Patient histories of hypertension, smoking habits, and alcohol consumption were examined. We evaluated brain atrophy using the brain atrophy index (BAI; the ratio of the brain area to the intracranial area) and the ventricular atrophy index (VAI; the ratio of the ventricular area to the brain area) on MRI T1-weighted images at the levels of the basal ganglia and lateral ventricle in horizontal sections. There were no differences in age, sex, dyslipidemia, body mass index (BMI), smoking habit, and alcohol consumption between the normal group and the SBI or hypertension group. The BAI was significantly lower at entry for the SBI (+) group than for the SBI (-) group at both the basal ganglia and lateral ventricle levels (basal ganglia level, p=0.02; and lateral ventricle level, p=0.05). Moreover, the VAI was significantly higher at entry for the SBI (+) group than for the SBI (-) group at the lateral ventricle level (p=0.03). Furthermore, the BAI was significantly lower at entry for the hypertensive group than for the non-hypertensive group at the basal ganglia level (p=0.007). There were no significant differences in the annual variations of the BAI and VAI between the normal group and the SBI (+) or hypertensive group. The present results suggest that the SBI and hypertension are accelerating factors for brain atrophy and ventricular dilatation. (author)

  5. The influences of silent cerebral infarction and hypertension on brain atrophy in normal adults

    Energy Technology Data Exchange (ETDEWEB)

    Zhefeng, Quan; Bokura, Hirokazu; Iijima, Kenichi; Oguro, Hiroaki; Yamaguchi, Shuhei [Shimane Univ., Faculty of Medicine, Izumo, Shimane (Japan)

    2008-03-15

    We studied the influences of silent brain infarction (SBI) and hypertension on brain atrophy and its longitudinal progression in healthy adults. MRI scans were performed on 109 neurologically normal adults (mean age, 58.6{+-}5.8 years), with follow-up at an average of 4.9 years later. Patient histories of hypertension, smoking habits, and alcohol consumption were examined. We evaluated brain atrophy using the brain atrophy index (BAI; the ratio of the brain area to the intracranial area) and the ventricular atrophy index (VAI; the ratio of the ventricular area to the brain area) on MRI T1-weighted images at the levels of the basal ganglia and lateral ventricle in horizontal sections. There were no differences in age, sex, dyslipidemia, body mass index (BMI), smoking habit, and alcohol consumption between the normal group and the SBI or hypertension group. The BAI was significantly lower at entry for the SBI (+) group than for the SBI (-) group at both the basal ganglia and lateral ventricle levels (basal ganglia level, p=0.02; and lateral ventricle level, p=0.05). Moreover, the VAI was significantly higher at entry for the SBI (+) group than for the SBI (-) group at the lateral ventricle level (p=0.03). Furthermore, the BAI was significantly lower at entry for the hypertensive group than for the non-hypertensive group at the basal ganglia level (p=0.007). There were no significant differences in the annual variations of the BAI and VAI between the normal group and the SBI (+) or hypertensive group. The present results suggest that the SBI and hypertension are accelerating factors for brain atrophy and ventricular dilatation. (author)

  6. Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

    Science.gov (United States)

    Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

    2015-05-26

    Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (Pdistribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (Pdistribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Isolation and genome-wide expression and methylation characterization of CD31+ cells from normal and malignant human prostate tissue

    Science.gov (United States)

    Luo, Wei; Hu, Qiang; Wang, Dan; Deeb, Kristin K.; Ma, Yingyu; Morrison, Carl D.; Liu, Song; Johnson, Candace S.; Trump, Donald L.

    2013-01-01

    Endothelial cells (ECs) are an important component involved in the angiogenesis. Little is known about the global gene expression and epigenetic regulation in tumor endothelial cells. The identification of gene expression and epigenetic difference between human prostate tumor-derived endothelial cells (TdECs) and those in normal tissues may uncover unique biological features of TdEC and facilitate the discovery of new anti-angiogenic targets. We established a method for isolation of CD31+ endothelial cells from malignant and normal prostate tissues obtained at prostatectomy. TdECs and normal-derived ECs (NdECs) showed >90% enrichment in primary culture and demonstrated microvascular endothelial cell characteristics such as cobblestone morphology in monolayer culture, diI-acetyl-LDL uptake and capillary-tube like formation in Matrigel®. In vitro primary cultures of ECs maintained expression of endothelial markers such as CD31, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2. We then conducted a pilot study of transcriptome and methylome analysis of TdECs and matched NdECs from patients with prostate cancer. We observed a wide spectrum of differences in gene expression and methylation patterns in endothelial cells, between malignant and normal prostate tissues. Array-based expression and methylation data were validated by qRT-PCR and bisulfite DNA pyrosequencing. Further analysis of transcriptome and methylome data revealed a number of differentially expressed genes with loci whose methylation change is accompanied by an inverse change in gene expression. Our study demonstrates the feasibility of isolation of ECs from histologically normal prostate and prostate cancer via CD31+ selection. The data, although preliminary, indicates that there exist widespread differences in methylation and transcription between TdECs and NdECs. Interestingly, only a small

  8. SU-E-J-264: Using Magnetic Resonance Imaging-Derived Features to Quantify Radiotherapy-Induced Normal Tissue Morbidity

    Energy Technology Data Exchange (ETDEWEB)

    Thor, M; Tyagi, N; Deasy, J [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2015-06-15

    Purpose: The aim of this study was to explore the use of Magnetic Resonance Imaging (MRI)-derived features as indicators of Radiotherapy (RT)-induced normal tissue morbidity. We also investigate the relationship between these features and RT dose in four critical structures. Methods: We demonstrate our approach for four patients treated with RT for base of tongue cancer in 2005–2007. For each patient, two MRI scans (T1-weighted pre (T1pre) and post (T1post) gadolinium contrast-enhancement) were acquired within the first six months after RT. The assessed morbidity endpoint observed in 2/4 patients was Grade 2+ CTCAEv.3 trismus. Four ipsilateral masticatory-related structures (masseter, lateral and medial pterygoid, and the temporal muscles) were delineated on both T1pre and T1post and these scans were co-registered to the treatment planning CT using a deformable demons algorithm. For each structure, the maximum and mean RT dose, and six MRI-derived features (the second order texture features entropy and homogeneity, and the first order mean, median, kurtosis, and skewness) were extracted and compared structure-wise between patients with and without trismus. All MRI-derived features were calculated as the difference between T1pre and T1post, ΔS. Results: For 5/6 features and all structures, ΔS diverged between trismus and non-trismus patients particularly for the masseter, lateral pterygoid, and temporal muscles using the kurtosis feature (−0.2 vs. 6.4 for lateral pterygoid). Both the maximum and mean RT dose in all four muscles were higher amongst the trismus patients (with the maximum dose being up to 25 Gy higher). Conclusion: Using MRI-derived features to quantify RT-induced normal tissue complications is feasible. We showed that several features are different between patients with and without morbidity and that the RT dose in all investigated structures are higher amongst patients with morbidity. MRI-derived features, therefore, has the potential to

  9. Accuracy of real-time shear wave elastography in the assessment of normal liver tissue in the guinea pig (cavia porcellus).

    Science.gov (United States)

    Glińska-Suchocka, K; Kubiak, K; Spużak, J; Jankowski, M; Borusewicz, P

    2017-03-28

    Shear wave elastography is a novel technique enabling real-time measurement of the elasticity of liver tissue. The color map is superimposed on the classic ultrasound image of the assessed tissue, which enables a precise evaluation of the stiffness of the liver tissue. The aim of the study was to assess the stiffness of normal liver tissue in the guinea pig using shear wave elastography. The study was carried out on 36 guinea pigs using the SuperSonic Imagine Aixplorer scanner, and a 1 to 6 MH convex SC6-1 transducer. An ultrasound guided Try-Cut liver core needle biopsy was carried out in all the studied animals and the collected samples were examined to exclude pathological lesions. The mean liver tissue stiffness ranged from 0.89 to 5.40 kPa. We found that shear wave elastography is an easy, non-invasive technique that can be used to assess the stiffness of liver tissue. The obtained results can be used in future studies to assess the types and changes of liver tissue in the course of various types of liver disease.

  10. Age-related changes in normal adult pancreas: MR imaging evaluation

    International Nuclear Information System (INIS)

    Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Sone, Teruki; Noda, Yasufumi; Higaki, Atsushi; Kanki, Akihiko; Tanimoto, Daigo; Higashi, Hiroki

    2012-01-01

    Objective: To investigate age-related changes in normal adult pancreas as identified by magnetic resonance imaging (MRI). Materials and methods: We examined 115 patients without pancreatic diseases (21–90 years) who underwent upper abdominal MRI to evaluate the normal pancreatic MRI findings related to aging. The parameters examined were the pancreatic anteroposterior (AP) diameter, pancreatic lobulation, pancreatic signal intensity (SI), depiction of the main pancreatic duct (MPD), grade of the visual SI decrease on the opposed-phase T1-weighted images compared with in-phase images, and enhancement effect of the pancreas in the arterial phase of dynamic imaging. Results: The pancreatic AP diameter significantly reduced (head, p = 0.0172; body, p = 0.0007; tail, p < 0.0001), and lobulation (p < 0.0001) and parenchymal fatty change (p < 0.0001) became more evident with aging. No significant correlation was observed between aging and pancreatic SI, however the SI on the in-phase T1-weighted images tended to decrease with aging. No significant correlation was observed between aging and the depiction of the MPD as well as aging and contrast enhancement. Conclusion: MRI findings of pancreatic atrophy, lobulation, and fatty degeneration are characteristic changes related to aging, and it is necessary to recognize these changes in the interpretation of abdominal MRI in patients with and without pancreatic disease

  11. Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

    Directory of Open Access Journals (Sweden)

    Saurabh Chattopadhyay

    Full Text Available Angiotensin-converting enzyme (ACE regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS. Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

  12. Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

    Science.gov (United States)

    Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

    2014-01-01

    Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

  13. Normal reference values for vertebral artery flow volume by color Doppler sonography in Korean adults

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    Hong, Hyun Sook; Cha, Jang Gyu; Park, Seong Jin; Joh, Joon Hee; Park, Jai Soung; Kim, Dae Ho; Lee, Hae Kyung; Ahn, Hyun Cheol [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of)

    2003-09-15

    Vertebrobasilar ischemia has been attributed to a reduction of net vertebral artery flow volume. This study was to establish the reference values for the flow volume of the vertebral artery using color Doppler sonography in the normal Korea adults. Thirty five normal Korea adults without any underlying disease including hypertension, hyperlipidemia, diabetes, heart disease, obesity (body mas index>30), or carotid artery stenosis was included. There were 17 males and 18 females, age ranged from 20 to 53 years (average=32.86 years). Flow velocities and vessel diameters were recorded in the intertransverse (V2) segment, usually at C5-6 level, bilaterally. The flow volume (Q) was calculated. (Q=time averaged mean velocity x cross sectional area of vessel) A lower Flow velocity and smaller vessel diameter were measured on the right side compared to those of the left side, resulting in a lower flow volume. The calculated flow volumes using the equation were 77.0 +- 39.7 ml/min for the right side and 127.6 +- 71.0 ml/min for the left side (p=0.0001) while the net vertebral artery flow volume was 204.6 +- 81.8 ml/min. Decrease in the vertebral artery flow volume was statistically significant with advanced age. (r=-0.36, p=0.032). Vertebral artery blood flow volume was 191.20 +- 59.19 ml/min in male, and 217.28 +- 98.67 ml/min in female (p=0.6). The normal range for the net vertebral artery flow volume defined by the 5th to 95th percentiles was between 110.06 and 364.1 ml/min. The normal range for the net vertebral artery flow volume was between 110.06 and 364.1 ml/min. Vertebral artery flow volume decreased with the increase of age. However, gender did not affect the blood flow volume.

  14. Normal reference values for vertebral artery flow volume by color Doppler sonography in Korean adults

    International Nuclear Information System (INIS)

    Hong, Hyun Sook; Cha, Jang Gyu; Park, Seong Jin; Joh, Joon Hee; Park, Jai Soung; Kim, Dae Ho; Lee, Hae Kyung; Ahn, Hyun Cheol

    2003-01-01

    Vertebrobasilar ischemia has been attributed to a reduction of net vertebral artery flow volume. This study was to establish the reference values for the flow volume of the vertebral artery using color Doppler sonography in the normal Korea adults. Thirty five normal Korea adults without any underlying disease including hypertension, hyperlipidemia, diabetes, heart disease, obesity (body mas index>30), or carotid artery stenosis was included. There were 17 males and 18 females, age ranged from 20 to 53 years (average=32.86 years). Flow velocities and vessel diameters were recorded in the intertransverse (V2) segment, usually at C5-6 level, bilaterally. The flow volume (Q) was calculated. (Q=time averaged mean velocity x cross sectional area of vessel) A lower Flow velocity and smaller vessel diameter were measured on the right side compared to those of the left side, resulting in a lower flow volume. The calculated flow volumes using the equation were 77.0 ± 39.7 ml/min for the right side and 127.6 ± 71.0 ml/min for the left side (p=0.0001) while the net vertebral artery flow volume was 204.6 ± 81.8 ml/min. Decrease in the vertebral artery flow volume was statistically significant with advanced age. (r=-0.36, p=0.032). Vertebral artery blood flow volume was 191.20 ± 59.19 ml/min in male, and 217.28 ± 98.67 ml/min in female (p=0.6). The normal range for the net vertebral artery flow volume defined by the 5th to 95th percentiles was between 110.06 and 364.1 ml/min. The normal range for the net vertebral artery flow volume was between 110.06 and 364.1 ml/min. Vertebral artery flow volume decreased with the increase of age. However, gender did not affect the blood flow volume.

  15. Can fruits and vegetables be used as substitute phantoms for normal human brain tissues in magnetic resonance imaging?

    International Nuclear Information System (INIS)

    Teramoto, Daisuke; Ushioda, Yuichi; Sasaki, Ayaka; Sakurai Yuki; Nagahama, Hiroshi; Nakamura, Manami; Sugimori, Hiroyuki; Sakata, Motomichi

    2013-01-01

    Various custom-made phantoms designed to optimize magnetic resonance imaging (MRI) sequences have been created and subsequently reported in Japanese Society of Radiological Technology (JSRT). However, custom-made phantoms that correctly match the T 1 -value and T 2 -values of human brain tissue (gray matter and white matter) cannot be made easily or quickly. The aim of this project was to search for alternative materials, such as fruits and vegetables, for optimizing MRI sequences. The following eight fruits and vegetables were investigated: apple, tomato, melon, apple mango (Mangifera indica), banana, avocado, peach, and eggplant. Their potential was studied for use in modeling phantoms of normal human brain tissues. MRI (T 1 - and T 2 -weighted sequences) was performed on the human brain and the fruits and vegetables using various concentrations of contrast medium (gadolinium) in the same size tubes as the custom-made phantom. The authors compared the signal intensity (SI) in human brain tissue (gray matter and white matter) with that of the fruits and the custom-made phantom. The T 1 and T 2 values were measured for banana tissue and compared with those for human brain tissue in the literature. Our results indicated that banana tissue is similar to human brain tissue (both gray matter and white matter). Banana tissue can thus be employed as an alternative phantom for the human brain for the purpose of MRI. (author)

  16. Spiral wave classification using normalized compression distance: Towards atrial tissue spatiotemporal electrophysiological behavior characterization.

    Science.gov (United States)

    Alagoz, Celal; Guez, Allon; Cohen, Andrew; Bullinga, John R

    2015-08-01

    Analysis of electrical activation patterns such as re-entries during atrial fibrillation (Afib) is crucial in understanding arrhythmic mechanisms and assessment of diagnostic measures. Spiral waves are a phenomena that provide intuitive basis for re-entries occurring in cardiac tissue. Distinct spiral wave behaviors such as stable spiral waves, meandering spiral waves, and spiral wave break-up may have distinct electrogram manifestations on a mapping catheter. Hence, it is desirable to have an automated classification of spiral wave behavior based on catheter recordings for a qualitative characterization of spatiotemporal electrophysiological activity on atrial tissue. In this study, we propose a method for classification of spatiotemporal characteristics of simulated atrial activation patterns in terms of distinct spiral wave behaviors during Afib using two different techniques: normalized compressed distance (NCD) and normalized FFT (NFFTD). We use a phenomenological model for cardiac electrical propagation to produce various simulated spiral wave behaviors on a 2D grid and labeled them as stable, meandering, or breakup. By mimicking commonly used catheter types, a star shaped and a circular shaped both of which do the local readings from atrial wall, monopolar and bipolar intracardiac electrograms are simulated. Virtual catheters are positioned at different locations on the grid. The classification performance for different catheter locations, types and for monopolar or bipolar readings were also compared. We observed that the performance for each case differed slightly. However, we found that NCD performance is superior to NFFTD. Through the simulation study, we showed the theoretical validation of the proposed method. Our findings suggest that a qualitative wavefront activation pattern can be assessed during Afib without the need for highly invasive mapping techniques such as multisite simultaneous electrogram recordings.

  17. Comparison of radiosensitivities of human autologous normal and neoplastic thyroid epithelial cells

    International Nuclear Information System (INIS)

    Miller, R.C.; Kopecky, K.J.; Hiraoka, T.; Ezaki, H.; Clifton, K.H.

    1986-01-01

    Studies were conducted to examine differences between the radiosensitivities of normal and neoplastic epithelial cells of the human thyroid. Freshly excised thyroid tissues from the tumours of eight patients with papillary carcinoma (PC) and five with follicular adenoma (FA) were cultured in vitro separately from normal thyroid tissue obtained from the surgical margins of the same patients. Plating efficiency of unirradiated control tissue was lower, on average for tumour tissue compared with normal tissue. Radiosensitivity, measured by the 37% inactivation dose D 0 , was greater for carcinoma tissue than for normal tissue in seven out of eight PC cases. Adenomatous tissue was less radiosensitive than normal tissue in four out of five FA cases. This is the first report comparing the radiosensitivity of autologous normal and abnormal epithelial tissue from the human thyroid. (author)

  18. The dynamic DNA methylation landscape of the mutL homolog 1 shore is altered by MLH1-93G>A polymorphism in normal tissues and colorectal cancer.

    Science.gov (United States)

    Savio, Andrea J; Mrkonjic, Miralem; Lemire, Mathieu; Gallinger, Steven; Knight, Julia A; Bapat, Bharat

    2017-01-01

    Colorectal cancers (CRCs) undergo distinct genetic and epigenetic alterations. Expression of mutL homolog 1 ( MLH1 ), a mismatch repair gene that corrects DNA replication errors, is lost in up to 15% of sporadic tumours due to mutation or, more commonly, due to DNA methylation of its promoter CpG island. A single nucleotide polymorphism (SNP) in the CpG island of MLH1 ( MLH1 -93G>A or rs1800734) is associated with CpG island hypermethylation and decreased MLH1 expression in CRC tumours. Further, in peripheral blood mononuclear cell (PBMC) DNA of both CRC cases and non-cancer controls, the variant allele of rs1800734 is associated with hypomethylation at the MLH1 shore, a region upstream of its CpG island that is less dense in CpG sites . To determine whether this genotype-epigenotype association is present in other tissue types, including colorectal tumours, we assessed DNA methylation in matched normal colorectal tissue, tumour, and PBMC DNA from 349 population-based CRC cases recruited from the Ontario Familial Colorectal Cancer Registry. Using the semi-quantitative real-time PCR-based MethyLight assay, MLH1 shore methylation was significantly higher in tumour tissue than normal colon or PBMCs ( P  MLH1 was not associated with MSI status or promoter CpG island hypermethylation, regardless of genotype. To confirm these results, bisulfite sequencing was performed in matched tumour and normal colorectal specimens from six CRC cases, including two cases per genotype (wildtype, heterozygous, and homozygous variant). Bisulfite sequencing results corroborated the methylation patterns found by MethyLight, with significant hypomethylation in normal colorectal tissue of variant SNP allele carriers. These results indicate that the normal tissue types tested (colorectum and PBMC) experience dynamic genotype-associated epigenetic alterations at the MLH1 shore, whereas tumour DNA incurs aberrant hypermethylation compared to normal DNA.

  19. Interleukin-6 Regulates Adult Neural Stem Cell Numbers during Normal and Abnormal Post-natal Development

    Directory of Open Access Journals (Sweden)

    Mekayla A. Storer

    2018-05-01

    Full Text Available Summary: Circulating systemic factors can regulate adult neural stem cell (NSC biology, but the identity of these circulating cues is still being defined. Here, we have focused on the cytokine interleukin-6 (IL-6, since increased circulating levels of IL-6 are associated with neural pathologies such as autism and bipolar disorder. We show that IL-6 promotes proliferation of post-natal murine forebrain NSCs and that, when the IL-6 receptor is inducibly knocked out in post-natal or adult neural precursors, this causes a long-term decrease in forebrain NSCs. Moreover, a transient circulating surge of IL-6 in perinatal or adult mice causes an acute increase in neural precursor proliferation followed by long-term depletion of adult NSC pools. Thus, IL-6 signaling is both necessary and sufficient for adult NSC self-renewal, and acute perturbations in circulating IL-6, as observed in many pathological situations, have long-lasting effects on the size of adult NSC pools. : In this report, Storer and colleagues demonstrate that the circulating cytokine IL-6, which is elevated in humans in different pathological situations, can perturb neural stem cell biology after birth. They show that IL-6 signaling is essential for self-renewal and maintenance of post-natal and adult NSCs in the murine forebrain under normal homeostatic conditions. Keywords: interleukin-6, neural stem cell, adult neurogenesis, CNS cytokines, postnatal brain development, stem cell depletion, neural stem cell niche, circulating stem cell factors, olfactory bulb

  20. Effects of cigarette smoking on cerebral blood flow in normal adults

    Energy Technology Data Exchange (ETDEWEB)

    Shinohara, Takao [Tokyo Medical Coll. (Japan)

    1997-11-01

    To elucidate the pharmacological effects of cigarette smoking on cerebral function and blood flow in normal adults, cerebral blood flow (CBF) was measured by positron emission tomography (PET) in 10 right-handed male healthy volunteers with a smoking habit after 12-hour abstinence. By the oxygen-15 intravenous injection method, quantitative CBF was measured repeatedly 6 times; during normal breathing (baseline), 5% CO{sub 2} inhalation and cigarette smoking. Sham smoking was performed during baseline and CO{sub 2} inhalation. To eliminate the effects from PaCO{sub 2}, CBF was adjusted based on the vascular reactivity to CO{sub 2} and PaCO{sub 2} during smoking. Pulse rate, systemic blood pressure and arterial nicotine level were increased during smoking. In the overall comparison, there was no significant change in the mean CBF during smoking as compared with baseline. Out of 19 sessions, CBF increased significantly in 7 sessions, while CBF decreased in 7 sessions and was unchanged in 5 sessions. The arterial concentration of nicotine correlated inversely with CBF. When the baseline CBF was relatively low, CBF increased during smoking, while it decreased when the baseline value was high. In the 3-dimensional statistical analysis of normalized CBF, a significant increase was seen in the nucleus accumbens, which is assumed to be related to the drug habits or addiction in previous studies. In the first smoking after abstinence, CBF increased in the orbitofrontal gyri, and this can be linked to reward or relaxation. By contrast, a significant decrease was observed in the occipital lobes and paracentral areas. (author)

  1. Effects of cigarette smoking on cerebral blood flow in normal adults

    International Nuclear Information System (INIS)

    Shinohara, Takao

    1997-01-01

    To elucidate the pharmacological effects of cigarette smoking on cerebral function and blood flow in normal adults, cerebral blood flow (CBF) was measured by positron emission tomography (PET) in 10 right-handed male healthy volunteers with a smoking habit after 12-hour abstinence. By the oxygen-15 intravenous injection method, quantitative CBF was measured repeatedly 6 times; during normal breathing (baseline), 5% CO 2 inhalation and cigarette smoking. Sham smoking was performed during baseline and CO 2 inhalation. To eliminate the effects from PaCO 2 , CBF was adjusted based on the vascular reactivity to CO 2 and PaCO 2 during smoking. Pulse rate, systemic blood pressure and arterial nicotine level were increased during smoking. In the overall comparison, there was no significant change in the mean CBF during smoking as compared with baseline. Out of 19 sessions, CBF increased significantly in 7 sessions, while CBF decreased in 7 sessions and was unchanged in 5 sessions. The arterial concentration of nicotine correlated inversely with CBF. When the baseline CBF was relatively low, CBF increased during smoking, while it decreased when the baseline value was high. In the 3-dimensional statistical analysis of normalized CBF, a significant increase was seen in the nucleus accumbens, which is assumed to be related to the drug habits or addiction in previous studies. In the first smoking after abstinence, CBF increased in the orbitofrontal gyri, and this can be linked to reward or relaxation. By contrast, a significant decrease was observed in the occipital lobes and paracentral areas. (author)

  2. Effect of ground cinnamon on postprandial blood glucose concentration in normal-weight and obese adults.

    Science.gov (United States)

    Magistrelli, Ashley; Chezem, Jo Carol

    2012-11-01

    In healthy normal-weight adults, cinnamon reduces blood glucose concentration and enhances insulin sensitivity. Insulin resistance, resulting in increased fasting and postprandial blood glucose and insulin levels, is commonly observed in obese individuals. The objective of the study was to compare declines in postprandial glycemic response in normal-weight and obese subjects with ingestion of 6 g ground cinnamon. In a crossover study, subjects consumed 50 g available carbohydrate in instant farina cereal, served plain or with 6 g ground cinnamon. Blood glucose concentration, the main outcome measure, was assessed at minutes 0, 15, 30, 45, 60, 90, and 120. Repeated-measures analysis of variance evaluated the effects of body mass index (BMI) group, dietary condition, and time on blood glucose. Paired t-test assessed blood glucose at individual time points and glucose area under the curve (AUC) between dietary conditions. Thirty subjects between the ages of 18 and 30 years, 15 with BMIs between 18.5 and 24.9 and 15 with BMIs of 30.0 or more, completed the study. There was no significant difference in blood glucose between the two BMI groups at any time point. However, in a combined analysis of all subjects, the addition of cinnamon to the cereal significantly reduced 120-minute glucose AUC (P=0.008) and blood glucose at 15 (P=0.001), 30 (Pblood glucose was significantly higher with cinnamon consumption (Pglucose response in normal weight and obese adults. Copyright © 2012 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  3. Human adipose tissue from normal and tumoral breast regulates the behavior of mammary epithelial cells.

    Science.gov (United States)

    Pistone Creydt, Virginia; Fletcher, Sabrina Johanna; Giudice, Jimena; Bruzzone, Ariana; Chasseing, Norma Alejandra; Gonzalez, Eduardo Gustavo; Sacca, Paula Alejandra; Calvo, Juan Carlos

    2013-02-01

    Stromal-epithelial interactions mediate both breast development and breast cancer progression. In the present work, we evaluated the effects of conditioned media (CMs) of human adipose tissue explants from normal (hATN) and tumor (hATT) breast on proliferation, adhesion, migration and metalloproteases activity on tumor (MCF-7 and IBH-7) and non-tumor (MCF-10A) human breast epithelial cell lines. Human adipose tissues were obtained from patients and the conditioned medium from hATN and hATT collected after 24 h of incubation. MCF-10A, MCF-7 and IBH-7 cells were grown and incubated with CMs and proliferation and adhesion, as well as migration ability and metalloprotease activity, of epithelial cells after exposing cell cultures to hATN- or hATT-CMs were quantified. The statistical significance between different experimental conditions was evaluated by one-way ANOVA. Tukey's post hoc tests were performed. Tumor and non-tumor breast epithelial cells significantly increased their proliferation activity after 24 h of treatment with hATT-CMs compared to control-CMs. Furthermore, cellular adhesion of these two tumor cell lines was significantly lower with hATT-CMs than with hATN-CMs. Therefore, hATT-CMs seem to induce significantly lower expression or less activity of the components involved in cellular adhesion than hATN-CMs. In addition, hATT-CMs induced pro-MMP-9 and MMP-9 activity and increased the migration of MCF-7 and IBH-7 cells compared to hATN-CMs. We conclude that the microenvironment of the tumor interacts in a dynamic way with the mutated epithelium. This evidence leads to the possibility to modify the tumor behavior/phenotype through the regulation or modification of its microenvironment. We developed a model in which we obtained CMs from adipose tissue explants completely, either from normal or tumor breast. In this way, we studied the contribution of soluble factors independently of the possible effects of direct cell contact.

  4. Normal bone density in male pseudohermaphroditism due to 5a- reductase 2 deficiency

    Directory of Open Access Journals (Sweden)

    Costa Elaine Maria Frade

    2001-01-01

    Full Text Available Bone is an androgen-dependent tissue, but it is not clear whether the androgen action in bone depends on testosterone or on dihydrotestosterone. Patients with 5alpha-reductase 2 deficiency present normal levels of testosterone and low levels of dihydrotestosterone, providing an in vivo human model for the analysis of the effect of testosterone on bone. OBJECTIVE: To analyze bone mineral density in 4 adult patients with male pseudohermaphroditism due to 5alpha-reductase 2 deficiency. RESULTS: Three patients presented normal bone mineral density of the lumbar column (L1-L4 and femur neck, and the other patient presented a slight osteopenia in the lumbar column. CONCLUSION: Patients with dihydrotestosterone deficiency present normal bone mineral density, suggesting that dihydrotestosterone is not the main androgen acting in bone.

  5. Obese adults with primary growth hormone resistance (Laron Syndrome) have normal endothelial function.

    Science.gov (United States)

    Shechter, M; Ginsberg, S; Scheinowitz, M; Feinberg, M S; Laron, Z

    2007-04-01

    Classic Laron Syndrome (LS) is a recessive disease of insulin-like growth factor I (IGF-I) deficiency and primary growth hormone insensitivity, clinically characterized by dwarfism and marked obesity. The aim of the current study was to investigate the impact of long-term IGF-I deficiency on flow-mediated dilation (FMD) in 11 non-IGF-I-treated LS adults with long-term IGF-I deficiency who on stress echocardiography were found to have reduced cardiac dimensions and output, but normal left ventricular (LV) ejection fraction at rest and LV contractile reserve following stress. Following an overnight fast we assessed percent improvement in endothelium-dependent FMD (%FMD) and endothelium-independent nitroglycerin (%NTG)-mediated vasodilation non-invasively in the brachial artery, using high resolution ultrasound in 11 non-treated adult patients with LS without known coronary artery disease, and compared them to 11 age- and sex-matched healthy controls. All subjects underwent symptom-limited exercise testing (Bruce protocol). LS patients had a significantly higher body mass index (29+/-6 vs. 25+/-2 kg/m(2), p=0.04), lower low-density lipoprotein cholesterol (142+/-28 vs. 176+/-12 mg/dl, p=0.03) and a smaller mean brachial artery diameter (4.63+/-0.72 vs. 5.70+/-1.06 mm, p=0.01) compared to controls. However, brachial artery %FMD and %NTG were not significantly different between the LS patients and controls (13.1+/-6.2% vs. 15.4+/-5.2%, p=0.28 and 22.3+/-6.0% vs. 18.9+/-6.2%, p=0.30; respectively). Cardiac performance, assessed by exercise duration time and metabolic equivalents (METs), was significantly greater in control subjects than in LS patients (10.3+/-2.0 vs. 6.0+/-1.4 min, p<0.01 and 10.2+/-2.0 vs. 7.2+/-1.4 METs, p<0.01; respectively). FMD was found to be within normal limits in non-IGF-I-treated adult patients with LS, despite congenital absence of IGF-I and obesity.

  6. A hybrid electron and photon IMRT planning technique that lowers normal tissue integral patient dose using standard hardware.

    Science.gov (United States)

    Rosca, Florin

    2012-06-01

    To present a mixed electron and photon IMRT planning technique using electron beams with an energy range of 6-22 MeV and standard hardware that minimizes integral dose to patients for targets as deep as 7.5 cm. Ten brain cases, two lung, a thyroid, an abdominal, and a parotid case were planned using two planning techniques: a photon-only IMRT (IMRT) versus a mixed modality treatment (E+IMRT) that includes an enface electron beam and a photon IMRT portion that ensures a uniform target coverage. The electron beam is delivered using a regular cutout placed in an electron cone. The electron energy was chosen to provide a good trade-off between minimizing integral dose and generating a uniform, deliverable plan. The authors choose electron energies that cover the deepest part of PTV with the 65%-70% isodose line. The normal tissue integral dose, the dose for ring structures around the PTV, and the volumes of the 75%, 50%, and 25% isosurfaces were used to compare the dose distributions generated by the two planning techniques. The normal tissue integral dose was lowered by about 20% by the E+IMRT plans compared to the photon-only IMRT ones for most studied cases. With the exception of lungs, the dose reduction associated to the E+IMRT plans was more pronounced further away from the target. The average dose ratio delivered to the 0-2 cm and the 2-4 cm ring structures for brain patients for the two planning techniques were 89.6% and 70.8%, respectively. The enhanced dose sparing away from the target for the brain patients can also be observed in the ratio of the 75%, 50%, and 25% isodose line volumes for the two techniques, which decreases from 85.5% to 72.6% and further to 65.1%, respectively. For lungs, the lateral electron beams used in the E+IMRT plans were perpendicular to the mostly anterior/posterior photon beams, generating much more conformal plans. The authors proved that even using the existing electron delivery hardware, a mixed electron/photon planning

  7. Cell kinetical aspect of normal tissue damages in relation to radiosensitivity of cells, especially from the points of LQ model

    International Nuclear Information System (INIS)

    Tsubouchi, Susumu; Oohara, Hiroshi.

    1989-01-01

    Several points on the early and late radiation induced-normal tissue damages in terms of LQ model in multifractionation experiments of isoeffect were discussed from two fractors, (1) dose-responses of cell survivals or of tissue damages and (2) principles of the model. Application of the model to the both early and late tissue damages was fairly difficult in several tissues and several experimental conditions. In early damages, cell survival curve of single irradiation did not always fit to LQ model and further more incomlete repair as well as repopulation in multifractionation experiment contradicted the model especially in low dose fractionation. In late damages, the damages themselves did not express directly cell survival but probably indicate the degree of functional cell damage at the level of 10 -1 . As most isoeffects in early damages were taken at the level of 10 -3 , the comparison of two results from early and late tissue damages indicated the lack of coordinations both conceptionally and experimentally. (author)

  8. Trace element load in cancer and normal lung tissue

    International Nuclear Information System (INIS)

    Kubala-Kukus, A.; Braziewicz, J.; Banas, D.; Majewska, U.; Gozdz, S.; Urbaniak, A.

    1999-01-01

    Samples of malignant and benign human lung tissues were analysed by two complementary methods, i.e., particle induced X-ray emission (PIXE) and total reflection X-ray fluorescence (TRXRF). The concentration of trace elements of P, S, K, Ca, Ti, Cr, Mn, Fe, Cu, Zn, Se, Sr, Hg and Pb was determined in squamous cancer of lung tissue from 65 people and in the benign lung tumour tissue from 5 people. Several elements shows enhancement in cancerous lung tissue of women in comparison to men, i.e., titanium show maximum enhancement by 48% followed by Cr (20%) and Mn (36%). At the same time trace element concentration of Sr and Pb are declaimed by 30% and 20% in women population. Physical basis of used analytical methods, experimental set-up and the procedure of sample preparation are described

  9. Immunobiotic Lactobacillus strains augment NLRP3 expression in newborn and adult porcine gut-associated lymphoid tissues.

    Science.gov (United States)

    Tohno, Masanori; Shimosato, Takeshi; Aso, Hisashi; Kitazawa, Haruki

    2011-12-15

    We isolated cDNA encoding porcine nucleotide-binding domain-like receptor family, pryin domain containing 3 (NLRP3) from Peyer's patches. The complete nucleotide open reading frame of porcine NLRP3 contains 3108-bp encoding a deduced polypeptide of 1036-amino acid residues. The porcine NLRP3 amino acid sequence is more similar to the longest isoform of human than the mouse counterpart. The predicted amino acid sequence of porcine NLRP3 presented nine C-terminal leucine-rich repeat domains. In newborn swine, the expression of NLRP3 was detected at higher levels in spleen and mesenteric lymph nodes, while lower levels were observed in intestinal tissues. In adult swine, NLRP3 was strongly expressed in Peyer's patches and the mesenteric lymph nodes, and the expression level in the lower intestinal tissues was comparable to that in spleen. Toll-like receptor and nucleotide-binding domain ligands, as well as Lactobacillus delbrueckii subsp. bulgaricus and Lactobacillus gasseri, enhanced NLRP3 expression in gut-associated lymphoid tissues (GALT) of newborn and adult swine. Our results should aid in understanding the intestinal immunoregulatory mechanisms underlying NLRP3 activation and the priming ability of immunobiotic lactic acid bacteria in porcine GALT. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) in pediatric and young adult patients: Results from a prospective study using limited-margin radiotherapy.

    Science.gov (United States)

    Tinkle, Christopher L; Fernandez-Pineda, Israel; Sykes, April; Lu, Zhaohua; Hua, Chia-Ho; Neel, Michael D; Bahrami, Armita; Shulkin, Barry L; Kaste, Sue C; Pappo, Alberto; Spunt, Sheri L; Krasin, Matthew J

    2017-11-15

    Indications for and delivery of adjuvant therapies for pediatric nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) have been derived largely from adult studies; therefore, significant concern remains regarding radiation exposure to normal tissue. The authors report long-term treatment outcomes and toxicities for pediatric and young adult patients with high-grade NRSTS who were treated on a prospective trial using limited-margin radiotherapy. Sixty-two patients (ages 3-22 years) with predominantly high-grade NRSTS requiring radiation were treated on a phase 2 institutional study of conformal external-beam radiotherapy and/or brachytherapy using a 1.5-cm to 2-cm anatomically constrained margin. The estimated cumulative incidence of local failure, Gray's method estimated cumulative incidence of local failure, Kaplan-Meier method estimated survival, competing-risk regression model determined predictors of disease outcome, and toxicity was reported according to CTCAE v2.0. At a median follow-up of 5.1 years (range, 0.2-10.9 years), 9 patients had experienced local failure. The 5-year overall cumulative incidence of local failure was 14.8% (95% confidence interval [CI], 7.2%-25%), and all but 1 local failure occurred outside the highest-dose irradiation volume. The 5-year Kaplan-Meier estimates for event-free and overall survival were 49.3% (95% CI, 36.3%-61.1%) and 67.9% (95% CI, 54.2%-78.3%), respectively. Multivariable analysis indicated that younger age was the only independent predictor of local recurrence (P = .004). The 5-year cumulative incidence of grade 3 or 4 late toxicity was 15% (95% CI, 7.2%-25.3%). The delivery of limited-margin radiotherapy using conformal external-beam radiotherapy or brachytherapy provides a high rate of local tumor control without an increase in marginal failures and with acceptable treatment-related morbidity. Cancer 2017;123:4419-29. © 2017 American Cancer Society. © 2017 American Cancer Society.

  11. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    International Nuclear Information System (INIS)

    Guizar-Sahagun, G.; Rivera, F.; Babinski, E.; Berlanga, E.; Madrazo, M.; Franco-Bourland, R.; Grijalva, I.; Gonzalez, J.; Contreras, B.; Madrazo, I.

    1994-01-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  12. Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Guizar-Sahagun, G [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Inst. Mexicano del Seguro Social, Mexico City (Mexico); Rivera, F [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico); Babinski, E [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico); Berlanga, E [Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico); Madrazo, M [Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico); Franco-Bourland, R [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Biochemistry, Inst. Nacional de la Nutricion, Mexico City (Mexico); Grijalva, I [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo

    1994-08-01

    We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

  13. Normal bone and soft tissue distribution of fluorine-18-sodium fluoride and artifacts on 18F-NaF PET/CT bone scan: a pictorial review.

    Science.gov (United States)

    Sarikaya, Ismet; Elgazzar, Abdelhamid H; Sarikaya, Ali; Alfeeli, Mahmoud

    2017-10-01

    Fluorine-18-sodium fluoride (F-NaF) PET/CT is a relatively new and high-resolution bone imaging modality. Since the use of F-NaF PET/CT has been increasing, it is important to accurately assess the images and be aware of normal distribution and major artifacts. In this pictorial review article, we will describe the normal uptake patterns of F-NaF in the bone tissues, particularly in complex structures, as well as its physiologic soft tissue distribution and certain artifacts seen on F-NaF PET/CT images.

  14. Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

    Energy Technology Data Exchange (ETDEWEB)

    Wendler, J. J., E-mail: johann.wendler@med.ovgu.de; Porsch, M.; Huehne, S.; Baumunk, D. [University of Magdeburg, Department of Urology (Germany); Buhtz, P. [Institute of Pathology, University of Magdeburg (Germany); Fischbach, F.; Pech, M. [University of Magdeburg, Department of Radiology (Germany); Mahnkopf, D. [Institute of Medical Technology and Research (Germany); Kropf, S. [Institute of Biometry, University of Magdeburg (Germany); Roessner, A. [Institute of Pathology, University of Magdeburg (Germany); Ricke, J. [University of Magdeburg, Department of Radiology (Germany); Schostak, M.; Liehr, U.-B. [University of Magdeburg, Department of Urology (Germany)

    2013-04-15

    Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

  15. Short- and Mid-term Effects of Irreversible Electroporation on Normal Renal Tissue: An Animal Model

    International Nuclear Information System (INIS)

    Wendler, J. J.; Porsch, M.; Hühne, S.; Baumunk, D.; Buhtz, P.; Fischbach, F.; Pech, M.; Mahnkopf, D.; Kropf, S.; Roessner, A.; Ricke, J.; Schostak, M.; Liehr, U.-B.

    2013-01-01

    Irreversible electroporation (IRE) is a novel nonthermal tissue ablation technique by high current application leading to apoptosis without affecting extracellular matrix. Previous results of renal IRE shall be supplemented by functional MRI and differentiated histological analysis of renal parenchyma in a chronic treatment setting. Three swine were treated with two to three multifocal percutaneous IRE of the right kidney. MRI was performed before, 30 min (immediate-term), 7 days (short-term), and 28 days (mid-term) after IRE. A statistical analysis of the lesion surrounded renal parenchyma intensities was made to analyze functional differences depending on renal part, side and posttreatment time. Histological follow-up of cortex and medulla was performed after 28 days. A total of eight ablations were created. MRI showed no collateral damage of surrounded tissue. The highest visual contrast between lesions and normal parenchyma was obtained by T2-HR-SPIR-TSE-w sequence of DCE-MRI. Ablation zones showed inhomogeneous necroses with small perifocal edema in the short-term and sharp delimitable scars in the mid-term. MRI showed no significant differences between adjoined renal parenchyma around ablations and parenchyma of untreated kidney. Histological analysis demonstrated complete destruction of cortical glomeruli and tubules, while collecting ducts, renal calyxes, and pelvis of medulla were preserved. Adjoined kidney parenchyma around IRE lesions showed no qualitative differences to normal parenchyma of untreated kidney. This porcine IRE study reveals a multifocal renal ablation, while protecting surrounded renal parenchyma and collecting system over a mid-term period. That offers prevention of renal function ablating centrally located or multifocal renal masses.

  16. Differentiation of adult-type Leydig cells occurs in gonadotrophin-deficient mice

    Directory of Open Access Journals (Sweden)

    Charlton HM

    2003-02-01

    Full Text Available Abstract During mammalian testis development distinct generations of fetal and adult Leydig cells arise. Luteinising hormone (LH is required for normal adult Leydig cell function and for the establishment of normal adult Leydig cell number but its role in the process of adult Leydig cell differentiation has remained uncertain. In this study we have examined adult Leydig cell differentiation in gonadotrophin-releasing hormone (GnRH-null mice which are deficient in circulating gonadotrophins. Adult Leydig cell differentiation was assessed by measuring expression of mRNA species encoding four specific markers of adult Leydig cell differentiation in the mouse. Each of these markers (3β-hydroxysteroid dehydrogenase type VI (3βHSD VI, 17β-hydroxysteroid dehydrogenase type III (17βHSD III, prostaglandin D (PGD-synthetase and oestrogen sulphotransferase (EST is expressed only in the adult Leydig cell lineage in the normal adult animal. Real-time PCR studies showed that all four markers are expressed in adult GnRH-null mice. Localisation of 3βHSD VI and PGD-synthetase expression by in situ hybridisation confirmed that these genes are expressed in the interstitial tissue of the GnRH-null mouse. Treatment of animals with human chorionic gonadotrophin increased expression of 3βHSD VI and 17βHSD III within 12 hours further indicating that differentiated, but unstimulated cells already exist in the GnRH-null mouse. Thus, while previous studies have shown that LH is required for adult Leydig cell proliferation and activity, results from the present study show that adult Leydig cell differentiation will take place in animals deficient in LH.

  17. Automated tissue classification of pediatric brains from magnetic resonance images using age-specific atlases

    Science.gov (United States)

    Metzger, Andrew; Benavides, Amanda; Nopoulos, Peg; Magnotta, Vincent

    2016-03-01

    The goal of this project was to develop two age appropriate atlases (neonatal and one year old) that account for the rapid growth and maturational changes that occur during early development. Tissue maps from this age group were initially created by manually correcting the resulting tissue maps after applying an expectation maximization (EM) algorithm and an adult atlas to pediatric subjects. The EM algorithm classified each voxel into one of ten possible tissue types including several subcortical structures. This was followed by a novel level set segmentation designed to improve differentiation between distal cortical gray matter and white matter. To minimize the req uired manual corrections, the adult atlas was registered to the pediatric scans using high -dimensional, symmetric image normalization (SyN) registration. The subject images were then mapped to an age specific atlas space, again using SyN registration, and the resulting transformation applied to the manually corrected tissue maps. The individual maps were averaged in the age specific atlas space and blurred to generate the age appropriate anatomical priors. The resulting anatomical priors were then used by the EM algorithm to re-segment the initial training set as well as an independent testing set. The results from the adult and age-specific anatomical priors were compared to the manually corrected results. The age appropriate atlas provided superior results as compared to the adult atlas. The image analysis pipeline used in this work was built using the open source software package BRAINSTools.

  18. Normal foot and ankle

    International Nuclear Information System (INIS)

    Weissman, S.D.

    1989-01-01

    The foot may be thought of as a bag of bones tied tightly together and functioning as a unit. The bones re expected to maintain their alignment without causing symptomatology to the patient. The author discusses a normal radiograph. The bones must have normal shape and normal alignment. The density of the soft tissues should be normal and there should be no fractures, tumors, or foreign bodies

  19. A new plan-scoring method using normal tissue complication probability for personalized treatment plan decisions in prostate cancer

    Science.gov (United States)

    Kim, Kwang Hyeon; Lee, Suk; Shim, Jang Bo; Yang, Dae Sik; Yoon, Won Sup; Park, Young Je; Kim, Chul Yong; Cao, Yuan Jie; Chang, Kyung Hwan

    2018-01-01

    The aim of this study was to derive a new plan-scoring index using normal tissue complication probabilities to verify different plans in the selection of personalized treatment. Plans for 12 patients treated with tomotherapy were used to compare scoring for ranking. Dosimetric and biological indexes were analyzed for the plans for a clearly distinguishable group ( n = 7) and a similar group ( n = 12), using treatment plan verification software that we developed. The quality factor ( QF) of our support software for treatment decisions was consistent with the final treatment plan for the clearly distinguishable group (average QF = 1.202, 100% match rate, n = 7) and the similar group (average QF = 1.058, 33% match rate, n = 12). Therefore, we propose a normal tissue complication probability (NTCP) based on the plan scoring index for verification of different plans for personalized treatment-plan selection. Scoring using the new QF showed a 100% match rate (average NTCP QF = 1.0420). The NTCP-based new QF scoring method was adequate for obtaining biological verification quality and organ risk saving using the treatment-planning decision-support software we developed for prostate cancer.

  20. Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yu-Zhe Song

    Full Text Available The X-ray repair cross-complementing group 3 (XRCC3 protein plays an important role in the repair of DNA double-strand breaks. The relationship between XRCC3 polymorphisms and the risk of radiation-induced adverse effects on normal tissue remains inconclusive. Thus, we performed a meta-analysis to elucidate the association between XRCC3 polymorphisms and radiation-induced adverse effects on normal tissue. All eligible studies up to December 2014 were identified through a search of the PubMed, Embase and Web of Science databases. Seventeen studies involving 656 cases and 2193 controls were ultimately included in this meta-analysis. The pooled odds ratios (ORs with corresponding 95% confidence intervals (CIs were calculated to evaluate the association between XRCC3 polymorphisms and the risk of radiation-induced normal tissue adverse effects. We found that the XRCC3 p.Thr241Met (rs861539 polymorphism was significantly associated with early adverse effects induced by radiotherapy (OR = 1.99, 95%CI: 1.31-3.01, P = 0.001. A positive association lacking statistical significance with late adverse effects was also identified (OR = 1.28, 95%CI: 0.97-1.68, P = 0.08. In addition, the rs861539 polymorphism was significantly correlated with a higher risk of adverse effects induced by head and neck area irradiation (OR = 2.41, 95%CI: 1.49-3.89, p = 0.0003 and breast irradiation (OR = 1.41, 95%CI: 1.02-1.95, p = 0.04, whereas the correlation was not significant for lung irradiation or pelvic irradiation. Furthermore, XRCC3 rs1799794 polymorphism may have a protective effect against late adverse effects induced by radiotherapy (OR = 0.47, 95%CI: 0.26-0.86, P = 0.01. Well-designed large-scale clinical studies are required to further validate our results.

  1. Normal-tissue radioprotection by overexpression of the copper-zinc and manganese superoxide dismutase genes

    Energy Technology Data Exchange (ETDEWEB)

    Veldwijk, Marlon R. [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Herskind, Carsten; Wenz, Frederik [Dept. of Radiation Oncology, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Sellner, Leopold; Zeller, W. Jens [Pharmacology of Cancer Treatment (G402), German Cancer Research Center, Heidelberg (Germany); Radujkovic, Aleksandar [Dept. of Internal Medicine V, Univ. of Heidelberg (Germany); Laufs, Stephanie [Dept. of Experimental Surgery, Univ. Medical Center Mannheim, Univ. of Heidelberg, Mannheim (Germany); Molecular Oncology of Solid Tumors (G360), German Cancer Research Center, Heidelberg (Germany); Fruehauf, Stefan [Center for Tumor Diagnostic and Therapy, Paracelsus-Klinik, Osnabrueck (Germany)

    2009-08-15

    Background and Purpose: Protection of normal tissue against radiation-induced damage may increase the therapeutic ratio of radiotherapy. A promising strategy for testing this approach is gene therapy-mediated overexpression of the copper-zinc (CuZnSOD) or manganese superoxide dismutase (MnSOD) using recombinant adeno-associated viral (rAAV2) vectors. The purpose of this study was to test the modulating effects of the SOD genes on human primary lung fibroblasts (HPLF) after irradiation. Material and Methods: HPLF were transduced with rAAV2 vectors containing cDNA for the CuZnSOD, MnSOD or a control gene. The cells were irradiated (1-6 Gy), and gene transfer efficiency, apoptosis, protein expression/activity, and radiosensitivity measured by the colony-forming assay determined. Results: After transduction, 90.0% {+-} 6.4% of the cells expressed the transgene. A significant fivefold overexpression of both SOD was confirmed by an SOD activity assay (control: 21.1 {+-} 12.6, CuZnSOD: 95.1 {+-} 17.1, MnSOD: 108.5 {+-} 36.0 U SOD/mg protein) and immunohistochemistry. CuZnSOD and MnSOD overexpression resulted in a significant radioprotection of HPLF compared to controls (surviving fraction [SF] ratio SOD/control > 1): CuZnSOD: 1.18-fold (95% confidence interval [CI]: 1.06-1.32; p = 0.005), MnSOD: 1.23-fold (95% CI: 1.07-1.43; p = 0.01). Conclusion: Overexpression of CuZnSOD and MnSOD in HPLF mediated an increase in clonogenic survival after irradiation compared to controls. In previous works, a lack of radioprotection in SOD-overexpressing tumor cells was observed. Therefore, the present results suggest that rAAV2 vectors are promising tools for the delivery of radioprotective genes in normal tissue. (orig.)

  2. Tracing the destiny of mesenchymal stem cells from embryo to adult bone marrow and white adipose tissue via Pdgfrα expression.

    Science.gov (United States)

    Miwa, Hiroyuki; Era, Takumi

    2018-01-29

    Mesenchymal stem cells (MSCs) are somatic stem cells that can be derived from adult bone marrow (BM) and white adipose tissue (WAT), and that display multipotency and self-renewal capacity. Although MSCs are essential for tissue formation and have already been used in clinical therapy, the origins and markers of these cells remain unknown. In this study, we first investigated the developmental process of MSCs in mouse embryos using the gene encoding platelet-derived growth factor receptor α ( Pdgfra ) as a marker. We then traced cells expressing Pdgfra and other genes (brachyury, Sox1 and Pmx1 ) in various mutant mouse embryos until the adult stage. This tracing of MSC origins and destinies indicates that embryonic MSCs emerge in waves and that almost all adult BM MSCs and WAT MSCs originate from mesoderm and embryonic Pdgfrα-positive cells. Furthermore, we demonstrate that adult Pdgfrα-positive cells are involved in some pathological conditions. © 2018. Published by The Company of Biologists Ltd.

  3. Determination of Radiation Absorbed Dose to Primary Liver Tumors and Normal Liver Tissue Using Post Radioembolization 90Y PET

    Directory of Open Access Journals (Sweden)

    Shyam Mohan Srinivas

    2014-10-01

    Full Text Available Background: Radioembolization with Yttrium-90 (90Y microspheres is becoming a more widely used transcatheter treatment for unresectable hepatocellular carcinoma (HCC. Using post-treatment 90Y PET/CT scans,the distribution of microspheres within the liver can be determined and quantitatively assessesed . We studied the radiation dose of 90Y delivered to liver and treated tumors.Methods: This retrospective study of 56 patients with HCC, including analysis of 98 liver tumors, measured and correlated the dose of radiation delivered to liver tumors and normal liver tissue using glass microspheres (TheraSpheres® to the frequency of complications with mRECIST. 90Y PET/CT and triphasic liver CT scans were used to contour treated tumor and normal liver regions and determine their respective activity concentrations. An absorbed dose factor was used to convert the measured activity concentration (Bq/mL to an absorbed dose (Gy.Results: The 98 studied tumors received a mean dose of 169 Gy (mode 90-120 Gy;range 0-570 Gy. Tumor response by mRECIST criteria was performed for 48 tumors that had follow up scans. There were 21 responders (mean dose 215 Gy and 27 nonresponders (mean dose 167 Gy. The association between mean tumor absorbed dose and response suggests a trend but did not reach statistical significance (p=0.099. Normal liver tissue received a mean dose of 67 Gy (mode 60-70 Gy; range 10-120 Gy. There was a statistically significant association between absorbed dose to normal liver and the presence of two or more severe complications (p=0.036.Conclusion: Our cohort of patients showed a possible dose response trend for the tumors. Collateral dose to normal liver is nontrivial and can have clinical implications. These methods help us understand whether patient adverse events, treatment success, or treatment failure can be attributed to the dose which the tumor or normal liver received.

  4. Computed tomography of the llama head: technique and normal anatomy

    International Nuclear Information System (INIS)

    Hathcock, J.T.; Pugh, D.G.; Cartee, R.E.; Hammond, L.

    1996-01-01

    Computed tomography was performed on the head of 6 normal adult llamas. The animals were under general anesthesia and positioned in dorsal recumbency on the scanning table. The area scanned was from the external occipital protuberance to the rostral portion of the nasal passage, and the images are presented in both a bone window and a soft tissue window to allow evaluation and identification of the anatomy of the head. Computed tomography of the llama head can be accomplished by most computed tomography scanners utilizing a technique similar to that used in small animals with minor modification of the scanning table

  5. Rectification of pulsatile stress on soft tissues: a mechanism for normal-pressure hydrocephalus

    Science.gov (United States)

    Jalikop, Shreyas; Hilgenfeldt, Sascha

    2011-11-01

    Hydrocephalus is a pathological condition of the brain that occurs when cerebrospinal fluid (CSF) accumulates excessively in the brain cavities, resulting in compression of the brain parenchyma. Counter-intuitively, normal-pressure hydrocephalus (NPH) does not show elevated pressure differences across the compressed parenchyma. We investigate the effects of nonlinear tissue mechanics and periodic driving in this system. The latter is due to the cardiac cycle, which provides significant intracranial pressure and volume flow rate fluctuations. Nonlinear rectification of the periodic driving within a model of fluid flow in poroelastic material can lead to compression or expansion of the parenchyma, and this effect does not rely on changes in the mean intracranial pressure. The rectification effects can occur gradually over several days, in agreement with clinical studies of NPH.

  6. Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats

    OpenAIRE

    Peixoto, T.C.; Moura, E.G.; Oliveira, E.; Younes-Rapozo, V.; Soares, P.N.; Rodrigues, V.S.T.; Santos, T.R.; Peixoto-Silva, N.; Carvalho, J.C.; Calvino, C.; Conceição, E.P.S.; Guarda, D.S.; Claudio-Neto, S.; Manhães, A.C.; Lisboa, P.C.

    2018-01-01

    Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower ...

  7. Normal width of the anterior commissure of true vocal cord in Korea adults measured by helical CT

    International Nuclear Information System (INIS)

    Lim, Woo Young; Lim, Dong Hoon; Moon, Jang Il; Ko, Yong Seok; Byeon, Joo Nam; Oh, Jae Hee

    1998-01-01

    To evaluate the mean width of anterior commissure of true vocal cord in Korean adults by measuring its dimension on spiral CT scans. We reviewed the CT scans of 53 Korean adults(age range, 23-73years; mean age 39.2 years;M:F=3D41:12) without laryngeal disorders. Soiral CT scanning was performed around the anterior commissure with 1mm slice thickness and table incrementation for 15 seconds. The anteroposterior width of the anterior commissure was measured on CT scan where the true vocal cord and arytenoid, cricoid and thyroid cartilages were all present. We determined the mean width of the anterior commissure and whether there was a relationship between age and the width of the anterior commissure. The width of the anterior commissure was between 0.9mm and 2.3mm;mean width was 1.60±0.38mm(mean±SD). Using two SDs above the mean would have defined 2.36mm as the upper limit of normal width. Statistically, no significant correlation existed between the age and the width of the anterior commissure(p>0.05). An awareuess of the normal width range of the anterior commissure in Korean adults evaluated by spiral CT enhances the possibility of early detection of invasion of the anterior commissure by glottic cancer.=20

  8. Exatecan in pretreated adult patients with advanced soft tissue sarcoma: results of a phase II--study of the EORTC Soft Tissue and Bone Sarcoma Group

    DEFF Research Database (Denmark)

    Reichardt, P; Nielsen, Ole Steen; Bauer, S

    2007-01-01

    No standard treatment is established for patients with advanced soft tissue sarcoma after previous chemotherapy with anthracyclines and ifosfamide, given either in combination or sequentially. Exatecan (DX-8951f) is a totally synthetic analogue of the topoisomerase I-inhibitor camptothecin, which...... was synthesised to impart increased aqueous solubility, greater tumour efficacy, and less toxicity than camptothecin itself, topotecan or irinotecan. Since some activity against soft tissue sarcomas, especially leiomyosarcomas, has been reported for topoisomerase I-inhibitors, a study with a new and more potent...... agent seemed justified. We report on a prospective multicentre phase II study of Exatecan in adult soft tissue sarcomas failing 1 or 2 lines of chemotherapy in advanced phase, performed within the STBSG of EORTC. Thirty-nine patients (16 leiomyosarcomas and 23 other histologies) were included in two...

  9. Anatomical Network Comparison of Human Upper and Lower, Newborn and Adult, and Normal and Abnormal Limbs, with Notes on Development, Pathology and Limb Serial Homology vs. Homoplasy.

    Science.gov (United States)

    Diogo, Rui; Esteve-Altava, Borja; Smith, Christopher; Boughner, Julia C; Rasskin-Gutman, Diego

    2015-01-01

    How do the various anatomical parts (modules) of the animal body evolve into very different integrated forms (integration) yet still function properly without decreasing the individual's survival? This long-standing question remains unanswered for multiple reasons, including lack of consensus about conceptual definitions and approaches, as well as a reasonable bias toward the study of hard tissues over soft tissues. A major difficulty concerns the non-trivial technical hurdles of addressing this problem, specifically the lack of quantitative tools to quantify and compare variation across multiple disparate anatomical parts and tissue types. In this paper we apply for the first time a powerful new quantitative tool, Anatomical Network Analysis (AnNA), to examine and compare in detail the musculoskeletal modularity and integration of normal and abnormal human upper and lower limbs. In contrast to other morphological methods, the strength of AnNA is that it allows efficient and direct empirical comparisons among body parts with even vastly different architectures (e.g. upper and lower limbs) and diverse or complex tissue composition (e.g. bones, cartilages and muscles), by quantifying the spatial organization of these parts-their topological patterns relative to each other-using tools borrowed from network theory. Our results reveal similarities between the skeletal networks of the normal newborn/adult upper limb vs. lower limb, with exception to the shoulder vs. pelvis. However, when muscles are included, the overall musculoskeletal network organization of the upper limb is strikingly different from that of the lower limb, particularly that of the more proximal structures of each limb. Importantly, the obtained data provide further evidence to be added to the vast amount of paleontological, gross anatomical, developmental, molecular and embryological data recently obtained that contradicts the long-standing dogma that the upper and lower limbs are serial homologues

  10. Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

    Science.gov (United States)

    Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

    2016-12-01

    Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. CT measurement of normal pericardial thickness in adults on computed tomography

    International Nuclear Information System (INIS)

    Choi, Young Woo; Park, Chan Sup; Jeon, Yong Sun; Bae, In Young; Choi, Sung Gyu; Koo, Jin Hoe; Chung, Won Kyun

    1998-01-01

    The purpose of this study was to establish, using computed tomography, the normal thickness of the pericardium in adults. Materials and Methods: CT scans of 50 patients, including sections through the level of the heart, were reviewed. Patients were excluded if there were any suspicions of pericardial abnormality such as infectious or neoplastic diseases. Twenty-four of the 50 were men and 26 were women; their mean age was 47.0(range,18-76) years. We measured pericardial thickness at the level of the right ventricle, interventricular septum and left ventricle, and also compared pericardial thickness in terms of age and sex. Results: In all patients, the pericardium was observed in the right ventricular region; in 41 (82%) at the interventricular septum; and in 41 (82%) along the left ventricle. The mean thickness of normal pericardium at the level of the right ventricle, interventricular septum, and left ventricle was 1.8 mm ± 0.5 mm, 1.8 mm ± 0.4 mm, and 1.7 mm ± 0.5 mm, respectively. No statistically significant correlation was apparent between pericardial thickness and age group (p > 0.63, ANOVA test). Mean pericardial thickness was 1.9 mm ± 0.6 mm in males and 1.7 mm ± 0.4 mm in females; thus, no statistically significant correlation was apparent between pericardial thickness and sex (p >0.29, Student's t-test). Conclusion: The pericardium was best visualized in sections through the right ventricle.The mean thickness of normal pericardium was 1.8 mm ± 0.5 mm and pericardial thickness did not differ according to age or sex

  12. Bone marrow stromal cells elicit tissue sparing after acute but not delayed transplantation into the contused adult rat thoracic spinal cord.

    NARCIS (Netherlands)

    Tewarie, R.D.; Hurtado, A.; Ritfeld, G.J.; Rahiem, S.T.; Wendell, D.F.; Barroso, M.M.; Grotenhuis, J.A.; Oudega, M.

    2009-01-01

    Bone marrow stromal cells (BMSC) transplanted into the contused spinal cord may support repair by improving tissue sparing. We injected allogeneic BMSC into the moderately contused adult rat thoracic spinal cord at 15 min (acute) and at 3, 7, and 21 days (delayed) post-injury and quantified tissue

  13. The Differential Expression of Aqueous Soluble Proteins in Breast Normal and Cancerous Tissues in Relation to Ethnicity of the Patients; Chinese, Malay and Indian

    Directory of Open Access Journals (Sweden)

    Seng Liang

    2010-01-01

    Full Text Available Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC. A proteomic approach was applied in this study to identify changes in the protein profile of cancerous tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort.

  14. Comparative tissue distribution profiles of five major bio-active components in normal and blood deficiency rats after oral administration of Danggui Buxue Decoction by UPLC-TQ/MS.

    Science.gov (United States)

    Shi, Xuqin; Tang, Yuping; Zhu, Huaxu; Li, Weixia; Li, Zhenhao; Li, Wei; Duan, Jin-ao

    2014-01-01

    Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) were frequently combined and used in China as herbal pair called as Danggui Buxue Decoction (DBD) for treatment of blood deficiency syndrome, such as women's ailments. This study is to investigate the tissue distribution profiles of five major bio-active constituents (ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV) in DBD after oral administration of DBD in blood deficiency rats, and to compare the difference between normal and blood deficiency rats. The blood deficiency rats were induced by bleeding from orbit at the dosages of 5.0mLkg(-1) every day, and the experimental period was 12 days. At the finally day of experimental period, both normal and blood deficiency rats were orally administrated with DBD, and then the tissues samples were collected at different time points. Ferulic acid, caffeic acid, calycosin-7-O-β-glucoside, ononin and astragaloside IV in different tissues were detected simultaneously by UPLC-TQ/MS, and the histograms were drawn. The results showed that the overall trend was CLiver>CKidney>CHeart>CSpleen>CLung, CC-30min>CM-30min>CM-60min>CC-5min>CM-5min>CC-60min>CM-240min>CC-240min. The contents of the detected compounds in liver were more than that in other tissues no matter in normal or blood deficiency rats. Compared to normal rats, partial contents of the compounds in blood deficiency rats' tissues at different time points had significant difference (Pdistribution investigation in blood deficiency animals which is conducted by bleeding. And the results demonstrated that the five DBD components in normal and blood deficiency rats had obvious differences in some organs and time points, suggesting that the blood flow and perfusion rate of the organ were altered in blood deficiency animals. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

    International Nuclear Information System (INIS)

    Rodrigues-Peres, Raquel Mary; Cadore, Solange; Febraio, Stefanny; Heinrich, Juliana Karina; Serra, Katia Piton; Derchain, Sophie F M; Vassallo, Jose; Sarian, Luis Otavio

    2013-01-01

    Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels. A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS. The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02). Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next logical step is the assessment of whether the aluminum

  16. Normal appendix in adults: MDCT findings about the location, thickness and the presence or absence of intraluminal gas

    International Nuclear Information System (INIS)

    Oh, Kyoung Jin; Cho, June Sik; Shin, Kyung Sook; Kim, Ha Young; Lim, Sae Kyung; Ohm, Joon Young; Yoon, Chung Dae; Shin, Byung Seok

    2006-01-01

    We wanted to examine the usefulness of multi-detector CT (MDCT) with multiplanar reformations for evaluating the location, thickness and the presence or absence of intraluminal gas in the normal appendix of adults. From December 2004 to June 2005, we evaluated normal appendices in 427 consecutive adult patients who were scanned with 16-slice MDCT. All these patients had no clinical findings of appendicitis. There were 251 men and 176 women. The age range was 19-84 years (mean age: 55 years). The contrast-enhanced MDCT scans during the portal phase were obtained with 0.75 mm detector collimation and they were reviewed with using the multiplanar reconstruction images (3 mm section thickness). The MDCT images of normal appendices on a PACS monitor were retrospectively analyzed. We analyzed the location, thickness and the presence or absence of intraluminal gas by consensus of two abdominal radiologists. The positions of normal appendices were classified as type I (postileal and medial paracecal), type II (subcecal), type III (retrocecal and retrocolic or laterocolic), type IV (preileal and medical colic) and type V (lower pelvic cavity). The five types of appendiceal locations were as follows: type I (n = 187; 44%), type II (n 78; 18%), type III (n = 92, 22%), type IV (n = 39; 9%) and type V (n = 31; 7%). The appendiceal tips in 29 cases (7%) were unusually located in the right subhepatic space, the small bowel mesentery and the right adnexa. The mean thickness of 427 appendices was 5.8 ± 0.9 mm (range: 3.8-9.2 mm). The appendiceal mean thickness was 5.9 ± 0.9 mm in men and 5.7 ± 0.9 mm in women (ρ < 0.05). 384 (90%) of 427 appendices had intraluminal gas and 43 (10%) had no intraluminal gas, and their mean thickness was 5.9 mm (range: 3.8-9.2 mm) and 5.3 mm (3.8-7.3 mm), respectively (ρ < 0.05). MDCT with multiplanar reformations was useful for evaluating the location, thickness and the presence or absence of intraluminal gas in normal appendix of adults. These

  17. UPLC-MS method for quantification of pterostilbene and its application to comparative study of bioavailability and tissue distribution in normal and Lewis lung carcinoma bearing mice.

    Science.gov (United States)

    Deng, Li; Li, Yongzhi; Zhang, Xinshi; Chen, Bo; Deng, Yulin; Li, Yujuan

    2015-10-10

    A UPLC-MS method was developed for determination of pterostilbene (PTS) in plasma and tissues of mice. PTS was separated on Agilent Zorbax XDB-C18 column (50 × 2.1 mm, 1.8 μm) with gradient mobile phase at the flow rate of 0.2 ml/min. The detection was performed by negative ion electrospray ionization in multiple reaction monitoring mode. The linear calibration curve of PTS in mouse plasma and tissues ranged from 1.0 to 5000 and 0.50 to 500 ng/ml (r(2)>0.9979), respectively, with lowest limits of quantification (LLOQ) were between 0.5 and 2.0 ng/ml, respectively. The accuracy and precision of the assay were satisfactory. The validated method was applied to the study of bioavailability and tissue distribution of PTS in normal and Lewis lung carcinoma (LLC) bearing mice. The bioavailability of PTS (dose 14, 28 and 56 mg/kg) in normal mice were 11.9%, 13.9% and 26.4%, respectively; and the maximum level (82.1 ± 14.2 μg/g) was found in stomach (dose 28 mg/kg). The bioavailability, peak concentration (Cmax), time to peak concentration (Tmax) of PTS in LLC mice was increased compared with normal mice. The results indicated the UPLC-MS method is reliable and bioavailability and tissue distribution of PTS in normal and LLC mice were dramatically different. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Appropriate slice location to assess maximal cross-sectional area of individual rotator cuff muscles in normal adults and athletes

    International Nuclear Information System (INIS)

    Yanagisawa, Osamu; Dohi, Michiko; Okuwaki, Toru; Tawara, Noriyuki; Takahashi, Hideyuki; Niitsu, Mamoru

    2009-01-01

    We investigated appropriate slice locations for magnetic resonance (MR) imaging evaluation of the maximal cross-sectional area (CSA) of individual rotator cuff (RC) muscles in normal adults and athletes. We used a 1.5-tesla MR system with body-array and spine coils to obtain oblique sagittal T 1 -weighted shoulder images of 29 normal adults (16 men, 13 women); 6 national-level competitive swimmers (4 men, 2 women); 10 collegiate-level female badminton players; and 7 collegiate-level male rowers. We calculated the supraspinatus, infraspinatus, teres minor, and subscapularis CSAs at the 0-1 locations on the scapula (dividing scapula width into 11 locations), 0 representing the medial border of the scapula and 1, the glenoid fossa surface. We evaluated the differences in CSAs at relative locations on the scapula for each muscle in normal adults, swimmers, badminton players, and rowers using a one-way analysis of variance followed by the Tukey test (P<0.05). The supraspinatus CSAs were maximal at 0.7 for all groups. The infraspinatus CSAs were maximal at 0.5 for normal men and women and badminton players, 0.4- and 0.5 locations for swimmers, and 0.4 for rowers. The teres minor CSAs were maximal at 0.9 for all groups except the swimmers (1 location). The subscapularis CSAs were maximal at 0.7 in men, swimmers, and badminton players and 0.6 in women and rowers. The appropriate slice locations for evaluating maximal CSAs are slightly lateral to the center of the scapula for the supraspinatus and subscapularis, at approximately the center of the scapula for the infraspinatus, and near the glenoid fossa for the teres minor. These slice locations should be clinically useful for morphological and/or function-related assessments of shoulder RC muscles. (author)

  19. Intra-operative on-line discrimination of kidney cancer from normal tissue by IR ATR spectroscopy of extracellular fluid

    Science.gov (United States)

    Urboniene, V.; Velicka, M.; Ceponkus, J.; Pucetaite, M.; Jankevicius, F.; Sablinskas, V.; Steiner, G.

    2016-03-01

    Determination of cancerous and normal kidney tissues during partial, simple or radical nephrectomy surgery was performed by using differences in the IR absorption spectra of extracellular fluid taken from the corresponding tissue areas. The samples were prepared by stamping of the kidney tissue on ATR diamond crystal. The spectral measurements were performed directly in the OR during surgery for 58 patients. It was found that intensities of characteristic spectral bands of glycogen (880-1200 cm-1) in extracellular fluid are sensitive to the type of the tissue and can be used as spectral markers of tumours. Characteristic spectral band of lactic acid (1730 cm-1) - product of the anaerobic glycolysis, taking place in the cancer cells is not suitable for use as a spectral marker of cancerous tissue, since it overlaps with the band of carbonyl stretch in phospholipids and fatty acids. Results of hierarchical cluster analysis of the spectra show that the spectra of healthy and tumour tissue films can be reliably separated into two groups. On the other hand, possibility to differentiate between tumours of different types and grades remains in question. While the fluid from highly malignant G3 tumour tissue contains highly pronounced glycogen spectral bands and can be well separated from benign and G1 tumours by principal component analysis, the variations between spectra from sample to sample prevent from obtaining conclusive results about the grouping between different tumour types and grades. The proposed method is instant and can be used in situ and even in vivo.

  20. Identification of valid reference genes for the normalization of RT qPCR gene expression data in human brain tissue

    Directory of Open Access Journals (Sweden)

    Ravid Rivka

    2008-05-01

    Full Text Available Abstract Background Studies of gene expression in post mortem human brain can contribute to understanding of the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD, Parkinson's disease (PD and dementia with Lewy bodies (DLB. Quantitative real-time PCR (RT qPCR is often used to analyse gene expression. The validity of results obtained using RT qPCR is reliant on accurate data normalization. Reference genes are generally used to normalize RT qPCR data. Given that expression of some commonly used reference genes is altered in certain conditions, this study aimed to establish which reference genes were stably expressed in post mortem brain tissue from individuals with AD, PD or DLB. Results The present study investigated the expression stability of 8 candidate reference genes, (ubiquitin C [UBC], tyrosine-3-monooxygenase [YWHAZ], RNA polymerase II polypeptide [RP II], hydroxymethylbilane synthase [HMBS], TATA box binding protein [TBP], β-2-microglobulin [B2M], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], and succinate dehydrogenase complex-subunit A, [SDHA] in cerebellum and medial temporal gyrus of 6 AD, 6 PD, 6 DLB subjects, along with 5 matched controls using RT qPCR (TaqMan® Gene Expression Assays. Gene expression stability was analysed using geNorm to rank the candidate genes in order of decreasing stability in each disease group. The optimal number of genes recommended for accurate data normalization in each disease state was determined by pairwise variation analysis. Conclusion This study identified validated sets of mRNAs which would be appropriate for the normalization of RT qPCR data when studying gene expression in brain tissue of AD, PD, DLB and control subjects.

  1. Development and application of the Chinese adult female computational phantom Rad-HUMAN

    International Nuclear Information System (INIS)

    Wu, Yican; Cheng, Mengyun; Wang, Wen; Fan, Yanchang; Zhao, Kai; He, Tao; Pei, Xi; Shang, Leiming; Chen, Chaobin; Long, Pengcheng; Cao, Ruifen; Wang, Guozhong; Zhou, Shaoheng; Yu, Shengpeng; Hu, Liqin; Zeng, Q.

    2013-01-01

    Rad-HUMAN is a whole-body numerical phantom of a Chinese adult woman which contains 46 organs and tissues and was created by MCAM6 software using the color photographs of the Chinese Visible Human dataset. This dataset was obtained from a 22-year old Chinese female cadaver judged to represent normal human anatomy as much as possible. The density and elemental composition recommended in the ICRP Publication 89 and in the ICRU report 44 were assigned to the organ and tissue in Rad-HUMAN for radiation protection purpose. The last step was to implement the anatomical data into a Monte Carlo code. Rad-HUMAN contains more than 28.8 billion tiny volume units, which produces an accurately whole-body numerical phantom of a Chinese adult female

  2. Ex-Vivo Tissues Engineering Modeling for Reconstructive Surgery Using Human Adult Adipose Stem Cells and Polymeric Nanostructured Matrix.

    Science.gov (United States)

    Morena, Francesco; Argentati, Chiara; Calzoni, Eleonora; Cordellini, Marino; Emiliani, Carla; D'Angelo, Francesco; Martino, Sabata

    2016-03-31

    The major challenge for stem cell translation regenerative medicine is the regeneration of damaged tissues by creating biological substitutes capable of recapitulating the missing function in the recipient host. Therefore, the current paradigm of tissue engineering strategies is the combination of a selected stem cell type, based on their capability to differentiate toward committed cell lineages, and a biomaterial, that, due to own characteristics (e.g., chemical, electric, mechanical property, nano-topography, and nanostructured molecular components), could serve as active scaffold to generate a bio-hybrid tissue/organ. Thus, effort has been made on the generation of in vitro tissue engineering modeling. Here, we present an in vitro model where human adipose stem cells isolated from lipoaspirate adipose tissue and breast adipose tissue, cultured on polymeric INTEGRA ® Meshed Bilayer Wound Matrix (selected based on conventional clinical applications) are evaluated for their potential application for reconstructive surgery toward bone and adipose tissue. We demonstrated that human adipose stem cells isolated from lipoaspirate and breast tissue have similar stemness properties and are suitable for tissue engineering applications. Finally, the overall results highlighted lipoaspirate adipose tissue as a good source for the generation of adult adipose stem cells.

  3. An anatomical study of normal variations of circle of Willis in 132 fetus, newborn and adult

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    Bateni F

    2009-09-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Several studies have investigated the variations in the anatomy of each segment of circle of Willis whereas a few have addressed the variations of this arterial circle as a whole. In this study the entire circle of Willis and its variations were studied in a cohort of Iranian people and compared with previous reports."n"nMethods: Anatomical variations of the circle of Willis in 132 brains of Iranian cadavers (102 male adults and 30 fetuses and infants were studied. The dissection process was digitally filmed for further studies. Using computer software the external diameters of the vessels were measured and the circle variations were classified. The variations of the circle as a whole and segmental variations were compared with previous studies. "n"nResults: Uni-and bilateral hypoplasia of posterior communicating arteries (PcoAs constituted the most common variation in our study which was similar to previous works. Aplasia of the anterior cerebral artery (A1 and the posterior cerebral artery (P1 were not observed. In 3.3% of fetuses and infants and 3% of adult instances both right and left posterior communicating arteries were absent. There was one case of anterior communicating artery (AcoA aplasia in

  4. Differential expression of GSK3β and pS9GSK3β in normal human tissues: can pS9GSK3β be an epithelial marker?

    Science.gov (United States)

    Lee, Hojung; Ro, Jae Y

    2015-01-01

    Glycogen synthase kinase 3β (GSK3β) and phosphorylated GSK3β at Ser9 (pS9GSK3β) are crucial in cellular proliferation and metabolism. GSK3β and pS9GSK3β are deregulated in many diseases including tumors. Data on altered expression of GSK3β and pS9GSK3β are mainly limited to tumor tissues, thus the expression of GSK3β and pS9GSK3β in normal human tissue has been largely unknown. Thus, we examined the immunohistochemical localization of GSK3β and pS9GSK3β in human fetal and adult tissues, and also compared the expression pattern of GSK3β and pS9GSK3β with that of the CK7 and CK20. We found GSK3β expression in neurons of brain, myenteric plexus in gastrointestinal tract, squamous epithelium of skin, and mammary gland. The expression of pS9GSK3β was restricted to the epithelial cells of breast and pancreaticobiliary duct, distal nephron of kidney, gastrointestinal tract, fallopian tube, epididymis, secretory cell of prostatic gland, and umbrella cell of urinary tract. The staining pattern of pS9GSK3β and CK7 was overlapped in most organs except for gastrointestinal tract where CK7 was negative and CK20 was positive. Our results show that the expression of GSK3β may be associated with differentiation of ectodermal derived tissues and pS9GSK3β with that of epithelial cells of endodermal derived tissues in human. In addition, the expression of pS9GSK3β in the selective epithelial cells may indicate its association with secretory or barrier function of specific cells and may serve as another immunohistochemical marker for epithelial cells.

  5. A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts

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    Max Nobis

    2017-10-01

    Full Text Available The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time.

  6. The SOD Mimic, MnTE-2-PyP, Protects from Chronic Fibrosis and Inflammation in Irradiated Normal Pelvic Tissues

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    Shashank Shrishrimal

    2017-11-01

    Full Text Available Pelvic radiation for cancer therapy can damage a variety of normal tissues. In this study, we demonstrate that radiation causes acute changes to pelvic fibroblasts such as the transformation to myofibroblasts and the induction of senescence, which persist months after radiation. The addition of the manganese porphyrin, MnTE-2-PyP, resulted in protection of these acute changes in fibroblasts and this protection persisted months following radiation exposure. Specifically, at two months post-radiation, MnTE-2-PyP inhibited the number of α-smooth muscle actin positive fibroblasts induced by radiation and at six months post-radiation, MnTE-2-PyP significantly reduced collagen deposition (fibrosis in the skin and bladder tissues of irradiated mice. Radiation also resulted in changes to T cells. At two months post-radiation, there was a reduction of Th1-producing splenocytes, which resulted in reduced Th1:Th2 ratios. MnTE-2-PyP maintained Th1:Th2 ratios similar to unirradiated mice. At six months post-radiation, increased T cells were observed in the adipose tissues. MnTE-2-PyP treatment inhibited this increase. Thus, MnTE-2-PyP treatment maintains normal fibroblast function and T cell immunity months after radiation exposure. We believe that one of the reasons MnTE-2-PyP is a potent radioprotector is due to its protection of multiple cell types from radiation damage.

  7. Ultrasound evaluation of normal and abnormal fetuses: comparison of conventional, tissue harmonic, and pulse- inversion harmonic imaging techniques

    International Nuclear Information System (INIS)

    Ryu, Jeong Ah; Kim, Bohyun; Kim, Sooah; Yang, Soon Ha; Choi, Moon Hae; Ahn, Hyeong Sik

    2003-01-01

    To determine the usefulness of tissue harmonic imaging (THI) and pulse-inversion harmonic imaging (PIHI) in the evaluation of normal and abnormal fetuses. Forty-one pregnant women who bore a total of 31 normal and ten abnormal fetuses underwent conventional ultrasonography (CUS), and then THI and PIHI. US images of six organ systems, namely the brain, spine, heart, abdomen, extremities and face were compared between the three techniques in terms of overall conspicuity and the definition of borders and internal structures. For the brain, heart, abdomen and face, overall conspicuity at THI and PIHI was significantly better than at CUS (p < 0.05). There was, though, no significant difference between THI and PIHI. Affected organs in abnormal fetuses were more clearly depicted at THI and PIHI than at CUS. Both THI and PIHI appear to be superior to CUS for the evaluation of normal or abnormal structures, particularly the brain, heart, abdomen and face

  8. Angular photogrammetric analysis of the soft-tissue facial profile of Indian adults

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    K Saravana Pandian

    2018-01-01

    Full Text Available Introduction: Soft-tissue analysis has become an important component of orthodontic diagnosis and treatment planning. Photographic evaluation of an orthodontic patient is a very close representation of the appearance of the person. The previously established norms for soft-tissue analysis will vary for different ethnic groups. Thus, there is a need to develop soft-tissue facial profile norms pertaining to Indian ethnic groups. Aim and Objectives: The aim of this study is to establish the angular photogrammetric standards of soft-tissue facial profile for Indian males and females and also to compare sexual dimorphism present between them. Materials and Methods: The lateral profile photographs of 300 random participants (150 males and 150 females between ages 18 and 25 years were taken and analyzed using FACAD tracing software. Inclusion criteria were angles Class I molar occlusion with acceptable crowding and proclination, normal growth and development with well-aligned dental arches, and full complements of permanent teeth irrespective of third molar status. This study was conducted in Indian population, and samples were taken from various cities across India. Descriptive statistical analysis was carried out, and sexual dimorphism was evaluated by Student's t-test between males and females. Results: The results of the present study showed statistically significant (P < 0.05 gender difference in 5 parameters out of 12 parameters in Indian population. Conclusion: In the present study, soft-tissue facial measurements were established by means of photogrammetric analysis to facilitate orthodontists to carry out more quantitative evaluation and make disciplined decisions. The mean values obtained can be used for comparison with records of participants with the same characteristics by following this photogrammetric technique.

  9. Modulation of the Rho/ROCK pathway in heart and lung after thorax irradiation reveals targets to improve normal tissue toxicity.

    Science.gov (United States)

    Monceau, Virginie; Pasinetti, Nadia; Schupp, Charlotte; Pouzoulet, Fred; Opolon, Paule; Vozenin, Marie-Catherine

    2010-11-01

    The medical options available to prevent or treat radiation-induced injury are scarce and developing effective countermeasures is still an open research field. In addition, more than half of cancer patients are treated with radiation therapy, which displays a high antitumor efficacy but can cause, albeit rarely, disabling long-term toxicities including radiation fibrosis. Progress has been made in the definition of molecular pathways associated with normal tissue toxicity that suggest potentially effective therapeutic targets. Targeting the Rho/ROCK pathway seems a promising anti-fibrotic approach, at least in the gut; the current study was performed to assess whether this target was relevant to the prevention and/or treatment of injury to the main thoracic organs, namely heart and lungs. First, we showed activation of two important fibrogenic pathways (Smad and Rho/ROCK) in response to radiation-exposure to adult cardiomyocytes; we extended these observations in vivo to the heart and lungs of mice, 15 and 30 weeks post-irradiation. We correlated this fibrogenic molecular imprint with alteration of heart physiology and long-term remodelling of pulmonary and cardiac histological structures. Lastly, cardiac and pulmonary radiation injury and bleomycin-induced pulmonary fibrosis were successfully modulated using Rho/ROCK inhibitors (statins and Y-27632) and this was associated with a normalization of fibrogenic markers. In conclusion, the present paper shows for the first time, activation of Rho/ROCK and Smad pathways in pulmonary and cardiac radiation-induced delayed injury. Our findings thereby reveal a safe and efficient therapeutic opportunity for the abrogation of late thoracic radiation injury, potentially usable either before or after radiation exposure; this approach is especially attractive in (1) the radiation oncology setting, as it does not interfere with prior anti-cancer treatment and in (2) radioprotection, as applicable to the treatment of established

  10. Quantifiable biomarkers of normal aging in the Japanese medaka fish (Oryzias latipes.

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    Lingling Ding

    2010-10-01

    Full Text Available Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes, a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research.The median lifespan of medaka was approximately 22 months under laboratory conditions. We performed quantitative histological analysis of tissues from age-grouped individuals representing young adults (6 months old, mature adults (16 months old, and adults that had survived beyond the median lifespan (24 months. Livers of 24-month old individuals showed extensive morphologic changes, including spongiosis hepatis, steatosis, ballooning degeneration, inflammation, and nuclear pyknosis. There were also phagolysosomes, vacuoles, and residual bodies in parenchymal cells and congestion of sinusoidal vessels. Livers of aged individuals were characterized by increases in lipofuscin deposits and in the number of TUNEL-positive apoptotic cells. Some of these degenerative characteristics were seen, to a lesser extent, in the livers of 16-month old individuals, but not in 6-month old individuals. The basal layer of the dermis showed an age-dependent decline in the number of dividing cells and an increase in senescence-associated β-galactosidase. The hearts of aged individuals were characterized by fibrosis and lipofuscin deposition. There was also a loss of pigmented cells from the retinal epithelium. By contrast, age-associated changes were not apparent in skeletal muscle, the ocular lens, or the brain.The results provide a set of markers that can be used to trace the process of normal tissue aging in medaka and to evaluate the effect of environmental stressors.

  11. Telomere erosion varies during in vitro aging of normal human fibroblasts from young and adult donors.

    Science.gov (United States)

    Figueroa, R; Lindenmaier, H; Hergenhahn, M; Nielsen, K V; Boukamp, P

    2000-06-01

    The life span of normal fibroblasts in vitro (Hayflick limit) depends on donor age, and telomere shortening has been proposed as a potential mechanism. By quantitative fluorescence in situ hybridization and Southern blot analysis, we show progressive telomere loss to about 5 kb mean telomere restriction fragment length in fibroblasts from two adult donors within 40 population doublings, whereas in fibroblasts from two infant donors, telomere erosion is reduced, leaving a mean telomere restriction fragment length of approximately 7 kb at senescence (after approximately 60 population doublings). Aging of fibroblasts from both infant and adult donors was not accompanied by chromosomal abnormalities but was correlated with increased telomere repeat-binding factor 2 expression at both the protein and transcriptional level.

  12. Classification between normal and tumor tissues based on the pair-wise gene expression ratio

    International Nuclear Information System (INIS)

    Yap, YeeLeng; Zhang, XueWu; Ling, MT; Wang, XiangHong; Wong, YC; Danchin, Antoine

    2004-01-01

    Precise classification of cancer types is critically important for early cancer diagnosis and treatment. Numerous efforts have been made to use gene expression profiles to improve precision of tumor classification. However, reliable cancer-related signals are generally lacking. Using recent datasets on colon and prostate cancer, a data transformation procedure from single gene expression to pair-wise gene expression ratio is proposed. Making use of the internal consistency of each expression profiling dataset this transformation improves the signal to noise ratio of the dataset and uncovers new relevant cancer-related signals (features). The efficiency in using the transformed dataset to perform normal/tumor classification was investigated using feature partitioning with informative features (gene annotation) as discriminating axes (single gene expression or pair-wise gene expression ratio). Classification results were compared to the original datasets for up to 10-feature model classifiers. 82 and 262 genes that have high correlation to tissue phenotype were selected from the colon and prostate datasets respectively. Remarkably, data transformation of the highly noisy expression data successfully led to lower the coefficient of variation (CV) for the within-class samples as well as improved the correlation with tissue phenotypes. The transformed dataset exhibited lower CV when compared to that of single gene expression. In the colon cancer set, the minimum CV decreased from 45.3% to 16.5%. In prostate cancer, comparable CV was achieved with and without transformation. This improvement in CV, coupled with the improved correlation between the pair-wise gene expression ratio and tissue phenotypes, yielded higher classification efficiency, especially with the colon dataset – from 87.1% to 93.5%. Over 90% of the top ten discriminating axes in both datasets showed significant improvement after data transformation. The high classification efficiency achieved suggested

  13. Normal tissue complication probabilities correlated with late effects in the rectum after prostate conformal radiotherapy

    International Nuclear Information System (INIS)

    Dale, Einar; Olsen, Dag R.; Fossa, Sophie D.

    1999-01-01

    Purpose: Radiation therapy of deep-sited tumours will always result in normal tissue doses to some extent. The aim of this study was to calculate different risk estimates of late effects in the rectum for a group of cancer prostate patients treated with conformal radiation therapy (CRT) and correlate these estimates with the occurrences of late effects. Since the rectum is a hollow organ, several ways of generating dose-volume distributions over the organ are possible, and we wanted to investigate two of them. Methods and Materials: A mathematical model, known as the Lyman-Kutcher model, conventionally used to estimate normal tissue complication probabilities (NTCP) associated with radiation therapy, was applied to a material of 52 cancer prostate patients. The patients were treated with a four field box technique, with the rectum as organ at risk. Dose-volume histograms (DVH) were generated for the whole rectum (including the cavity) and of the rectum wall. One to two years after the treatment, the patients completed a questionnaire concerning bowel (rectum) related morbidity quantifying the extent of late effects. Results: A correlation analysis using Spearman's rank correlation coefficient, for NTCP values calculated from the DVHs and the patients' scores, gave correlation coefficients which were not statistically significant at the p max , of the whole rectum, correlated better to observed late toxicity than D max derived from histograms of the rectum wall. Correlation coefficients from 'high-dose' measures were larger than those calculated from the NTCP values. Accordingly, as the volume parameter of the Lyman-Kutcher model was reduced, raising the impact of small high-dose volumes on the NTCP values, the correlation between observed effects and NTCP values became significant at p < 0.01 level. Conclusions: 1) High-dose levels corresponding to small volume fractions of the cumulative dose-volume histograms were best correlated with the occurrences of late

  14. The cellular distribution of histone H5 in embryonic and adult tissues of Xenopus laevis and chicken

    NARCIS (Netherlands)

    Moorman, A. F.; de Boer, P. A.; Lamers, W. H.; Charles, R.

    1986-01-01

    The cellular distribution of histone H5 in embryonic and adult tissues of Xenopus laevis and chicken has been established with monoclonal antibodies to histone H5. Both in Xenopus and in chicken, the protein has presumably a more widespread cellular distribution than hitherto expected but is absent

  15. Distribution and ultrastructure of pigment cells in the skins of normal and albino adult turbot, Scophthalmus Maximus

    Institute of Scientific and Technical Information of China (English)

    GUO Huarong; HUANG Bing; QI Fei; ZHANG Shicui

    2007-01-01

    The distribution and ultrastructure of pigment cells in skins of normal and albino adult turbots were examined with transmission electron microscopy (TEM). Three types of pigment cells of melanophore, iridophore and xanthophore have been recognized in adult turbot skins. The skin color depends mainly on the amount and distribution of melanophore and iridophore, as xanthophore is quite rare. No pigment cells can be found in the epidermis of the skins. In the pigmented ocular skin of the turbot, melanophore and iridophore are usually co-localized in the dermis. This is quite different from the distribution in larvae skin. In albino and white blind skins of adult turbots, however, only iridophore monolayer still exists, while the melanophore monolayer disappears. This cytological evidence explains why the albino adult turbot, unlike its larvae, could never resume its body color no matter what environmental and nutritional conditions were provided. Endocytosis is quite active in the cellular membrane of the iridophore. This might be related to the formation of reflective platelet and stability of the iridophore.

  16. Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults.

    Science.gov (United States)

    Nugent, Scott; Castellano, Christian-Alexandre; Goffaux, Philippe; Whittingstall, Kevin; Lepage, Martin; Paquet, Nancy; Bocti, Christian; Fulop, Tamas; Cunnane, Stephen C

    2014-06-01

    Several studies have suggested that glucose hypometabolism may be present in specific brain regions in cognitively normal older adults and could contribute to the risk of subsequent cognitive decline. However, certain methodological shortcomings, including a lack of partial volume effect (PVE) correction or insufficient cognitive testing, confound the interpretation of most studies on this topic. We combined [(18)F]fluorodeoxyglucose ([(18)F]FDG) positron emission tomography (PET) and magnetic resonance (MR) imaging to quantify cerebral metabolic rate of glucose (CMRg) as well as cortical volume and thickness in 43 anatomically defined brain regions from a group of cognitively normal younger (25 ± 3 yr old; n = 25) and older adults (71 ± 9 yr old; n = 31). After correcting for PVE, we observed 11-17% lower CMRg in three specific brain regions of the older group: the superior frontal cortex, the caudal middle frontal cortex, and the caudate (P ≤ 0.01 false discovery rate-corrected). In the older group, cortical volumes and cortical thickness were 13-33 and 7-18% lower, respectively, in multiple brain regions (P ≤ 0.01 FDR correction). There were no differences in CMRg between individuals who were or were not prescribed antihypertensive medication. There were no significant correlations between CMRg and cognitive performance or metabolic parameters measured in fasting plasma. We conclude that highly localized glucose hypometabolism and widespread cortical thinning and atrophy can be present in older adults who are cognitively normal, as assessed using age-normed neuropsychological testing measures. Copyright © 2014 the American Physiological Society.

  17. ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

    Science.gov (United States)

    Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

    2016-05-01

    ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

  18. Stages of Adult Soft Tissue Sarcoma

    Science.gov (United States)

    ... deep (in the muscle and may be in connective or subcutaneous tissue). In stage IB , the tumor is low-grade (likely to grow and spread ... deep (in the muscle and may be in connective or subcutaneous tissue). In stage IIB , the tumor is mid-grade (somewhat likely to grow and ...

  19. Dietary intake and burden of lanthanide in main organs and tissues for Chinese man

    International Nuclear Information System (INIS)

    Zhu Hongda; Liu Qingfeng; Ouyang Li; Liu Husheng; Wang Naifen; Liu Yaqiong; Zhang Yongbao; Wang Ke; Chen Rusong

    2004-01-01

    Objective: To determine lanthanide concentrations in dietary foods and main organs or tissues for Chinese adult man and to estimate their daily intakes by ingestion and organ or tissue burdens. Methods: Ten kinds of organ or tissue samples collected in autopsy from 21 supplemental subjects of 4 areas with different dietary types in China who died suddenly, and had been healthy and normal before death. The concentrations of 11 lanthanide in foods and 14 lanthanide in these organ or tissue samples, including those collected from 31 subjects in the past, were analyzed by using ICP-MS or INAA technique as well as necessary QC measures. With uses of the local diet composition and relevant organ or tissue weights for Chinese Reference Man, their daily intakes and organ or tissue burdens were estimated. Results: The concentrations of 14 lanthanide in 12 categories of foods and 10 kinds of organ or tissue samples, their dietary daily intakes and organ or tissue burdens for Chinese adult men were obtained. Conclusion: Besides updating the relevant data of La, Ce and Eu in 5 kinds of organ or tissue and diet, this research obtained data on concentrations of other 11 lanthanide in Chinese foods and 10 kinds of organ or tissue, their daily intakes and burdens for the first time in China. The results provide more systematic bases for developing the parameters of Chinese Reference Man than before. This study provides also comparative data for different kinds of lanthanide, foods, organs or tissues and also the background values of Chinese soil

  20. Transcriptome profiling of the cancer, adjacent non-tumor and distant normal tissues from a colorectal cancer patient by deep sequencing.

    Directory of Open Access Journals (Sweden)

    Yan'an Wu

    Full Text Available Colorectal cancer (CRC is one of the most commonly diagnosed cancers in the world. A genome-wide screening of transcriptome dysregulation between cancer and normal tissue would provide insight into the molecular basis of CRC initiation and progression. Compared with microarray technology, which is commonly used to identify transcriptional changes, the recently developed RNA-seq technique has the ability to detect other abnormal regulations in the cancer transcriptome, such as alternative splicing, novel transcripts or gene fusion. In this study, we performed high-throughput transcriptome sequencing at ~50× coverage on CRC, adjacent non-tumor and distant normal tissue. The results revealed cancer-specific, differentially expressed genes and differential alternative splicing, suggesting that the extracellular matrix and metabolic pathways are activated and the genes related to cell homeostasis are suppressed in CRC. In addition, one tumor-restricted gene fusion, PRTEN-NOTCH2, was also detected and experimentally confirmed. This study reveals some common features in tumor invasion and provides a comprehensive survey of the CRC transcriptome, which provides better insight into the complexity of regulatory changes during tumorigenesis.

  1. Classification of Laser Induced Fluorescence Spectra from Normal and Malignant bladder tissues using Learning Vector Quantization Neural Network in Bladder Cancer Diagnosis

    DEFF Research Database (Denmark)

    Karemore, Gopal Raghunath; Mascarenhas, Kim Komal; Patil, Choudhary

    2008-01-01

    In the present work we discuss the potential of recently developed classification algorithm, Learning Vector Quantization (LVQ), for the analysis of Laser Induced Fluorescence (LIF) Spectra, recorded from normal and malignant bladder tissue samples. The algorithm is prototype based and inherently...

  2. Detection of normal plantar fascia thickness in adults via the ultrasonographic method.

    Science.gov (United States)

    Abul, Kadir; Ozer, Devrim; Sakizlioglu, Secil Sezgin; Buyuk, Abdul Fettah; Kaygusuz, Mehmet Akif

    2015-01-01

    Heel pain is a prevalent concern in orthopedic clinics, and there are numerous pathologic abnormalities that can cause heel pain. Plantar fasciitis is the most common cause of heel pain, and the plantar fascia thickens in this process. It has been found that thickening to greater than 4 mm in ultrasonographic measurements can be accepted as meaningful in diagnoses. Herein, we aimed to measure normal plantar fascia thickness in adults using ultrasonography. We used ultrasonography to measure the plantar fascia thickness of 156 healthy adults in both feet between April 1, 2011, and June 30, 2011. These adults had no previous heel pain. The 156 participants comprised 88 women (56.4%) and 68 men (43.6%) (mean age, 37.9 years; range, 18-65 years). The weight, height, and body mass index of the participants were recorded, and statistical analyses were conducted. The mean ± SD (range) plantar fascia thickness measurements for subgroups of the sample were as follows: 3.284 ± 0.56 mm (2.4-5.1 mm) for male right feet, 3.3 ± 0.55 mm (2.5-5.0 mm) for male left feet, 2.842 ± 0.42 mm (1.8-4.1 mm) for female right feet, and 2.8 ± 0.44 mm (1.8-4.3 mm) for female left feet. The overall mean ± SD (range) thickness for the right foot was 3.035 ± 0.53 mm (1.8-5.1 mm) and for the left foot was 3.053 ± 0.54 mm (1.8-5.0 mm). There was a statistically significant and positive correlation between plantar fascia thickness and participant age, weight, height, and body mass index. The plantar fascia thickness of adults without heel pain was measured to be less than 4 mm in most participants (~92%). There was no statistically significant difference between the thickness of the right and left foot plantar fascia.

  3. The immune cell composition in Barrett's metaplastic tissue resembles that in normal duodenal tissue.

    Directory of Open Access Journals (Sweden)

    Alexandra Lind

    Full Text Available BACKGROUND AND OBJECTIVE: Barrett's esophagus (BE is characterized by the transition of squamous epithelium into columnar epithelium with intestinal metaplasia. The increased number and types of immune cells in BE have been indicated to be due to a Th2-type inflammatory process. We tested the alternative hypothesis that the abundance of T-cells in BE is caused by a homing mechanism that is found in the duodenum. PATIENTS AND METHODS: Biopsies from BE and duodenal tissue from 30 BE patients and duodenal tissue from 18 controls were characterized by immmunohistochemistry for the presence of T-cells and eosinophils(eos. Ex vivo expanded T-cells were further phenotyped by multicolor analysis using flowcytometry. RESULTS: The high percentage of CD4(+-T cells (69±3% (mean±SEM/n = 17, by flowcytometry, measured by flowcytometry and immunohistochemistry, and the presence of non-activated eosinophils found in BE by immunohistochemical staining, were not different from that found in duodenal tissue. Expanded lymphocytes from these tissues had a similar phenotype, characterized by a comparable but low percentage of αE(CD103 positive CD4(+cells (44±5% in BE, 43±4% in duodenum of BE and 34±7% in duodenum of controls and a similar percentage of granzyme-B(+CD8(+ cells(44±5% in BE, 33±6% in duodenum of BE and 36±7% in duodenum of controls. In addition, a similar percentage of α4β7(+ T-lymphocytes (63±5% in BE, 58±5% in duodenum of BE and 62±8% in duodenum of controls was found. Finally, mRNA expression of the ligand for α4β7, MAdCAM-1, was also similar in BE and duodenal tissue. No evidence for a Th2-response was found as almost no IL-4(+-T-cells were seen. CONCLUSION: The immune cell composition (lymphocytes and eosinophils and expression of intestinal adhesion molecule MAdCAM-1 is similar in BE and duodenum. This supports the hypothesis that homing of lymphocytes to BE tissue is mainly caused by intestinal homing signals rather than to an

  4. Adult Head and Neck Soft Tissue Sarcomas: Treatment and Outcome

    Directory of Open Access Journals (Sweden)

    Rabindra P. Singh

    2008-01-01

    Thirty-six patients were seen, of whom 24 were treated at this unit, the remainder only receiving advice. The median age of the patients was 46 years. Most of the sarcomas were deep and of high or intermediate grade with a median size of 5.5 cm. Eleven different histological subtypes were identified. Wide excision was possible only in 21% of the cases. 42% of the patients developed local recurrence and 42% developed metastatic disease usually in the lungs. Overall survival was 49% at 5 years. Tumour size was the most important prognostic factor. Adult head and neck soft tissue sarcomas have a high mortality rate with a high risk of local recurrence and metastatic disease. The rarity of the disease would suggest that centralisation of care could lead to increased expertise and better outcomes.

  5. Normally occurring intersexuality and testosterone induced plasticity in the copulatory system of adult leopard geckos.

    Science.gov (United States)

    Holmes, Melissa M; Putz, Oliver; Crews, David; Wade, Juli

    2005-04-01

    The copulatory neuromuscular system of lizards is highly sexually dimorphic. Adult males possess bilateral penises called hemipenes, which are independently controlled by two muscles, the retractor penis magnus (RPM) and transversus penis (TPN). These structures are not obvious in adult females. However, in adult female leopard geckos (Eublepharis macularius), testosterone induces hemipene growth. We investigated whether these structures develop de novo in adulthood or are histologically present as rudimentary structures in the female leopard gecko. We also investigated the extent of sexual dimorphisms and plasticity in the associated neuromuscular components. To do this, we compared copulatory morphology (sizes of hemipenes, RPM and TPN muscle fibers, and associated motoneurons, as well as motoneuron and RPM fiber number) in adult females treated with testosterone, control females, and control males. All of the geckos possessed hemipenes, RPMs and TPNs, but these structures were indeed vestigial in control females. Testosterone induced striking increases in hemipene and copulatory muscle fiber size in females, but not to levels equivalent to control males. In parallel, males with increased levels of androgenic activity had larger hemipenes, suggesting naturally occurring steroid-induced plasticity. Copulatory motoneurons were not sexually dimorphic in size or number, and these measures did not respond to testosterone. The data demonstrate that the copulatory system of leopard geckos, in which gonadal sex is determined by egg incubation temperature, differs from that of many species (both reptilian and mammalian) with genotypic sex determination. Indeed, the system is remarkable in that adult females have normally occurring intersex characteristics and they exhibit substantial steroid-induced morphological plasticity in adulthood.

  6. Postprandial Responses to Lipid and Carbohydrate Ingestion in Repeated Subcutaneous Adipose Tissue Biopsies in Healthy Adults

    Directory of Open Access Journals (Sweden)

    Aimee L. Dordevic

    2015-07-01

    Full Text Available Adipose tissue is a primary site of meta-inflammation. Diet composition influences adipose tissue metabolism and a single meal can drive an inflammatory response in postprandial period. This study aimed to examine the effect lipid and carbohydrate ingestion compared with a non-caloric placebo on adipose tissue response. Thirty-three healthy adults (age 24.5 ± 3.3 year (mean ± standard deviation (SD; body mass index (BMI 24.1 ± 3.2 kg/m2, were randomised into one of three parallel beverage groups; placebo (water, carbohydrate (maltodextrin or lipid (dairy-cream. Subcutaneous, abdominal adipose tissue biopsies and serum samples were collected prior to (0 h, as well as 2 h and 4 h after consumption of the beverage. Adipose tissue gene expression levels of monocyte chemoattractant protein-1 (MCP-1, interleukin 6 (IL-6 and tumor necrosis factor-α (TNF-α increased in all three groups, without an increase in circulating TNF-α. Serum leptin (0.6-fold, p = 0.03 and adipose tissue leptin gene expression levels (0.6-fold, p = 0.001 decreased in the hours following the placebo beverage, but not the nutrient beverages. Despite increased inflammatory cytokine gene expression in adipose tissue with all beverages, suggesting a confounding effect of the repeated biopsy method, differences in metabolic responses of adipose tissue and circulating adipokines to ingestion of lipid and carbohydrate beverages were observed.

  7. The clinical significance of normal mammograms and normal sonograms in patients with palpable abnormalities of the breast

    International Nuclear Information System (INIS)

    Lee, Jin Hwa; Yoon, Seong Kuk; Choi, Sun Seob; Nam, Kyung Jin; Cho, Se Heon; Kim, Dae Cheol; Kim, Jung Il; Kim, Eun Kyung

    2006-01-01

    We wanted to evaluate the clinical significance of normal mammograms and normal sonograms in patients with palpable abnormalities of the breast. From Apr 2003 to Feb 2005, 107 patients with 113 palpable abnormalities who had combined normal sonographic and normal mammographic findings were retrospectively studied. The evaluated parameters included age of the patients, the clinical referrals, the distribution of the locations of the palpable abnormalities, whether there was a past surgical history, the mammographic densities and the sonographic echo patterns (purely hyperechoic fibrous tissue, mixed fibroglandular breast tissue, predominantly isoechoic glandular tissue and isoechoic subcutaneous fat tissue) at the sites of clinical concern, whether there was a change in imaging and/or the physical examination results at follow-up, and whether there were biopsy results. This study period was chosen to allow a follow-up period of at least 12 months. The patients' ages ranged from 22 to 66 years (mean age: 48.8 years) and 62 (58%) of the 107 patients were between 41 and 50 years old (58%). The most common location of the palpable abnormalities was the upper outer portion of the breast (45%) and most of the mammographic densities were dense patterns (BI-RADS Type 3 or 4: 91%). Our cases showed similar distribution for all the types of sonographic echo patterns. 23 patients underwent biopsy; all the biopsy specimens were benign. For the 84 patients with 90 palpable abnormalities who were followed, there was no interval development of breast cancer in the areas of clinical concern. Our results suggest that we can follow up and prevent unnecessary biopsies in women with palpable abnormalities when both the mammography and ultrasonography show normal tissue, but this study was limited by its small sample size. Therefore, a larger study will be needed to better define the negative predictive value of combined normal sonographic and mammographic findings

  8. Relative expression of rRNA transcripts and 45S rDNA promoter methylation status are dysregulated in tumors in comparison with matched-normal tissues in breast cancer.

    Science.gov (United States)

    Karahan, Gurbet; Sayar, Nilufer; Gozum, Gokcen; Bozkurt, Betul; Konu, Ozlen; Yulug, Isik G

    2015-06-01

    Ribosomal RNA (rRNA) expression, one of the most important factors regulating ribosome production, is primarily controlled by a CG-rich 45 S rDNA promoter. However, the DNA methylation state of the 45 S rDNA promoter, as well as its effect on rRNA gene expression in types of human cancers is controversial. In the present study we analyzed the methylation status of the rDNA promoter (-380 to +53 bp) as well as associated rRNA expression levels in breast cancer cell lines and breast tumor-normal tissue pairs. We found that the aforementioned regulatory region was extensively methylated (74-96%) in all cell lines and in 68% (13/19 tumor-normal pairs) of the tumors. Expression levels of rRNA transcripts 18 S, 28 S, 5.8 S and 45 S external transcribed spacer (45 S ETS) greatly varied in the breast cancer cell lines regardless of their methylation status. Analyses of rRNA transcript expression levels in the breast tumor and normal matched tissues showed no significant difference when normalized with TBP. On the other hand, using the geometric mean of the rRNA expression values (GM-rRNA) as reference enabled us to identify significant changes in the relative expression of rRNAs in the tissue samples. We propose GM-rRNA normalization as a novel strategy to analyze expression differences between rRNA transcripts. Accordingly, the 18S rRNA/GM-rRNA ratio was significantly higher whereas the 5.8S rRNA/GM-rRNA ratio was significantly lower in breast tumor samples than this ratio in the matched normal samples. Moreover, the 18S rRNA/GM-rRNA ratio was negatively correlated with the 45 S rDNA promoter methylation level in the normal breast tissue samples, yet not in the breast tumors. Significant correlations observed between the expression levels of rRNA transcripts in the normal samples were lost in the tumor samples. We showed that the expression of rRNA transcripts may not be based solely on promoter methylation. Carcinogenesis may cause dysregulation of the correlation

  9. Extracellular Matrix, Nuclear and Chromatin Structure and GeneExpression in Normal Tissues and Malignant Tumors: A Work inProgress

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, Virginia A.; Xu, Ren; Bissell, Mina J.

    2006-08-01

    Almost three decades ago, we presented a model where theextracellular matrix (ECM) was postulated to influence gene expressionand tissue-specificity through the action of ECM receptors and thecytoskeleton. This hypothesis implied that ECM molecules could signal tothe nucleus and that the unit of function in higher organisms was not thecell alone, but the cell plus its microenvironment. We now know that ECMinvokes changes in tissue and organ architecture and that tissue, cell,nuclear, and chromatin structure are changed profoundly as a result ofand during malignant progression. Whereas some evidence has beengenerated for a link between ECM-induced alterations in tissuearchitecture and changes in both nuclear and chromatin organization, themanner by which these changes actively induce or repress gene expressionin normal and malignant cells is a topic in need of further attention.Here, we will discuss some key findings that may provide insights intomechanisms through which ECM could influence gene transcription and howtumor cells acquire the ability to overcome these levels ofcontrol.

  10. Normal pressure hydrocephalus

    Science.gov (United States)

    Hydrocephalus - occult; Hydrocephalus - idiopathic; Hydrocephalus - adult; Hydrocephalus - communicating; Dementia - hydrocephalus; NPH ... Ferri FF. Normal pressure hydrocephalus. In: Ferri FF, ed. ... Elsevier; 2016:chap 648. Rosenberg GA. Brain edema and disorders ...

  11. Changes in the rate of proliferation in normal tissues after irradiation

    International Nuclear Information System (INIS)

    Denekamp, J.

    1975-01-01

    In tissues where reproductive cell death is known to cause the functional tissue damage (e.g., intestine and skin), repopulation becomes important only after the death of the radiation-damaged cells. Since these tissues have a fairly rapid turnover, this can occur within a short period of time and can assist in the healing of tissues during fractionated therapy. However, in tissues which express their damage late, such as the lung, it is very unlikely that repopulation will be stimulated before cell death is manifested and this does not occur during the period over which fractionated radiotherapy is administered. Although repopulation may be of no importance in these tissues, e.g., lungs and kidneys, there appears to be some other ''repair'' process which requires additional radiation dose to be administered to achieve the same endpoint if the overall time is increased

  12. Human paraoxonase and HDL-cholesterol in pakistan patients with acute myocardial infarction and normal healthy adults

    International Nuclear Information System (INIS)

    Iqbal, I.P.; Khan, A.H.; Mehboobali, N.

    2007-01-01

    Human serum paraoxonase is a high density lipoprotein (HDL)-bound enzyme exhibiting antiatherogenic properties. The aim of this study was to investigate any relationship between serum paraoxonase activity and serum levels of HDL-cholesterol in Pakistani patients with acute myocardial infarction (AMI) compared to normal healthy subjects and to examine possible association between serum paraoxonase activity and AMI in Pakistani population. In a case-control study, serum paraoxonase activity and serum levels of HDL-cholesterol and LDL-cholesterol were monitored in 164 Pakistani patients with AMI and 106 normal healthy adults matched for gender, BMI and age within 10 years. Mean serum concentration of HDL-cholesterol and mean serum paraoxonase activity in AMI patients were not significantly different from the corresponding values in normal healthy subjects. Mean serum paraoxonase activity value was significantly lower in normal healthy subjects with low HDL-cholesterol (serum levels < 40mg/dl) compared to the value in those with normal levels of HDL-cholesterol (P=0.04). In AMI patients, paraoxonase activity was lower in subjects with low HDL-cholesterol compared to those with normal levels of HDL-cholesterol, however, the decrease was not statistically significant. Correlation analyses of the data revealed a moderate association of paraoxonase activity with HDL-cholesterol (Pearson's r= 0.225, P<0.01 for AMI patients and r=0.281, P<0.01 for normal healthy controls). Seventy three percent of normal healthy subjects and 65% of AMI patients in this study had low HDL-cholesterol. Low serum paraoxonase activity and high prevalence of low HDL-cholesterol in Pakistani population could be contributing to the high rates of coronary heart disease in this population. (author)

  13. Differences of Sagittal Lumbosacral Parameters between Patients with Lumbar Spondylolysis and Normal Adults.

    Science.gov (United States)

    Yin, Jin; Peng, Bao-Gan; Li, Yong-Chao; Zhang, Nai-Yang; Yang, Liang; Li, Duan-Ming

    2016-05-20

    Recent studies have suggested an association between elevated pelvic incidence (PI) and the development of lumbar spondylolysis. However, there is still lack of investigation for Han Chinese people concerning the normal range of spinopelvic parameters and relationship between abnormal sagittal parameters and lumbar diseases. The objective of the study was to investigate sagittal lumbosacral parameters of adult lumbar spondylolysis patients in Han Chinese population. A total of 52 adult patients with symptomatic lumbar spondylolysis treated in the General Hospital of Armed Police Force (Beijing, China) were identified as the spondylolysis group. All the 52 patients were divided into two subgroups, Subgroup A: 36 patients with simple lumbar spondylolysis, and Subgroup B: 16 patients with lumbar spondylolysis accompanying with mild lumbar spondylolisthesis (slip percentage spondylolysis group and the control group with independent-sample t- test. There were no statistically significant differences of all seven sagittal lumbosacral parameters between Subgroup A and Subgroup B. PI, PT, SS, and LL were higher (P spondylolysis group than those in the control group, but STA was lower (P spondylolysis group. Current study results suggest that increased PI and decreased STA may play important roles in the pathology of lumbar spondylolysis in Han Chinese population.

  14. [Performance of normal young adults in two temporal resolution tests].

    Science.gov (United States)

    Zaidan, Elena; Garcia, Adriana Pontin; Tedesco, Maria Lucy Fraga; Baran, Jane A

    2008-01-01

    temporal auditory processing is defined as the perception of sound or of sound alteration within a restricted time interval and is considered a fundamental ability for the auditory perception of verbal and non verbal sounds, for the perception of music, rhythm, periodicity and in the discrimination of pitch, duration and of phonemes. to compare the performance of normal Brazilian adults in two temporal resolution tests: the Gaps-in-Noise Test (GIN) and the Random Gap Detection Test (RGDT), and to analyze potential differences of performance in these two tests. twenty-five college students with normal hearing (11 males and 14 females) and no history of educational, neurological and/or language problems, underwent the GIN and RGDT at 40dB SL. statistically significant gender effects for both tests were found, with female participants showing poorer performance on both temporal processing tests. In addition, a comparative analysis of the results obtained in the GIN and RGDT revealed significant differences in the threshold measures derived for these two tests. In general, significantly better gap detection thresholds were observed for both male and female participants on the GIN test when compared to the results obtained for the RGDT. male participants presented better performances on both RGDT and GIN, when compared to the females. There were no differences in performance between right and left ears on the GIN test. Participants of the present investigation, males and females, performed better on the GIN when compared to the RGDT. The GIN presented advantages over the RGDT, not only in terms of clinical validity and sensibility, but also in terms of application and scoring.

  15. A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD).

    Science.gov (United States)

    Luxton, Gary; Keall, Paul J; King, Christopher R

    2008-01-07

    To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within approximately 0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD(50), and conversely m and TD(50) are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d(ref), n, v(eff) and the Niemierko equivalent uniform dose (EUD), where d(ref) and v(eff) are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data.

  16. A new formula for normal tissue complication probability (NTCP) as a function of equivalent uniform dose (EUD)

    International Nuclear Information System (INIS)

    Luxton, Gary; Keall, Paul J; King, Christopher R

    2008-01-01

    To facilitate the use of biological outcome modeling for treatment planning, an exponential function is introduced as a simpler equivalent to the Lyman formula for calculating normal tissue complication probability (NTCP). The single parameter of the exponential function is chosen to reproduce the Lyman calculation to within ∼0.3%, and thus enable easy conversion of data contained in empirical fits of Lyman parameters for organs at risk (OARs). Organ parameters for the new formula are given in terms of Lyman model m and TD 50 , and conversely m and TD 50 are expressed in terms of the parameters of the new equation. The role of the Lyman volume-effect parameter n is unchanged from its role in the Lyman model. For a non-homogeneously irradiated OAR, an equation relates d ref , n, v eff and the Niemierko equivalent uniform dose (EUD), where d ref and v eff are the reference dose and effective fractional volume of the Kutcher-Burman reduction algorithm (i.e. the LKB model). It follows in the LKB model that uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP and is used to generate a table of EUD versus normal tissue complication probability for the Emami-Burman parameter fits as well as for OAR parameter sets from more recent data

  17. Gene expression profiling of histologically normal breast tissue in females with human epidermal growth factor receptor 2‑positive breast cancer.

    Science.gov (United States)

    Zubor, Pavol; Hatok, Jozef; Moricova, Petra; Kapustova, Ivana; Kajo, Karol; Mendelova, Andrea; Sivonova, Monika Kmetova; Danko, Jan

    2015-02-01

    Gene expression profile‑based taxonomy of breast cancer (BC) has been described as a significant breakthrough in comprehending the differences in the origin and behavior of cancer to allow individually tailored therapeutic approaches. In line with this, we hypothesized that the gene expression profile of histologically normal epithelium (HNEpi) could harbor certain genetic abnormalities predisposing breast tissue cells to develop human epidermal growth factor receptor 2 (HER2)‑positive BC. Thus, the aim of the present study was to assess gene expression in normal and BC tissue (BCTis) from patients with BC in order to establish its value as a potential diagnostic marker for cancer development. An array study evaluating a panel of 84 pathway‑ and disease‑specific genes in HER2‑positive BC and tumor‑adjacent HNEpi was performed using quantitative polymerase chain reaction in 12 patients using microdissected samples from frozen tissue. Common prognostic and predictive parameters of BC were assessed by immunohistochemistry and in situ hybridization. In the BCTis and HNEpi samples of 12 HER2‑positive subjects with BC, the expression of 2,016 genes was assessed. A total of 39.3% of genes were deregulated at a minimal two‑fold deregulation rate and 10.7% at a five‑fold deregulation rate in samples of HNEpi or BCTis. Significant differences in gene expression between BCTis and HNEpi samples were revealed for BCL2L2, CD44, CTSD, EGFR, ERBB2, ITGA6, NGFB, RPL27, SCBG2A1 and SCGB1D2 genes (Pbreast tissue revealed gene expression abnormalities that may represent potential markers of increased risk for HER2‑positive malignant transformation of breast tissue, and may be able to be employed as predictors of prognosis.

  18. Diagnosis of breast cancer by tissue analysis

    Institute of Scientific and Technical Information of China (English)

    Debnath Bhattacharyya; Samir Kumar Bandyopadhyay; Tai-hoon Kim

    2013-01-01

    In this paper,we propose a technique to locate abnormal growth of cells in breast tissue and suggest further pathological test,when require.We compare normal breast tissue with malignant invasive breast tissue by a series of image processing steps.Normal ductal epithelial cells and ductal/lobular invasive carcinogenic cells also consider for comparison here in this paper.In fact,features of cancerous breast tissue (invasive) are extracted and analyses with normal breast tissue.We also suggest the breast cancer recognition technique through image processing and prevention by controlling p53 gene mutation to some extent.

  19. Rethinking schizophrenia in the context of normal neurodevelopment

    Science.gov (United States)

    Catts, Vibeke S.; Fung, Samantha J.; Long, Leonora E.; Joshi, Dipesh; Vercammen, Ans; Allen, Katherine M.; Fillman, Stu G.; Rothmond, Debora A.; Sinclair, Duncan; Tiwari, Yash; Tsai, Shan-Yuan; Weickert, Thomas W.; Shannon Weickert, Cynthia

    2013-01-01

    The schizophrenia brain is differentiated from the normal brain by subtle changes, with significant overlap in measures between normal and disease states. For the past 25 years, schizophrenia has increasingly been considered a neurodevelopmental disorder. This frame of reference challenges biological researchers to consider how pathological changes identified in adult brain tissue can be accounted for by aberrant developmental processes occurring during fetal, childhood, or adolescent periods. To place schizophrenia neuropathology in a neurodevelopmental context requires solid, scrutinized evidence of changes occurring during normal development of the human brain, particularly in the cortex; however, too often data on normative developmental change are selectively referenced. This paper focuses on the development of the prefrontal cortex and charts major molecular, cellular, and behavioral events on a similar time line. We first consider the time at which human cognitive abilities such as selective attention, working memory, and inhibitory control mature, emphasizing that attainment of full adult potential is a process requiring decades. We review the timing of neurogenesis, neuronal migration, white matter changes (myelination), and synapse development. We consider how molecular changes in neurotransmitter signaling pathways are altered throughout life and how they may be concomitant with cellular and cognitive changes. We end with a consideration of how the response to drugs of abuse changes with age. We conclude that the concepts around the timing of cortical neuronal migration, interneuron maturation, and synaptic regression in humans may need revision and include greater emphasis on the protracted and dynamic changes occurring in adolescence. Updating our current understanding of post-natal neurodevelopment should aid researchers in interpreting gray matter changes and derailed neurodevelopmental processes that could underlie emergence of psychosis. PMID

  20. Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

    Science.gov (United States)

    2013-01-01

    Background Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels. Methods A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS. Results The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02). Conclusions Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next