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Sample records for acute normal tissue

  1. Dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with high-dose-rate brachytherapy for large prostate volumes

    Energy Technology Data Exchange (ETDEWEB)

    Yang, George; Strom, Tobin J.; Shrinath, Kushagra; Mellon, Eric A.; Fernandez, Daniel C.; Biagioli, Matthew C. [Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Wilder, Richard B., E-mail: mcbiagioli@yahoo.com [Cancer Treatment Centers of America, Newnan, GA (United States)

    2015-05-15

    Purpose: to evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes. Materials and methods: one hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL) were treated with high-dose-rate (HDR) brachytherapy ± intensity modulated radiation therapy (IMRT) to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38%) unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Results: median follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3%) patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17%) patients developed Grade 2 acute urinary retention. American Urological Association (AUA) symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p-0.04). There was no ≥ Grade 3 acute toxicity. Conclusions: dosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes. (author)

  2. Dosimetric Coverage of the Prostate, Normal Tissue Sparing, and Acute Toxicity with High-Dose-Rate Brachytherapy for Large Prostate Volumes

    Directory of Open Access Journals (Sweden)

    George Yang

    2015-06-01

    Full Text Available ABSTRACTPurposeTo evaluate dosimetric coverage of the prostate, normal tissue sparing, and acute toxicity with HDR brachytherapy for large prostate volumes.Materials and MethodsOne hundred and two prostate cancer patients with prostate volumes >50 mL (range: 5-29 mL were treated with high-dose-rate (HDR brachytherapy ± intensity modulated radiation therapy (IMRT to 4,500 cGy in 25 daily fractions between 2009 and 2013. HDR brachytherapy monotherapy doses consisted of two 1,350-1,400 cGy fractions separated by 2-3 weeks, and HDR brachytherapy boost doses consisted of two 950-1,150 cGy fractions separated by 4 weeks. Twelve of 32 (38% unfavorable intermediate risk, high risk, and very high risk patients received androgen deprivation therapy. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.ResultsMedian follow-up was 14 months. Dosimetric goals were achieved in over 90% of cases. Three of 102 (3% patients developed Grade 2 acute proctitis. No variables were significantly associated with Grade 2 acute proctitis. Seventeen of 102 (17% patients developed Grade 2 acute urinary retention. American Urological Association (AUA symptom score was the only variable significantly associated with Grade 2 acute urinary retention (p=0.04. There was no ≥ Grade 3 acute toxicity.ConclusionsDosimetric coverage of the prostate and normal tissue sparing were adequate in patients with prostate volumes >50 mL. Higher pre-treatment AUA symptom scores increased the relative risk of Grade 2 acute urinary retention. However, the overall incidence of acute toxicity was acceptable in patients with large prostate volumes.

  3. TU-F-12A-09: GLCM Texture Analysis for Normal-Tissue Toxicity: A Prospective Ultrasound Study of Acute Toxicity in Breast-Cancer Radiotherapy

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    Liu, T; Yang, X; Curran, W; Torres, M [Department of Radiation Oncology and Winship Cancer Institute, Emory University, Atlanta, GA (United States)

    2014-06-15

    Purpose: To evaluate the morphologic and structural integrity of the breast glands using sonographic textural analysis, and identify potential early imaging signatures for radiation toxicity following breast-cancer radiotherapy (RT). Methods: Thirty-eight patients receiving breast RT participated in a prospective ultrasound imaging study. Each participant received 3 ultrasound scans: 1 week before RT (baseline), and at 6-week and 3-month follow-ups. Patients were imaged with a 10-MHz ultrasound on the four quadrant of the breast. A second order statistical method of texture analysis, called gray level co-occurrence matrix (GLCM), was employed to assess RT-induced breast-tissue toxicity. The region of interest (ROI) was 28 mm × 10 mm in size at a 10 mm depth under the skin. Twenty GLCM sonographic features, ratios of the irradiated breast and the contralateral breast, were used to quantify breast-tissue toxicity. Clinical assessment of acute toxicity was conducted using the RTOG toxicity scheme. Results: Ninety-seven ultrasound studies (776 images) were analyzed; and 5 out of 20 sonographic features showed significant differences (p < 0.05) among the baseline scans, the acute toxicity grade 1 and 2 groups. These sonographic features quantified the degree of tissue damage through homogeneity, heterogeneity, randomness, and symmetry. Energy ratio value decreased from 108±0.05 (normal) to 0.99±0.05 (Grade 1) and 0.84±0.04 (Grade 2); Entropy ratio value increased from 1.01±0.01 to 1.02±0.01 and 1.04±0.01; Contrast ratio value increased from 1.03±0.03 to 1.07±0.06 and 1.21±0.09; Variance ratio value increased from 1.06±0.03 to 1.20±0.04 and 1.42±0.10; Cluster Prominence ratio value increased from 0.98±0.02 to 1.01±0.04 and 1.25±0.07. Conclusion: This work has demonstrated that the sonographic features may serve as imaging signatures to assess radiation-induced normal tissue damage. While these findings need to be validated in a larger cohort, they suggest

  4. The {sup 57}Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

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    Oshtrakh, M. I., E-mail: oshtrakh@gmail.com; Alenkina, I. V. [Ural Federal University, Department of Physical Techniques and Devices for Quality Control, Institute of Physics and Technology (Russian Federation); Vinogradov, A. V.; Konstantinova, T. S. [Ural State Medical University (Russian Federation); Semionkin, V. A. [Ural Federal University, Department of Physical Techniques and Devices for Quality Control, Institute of Physics and Technology (Russian Federation)

    2015-04-15

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the {sup 57}Fe hyperfine parameters for normal and patient’s tissues were detected and related to small variations in the {sup 57}Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients’ spleen and liver tissues.

  5. The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

    Science.gov (United States)

    Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

    2015-04-01

    Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57Fe hyperfine parameters for normal and patient's tissues were detected and related to small variations in the 57Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients' spleen and liver tissues.

  6. Radioprotection of normal tissue cells

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    Maier, Patrick; Wenz, Frederik; Herskind, Carsten [Heidelberg University, Department of Radiation Oncology Universitaetsmedizin Mannheim, Medical Faculty Mannheim, Mannheim (Germany)

    2014-08-15

    Improvements of radiotherapy in combination with surgery and systemic therapy have resulted in increased survival rates of tumor patients. However, radiation-induced normal tissue toxicity is still dose limiting. Several strategies have been pursued with the goal to develop substances which may prevent or reduce damage to normal tissue. Drugs applied before radiotherapy are called radioprotectors; those given after radiotherapy to reduce long-term effects are radiomitigators. Despite more than 50 years of research, until now only two substances, amifostine and palifermin, have overcome all obstacles of clinical approval and are applied during radiotherapy of head and neck cancer or total body irradiation, respectively. However, better understanding of the cellular pathways involved in radiation response has allowed the development of several highly promising drugs functioning as scavengers of reactive oxygen species or targeting specific molecules involved in regulation of cell death pathways or cell cycle arrest. The present review describes the major targets for radioprotectors or radiomitigators currently tested in clinical trials. (orig.) [German] Verbesserungen in der Radiotherapie in Kombination mit Chirurgie und Chemotherapie fuehrten zu erhoehten Ueberlebensraten von Tumorpatienten. Trotzdem sind Strahlenfolgen am Normalgewebe weiterhin dosislimitierend. Verschiedene Ansaetze wurden verfolgt, um Substanzen zu entwickeln, die Normalgewebstoxizitaeten verhindern oder verringern. Medikamente, die vor der Radiotherapie verabreicht werden, heissen Radioprotektoren, solche die danach gegeben werden, um langfristige Effekte zu reduzieren, Radiomitigatoren. Trotz mehr als 50 Jahre Forschung ueberwanden nur zwei Substanzen, Amifostin und Palifermin, alle Huerden der klinischen Pruefung und sind fuer die Anwendung waehrend der Radiotherapie von Kopf-Hals-Tumoren bzw. bei Ganzkoerperbestrahlung zugelassen. Jedoch erlaubte das bessere Verstaendnis der Signalwege

  7. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

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    Simpson, Daniel R.; Song, William Y. [Center for Advanced Radiotherapy Technologies, Department of Radiation Oncology, University of California San Diego, La Jolla, CA (United States); Moiseenko, Vitali [Department of Medical Physics, Vancouver Cancer Centre, BC (Canada); Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J. [Center for Advanced Radiotherapy Technologies, Department of Radiation Oncology, University of California San Diego, La Jolla, CA (United States); Mell, Loren K., E-mail: lmell@ucsd.edu [Center for Advanced Radiotherapy Technologies, Department of Radiation Oncology, University of California San Diego, La Jolla, CA (United States)

    2012-05-01

    Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I-III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade {>=}2 GI toxicity and the volume of bowel receiving {>=}45 Gy (V{sub 45}) using the logistic model. Results: Twenty-three patients (46%) had Grade {>=}2 GI toxicity. The mean (SD) V{sub 45} was 143 mL (99). The mean V{sub 45} values for patients with and without Grade {>=}2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V{sub 45} >150 mL. The proportion of patients with Grade {>=}2 GI toxicity with and without V{sub 45} >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and {gamma} were 161 mL (95% confidence interval [CI] 60-399) and 0.31 (95% CI 0.04-0.63), respectively. On multivariable logistic regression, increased V{sub 45} was associated with an increased odds of Grade {>=}2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04-4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V{sub 45} is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V{sub 45} could reduce the risk of Grade {>=}2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  8. Impact of Chemotherapy on Normal Tissue Complication Probability Models of Acute Hematologic Toxicity in Patients Receiving Pelvic Intensity Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bazan, Jose G.; Luxton, Gary; Kozak, Margaret M.; Anderson, Eric M.; Hancock, Steven L.; Kapp, Daniel S.; Kidd, Elizabeth A.; Koong, Albert C.; Chang, Daniel T., E-mail: dtchang@stanford.edu

    2013-12-01

    Purpose: To determine how chemotherapy agents affect radiation dose parameters that correlate with acute hematologic toxicity (HT) in patients treated with pelvic intensity modulated radiation therapy (P-IMRT) and concurrent chemotherapy. Methods and Materials: We assessed HT in 141 patients who received P-IMRT for anal, gynecologic, rectal, or prostate cancers, 95 of whom received concurrent chemotherapy. Patients were separated into 4 groups: mitomycin (MMC) + 5-fluorouracil (5FU, 37 of 141), platinum ± 5FU (Cis, 32 of 141), 5FU (26 of 141), and P-IMRT alone (46 of 141). The pelvic bone was contoured as a surrogate for pelvic bone marrow (PBM) and divided into subsites: ilium, lower pelvis, and lumbosacral spine (LSS). The volumes of each region receiving 5-40 Gy were calculated. The endpoint for HT was grade ≥3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability was calculated using the Lyman-Kutcher-Burman model. Logistic regression was used to analyze association between HT3+ and dosimetric parameters. Results: Twenty-six patients experienced HT3+: 10 of 37 (27%) MMC, 14 of 32 (44%) Cis, 2 of 26 (8%) 5FU, and 0 of 46 P-IMRT. PBM dosimetric parameters were correlated with HT3+ in the MMC group but not in the Cis group. LSS dosimetric parameters were well correlated with HT3+ in both the MMC and Cis groups. Constrained optimization (0normal tissue complication probability curve compared with treatment with Cis. Dose tolerance of PBM and the LSS subsite may be lower for

  9. Extraintestinal heterotopic gastric tissue simulating acute appendicitis

    Institute of Scientific and Technical Information of China (English)

    Elizabeth Bender; Steven P Schmidt

    2008-01-01

    We describe the case of a 68-year-old otherwise healthy male who presented to our emergency room with signs and symptoms of acute appendicitis. Exploratory surgery revealed a normal appendix. Further examination revealed an enlarged lymph node-like mass of tissue near the appendix, in the ileocecal mesentery. This mass was removed and was found to be inflamed heterotopic gastric tissue. Although reports of heterotopic gastric tissue in the literature are common, we believe that this case represents the first report of inflamed heterotopic gastric tissue simulating appendicitis.

  10. 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)

  11. Genetic polymorphisms of PAI-1 and PAR-1 are associated with acute normal tissue toxicity in Chinese rectal cancer patients treated with pelvic radiotherapy.

    Science.gov (United States)

    Zhang, Hui; Wang, Mengyun; Shi, Tingyan; Shen, Lijun; Zhu, Ji; Sun, Menghong; Deng, Yun; Liang, Liping; Li, Guichao; Wu, Yongxin; Fan, Ming; Wei, Qingyi; Zhang, Zhen

    2015-01-01

    Plasminogen activator inhibitor type 1 (PAI-1) and protease-activated receptor-1 (PAR-1) are crucial mediators of the intestinal microenvironment and are involved in radiation-induced acute and chronic injury. To evaluate whether genetic polymorphisms of PAI-1 and PAR-1 were predictors of radiation-induced injury in patients with rectal cancer, we retrospectively evaluated 356 rectal cancer patients who had received pelvic radiotherapy and analyzed the association of genetic polymorphisms of PAI-1 and PAR-1 with acute toxicities after radiotherapy. Acute adverse events were scored, including dermatitis, fecal incontinence (anal toxicity), hematological toxicity, diarrhea, and vomiting. The patients were grouped into grade ≥2 and grade 0-1 toxicity groups to analyze the acute toxicities. Genotyping of six single nucleotide polymorphisms (SNPs) of PAI-1 and PAR-1 was performed using TaqMan assays. A logistic regression model was used to estimate the odds ratios and 95% confidence intervals. Of the 356 individuals, 264 (72.5%) had grade ≥2 total toxicities; within this group, there were 65 (18.3%) individuals who reached grade ≥3 toxicities. There were 19.5% (69/354) and 36.9% (130/352) patients that developed grade ≥2 toxicities for diarrhea and fecal incontinence, respectively. The variant genotype GG of rs1050955 in PAI-1 was found to be negatively associated with the risk of diarrhea and incontinence (PPAI-1 were associated with an increased risk of incontinence. The CT genotype of PAR-1 rs32934 was associated with an increased risk of total toxicity compared with the CC allele. Our results demonstrated that SNPs in the PAI-1 and PAR-1 genes were associated with acute injury in rectal cancer patients treated with pelvic irradiation. These SNPs may be useful biomarkers for predicting acute radiotoxicity in patients with rectal cancer if validated in future studies.

  12. Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

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    Dong, Lihua [Department of Radiation Oncology, The First Hospital of Jilin University, Changchun (China); Cui, Jingkun [Department of Internal Medicine, Nanling School District Hospital of Jilin University, Changchun (China); Tang, Fengjiao; Cong, Xiaofeng [Cancer Center, The First Hospital of Jilin University, Changchun (China); Han, Fujun, E-mail: fujun_han@aliyun.com [Cancer Center, The First Hospital of Jilin University, Changchun (China)

    2015-04-01

    Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATM polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was

  13. EGFR-inhibitors, radiotherapy and normal tissue toxicity

    DEFF Research Database (Denmark)

    Eriksen, J. G.

    2015-01-01

    will be explained with references to the current knowledge of the biology of skin toxicity. Treatment options for acute side-effects in skin and mucosa after bio-radiotherapy is rarely causal. A few attempts have been done; some of them aiming to rephosphorylate the EGFreceptor in the skin with vitamin K3. The talk......EGFR-inhibitors have been used in several clinical settings during the last decade and side-effects related to normal tissues like the skin, mucosa and kidney has been well described. However, when EGFR-inhibitors are combined with radiotherapy, then different skin and mucosa toxicity profiles can...... will discuss the available data from these studies. Across several tumour sites and for different EGFR-inhibitors, a correlation between skin toxicity and tumour response has also been documented. The reason for this correlation is not obvious but probably related to genetic alterations or certain genetic...

  14. Normal tissue dose conformality measures to guide radiotherapy fractionation decisions

    Energy Technology Data Exchange (ETDEWEB)

    Myerson, Robert J. [Department of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri 63110 (United States)

    2011-04-15

    Purpose: To determine conditions under which hypofractionation could be favorable for a normal tissue--even if tumor [{alpha}/{beta}] exceeds the normal tissue's [{alpha}/{beta}]. Methods: The hypofractionation sufficiency condition (HSC) for an organ is defined as a dose conformality constraint such that, if satisfied, a family of tumor control probability isoeffective fractionation schemes will show decreasing normal tissue complication probability with decreasing number of fractions. Results: In the extended equivalent uniform dose (EUD) model [obtained by replacing dose with linear quadratic (LQ) 2 Gy equivalent dose], the HSC for a normal organ is proven to be satisfied if a suitably weighted average of the relative dose [hypofractionation sufficiency index (HSI)] is less than the ratio of normal tissue to tumor [{alpha}/{beta}]. The HSI is determined solely by dose distribution and the normal tissue volume factor, ''a.'' If the HSC is satisfied for every normal tissue of concern, then there is a therapeutic gain with hypofractionation. The corresponding multifractionation sufficiency condition (therapeutic gain with increasing number of fractions) and multifractionation sufficiency index (MSI) are also derived. A sample clinical case is presented. Conclusions: Within the context of the LQ/EUD models, conformality measures (HSI and MSI) can be used to inform fractionation decisions.

  15. 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

  16. A Compendium of Canine Normal Tissue Gene Expression

    OpenAIRE

    Joseph Briggs; Melissa Paoloni; Qing-Rong Chen; Xinyu Wen; Javed Khan; Chand Khanna

    2011-01-01

    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 platf...

  17. Photon emission from normal and tumor human tissues.

    Science.gov (United States)

    Grasso, F; Grillo, C; Musumeci, F; Triglia, A; Rodolico, G; Cammisuli, F; Rinzivillo, C; Fragati, G; Santuccio, A; Rodolico, M

    1992-01-15

    Photon emission in the visible and near ultraviolet range by samples of human tissue removed during surgery has been measured by means of a low noise photomultiplier coupled to a data acquisition system. The results show that among the 25 analyzed samples the 9 from normal tissues had an emission rate of the order of some tens of photons/cm2 min, while most of the 16 tumor tissue samples had a very much higher rate.

  18. Oncopression: gene expression compendium for cancer with matched normal tissues.

    Science.gov (United States)

    Lee, Jungsul; Choi, Chulhee

    2017-07-01

    Expression profile of normal tissue is primary source to find genes showing aberrant expression pattern specific in matched cancer tissue, but sample number of normal control in public gene expression repositories is disproportionally small compared to cancer and scattered in several datasets. We built oncopression by integrating several datasets into one large dataset for comprehensive analysis about 25 types of human cancers including 20 640 cancer samples and 6801 normal control profiles. Expression profiles in cancers can be directly compared to normal tissue counterparts. Validity of the integration was tested using immunohistochemical staining results and principal component analysis. We have utilized the pre-release version of oncopression to identify cancer-specific genes in several studies. Free access at http://www.oncopression.com and all expression data are available for download at the site. cchoi@kaist.ac.kr or jungsullee@gmail.com. Supplementary data are available at Bioinformatics online.

  19. Microarray expression profiling in adhesion and normal peritoneal tissues.

    Science.gov (United States)

    Ambler, Dana R; Golden, Alicia M; Gell, Jennifer S; Saed, Ghassan M; Carey, David J; Diamond, Michael P

    2012-05-01

    To identify molecular markers associated with adhesion and normal peritoneal tissue using microarray expression profiling. Comparative study. University hospital. Five premenopausal women. Adhesion and normal peritoneal tissue samples were obtained from premenopausal women. Ribonucleic acid was extracted using standard protocols and processed for hybridization to Affymetrix Whole Transcript Human Gene Expression Chips. Microarray data were obtained from five different patients, each with adhesion tissue and normal peritoneal samples. Real-time polymerase chain reaction was performed for confirmation using standard protocols. Gene expression in postoperative adhesion and normal peritoneal tissues. A total of 1,263 genes were differentially expressed between adhesion and normal tissues. One hundred seventy-three genes were found to be up-regulated and 56 genes were down-regulated in the adhesion tissues compared with normal peritoneal tissues. The genes were sorted into functional categories according to Gene Ontology annotations. Twenty-six up-regulated genes and 11 down-regulated genes were identified with functions potentially relevant to the pathophysiology of postoperative adhesions. We evaluated and confirmed expression of 12 of these specific genes via polymerase chain reaction. The pathogenesis, natural history, and optimal treatment of postoperative adhesive disease remains unanswered. Microarray analysis of adhesions identified specific genes with increased and decreased expression when compared with normal peritoneum. Knowledge of these genes and ontologic pathways with altered expression provide targets for new therapies to treat patients who have or are at risk for postoperative adhesions. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Normal Caloric Responses during Acute Phase of Vestibular Neuritis

    Science.gov (United States)

    Lee, Sun-Uk; Park, Seong-Ho; Kim, Hyo-Jung; Koo, Ja-Won

    2016-01-01

    Background and Purpose We report a novel finding of caloric conversion from normal responses into unilateral paresis during the acute phase of vestibular neuritis (VN). Methods We recruited 893 patients with a diagnosis of VN at Dizziness Clinic of Seoul National University Bundang Hospital from 2003 to 2014 after excluding 28 patients with isolated inferior divisional VN (n=14) and those without follow-up tests despite normal caloric responses initially (n=14). We retrospectively analyzed the neurotological findings in four (0.5%) of the patients who showed a conversion from initially normal caloric responses into unilateral paresis during the acute phase. Results In those four patients, the initial caloric tests were performed within 2 days of symptom onset, and conversion into unilateral caloric paresis was documented 1–4 days later. The clinical and laboratory findings during the initial evaluation were consistent with VN in all four patients except for normal findings in bedside head impulse tests in one of them. Conclusions Normal findings in caloric tests should be interpreted with caution during the acute phase of suspected VN. Follow-up evaluation should be considered when the findings of the initial caloric test are normal, but VN remains the most plausible diagnosis. PMID:26932259

  1. A Compendium of Canine Normal Tissue Gene Expression

    Science.gov (United States)

    Chen, Qing-Rong; Wen, Xinyu; Khan, Javed; Khanna, Chand

    2011-01-01

    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. PMID:21655323

  2. A compendium of canine normal tissue gene expression.

    Directory of Open Access Journals (Sweden)

    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.

  3. Distribution of Tissue Water and Electrolytes in Normal Rhesus Macaques.

    Science.gov (United States)

    1978-03-02

    reported for hyperthermia, 26 deoxycorticosterone acetate administration,1’3 hypocalcemic tetany)’6 respiratory acidosis and alkalosis , 27’28 and...continuing respiratory work performed by the diaphragm of monkeys. As a rule, values for tissue intracellular water should be greater than those of...C. B., and Lamber t , H.: Card iac and Skeletal Muscle Electrolytes In Acute Respiratory Alkalemia and Acidemia. J Appl Physiol , 15, (1960): 459

  4. Electrical impedance characterization of normal and cancerous human hepatic tissue.

    Science.gov (United States)

    Laufer, Shlomi; Ivorra, Antoni; Reuter, Victor E; Rubinsky, Boris; Solomon, Stephen B

    2010-07-01

    The four-electrode method was used to measure the ex vivo complex electrical impedance of tissues from 14 hepatic tumors and the surrounding normal liver from six patients. Measurements were done in the frequency range 1-400 kHz. It was found that the conductivity of the tumor tissue was much higher than that of the normal liver tissue in this frequency range (from 0.14 +/- 0.06 S m(-1) versus 0.03 +/- 0.01 S m(-1) at 1 kHz to 0.25 +/- 0.06 S m(-1) versus 0.15 +/- 0.03 S m(-1) at 400 kHz). The Cole-Cole models were estimated from the experimental data and the four parameters (rho(0), rho(infinity), alpha, f(c)) were obtained using a least-squares fit algorithm. The Cole-Cole parameters for the cancerous and normal liver are 9 +/- 4 Omega m(-1), 2.2 +/- 0.7 Omega m(-1), 0.5 +/- 0.2, 140 +/- 103 kHz and 50 +/- 28 Omega m(-1), 3.2 +/- 0.6 Omega m(-1), 0.64 +/- 0.04, 10 +/- 7 kHz, respectively. These data can contribute to developing bioelectric applications for tissue diagnostics and in tissue treatment planning with electrical fields such as radiofrequency tissue ablation, electrochemotherapy and gene therapy with reversible electroporation, nanoscale pulsing and irreversible electroporation.

  5. Pharmacokinetic modeling of ascorbate diffusion through normal and tumor tissue.

    Science.gov (United States)

    Kuiper, Caroline; Vissers, Margreet C M; Hicks, Kevin O

    2014-12-01

    Ascorbate is delivered to cells via the vasculature, but its ability to penetrate into tissues remote from blood vessels is unknown. This is particularly relevant to solid tumors, which often contain regions with dysfunctional vasculature, with impaired oxygen and nutrient delivery, resulting in upregulation of the hypoxic response and also the likely depletion of essential plasma-derived biomolecules, such as ascorbate. In this study, we have utilized a well-established multicell-layered, three-dimensional pharmacokinetic model to measure ascorbate diffusion and transport parameters through dense tissue in vitro. Ascorbate was found to penetrate the tissue at a slightly lower rate than mannitol and to travel via the paracellular route. Uptake parameters into the cells were also determined. These data were fitted to the diffusion model, and simulations of ascorbate pharmacokinetics in normal tissue and in hypoxic tumor tissue were performed with varying input concentrations, ranging from normal dietary plasma levels (10-100 μM) to pharmacological levels (>1 mM) as seen with intravenous infusion. The data and simulations demonstrate heterogeneous distribution of ascorbate in tumor tissue at physiological blood levels and provide insight into the range of plasma ascorbate concentrations and exposure times needed to saturate all regions of a tumor. The predictions suggest that supraphysiological plasma ascorbate concentrations (>100 μM) are required to achieve effective delivery of ascorbate to poorly vascularized tumor tissue.

  6. 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 "n...

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

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    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...

  8. Study of normal colorectal tissue by FT-Raman spectroscopy.

    Science.gov (United States)

    Andrade, P O; Bitar, R A; Yassoyama, K; Martinho, H; Santo, A M E; Bruno, P M; Martin, A A

    2007-03-01

    FT-Raman spectroscopy was employed to study normal human colorectal tissues in vitro with the aim of evaluating the spectral differences of the complex colon mucous in order to establish a characteristic Raman spectrum. The samples were collected from 39 patients, providing 144 spectra for the statistical analysis. The results enable one to establish three well-defined spectroscopic groups of non-altered colorectal tissues that were consistently checked by statistical (clustering) and biological (histopathology) analyses: group 1 is represented by samples with the presence of epithelial layer, connective tissue papillae, and smooth muscle tissue; group 2 comprises tissues with epithelial layer and connective tissue papillae; group 3 presented mostly fatty and slack conjunctive tissue. The study reveals the existence of an intrinsic spectral variability for each patient that must be considered when sampling tissues fragments to build a spectral database. This is the first step for future studies and applications of Raman spectroscopy to optical biopsy and diagnosis of colorectal cancer.

  9. Ara-C cytokinetic studies in normal tissues in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Pallavicini, M.G.; Gray, J.W.

    1982-01-01

    The importance of including normal tissues in the design of cytokinetic-based chemotherapeutic schedules is becoming increasingly apparent. However, the lack of rapid analytical techniques to obtain quantitative cytokinetic data on target subpopulations in heterogenous normal tissues, such as the gastrointestinal and hematopoietic system, has limited the inclusion of these tissues in therapy design. Once target subpopulations are identified and/or discriminated, flow cytometry in conjunction with radioactivity measurements by liquid scintillation counting can be used to rapidly obtain quantitative cytokinetic data during drug therapy. The present paper reviews our current cytokinetic techniques and the applications and limitations of these techniques in the analysis of Ara-C induced perturbations in the small intestine and hematopoetic system. Cell cycle information both prior to and 30 hrs following a single Ara-C treatment was obtained in the intestinal crypts and femoral marrow population using radioactive precursor uptake and flow cytometric techniques. In addition, the relationship between crypt cell survival and animal lethality following Ara-C treatment was determined to better understand the impact of a damage to a regenerative population on the ''clinical endpoint'' of animal survival. Understanding the principles behind the normal tissue toxicity which occurs during multidose treatment will hopefully allow modulation of this toxicity through the rational design of optimal chemotherapeutic schedules.

  10. Ara-C cytokinetic studies in normal tissues in vivo.

    Science.gov (United States)

    Pallavicini, M G; Gray, J W

    1982-01-01

    The importance of including normal tissues in the design of cytokinetic-based chemotherapeutic schedules is becoming increasingly apparent. However, the lack of rapid analytical techniques to obtain quantitative cytokinetic data on target subpopulations in heterogenous normal tissues, such as the gastrointestinal and hematopoietic system, has limited the inclusion of these tissues in therapy design. Once target subpopulations are identified and/or discriminated, flow cytometry in conjunction with radioactivity measurements by liquid scintillation counting can be used to rapidly obtain quantitative cytokinetic data during drug therapy. The present paper reviews our current cytokinetic techniques and the applications and limitations of these techniques in the analysis of Ara-C-induced perturbations in the small intestine and hematopoietic system. Cell cycle information both prior to and 30 hrs following a single Ara-C treatment was obtained in the intestinal crypts and femoral marrow population using radioactive precursor uptake and flow cytometric techniques. In addition, the relationship between crypt cell survival and animal lethality following Ara-C treatment was determined to better understand the impact of a damage to a regenerative population on the "clinical endpoint" of animal survival. Understanding the principles behind the normal tissue toxicity which occurs during multidose treatment will hopefully allow modulation of this toxicity through the rational design of optimal chemotherapeutic schedules.

  11. Lung tissue remodeling in the acute respiratory distress syndrome

    Directory of Open Access Journals (Sweden)

    Souza Alba Barros de

    2003-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is characterized by diffuse alveolar damage, and evolves progressively with three phases: exsudative, fibroproliferative, and fibrotic. In the exudative phase, there are interstitial and alveolar edemas with hyaline membrane. The fibropro­liferative phase is characterized by exudate organization and fibroelastogenesis. There is proliferation of type II pneumocytes to cover the damaged epithelial surface, followed by differentiation into type I pneumocytes. The fibroproliferative phase starts early, and its severity is related to the patient?s prognosis. The alterations observed in the phenotype of the pulmonary parenchyma cells steer the tissue remodeling towards either progressive fibrosis or the restoration of normal alveolar architecture. The fibrotic phase is characterized by abnormal and excessive deposition of extracellular matrix proteins, mainly collagen. The dynamic control of collagen deposition and degradation is regulated by metalloproteinases and their tissular regulators. The deposition of proteoglycans in the extracellular matrix of ARDS patients needs better study. The regulation of extracellular matrix remodeling, in normal conditions or in several pulmonary diseases, such as ARDS, results from a complex mechanism that integrate the transcription of elements that destroy the matrix protein and produce activation/inhibition of several cellular types of lung tissue. This review article will analyze the ECM organization in ARDS, the different pulmonary parenchyma remodeling mechanisms, and the role of cytokines in the regulation of the different matrix components during the remodeling process.

  12. Normal tissue toxicity after small field hypofractionated stereotactic body radiation

    OpenAIRE

    Constine Louis S; Milano Michael T; Okunieff Paul

    2008-01-01

    Abstract Stereotactic body radiation (SBRT) is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review ...

  13. EXPRESSION MECHANISM AND CLINICAL SIGNIFICANCE OF NOB1 IN GASTRIC CANCER TISSUE AND ADJACENT NORMAL TISSUE.

    Science.gov (United States)

    Zhou, W-P; Liu, X; Yang, Y; Liu, Y-F

    2015-01-01

    This paper studies the effect and relationship of NOB1 in the development of gastric cancer, based on an analysis of NOB1expression in gastric cancer tissue and adjacent tissue. Thirty gastric cancer tissue samples taken during surgery with complete pathological data and their related adjacent normal tissue were examined in this study. NOB1 protein expression in gastric cancer tissue and adjacent normal tissue was detected by immunohistochemistry (IHC). Real-time PCR was used to detect NOB1 mRNA expression, which provided a basis on which to explore the clinical pathological characteristics for patients with gastric cancer. Results show that NOB1 protein in gastric cancer tissue and adjacent normal tissue were diffusely expressed both in the cytoplasm and nucleus. The positive expression rate in gastric cancer tissue was 73%, higher than that in adjacent normal tissue (47%). Both the reference NAPDH and NOB1 amplification are reflected in the amplification curve in standard S-shape and the unimodal solubility curve which was not altered by non-specific amplification and primer dimer. NOB1 mRNA relative expression in cancer tissue was 4.899∓1.412. NOB1 expression had no direct relationship with the patients’ age, gender, tumor differentiation or infiltration degree, lymphatic metastasis, distant metastasis nor pTNM periodization, but was directly related to the size of the tumor. All the findings in this paper suggest that NOB1 can be one of the focuses for diagnosing and treating gastric cancer and that its protein expression is likely to increase with the growth of tumor, thus playing a great role in the incidence and development of gastric cancer.

  14. Detection of lobular structures in normal breast tissue.

    Science.gov (United States)

    Apou, Grégory; Schaadt, Nadine S; Naegel, Benoît; Forestier, Germain; Schönmeyer, Ralf; Feuerhake, Friedrich; Wemmert, Cédric; Grote, Anne

    2016-07-01

    Ongoing research into inflammatory conditions raises an increasing need to evaluate immune cells in histological sections in biologically relevant regions of interest (ROIs). Herein, we compare different approaches to automatically detect lobular structures in human normal breast tissue in digitized whole slide images (WSIs). This automation is required to perform objective and consistent quantitative studies on large data sets. In normal breast tissue from nine healthy patients immunohistochemically stained for different markers, we evaluated and compared three different image analysis methods to automatically detect lobular structures in WSIs: (1) a bottom-up approach using the cell-based data for subsequent tissue level classification, (2) a top-down method starting with texture classification at tissue level analysis of cell densities in specific ROIs, and (3) a direct texture classification using deep learning technology. All three methods result in comparable overall quality allowing automated detection of lobular structures with minor advantage in sensitivity (approach 3), specificity (approach 2), or processing time (approach 1). Combining the outputs of the approaches further improved the precision. Different approaches of automated ROI detection are feasible and should be selected according to the individual needs of biomarker research. Additionally, detected ROIs could be used as a basis for quantification of immune infiltration in lobular structures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Cross-tissue Analysis of Gene and Protein Expression in Normal and Cancer Tissues.

    Science.gov (United States)

    Kosti, Idit; Jain, Nishant; Aran, Dvir; Butte, Atul J; Sirota, Marina

    2016-05-04

    The central dogma of molecular biology describes the translation of genetic information from mRNA to protein, but does not specify the quantitation or timing of this process across the genome. We have analyzed protein and gene expression in a diverse set of human tissues. To study concordance and discordance of gene and protein expression, we integrated mass spectrometry data from the Human Proteome Map project and RNA-Seq measurements from the Genotype-Tissue Expression project. We analyzed 16,561 genes and the corresponding proteins in 14 tissue types across nearly 200 samples. A comprehensive tissue- and gene-specific analysis revealed that across the 14 tissues, correlation between mRNA and protein expression was positive and ranged from 0.36 to 0.5. We also identified 1,012 genes whose RNA and protein expression was correlated across all the tissues and examined genes and proteins that were concordantly and discordantly expressed for each tissue of interest. We extended our analysis to look for genes and proteins that were differentially correlated in cancer compared to normal tissues, showing higher levels of correlation in normal tissues. Finally, we explored the implications of these findings in the context of biomarker and drug target discovery.

  16. Dietary carotenoids in normal and pathological tissues of corpus uteri.

    Directory of Open Access Journals (Sweden)

    Sławomir Wołczyński

    2008-12-01

    Full Text Available Carotenoids and retinyl esters are the source of vitamin A in the human body and its natural derivatives takes part in the regulation of cell replication and differentiation in the human endometrium, may induce the leiomyoma growth and has a role in differentiation of endometrial adenocarcinoma. The aim of the study was to demonstrate the presence of carotenoids in tissues from the normal uterus and from various tumors of the uterine corpus, as well as to compare the total content, major carotenoids and % of carotenoids belonging to the provitamin A group between the tissues examined. Using three independent methods of chromatography (CC, TLC, HPLC we analysed 140 human samples. We identified 13 carotenoids belonging to the eg. provitamin A group and epoxy carotenoids. In all the samples beta-carotene, beta-cryptoxanthin, lutein, neoxanthin, violaxanthin and mutatoxanthin were isolated. In normal tissues, the mean carotenoid content was the highest in the follicular phase endometrium (9.9 microg/g, while the highest percentage of carotenoids belonging to provitamin A group was found in the luteal phase (18.2%. In the pathological group, the highest mean values were demonstrated for epithelial lesions (8.0 microg/g, and within this group - in endometrioid adenocarcinoma (10.8 microg/g. In both groups, violaxanthin, beta-cryptoxanthin, lutein epoxide and mutatoxanthin were the predominant carotenoids. We have demonstrated that all uterine tissues show a concentration of beta-carotene and beta-cryptoxanthin, being the source of vitamin A. The highest total values of carotenoids obtained in the group of endometrioid adenocarcinoma seem to confirm certain enzymatic defects in carotenoid metabolism in the course of the neoplastic process or some metabolic modifications. The finding of astaxanthin - the major antioxidant among carotenoids - in 63% of tissues examined is also significant.

  17. Dopamine regulates angiogenesis in normal dermal wound tissues.

    Directory of Open Access Journals (Sweden)

    Saurav Shome

    Full Text Available Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D(2 DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D(2 DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D(2 DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5β1 integrin, which play a pivotal role in wound angiogenesis. Since D(2 DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities.

  18. Gene expression profiles in liver cancer and normal liver tissues

    Institute of Scientific and Technical Information of China (English)

    Lian Xin Liu; Hong Chi Jiang; An Long Zhu; Jin Zhou; Xiu Qin Wang; Min Wu

    2000-01-01

    AIM To describe a liver cancer = specific gene expression profile and to identify genes that showed alteredexpression between liver cancer tissues and their adjacent nearly normal tissues.METHODS The cDNA probes which were labeled with a-32P dATP were synthesized from total RNA ofliver cancer and adjacent normal tissues and hybridized separately to two identical Atlas human cancer eDNAexpression array membranes containing 588 known genes.RESULTS Autoradiographic results were analyzed by specific Atlas ImageTM (version 1. 0) software.Among the 588 genes analyzed, 18 genes were found up-regulated in cancer, including TFDP2, Aktl, E2F-3etc, and 25 genes were down-regulated in cancer, including TDGF1, BAK, LAR, etc. Expression levels ofgenes that associated with the regulation of cell proliferation, apoptosis, differentiation, cell-cellinteraction, invasion regulators and eytokines altered mostly.CONCLUSION The result obtained from Atlas microarray provides a comprehensive liver cancer-specificexpression profile. The results can lead to the identification of liver cancer-specific biomarkers and may behelpful in early diagnosis and dentifiction of target genes for designing rational therapeutic strategies.

  19. Toward Signaling-Driven Biomarkers Immune to Normal Tissue Contamination

    Science.gov (United States)

    Stansfield, John C.; Rusay, Matthew; Shan, Roger; Kelton, Conor; Gaykalova, Daria A.; Fertig, Elana J.; Califano, Joseph A.; Ochs, Michael F.

    2016-01-01

    The goal of this study was to discover a minimally invasive pathway-specific biomarker that is immune to normal cell mRNA contamination for diagnosing head and neck squamous cell carcinoma (HNSCC). Using Elsevier’s MedScan natural language processing component of the Pathway Studio software and the TRANSFAC database, we produced a curated set of genes regulated by the signaling networks driving the development of HNSCC. The network and its gene targets provided prior probabilities for gene expression, which guided our CoGAPS matrix factorization algorithm to isolate patterns related to HNSCC signaling activity from a microarray-based study. Using patterns that distinguished normal from tumor samples, we identified a reduced set of genes to analyze with Top Scoring Pair in order to produce a potential biomarker for HNSCC. Our proposed biomarker comprises targets of the transcription factor (TF) HIF1A and the FOXO family of TFs coupled with genes that show remarkable stability across all normal tissues. Based on validation with novel data from The Cancer Genome Atlas (TCGA), measured by RNAseq, and bootstrap sampling, the biomarker for normal vs. tumor has an accuracy of 0.77, a Matthews correlation coefficient of 0.54, and an area under the curve (AUC) of 0.82. PMID:26884679

  20. Con A affinity glycoproteomics of normal human liver tissue

    Institute of Scientific and Technical Information of China (English)

    SUN QiangLing; LU HaoJie; LIU YinKun; LU WenJing; CHENG Gang; ZHOU HaiJun; ZHOU XinWen; WEI LiMing; DAI Zhi; GUO Kun

    2007-01-01

    In order to establish the novel high throughput, high efficiency and Iow cost technological platform for the research of N-glycoproteomics, to resolve the significance of characteristic expression profile of glycoprotein and to find the proteins with biological functional importance, the glycoproteins with high-mannose core and the two antennary types were purified and enriched by the Con A affinity chromatography. Con A affinity protein expression profiles of normal human liver tissue were generated by using SDS-PAGE, two-dimensional electrophoresis (2-DE) followed by fast fluorescence staining based on multiplexed proteomics (MP) technology. 301 visible protein spots on the gel were detected and 85 of glycoproteins were further successfully identified via peptide mass fingerprinting (PMF) by a matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS/MS) and annotated to IPI databases. Identified glycoproteins definitely take part in the regulation of cell cycle and metabolic processes. The glycosylation sites were predicted with NetNGlyc 1.0 and NetOGlyc 3.1 software, meanwhile they were classified according to the geneontology methods. The construction of Con A affinity glycoprotein database of normal human liver tissue would contribute to the subsequent research.

  1. Genetic variation in normal tissue toxicity induced by ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Popanda, Odilia, E-mail: o.popanda@dkfz.de [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Marquardt, Jens Uwe [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Chang-Claude, Jenny [Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Schmezer, Peter [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2009-07-10

    Radiotherapy is an important weapon in the treatment of cancer, but adverse reactions developing in the co-irradiated normal tissue can be a threat for patients. Early reactions might disturb the usual application schedule and limit the radiation dose. Late appearing and degenerative reactions might reduce or destroy normal tissue function. Genetic markers conferring the ability to identify hyper-sensitive patients in advance would considerably improve therapy. Association studies on genetic variation and occurrence of side effects should help to identify such markers. This survey includes published studies and novel data from our own laboratory. It illustrates the presence of candidate polymorphisms in genes involved in the cellular response to irradiation which could be used as predictive markers for radiosensitivity in breast or prostate cancer patients. For other tumor types such as head and neck cancers or brain tumors, the available data are much more limited. In any case, further validation of these markers is needed in large patient cohorts with systematically recorded data on side effects and patient characteristics. Genetic variation contributing to radiosensitivity should be screened on a broader basis using newly developed, more comprehensive approaches such as genome-wide association studies.

  2. Con A affinity glycoproteomics of normal human liver tissue

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In order to establish the novel high throughput, high efficiency and low cost technological platform for the research of N-glycoproteomics, to resolve the significance of characteristic expression profile of glycoprotein and to find the proteins with biological functional importance, the glycoproteins with high-mannose core and the two antennary types were purified and enriched by the Con A affinity chromatography. Con A affinity protein expression profiles of normal human liver tissue were gener- ated by using SDS-PAGE, two-dimensional electrophoresis (2-DE) followed by fast fluorescence stain- ing based on multiplexed proteomics (MP) technology. 301 visible protein spots on the gel were de- tected and 85 of glycoproteins were further successfully identified via peptide mass fingerprinting (PMF) by a matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF- MS/MS) and annotated to IPI databases. Identified glycoproteins definitely take part in the regulation of cell cycle and metabolic processes. The glycosylation sites were predicted with NetNGlyc 1.0 and NetOGlyc 3.1 software, meanwhile they were classified according to the geneontology methods. The construction of Con A affinity glycoprotein database of normal human liver tissue would contribute to the subsequent research.

  3. 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.

  4. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome.

    Science.gov (United States)

    Ley, Timothy J; Mardis, Elaine R; Ding, Li; Fulton, Bob; McLellan, Michael D; Chen, Ken; Dooling, David; Dunford-Shore, Brian H; McGrath, Sean; Hickenbotham, Matthew; Cook, Lisa; Abbott, Rachel; Larson, David E; Koboldt, Dan C; Pohl, Craig; Smith, Scott; Hawkins, Amy; Abbott, Scott; Locke, Devin; Hillier, Ladeana W; Miner, Tracie; Fulton, Lucinda; Magrini, Vincent; Wylie, Todd; Glasscock, Jarret; Conyers, Joshua; Sander, Nathan; Shi, Xiaoqi; Osborne, John R; Minx, Patrick; Gordon, David; Chinwalla, Asif; Zhao, Yu; Ries, Rhonda E; Payton, Jacqueline E; Westervelt, Peter; Tomasson, Michael H; Watson, Mark; Baty, Jack; Ivanovich, Jennifer; Heath, Sharon; Shannon, William D; Nagarajan, Rakesh; Walter, Matthew J; Link, Daniel C; Graubert, Timothy A; DiPersio, John F; Wilson, Richard K

    2008-11-06

    Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.

  5. Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype.

    Science.gov (United States)

    Cazzaniga, Giovanni; Dell'Oro, Maria Grazia; Mecucci, Cristina; Giarin, Emanuela; Masetti, Riccardo; Rossi, Vincenzo; Locatelli, Franco; Martelli, Massimo F; Basso, Giuseppe; Pession, Andrea; Biondi, Andrea; Falini, Brunangelo

    2005-08-15

    Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein involved in leukemia-associated chromosomal translocations, and it regulates the alternate reading frame (ARF)-p53 tumor-suppressor pathway. Recently, it has been demonstrated that mutations of the NPM1 gene alter the protein at its C-terminal, causing its cytoplasmic localization. Cytoplasmic NPM was detected in 35% of adult patients with primary non-French-American-British (FAB) classification M3 acute myeloid leukemia (AML), associated mainly with normal karyotype. We evaluated the prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP-AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107 successfully analyzed patients. NPM1-mutated patients carried a normal karyotype (7/26, 27.1%) and were older in age. Thus, the NPM1 mutation is a frequent abnormality in AML patients without known genetic marker; the mutation may represent a new target to monitor minimal residual disease in AML and a potential candidate for alternative and targeted treatments.

  6. Normal tissue toxicity after small field hypofractionated stereotactic body radiation

    Directory of Open Access Journals (Sweden)

    Constine Louis S

    2008-10-01

    Full Text Available Abstract Stereotactic body radiation (SBRT is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review will discuss the basic principles of SBRT, the radiobiology of hypofractionated radiation and the outcome from published clinical trials of SBRT, with a focus on late toxicity after SBRT. While clinical data has shown SBRT to be safe in most circumstances, more data is needed to refine the ideal dose-volume metrics.

  7. Normal tissue toxicity after small field hypofractionated stereotactic body radiation

    Science.gov (United States)

    Milano, Michael T; Constine, Louis S; Okunieff, Paul

    2008-01-01

    Stereotactic body radiation (SBRT) is an emerging tool in radiation oncology in which the targeting accuracy is improved via the detection and processing of a three-dimensional coordinate system that is aligned to the target. With improved targeting accuracy, SBRT allows for the minimization of normal tissue volume exposed to high radiation dose as well as the escalation of fractional dose delivery. The goal of SBRT is to minimize toxicity while maximizing tumor control. This review will discuss the basic principles of SBRT, the radiobiology of hypofractionated radiation and the outcome from published clinical trials of SBRT, with a focus on late toxicity after SBRT. While clinical data has shown SBRT to be safe in most circumstances, more data is needed to refine the ideal dose-volume metrics. PMID:18976463

  8. 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.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    haplotypes, and handling of confounding factors. Finally, candidate gene studies elucidating the genetic component of radiation-induced morbidity and the functional consequences of single nucleotide polymorphisms by studying intermediate phenotypes will be discussed. Udgivelsesdato: 2008-Apr......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...... of radiation-induced morbidity and highlights some recent successful whole-genome association studies showing feasibility in other research areas. Future genetic association studies are discussed in relation to methodological problems such as the characterization of clinical and biological phenotypes, genetic...

  10. 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.

  11. Soft tissue cephalometric norms in Iranian normal subjects

    Directory of Open Access Journals (Sweden)

    Hossein Aghili

    2016-04-01

    Full Text Available Soft tissue analysis has been proposed by many authors as a reliable guide in treatment planning. Thus establishing population norms is an important issue in orthodontic treatment. The aim of this study was to determine the mean values of some of the soft tissue facial traits in Iranian subjecsts as determined by Bergman. Lateral cephalograms of 120 Iranian subjects (60 males and 60 females in five age groups (n= 24 with well balanced face and normal occlusion were used.statistical analyses were done by means of unpaired student’s t-test and one way AOVA. The associations of variables with age and also with each other were assessed using Pearson’s correlation coefficient. The norms valuesfor Iranian subjects differ from those of Bergman in upper and lower lip thicknesses, facial profile angle and upper lip length (in males.sexual dimorphism was determined in lower facial height, upper lip length, upper lip thickness and lower lip thickness. All of the variables were significantly correlated with age except for facial profile angle. Iranian norms differ from those of other population which are usually used. Therefore, when planning a treatment for this population their own norms should be employed

  12. Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation.

    Directory of Open Access Journals (Sweden)

    Bong-Sung Kim

    Full Text Available Macrophage migration inhibitory factor (MIF is a pleiotropic cytokine and has been implicated in inflammatory diseases. However, little is known about the regulation of MIF in adipose tissue and its impact on wound healing. The aim of this study was to investigate MIF expression in inflamed adipose and determine its role in inflammatory cell recruitment and wound healing. Adipose tissue was harvested from subcutaneous adipose tissue layers of 24 healthy subjects and from adipose tissue adjacent to acutely inflamed wounds of 21 patients undergoing wound debridement. MIF protein and mRNA expression were measured by ELISA and RT-PCR. Cell-specific MIF expression was visualized by immunohistochemistry. The functional role of MIF in cell recruitment was investigated by a chemotaxis assay and by flow cytometry of labeled macrophages that were injected into Mif-/-and wildtype mice. Wound healing was evaluated by an in vitro scratch assay on human fibroblast monolayers. MIF protein levels of native adipose tissue and supernatants from acutely inflamed wounds were significantly elevated when compared to healthy controls. MIF mRNA expression was increased in acutely inflamed adipose tissue indicating the activation of MIF gene transcription in response to adipose tissue inflammation. MIF is expressed in mature adipocytes and in infiltrated macrophages. Peripheral blood mononuclear cell migration was significantly increased towards supernatants derived from inflamed adipose tissue. This effect was partially abrogated by MIF-neutralizing antibodies. Moreover, when compared to wildtype mice, Mif-/-mice showed reduced infiltration of labeled macrophages into LPS-stimulated epididymal fat pads in vivo. Finally, MIF antibodies partially neutralized the detrimental effect of MIF on fibroblast wound healing. Our results indicate that increased MIF expression and rapid activation of the MIF gene in fat tissue adjacent to acute wound healing disorders may play a

  13. Multispectral imaging of acute wound tissue oxygenation

    Directory of Open Access Journals (Sweden)

    Audrey Huong

    2017-05-01

    Full Text Available This paper investigates the appropriate range of values for the transcutaneous blood oxygen saturation (StO2 of granulating tissues and the surrounding tissue that can ensure timely wound recovery. This work has used a multispectral imaging system to collect wound images at wavelengths ranging between 520nm and 600nm with a resolution of 10nm. As part of this research, a pilot study was conducted on three injured individuals with superficial wounds of different wound ages at different skin locations. The StO2 value predicted for the examined wounds using the Extended Modified Lambert–Beer model revealed a mean StO2 of 61±10.3% compared to 41.6±6.2% at the surrounding tissues, and 50.1±1.53% for control sites. These preliminary results contribute to the existing knowledge on the possible range and variation of wound bed StO2 that are to be used as indicators of the functioning of the vasomotion system and wound health. This study has concluded that a high StO2 of approximately 60% and a large fluctuation in this value should precede a good progression in wound healing.

  14. Late-responding normal tissue cells benefit from high-precision radiotherapy with prolonged fraction delivery times via enhanced autophagy

    Science.gov (United States)

    Yao, Qiwei; Zheng, Rong; Xie, Guozhu; Liao, Guixiang; Du, Shasha; Ren, Chen; Li, Rong; Lin, Xiaoshan; Hu, Daokun; Yuan, Yawei

    2015-01-01

    High-precision radiotherapy (HPR) has established its important role in the treatment of tumors due to its precise dose distribution. Given its more complicated delivery process, HPR commonly requires more fraction delivery time (FDT). However, it is unknown whether it has an identical response of prolonged FDT on different normal tissues. Our results showed that fractionated irradiation with prolonged FDTs (15, 36, and 50 minutes) enhanced cell surviving fractions for normal tissue cells compared with irradiation with an FDT of 2 minutes. However, the late-responding normal cell line HEI-OC1 was more responsive to prolonged FDTs and demonstrated higher surviving fractions and significantly decreased apoptosis and DNA damage compared to the acute-responding normal cell line HaCaT. Increased autophagy mediated via the ATM-AMPK pathway was observed in HEI-OC1 cells compared with HaCaT cells when irradiated with prolonged FDTs. Furthermore, treatment with the autophagy inhibitor 3-MA or ATM inhibitor KU55933 resulted in enhanced ROS accumulation and attenuation of the effect of prolonged FDT-mediated protection on irradiated HEI-OC1 cells. Our results indicated that late-responding normal tissue cells benefitted more from prolonged FDTs compared with acute-responding tissue cells, which was mainly attributed to enhanced cytoprotective autophagy mediated via the ATM/AMPK signaling pathway. PMID:25766900

  15. EpCAM expression in normal, non-pathological tissues.

    Science.gov (United States)

    Schmelzer, Eva; Reid, Lola M

    2008-01-01

    Epithelial Cell Adhesion Molecule (EpCAM) is a transmembrane glycoprotein that is associated with various cancers. Most normal, non-pathological epithelial tissue is EpCAM positive with the exception of epidermal keratinocytes, gastric parietal cells, myoepithelial cells, thymic cortical epithelial, and hepatocytes. However, during early liver development EpCAM expression is also observed. In our studies, we have demonstrated that EpCAM is expressed in non-pathological human livers on hepatic progenitors in livers of all donor ages, from 16 weeks gestation fetal livers to adult. Hepatic progenitors of the liver consist of the stem cells and their descendants, the hepatoblasts, that give rise to the hepatocytic and biliary lineages. Both hepatic stem cells and most hepatoblasts express EpCAM, but only hepatoblasts are alpha-fetoprotein positive. The percentage of EpCAM positive progenitors in human livers varies with donor age and is about 2.5% in the adult and 12.1% in fetuses. In vivo, hepatic stem cells have been found associated with the canals of Hering. Xeno-transplantation experiments with EpCAM positive human liver cells have revealed their potential for proliferation and differentiation to mature liver parenchymal cells.

  16. Extensive Hidden Genomic Mosaicism Revealed in Normal Tissue.

    Science.gov (United States)

    Vattathil, Selina; Scheet, Paul

    2016-03-03

    Genomic mosaicism arising from post-zygotic mutation has recently been demonstrated to occur in normal tissue of individuals ascertained with varied phenotypes, indicating that detectable mosaicism may be less an exception than a rule in the general population. A challenge to comprehensive cataloging of mosaic mutations and their consequences is the presence of heterogeneous mixtures of cells, rendering low-frequency clones difficult to discern. Here we applied a computational method using estimated haplotypes to characterize mosaic megabase-scale structural mutations in 31,100 GWA study subjects. We provide in silico validation of 293 previously identified somatic mutations and identify an additional 794 novel mutations, most of which exist at lower aberrant cell fractions than have been demonstrated in previous surveys. These mutations occurred across the genome but in a nonrandom manner, and several chromosomes and loci showed unusual levels of mutation. Our analysis supports recent findings about the relationship between clonal mosaicism and old age. Finally, our results, in which we demonstrate a nearly 3-fold higher rate of clonal mosaicism, suggest that SNP-based population surveys of mosaic structural mutations should be conducted with haplotypes for optimal discovery.

  17. Extensive Hidden Genomic Mosaicism Revealed in Normal Tissue

    Science.gov (United States)

    Vattathil, Selina; Scheet, Paul

    2016-01-01

    Genomic mosaicism arising from post-zygotic mutation has recently been demonstrated to occur in normal tissue of individuals ascertained with varied phenotypes, indicating that detectable mosaicism may be less an exception than a rule in the general population. A challenge to comprehensive cataloging of mosaic mutations and their consequences is the presence of heterogeneous mixtures of cells, rendering low-frequency clones difficult to discern. Here we applied a computational method using estimated haplotypes to characterize mosaic megabase-scale structural mutations in 31,100 GWA study subjects. We provide in silico validation of 293 previously identified somatic mutations and identify an additional 794 novel mutations, most of which exist at lower aberrant cell fractions than have been demonstrated in previous surveys. These mutations occurred across the genome but in a nonrandom manner, and several chromosomes and loci showed unusual levels of mutation. Our analysis supports recent findings about the relationship between clonal mosaicism and old age. Finally, our results, in which we demonstrate a nearly 3-fold higher rate of clonal mosaicism, suggest that SNP-based population surveys of mosaic structural mutations should be conducted with haplotypes for optimal discovery. PMID:26942289

  18. On radiation damage to normal tissues and its treatment. Pt. 2; Anti-inflammatory drugs

    Energy Technology Data Exchange (ETDEWEB)

    Michalowski, A.S. (MRC Cyclotron Unit, Hammersmith Hospital, London (United Kingdom))

    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[sub 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.).

  19. Genomic determinants of normal tissue toxicity after radiotherapy for head and neck malignancy: a systematic review.

    Science.gov (United States)

    Ghazali, Naseem; Shaw, Richard J; Rogers, Simon N; Risk, Janet M

    2012-11-01

    Interindividual variations in radiotoxicity responses exist despite uniform treatment protocols. It is speculated that normal genetic variants, particularly single nucleotide polymorphisms (SNPs) may influence normal head and neck (HN) tissue radiotoxicity. This first-ever systematic review was undertaken to evaluate the association of SNPs with normal HN tissues radiotoxicity. Multiple databases (1950-February 2012) were reviewed using a combination of related keywords and MeSH terms. All published HN radiotoxicity studies with sufficient relevant data for extraction were included. The outcomes evaluated were acute and late radiotoxicity endpoints. Methodological quality assessment based on the STrengthening the REporting of Genetic Association (STREGA) statement was performed. Seven articles from 692 articles searched fulfilled the eligibility criteria. Recruited sample sizes were small (range, 32-140). There were 5/7 case-control studies. All studies used multimodality treatment with heterogeneous radiation parameters. Candidate gene approach was used in all studies. Fourteen SNPs from 9 genes were evaluated from the following pathways: DNA damage response, radiation fibrogenesis and oxidative/xenobiotic metabolism. Acute radiotoxicity events were associated with SNPs of DNA repair genes (OR, 3.01-4.08). SNPs of TGFβ1 were associated with osteoradionecrosis (OR, 4.2) and subcutaneous fibrosis. Genetic association studies in HN radiotoxicity currently provide hypothesis-generating findings that require validation in larger studies. Future studies must incorporate critical methodological issues and technological improvements, including using a genome-wide approach. Headway is possible through case-pooling of existing clinical trial data which could create a larger sample size of well-characterized treatment and endpoints. Also, on-going HN cancer clinical trials should consider extending their toxicity evaluation to include genetic association studies. Copyright

  20. 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.

  1. Induction in myeloid leukemic cells of genes that are expressed in different normal tissues

    OpenAIRE

    2005-01-01

    Using DNA microarray and cluster analysis of expressed genes in a cloned line (M1-t-p53) of myeloid leukemic cells, we have analyzed the expression of genes that are preferentially expressed in different normal tissues. Clustering of 547 highly expressed genes in these leukemic cells showed 38 genes preferentially expressed in normal hematopoietic tissues and 122 other genes preferentially expressed in different normal non-hematopoietic tissues including neuronal tissues, muscle, liver and te...

  2. Angiotensin II does not acutely regulate conduction velocity in rat atrial tissue

    DEFF Research Database (Denmark)

    Olsen, Kristine B; Braunstein, Thomas H; Sørensen, Charlotte M;

    2011-01-01

    . The aim of the current study was to investigate the acute effect of Ang II on conduction velocity (CV) in atrial tissue from normal and chronically infarcted rats. Methods. Contractile force was measured and CV was determined from the conduction time between electrodes placed on the tissue preparation...... and functional in the free wall preparation. The difference between free wall and auricle was probably not caused by differences in receptor expression since equal amounts of AT1 mRNA were present. To test if myocardial infarction (MI) sensitizes the atrium to Ang II, free atrial wall from rats subjected to 4...

  3. Iron in spleen and liver: Some cases of normal tissues and tissues from patients with hematological malignancies

    Science.gov (United States)

    Alenkina, Irina V.; Oshtrakh, Michael I.; Felner, Israel; Vinogradov, Alexander V.; Konstantinova, Tatiana S.; Semionkin, Vladimir A.

    2016-10-01

    Iron deposits in spleen and liver tissues obtained from several healthy people and patients with mantle cell lymphoma, acute myeloid leukemia and primary myelofibrosis were studied using Mössbauer spectroscopy and magnetization measurements. The results obtained demonstrated differences in the iron content in tissues as well as some variations in the ferrihydrite-like iron core structure in the iron storage proteins in these tissues. The presence of tiny amount of magnetite and paramagnetic component in spleen and liver tissue was also detected in different quantities in the studied tissues.

  4. Radiation effect in normal tissue. Principles of damage and protection; Strahlenwirkung am Normalgewebe. Prinzipien der Schaedigung und Protektion

    Energy Technology Data Exchange (ETDEWEB)

    Doerr, W. [Universitaetsklinikum Dresden (Germany). Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie; Universitaetsklinikum Dresden (Germany). OncoRay - Zentrum fuer Strahlenforschung in der Onkologie

    2010-07-01

    The curative effectivity of external or internal radiotherapy necessitates exposure of normal tissues with significant radiation doses, and hence must be associated with an accepted rate of side effects. These complications can not a priori be considered as an indication of a too aggressive therapy. Based on the time of first diagnosis, early (acute) and late (chronic) radiation sequelae in normal tissues can be distinguished. Early reactions per definition occur within 90 days after onset of the radiation exposure. They are based on impairment of cell production in turnover tissues, which in face of ongoing cell loss results in hypoplasia and eventually a complete loss of functional cells. The latent time is largely independent of dose and is defined by tissue biology (turnover time). Usually, complete healing of early reactions is observed. Late radiation effects can occur after symptom-free latent times of months to many years, with an inverse dependence of latency on dose. Late normal tissue changes are progressive and usually irreversible. They are based on a complex interaction of damage to various cell populations (organ parenchyma, connective tissue, capillaries), with a contribution from macrophages. Late effects are sensitive for a reduction in dose rate (recovery effects). A number of biologically based strategies for protection of normal tissues or for amelioration of radiation effects was and still is tested in experimental systems, yet, only a small fraction of these approaches has so far been introduced into clinical studies. One advantage of most of the methods is that they may be effective even if the treatment starts way after the end of radiation exposure. For a clinical exploitation, hence, the availability of early indicators for the progression of subclinical damage in the individual patient would be desirable. Moreover, there is need to further investigate the molecular pathogenesis of normal tissue effects in more detail, in order to

  5. Normal morphogenesis of epithelial tissues and progression of epithelial tumors.

    Science.gov (United States)

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A

    2012-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted.

  6. DEK oncogene expression during normal hematopoiesis and in Acute Myeloid Leukemia (AML).

    Science.gov (United States)

    Logan, Gemma E; Mor-Vaknin, Nirit; Braunschweig, Till; Jost, Edgar; Schmidt, Pia Verena; Markovitz, David M; Mills, Ken I; Kappes, Ferdinand; Percy, Melanie J

    2015-01-01

    DEK is important in regulating cellular processes including proliferation, differentiation and maintenance of stem cell phenotype. The translocation t(6;9) in Acute Myeloid Leukemia (AML), which fuses DEK with NUP214, confers a poor prognosis and a higher risk of relapse. The over-expression of DEK in AML has been reported, but different studies have shown diminished levels in pediatric and promyelocytic leukemias. This study has characterized DEK expression, in silico, using a large multi-center cohort of leukemic and normal control cases. Overall, DEK was under-expressed in AML compared to normal bone marrow (NBM). Studying specific subtypes of AML confirmed either no significant change or a significant reduction in DEK expression compared to NBM. Importantly, the similarity of DEK expression between AML and NBM was confirmed using immunohistochemistry analysis of tissue mircorarrays. In addition, stratification of AML patients based on median DEK expression levels indicated that DEK showed no effect on the overall survival of patients. DEK expression during normal hematopoiesis did reveal a relationship with specific cell types implicating a distinct function during myeloid differentiation. Whilst DEK may play a potential role in hematopoiesis, it remains to be established whether it is important for leukemagenesis, except when involved in the t(6;9) translocation. Copyright © 2014. Published by Elsevier Inc.

  7. Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Thomsen, C; Sørensen, P G; Karle, H

    1987-01-01

    osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla...

  8. Heterogeneous nuclear expression of the promyelocytic leukemia (PML) protein in normal and neoplastic human tissues.

    Science.gov (United States)

    Gambacorta, M.; Flenghi, L.; Fagioli, M.; Pileri, S.; Leoncini, L.; Bigerna, B.; Pacini, R.; Tanci, L. N.; Pasqualucci, L.; Ascani, S.; Mencarelli, A.; Liso, A.; Pelicci, P. G.; Falini, B.

    1996-01-01

    The RING-finger promyelocytic leukemia (PML) protein is the product of the PML gene that fuses with the retinoic acid receptor-alpha gene in the t(15; 17) translocation of acute promyelocytic leukemia. Wild-type PML localizes in the nucleus with a typical speckled pattern that is a consequence of the concentration of the protein within discrete subnuclear domains known as nuclear bodies. Delocalization of PML from nuclear bodies has been documented in acute promyelocytic leukemia cells and suggested to contribute to leukemogenesis. In an attempt to get new insights into the function of the wild-type PML protein and to investigate whether it displays an altered expression pattern in neoplasms other than acute promyelocytic leukemia, we stained a large number of normal and neoplastic human tissues with a new murine monoclonal antibody (PG-M3) directed against the amino-terminal region of PML. As the PG-M3 epitope is partially resistant to fixatives, only cells that overexpress PML are detected by the antibody in microwave-heated paraffin sections. Among normal tissues, PML was characteristically up-regulated in activated epithelioid histiocytes and fibroblasts in a variety of pathological conditions, columnar epithelium in small active thyroid follicles, well differentiated foamy cells in the center of sebaceous glands, and hypersecretory endometria (Arias-Stella). Interferons, the PML of which is a primary target gene, and estrogens are likely to represent some of the cytokines and/or hormones that may be involved in the up-regulation of PML under these circumstances. In keeping with this concept, we found that PML is frequently overexpressed in Hodgkin and Reed-Sternberg cells of Hodgkin's disease, a tumor of cytokine-producing cells. Among solid tumors, overexpression of PML was frequently found in carcinomas of larynx and thyroid (papillary), epithelial thymomas, and Kaposi's sarcoma, whereas carcinomas of the lung, thyroid (follicular), breast, and colon were

  9. Infrared imaging of normal and diseased cervical tissue sections

    Science.gov (United States)

    Wood, Bayden R.; Bambery, Keith R.; Miller, Lisa M.; Quinn, Michael; Chiriboga, Luis; Diem, Max; McNaughton, Don

    2005-02-01

    Synchrotron FTIR maps, focal plane array and linear array images recorded of 4 μm cervical biopsy sections from the surface epithelium and glandular endometrium are compared in terms of spatial resolution and applicability to the clinical environment. Synchrotron FTIR maps using a 10 μm aperture appear to provide a better spatial resolution capable of discerning single nuclei in the tissue matrix. Unsupervised hierarchical cluster analysis performed on the synchrotron, focal plane array and linear array data in the 1700-1400 cm-1 region show very similar clusters and mean-extracted spectra, demonstrating the robustness of FTIR microscopy and UHCA in the analysis of tissue sections. Maps recorded with the focal plane array using a conventional globar source take one-fortieth of the time but the spatial resolution precludes true single cell analysis in the tissue matrix. The high spatial resolution achieved with the synchrotron shows potential as a gold standard for FTIR diagnosis of cervical samples.

  10. 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.

  11. Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues

    Science.gov (United States)

    2013-09-01

    in Figure 1, telomere shortening occurs specifically in luminal epithelial cells, but not in myoepithelial cells, in histologically normal terminal...the adjacent myoepithelial cells (panel A). In contrast, some TDLUs demonstrate dim telomere signals in the luminal cells when compared to the...adjacent myoepithelial cells (panel B). Through digital image analysis, quantitative determination of the telomere FISH signals confirms this moderated

  12. Reference genes for normalization: A study of rat brain tissue

    DEFF Research Database (Denmark)

    Bonefeld, Birgit; Elfving, Betina; Wegener, Gregers

    2008-01-01

    Quantitative real-time polymerase chain reaction (qPCR) has become a widely used tool in the search for disease genes. When examining gene expression with qPCR in psychiatric diseases, endogenous reference gene(s) must be used for normalization. Traditionally, genes such as beta-actin (ActB), Gap...

  13. Expression Quantitative Trait loci (QTL) in tumor adjacent normal breast tissue and breast tumor tissue

    Science.gov (United States)

    Quiroz-Zárate, Alejandro; Harshfield, Benjamin J.; Hu, Rong; Knoblauch, Nick; Beck, Andrew H.; Hankinson, Susan E.; Carey, Vincent; Tamimi, Rulla M.; Hunter, David J.; Quackenbush, John; Hazra, Aditi

    2017-01-01

    We investigate 71 single nucleotide polymorphisms (SNPs) identified in meta-analytic studies of genome-wide association studies (GWAS) of breast cancer, the majority of which are located in intergenic or intronic regions. To explore regulatory impacts of these variants we conducted expression quantitative loci (eQTL) analyses on tissue samples from 376 invasive postmenopausal breast cancer cases in the Nurses’ Health Study (NHS) diagnosed from 1990–2004. Expression analysis was conducted on all formalin-fixed paraffin-embedded (FFPE) tissue samples (and on 264 adjacent normal samples) using the Affymetrix Human Transcriptome Array. Significance and ranking of associations between tumor receptor status and expression variation was preserved between NHS FFPE and TCGA fresh-frozen sample sets (Spearman r = 0.85, p<10^-10 for 17 of the 21 Oncotype DX recurrence signature genes). At an FDR threshold of 10%, we identified 27 trans-eQTLs associated with expression variation in 217 distinct genes. SNP-gene associations can be explored using an open-source interactive browser distributed in a Bioconductor package. Using a new a procedure for testing hypotheses relating SNP content to expression patterns in gene sets, defined as molecular function pathways, we find that loci on 6q14 and 6q25 affect various gene sets and molecular pathways (FDR < 10%). Although the ultimate biological interpretation of the GWAS-identified variants remains to be uncovered, this study validates the utility of expression analysis of this FFPE expression set for more detailed integrative analyses. PMID:28152060

  14. Expression of BCRP Gene in the Normal Lung Tissue and Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the expression of novel multidrugresistance transporter (BCRP gene) from human MCF-7/AdrVp breast cancer cells in normal lung tissue and non-small lung cancer tissue. Methods: RNA was extracted immediately from fresh normal lung tissue and viable tumor tissue harvested from surgically resected specimens of non-small cell lung cancer patients. cDNA of BCRP gene was prepared by RT-PCR and was then amplified by PCR. cDNA products from those specimens were transferred to blotting membrane through electrophoresis and transferring technique and southern blot hybridization was eventually performed to detect the expression of BCRP gene. Results: RNA were extracted from 8 tumor tissue alone and 12 pairs of tumor tissue and normal lung tissue harvested from the same lung. Four patients' RNA samples with poor quality due to degrading were discarded. cDNA products of BCRP gene were obtained by RT-PCR and were then amplified by PCR in the remain 16 patients' RNA samples. Through southern blot hybridization, BCRP gene was found to be slightly expressed in various amounts in all normal lung tissue (10/10) and only in a half of tumor tissue samples (8/16). Conclusion: BCRP gene is slightly expressed in different amount in all normal lung tissue and only in a half of tumor tissue of non-small cell lung cancer patients. It is possible to induce it's overexpression and to develop multidrug resistance during chemotherapy if using anthracycline anticancer drugs.

  15. Discrimination between normal breast tissue and tumor tissue using CdTe series detector developed for photon-counting mammography

    Science.gov (United States)

    Okamoto, Chizuru; Ihori, Akiko; Yamakawa, Tsutomu; Yamamoto, Shuichiro; Okada, Masahiro; Kato, Misa; Nakajima, Ai; Kodera, Yoshie

    2016-03-01

    We propose a new mammography system using a cadmium telluride (CdTe) series photon-counting detector, having high absorption efficiency over a wide energy range. In a previous study, we showed that the use of high X-ray energy in digital mammography is useful from the viewpoint of exposure dose and image quality. In addition, the CdTe series detector can acquire X-ray spectrum information following transmission through a subject. This study focused on the tissue composition identified using spectral information obtained by a new photon-counting detector. Normal breast tissue consists entirely of adipose and glandular tissues. However, it is very difficult to find tumor tissue in the region of glandular tissue via a conventional mammogram, especially in dense breast because the attenuation coefficients of glandular tissue and tumor tissue are very close. As a fundamental examination, we considered a simulation phantom and showed the difference between normal breast tissue and tumor tissue of various thicknesses in a three-dimensional (3D) scatter plot. We were able to discriminate between both types of tissues. In addition, there was a tendency for the distribution to depend on the thickness of the tumor tissue. Thinner tumor tissues were shown to be closer in appearance to normal breast tissue. This study also demonstrated that the difference between these tissues could be made obvious by using a CdTe series detector. We believe that this differentiation is important, and therefore, expect this technology to be applied to new tumor detection systems in the future.

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

    OpenAIRE

    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 ...

  17. The Acid Soluble Disulphide and Mixed Disulphide Levels of Some Normal Tissues and Transplanted Tumours

    Science.gov (United States)

    Calcutt, G.; Ting, S. M.

    1970-01-01

    The acid soluble disulphides and mixed disulphides of a range of normal rat and mouse tissues and a number of transplanted rat or mouse tumours were measured. The result were considered in relation to other workers' data. It is noted that more radioresponsive tissues have higher levels than the more radioresistant tissues. PMID:5475758

  18. Autophagy, Innate Immunity and Tissue Repair in Acute Kidney Injury

    Directory of Open Access Journals (Sweden)

    Pu Duann

    2016-05-01

    Full Text Available Kidney is a vital organ with high energy demands to actively maintain plasma hemodynamics, electrolytes and water homeostasis. Among the nephron segments, the renal tubular epithelium is endowed with high mitochondria density for their function in active transport. Acute kidney injury (AKI is an important clinical syndrome and a global public health issue with high mortality rate and socioeconomic burden due to lack of effective therapy. AKI results in acute cell death and necrosis of renal tubule epithelial cells accompanied with leakage of tubular fluid and inflammation. The inflammatory immune response triggered by the tubular cell death, mitochondrial damage, associative oxidative stress, and the release of many tissue damage factors have been identified as key elements driving the pathophysiology of AKI. Autophagy, the cellular mechanism that removes damaged organelles via lysosome-mediated degradation, had been proposed to be renoprotective. An in-depth understanding of the intricate interplay between autophagy and innate immune response, and their roles in AKI pathology could lead to novel therapies in AKI. This review addresses the current pathophysiology of AKI in aspects of mitochondrial dysfunction, innate immunity, and molecular mechanisms of autophagy. Recent advances in renal tissue regeneration and potential therapeutic interventions are also discussed.

  19. Leg contracture in mice: an assay of normal tissue response

    Energy Technology Data Exchange (ETDEWEB)

    Stone, H.B.

    1984-07-01

    Leg contracture, defined as the difference in extensibility of the control and irradiated hind legs of mice, was found to correlate with single doses of radiation from about 20 to 80 Gy. The time of development of the early phase of the response coincided with that reported for the appearance of the acute skin response, and in some cases, partially reversed as this reaction healed. The contracture then progressed again at a moderate rate through 90 days, and then more slowly through one year. Skin contraction, measured by decrease in intertattoo distance, was assayed in the same mice. It followed the same time course as leg contracture, but had a different dose-response relationship. To determine the contribution of skin contraction to the overall leg contracture response, mice were sacrificed and the leg contracture measured before and after the removal of the skin of the leg. After doses of up to 30 Gy, little contracture remained from skinning the leg, indicating that skin contraction was largely responsible for leg contracture in this dose range. After doses of about 45 Gy and above, some contracture remained in the skinned legs, although less than in intact legs. There was little or no enhancement of either skin contraction or leg contracture by the hypoxic cell sensitizers metronidazole or misonidazole.

  20. Preparing normal tissue cells for space flight experiments.

    Science.gov (United States)

    Koch, Claudia; Kohn, Florian P M; Bauer, Johann

    2016-01-01

    Deterioration of health is a problem in modern space flight business. In order to develop countermeasures, research has been done on human bodies and also on single cells. Relevant experiments on human cells in vitro are feasible when microgravity is simulated by devices such as the Random Positioning Machine or generated for a short time during parabolic flights. However, they become difficult in regard to performance and interpretation when long-term experiments are designed that need a prolonged stay on the International Space Station (ISS). One huge problem is the transport of living cells from a laboratory on Earth to the ISS. For this reason, mainly rapidly growing, rather robust human cells such as cancer cells, embryonic cells, or progenitor cells have been investigated on the ISS up to now. Moreover, better knowledge on the behavior of normal mature cells, which mimic the in vivo situation, is strongly desirable. One solution to the problem could be the use of redifferentiable cells, which grow rapidly and behave like cancer cells in plain medium, but are reprogrammed to normal cells when substances like retinoic acid are added. A list of cells capable of redifferentiation is provided, together with names of suitable drugs, in this review.

  1. 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

  2. Raman spectra of normal and cancerous mouse mammary gland tissue using near infrared excitation energy

    Science.gov (United States)

    Naik, Vaman; Serhatkulu, G. K.; Dai, H.; Shukla, N.; Weber, R.; Thakur, J. S.; Freeman, D. C.; Pandya, A. K.; Auner, G. W.; Naik, R.; Miller, R. F.; Cao, A.; Klein, M. D.; Rabah, R.

    2006-03-01

    Raman spectra of normal mammary gland tissues, malignant mammary gland tumors, and lymph nodes have been recorded using fresh tissue from mice. Tumors were induced in mice by subcutaneously injecting 4T1 BALB/c mammary tumor (a highly malignant) cell line. The Raman spectra were collected using the same tissues that were examined by histopathology for determining the cancerous/normal state of the tissue. Differences in various peak intensities, peak shifts and peak ratios were analyzed to determine the Raman spectral features that differentiate mammary gland tumors from non-tumorous tissue. Tissues that were confirmed by pathology as cancerous (tumors) show several distinctive features in the Raman spectra compared to the spectra of the normal tissues. For example, the cancerous tissues show Raman peaks at 621, 642, 1004, 1032, 1175 and 1208 cm-1 that are assignable to amino acids containing aromatic side-chains such as phenylalanine, tryptophan and tyrosine. Further, the cancerous tissues show a greatly reduced level of phospholipids compared to the normal tissues. The Raman spectral regions that are sensitive to pathologic alteration in the tissue will be discussed.

  3. Gene expression arrays as a tool to unravel mechanisms of normal tissue radiation injury and prediction of response

    Institute of Scientific and Technical Information of China (English)

    Jacqueline JCM Kruse; Fiona A Stewart

    2007-01-01

    Over the past 5 years there has been a rapid increase in the use of microarray technology in the field of cancer research. The majority of studies use microarray analysis of tumor biopsies for profiling of molecular characteristics in an attempt to produce robust classifiers for prognosis. There are now several published gene sets that have been shown to predict for aggressive forms of breast cancer, where patients are most likely to benefit from adjuvant chemotherapy and tumors most likely to develop distant metastases, or be resistant to treatment. The number of publications relating to the use of microarrays for analysis of normal tissue damage, after cancer treatment or genotoxic exposure, is much more limited. A PubMed literature search was conducted using the following keywords and combination of terms: radiation, normal tissue, microarray, gene expression profiling, prediction. With respect to normal tissue radiation injury, microarrays have been used in three ways: (1) to generate gene signatures to identify sensitive and resistant populations (prognosis); (2) to identify sets of biomarker genes for estimating radiation exposure, either accidental or as a result of terrorist attack (diagnosis); (3) to identify genes and pathways involved in tissue response to injury (mechanistic). In this article we will review all (relevant) papers that covered our literature search criteria on microarray technology as it has been applied to normal tissue radiation biology and discuss how successful this has been in defining predisposition markers for radiation sensitivity or how it has helped us to unravel molecular mechanisms leading to acute and late tissue toxicity. We also discuss some of the problems and limitations in application and interpretation of such data.

  4. 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.

  5. Acute Pancreatitis with Normal Serum Lipase and Amylase: A Rare Presentation

    Directory of Open Access Journals (Sweden)

    Arvind K Mathur

    2016-08-01

    Full Text Available Acute pancreatitis presenting with normal serum amylase and lipase levels is a rare phenomenon. It is thought that typically, acute inflammation and auto-digestion of the pancreas leads to the release of both amylase and lipase, leading to elevated levels in the blood. For this reason, normal serum amylase and lipase levels in a patient with acute abdominal pain would typically rule out acute pancreatitis in favor of another diagnosis. Here we present two cases of acutely ill patients that were confirmed to have acute pancreatitis radiologically but with serum amylase and lipase levels that remained within the normal range throughout their illnesses for both patients. These cases suggest that while an important diagnostic tool, serum amylase and lipase should not be used as the sole factor to either diagnose or rule out acute pancreatitis. Instead, these laboratory markers should be viewed in the context of the patient’s overall presentation, weighted equally with the presenting signs, symptoms, and imaging studies to help guide toward a diagnosis.

  6. Scattering properties of normal and cancerous tissues from human stomach based on phase-contrast microscope

    Science.gov (United States)

    Zhang, Hui; Li, Zhifang; Li, Hui

    2012-12-01

    In order to study scattering properties of normal and cancerous tissues from human stomach, we collect images for human gastric specimens by using phase-contrast microscope. The images were processed by the way of mathematics morphology. The equivalent particle size distribution of tissues can be obtained. Combining with Mie scattering theory, the scattering properties of tissues can be calculated. Assume scattering of light in biological tissue can be seen as separate scattering events by different particles, total scattering properties can be equivalent to as scattering sum of particles with different diameters. The results suggest that scattering coefficient of the cancerous tissue is significantly higher than that of normal tissue. The scattering phase function is different especially in the backscattering area. Those are significant clinical benefits to diagnosis cancerous tissue

  7. Origin and quantification of differences between normal and tumor tissues observed by terahertz spectroscopy

    Science.gov (United States)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-09-01

    The origin of the differences in the refractive index observed between normal and tumor tissues using terahertz spectroscopy has been described quantitatively. To estimate water content differences in tissues, we prepared fresh and paraffin-embedded samples from rats. An approximately 5% increase of water content in tumor tissues was calculated from terahertz time domain spectroscopy measurements compared to normal tissues. A greater than 15% increase in percentage of cell nuclei per unit area in tumor tissues was observed by hematoxylin and eosin stained samples, which generates a higher refractive index of biological components other than water. Both high water content and high cell density resulted in higher refractive index by approximately 0.05 in tumor tissues. It is predicted that terahertz spectroscopy can also be used to detect brain tumors in human tissue due to the same underlying mechanism as in rats.

  8. Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis.

    Science.gov (United States)

    Margan, Madalin Marius; Jitariu, Andreea Adriana; Cimpean, Anca Maria; Nica, Cristian; Raica, Marius

    2016-06-01

    Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis.

  9. "COMPARISON BETWEEN NUMBER OF NERVE FIBERS IN NORMAL BREAST TISSUE, BENIGN LESIONS AND MALIGNANT BREAST TUMORS"

    Directory of Open Access Journals (Sweden)

    H. Soltanghoraiee

    2004-10-01

    Full Text Available Breast cancer is common and is considered second cause of cancer related mortality in females. Regarding importance of breast cancer, more investigation in this field is recommended. For many years investigators believed that neoplasms were not innervated but new findings have proved otherwise. This descriptive study was carried out to compare number of nerve fibers in benign, malignant and normal breast tissue. Of each group several slides were reviewed and 3608.50 mm2 of malignant tumors (ductal carcinoma, 3641 mm2 of benign tumors (fibroadenoma and 2331.25 mm2 of normal breast tissue (mammoplasty were assessed. Numbers of nerve fibers were compared and a significant increase in nerve fibers was found in malignant tumors compared with benign tumors and normal breast tissue. Accuracy of hematoxylin and eosin method were examined by immunohistochemistry staining (neurofilament method and affirmed. These results reveal that malignant tumors of breast have more nerve fibers than normal breast tissue or benign tumors.

  10. Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

    NARCIS (Netherlands)

    Benderitter, Marc; Caviggioli, Fabio; Chapel, Alain; Coppes, Robert P.; Guha, Chandan; Klinger, Marco; Malard, Olivier; Stewart, Fiona; Tamarat, Radia; Van Luijk, Peter; Limoli, Charles L.

    2014-01-01

    Significance: Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for

  11. 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

  12. Distinct Effects of Ionizing Radiation on In vivo Murine Kidney and Brain Normal Tissue Gene Expression

    National Research Council Canada - National Science Library

    Weiling Zhao; Eric Y. Chuang; Mark Mishra; Rania Awwad; Kheem Bisht; Lunching Sun; Phuongmai Nguyen; J. Daniel Pennington; Tony Jau Cheng Wang; C. Matthew Bradbury; Lei Huang; Zhijun Chen; Gil Bar-Sela; Michael E.C. Robbins; David Gius

    2006-01-01

    Purpose: There is a growing awareness that radiation-induced normal tissue injury in late-responding organs, such as the brain, kidney, and lung, involves complex and dynamic responses between multiple cell...

  13. Stem Cell Therapies for the Treatment of Radiation-Induced Normal Tissue Side Effects

    NARCIS (Netherlands)

    Benderitter, Marc; Caviggioli, Fabio; Chapel, Alain; Coppes, Robert P.; Guha, Chandan; Klinger, Marco; Malard, Olivier; Stewart, Fiona; Tamarat, Radia; Van Luijk, Peter; Limoli, Charles L.

    2014-01-01

    Significance: Targeted irradiation is an effective cancer therapy but damage inflicted to normal tissues surrounding the tumor may cause severe complications. While certain pharmacologic strategies can temper the adverse effects of irradiation, stem cell therapies provide unique opportunities for re

  14. Ex-Vivo Characterization of Bioimpedance Spectroscopy of Normal, Ischemic and Hemorrhagic Rabbit Brain Tissue at Frequencies from 10 Hz to 1 MHz

    Science.gov (United States)

    Yang, Lin; Zhang, Ge; Song, Jiali; Dai, Meng; Xu, Canhua; Dong, Xiuzhen; Fu, Feng

    2016-01-01

    Stroke is a severe cerebrovascular disease and is the second greatest cause of death worldwide. Because diagnostic tools (CT and MRI) to detect acute stroke cannot be used until the patient reaches the hospital setting, a portable diagnostic tool is urgently needed. Because biological tissues have different impedance spectra under normal physiological conditions and different pathological states, multi-frequency electrical impedance tomography (MFEIT) can potentially detect stroke. Accurate impedance spectra of normal brain tissue (gray and white matter) and stroke lesions (ischemic and hemorrhagic tissue) are important elements when studying stroke detection with MFEIT. To our knowledge, no study has comprehensively measured the impedance spectra of normal brain tissue and stroke lesions for the whole frequency range of 1 MHz within as short as possible an ex vivo time and using the same animal model. In this study, we established intracerebral hemorrhage and ischemic models in rabbits, then measured and analyzed the impedance spectra of normal brain tissue and stroke lesions ex vivo within 15 min after animal death at 10 Hz to 1 MHz. The results showed that the impedance spectra of stroke lesions significantly differed from those of normal brain tissue; the ratio of change in impedance of ischemic and hemorrhagic tissue with regard to frequency was distinct; and tissue type could be discriminated according to its impedance spectra. These findings further confirm the feasibility of detecting stroke with MFEIT and provide data supporting further study of MFEIT to detect stroke. PMID:27869707

  15. ACUTE RENAL FAILURE WITH NORMAL PLASMA UREA LEVEL SECONDARY TO ACUTE PYELONEPHITIS IN A SINGLE KIDNEY PATIENT

    Directory of Open Access Journals (Sweden)

    Algranati L

    2007-04-01

    Full Text Available SUMMARY: Acute renal failure is a syndrome that usually runs with an increase in creatinine and urea plasma levels. However, there are clinical situations in which this syndrome may run with an increase in plasma creatinine keeping normal the urea one. In this report we present a case of acute renal failure with normal plasma urea level secondary to an acute pyelonephritis in a single kidney patient. The patient had an increased fractional excretion of urea which could explain the normal plasma urea levels found despite of his reduced glomerular filtration. This increased urea excretion state was interpreted as a consequence of the nephrogenic diabetes insipidus and alteration of the intra-renal urea reciclying process that the acute pyelonephritis induced. In conclusion: Acute pyelonephritis in a single kidney patient can appear as a pattern of acute renal failure with normal plasma urea levels.RESUMEN: La insuficiencia renal aguda es un sindrome que característicamente cursa con niveles plasmáticos elevados de urea y creatinina. Sin embargo, hay situaciones clínicas en las cuales este sindrome puede cursar con un incremento de la creatininemia sin presentar elevación de la uremia. En este reporte presentamos un caso clínico de una insuficiencia renal aguda con uremia normal secundaria a una pielonefritis aguda en un paciente con riñón único. El paciente presentaba una elevada excreción fraccional de urea lo cual podía explicar su uremia normal pese a estar cursando una caída del filtrado gomerular. Dicha excreción de urea elevada fue interpretada como secundaria a una diabetes insipida nefrogénica y una alteración en el recirculado intra-renal de la urea ambos producto de la pielonefritis aguda. Concluimos que la pielonefritis aguda en un paciente mono-reno puede presentarse con un patrón de insuficiencia renal aguda con uremia normal.

  16. Molecular forms of trefoil factor 1 in normal gastric mucosa and its expression in normal and abnormal gastric tissues

    Institute of Scientific and Technical Information of China (English)

    Jian-Lin Ren; Jin-Yan Luo; Ya-Pi Lu; Lin Wang; Hua-Xiu Shi

    2006-01-01

    AIM: To study the molecular forms of trefoil factor 1 (TFF1) in normal gastric mucosa and its expression in normal and abnormal gastric tissues (gastric carcinoma, atypical hyperplasia and intestinalized gastric mucosa) and the role of TFF1 in the carcinogenesis and progression of gastric carcinoma and its molecular biological mechanism underlying gastric mucosa protection.METHODS: The molecular forms of TFF1 in normal gastric mucosa were observed by Western blot. The expression of TFF1 in normal and abnormal gastric tissues (gastric carcinoma, atypical hyperplasia and intestinalized gastric mucosa) was also assayed by immunohistochemical method. The average positive AO was estimated by Motic Images Advanced 3.0 software.RESULTS: Three patterns of TFF1 were found in normal gastric mucosa: monomer, dimmer, and TFF1 compound whose molecular weight is about 21 kDa.The concentration of TFF1 compound was the highest among these three patterns. TFF1 was expressed mainly in epithelial cytoplasm of the mucosa in gastric body and antrum, especially around the nuclei. The closer the TFF1 to the lumen, the higher the expression of TFF1.The expression of TFF1 in peripheral tissue of gastric carcinoma (0.51 ± 0.07) was higher than that in normal gastric mucosa (0.44 ± 0.06, P < 0.001). The expression of TFF1 in gastric adenocarcinoma was positively related to the differentiation of adenocarcinoma. The lower the differentiation of adenocarcinoma was, the weaker the expression of TFF1. No TFF1 was expressed in poorly-differentiated adenocarcinoma. The expression of TFF1 in moderately-well differentiated adenocarcinoma (0.45± 0.07) was a little lower than that in normal mucosa (P > 0.05). The expression of TFF1 in gastric mucosa with atypical hyperplasia (0.57 ± 0.03) was significantly higher than that in normal gastric mucosa (P < 0.001).No TFF1 was expressed in intestinalized gastric mucosa.There was no statistically significant difference between the expressions of

  17. Normal tissue studies in radiation oncology: A systematic review of highly cited articles and citation patterns

    OpenAIRE

    Nieder, Carsten; Andratschke, Nicolaus H.; GROSU, ANCA L.

    2014-01-01

    Radiation therapy is one of the cornerstones of modern multidisciplinary cancer treatment. Normal tissue tolerance is critical as radiation-induced side effects may compromise organ function and quality of life. The importance of normal tissue research is reflected by the large number of scientific articles, which have been published between 2006 and 2010. The present study identified important areas of research as well as seminal publications. The article citation rate is among the potential...

  18. MicroRNA and target gene expression based clustering of oral cancer, precancer and normal tissues.

    Science.gov (United States)

    Roy, Roshni; Singh, Richa; Chattopadhyay, Esita; Ray, Anindita; Sarkar, Navonil De; Aich, Ritesh; Paul, Ranjan Rashmi; Pal, Mousumi; Roy, Bidyut

    2016-11-15

    Development of oral cancer is usually preceded by precancerous lesion. Despite histopathological diagnosis, development of disease specific biomarkers continues to be a promising field of study. Expression of miRNAs and their target genes was studied in oral cancer and two types of precancer lesions to look for disease specific gene expression patterns. Expression of miR-26a, miR-29a, miR-34b and miR-423 and their 11 target genes were determined in 20 oral leukoplakia, 20 lichen planus and 20 cancer tissues with respect to 20 normal tissues using qPCR assay. Expression data were, then, used for cluster analysis of normal as well as disease tissues. Expression of miR-26a and miR-29a was significantly down regulated in leukoplakia and cancer tissues but up regulated in lichen planus tissues. Expression of target genes such as, ADAMTS7, ATP1B1, COL4A2, CPEB3, CDK6, DNMT3a and PI3KR1 was significantly down regulated in at least two of three disease types with respect to normal tissues. Negative correlations between expression levels of miRNAs and their targets were observed in normal tissues but not in disease tissues implying altered miRNA-target interaction in disease state. Specific expression profile of miRNAs and target genes formed separate clusters of normal, lichen planus and cancer tissues. Our results suggest that alterations in expression of selected miRNAs and target genes may play important roles in development of precancer to cancer. Expression profiles of miRNA and target genes may be useful to differentiate cancer and lichen planus from normal tissues, thereby bolstering their role in diagnostics. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Doppler sonography in renal transplants; differential diagnosis of normal from acute rejection

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Gyeh Yon; Lee, M. H.; Son, K. M.; Shin, K. S.; Park, Y. H. [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1990-12-15

    We undertook a combined retrospective and prospective analysis of duplex Doppler examinations performed over a perion of 10 months in order to assess the value of Doppler study(DS)in evaluating renal allograft dysfunction. A total of 110 DS on 82 transplant patients were performed including 79 normal transplants, 29 acute rejections and 2 acute tubular necrosis(ATN). Resistive Index(RI) in 79 normal transplants ranged from 0.44 to 0.7 (Mean;0.59+0.07) in the arcuate artery, and from 0.45 to 0.75(mean;0.61+0.08) in the interlobar artery. RI in 29 cases of acute rejection ranged from 0.61 to 1.0 (mean; 0.77+0.10) in the interlobar artery. In ATNRI ranged from 0.59 to 0.63 (mean 0.62) in the arcuate artery, and from 0.59 to 0.62(mean 0.61) in the interlobar artery. The RI in acute rejection is significantly higher than that of the normal transplants (p<0.001). With a resistive index greater than 0.8, 100% positive predictive value was obtained for the diagnosis of acute rejection. The value less than 0.7 was unlikely to suggest acute rejection(negative predictive value 92%)

  20. Tissue specific DNA methylation in normal human breast epithelium and in breast cancer.

    Science.gov (United States)

    Avraham, Ayelet; Cho, Sean Soonweng; Uhlmann, Ronit; Polak, Mia Leonov; Sandbank, Judith; Karni, Tami; Pappo, Itzhak; Halperin, Ruvit; Vaknin, Zvi; Sella, Avishay; Sukumar, Saraswati; Evron, Ella

    2014-01-01

    Cancer is a heterogeneous and tissue-specific disease. Thus, the tissue of origin reflects on the natural history of the disease and dictates the therapeutic approach. It is suggested that tissue differentiation, mediated mostly by epigenetic modifications, could guide tissue-specific susceptibility and protective mechanisms against cancer. Here we studied breast specific methylation in purified normal epithelium and its reflection in breast cancers. We established genome wide methylation profiles of various normal epithelial tissues and identified 110 genes that were differentially methylated in normal breast epithelium. A number of these genes also showed methylation alterations in breast cancers. We elaborated on one of them, TRIM29 (ATDC), and showed that its promoter was hypo-methylated in normal breast epithelium and heavily methylated in other normal epithelial tissues. Moreover, in breast carcinomas methylation increased and expression decreased whereas the reverse was noted for multiple other carcinomas. Interestingly, TRIM29 regulation in breast tumors clustered according to the PAM50 classification. Thus, it was repressed in the estrogen receptor positive tumors, particularly in the more proliferative luminal B subtype. This goes in line with previous reports indicating tumor suppressive activity of TRIM29 in estrogen receptor positive luminal breast cells in contrast to oncogenic function in pancreatic and lung cancers. Overall, these findings emphasize the linkage between breast specific epigenetic regulation and tissue specificity of cancer.

  1. Comparison of the histological morphology between normal skin and scar tissue.

    Science.gov (United States)

    Yang, Shao-wei; Geng, Zhi-jun; Ma, Kui; Sun, Xiao-yan; Fu, Xiao-bing

    2016-04-01

    Skin wound healing is a complex event, and interrupted wound healing process could lead to scar formation. The aim of this study was to examine the morphological changes of scar tissue. Pathological staining (HE staining, Masson's trichrome staining, methenamine silver staining) was used to evaluate the morphological changes of regenerating epidermis in normal skin and scar tissue, and immunofluorescence staining to detect the expression of collagen IV, a component of basement membrane (BM), and the expression of integrinβ4, a receptor for BM laminins. Additionally, the expression of CK14, CK5, and CK10 was measured to evaluate the proliferation and differentiation of keratinocytes in normal skin and scar tissue. The results showed that the structure of the skin was histologically changed in scar tissue. Collagen IV, expressed under the epidermis of normal skin, was reduced distinctly in scar tissue. Integrinβ4, expressed in the basal layer of normal skin, was found absent in the basal layer of scar tissue. Additionally, it was found that keratinocytes in scarring epidermis were more proliferative than in normal skin. These results indicate that during the skin wound healing, altered formation of BM may affect the proliferation of keratinocytes, reepithelial and tissue remodeling, and then result in scar formation. Thus, remodeling BM structure during wound repair may be beneficial for improving healing in cutaneous wounds during clinical practice.

  2. Expression of Resistin Protein in Normal Human Subcutaneous Adipose Tissue and Pregnant Women Subcutaneous Adipose Tissue and Placenta

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yongming; GUO Tiecheng; ZHANG Muxun; GUO Wei; YU Meixia; XUE Keying; HUANG Shiang; CHEN Yanhong; ZHU Huanli; XU Lijun

    2006-01-01

    The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabetes mellitus (T2DM), pregnant physiological insulin resistance (IR) and gestational diabetes mellitus (GDM) was investigated. The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta was detected by using Western blotting method.Fasting serum glucose concentration was measured by glucose oxidase assay. Serum cholesterol (CHOL), serum triglycerides (TG), serum HDL cholesterol (HDL-C) and serum LDL cholesterol (LDL-C) were determined by full automatic biochemical instrument. Fasting insulin was measured by enzyme immunoassay to calculate insulin resistance index (IRI). Height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured to calculate body mass index (BMI) and body fat percentage (BF %). Resistin protein expression in pregnant women placental tissue (67 905±8441) (arbitrary A values) was much higher than that in subcutaneous adipose tissue in pregnant women abdomen (40 718 ± 3818, P < 0.01), non-pregnant women abdomen (38 288±2084, P<0.01), normal human abdomen (39 421±6087, P<0.01)and thigh (14 942 ±6706, P<0. 001) respectively. The resistin expression in abdominal subcutaneous adipose tissue showed no significant difference among pregnant, non-pregnant women and normal human, but much higher than that in thigh subcutaneous adipose tissue (P<0. 001). Pearson analysis revealed that resistin protein was correlated with BMI (r=0.42), fasting insulin concentration (r=0.38),IRI (r=0. 34), BF % (r=0.43) and fasting glucose (r=0. 39), but not with blood pressure,CHOL, TG, HDL-C and LDL-C. It was suggested that resistin protein expression in human abdominal subcutaneous adipose tissue was much higher

  3. Selective radioprotection of normal tissues by bowman-birk proteinase inhibitor (BBI) in mice

    Energy Technology Data Exchange (ETDEWEB)

    Dittmann, K.; Toulany, M.; Peter Rodemann, H. [Div. of Radiobiology and Environmental Research, Dept. of Radiation Oncology, Univ. of Tuebingen (Germany); Classen, J.; Heinrich, V. [Dept. of Radiation Oncology, Univ. of Tuebingen (Germany); Milas, L. [Dept. of Experimental Radiation Oncology, The Univ. of Texas, M.D. Anderson Cancer Center, Houston, TX (United States)

    2005-03-01

    Background and purpose: the efficacy of radiotherapy is limited by the response of normal tissues within the radiation field. The application of normal-tissue-specific radioprotectors may improve the therapeutic benefit of radiotherapy. The purpose of the present study was to explore the in vivo normal-tissue radioprotective potential of Bowman-Birk proteinase inhibitor (BBI), which acts as a normal-cell-specific radioprotector in vitro. Material and methods: the leg contracture assay in mice, a model system assessing radiation-induced fibrotic processes, was used. To determine whether BBI acts also as a radioprotector of tumors (i.e., FSA and FSAII), the tumor growth delay assay was used. Results: radiation induced leg contracture in mice with a maximum of about 8 mm at day 150 after irradiation. Treatment of mice with 100 mg/kg BBI before irradiation reduced leg contracture by > 4 mm, by about 50% (p < 0.05, t-test). Doses < 100 mg/kg were ineffective, and doses > 100 mg/kg did not further increase the degree of radioprotection. By contrast, BBI did not induce radioprotection of either TP53-mutated FSA or TP53-normal FSAII tumor xenografts in mice, which argues for normal-tissue-specific effect. Conclusion: BBI acts as a potent selective normal-tissue radioprotector in vitro and in vivo, apparently without protecting tumors, and thus has the potential to improve clinical radiotherapy. (orig.)

  4. Indentation loading response of a resonance sensor--discriminating prostate cancer and normal tissue.

    Science.gov (United States)

    Jalkanen, Ville; Andersson, Britt M; Bergh, Anders; Ljungberg, Börje; Lindahl, Olof A

    2013-10-01

    Prostate cancer is the most common type of cancer among men worldwide. Mechanical properties of prostate tissue are promising for distinguishing prostate cancer from healthy prostate tissue. The aim was to investigate the indentation loading response of a resonance sensor for discriminating prostate cancer tissue from normal tissue. Indentation measurements were done on prostate tissue specimens ex vivo from 10 patients from radical prostatectomy. The measurement areas were analysed using standard histological methods. The stiffness parameter was linearly dependent on the loading force (average R(2 )= 0.90) and an increased loading force caused a greater stiffness contrast of prostate cancer vs normal tissue. The accuracy of the stiffness contrast was assessed by the ROC curve with the area under the curve being 0.941 for a loading force of 12.8 mN. The results are promising for the development of a resonance sensor instrument for detecting prostate cancer.

  5. Classification of normal and cancerous lung tissues by electrical impendence tomography.

    Science.gov (United States)

    Gao, Jianling; Yue, Shihong; Chen, Jun; Wang, Huaxiang

    2014-01-01

    Biological tissue impedance spectroscopy can provide rich physiological and pathological information by measuring the variation of the complex impedance of biological tissues under various frequencies of driven current. Electrical Impedance Tomography (EIT) technique can measure the impedance spectroscopy of biological tissue in medical field. Before application, a key problem must be solved on how to generally distinguish normal tissues from the cancerous in terms of measurable EIT data. In this paper, the impedance spectroscopy characteristics of human lung tissue are studied. On the basis of the measured data of 109 lung cancer patients, Cole-Cole Circle radius (CCCR) and the complex modulus are extracted. In terms of the two characteristics, 71.6% and 66.4% samples of cancerous and normal tissues can be correctly classified, respectively. Furthermore, two characteristics of the measured EIT data of each patient consist of a two-dimensional vector and all such vectors comprise a set of vectors. When classifying the vector set, the rate of correctly partitioning normal and cancerous tissues can be raised to 78.2%. The main factors to affect the classification results on normal and cancerous tissues are generally analyzed. The proposed method will play an important role in further working out an efficient and feasible diagnostic method for potential lung cancer patients, and provide theoretical basis and reference data for electrical impedance tomography technology in monitoring pulmonary function.

  6. Plasminogen activators in normal tissue and carcinomas of the human oesophagus and stomach.

    OpenAIRE

    Sier, C. F.; Verspaget, H W; Griffioen, G.; GANESH, S.; Vloedgraven, H. J.; Lamers, C B

    1993-01-01

    Carcinogenesis in the human colon is associated with a marked increase of urokinase type plasminogen activator and a decrease of tissue type plasminogen activator. This study was performed to determine the concentrations of urokinase type plasminogen activator and tissue type plasminogen activator in normal tissue and carcinomas along the upper part of the gastrointestinal tract. Activity and antigen levels of both activators were determined in homogenates of endoscopically obtained biopsies ...

  7. The Sodium Iodide Symporter (NIS) and Potential Regulators in Normal, Benign and Malignant Human Breast Tissue

    OpenAIRE

    James Ryan; Curran, Catherine E.; Emer Hennessy; John Newell; Morris, John C.; Kerin, Michael J.; Dwyer, Roisin M

    2011-01-01

    INTRODUCTION: The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. METHODS: Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), t...

  8. Detection of Hyperechoic Inflammatory Fatty Tissue during Transabdominal Ultrasonography: Diagnostic Role in Acute Abdomen

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seong Jin; Lee, Hae Kyung; Yi, Bum Ha [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Kim, Hyun Cheol [Soonchunhyang University Cheonan Hospital, Cheonan (Korea, Republic of)

    2005-12-15

    To assess the incidence and diagnostic role of hyperechoic inflammatory fatty tissue (HIFT) in transabdominal ultrasonography (TAUS) for acute abdomen. With TAUS, we examined 98 consecutive patients (68 women, 30 men: mean age, 32 years: age range, 4-84 years) having acute abdominal pain. We examined the abdomen and pelvis by TAUS to determine the cause of acute abdomen, to check for the presence of HIFT, and to investigate whether it was easier and earlier to find the main cause and HIFT presence. We also prospectively evaluated the shape, distribution, and diagnostic role of HIFT. Final diagnoses consisted of 47 cases of acute appendicitis, 14 of enterocolitis, 13 of PID, 7 of gynecological hemoperitoneum, 5 of colonic diverticulitis, 3 of ovarian torsion, 2 of colon perforation, 2 of only presence of non-specific HIFT, 1 of mesenteric lymphadenitis, and 4 of normal. HIFT were seen in 67 patients (68.4%), including 44/47(93.6%) of acute appendicitis, 2/14(14.3%) of enterocolitis, 11/13(84.6%) of PID, 0/7 of hemoperitoneum, 5/5 of colonic diverticulitis, 0/3 of ovarian torsion, 2/2 of colon perforation, and 1/1 mesenteric lymphadenitis. HIFT were detected earlier than the main cause in 17/44 of acute appendicitis, 6/11 of PID, and 4/5 of colonic diverticulitis. In acute appendicitis, the shape of HIFT appeared as fat thickening along the mesoappendix in 12/44, fat thickening along the mesoappendix and the opposite side in 13/44, fat encircled appendix in 6/44, fatty mass wrapping abscess in 10/44, and diffuse intraperitoneal fat thickening in 3/44. In PID, HIFT appeared as a single fatty mass in the pelvis and lower abdomen in 6/11, wrapping pelvic abscess in 2/11, and multiple fatty masses scattered in abdomen and pelvis in 3/11. In colonic diverticulitis, all 5 cases appeared as hyperechoic hemispheric mass covering the inflamed diverticulum. HIFT are a usual US finding in patients with acute abdomen, particularly on abdominal and pelvic inflammatory conditions

  9. Expression of TMEM166 protein in human normal and tumor tissues.

    Science.gov (United States)

    Xu, Dong; Yang, Fan; He, Huiying; Hu, Jia; Lv, Xiaodong; Ma, Dalong; Chen, Ying Yu

    2013-12-01

    Transmembrane protein 166 (TMEM166) is a novel human regulator involved in both autophagy and apoptosis. In this study, we generated a specific rabbit polyclonal antibody against human TMEM166 and assessed the expression of this protein in various human normal and tumor tissue samples by tissue microarray-based immunohistochemical analysis. Varying TMEM166 protein levels were expressed in a cell-type and tissue-type-specific manner in detected tissues or organs. Strong TMEM166 expression was shown in the glomerular zona of the adrenal cortex, chromophil cells of the pituitary gland, islet cells, squamous epithelium of the esophagus mucosa, the fundic gland, and hepatocytes. Moderate or weak TMEM166 staining was identified in the parathyroid gland, the testis, vaginal stratified squamous cells, lung macrophages, hematopoietic cells, renal tubular epithelial cells, macrophages in the spleen red pulp, and neuronal cells in the cerebral cortex. Some tissues failed to stain for TMEM166, such as adipose tissue, colon, cerebellum, lymph node, mammary gland, ovary, prostate, rectum, skin, small intestine, thyroid gland, tonsil, and thymus. In comparing human normal and tumor tissues, TMEM166 expression was widely downregulated in the cancer tissues. Our studies provide the basis for future investigations into cell-type-specific functions of this protein in human normal and tumor tissues.

  10. ACUTE RENAL FAILURE WITH NORMAL PLASMA UREA LEVEL SECONDARY TO ACUTE PYELONEPHITIS IN A SINGLE KIDNEY PATIENT

    Directory of Open Access Journals (Sweden)

    Imperiali N

    2006-03-01

    Full Text Available SUMMARYAcute renal failure is a syndrome that usually runs with an increase in creatinine and urea plasma levels. However, there are clinical situations in which this syndrome may run with an increase in plasma creatinine keeping normal the urea one.In this report we present a case of acute renal failure with normal plasma urea level secondary to an acute pyelonephritis in a single kidney patient. The patient had an increased fractional excretion of urea which could explain the normal plasma urea levels found despite of his reduced glomerular filtration. This increased urea excretion state was interpreted as a consequence of the nephrogenic diabetes insipidus and alteration of the intra-renal urea reciclying process that the acute pyelonephritis induced. In conclusion: Acute pyelonephritis in a single kidney patient can appear as a pattern of acute renal failure with normal plasma urea levels. RESUMEN:La insuficiencia renal aguda es un sindrome que característicamente cursa con niveles plasmáticos elevados de urea y creatinina. Sin embargo, hay situaciones clínicas en las cuales este sindrome puede cursar con un incremento de la creatininemia sin presentar elevación de la uremia.En este reporte presentamos un caso clínico de una insuficiencia renal aguda con uremia normal secundaria a una pielonefritis aguda en un paciente con riñón único. El paciente presentaba una elevada excreción fraccional de urea lo cual podía explicar su uremia normal pese a estar cursando una caída del filtrado gomerular. Dicha excreción de urea elevada fue interpretada como secundaria a una diabetes insipida nefrogénica y una alteración en el recirculado intra-renal de la urea ambos producto de la pielonefritis aguda. Concluimos que la pielonefritis aguda en un paciente mono-reno puede presentarse con un patrón de insuficiencia renal aguda con uremia normal.

  11. Tissue toxicity induced by ionizing radiation to the normal intestine: Understanding the pathophysiological mechanisms to improve the medical management

    Institute of Scientific and Technical Information of China (English)

    MC Vozenin-Brotons

    2007-01-01

    @@ At the present time, more than one-half of all cancer patients are treated with radiation therapy. Despite a good therapeutic index, radiotherapy can disable normal tissue injury to normal tissues in long-term cancer survivors.

  12. Raman Spectroscopic Methods for Classification of Normal and Malignant Hypopharyngeal Tissues: An Exploratory Study

    Directory of Open Access Journals (Sweden)

    Parul Pujary

    2011-01-01

    Full Text Available Laryngeal cancer is more common in males. The present study is aimed at exploration of potential of conventional Raman spectroscopy in classifying normal from a malignant laryngopharyngeal tissue. We have recorded Raman spectra of twenty tissues (aryepiglottic fold using an in-house built Raman setup. The spectral features of mean malignant spectrum suggests abundance proteins whereas spectral features of mean normal spectrum indicate redundancy of lipids. PCA was employed as discriminating algorithm. Both, unsupervised and supervised modes of analysis as well as match/mismatch “limit test” methodology yielded clear classification among tissue types. The findings of this study demonstrate the efficacy of conventional Raman spectroscopy in classification of normal and malignant laryngopharyngeal tissues. A rigorous evaluation of the models with development of suitable fibreoptic probe may enable real-time Raman spectroscopic diagnosis of laryngopharyngeal cancers in future.

  13. 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

  14. Adipose tissue supports normalization of macrophage and liver lipid handling in obesity reversal.

    Science.gov (United States)

    Vatarescu, Maayan; Bechor, Sapir; Haim, Yulia; Pecht, Tal; Tarnovscki, Tanya; Slutsky, Noa; Nov, Ori; Shapiro, Hagit; Shemesh, Avishai; Porgador, Angel; Bashan, Nava; Rudich, Assaf

    2017-06-01

    Adipose tissue inflammation and dysfunction are considered central in the pathogenesis of obesity-related dysmetabolism, but their role in the rapid metabolic recovery upon obesity reversal is less well defined. We hypothesized that changes in adipose tissue endocrine and paracrine mechanisms may support the rapid improvement of obesity-induced impairment in cellular lipid handling. C57Bl-6J mice were fed ad libitum either normal chow (NC) or high-fat diet (HFF) for 10 weeks. A dietary obesity reversal group was fed HFF for 8 weeks and then switched to NC for 2 weeks (HFF→NC). Whole-body glucose homeostasis rapidly nearly normalized in the HFF→NC mice (fasting glucose and insulin fully normalized, glucose and insulin tolerance tests reversed 82% to the NC group levels). During 2 weeks of the dietary reversal, the liver was significantly cleared from ectopic fat, and functionally, glucose production from pyruvate, alanine or fructose was normalized. In contrast, adipose tissue inflammation (macrophage infiltration and polarization) largely remained as in HFF, though obesity-induced adipose tissue macrophage lipid accumulation decreased by ~50%, and adipose tissue MAP kinase hyperactivation was reversed. Ex vivo, mild changes in adipose tissue adipocytokine secretion profile were noted. These corresponded to partial or full reversal of the excess cellular lipid droplet accumulation induced by HFF adipose tissue conditioned media in hepatoma or macrophage cells, respectively. We propose that early after initiating reversal of nutritional obesity, rapid metabolic normalization largely precedes resolution of adipose tissue inflammation. Nevertheless, we demonstrate a hitherto unrecognized contribution of adipose tissue to the rapid improvement in lipid handling by the liver and by macrophages. © 2017 The authors.

  15. [Modified method of constructing tissue microarray which contains keloid and normal skin].

    Science.gov (United States)

    Zhang, Zhenyu; Chen, Junjie; Cen, Ying; Zhao, Sha; Liao, Dianying; Gong, Jing

    2010-08-01

    To seek for a method of constructing the tissue microarray which contains keloid, skin around keloid, and normal skin. The specimens were gained from patients of voluntary donation between March and May 2009, including the tissues of keloid (27 cases), skin around keloid (13 cases), and normal skin (27 cases). The specimens were imbedded by paraffin as donor blocks. The traditional method of constructing the tissue microarray and section were modified according to the histological characteristics of the keloid and skin tissue and the experimental requirement. The tissue cores were drilled from donor blocks and attached securely on the adhesive platform which was prepared. The adhesive platform with tissue cores in situ was placed into an imbedding mold, which then was preheated briefly. Paraffin at approximately 70 degrees C was injected to fill the mold and then cooled to room temperature. Then HE staining, immunohistochemistry staining were performed and the results were observed by microscope. The constructed tissue microarray block contained 67 cores as designed and displayed smooth surface with no crack. All the cores distributed regularly, had no disintegration or manifest shift. HE staining of tissue microarray section showed that all cores had equal thickness, distinct layer, manifest contradistinction, well-defined edge, and consistent with original pathological diagnosis. Immunohistochemistry staining results demonstrated that all cores contained enough tissue dose to apply group comparison. However, in tissue microarray which was made as traditional method, many cores missed and a few cores shifted obviously. Applying modified method can successfully construct tissue microarray which is composed of keloid, skin around keloid, and normal skin. This tissue microarray will become an effective tool of researching the pathogenesis of keloid.

  16. Intraoperative near-infrared imaging can distinguish cancer from normal tissue but not inflammation.

    Directory of Open Access Journals (Sweden)

    David Holt

    Full Text Available Defining tumor from non-tumor tissue is one of the major challenges of cancer surgery. Surgeons depend on visual and tactile clues to select which tissues should be removed from a patient. Recently, we and others have hypothesized near-infrared (NIR imaging can be used during surgery to differentiate tumors from normal tissue.We enrolled 8 canines and 5 humans undergoing cancer surgery for NIR imaging. The patients were injected with indocyanine green (ICG, an FDA approved non-receptor specific NIR dye that accumulates in hyperpermeable tissues, 16-24 hours prior to surgery. During surgery, NIR imaging was used to discriminate the tumor from non-tumor tissue.NIR imaging identified all tumors with a mean signal-to-background ratio of 6.7. Optical images were useful during surgery in discriminating normal tissue from cancer. In 3 canine cases and 1 human case, the tissue surrounding the tumor was inflamed due to obstruction of the vascular supply due to mass effect. In these instances, NIR imaging could not distinguish tumor tissue from tissue that was congested, edematous and did not contain cancer.This study shows that NIR imaging can identify tumors from normal tissues, provides excellent tissue contrast, and it facilitates the resection of tumors. However, in situations where there is significant peritumoral inflammation, NIR imaging with ICG is not helpful. This suggests that non-targeted NIR dyes that accumulate in hyperpermeable tissues will have significant limitations in the future, and receptor-specific NIR dyes may be necessary to overcome this problem.

  17. Acute tissue death (white syndrome) affects the microenvironment of tabular Acropora corals

    DEFF Research Database (Denmark)

    Andersen, Sandra Breum; Vestergaard, Maj; Ainsworth, Tracy D.

    2010-01-01

    White syndrome (WS) is a collective term for coral diseases that cause acute tissue loss, resulting in apparently healthy tissue bordering on exposed skeleton. In this study, the microenvironmental condition and tissue structure of WS-affected tabular acroporid corals were assessed by O2 microele......White syndrome (WS) is a collective term for coral diseases that cause acute tissue loss, resulting in apparently healthy tissue bordering on exposed skeleton. In this study, the microenvironmental condition and tissue structure of WS-affected tabular acroporid corals were assessed by O2...

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

    Institute of Scientific and Technical Information of China (English)

    Ben-Zhou Feng

    2016-01-01

    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.

  19. Acute myocardial infarction with normal coronary arteries in a patient with dermatomyositis. Case report.

    Science.gov (United States)

    Badui, E; Valdespino, A; Lepe, L; Rangel, A; Campos, A; Leon, F

    1996-08-01

    The authors present a forty-year-old man, with a history of dermatomyositis for the past twelve years, managed intermittently with prednisone. During an exacerbation of his illness he developed an acute anterior wall myocardial infarction with normal coronary arteries. A literature review indicates this represents a rare association.

  20. Integrative prognostic risk score in acute myeloid leukemia with normal karyotype

    NARCIS (Netherlands)

    F. Damm (Frederik); M. Heuser (Michael); H.M. Morgan (Helen); K. Wagner (Katharina); K. Görlich (Kerstin); A. Großhennig (Anika); I. Hamwi (Iyas); F. Thol (Felicitas); E. Surdziel (Ewa); W. Fiedler (Walter); M. Lübbert (Michael); L. Kanz (Lothar); C. Reuter (Christoph); G. Heil (Gerhard); H.R. Delwel (Ruud); B. Löwenberg (Bob); P.J.M. Valk (Peter); J. Krauter; A. Ganser (Arnold)

    2011-01-01

    textabstractTo integrate available clinical and molecular information for cytogenetically normal acute myeloid leukemia (CN-AML) patients into one risk score, 275 CN-AML patients from multicenter treatment trials AML SHG Hannover 0199 and 0295 and 131 patients from HOVON/SAKK protocols as external c

  1. Computed tomography coronary angiography in patients with acute myocardial infarction and normal invasive coronary angiography

    NARCIS (Netherlands)

    Panayi, Georgios; Wieringa, Wouter G.; Alfredsson, Joakim; Carlsson, Jorg; Karlsson, Jan-Erik; Persson, Anders; Engvall, Jan; Pundziute, Gabija; Swahn, Eva

    2016-01-01

    Background: Three to five percent of patients with acute myocardial infarction (AMI) have normal coronary arteries on invasive coronary angiography (ICA). The aim of this study was to assess the presence and characteristics of atherosclerotic plaques on computed tomography coronary angiography

  2. Acute efects of the Paulinia cupana, "Guaraná" on the cognition of normal volunteers

    Directory of Open Access Journals (Sweden)

    José Carlos Fernandes Galduróz

    Full Text Available The authors studied the acute effects of "Guaraná", when compared to caffeine and placebo, (double blind study on cognition, anxiety and sleep in 30 normal volunteers. Although results were negative it cannot be concluded that "Guaraná" is harmless. Other studies shall be undertaken, administering "Guaraná" on a long term basis, as popularly proclaimed.

  3. Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues.

    Science.gov (United States)

    Chesters, P M; Heritage, J; McCance, D J

    1983-04-01

    Available evidence suggests that BK virus (BKV) and JC virus (JCV) persist in the kidneys of healthy individuals after primary infection and may reactivate when the host's immune response is impaired. Data supporting this hypothesis are presented. A previous study had shown BKV to be present in the kidneys of eight (57%) of 14 subjects. In the present study, which extended the investigation to a total of 30 subjects, BKV DNA was found in the renal tissues of 10 (33%) subjects, and JCV DNA was found in the renal tissues of three (10%) subjects. The viral DNA detected appeared not to be integrated with host DNA and to be isolated in foci. Investigation of normal and diseased brain tissue, including tissue from six subjects with multiple sclerosis, failed to reveal the presence of either JCV DNA or BKV DNA.

  4. Improved normal tissue protection by proton and X-ray microchannels compared to homogeneous field irradiation.

    Science.gov (United States)

    Girst, S; Marx, C; Bräuer-Krisch, E; Bravin, A; Bartzsch, S; Oelfke, U; Greubel, C; Reindl, J; Siebenwirth, C; Zlobinskaya, O; Multhoff, G; Dollinger, G; Schmid, T E; Wilkens, J J

    2015-09-01

    The risk of developing normal tissue injuries often limits the radiation dose that can be applied to the tumour in radiation therapy. Microbeam Radiation Therapy (MRT), a spatially fractionated photon radiotherapy is currently tested at the European Synchrotron Radiation Facility (ESRF) to improve normal tissue protection. MRT utilizes an array of microscopically thin and nearly parallel X-ray beams that are generated by a synchrotron. At the ion microprobe SNAKE in Munich focused proton microbeams ("proton microchannels") are studied to improve normal tissue protection. Here, we comparatively investigate microbeam/microchannel irradiations with sub-millimetre X-ray versus proton beams to minimize the risk of normal tissue damage in a human skin model, in vitro. Skin tissues were irradiated with a mean dose of 2 Gy over the irradiated area either with parallel synchrotron-generated X-ray beams at the ESRF or with 20 MeV protons at SNAKE using four different irradiation modes: homogeneous field, parallel lines and microchannel applications using two different channel sizes. Normal tissue viability as determined in an MTT test was significantly higher after proton or X-ray microchannel irradiation compared to a homogeneous field irradiation. In line with these findings genetic damage, as determined by the measurement of micronuclei in keratinocytes, was significantly reduced after proton or X-ray microchannel compared to a homogeneous field irradiation. Our data show that skin irradiation using either X-ray or proton microchannels maintain a higher cell viability and DNA integrity compared to a homogeneous irradiation, and thus might improve normal tissue protection after radiation therapy.

  5. 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

  6. High quality and quantity Genome-wide germline genotypes from FFPE normal tissue

    Directory of Open Access Journals (Sweden)

    Georgelas Ann

    2011-05-01

    Full Text Available Abstract Background Although collections of formalin fixed paraffin embedded (FFPE samples exist, sometimes representing decades of stored samples, they have not typically been utilized to their full potential. Normal tissue from such samples would be extremely valuable for generation of genotype data for individuals who cannot otherwise provide a DNA sample. Findings We extracted DNA from normal tissue identified in FFPE tissue blocks from prostate surgery and obtained complete genome wide genotype data for over 500,000 SNP markers for these samples, and for DNA extracted from whole blood for 2 of the cases, for comparison. Four of the five FFPE samples of varying age and amount of tissue had identifiable normal tissue. We obtained good quality genotype data for between 89 and 99% of all SNP markers for the 4 samples from FFPE. Concordance rates of over 99% were observed for the 2 samples with DNA from both FFPE and from whole blood. Conclusions DNA extracted from normal FFPE tissue provides excellent quality and quantity genome-wide genotyping data representing germline DNA, sufficient for both linkage and association analyses. This allows genetic analysis of informative individuals who are no longer available for sampling in genetic studies.

  7. Nanog expression in heart tissues induced by acute myocardial infarction.

    Science.gov (United States)

    Luo, Huanhuan; Li, Qiong; Pramanik, Jogen; Luo, Jiankai; Guo, Zhikun

    2014-10-01

    Nanog is a potential stem cell marker and is considered a regeneration factor during tissue repair. In the present study, we investigated expression patterns of nanog in the rat heart after acute myocardial infarction by semi-quantitative RT-PCR, immunohistochemistry and Western blot analyses. Our results show that nanog at both mRNA and protein levels is positively expressed in myocardial cells, fibroblasts and small round cells in different myocardial zones at different stages after myocardial infarction, showing a spatio-temporal and dynamic change. After myocardial infarction, the nanog expression in fibroblasts and small round cells in the infarcted zone (IZ) is much stronger than that in the margin zone (MZ) and remote infarcted zone (RIZ). From day 7 after myocardial infarction, the fibroblasts and small cells strongly expressed nanog protein in the IZ, and a few myocardial cells in the MZ and the RIZ and the numbers of nanog-positive fibroblasts and small cells reached the highest peak at 21 days after myocardial infarction, but in this period the number of nanog-positive myocardial cells decreased gradually. At 28 days after myocardial infarction, the numbers of all nanog-positive cells decreased into a low level. Therefore, our data suggest that all myocardial cells, fibroblasts and small round cells are involved in myocardial reconstruction after cardiac infarction. The nanog-positive myocardial cells may respond to early myocardial repair, and the nanog-positive fibroblasts and small round cells are the main source for myocardial reconstruction after cardiac infarction.

  8. 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.

  9. Normal human epithelial cells regulate the size and morphology of tissue-engineered capillaries.

    Science.gov (United States)

    Rochon, Marie-Hélène; Fradette, Julie; Fortin, Véronique; Tomasetig, Florence; Roberge, Charles J; Baker, Kathleen; Berthod, François; Auger, François A; Germain, Lucie

    2010-05-01

    The survival of thick tissues/organs produced by tissue engineering requires rapid revascularization after grafting. Although capillary-like structures have been reconstituted in some engineered tissues, little is known about the interaction between normal epithelial cells and endothelial cells involved in the in vitro angiogenic process. In the present study, we used the self-assembly approach of tissue engineering to examine this relationship. An endothelialized tissue-engineered dermal substitute was produced by adding endothelial cells to the tissue-engineered dermal substitute produced by the self-assembly approach. The latter consists in culturing fibroblasts in the medium supplemented with serum and ascorbic acid. A network of tissue-engineered capillaries (TECs) formed within the human extracellular matrix produced by dermal fibroblasts. To determine whether epithelial cells modify TECs, the size and form of TECs were studied in the endothelialized tissue-engineered dermal substitute cultured in the presence or absence of epithelial cells. In the presence of normal keratinocytes from skin, cornea or uterine cervix, endothelial cells formed small TECs (cross-sectional area estimated at less than 50 microm(2)) reminiscent of capillaries found in the skin's microcirculation. In contrast, TECs grown in the absence of epithelial cells presented variable sizes (larger than 50 microm(2)), but the addition of keratinocyte-conditioned media or exogenous vascular endothelial growth factor induced their normalization toward a smaller size. Vascular endothelial growth factor neutralization inhibited the effect of keratinocyte-conditioned media. These results provide new direct evidence that normal human epithelial cells play a role in the regulation of the underlying TEC network, and advance our knowledge in tissue engineering for the production of TEC networks in vitro.

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

    Energy Technology Data Exchange (ETDEWEB)

    Soendergaard, Jimmi; Hoeyer, Morten; Wright, Pauliina; Grau, Cai; Muren, Ludvig Paul (Dept. of Oncology, Aarhus Univ. Hospital, Aarhus (Denmark)); Petersen, Joergen B. (Dept. of Medical Physics, Aarhus Univ. Hospital, Aarhus (Denmark))

    2009-02-15

    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 cm3 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 < 0.05), e.g. from 180 to 121 cm3 at 50 Gy, while the gEUD was reduced from 58 to 53 Gy (p < 0.05). Similar patterns were seen for the bowel cavity. For the rectum, IMRT reduced the maximum dose as well as the volumes receiving more than 50 and 60 Gy (p < 0.05), e.g. from 72 to 48 cm3 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.

  11. Profiling gene expression patterns of nasopharyngeal carcinoma and normal nasopharynx tissues with cDNA microarray

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    5 μg of total RNAs from normal nasopharynx and nasopharyngeal carcinoma tissue have been labeled with α-32P-dCTP during reverse transcription. The synthesized cDNA probes have been hybridized to high-density cDNA microarray containing 5184 genes or expression sequence tags (ESTs). Then image analysis software has been applied to comparing their expression profiles. Results show that 187 ESTs were of density value above 200 in nasopharyngeal carcinoma tissue while there were 307 such ESTs in normal nasopharynx tissue; 38 ESTs were strongly expressed in nasopharynx, but weakly expressed in nasopharyngeal carcinoma; 48 ESTs were strongly expressed in nasopharyngeal carcinoma, but weakly expressed in normal nasopharynx. These results suggest that there may exist some new differentially expressed genes involved in nasopharyngeal carcinoma development. Furthermore, the results strongly indicate that high-density cDNA microarray is a powerful and efficient tool for large-scale screening differentially expressed genes.

  12. Static jaw collimation settings to minimize radiation dose to normal brain tissue during stereotactic radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Han, Eun Young, E-mail: eyhan@uams.edu [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Zhang Xin; Yan Yulong; Sharma, Sunil; Penagaricano, Jose [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States); Moros, Eduardo [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL (United States); Corry, Peter [Department of Radiation Oncology, University of Arkansas for Medical Sciences, Little Rock, AR (United States)

    2012-01-01

    At University of Arkansas for Medical Sciences (UAMS) intracranial stereotactic radiosurgery (SRS) is performed by using a linear accelerator with an add-on micromultileaf collimator (mMLC). In our clinical setting, static jaws are automatically adapted to the furthest edge of the mMLC-defined segments with 2-mm (X jaw) and 5-mm (Y jaw) margin and the same jaw values are applied for all beam angles in the treatment planning system. This additional field gap between the static jaws and the mMLC allows additional radiation dose to normal brain tissue. Because a radiosurgery procedure consists of a single high dose to the planning target volume (PTV), reduction of unnecessary dose to normal brain tissue near the PTV is important, particularly for pediatric patients whose brains are still developing or when a critical organ, such as the optic chiasm, is near the PTV. The purpose of this study was to minimize dose to normal brain tissue by allowing minimal static jaw margin around the mMLC-defined fields and different static jaw values for each beam angle or arc. Dose output factors were measured with various static jaw margins and the results were compared with calculated doses in the treatment planning system. Ten patient plans were randomly selected and recalculated with zero static jaw margins without changing other parameters. Changes of PTV coverage, mean dose to predefined normal brain tissue volume adjacent to PTV, and monitor units were compared. It was found that the dose output percentage difference varied from 4.9-1.3% for the maximum static jaw opening vs. static jaw with zero margins. The mean dose to normal brain tissue at risk adjacent to the PTV was reduced by an average of 1.9%, with negligible PTV coverage loss. This dose reduction strategy may be meaningful in terms of late effects of radiation, particularly in pediatric patients. This study generated clinical knowledge and tools to consistently minimize dose to normal brain tissue.

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

    Directory of Open Access Journals (Sweden)

    Nardulli Ann M

    2010-01-01

    Full Text Available Abstract Background 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. Methods 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. Results We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue. Conclusions 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.

  14. 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.

  15. Differentiation of cancerous and normal brain tissue using label free fluorescence and Stokes shift spectroscopy

    Science.gov (United States)

    Zhou, Yan; Wang, Leana; Liu, Cheng-hui; He, Yong; Yu, Xinguang; Cheng, Gangge; Wang, Peng; Shu, Cheng; Alfano, Robert R.

    2016-03-01

    In this report, optical biopsy was applied to diagnose human brain cancer in vitro for the identification of brain cancer from normal tissues by native fluorescence and Stokes shift spectra (SSS). 77 brain specimens including three types of human brain tissues (normal, glioma and brain metastasis of lung cancers) were studied. In order to observe spectral changes of fluorophores via fluorescence, the selected excitation wavelength of UV at 300 and 340 nm for emission spectra and a different Stokes Shift spectra with intervals Δλ = 40 nm were measured. The fluorescence spectra and SSS from multiple key native molecular markers, such as tryptophan, collagen, NADH, alanine, ceroid and lipofuscin were observed in normal and diseased brain tissues. Two diagnostic criteria were established based on the ratios of the peak intensities and peak position in both fluorescence and SSS spectra. It was observed that the ratio of the spectral peak intensity of tryptophan (340 nm) to NADH (440 nm) increased in glioma, meningioma (benign), malignant meninges tumor, and brain metastasis of lung cancer tissues in comparison with normal tissues. The ratio of the SS spectral peak (Δλ = 40 nm) intensities from 292 nm to 366 nm had risen similarly in all grades of tumors.

  16. Acute myocarditis with normal wall motion detected with 2D speckle tracking echocardiography

    Directory of Open Access Journals (Sweden)

    Thomas Sturmberger

    2016-05-01

    Full Text Available We present the case of a 26-year-old male with acute tonsillitis who was referred for coronary angiography because of chest pain, elevated cardiac biomarkers, and biphasic T waves. The patient had no cardiovascular risk factors. Echocardiography showed no wall motion abnormalities and no pericardial effusion. 2D speckle tracking revealed distinct decreased regional peak longitudinal systolic strain in the lateral and posterior walls. Ischemic disease was extremely unlikely in view of his young age, negative family history regarding coronary artery disease, and lack of regional wall motion abnormalities on the conventional 2D echocardiogram. Coronary angiography was deferred as myocarditis was suspected. To confirm the diagnosis, cardiac magnetic resonance tomography (MRT was performed, showing subepicardial delayed hyperenhancement in the lateral and posterior walls correlating closely with the strain pattern obtained by 2D speckle tracking echocardiography. With a working diagnosis of acute myocarditis associated with acute tonsillitis, we prescribed antibiotics and nonsteroidal anti-inflammatory drugs. The patient’s clinical signs resolved along with normalization of serum creatine kinase (CK levels, and the patient was discharged on the third day after admission. Learning points: • Acute myocarditis can mimic acute coronary syndromes. • Conventional 2D echocardiography lacks specific features for detection of subtle regional wall motion abnormalities. • 2D speckle tracking expands the scope of echocardiography in identifying myocardial dysfunction derived from edema in acute myocarditis.

  17. Hypomethylation of L1 retrotransposons in colorectal cancer and adjacent normal tissue.

    Science.gov (United States)

    Suter, Catherine M; Martin, David I; Ward, Robyn L

    2004-03-01

    Malignant cells often exhibit perturbations in the pattern of cytosine methylation. Hypermethylation of CpG islands has been extensively documented, but genome-wide hypomethylation is also a common feature of malignant cells. The bulk of cytosine methylation in the mammalian genome occurs on repetitive elements. This study analysed the methylation status of L1 retrotransposons in colorectal cancer. Methylation-sensitive Southern blotting was used to determine L1 promoter methylation in colon tumours, adjacent normal tissue, and normal colonic mucosa from healthy individuals. Hypomethylation of L1 promoter sequences was detected in all tumours but was also detected in the histologically normal colonic mucosa of 6 of 19 cancer patients, even at a considerable distance from the tumour. L1 hypomethylation was not detected in matched normal peripheral blood, lymph node or smooth muscle tissue from cancer patients or in the colonic mucosa of 14 healthy individuals. We also assayed for the total proportion of methylated CpG in normal bowel specimens from normal and colon cancer patients. Normal mucosa from cancer patients exhibited lower levels of genomic methylation than the mucosa from healthy individuals, and levels were significantly lower in those patients exhibiting L1 promoter hypomethylation. These results suggest that genomic hypomethylation is an early event in tumourigenesis. Progressive demethylation of L1 promoter sequences could lead to disturbance of normal gene expression and facilitate the process of neoplastic progression.

  18. Ultrasonic tissue characterization with integrated backscatter. Acute myocardial ischemia, reperfusion, and stunned myocardium in patients

    Energy Technology Data Exchange (ETDEWEB)

    Milunski, M.R.; Mohr, G.A.; Perez, J.E.; Vered, Z.; Wear, K.A.; Gessler, C.J.; Sobel, B.E.; Miller, J.G.; Wickline, S.A. (Washington Univ., St. Louis, MO (USA))

    1989-09-01

    We have previously shown in studies of experimental animals that myocardium exhibits a cardiac cycle-dependent variation of integrated backscatter that reflects regional myocardial contractile performance and that is blunted promptly after arterial occlusion and recovers after reperfusion. To define the clinical utility of ultrasonic tissue characterization with integrated backscatter for detection of acute myocardial infarction and reperfusion, 21 patients (14 men and seven women) were studied in the cardiac care unit within the first 24 hours (mean time, 11.3 hours; range, 3.5-23.8 hours) after the onset of symptoms indicative of acute myocardial infarction with conventional two-dimensional and M-mode echocardiography and with analysis of integrated backscatter. The magnitude of cyclic variation of integrated backscatter was measured from several sites within acute infarct regions and normal regions remote from the infarct zone for each patient. The average magnitude of cyclic variation among all patients (n = 21) was 4.8 +/- 0.5 dB in normal regions compared with 0.8 +/- 0.3 dB in infarct regions (p less than 0.05) within the first 24 hours after the onset of symptoms. Among the patients who had two studies, 15 (mean, 7.1 days; range, 2-31 days for second study) underwent coronary arteriography to define vessel patency. In patients with vessels with documented patency (n = 10), the magnitude of cyclic variation in infarct regions increased over time from 1.3 +/- 0.6 to 2.5 +/- 0.5 dB from the initial to final study (p less than 0.05). Patients with occluded infarct-related arteries (n = 5) exhibited no significant recovery of cyclic variation (0.3 +/- 0.3-0.6 +/- 0.3 dB). A blinded analysis of standard two-dimensional echocardiographic images revealed no significant recovery of wall thickening in either group over the same time intervals.

  19. Significance of differential metal loads in normal versus cancerous cadaver tissues - biomed 2010.

    Science.gov (United States)

    Farah, Ibrahim O; Trimble, Quannesha; Ndebele, Kenneth; Mawson, Anthony

    2010-01-01

    The bodys elemental/ metal loads are known to exert essential influence in maintaining normal and abnormal metabolism leading to eventual pathology of some forms of cancer phenotypes. Accumulation of potentially toxic or nonessential trace metals has been observed but not highly noted as an active factor in toxicogenesis and in the development of many diseases including cancers. The compositional balance and distribution of trace metals in various body tissues are essential key players in homeostasis in life. To this end the etiology of diseases including cancer has been linked with the accumulation of potentially toxic or nonessential trace metals. However, scarce literature / experimental evidence exist as a scientific proof that metal concentrations play important role in the etiology and development of cancer phenotypes. The aim of this study was to investigate the differential relationship of metal concentrations and profiles in cancer and normal tissues from cadavers of humans. The originated hypothesis was that elemental / metal concentrations and profiles seen in post mortem will show significant differences between normal and cancer-derived tissues as well as between various tissue types in humans. This study also establishes critical elemental /metal profiles that may be relevant in providing correlations with the development of three major cancers. Normal human and tumor tissues of cadaverous lung, breast and liver tissues used in this study were obtained from US Biomax Company. Tissue samples were prepared using standardized digestion procedures necessary for use with the Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES). This equipment was utilized to determine the concentrations and profiles of 21 elements including Ag, Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Na, Ni, Pb, Sb, Se, Sr, Tl, V, and Zn. Twelve major elements of Al, Ba, Ca, Cr, Cu, Fe, Mg, Na, Pb, Se, Sr, and Zn were found to be significantly different in term of their

  20. 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.

  1. 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.

    2016-11-01

    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 (pcancerous tissues (pcancer 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.

  2. 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.

  3. 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.

  4. 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

  5. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Science.gov (United States)

    He, Xiaolin; Han, Bing; Mura, Marco; Li, Li; Cypel, Marcelo; Soderman, Avery; Picha, Kristen; Yang, Jing; Liu, Mingyao

    2008-01-30

    Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS). Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. Human tissue factor knock-in (hTF-KI) transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859) were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v.) attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  6. Modeling Radiotherapy Induced Normal Tissue Complications: An Overview beyond Phenomenological Models

    Science.gov (United States)

    Benassi, Marcello; Strigari, Lidia

    2016-01-01

    An overview of radiotherapy (RT) induced normal tissue complication probability (NTCP) models is presented. NTCP models based on empirical and mechanistic approaches that describe a specific radiation induced late effect proposed over time for conventional RT are reviewed with particular emphasis on their basic assumptions and related mathematical translation and their weak and strong points. PMID:28044088

  7. 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

  8. 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

  9. Tissue factor pathway inhibitor relates to fibrin degradation in patients with acute deep venous thrombosis

    DEFF Research Database (Denmark)

    Sidelmann, Johannes J; Bladbjerg, Else-Marie; Gram, Jørgen

    2008-01-01

    Reduced concentration of tissue factor pathway inhibitor is a risk factor for development of deep venous thrombosis, whereas elevated concentrations of tissue factor pathway inhibitor are observed in patients with acute myocardial infarction and disseminated intravascular coagulation. Presently, we...... studied the association between inflammation, endothelial cell perturbation, fibrin degradation and the concentration of tissue factor pathway inhibitor in patients suspected for acute deep venous thrombosis. We determined the tissue factor pathway inhibitor -33T/C polymorphism, free and total tissue...... factor pathway inhibitor, C-reactive protein, von Willebrand factor and D-Dimer in 160 consecutive patients admitted to hospital with a tentative diagnosis of acute deep venous thrombosis. Deep venous thrombosis was identified in 57 patients (18 distal and 39 proximal). The distribution of the tissue...

  10. Pancreatic stellate cells and CX3CR1: occurrence in normal pancreas, acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist

    Science.gov (United States)

    Uchida, Masahiko; Ito, Tetsuhide; Nakamura, Taichi; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Takayanagi, Ryoichi; Jensen, Robert T.

    2014-01-01

    Objectives Numerous studies suggest important roles of the chemokine, fractalkine (CX3CL1) in acute/chronic pancreatitis, however the possible mechanisms of the effects are unclear. Pancreatic stellate cells (PSCs) can play important roles in pancreatitis, secreting inflammatory cytokines/chemokines, as well as proliferation. Therefore, we investigated CX3CL1 receptor (CX3CR1) occurrence in normal pancreas and pancreatitis (acute/chronic) tissues, and the effects of CX3CL1 on activated-PSCs. Methods CX3CR1 expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues were evaluated with immunohistochemical analysis. CX3CR1 expression and effects of CX3CL1 on activated-PSCs were examined with realtime-PCR, BrdU assays and Western Blotting. Results In normal pancreas, acinar cells expressed CX3CR1 within granule-like-formations in the cytoplasm, whereas in acute/chronic pancreatitis, acinar, ductal and activated-PSCs expressed CX3CR1 on cell membranes. With activation of normal PSCs, CX3CR1 is increased. CX3CL1 activated multiple signaling cascades in PSCs. CX3CL1, did not induce inflammatory-genes expression in activated-PSCs, but induced proliferation. Conclusions CX3CR1s are expressed in normal pancreas. Expression is increased in acute/chronic pancreatitis and the CX3CR1s are activated. CX3CL1 induces proliferation of activated-PSCs without increasing release of inflammatory-mediators. These results suggest that CX3CR1 activation of PSCs could be important in their effects in pancreatitis, especially to PSCs proliferation in pancreatitis where CX3CL1 levels are elevated. PMID:24681877

  11. [Acute myocardial infarction with normal coronary arteries as initial manifestation of polyarteritis nodosa. A case report].

    Science.gov (United States)

    Badui, E; Rangel, A; Ramos, M A; Enciso, R; Solorio, S; Lepe, L; Miranda, J

    1997-01-01

    A thirty four-year-old-white man in good health developed an acute anterior wall myocardial infarction (AMI), Killip II with normal coronary arteries. No thrombolytic therapy was given. Selective angiography revealed multiple aneurysms in mesenteric and renal arteries. The diagnosis of polyarteritis nodosa (PAN) was performed. AMI in PAN is secondary to arteritis with thrombosis, or to atherosclerosis due to steroid therapy. This case, having multiorgan vascular aneurysms involvement without previous cardiac symptomatology nor steroid therapy, presented as his first cardiac complication an AMI with normal coronary arteries probably due to selective arteritis.

  12. Pharmacodynamic study on acute hypotensive activities of Carissa carandas extract in normal rats.

    Science.gov (United States)

    Shamim, Sumbul; Ahmad, Syed Iqbal

    2012-07-01

    This study aims to evaluate the effect of Carissa carandas extract on cardiovascular function of normal rats. Intravenous bolus injection of this extract in the doses of 5 mg kg(-1)_-45 mg kg(-1), produced dose dependent reduction in arterial blood pressure (p0.05). It was concluded that the Carissa carandas Ethanol extract possess potent acute hypotensive effect in normal rats. It stimulates the muscarinic receptors located on the endothelial cells of the vasculature. This stimulation results in the release of endothelial-derived relaxing factors (EDRFs) or nitric oxide that diffuses to vasculature smooth muscles and causes their relaxation.

  13. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    OpenAIRE

    2015-01-01

    B-cell acute lymphoblastic leukemia (B-ALL) is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintena...

  14. Gene expression profiling of normal thyroid tissue from patients with thyroid carcinoma.

    Science.gov (United States)

    Ria, Roberto; Simeon, Vittorio; Melaccio, Assunta; Di Meo, Giovanna; Trino, Stefania; Mazzoccoli, Carmela; Saltarella, Ilaria; Lamanuzzi, Aurelia; Morano, Annalisa; Gurrado, Angela; Pasculli, Alessandro; Lastilla, Gaetano; Musto, Pellegrino; Reale, Antonia; Dammacco, Franco; Vacca, Angelo; Testini, Mario

    2016-05-17

    Gene expression profiling (GEP) of normal thyroid tissue from 43 patients with thyroid carcinoma, 6 with thyroid adenoma, 42 with multinodular goiter, and 6 with Graves-Basedow disease was carried out with the aim of achieving a better understanding of the genetic mechanisms underlying the role of normal cells surrounding the tumor in the thyroid cancer progression. Unsupervised and supervised analyses were performed to compare samples from neoplastic and non-neoplastic diseases. GEP and subsequent RT-PCR analysis identified 28 differentially expressed genes. Functional assessment revealed that they are involved in tumorigenesis and cancer progression. The distinct GEP is likely to reflect the onset and/or progression of thyroid cancer, its molecular classification, and the identification of new potential prognostic factors, thus allowing to pinpoint selective gene targets with the aim of realizing more precise preoperative diagnostic procedures and novel therapeutic approaches.This study is focused on the gene expression profiling analysis followed by RT-PCR of normal thyroid tissues from patients with neoplastic and non-neoplastic thyroid diseases. Twenty-eight genes were found to be differentially expressed in normal cells surrounding the tumor in the thyroid cancer. The genes dysregulated in normal tissue samples from patients with thyroid tumors may represent new molecular markers, useful for their diagnostic, prognostic and possibly therapeutic implications.

  15. Vitronectin (serum spreading factor): its localisation in normal and fibrotic tissue.

    Science.gov (United States)

    Reilly, J T; Nash, J R

    1988-12-01

    The distribution of vitronectin and fibronectin in normal and fibrotic tissue was directly compared using indirect immunofluorescence. Both glycoproteins were ubiquitiously localised to loose connective tissue. Vitronectin, unlike fibronectin, was not detected in basement membranes, in normal renal glomeruli, or around smooth muscle cells of both musculares mucosae and propria of the gastrointestinal tract. The presence of vitronectin could not be shown in washed permeabilised platelets. Vitronectin was very much increased in reactive and fibrotic tissue, as was fibronectin. This was observed in lymph nodes affected by both nodular sclerosing Hodgkin's disease and by metastatic carcinoma as well as in myelofibrotic bone marrow and sclerotic glomeruli. These findings suggest that vitronectin may have an important role in the processes of inflammation and repair.

  16. [Measurement of T and DHT contents in normal and diseased human prostate tissues].

    Science.gov (United States)

    Zhang, Y; Ye, L; Ding, Q; Fang, Z; Yao, M; Shi, D

    2000-07-01

    To measure T and DHT contents in normal and diseased human prostate tissues. Serum and prostatic T and DHT levels were measured in patients with normal, benign prostatic hyperplasia and prostate cancer. A decline was observed in serum T level, but no change in DHT concentration with aging. There were no significant differences in both blood T and DHT levels between the patients with BPH or PCA and normal controls. Serum T level remained constant. There were excessive accumulation of DHT in BPH, and cancerous prostate tissues were responsible for the pathogenesis of BPH and PCA. Finasteride treatment did not produce a reduction in prostatic DHT content. More than one form of 5a-reductases is responsible for the high level of DHT in the gland.

  17. Magnetic resonance spectroscopy features of normal-appearing white matter in patients with acute brucellosis

    Energy Technology Data Exchange (ETDEWEB)

    Kayabas, Uner [Department of Infectious Disease and Clinical Microbiology, Inonu University, Medical Faculty, TR-44280 Malatya (Turkey)], E-mail: ukayabas@inonu.edu.tr; Alkan, Alpay; Firat, Ahmet Kemal; Karakas, Hakki Muammer [Department of Radiology, Inonu University, Medical Faculty, TR-44280 Malatya (Turkey); Bayindir, Yasar; Yetkin, Funda [Department of Infectious Disease and Clinical Microbiology, Inonu University, Medical Faculty, TR-44280 Malatya (Turkey)

    2008-03-15

    We aimed to evaluate whether the subtle metabolic cerebral changes are present in normal-appearing white matter on conventional MRI, in patients with acute brucellosis, by using MR spectroscopy (MRS). Sixteen patients with acute brucellosis and 13 healthy control subjects were investigated with conventional MRI and single-voxel MRS. Voxels were placed in normal-appearing parietal white matter (NAPWM). N-Acetyl aspartate (NAA)/creatine (Cr) and choline (Cho)/Cr ratios were calculated. There was no significant difference between the study subjects and the control group in NAA/Cr ratios obtained from NAPWM. However, the Cho/Cr ratios were significantly higher in patients with acute brucellosis compared to controls (p = 0.01). MRS revealed metabolic changes in normal-appearing white matter of patients with brucellosis. Brucellosis may cause subtle cerebral alterations, which may only be discernible with MRS. Increased Cho/Cr ratio possibly represents an initial phase of inflammation and/or demyelination process of brucellosis.

  18. Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies.

    Science.gov (United States)

    Hwang, Pei-Ing; Wu, Huan-Bin; Wang, Chin-Di; Lin, Bai-Ling; Chen, Cheng-Tao; Yuan, Shinsheng; Wu, Guani; Li, Ker-Chau

    2011-09-01

    To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue. By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific Gene Expression Templates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis.Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity. These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.

  19. Tissue-specific gene expression templates for accurate molecular characterization of the normal physiological states of multiple human tissues with implication in development and cancer studies

    Directory of Open Access Journals (Sweden)

    Yuan Shinsheng

    2011-09-01

    Full Text Available Abstract Background To elucidate the molecular complications in many complex diseases, we argue for the priority to construct a model representing the normal physiological state of a cell/tissue. Results By analyzing three independent microarray datasets on normal human tissues, we established a quantitative molecular model GET, which consists of 24 tissue-specific Gene Expression Templates constructed from a set of 56 genes, for predicting 24 distinct tissue types under disease-free condition. 99.2% correctness was reached when a large-scale validation was performed on 61 new datasets to test the tissue-prediction power of GET. Network analysis based on molecular interactions suggests a potential role of these 56 genes in tissue differentiation and carcinogenesis. Applying GET to transcriptomic datasets produced from tissue development studies the results correlated well with developmental stages. Cancerous tissues and cell lines yielded significantly lower correlation with GET than the normal tissues. GET distinguished melanoma from normal skin tissue or benign skin tumor with 96% sensitivity and 89% specificity. Conclusions These results strongly suggest that a normal tissue or cell may uphold its normal functioning and morphology by maintaining specific chemical stoichiometry among genes. The state of stoichiometry can be depicted by a compact set of representative genes such as the 56 genes obtained here. A significant deviation from normal stoichiometry may result in malfunction or abnormal growth of the cells.

  20. The treatment of acute soft tissue trauma in Danish emergency rooms

    DEFF Research Database (Denmark)

    Johannsen, F; Langberg, Henning

    1997-01-01

    Rest, ice, compression, elevation (RICE) is the most recommended treatment for acute traumatic soft tissue injuries. A questionnaire was given to all Danish emergency rooms (n = 5) regarding their routines for acute treatment of ankle sprains and muscle contusions. Complete answers were received ...

  1. Statin Use and Functional Outcome after Tissue Plasminogen Activator Treatment in Acute Ischaemic Stroke

    NARCIS (Netherlands)

    Miedema, I; Uyttenboogaart, M; Koopman, K; De Keyser, J; Luijckx, G J

    2010-01-01

    Background: Preliminary findings suggest that statins may have a neuroprotective effect in patients with acute ischaemic stroke. This study investigated whether patients prior on statin therapy and treated with tissue plasminogen activator (tPA) for acute ischaemic stroke have a better functional ou

  2. Evaluation of algorithm methods for fluorescence spectra of cancerous and normal human tissues

    Science.gov (United States)

    Pu, Yang; Wang, Wubao; Alfano, Robert R.

    2016-03-01

    The paper focus on the various algorithms on to unravel the fluorescence spectra by unmixing methods to identify cancerous and normal human tissues from the measured fluorescence spectroscopy. The biochemical or morphologic changes that cause fluorescence spectra variations would appear earlier than the histological approach; therefore, fluorescence spectroscopy holds a great promise as clinical tool for diagnosing early stage of carcinomas and other deceases for in vivo use. The method can further identify tissue biomarkers by decomposing the spectral contributions of different fluorescent molecules of interest. In this work, we investigate the performance of blind source un-mixing methods (backward model) and spectral fitting approaches (forward model) in decomposing the contributions of key fluorescent molecules from the tissue mixture background when certain selected excitation wavelength is applied. Pairs of adenocarcinoma as well as normal tissues confirmed by pathologist were excited by selective wavelength of 340 nm. The emission spectra of resected fresh tissue were used to evaluate the relative changes of collagen, reduced nicotinamide adenine dinucleotide (NADH), and Flavin by various spectral un-mixing methods. Two categories of algorithms: forward methods and Blind Source Separation [such as Principal Component Analysis (PCA) and Independent Component Analysis (ICA), and Nonnegative Matrix Factorization (NMF)] will be introduced and evaluated. The purpose of the spectral analysis is to discard the redundant information which conceals the difference between these two types of tissues, but keep their diagnostically significance. The facts predicted by different methods were compared to the gold standard of histopathology. The results indicate that these key fluorophores within tissue, e.g. tryptophan, collagen, and NADH, and flavin, show differences of relative contents of fluorophores among different types of human cancer and normal tissues. The

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

    Energy Technology Data Exchange (ETDEWEB)

    Leitao, Roberta G.; Anjos, Marcelino J.; Canellas, Catarine G.L.; Lopes, Ricardo T., E-mail: roberta@lin.ufrj.b [Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Lab. de Instrumentacao Nuclear; Correia, Rodrigo C., E-mail: marcelin@lin.ufrj.b [Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, RJ (Brazil). Inst. de Fisica; Palumbo Junior, Antonio; Souza, Pedro A.V.R.; Nasciutti, Luiz E., E-mail: nasciutt@ufrj.b [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Centro de Ciencias da Saude. Lab. de Interacoes Celulares; Ferreira, Luiz C., E-mail: luiz.ferreira@ipec.fiocruz.b [Fundacao Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil)

    2009-07-01

    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 alpha = 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. Label-free discrimination of normal and pulmonary cancer tissues using multiphoton fluorescence ratiometric microscopy

    Science.gov (United States)

    Wang, Chun-Chin; Wu, Ruei-Jr; Lin, Sung-Jan; Chen, Yang-Fang; Dong, Chen-Yuan

    2010-07-01

    We performed multiphoton excited autofluorescence and second harmonic generation microscopy for the distinction of normal, lung adenocarcinoma (LAC), and squamous cell carcinoma (SCC) specimens. In addition to morphological distinction, we derived quantitative metrics of cellular redox ratios for cancer discrimination. Specifically, the redox ratios of paired normal/SCC and normal/LAC specimens were found to be 0.53±0.05/0.41±0.06 and 0.56±0.02/0.35±0.06, respectively. The lower redox ratios in cancer specimens, indicating an increase in metabolic activity. These results show that the combination of morphological multiphoton imaging along with redox ratio indices can be used for the discrimination of normal and pulmonary cancer tissues.

  5. The sodium iodide symporter (NIS and potential regulators in normal, benign and malignant human breast tissue.

    Directory of Open Access Journals (Sweden)

    James Ryan

    Full Text Available INTRODUCTION: The presence, relevance and regulation of the Sodium Iodide Symporter (NIS in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. METHODS: Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10 were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ, oestrogen (ERα, thyroid hormones (THRα, THRβ, and also phosphoinositide-3-kinase (PI3K. Breast cancer cells were treated with Retinoic acid (ATRA, Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. RESULTS: The lowest levels of NIS were detected in normal tissue (Mean(SEM 0.70(0.12 Log(10 Relative Quantity (RQ with significantly higher levels observed in fibroadenoma (1.69(0.21 Log(10RQ, p<0.005 and malignant breast tissue (1.18(0.07 Log(10RQ, p<0.05. Significant positive correlations were observed between human NIS and ERα (r = 0.22, p<0.05 and RARα (r = 0.29, p<0.005, with the strongest relationship observed between NIS and RARβ (r = 0.38, p<0.0001. An inverse relationship between NIS and PI3K expression was also observed (r =  0.21, p<0.05. In vitro, ATRA, Estradiol and Thyroxine individually stimulated significant increases in NIS expression (range 6-16 fold, while ATRA and Thyroxine combined caused the greatest increase (range 16-26 fold. CONCLUSION: Although NIS expression is significantly higher in malignant compared to normal breast tissue, the highest level was detected in fibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones.

  6. Metabolic imaging in microregions of tumors and normal tissues with bioluminescence and photon counting

    Energy Technology Data Exchange (ETDEWEB)

    Mueller-Klieser, W.; Walenta, S.; Paschen, W.; Kallinowski, F.; Vaupel, P.

    1988-08-03

    A method has been developed for metabolic imaging on a microscopic level in tumors, tumor spheroids, and normal tissues. The technique makes it possible to determine the spatial distribution of glucose, lactate, and ATP in absolute terms at similar locations within tissues or cell aggregates. The substrate distributions are registered in serial cryostat sections from tissue cryobiopsies or from frozen spheroids with the use of bioluminescence reactions. The light emission is measured directly by a special imaging photon counting system enabling on-line image analysis. The technique has been applied to human breast cancer xenografts, to spheroids originating from a human colon adenocarcinoma, and to skeletal rat muscle. Preliminary data obtained indicate that heterogeneities in the substrate distributions measured are much more pronounced in tumors than in normal tissue. There was no obvious correlation among the three quantities measured at similar locations within the tissues. The distribution of ATP corresponded well with the histological structure of larger spheroids; values were low in the necrotic center and high in the viable rim of these cell aggregates.

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

    Energy Technology Data Exchange (ETDEWEB)

    Saiki, Mitiko; Genezini, Frederico A., E-mail: mitiko@ipen.br, E-mail: fredzini@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro do Reator de Pesquisas; Leite, Renata E.P.; Grinberg, Lea T.; Ferretti, Renata E.L.; Suemoto, Claudia; Pasqualucci, Carlos A.; Jacob-Filho, Wilson, E-mail: renataleite@usp.br, E-mail: lea@grinberg.com.br, E-mail: reloah@usp.br, E-mail: farfel@usp.br, E-mail: csuemoto@gmail.com, E-mail: cpasqua@usp.br, E-mail: wijac@usp.br [Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Fac. de Medicina

    2013-07-01

    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)

  8. 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.

  9. Static jaw collimation settings to minimize radiation dose to normal brain tissue during stereotactic radiosurgery.

    Science.gov (United States)

    Han, Eun Young; Zhang, Xin; Yan, Yulong; Sharma, Sunil; Penagaricano, Jose; Moros, Eduardo; Corry, Peter

    2012-01-01

    At the University of Arkansas for Medical Sciences (UAMS) intracranial stereotactic radiosurgery (SRS) is performed by using a linear accelerator with an add-on micromultileaf collimator (mMLC). In our clinical setting, static jaws are automatically adapted to the furthest edge of the mMLC-defined segments with 2-mm (X jaw) and 5-mm (Y jaw) margin and the same jaw values are applied for all beam angles in the treatment planning system. This additional field gap between the static jaws and the mMLC allows additional radiation dose to normal brain tissue. Because a radiosurgery procedure consists of a single high dose to the planning target volume (PTV), reduction of unnecessary dose to normal brain tissue near the PTV is important, particularly for pediatric patients whose brains are still developing or when a critical organ, such as the optic chiasm, is near the PTV. The purpose of this study was to minimize dose to normal brain tissue by allowing minimal static jaw margin around the mMLC-defined fields and different static jaw values for each beam angle or arc. Dose output factors were measured with various static jaw margins and the results were compared with calculated doses in the treatment planning system. Ten patient plans were randomly selected and recalculated with zero static jaw margins without changing other parameters. Changes of PTV coverage, mean dose to predefined normal brain tissue volume adjacent to PTV, and monitor units were compared. It was found that the dose output percentage difference varied from 4.9-1.3% for the maximum static jaw opening vs. static jaw with zero margins. The mean dose to normal brain tissue at risk adjacent to the PTV was reduced by an average of 1.9%, with negligible PTV coverage loss. This dose reduction strategy may be meaningful in terms of late effects of radiation, particularly in pediatric patients. This study generated clinical knowledge and tools to consistently minimize dose to normal brain tissue.

  10. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    Directory of Open Access Journals (Sweden)

    Armando Vilchis-Ordoñez

    2015-01-01

    Full Text Available B-cell acute lymphoblastic leukemia (B-ALL is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1β, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13+CD33+ population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow.

  11. Acute hypotensive and diuretic activities of Artemisia herba alba aqueous extract in normal rats

    Institute of Scientific and Technical Information of China (English)

    Naoufel Ali Zeggwagh; Jean Baptiste Michel; Mohamed Eddouks

    2014-01-01

    Objective:To evaluate the effect of Artemisia herba alba (A. herba alba) intravenous injection on cardiovascular and renal function in normal rats. Methods:The effect of intravenous injection of A. herba alba extract at the different doses of 50, 100 and 200 mg/kg was investigated in normal rats. Diuresis, heart frequency and electrolytes concentrations were analyzed. Results: Intravenous bolus injection of A. herba alba at the different doses of 50, 100 and 200 mg/kg produced a dose dependent reduction in arterial blood pressure (P Conclusions: We conclude that the aqueous A. herba alba extract possesses a potent acute hypotensive effect on normal rats. In addition, A. herba alba perfusion may affect renal function to increase urine and electrolytes excretion.

  12. Label-free discrimination of normal and fibroadenomal breast tissues using second harmonic generation imaging.

    Science.gov (United States)

    Zheng, Liqin; Zhuo, Shuangmu; Chen, Gang; Zhu, Xiaoqin; Jiang, Xingshan; Yan, Jun; Chen, Jianxin; Xie, Shusen

    2011-01-01

    Early detection of fibroadenoma (FA) is critical for preventing subsequent breast cancer. In this work, we show that label-free second harmonic generation (SHG) imaging is feasible and effective in quantitatively differentiating the fibroadenomal tissue from normal breast tissue. With the advent of the clinical portability of miniature SHG microscopy, we believe that the technique has great potential in offering a noninvasive in vivo imaging tool for early detection of FA and monitoring the treatment responses of FA in clinics. Copyright © 2011 Wiley Periodicals, Inc.

  13. Enhancing tissue permeability with MRI guided preclinical focused ultrasound system in rabbit muscle: From normal tissue to VX2 tumor.

    Science.gov (United States)

    Sun, Yao; Xiong, Xiaobing; Pandya, Darpan; Jung, Youngkyoo; Mintz, Akiva; Hayasaka, Satoru; Wadas, Thaddeus J; Li, King C P

    2017-06-28

    High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing physical energy based modality to ablate solid tumors with high power, or increase local permeability in tissues/tumors in pulsed mode with relatively low power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU (pHIFU) is present in the majority of novel applications recently developed for enhancing the delivery of drugs and genes. Previous studies have demonstrated the capability of pHIFU to change tissue local permeability for enhanced drug delivery in both mouse tumors and mouse muscle. Further study based on bulk tissues in large animals and clinical HIFU system revealed correlation between therapeutic effect and thermal parameters, which was absent in the previous mouse studies. In this study, we further investigated the relation between the therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues based on a rabbit model and a preclinical HIFU system. Correlation between therapeutic effect and thermal parameters was confirmed in our study on the same bulk tissues although different HIFU systems were used. Following the study in bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors implanted on both hind limbs of rabbits and investigated the feasibility to enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU technique. A radiolabeled peptidomimetic integrin antagonist, (111)In-DOTA-IA, was used following pHIFU treatment in our study to target VX2 tumor and serve as the radiotracer for follow-up single-photon emission computed tomography (SPECT) scanning. The results have shown significantly elevated uptake of (111)In-DOTA-IA in the area of VX2 tumors pretreated by pHIFU compared with the control VX2 tumors not being pretreated by pHIFU, and statistical analysis revealed averaged 34.5% enhancement 24h after systematic delivery of (111)In-DOTA-IA in VX2 tumors pretreated by pHIFU compared

  14. 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.

  15. Comparison of nuclear matrix proteins between gastric cancer and normal gastric tissue

    Institute of Scientific and Technical Information of China (English)

    Qin-Xian Zhang; Yi Ding; Zhuo Li; Xiao-Ping Le; Wei Zhang; Ling Sun; Hui-Rong Shi

    2004-01-01

    AIM: To study the alteration of nuclear matrix proteins (NMPs) in gastric cancer.METHODS: The NMPs extracted from 22 cases of gastric cancer and normal gastric tissues were investigated by SDS-PAGE technique and the data were analyzed using Genetools analysis software.RESULTS: Compared with normal gastric tissue, the expression of 30 ku and 28 ku NMPs in gastric cancer decreased significantly (P=0.002, P=0.001, P<0.05). No significant difference was found in the expression of the two NMPs between the various differentiated grades (P=0.947, P=0.356) and clinical stages of gastric cancer (P=0.920, P=0.243, P>0.05).CONCLUSION: The results suggested that the alteration of NMPs in gastric cancer occurred at the early stage of gastric cancer development.

  16. 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.

  17. Clinical objectives and normal tissue responses in combined chemotherapy and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Peckham, M.J.; Collis, C.H. (Institute of Cancer Research, Sutton (UK). Surrey Branch; Royal Marsden Hospital, London (UK))

    1981-01-01

    It is clear that the risk of toxicity to normal tissues in combined therapy is reduced by separating drug administration and radiation exposure in time. The short-term interaction of drugs and radiation aimed at producing enhanced tumour cell kill is difficult to demonstrate in vivo in animal experiments and unlikely to be important in clinical practice. Increased toxicity of normal tissues in man has been manifest both in terms of early and late reactions and probably also in carcinogenesis. In the latter context choice of drug and possibly sequencing may be important in minimising the risk of tumour induction. There are few experimental studies examining moderately long time intervals between drug and radiation exposure. The administration of chemotherapy prior to irradiation may be less toxic than the converse sequence, although clinical data supporting this contention are limited at the present time.

  18. 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.

    2010-01-01

    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. PMID:20171511

  19. Normal tissue studies in radiation oncology: A systematic review of highly cited articles and citation patterns.

    Science.gov (United States)

    Nieder, Carsten; Andratschke, Nicolaus H; Grosu, Anca L

    2014-09-01

    Radiation therapy is one of the cornerstones of modern multidisciplinary cancer treatment. Normal tissue tolerance is critical as radiation-induced side effects may compromise organ function and quality of life. The importance of normal tissue research is reflected by the large number of scientific articles, which have been published between 2006 and 2010. The present study identified important areas of research as well as seminal publications. The article citation rate is among the potential indicators of scientific impact. Highly cited articles, arbitrarily defined as those with ≥15 citations, were identified via a systematic search of the citation database, Scopus. Up to 608 articles per year were published between 2006 and 2010, however, distribution, clinical prevention or mitigation studies are critical and must receive higher priority, funding and attention.

  20. Prolonged Incubation of Acute Neuronal Tissue for Electrophysiology and Calcium-imaging.

    Science.gov (United States)

    Cameron, Morven A; Kekesi, Orsolya; Morley, John W; Bellot-Saez, Alba; Kueh, Sindy; Breen, Paul; van Schaik, André; Tapson, Jonathan; Buskila, Yossi

    2017-02-15

    Acute neuronal tissue preparations, brain slices and retinal wholemount, can usually only be maintained for 6 - 8 h following dissection. This limits the experimental time, and increases the number of animals that are utilized per study. This limitation specifically impacts protocols such as calcium imaging that require prolonged pre-incubation with bath-applied dyes. Exponential bacterial growth within 3 - 4 h after slicing is tightly correlated with a decrease in tissue health. This study describes a method for limiting the proliferation of bacteria in acute preparations to maintain viable neuronal tissue for prolonged periods of time (>24 h) without the need for antibiotics, sterile procedures, or tissue culture media containing growth factors. By cycling the extracellular fluid through UV irradiation and keeping the tissue in a custom holding chamber at 15 - 16 °C, the tissue shows no difference in electrophysiological properties, or calcium signaling through intracellular calcium dyes at >24 h postdissection. These methods will not only extend experimental time for those using acute neuronal tissue, but will reduce the number of animals required to complete experimental goals, and will set a gold standard for acute neuronal tissue incubation.

  1. Expression pattern of epithelial cell adhesion molecule on normal and malignant colon tissues

    Institute of Scientific and Technical Information of China (English)

    Xin Xie; Chun-Yan Wang; Yun-Xin Cao; Wei Wang; Ran Zhuang; Li-Hua Chen; Na-Na Dang; Liang Fang; Bo-Quan Jin

    2005-01-01

    AIM: To investigate the expression pattern of epithelial cell adhesion molecule (Ep-CAM) on normal and malignant colon tissues to evaluate its diagnostic and therapeutic significance.METHODS: cDNA encoding Ep-CAv extracellular domain was cloned by reverse transcription-polymerase chain reaction (RT-PCR) from excised malignant colon tissues and inserted into a glutathione S-transferase (GST)-tagged vector. EpCAM-GST fusion protein was induced by isopropyl-β-D-thiogalactopyranoside (IPTG) and purified with glutathionesepharose. The Ep-CAM-GST fusion protein was mixed with Freund's adjuvant and Balb/c mice were immunized with it. Sp2/0 myeloma cells were fused with the spleen cells of the immunized mice. After having selected by indirect ELISA, the anti-Ep-CAM monoclonal antibodies (NAbs) were generated and the corresponding ascites were obtained.Finally, the human colon carcinoma tissue array prepared from seventy individual patients was stained with the antiEp-CAM NAbs.RESULTS: The isolated Ep-CAM cDNA sequence was identical to the data in GenBank. The expressed fusion protein was almost soluble and had a molecular weight (NW) of 53 ku.Four NAbs against Ep-CAM were obtained and designated as FMU-Ep1, FMU-Ep2, FMU-Ep3 and FMU-Ep4 respectively.Among them, FMU-Ep4 could recognize the natural EpCAM on Colo205 and SW480 cells, and all of them could be used for immunohistochemical staining of tissue sections.It was found that Ep-CAM was distributed differently in normal and various malignant colon tissues, including squamous cell carcinoma, signet-ring cell carcinoma and adenocarcinoma.In normal colon gland epithelia, Ep-CAM antigen was mainly distributed on the basolateral membrane and in the region between the basolateral membrane and the cytoplastic part near the nuclei, whereas the expression pattern of colon malignancies was mainly on the whole surface of epithelia and the expression was much higher than the normal colon tissues. The staining pattern of tissue array

  2. Uptake of 153Sm-EDTMP in normal, benign and malignant tumor tissue

    CERN Document Server

    Riegel, A

    2001-01-01

    The present study was designed to investigate and compare the uptake of 153Sm-EDTMP (153Samarium-ethylenediaminetetramethylene phosphonate)and 99mTc-DPD (99mTechnetium-dicarboxypropane diphosphonate) into different soft tissue sarcoma cell lines and various tissue specimen in vitro. After 10-120 minutes of incubation at 22 sup o C and 37 sup o C with 153Sm-EDTMP, the uptake kinetics of this tracer in human soft tissue sarcoma cells SW 684 (fibrosarcoma) and SW 1353 (chondrosarcoma) were assessed. The uptake was temperature-dependent and higher into fibrosarcoma than in chondrosarconma. Normal bone tissue samples of rat and human were incubated with 153Sm-EDTMP and 99mTc-DPD. The uptake of 99mTc-DPD was higher than that of 153Sm-EDTMP. Various benign and malignant bone and soft tissue tumors and metastases of different primaries were treated in the same way. The uptake was generally very low, in the metastatic tissue specimen in part possibly due to their osteolytic character.

  3. The myofibroblast, multiple origins for major roles in normal and pathological tissue repair

    Directory of Open Access Journals (Sweden)

    Micallef Ludovic

    2012-06-01

    Full Text Available Abstract Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myofibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases.

  4. The feasibility of using poroelastographic techniques for distinguishing between normal and lymphedematous tissues in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Righetti, Raffaella [Department of Diagnostic and Interventional Imaging, Ultrasonics Laboratory, University of Texas Medical School, Houston, TX (United States); Garra, Brian S [Department of Radiology, University of Vermont College of Medicine, Burlington, VT (United States); Mobbs, Louise M [Department of Radiology, Fletcher Allen Health Care, Burlington, VT (United States); Kraemer-Chant, Christina M [Department of Radiology, University of Vermont College of Medicine, Burlington, VT (United States); Ophir, Jonathan [Department of Diagnostic and Interventional Imaging, Ultrasonics Laboratory, University of Texas Medical School, Houston, TX (United States); Krouskop, Thomas A [Department of Diagnostic and Interventional Imaging, Ultrasonics Laboratory, University of Texas Medical School, Houston, TX (United States)

    2007-11-07

    Lymphedema is a common condition involving an abnormal accumulation of lymphatic fluid in the interstitial space that causes swelling, most often in the arm(s) and leg(s). Lymphedema is a significant lifelong concern that can be congenital or develop following cancer treatment or cancer metastasis. Common methods of evaluation of lymphedema are mostly qualitative making it difficult to reliably assess the severity of the disease, a key factor in choosing the appropriate treatment. In this paper, we investigate the feasibility of using novel elastographic techniques to differentiate between lymphedematous and normal tissues. This study represents the first step of a larger study aimed at investigating the combined use of elastographic and sonographic techniques for the detection and staging of lymphedema. In this preliminary study, poroelastographic images were generated from the leg (8) and arm (4) subcutis of five normal volunteers and seven volunteers having lymphedema, and the results were compared using statistical analyses. The preliminary results reported in this paper suggest that it may be feasible to perform poroelastography in different lymphedematous tissues in vivo and that poroelastography techniques may be of help in differentiating between normal and lymphedematous tissues.

  5. The feasibility of using poroelastographic techniques for distinguishing between normal and lymphedematous tissues in vivo

    Science.gov (United States)

    Righetti, Raffaella; Garra, Brian S.; Mobbs, Louise M.; Kraemer-Chant, Christina M.; Ophir, Jonathan; Krouskop, Thomas A.

    2007-11-01

    Lymphedema is a common condition involving an abnormal accumulation of lymphatic fluid in the interstitial space that causes swelling, most often in the arm(s) and leg(s). Lymphedema is a significant lifelong concern that can be congenital or develop following cancer treatment or cancer metastasis. Common methods of evaluation of lymphedema are mostly qualitative making it difficult to reliably assess the severity of the disease, a key factor in choosing the appropriate treatment. In this paper, we investigate the feasibility of using novel elastographic techniques to differentiate between lymphedematous and normal tissues. This study represents the first step of a larger study aimed at investigating the combined use of elastographic and sonographic techniques for the detection and staging of lymphedema. In this preliminary study, poroelastographic images were generated from the leg (8) and arm (4) subcutis of five normal volunteers and seven volunteers having lymphedema, and the results were compared using statistical analyses. The preliminary results reported in this paper suggest that it may be feasible to perform poroelastography in different lymphedematous tissues in vivo and that poroelastography techniques may be of help in differentiating between normal and lymphedematous tissues.

  6. Analysis of differentially expressed proteins in cancerous and normal colonic tissues

    Institute of Scientific and Technical Information of China (English)

    Lay-Harn Gam; Chiuan-Herng Leow; Che Nin Man; Boon-Hui Gooi; Manjit Singh

    2006-01-01

    AIM: To identify and analyze the differentially expressed proteins in normal and cancerous tissues of four patients suffering from colon cancer.METHODS: Colon tissues (normal and cancerous)were homogenized and the proteins were extracted using three protein extraction buffers. The extraction buffers were used in an orderly sequence of increasing extraction strength for proteins with hydrophobic properties. The protein extracts were separated using the SDS-PAGE method and the images were captured and analyzed using Quantity One software. The target protein bands were subjected to in-gel digestion with trypsin and finally analyzed using an ESI-ion trap mass spectrometer.RESULTS: A total of 50 differentially expressed proteins in colonic cancerous and normal tissues were identified.CONCLUSION: Many of the identified proteins have been reported to be involved in the progression of similar or other types of cancers. However, some of the identified proteins have not been reported before. In addition, a number of hypothetical proteins were also identified.

  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. Suitability of single tissue dielectric constant measurements to assess local tissue water in normal and lymphedematous skin.

    Science.gov (United States)

    Mayrovitz, Harvey N; Davey, Suzanne; Shapiro, Elizabeth

    2009-04-01

    Previous reports described the use of average tissue dielectric constant (TDC) measurements to assess local tissue water and its change. Our goal was to determine if a single TDC measurement could be used in place of the average of multiple measurements. The comparison criteria used to test this was the extent to which single and averaged measurements yielded similar TDC values in both normal and lymphedematous tissue. Measurements were made in two groups of women; a control group (n = 20) and a group with unilateral arm lymphedema (n = 10). In the control group, TDC was measured to multiple depths (0.5-5.0 mm) on both ventral forearms and to a depth of 2.5 mm on the lateral thorax on both body sides. In the lymphedematous group, TDC was measured on both ventral forearms to a depth of 2.5 mm. Results showed that the 95% confidence interval for differences between single and averaged TDC values was less than +/-1 TDC unit and that the limits of agreement between methods was less than +/-2.5 TDC units (+/-6.5%) for each condition, site and depth measured. This finding suggests that where this level of agreement is acceptable suitable clinical assessments can be made using a single TDC measurement.

  9. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Satoshi Matsuzaki

    2004-12-19

    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 {sigma}{sub {lambda}}, as well as the standard hole burning parameters (namely, {gamma} 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 (f{Delta}{mu}) for MF680 in tissue samples when burn laser polarization is parallel to the Stark field. Differences are detected between f{Delta}{mu}s 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

  11. HER1-4 protein concentrations in normal breast tissue from breast cancer patients are expressed by the same profile as in the malignant tissue

    DEFF Research Database (Denmark)

    Olsen, Dorte Aa; Ostergaard, Birthe; Bokmand, Susanne;

    2009-01-01

    and the proteins extracted. The tissue and serum concentrations of HER1-4 were determined quantitatively using a commercially available enzyme linked immunosorbent assay (ELISA) method. Results: HER1 was down regulated in cancer tissue when compared to autologous reference tissue (p=8x10(-6)), while HER2 (p...-4 system. We have mapped the protein concentrations of HER1-4 in breast cancer tissue, autologous reference tissue, normal breast tissue and serum samples, to see whether non-cancer cells from these patients express a protein profile indicating general activation. Methods: Tissue samples from malignant...

  12. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    Science.gov (United States)

    Ryan, James; Curran, Catherine E; Hennessy, Emer; Newell, John; Morris, John C; Kerin, Michael J; Dwyer, Roisin M

    2011-01-19

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro. Human breast tissue specimens (malignant n = 75, normal n = 15, fibroadenoma n = 10) were analysed by RQ-PCR targeting NIS, receptors for retinoic acid (RARα, RARβ), oestrogen (ERα), thyroid hormones (THRα, THRβ), and also phosphoinositide-3-kinase (PI3K). Breast cancer cells were treated with Retinoic acid (ATRA), Estradiol and Thyroxine individually and in combination followed by analysis of changes in NIS expression. The lowest levels of NIS were detected in normal tissue (Mean(SEM) 0.70(0.12) Log(10) Relative Quantity (RQ)) with significantly higher levels observed in fibroadenoma (1.69(0.21) Log(10)RQ, phuman NIS and ERα (r = 0.22, pfibroadenoma. The data presented supports a role for retinoic acid and estradiol in mammary NIS regulation in vivo, and also highlights potential thyroidal regulation of mammary NIS mediated by thyroid hormones.

  13. Functional link between ETB receptors and eNOS maintain tissue oxygenation in the normal liver.

    Science.gov (United States)

    Paxian, Markus; Keller, Steve A; Baveja, Rajiv; Korneszczuk, Katarzyna; Huynh, Toan T; Clemens, Mark G

    2004-01-01

    Endothelins and their receptors play a crucial role in regulating liver microcirculation in pathophysiological conditions. The authors investigated the functional significance of the coupling of ET(B) receptors and eNOS in maintaining regional perfusion and tissue oxygenation in the normal liver. The effect of endothelin-1 or the ET(B) agonist IRL1620 on oxygen consumption was determined in isolated perfused liver and isolated hepatocytes. Oxygen delivery to the liver tissue was determined in vivo. Following eNOS or iNOS blockade, either ET-1 or IRL1620 was infused via the portal vein. Hepatic tissue oxygenation, redox state, and microcirculation were investigated by intravital microscopy. Injury was estimated by serum LDH. Although IRL1620 and endothelin-1 increased oxygen consumption in isolated hepatocytes, in intact liver, endothelin decreased oxygen consumption while IRL1620 produced no change. In vivo, ET(B) stimulation modestly altered hepatic tissue P(O(2)), redox potential, and microcirculation. eNOS inhibition and ET(B) activation dramatically reduced microcirculatory blood flow, oxygen supply, and increased LDH release. Inhibition of iNOS resulted in small but not significant changes in these parameters. Concomitant ET(A)/ET(B) receptor activation increased microcirculatory failure and decreased tissue oxygen even without NOS inhibition. In contrast, hepatocellular injury was significantly increased following eNOS inhibition. Coupling between ET(B) receptor stimulation and eNOS activation decreases sinusoidal constriction and plays a functionally important role in maintaining microcirculation and tissue oxygenation in the normal liver.

  14. STUDY OF ECK GENE EXON-3 FROM HUMAN NORMAL TISSUE AND BREAST CANCER CELL LINE

    Institute of Scientific and Technical Information of China (English)

    李瑶琛; 孔令洪; 王一理; 司履生

    2003-01-01

    Objective To establish a method cloning the exon 3 of eck gene from normal tissue and ZR-75-1 cell line (a human breast cancer cell line)and study whether these genes exist mutant. Methods Designed a pair of specific primers and amplified the exon 3 of eck gene fragment from the extracted genomic DNA derived from normal epithelial cells from skin tissue and ZR-75-1 cell line respectively by PCR technique. Transformed the E.coil. JM109 with recombinant plamids constructed by inserting the amplified fragments into medium vector pUCm-T and sequenced these amplified fragments after primary screening of endonuclease restriction digestion and PCR amplification. Results ① Obtained the genomic DNA of human normal epithelial cells and ZR-75-1 cell line respectively. ② Obtained the amplified fragments of human exon 3 of eck gene through PCR technique. ③ Obtained the cloning vectors of exon 3 of eck gene of human normal epithelial cells and ZR-75-1 cell line respectively. ④ ZR-75-1 cell line exists mutation of nucleotides. Conclusion Successfully established the method of cloning the human exon 3 of eck gene and found some mutations in the detected samples. This study lays a foundation for further studying the function of eck gene in tumorgenesis.

  15. Effects of acute hypoxia on human adipose tissue lipoprotein lipase activity and lipolysis

    OpenAIRE

    Mahat, Bimit; Chassé, Étienne; Mauger, Jean-François; Imbeault, Pascal

    2016-01-01

    Background Adipose tissue regulates postprandial lipid metabolism by storing dietary fat through lipoprotein lipase-mediated hydrolysis of exogenous triglycerides, and by inhibiting delivery of endogenous non-esterified fatty acid to nonadipose tissues. Animal studies show that acute hypoxia, a model of obstructive sleep apnea, reduces adipose tissue lipoprotein lipase activity and increases non-esterified fatty acid release, adversely affecting postprandial lipemia. These observations remain...

  16. Distinctive Glycerophospholipid Profiles of Human Seminoma and Adjacent Normal Tissues by Desorption Electrospray Ionization Imaging Mass Spectrometry

    Science.gov (United States)

    Masterson, Timothy A.; Dill, Allison L.; Eberlin, Livia S.; Mattarozzi, Monica; Cheng, Liang; Beck, Stephen D. W.; Bianchi, Federica; Cooks, R. Graham

    2011-08-01

    Desorption electrospray ionization mass spectrometry (DESI-MS) has been successfully used to discriminate between normal and cancerous human tissue from different anatomical sites. On the basis of this, DESI-MS imaging was used to characterize human seminoma and adjacent normal tissue. Seminoma and adjacent normal paired human tissue sections (40 tissues) from 15 patients undergoing radical orchiectomy were flash frozen in liquid nitrogen and sectioned to 15 μm thickness and thaw mounted to glass slides. The entire sample was two-dimensionally analyzed by the charged solvent spray to form a molecular image of the biological tissue. DESI-MS images were compared with formalin-fixed, hematoxylin and eosin (H&E) stained slides of the same material. Increased signal intensity was detected for two seminolipids [seminolipid (16:0/16:0) and seminolipid (30:0)] in the normal tubule testis tissue; these compounds were undetectable in seminoma tissue, as well as from the surrounding fat, muscle, and blood vessels. A glycerophosphoinositol [PI(18:0/20:4)] was also found at increased intensity in the normal testes tubule tissue when compared with seminoma tissue. Ascorbic acid (i.e., vitamin C) was found at increased amounts in seminoma tissue when compared with normal tissue. DESI-MS analysis was successfully used to visualize the location of several types of molecules across human seminoma and normal tissues. Discrimination between seminoma and adjacent normal testes tubules was achieved on the basis of the spatial distributions and varying intensities of particular lipid species as well as ascorbic acid. The increased presence of ascorbic acid within seminoma compared with normal seminiferous tubules was previously unknown.

  17. Optical properties of human normal small intestine tissue determined by Kubelka-Munk method in vitro

    Institute of Scientific and Technical Information of China (English)

    Hua-Jiang Wei; Da Xing; Guo-Yong Wu; Ying Jin; Huai-Min Gu

    2003-01-01

    AIM: To study the optical properties of human normal small intestine tissue at 476.5 nm, 488 nm, 496.5 nm, 514.5 nm,532 nm, 808 nm wavelengths of laser irradiation.METHODS: A double-integrating-sphere system, the basic principle of measuring technology of light radiation, and an optical model of biological tissues were used in the study.RESULTS: The results of measurement showed that there were no significant differences in the absorption coefficients of human normal small intestine tissue at 476.5 nm, 488 nm,496.5 nm laser in the Kubelka-Munk two-flux model (P>0.05).The absorption coefficients of the tissue at 514.5 nm, 532 nm,808 nm laser irradiation were obviously increased with the decrease of these wavelengths. The scattering coefficients of the tissue at 476.5 nm, 488 nm, 496.5 nm laser irradiation were increased with the decrease of these wavelengths.The scattering coefficients at 496.5 nm, 514.5 nm, 532 nm laser irradiation were obviously increased with the increase of these wavelengths. The scattering coefficient of the tissue at 532 nm laser irradiation was bigger than that at 808 nm.There were no significant differences in the total attenuation coefficient of the tissue at 476.5 nm and 488 nm laser irradiation (P>0.05). The total attenuation coefficient of the tissue at 488 nm, 496.5 nm, 514.5 nm, 532 nm, 808 nm laser irradiation was obviously increased with the decrease of these wavelengths, and their effective attenuation coefficient revealed the same trend. There were no significant differences among the forward scattered photon fluxe,backward scattered photon fiuxe, and total scattered photon fiuxe of the tissue at 476.5 nm, 488 nm, 496.5 nm laser irradiation. They were all obviously increased with attenuation of tissue thickness. The attenuations of forward and backward scattered photon fluxes, and the total scattered photon fiuxe of the tissue at 514.5 nm laser irradiation were slower than those at 476.5 nm, 488 nm, 496.5 nm laser irradiation

  18. Iodotyrosine deiodination in the normal and acutely TSH-stimulated thyroid.

    Science.gov (United States)

    Conti, A; Studer, H

    1977-05-01

    The deiodination of L-MIT-125I was measured in rat thyroid homogenates and slices before and after acute TSH stimulation. Slices and homogenates were incubated with identical concentrations of tissue and substrate in the presence and absence of NADPH. 1 USP unit TSH added in vitro to thyroid slices failed to stimulate deiodination; a single in vivo ip injection of 3 USP units TSH was also unable to raise deiodinating activity. In contrast to TSH, NADPH added to homogenates and slices enhanced deiodination significantly. However, several arguments, including a review of the literature, strongly militate against the hypothesis of an increased intracellular concentration of the coenzyme NADPH being the prerequisite to enhanced deiodination. The results suggest that deiodinase activity in acutely stimulated thyroids is not limited by the intracellular concentration of the enzyme itself nor by the availability of co-enzyme. Therefore, the increased iodide release induced by acute TSH stimulation is a mere consequence of the enhanced thyroglobulin proteolysis and does not require higher enzyme concentration. It will be shown subsequently that a different conclusion must be drawn in experiments with chronic TSH stimulation.

  19. Hypertonic 3% Saline in Comparison with 0.9% (Normal Saline in Treatment of Acute Bronchiolitis

    Directory of Open Access Journals (Sweden)

    Abdul-karem Jasem Mohammed Al-bahadily

    2017-01-01

    Full Text Available BackgroundBronchiolitis is the commonest cause of lower respiratory tract infection in infant. Respiratory syncytial virus is the commonest cause of bronchiolitis. This study aimed to assess the efficacy of nebulized 3% hypertonic saline and salbutamol in the treatment of acute bronchiolitis in comparison with nebulized 0.9% saline and salbutamol.Materials and MethodsA prospective case second multicenter study was done at two pediatric tertiary centers at the period from 1st of December 2014 to 31 of March 2015. A total of 100 previously well infant and children of age 1-24 months with clinical diagnoses of bronchiolitis who were admitted to the hospital were included. They were divided into two groups, the study group received 4 ml of nebulized hypertonic 3% saline (for 14 days, and second group received 4 ml of nebulized normal 0.9% saline (for 14 days, each co-administer with 0.5 ml salbutamol.ResultsAll patients with acute bronchiolitis having similar baseline characteristic, mean age 4.9 + Standard deviation (SD months, male gender constitutes 68% of the patients and the majority (67% of the cases were below 6 months. The mean of clinical severity score at admission was 6.4 for normal saline (NS group and 6.6 for hypertonic 3% saline (HS group. The mean length of hospital stay of normal saline group = 4.3 + Standard deviation (SD day and for hypertonic saline group was = 4.7 + Standard deviation (SD day.ConclusionWe didn’t find any advantage of hypertonic 3% saline over 0.9% normal saline in terms of length of hospital stay and clinical severity score.

  20. Expression of prolactin receptors in normal canine mammary tissue, canine mammary adenomas and mammary adenocarcinomas

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    Michel Erika

    2012-05-01

    Full Text Available Abstract Background Mammary tumors represent the most common neoplastic disease in female dogs. Recently, the promoting role of prolactin (PRL in the development of human breast carcinoma has been shown. Possible proliferative, anti-apoptotic, migratory and angiogenic effects of PRL on human mammary cancer cells in vitro and in vivo were suggested. The effects of PRL are mediated by its receptor, and alterations in receptor expression are likely to play a role in tumor development. Currently, not much data is available about prolactin receptor (PRLR expression in canine mammary tumors. To set the basis for investigations on the role of PRL in mammary tumorigenesis in this species, prolactin receptor expression was evaluated by semi-quantitative real time PCR and immunohistochemistry on 10 formalin-fixed, paraffin-embedded samples each of canine non-neoplastic mammary tissue, mammary adenomas and adenocarcinomas. Results The highest PRLR expression levels were found in normal mammary tissue, while adenomas, and to an even higher degree adenocarcinomas, showed a significant decrease in prolactin receptor expression. Compared to normal tissue, PRLR mRNA was reduced 2.4 fold (p = 0.0261 in adenomas and 4.8 fold (p = 0.008 in adenocarcinomas. PRLR mRNA expression was significantly lower in malignant than in benign lesions (p = 0.0165. Immunohistochemistry demonstrated PRLR expression in all three tissue types with signals mostly limited to epithelial cells. Conclusions Malignant transformation of mammary tissue was associated with a decline in prolactin receptor expression. Further studies are warranted to address the functional significance of this finding.

  1. 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.

  2. [Advances of study on prognostic factors of molecular biology in acute myeloid leukemia with normal cytogenetics].

    Science.gov (United States)

    Han, Tian-Jie; Xu, Xiao-Ping

    2010-08-01

    Acute myeloid leukemia (AML) is a group of diseases with a conspicuous heterogeneity. Following the development of cytogenetics, multiple reproducible chromosome aberrations have been discovered in AML, many of which not only are diagnostic markers for specific AML subtypes but also significant prognostic factors for determining complete remission (CR), relapse risk, and overall survival (OS). However, with the foundation of available chromosome analysis, a large group of acute myeloid leukemia (AML) patients, 40% to 49% of adults and 25% of children had not been found abnormality of chromosome karyotype under microscope. These so-called cytogenetically normal acute myeloid leukemia (CN-AML) patients have usually been classified in an intermediate-risk prognostic category. Nevertheless, the outcome of the CN-AML patients are varied in clinical studies, likely because there exist diverse gene mutations in these patients according to recent researches. Those mutations at the molecular level, on basis of which AML could be further classified, are significantly associated with CN-AML patients and offer potential targets for specific therapeutic studies. The review focuses on research advances abroad in this field including gene mutations suggesting bad prognosis such as FMS-related tyrosine kinase 3 gene mutation, Baalc gene and ETS-related gene hyperexpression, Wilms' tumor gene mutation and other gene mutations as well as gene mutations suggesting good prognosis such as nucleophosmin gene mutation, mixed lineage leukemia-partial tandem duplication, CCAAT/enhancer-binding protein α gene mutation.

  3. 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

  4. Multidetector CT appearance of the pelvis after cesarean delivery: normal and abnormal acute findings.

    Science.gov (United States)

    Gui, Benedetta; Danza, Francesco Maria; Valentini, Anna Lia; Laino, Maria Elena; Caruso, Alessandro; Carducci, Brigida; Rodolfino, Elena; Devicienti, Ersilia; Bonomo, Lorenzo

    2016-01-01

    Cesarean section (CS) may have several acute complications that can occur in the early postoperative period. The most common acute complications are hematomas and hemorrhage, infection, ovarian vein thrombosis, uterine dehiscence and rupture. Pelvic hematomas usually occur at specific sites and include bladder flap hematoma (between the lower uterine segment and the bladder) and subfascial or rectus sheath hematoma (rectus sheath or prevescical space). Puerperal hemorrhage can be associated with uterine dehiscence or rupture. Pelvic infections include endometritis, abscess, wound infection, and retained product of conception. Radiologists play an important role in the diagnosis and management of postoperative complications as a result of increasing use of multidetector CT in emergency room. The knowledge of normal and abnormal postsurgical anatomy and findings should facilitate the correct diagnosis so that the best management can be chosen for the patient, avoiding unnecessary surgical interventions and additional treatments. In this article we review the surgical cesarean technique and imaging CT technique followed by description of normal and abnormal post-CS CT findings.

  5. Microarray analysis of differentially expressed genes in preeclamptic and normal placental tissues.

    Science.gov (United States)

    Ma, K; Lian, Y; Zhou, S; Hu, R; Xiong, Y; Ting, P; Xiong, Y; Li, X; Wang, X

    2014-01-01

    To detect the candidate genes for preeclampsia (PE). The gene expression profiles in preeclamptic and normal placental tissues were analyzed using cDNA microarray approach and the altered expression of important genes were further confirmed by real-time RT-PCR (reverse transcription polymerase chain reaction) technique. Total RNA was extracted from placental tissues of three cases with severe PE and from three cases with normal pregnancy. After scanning, differentially expressed genes were detected by software. In two experiments (the fluorescent labels were exchanged), a total of 111 differentially expressed genes were detected. In placental tissue ofpreeclamptic pregnancy, 68 differentially expressed genes were up-regulated, and 44 differentially expressed genes were down-regulated. Of these genes, 16 highly differentially expressed genes were confirmed by real-time fluorescent quantitative RT-PCR, and the result showed that the ratio of gene expression differences was comparable to that detected by cDNA microarray. The results of bioinformatic analysis showed that encoding products of differentially expressed genes were correlated to infiltration of placenta trophoblastic cells, immunomodulatory factors, pregnancy-associated plasma protein, signal transduction pathway, and cell adhesion. Further studies on the biological function and regulating mechanism of these genes will provide new clues for better understanding of etiology and pathogenesis of PE.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  7. Normal Saline Versus Hypertonic 3% Saline: It’s Efficacy in Non-Acute Rhinosinusitis

    Directory of Open Access Journals (Sweden)

    Nezamoddin Berjis

    2011-01-01

    Full Text Available Introduction: Sinusitis is one of the most common diseases in general and in otolaryngology practice, but the optimal therapeutic options have not yet been fully developed. This manuscript will try to compare normal saline nasal douching with hypertonic saline in reducing symptoms and improving its signs. Materials and Methods: One hundred and fourteen patients suffering from non acute rhinosinusitis, documented by history, physical examination and radiologic studies were divided into normal saline and hypertonic saline groups, each consisting of 57 patients. data were obtained by physical examination and a questionnaire.. Results:  Type of treatment had no significant effect on headache, morning dryness of mouth and pharynx and fatigue. Nontheless, nasal congestion, purulent discharge and postnasal discharge were reported to have improved in the group treated with hypertonic saline versus the normal saline group. Patient satisfaction also showed better scores in the hypertonic saline group. Conclusion: Hypertonic saline (3% is more effective for nasal irrigation  than normal saline in chronic rhinosinusitis.

  8. Phenotypic, genotypic, and functional characterization of normal and acute myeloid leukemia-derived marrow endothelial cells.

    Science.gov (United States)

    Pizzo, Russell J; Azadniv, Mitra; Guo, Naxin; Acklin, Joshua; Lacagnina, Kimberly; Coppage, Myra; Liesveld, Jane L

    2016-05-01

    In addition to participation in homing, egress, and transmigration of hematopoietic cells, marrow endothelium also contributes to cell proliferation and survival. Endothelial cells from multiple vascular beds are able to prevent spontaneous or therapy-induced apoptosis in acute myelogenous leukemia (AML) blasts. Marrow-derived endothelial cells from leukemia patients have not been well-characterized, and in this work, endothelial cells were purified from marrow aspirates from normal subjects or from newly diagnosed AML patients to compare these cells phenotypically and functionally. By reverse transcription polymerase chain reaction, these cells express CD31, Tie-2, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS), supporting endothelial origin. They take up acetyl low-density lipoprotein and are able to form tubular structures. Culture of AML cells with endothelial cells from both normal and AML subjects supported adhesion, transmigration, and leukemia colony-forming unit outgrowth. RNA-sequencing analysis revealed 130 genes significantly up- or downregulated in AML-derived endothelial cells as compared with those derived from normal marrow. The genes differentially expressed (p phenotype and function to their normal marrow-derived counterparts, but genomic analysis suggests a differential signature with altered expression of genes, which could play a role in leukemogenesis or leukemia cell maintenance in the marrow microenvironment. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  9. Hyperspectral microscopic analysis of normal, benign and carcinoma microarray tissue sections

    Science.gov (United States)

    Maggioni, Mauro; Davis, Gustave L.; Warner, Frederick J.; Geshwind, Frank B.; Coppi, Andreas C.; DeVerse, Richard A.; Coifman, Ronald R.

    2006-02-01

    We apply a unique micro-optoelectromechanical tuned light source and new algorithms to the hyper-spectral microscopic analysis of human colon biopsies. The tuned light prototype (Plain Sight Systems Inc.) transmits any combination of light frequencies, range 440nm 700nm, trans-illuminating H and E stained tissue sections of normal (N), benign adenoma (B) and malignant carcinoma (M) colon biopsies, through a Nikon Biophot microscope. Hyper-spectral photomicrographs, randomly collected 400X magnication, are obtained with a CCD camera (Sensovation) from 59 different patient biopsies (20 N, 19 B, 20 M) mounted as a microarray on a single glass slide. The spectra of each pixel are normalized and analyzed to discriminate among tissue features: gland nuclei, gland cytoplasm and lamina propria/lumens. Spectral features permit the automatic extraction of 3298 nuclei with classification as N, B or M. When nuclei are extracted from each of the 59 biopsies the average classification among N, B and M nuclei is 97.1%; classification of the biopsies, based on the average nuclei classification, is 100%. However, when the nuclei are extracted from a subset of biopsies, and the prediction is made on nuclei in the remaining biopsies, there is a marked decrement in performance to 60% across the 3 classes. Similarly the biopsy classification drops to 54%. In spite of these classification differences, which we believe are due to instrument and biopsy normalization issues, hyper-spectral analysis has the potential to achieve diagnostic efficiency needed for objective microscopic diagnosis.

  10. Quantitative analysis of collagen change between normal and cancerous thyroid tissues based on SHG method

    Science.gov (United States)

    Chen, Xiwen; Huang, Zufang; Xi, Gangqin; Chen, Yongjian; Lin, Duo; Wang, Jing; Li, Zuanfang; Sun, Liqing; Chen, Jianxin; Chen, Rong

    2012-03-01

    Second-harmonic generation (SHG) is proved to be a high spatial resolution, large penetration depth and non-photobleaching method. In our study, SHG method was used to investigate the normal and cancerous thyroid tissue. For SHG imaging performance, system parameters were adjusted for high-contrast images acquisition. Each x-y image was recorded in pseudo-color, which matches the wavelength range in the visible spectrum. The acquisition time for a 512×512-pixels image was 1.57 sec; each acquired image was averaged four frames to improve the signal-to-noise ratio. Our results indicated that collagen presence as determined by counting the ratio of the SHG pixels over the whole pixels for normal and cancerous thyroid tissues were 0.48+/-0.05, 0.33+/-0.06 respectively. In addition, to quantitatively assess collagen-related changes, we employed GLCM texture analysis to the SHG images. Corresponding results showed that the correlation both fell off with distance in normal and cancerous group. Calculated value of Corr50 (the distance where the correlation crossed 50% of the initial correlation) indicated significant difference. This study demonstrates that SHG method can be used as a complementary tool in thyroid histopathology.

  11. Measurement of the sound transmission characteristics of normal neck tissue using a reflectionless uniform tube.

    Science.gov (United States)

    Wu, Liang; Xiao, Ke; Dong, Jiaqi; Wang, Supin; Wan, Mingxi

    2014-07-01

    Understanding the sound transmission of the neck tissue is necessary and important in areas such as vocal function evaluation and electrolarynx improvement. In this paper, a simple method using a reflectionless tube was proposed to measure the neck frequency response function (NFRF) of ten normal subjects (five males and five females) during Mandarin vowel production. The NFRFs across different subjects producing different vowels were measured at different neck positions and compared to confirm the effectiveness of the method, and determine the NFRF variations in normal subjects. The results showed that the proposed method offered an easy and effective way to obtain an accurate NFRF. For normal subjects, the neck tissue can be treated as a low-pass filter, with a maximum gain at 310 Hz and a roll-off at a slope of -8.4 dB/octave, flattening out above 2000 Hz. The measurement position on the neck did not influence the shape of the NFRF, but did change the overall gains of the NFRF. In addition, there was a significant gender difference in NFRFs at the low frequencies. Finally, some potential applications of this method and the results are suggested.

  12. Global cortical thinning in acute anorexia nervosa normalizes following long-term weight restoration.

    Science.gov (United States)

    King, Joseph A; Geisler, Daniel; Ritschel, Franziska; Boehm, Ilka; Seidel, Maria; Roschinski, Benjamin; Soltwedel, Laura; Zwipp, Johannes; Pfuhl, Gerit; Marxen, Michael; Roessner, Veit; Ehrlich, Stefan

    2015-04-01

    Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation, extreme weight loss, and alterations in brain structure. Structural magnetic resonance imaging studies have documented brain volume reductions in acute AN, but it is unclear whether they are 1) regionally specific, or 2) reversible following weight restoration. Here, we measured cortical thickness (CT) for the first time in AN. Structural magnetic resonance imaging data were acquired from adolescent and young adult female patients with acute AN (n = 40), recovered patients following long-term weight restoration (n = 34), and an equal number of age-matched healthy control subjects. Group differences in CT were tested with well-validated procedures implemented in FreeSurfer. The mediating role of clinical variables including body mass index and drive for thinness were explored. For completeness, we also used FreeSurfer's subcortical segmentation stream to test group differences in volumes of select gray matter regions of interest. Vertex-wise analyses revealed significant thinning of over 85% of the cortical surface in patients with acute AN and CT normalization in recovered patients following long-term weight restoration, although normal age-related trajectories were absent in the disorder. This pattern of results was largely mirrored in subcortical volumes. We also observed a strong negative correlation between CT and drive for thinness in extrastriate regions involved in body perception. Structural brain anomalies in AN as expressed in CT and subcortical volume are primarily the consequence of malnutrition and unlikely to reflect premorbid trait markers or permanent scars, but longitudinal data are needed. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  13. 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.

  14. 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

  15. Innovation in tissue viability documentation for acute services.

    Science.gov (United States)

    Parnham, A

    2011-09-01

    This paper discusses the developmental process, outcome and delivery of an innovative approach to standardising tissue viability documentation across two sites within Nottingham University Hospitals NHS Trust, following the results of benchmarking pressure ulcer preventive care strategies and recommendations from pressure ulcer root cause analysis. It reflects upon the process, highlighting the lessons learnt.

  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. Monitoring late radiation damage in normal muscle tissue with electrical impedance spectroscopy

    Science.gov (United States)

    Osterman, Kendra Sunshine

    During radiation treatment for cancer, normal tissue will be exposed to radiation and it is the response of this tissue and the risk of complications that limits the prescribed dose and the efficacy of treatment. The response to radiation exposure is dose, time and tissue-type dependent and has been studied extensively in animal and human systems. However, there remains significant heterogeneity among individuals. Systematic and quantitative monitoring of tissue response with electrical impedance spectroscopy (EIS) might providing insight into early warning signs of late effects which could be used to alter the course of therapy on an individual patient basis. The implementation of EIS in three clinically relevant radiation settings is described. A kilovolt unit (orthovoltage, x-ray), a linear accelerator (x-ray), and an implantable radionuclide source (high dose rate, iridium-192 seed) were employed for the irradiation of muscle in the hind leg of rats. Doses of 70 Gy, 90 Gy, and 150 Gy were delivered with orthovoltage, nominal doses of 70 and 90 Gy which translate to doses of approximately 50 and 63 Gy at a 5mm distance from the center were employed with the linear accelerator, and doses of 26 and 52 Gy, at 5mm, were employed with the HDR system. The responses were monitored from 1--4 months post-irradiation. In all cases, EIS was capable of detecting a dose and time response, suggesting that EIS may indeed have a role to play in three of the most common irradiation procedures.

  18. Combined soft and skeletal tissue modelling of normal and dysmorphic midface postnatal development.

    Science.gov (United States)

    Ibrahim, Amel; Suttie, Michael; Bulstrode, Neil W; Britto, Jonathan A; Dunaway, David; Hammond, Peter; Ferretti, Patrizia

    2016-11-01

    Midface hypoplasia as exemplified by Treacher Collins Syndrome (TCS) can impair appearance and function. Reconstruction involves multiple invasive surgeries with variable long-term outcomes. This study aims to describe normal and dysmorphic midface postnatal development through combined modelling of skeletal and soft tissues and to develop a surgical evaluation tool. Midface skeletal and soft tissue surfaces were extracted from computed tomography scans of 52 control and 14 TCS children, then analysed using dense surface modelling. The model was used to describe midface growth, morphology, and asymmetry, then evaluate postoperative outcomes. Parameters responsible for the greatest variation in midface size and shape showed differences between TCS and controls with close alignment between skeletal and soft tissue models. TCS children exhibited midface dysmorphology and hypoplasia when compared with controls. Asymmetry was also significantly higher in TCS midfaces. Combined modelling was used to evaluate the impact of surgery in one TCS individual who showed normalisation immediately after surgery but reversion towards TCS dysmorphology after 1 year. This is the first quantitative analysis of postnatal midface development using combined modelling of skeletal and soft tissues. We also provide an approach for evaluation of surgical outcomes, laying the foundations for future development of a preoperative planning tool. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  19. The patterns and expression of KDR in normal tissues of human internal organs.

    Science.gov (United States)

    Huang, Jianfei; Zhu, Huijun; Wang, Xudong; Tang, Qi; Huang, Hua; Wu, Kerong; Zhu, Jin; Feng, Zhenqing; Shi, Gongshen

    2011-12-01

    KDR has been implicated for playing an important role in the formation of new blood vessels and in solid tumor growth. It was considered as one of the most important regulators of angiogenesis and a key target in anticancer treatment. In the present study, we characterized KDR mRNA and protein expression in normal tissues of perinatal and adult tissues using One-step Real-Time RT-PCR and immunohistochemistry with a self-made anti-KDR antibody. The expression of KDR mRNA and protein in perinatal internal organs were all higher than in adult organs including brain, kidney, liver, lung and heart, respectively. KDR protein was presented in the cell plasma membrane of human internal tissues. The expression of KDR protein was raised in macrophage of spleen, and decreased in neurons of brain, myocardium, bronchial epithelial cells and alveolar epithelial cell, proximal and distal tubules cells, and hepatic cells with the maturity process of human organs. Notably, the order of KDR protein expression from highest to lowest is as follows: brain, liver, heart, kidney, and lung in adult tissues with statistically significant. It follows that how to balance the potential therapeutic side effect with human internal organs in targeted therapy of over-expressing KDR tumor.

  20. 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.

  1. Myocardial infarction following recombinant tissue plasminogen activator treatment for acute ischemic stroke: a dangerous complication

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zhi-gang; WANG Rui-lan; YU Kang-long

    2012-01-01

    Thrombolysis with intravenous tissue plasminogen activator (t-PA) is currently an approved therapy for patients with acute ischemic stroke.Acute myocardial infarction (AMI) immediately following t-PA treatment for stroke is a rare but serious complication.A case of acute myocardial infarction (MI) following IV t-PA infusion for acute stroke was observed.This is a 52-year-old male with a known history of hypertension and chest pain,who subsequently developed MI four hours after IV t-PA was administered for acute ischemic stroke.The disruption of intra-cardiac thrombus and subsequent embolization to the coronary arteries may be an important mechanism.In addition.spontaneous recanalization of infarct-related arteries may be associated with 9reater myocardial salvage and better prognosis.

  2. Texture classification of normal tissues in computed tomography using Gabor filters

    Science.gov (United States)

    Dettori, Lucia; Bashir, Alia; Hasemann, Julie

    2007-03-01

    The research presented in this article is aimed at developing an automated imaging system for classification of normal tissues in medical images obtained from Computed Tomography (CT) scans. Texture features based on a bank of Gabor filters are used to classify the following tissues of interests: liver, spleen, kidney, aorta, trabecular bone, lung, muscle, IP fat, and SQ fat. The approach consists of three steps: convolution of the regions of interest with a bank of 32 Gabor filters (4 frequencies and 8 orientations), extraction of two Gabor texture features per filter (mean and standard deviation), and creation of a Classification and Regression Tree-based classifier that automatically identifies the various tissues. The data set used consists of approximately 1000 DIACOM images from normal chest and abdominal CT scans of five patients. The regions of interest were labeled by expert radiologists. Optimal trees were generated using two techniques: 10-fold cross-validation and splitting of the data set into a training and a testing set. In both cases, perfect classification rules were obtained provided enough images were available for training (~65%). All performance measures (sensitivity, specificity, precision, and accuracy) for all regions of interest were at 100%. This significantly improves previous results that used Wavelet, Ridgelet, and Curvelet texture features, yielding accuracy values in the 85%-98% range The Gabor filters' ability to isolate features at different frequencies and orientations allows for a multi-resolution analysis of texture essential when dealing with, at times, very subtle differences in the texture of tissues in CT scans.

  3. Model-integrated estimation of normal tissue contamination for cancer SNP allelic copy number data.

    Science.gov (United States)

    Stjernqvist, Susann; Rydén, Tobias; Greenman, Chris D

    2011-01-01

    SNP allelic copy number data provides intensity measurements for the two different alleles separately. We present a method that estimates the number of copies of each allele at each SNP position, using a continuous-index hidden Markov model. The method is especially suited for cancer data, since it includes the fraction of normal tissue contamination, often present when studying data from cancer tumors, into the model. The continuous-index structure takes into account the distances between the SNPs, and is thereby appropriate also when SNPs are unequally spaced. In a simulation study we show that the method performs favorably compared to previous methods even with as much as 70% normal contamination. We also provide results from applications to clinical data produced using the Affymetrix genome-wide SNP 6.0 platform.

  4. Euclidean and fractal geometry of microvascular networks in normal and neoplastic pituitary tissue.

    Science.gov (United States)

    Di Ieva, Antonio; Grizzi, Fabio; Gaetani, Paolo; Goglia, Umberto; Tschabitscher, Manfred; Mortini, Pietro; Rodriguez y Baena, Riccardo

    2008-07-01

    In geometrical terms, tumour vascularity is an exemplary anatomical system that irregularly fills a three-dimensional Euclidean space. This physical characteristic and the highly variable shapes of the vessels lead to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients and drugs, and the removal of metabolites. Although these biological characteristics are well known, quantitative analyses of newly formed vessels in two-dimensional histological sections still fail to view their architecture as a non-Euclidean geometrical entity, thus leading to errors in visual interpretation and discordant results from different laboratories concerning the same tumour. We here review the literature concerning microvessel density estimates (a Euclidean-based approach quantifying vascularity in normal and neoplastic pituitary tissues) and compare the results. We also discuss the limitations of Euclidean quantitative analyses of vascularity and the helpfulness of a fractal geometry-based approach as a better means of quantifying normal and neoplastic pituitary microvasculature.

  5. Coexpression of intermediate filaments in normal and neoplastic human tissues: a reappraisal.

    Science.gov (United States)

    Coggi, G; Dell'Orto, P; Braidotti, P; Coggi, A; Viale, G

    1989-01-01

    The current view that coexpression of intermediate filaments (IFs) must be considered a bizarre and unpredictable phenomenon, which seriously jeopardizes the use of their localization in diagnostic applications, is critically reviewed in light of the evidence so far acquired by investigations in vivo and in vitro. A less dogmatic approach, which considers IF expression the result of a series of interactions between cells and their microenvironment instead of a function of their histogenesis, not only justifies the complex variety of coexpressions observed in normal and neoplastic tissues but also confirms the usefulness of IF expression in diagnostic applications and offers new opportunities for investigations, with special regard to immunoelectron microscopy.

  6. Viruslike particles in the tissues of normal and gamma-irradiated Drosophila melanogaster.

    Science.gov (United States)

    Miquel, J.; Bensch, K. G.; Philpott, D. E.

    1972-01-01

    A new finding of viruslike particles in the salivary and accessory glands, muscles, and nerves of normal and gamma-irradiated Drosophila melanogaster is discussed. In morphology and size, the particles seemed identical to those described in earlier reports. On the basis of the available results, it cannot be affirmed that these particles infect only dividing cells, since they are found in all the Drosophila tissues so far examined. Their relation to the aging process is felt to be an interesting subject for further study.

  7. Expression of TRAIL and TRAIL receptors in normal and malignant tissues

    Institute of Scientific and Technical Information of China (English)

    Raymond A DANIELS; Gavin R SCREATON; Helen TURLEY; Fiona C KIMBERLEY; Xue Song LIU; Juthathip MONGKOLSAPAYA; Paul CH'EN; Xiao Ning XU; Boquan JIN; Francesco PEZZELLA

    2005-01-01

    TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, is a member of the TNF family of proteins.Tumour cells were initially found to have increased sensitivity to TRAIL compared with normal cells, raising hopes that TRAIL would prove useful as an anti-tumor agent. The production of reliable monoclonal antibodies against TRAIL and its receptors that can stain fixed specimens will allow a thorough analysis of their expression on normal and malignant tissues. Here we report the generation of monoclonal antibodies against TRAIL and its four membrane-bound receptors (TR1-4), which have been used to stain a range of normal and malignant cells, as routinely fixed specimens. Low levels of TRAIL expression were found to be limited mostly to smooth muscle in lung and spleen as well as glial cells in the cerebellum and follicular cells in the thyroid. Expression of the TRAIL decoy receptors (TR3 and 4) was not as widespread as indicated by Northern blotting, suggesting that they may be less important for the control of TRAIL cytotoxicity than previously thought. TR1 and TR2 expression increases significantly in a number of malignant tissues,but in some common malignancies their expression was low, or patchy, which may limit the therapeutic role of TRAIL.Taken together, we have a panel of monoclonal antibodies that will allow a better assessment of the normal role of TRAIL and allow assessment of biopsy material, possibly allowing the identification of tumors that may be amenable to TRAIL therapy.

  8. Amino acid uptake in arterio-venous serum of normal and cancerous colon tissues

    Institute of Scientific and Technical Information of China (English)

    Lin-Bo Wang; Jian-Guo Shen; Su-Zhan Zhang; Ke-Feng Ding; Shu Zheng

    2004-01-01

    AIM: To investigate the difference of amino acid uptake between normal and cancerous colon tissues.METHODS: Sixteen patients with colon cancer were enrolled in our study. Blood samples were taken during operations, serum amino acid concentrations of blood from cancerous or normal colon were analyzed. Amino acid uptake rate was calculated by the A-V difference and evaluated statistically.RESULTS: Except for methionine, the uptake rate of amino acids in cancer was higher than that in normal colon (25.01% vs-2.29%, P<0.01). The amino acid uptake rate did not correlate to the size of tumor mass (P>0.05). There was no statistical significance in the amino acid uptake rate according to the Dukes stage, though it was higher in patients with Dukes stage C or D than that with Dukes stage B (P>0.05).CONCLUSION: Abnormal synthetic metabolism of colon cancer may contribute to its higher amino acid uptake rate than that of normal colon.

  9. Phospholipase A2 changes and its significance on brain tissue of rat in severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yao Xuan; Chen Xi; Ji Zongzheng

    2007-01-01

    Objective To survey changes and the significance of phospholipase A2(PLA2) on brain tissue of SD rat in acute pancreatitis. Methods With retrograde injection of 3% taurocholate sodium into pancreatic and biliary duct, rat model of severe acute pancreatitis (SAP) was made,and it included four groups: the control group, the sham-operation group, the SAP group and the PLA2 inhibitor-treated group of SAP. Serum amylases, PLA2 and PLA2 in brain tissue were measured and the brain tissue changes were observed. Results There were no significant difference in serum amylases, PLA2 and PLA2 in brain tissue between the sham-operation and the control groups; the levels of serum amylases, PLA2 and PLA2 in brain tissue in the SAP group were higher than those in the control. In the SAP group expansion and hemorrhage of meninges, intracephalic arteriolar hyperemia, in meninges and cephalic-parenchyma infiltration of inflammatory cells and interval broaden were observed, significant differences were found between two groups.Compared with the SAP group, the level of serum amylase, PLA2 and PLA2 in brain tissue were reduced significantly in the treatment group of SAP. Pathological damages in the treatment group were significantly reduced when compared with the SAP group. Conclusion PLA2 might play an important role in brain tissue damages in severe acute pancreatitis.

  10. Fourier transform infrared microspectroscopy as a diagnostic tool for distinguishing between normal and malignant human gastric tissue

    Indian Academy of Sciences (India)

    Abasalt Hosseinzadeh Colagar; Mohammad Javad Chaichi; Tahereh Khadjvand

    2011-09-01

    Fourier transform infrared (FTIR) microspectroscopy can be considered to be a fast and non-invasive tool for distinguishing between normal and cancerous cells and tissues without the need for laborious and invasive sampling procedures. Gastric samples from four patients (age, 65±2 years) were analysed. Samples were obtained from the organs removed during gastrectomy and then classified as normal or cancerous. Classification was based on histopathological examinations at our institution. Formalin-fixed sections of gastric tissue were analysed by FTIR-microspectroscopy. To characterize differences between sections of normal and cancerous tissue, specific regions of the spectra were analysed to study variations in the levels of metabolites. To distinguish between two conditions (normal and cancerous), changes in the relative intensity of bands in the range 600–4000 cm−1 were analysed. A FTIR spectral map of the bands in the region 2800–3100 cm–1 and 900–1800 cm–1 were created to analyse pathological changes in tissues. The limited data available showed that normal gastric tissue had stronger absorption than cancerous tissue over a wide region in the four patients. There was a significant decrease in total biomolecular components for cancerous tissue compared with normal tissue.

  11. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

    Directory of Open Access Journals (Sweden)

    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  12. Acute appendicitis: Is removal of a normal appendix still existing and can we reduce its rate?

    Directory of Open Access Journals (Sweden)

    Khairy Gamal

    2009-01-01

    Full Text Available Background/Aim: To determine the incidence of negative appendectomies and to identify factors that may reduce the risk of having the normal appendices removed surgically. Design: Cross-sectional study. Setting: College of Medicine and King Khalid University Hospital, Riyadh, Saudi Arabia. Materials and Methods: The surgical and histological data of 852 patients who underwent appendicectomy were reviewed. All incidental or interval appendicectomies were excluded. Only patients who were admitted and whose appendices were removed and subjected to histology were included (585 patients. The data on patients who had a normal appendix on histology further analyzed to include demographics, specific investigations, operative findings of the appendix and additional operative findings that need other surgical procedures. Results: A normal appendix was removed in 54 (9.2% of the patients. Only 5.5% of those patients had a computed tomography (CT scan preoperatively and 3.7% had diagnostic laparoscopy. In 21 patients, additional operative and histological findings were obtained that might have caused the right lower abdominal pain. Conclusion: In spite of the advances in the diagnostic and imaging techniques, the rates of negative findings on appendicectomy have not decreased much. Clinical judgment is still the most important factor in the management of patients with suspected acute appendicitis. The routine use of CT scan or diagnostic laparoscopy for all patients who are suspected to have appendicitis is neither cost-effective nor safe.

  13. Tissue MicroArray (TMA) analysis of normal and persistent Chlamydophila pneumoniae infection.

    Science.gov (United States)

    Borel, Nicole; Mukhopadhyay, Sanghamitra; Kaiser, Carmen; Sullivan, Erin D; Miller, Richard D; Timms, Peter; Summersgill, James T; Ramirez, Julio A; Pospischil, Andreas

    2006-10-19

    Chlamydophila pneumoniae infection has been implicated as a potential risk factor for atherosclerosis, however the mechanism leading to persistent infection and its role in the disease process remains to be elucidated. We validated the use of tissue microarray (TMA) technology, in combination with immunohistochemistry (IHC), to test antibodies (GroEL, GroES, GspD, Ndk and Pyk) raised against differentially expressed proteins under an interferon-gamma (IFN-gamma) induced model of chlamydial persistence. In the cell pellet array, we were able to identify differences in protein expression patterns between untreated and IFN-gamma treated samples. Typical, large chlamydial inclusions could be observed in the untreated samples with all antibodies, whereas the number of inclusions were decreased and were smaller and atypical in shape in the IFN-gamma treated samples. The staining results obtained with the TMA method were generally similar to the changes observed between normal and IFN-gamma persistence using proteomic analysis. Subsequently, it was shown in a second TMA including archival atheromatous heart tissues from 12 patients undergoing heart transplantation, that GroEL, GroES, GspD and Pyk were expressed in atheromatous heart tissue specimens as well, and were detectable morphologically within lesions by IHC. TMA technology proved useful in documenting functional proteomics data with the morphologic distribution of GroEL, GroES, GspD, Ndk and Pyk within formalin-fixed, paraffin-embedded cell pellets and tissues from patients with severe coronary atherosclerosis. The antibodies GroEL and GroES, which were upregulated under persistence in proteomic analysis, displayed positive reaction in atheromatous heart tissue from 10 out of 12 patients. These may be useful markers for the detection of persistent infection in vitro and in vivo.

  14. Tissue MicroArray (TMA analysis of normal and persistent Chlamydophila pneumoniae infection

    Directory of Open Access Journals (Sweden)

    Timms Peter

    2006-10-01

    Full Text Available Abstract Background Chlamydophila pneumoniae infection has been implicated as a potential risk factor for atherosclerosis, however the mechanism leading to persistent infection and its role in the disease process remains to be elucidated. Methods We validated the use of tissue microarray (TMA technology, in combination with immunohistochemistry (IHC, to test antibodies (GroEL, GroES, GspD, Ndk and Pyk raised against differentially expressed proteins under an interferon-gamma (IFN-γ induced model of chlamydial persistence. Results In the cell pellet array, we were able to identify differences in protein expression patterns between untreated and IFN-γ treated samples. Typical, large chlamydial inclusions could be observed in the untreated samples with all antibodies, whereas the number of inclusions were decreased and were smaller and atypical in shape in the IFN-γ treated samples. The staining results obtained with the TMA method were generally similar to the changes observed between normal and IFN-γ persistence using proteomic analysis. Subsequently, it was shown in a second TMA including archival atheromatous heart tissues from 12 patients undergoing heart transplantation, that GroEL, GroES, GspD and Pyk were expressed in atheromatous heart tissue specimens as well, and were detectable morphologically within lesions by IHC. Conclusion TMA technology proved useful in documenting functional proteomics data with the morphologic distribution of GroEL, GroES, GspD, Ndk and Pyk within formalin-fixed, paraffin-embedded cell pellets and tissues from patients with severe coronary atherosclerosis. The antibodies GroEL and GroES, which were upregulated under persistence in proteomic analysis, displayed positive reaction in atheromatous heart tissue from 10 out of 12 patients. These may be useful markers for the detection of persistent infection in vitro and in vivo.

  15. Factors of late radiosensitivity of normal tissues; Facteurs de radiosensibilite tardive des tissus sains

    Energy Technology Data Exchange (ETDEWEB)

    Azria, A. [CRLC Val d' Aurelle-Paul-Lamarque, departement de radiotherapie, 34 - Montpellier (France); Pointreau, Y. [CHRU Bretonneau, 37 - Tours (France); Toledano, A. [Clinique Hartman, 92 - Neuilly-sur-Seine (France); Ozsahin, M. [CHU Vaudois, Lausanne (Switzerland)

    2010-07-15

    The impact of curative radiotherapy depends mainly on the total dose delivered homogeneously in the targeted volume. Nevertheless, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. Two different side effects (acute and late) can occur during and after radiotherapy. Of particular interest are the radiation-induced sequelae due to their irreversibility and the potential impact on daily quality of life. In a same population treated in one centre with the same technique, it appears that individual radiosensitivity clearly exists. In the hypothesis that genetic is involved in this area of research, lymphocytes seem to be the tissue of choice due to easy accessibility. Recently, low percentage of CD4 and CD8 lymphocyte apoptosis were shown to be correlated with high grade of sequelae. In addition, recent data suggest that patients with severe radiation-induced late side effects possess four or more single nucleotide polymorphisms (SNP) in candidate genes (ATM, SOD2, TGFB1, XRCC1, and XRCC3) and low radiation-induced CD8 lymphocyte apoptosis in vitro. On-going studies are being analyzing the entire genome using a Genome-wide association study (GWAS) analysis. (authors)

  16. Perfusion changes in the RIF-1 tumour and normal tissues after carbogen and nicotinamide, individually and combined.

    Science.gov (United States)

    Honess, D. J.; Bleehen, N. M.

    1995-01-01

    The strategy of combining carbogen breathing and nicotinamide to overcome chronic and acute hypoxia respectively is being evaluated clinically. The effects of both agents individually and in combination on relative perfusion of 400-700 mm3 RIF-1 tumours and normal tissues were measured by 86Rb extraction. Carbogen breathing alone for 6 min increased relative tumour perfusion by 50-70% compared with control at flow rates of 50 to 200 ml min-1, but the effect was lost at 300 ml min-1. All flow rates also produced similar increases in relative perfusion of lung, of between 36% and 58%, and smaller increases in skin, of between 20% and 34%. The minimum breathing time at 150 ml min-1 to produce a significant increase in relative tumour perfusion was 4.5 min, and the effect was maintained up to 9 min. Nicotinamide alone at 1000 mg kg-1 60 min before assay did not alter relative tumour perfusion. Comparing the combination of nicotinamide with 6 min carbogen breathing at 150 ml min-1 with carbogen breathing alone showed no difference in relative tumour perfusion; increases were of 36% and 42% respectively. Nicotinamide-induced alterations in microcirculation associated with reduction of acute hypoxia have therefore not been detected by 86Rb extraction. The perfusion-enhancing effect of carbogen in this tumour is probably an important component of its radiosensitising ability, in addition to its known ability to increase the oxygen-carrying capacity of the blood, and should be taken into consideration in clinical studies. PMID:7779707

  17. 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)

  18. Near-Infrared Spectroscopy as a Diagnostic Tool for Distinguishing between Normal and Malignant Colorectal Tissues

    Directory of Open Access Journals (Sweden)

    Hui Chen

    2015-01-01

    Full Text Available Cancer diagnosis is one of the most important tasks of biomedical research and has become the main objective of medical investigations. The present paper proposed an analytical strategy for distinguishing between normal and malignant colorectal tissues by combining the use of near-infrared (NIR spectroscopy with chemometrics. The successive projection algorithm-linear discriminant analysis (SPA-LDA was used to seek a reduced subset of variables/wavenumbers and build a diagnostic model of LDA. For comparison, the partial least squares-discriminant analysis (PLS-DA based on full-spectrum classification was also used as the reference. Principal component analysis (PCA was used for a preliminary analysis. A total of 186 spectra from 20 patients with partial colorectal resection were collected and divided into three subsets for training, optimizing, and testing the model. The results showed that, compared to PLS-DA, SPA-LDA provided more parsimonious model using only three wavenumbers/variables (4065, 4173, and 5758 cm−1 to achieve the sensitivity of 84.6%, 92.3%, and 92.3% for the training, validation, and test sets, respectively, and the specificity of 100% for each subset. It indicated that the combination of NIR spectroscopy and SPA-LDA algorithm can serve as a potential tool for distinguishing between normal and malignant colorectal tissues.

  19. Novel antioxidants are not toxic to normal tissues but effectively kill cancer cells

    Science.gov (United States)

    Kovalchuk, Anna; Aladedunye, Felix; Rodriguez-Juarez, Rocio; Li, Dongping; Thomas, James; Kovalchuk, Olga; Przybylski, Roman

    2013-01-01

    Free radicals are formed as a result of cellular processes and play a key role in predisposition to and development of numerous diseases and of premature aging. Recently, we reported the syntheses of a number of novel phenolic antioxidants for possible application in food industry. In the present study, analyses of the cellular processes and molecular gene expression effects of some of the novel antioxidants in normal human tissues and in cancer cells were undertaken. Results indicated that whereas the examined antioxidants showed no effects on morphology and gene expression of normal human oral and gingival epithelial tissues, they exerted a profound cell killing effect on breast cancer cells, including on chemotherapy-resistant breast cancer cells and on oral squamous carcinoma cells. Among the tested antioxidants, N-decyl-N-(3-methoxy-4-hydroxybenzyl)-3-(3,4-dihydroxyphenyl) propanamide and N-decyl-N-(3,5-dimethoxy-4-hydroxybenzyl)-3-(3,4-dihydroxyphenyl) propanamide were the most promising, with excellent potential for cancer treatment. Moreover, our gene expression databases can be used as a roadmap for future analysis of mechanisms of antioxidant action. PMID:23917379

  20. Expression Levels of RFP in Normal and Cancer Human Tissues via Real-time RT-PCR Detection

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Ret finger protein(RFP) is a member of the tripartite motif family, which is characterized by a conserved RING finger of motif, a B-box, and a coiled-coil domain(they are called RBCC generally). Although RFP was known to be an oncogene when its RBCC moiety was connected with a tyrosine kinase domain by DNA rearrangement, its biological function was not well defined. In this study, by using real-time RT-PCR, the RFP expressions in human and mouse normal tissues, and in the cervical squamous cell carcinoma, endometrial adenocarcinoma, gastric adenocarcinoma, esophageal squamous cell carcinoma, and brain cancer tissues were analyzed. The result of the study proved that the highest level of mRNA reverse transcription appeared in the normal testical tissue, whereas that in other normal tissues of human and mice were low. The mRNA reverse transcription level of RFP was higher in the endometrial adenocarcinoma tissue than in the cervical squamous cell carcinoma tissue; the mRNA reverse transcription level of RFP in the gastric adenocarcinoma tissue was significantly higher than that in the esophageal squamous cell carcinoma tissue. It was also found that the mRNA reverse transcription level of RFP in the brain cancer tissue was higher than that in the normal brain tissue. These results suggested that RFP could possibly be a useful molecular target for the development of new therapeutics for malignant tumors.

  1. Biomarkers and surrogate endpoints for normal-tissue effects of radiation therapy: the importance of dose-volume effects

    Science.gov (United States)

    Bentzen, Søren M.; Parliament, Matthew; Deasy, Joseph O.; Dicker, Adam; Curran, Walter J.; Williams, Jacqueline P.; Rosenstein, Barry S.

    2012-01-01

    Biomarkers are of interest for predicting or monitoring normal tissue toxicity of radiation therapy. Advances in molecular radiobiology provide novel leads in the search for normal tissue biomarkers with sufficient sensitivity and specificity to become clinically useful. This paper reviews examples of studies of biomarkers as predictive markers, as response markers or as surrogate endpoints for radiation side-effects. Single nucleotide polymorphisms (SNPs) are briefly discussed in the context of candidate gene and genome wide association studies. The importance of adjusting for radiation dose distribution in normal tissue biomarker studies is underlined. Finally, research priorities in this field are identified and discussed. PMID:20171510

  2. 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.

  3. Biochemical and hemodynamic changes in normal subjects during acute and rigorous bed rest and ambulation

    Science.gov (United States)

    Zorbas, Yan G.; Kakurin, Vassily J.; Afonin, Victor B.; Yarullin, Vladimir L.

    2002-06-01

    Rigorous bed rest (RBR) induces significant biochemical and circulatory changes. However, little is known about acute rigorous bed rest (ARBR). Measuring biochemical and circulatory variables during ARBR and RBR the aim of this study was to establish the significance of ARBR effect. Studies were done during 3 days of a pre-bed rest (BR) period and during 7 days of ARBR and RBR period. Thirty normal male individuals aged, 24.1±6.3 years were chosen as subjects. They were divided equally into three groups: 10 subjects placed under active control conditions served as unrestricted ambulatory control subjects (UACS), 10 subjects submitted to an acute rigorous bed rest served as acute rigorous bed rested subjects (ARBRS) and 10 subjects submitted to a rigorous bed rest served as rigorous bed rested subjects (RBRS). The UACS were maintained under an average running distance of 9.7 km day -1. For the ARBR effect simulation, ARBRS were submitted abruptly to BR for 7 days. They did not have any prior knowledge of the exact date and time when they would be asked to confine to RBR. For the RBR effect simulation, RBRS were subjected to BR for 7 days on a predetermined date and time known to them right away from the start of the study. Plasma renin activity (PRA), plasma cortisol (PC), plasma aldosterone (PA), plasma and urinary sodium (Na) and potassium (K) levels, heart rate (HR), cardiac output (CO), and arterial blood pressure (ABP) increased significantly, and urinary aldosterone (UA), stroke volume (SV) and plasma volume (PV) decreased significantly ( p0.05) in UACS compared with pre-BR control values. It was concluded that, the more abruptly muscular activity is restricted in experimental subjects while they are very active, the greater hemodynamic and biochemical change there is and probably in individuals whose muscular activity is abruptly terminated after an accident or sudden illness.

  4. Expression of Bcl-2 Family Member Bid in Normal and Malignant Tissues

    Directory of Open Access Journals (Sweden)

    Maryla Krajewska

    2002-01-01

    Full Text Available Bid is the only known Bcl-2 family member that can function as an agonist of proapoptotic Bcl-2-related proteins such as Bax and Bak. Expression of the proapoptotic Bcl-2 family protein Bid was assessed by immunoblotting and immunohistochemical methods in normal murine and human tissues, and in several types of human cancers and tumor cell lines. Bid expression in normal tissues varied widely, with prominent Bid immunostaining occurring in several types of short-lived cells (e.g., germinal center B cells, peripheral blood granulocytes, differentiated keratinocytes and in apoptosissensitive cells (e.g., adult neurons. Analysis of Bid expression by immunostaining of 100 colon, 95 ovarian, and 254 prostate cancers, as well as 59 brain tumors and 50 lymphomas, revealed evidence of altered Bid regulation in sometypes of cancers. Correlations with clinical outcome data revealed association of higher levels of Bid with longer recurrence-free survival in men with locally advanced (T3 stage prostate cancer (P=0.04. Immunoblot analysis of Bid protein levels in the NCI's panel of 60 human tumor cell lines revealed a correlation between higher levels of Bid and sensitivity to ribonucleotide reductase (RR-inhibiting drugs (P<0.0005. Overexpression of Bid in a model tumor cell line by gene transfection resulted in increased sensitivity to apoptosis induction by a RR inhibitor. Taken together, these observations suggest a potential role for Bid in tumor responses to specific chemotherapeutic drugs, and lay a foundation for future investigations of this member of the Bcl-2 family in healthy and diseased tissues.

  5. Connective tissue growth factor promoter activity in normal and wounded skin

    Directory of Open Access Journals (Sweden)

    Kapoor Mohit

    2008-10-01

    Full Text Available Abstract In skin, connective tissue growth factor (CTGF/CCN2 is induced during tissue repair. However, what the exact cell types are that express CTGF in normal and wounded skin remain controversial. In this report, we use transgenic knock-in mice in which the Pacific jellyfish Aequorea victoria enhanced green fluorescent protein (E-GFP gene has been inserted between the endogenous CTGF promoter and gene. Unwounded (day 0 and wounded (days 3 and 7 skin was examined for GFP to detect cells in which the CTGF promoter was active, α-smooth muscle actin (α-SMA to detect myofibroblasts, and NG2 expression to detect pericytes. In unwounded mice, CTGF expression was absent in epidermis and was present in a few cells in the dermis. Upon wounding, CTGF expression was induced in the dermis. Double immunolabeling revealed that CTGF-expressing cells also expressed α-SMA, indicating the CTGF was expressed in myofibroblasts. A subset (~30% of myofibroblasts were also NG2 positive, indicating that pericytes significantly contributed to the number of myofibroblasts in the wound. Pericytes also expressed CTGF. Collectively, these results indicate that CTGF expression in skin correlates with myofibroblast induction, and that CTGF-expressing pericytes are significant contributors to myofibroblast activity during cutaneous tissue repair.

  6. ACCURATE ACCUMULATION OF DOSE FOR IMPROVED UNDERSTANDING OF RADIATION EFFECTS IN NORMAL TISSUE

    Science.gov (United States)

    Jaffray, David A.; Lindsay, Patricia E.; Brock, Kristy K.; Deasy, Joseph O.; Tomé, W. A.

    2013-01-01

    The actual distribution of radiation dose accumulated in normal tissues over the complete course of radiation therapy is, in general, poorly quantified. Differences in the patient anatomy between planning and treatment can occur gradually (e.g., tumor regression, resolution of edema) or relatively rapidly (e.g., bladder filling, breathing motion) and these undermine the accuracy of the planned dose distribution. Current efforts to maximize the therapeutic ratio require models that relate the true accumulated dose to clinical outcome. The needed accuracy can only be achieved through the development of robust methods that track the accumulation of dose within the various tissues in the body. Specific needs include the development of segmentation methods, tissue-mapping algorithms, uncertainty estimation, optimal schedules for image-based monitoring, and the development of informatics tools to support subsequent analysis. These developments will not only improve radiation outcomes modeling but will address the technical demands of the adaptive radiotherapy paradigm. The next 5 years need to see academia and industry bring these tools into the hands of the clinician and the clinical scientist. PMID:20171508

  7. [Comparison of 51 element contents in normal human lung tissue over twenty years].

    Science.gov (United States)

    Zeng, Jing; Ouyang, Li; Wang, Xiao-Yan; Liu, Ya-Qiong; Xie, Qing; Chu, Hong-Da; Wu, Quan; Fan, Ti-Qiang; Wang, Jing-Yu

    2008-05-01

    Changes in content and distribution of elements in human tissues may reflect changes in environmental backgrounds, and are closely related to human health. To investigate the change in element background in normal lung tissue in different stage, we used ICP-MS, ICP-AES and GFAAS to determine 51 element contents in normal human lung samples of 1982-83 year (n = 7) and compare with those of 2004-05 year (n = 16). Samples were from healthy male adults who died suddenly, and were treated with microwave digestion and wet digestion method. The results show that the contents of 23 elements (Na, Mg, P, K, As, Mo, Ag, Ba, Bi, Y, La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) are significantly higher, and 6 elements (Zn, Ga, Ge, Se, Au and Zr) are significantly lower in the 2004-05 samples than those in the 1982-83 samples. This difference would be related to the changes in environmental backgrounds and people's living habit during twenty years. The distinctive decrease in contents of the 2004-05 samples for most measured rare earth elements (REEs) may be due to more rational usage of REEs in present, while were the soil and corps were largely abused in 1980s in China. The significant increase in contents of some useful micro-elements (Zn and Se ) in the present samples maybe because of the increased intake of these elements as people own more health consciousness. Besides, the increased contents of heavy metal Pb, Cd, Cr and Ni in the present samples may be related to the deterioration of air quality as industrialization course. More than half of measured elements have been significantly changed over twenty years, indicating that some normal value ranges of element contents should be adjusted according to the difference.

  8. Estimating developmental states of tumors and normal tissues using a linear time-ordered model

    Directory of Open Access Journals (Sweden)

    Xuan Zhenyu

    2011-02-01

    Full Text Available Abstract Background Tumor cells are considered to have an aberrant cell state, and some evidence indicates different development states appearing in the tumorigenesis. Embryonic development and stem cell differentiation are ordered processes in which the sequence of events over time is highly conserved. The "cancer attractor" concept integrates normal developmental processes and tumorigenesis into a high-dimensional "cell state space", and provides a reasonable explanation of the relationship between these two biological processes from theoretical viewpoint. However, it is hard to describe such relationship by using existed experimental data; moreover, the measurement of different development states is also difficult. Results Here, by applying a novel time-ordered linear model based on a co-bisector which represents the joint direction of a series of vectors, we described the trajectories of development process by a line and showed different developmental states of tumor cells from developmental timescale perspective in a cell state space. This model was used to transform time-course developmental expression profiles of human ESCs, normal mouse liver, ovary and lung tissue into "cell developmental state lines". Then these cell state lines were applied to observe the developmental states of different tumors and their corresponding normal samples. Mouse liver and ovarian tumors showed different similarity to early development stage. Similarly, human glioma cells and ovarian tumors became developmentally "younger". Conclusions The time-ordered linear model captured linear projected development trajectories in a cell state space. Meanwhile it also reflected the change tendency of gene expression over time from the developmental timescale perspective, and our finding indicated different development states during tumorigenesis processes in different tissues.

  9. 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.

  10. Connective Tissue Growth Factor Is Required for Normal Follicle Development and Ovulation

    Science.gov (United States)

    Nagashima, Takashi; Kim, Jaeyeon; Li, Qinglei; Lydon, John P.; DeMayo, Francesco J.; Lyons, Karen M.

    2011-01-01

    Connective tissue growth factor (CTGF) is a cysteine-rich protein the synthesis and secretion of which are hypothesized to be selectively regulated by activins and other members of the TGF-β superfamily. To investigate the in vivo roles of CTGF in female reproduction, we generated Ctgf ovarian and uterine conditional knockout (cKO) mice. Ctgf cKO mice exhibit severe subfertility and multiple reproductive defects including disrupted follicle development, decreased ovulation rates, increased numbers of corpus luteum, and smaller but functionally normal uterine horns. Steroidogenesis is disrupted in the Ctgf cKO mice, leading to increased levels of serum progesterone. We show that disrupted follicle development is accompanied by a significant increase in granulosa cell apoptosis. Moreover, despite normal cumulus expansion, Ctgf cKO mice exhibit a significant decrease in oocytes ovulated, likely due to impaired ovulatory process. During analyses of mRNA expression, we discovered that Ctgf cKO granulosa cells show gene expression changes similar to our previously reported granulosa cell-specific knockouts of activin and Smad4, the common TGF-β family intracellular signaling protein. We also discovered a significant down-regulation of Adamts1, a progesterone-regulated gene that is critical for the remodeling of extracellular matrix surrounding granulosa cells of preovulatory follicles. These findings demonstrate that CTGF is a downstream mediator in TGF-β and progesterone signaling cascades and is necessary for normal follicle development and ovulation. PMID:21868453

  11. Differentiating shunt-responsive normal pressure hydrocephalus from Alzheimer disease and normal aging: pilot study using automated MRI brain tissue segmentation.

    Science.gov (United States)

    Serulle, Yafell; Rusinek, Henry; Kirov, Ivan I; Milch, Hannah; Fieremans, Els; Baxter, Alexander B; McMenamy, John; Jain, Rajan; Wisoff, Jeffrey; Golomb, James; Gonen, Oded; George, Ajax E

    2014-10-01

    Evidence suggests that normal pressure hydrocephalus (NPH) is underdiagnosed in day to day radiologic practice, and differentiating NPH from cerebral atrophy due to other neurodegenerative diseases and normal aging remains a challenge. To better characterize NPH, we test the hypothesis that a prediction model based on automated MRI brain tissue segmentation can help differentiate shunt-responsive NPH patients from cerebral atrophy due to Alzheimer disease (AD) and normal aging. Brain segmentation into gray and white matter (GM, WM), and intracranial cerebrospinal fluid was derived from pre-shunt T1-weighted MRI of 15 shunt-responsive NPH patients (9 men, 72.6 ± 8.0 years-old), 17 AD patients (10 men, 72.1 ± 11.0 years-old) chosen as a representative of cerebral atrophy in this age group; and 18 matched healthy elderly controls (HC, 7 men, 69.7 ± 7.0 years old). A multinomial prediction model was generated based on brain tissue volume distributions. GM decrease of 33% relative to HC characterized AD (P normal GM volumes characterized NPH. A multinomial regression model based on gender, GM and ventricular volume had 96.3% accuracy differentiating NPH from AD and HC. In conclusion, automated MRI brain tissue segmentation differentiates shunt-responsive NPH with high accuracy from atrophy due to AD and normal aging. This method may improve diagnosis of NPH and improve our ability to distinguish normal from pathologic aging.

  12. 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.

  13. Differential expression of IGF-1 mRNA isoforms in colorectal carcinoma and normal colon tissue.

    Science.gov (United States)

    Kasprzak, Aldona; Szaflarski, Witold; Szmeja, Jacek; Andrzejewska, Małgorzata; Przybyszewska, Wiesława; Kaczmarek, Elżbieta; Koczorowska, Maria; Kościński, Tomasz; Zabel, Maciej; Drews, Michał

    2013-01-01

    RNA decreased as compared to the normal colon tissues, although however, with conservation of both gene promoter activities and with the continued principal splicing IGF-1 mRNA isoforms.

  14. [2 cases of acute disseminated intravascular coagulation in normal pregnancy and as the first symptom of acute promyelocytic leukemia].

    Science.gov (United States)

    Kardaszewicz, E; Bujak, M; Spychałowicz, W; Siudyka, A; Harbut-Gryłka, A

    Two cases of the acute disseminated intravascular coagulation (DIC) are presented. DIC in the first case was diagnosed in healthy pregnant woman without any obstetric pathology. This patient recovered completely. The acute DIC in another patient preceded the acute promyelocytic leukemia. The patient died despite a control of DIC. DIC therapy included antifibrinolytic agents and additionally corticoids in pregnant patient. Heparin was not administered because of post partum period and foreseen cytostatic therapy in the leukemic patient.

  15. Biochemical and biomolecular aspects of oxidative stress due to acute and severe hypoxia in human muscle tissue.

    Science.gov (United States)

    Corbucci, G G; Sessego, R; Velluti, C; Salvi, M

    1995-01-01

    Mitochondrial oxidative stress was investigated in severe and acute hypoxia and in reperfusion applied to human muscle tissues. The biochemical and biomolecular relationship between the response of the respiratory-chain enzymic complexes and the metabolism of specific hypoxia stress proteins (HSP) suggest an adaptive mechanism which antagonizes the oxidative damage due to acute and severe tissue hypoxia.

  16. 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....

  17. Modeling the response of normal and ischemic cardiac tissue to electrical stimulation

    Science.gov (United States)

    Kandel, Sunil Mani

    Heart disease, the leading cause of death worldwide, is often caused by ventricular fibrillation. A common treatment for this lethal arrhythmia is defibrillation: a strong electrical shock that resets the heart to its normal rhythm. To design better defibrillators, we need a better understanding of both fibrillation and defibrillation. Fundamental mysteries remain regarding the mechanism of how the heart responds to a shock, particularly anodal shocks and the resultant hyperpolarization. Virtual anodes play critical roles in defibrillation, and one cannot build better defibrillators until these mechanisms are understood. We are using mathematical modeling to numerically simulate observed phenomena, and are exploring fundamental mechanisms responsible for the heart's electrical behavior. Such simulations clarify mechanisms and identify key parameters. We investigate how systolic tissue responds to an anodal shock and how refractory tissue reacts to hyperpolarization by studying the dip in the anodal strength-interval curve. This dip is due to electrotonic interaction between regions of depolarization and hyperpolarization following a shock. The dominance of the electrotonic mechanism over calcium interactions implies the importance of the spatial distribution of virtual electrodes. We also investigate the response of localized ischemic tissue to an anodal shock by modeling a regional elevation of extracellular potassium concentration. This heterogeneity leads to action potential instability, 2:1 conduction block (alternans), and reflection-like reentry at the boarder of the normal and ischemic regions. This kind of reflection (reentry) occurs due to the delay between proximal and distal segments to re-excite the proximal segment. Our numerical simulations are based on the bidomain model, the state-of-the-art mathematical description of how cardiac tissue responds to shocks. The dynamic LuoRudy model describes the active properties of the membrane. To model ischemia

  18. FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics.

    Science.gov (United States)

    Wang, Lei; Xu, Wei-lai; Meng, Hai-tao; Qian, Wen-bin; Mai, Wen-yuan; Tong, Hong-yan; Mao, Li-ping; Tong, Yin; Qian, Jie-jing; Lou, Yin-jun; Chen, Zhi-mei; Wang, Yun-gui; Jin, Jie

    2010-10-01

    Mutations of fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) exon 12 genes are the most common abnormalities in adult acute myeloid leukemia (AML) with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction (PCR) and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication (FLT3/ITD) and exon 12 of the NPM1 gene. FLT3/ITD mutation was detected in 15 (19.7%) of 76 subjects, and NPM1 mutation in 20 (26.3%) subjects. Seven (9.2%) cases were positive for both FLT3/ITD and NPM1 mutations. Significantly more FLT3/ITD aberration was detected in subjects with French-American-British (FAB) M1 (42.8%). NPM1 mutation was frequently detected in subjects with M5 (47.1%) and infrequently in subjects with M2 (11.1%). FLT3 and NPM1 mutations were significantly associated with a higher white blood cell count in peripheral blood and a lower CD34 antigen expression, but not age, sex, or platelet count. Statistical analysis revealed that the FLT3/ITD-positive group had a lower complete remission (CR) rate (53.3% vs. 83.6%). Survival analysis showed that the FLT3/ITD-positive/NPM1 mutation-negative group had worse overall survival (OS) and relapse-free survival (RFS). The FLT3/ITD-positive/NPM1 mutation-positive group showed a trend towards favorable survival compared with the FLT3/ITD-positive/NPM1 mutation-negative group (P=0.069). Our results indicate that the FLT3/ITD mutation might be a prognostic factor for an unfavorable outcome in Chinese AML subjects with normal cytogenetics, while NPM1 mutation may be a favorable prognostic factor for OS and RFS in the presence of FLT3/ITD.

  19. Differentiating fibroadenoma and ductal carcinoma in situ from normal breast tissue by multiphoton microscopy

    Science.gov (United States)

    Nie, Yuting; Wu, Yan; Lian, Yuane; Fu, Fangmeng; Wang, Chuan; Chen, Jianxin

    2014-09-01

    Fibroadenoma (FA) is the most common benign tumor of the female breast and several studies have reported that women with it have increased risk of breast cancer. While the ductal carcinoma in situ (DCIS) is a very early form of breast cancer. Thus, early detections of FA and DCIS are critical for improving breast tumor outcome and survival. In this paper, we use multiphoton microscopy (MPM) to obtain the high-contrast images of fresh, unfixed, unstained human breast specimens (normal breast tissue, FA and DCIS). Our results show that MPM has the ability to identify the characteristics of FA and DCIS including changes of duct architecture and collagen morphology. These results are consistent with the histological results. With the advancement of MPM, the technique has potential ability to serve as a real-time noninvasive imaging tool for early detection of breast tumor.

  20. 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.

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

    Science.gov (United States)

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

    2012-03-15

    To study the impact of different statistical learning methods on the prediction performance of multivariate normal tissue complication probability (NTCP) models. In this study, three learning methods, stepwise selection, least absolute shrinkage and selection operator (LASSO), and Bayesian model averaging (BMA), were used to build NTCP models of xerostomia following radiotherapy treatment for head and neck cancer. Performance of each learning method was evaluated by a repeated cross-validation scheme in order to obtain a fair comparison among methods. It was found that the LASSO and BMA methods produced models with significantly better predictive power than that of the stepwise selection method. Furthermore, the LASSO method yields an easily interpretable model as the stepwise method does, in contrast to the less intuitive BMA method. The commonly used stepwise selection method, which is simple to execute, may be insufficient for NTCP modeling. The LASSO method is recommended. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. 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.

  3. Differential Expression of IGF Components and Insulin Receptor Isoforms in Human Seminoma Versus Normal Testicular Tissue

    Directory of Open Access Journals (Sweden)

    Tanja Pascale Neuvians

    2005-05-01

    Full Text Available Insulin-like growth factors (IGF have mitogenic and antiapoptotic functions, and may be involved in tumor growth. The purpose of the study was to investigate the role of IGF components in seminoma compared to normal testis. Normal testicular tissues from autopsy cases and seminoma from surgery cases were obtained for microarray and real-time reverse transcription polymerase chain reaction (RT-PCR analysis of IGF-1, IGF-2, IGF receptor type 1 (IGF-R1, IGF-R2, insulin receptor isoforms A (IR-A and B (IR-B, and IGF-binding proteins (IGFBP 1-6. IGF-2 was localized by immunohistochemistry. IGFBP-5 protein expression was evaluated by Western blot analysis. mRNA expression in microarray and real-time RT-PCR showed similar tendencies: IGF-1, IGF-R1, IGF-R2, IR-A, and IGFBP-2 were not different in both groups. IGF-2, IR-B, IGFBP-1, IGFBP-4, and IGFBP-6 mRNA were downregulated in seminoma. IGFBP-3 tended to be upregulated in pT1 seminoma, but downregulated in pT2 stages. IGFBP-5 and IGF-2 protein expression correlated with mRNA expression. In conclusion, downregulation of mainly inhibiting IGFBPs may allow a stimulated tumor growth. The downregulated IGF-2 does not seem to be involved in the growth regulation of seminoma. Constantly expressed genes (e.g., IGF-1, IGF-R1, IR-A, and IGFBP-2 may reflect an involvement in spermatogenesis, but may also play a major role in tumor growth as their expression is not downregulated despite the lack of spermatogenesis in tumor tissue.

  4. High-throughput biomarker segmentation on ovarian cancer tissue microarrays via hierarchical normalized cuts.

    Science.gov (United States)

    Janowczyk, Andrew; Chandran, Sharat; Singh, Rajendra; Sasaroli, Dimitra; Coukos, George; Feldman, Michael D; Madabhushi, Anant

    2012-05-01

    We present a system for accurately quantifying the presence and extent of stain on account of a vascular biomarker on tissue microarrays. We demonstrate our flexible, robust, accurate, and high-throughput minimally supervised segmentation algorithm, termed hierarchical normalized cuts (HNCuts) for the specific problem of quantifying extent of vascular staining on ovarian cancer tissue microarrays. The high-throughput aspect of HNCut is driven by the use of a hierarchically represented data structure that allows us to merge two powerful image segmentation algorithms-a frequency weighted mean shift and the normalized cuts algorithm. HNCuts rapidly traverses a hierarchical pyramid, generated from the input image at various color resolutions, enabling the rapid analysis of large images (e.g., a 1500 × 1500 sized image under 6 s on a standard 2.8-GHz desktop PC). HNCut is easily generalizable to other problem domains and only requires specification of a few representative pixels (swatch) from the object of interest in order to segment the target class. Across ten runs, the HNCut algorithm was found to have average true positive, false positive, and false negative rates (on a per pixel basis) of 82%, 34%, and 18%, in terms of overlap, when evaluated with respect to a pathologist annotated ground truth of the target region of interest. By comparison, a popular supervised classifier (probabilistic boosting trees) was only able to marginally improve on the true positive and false negative rates (84% and 14%) at the expense of a higher false positive rate (73%), with an additional computation time of 62% compared to HNCut. We also compared our scheme against a k-means clustering approach, which both the HNCut and PBT schemes were able to outperform. Our success in accurately quantifying the extent of vascular stain on ovarian cancer TMAs suggests that HNCut could be a very powerful tool in digital pathology and bioinformatics applications where it could be used to

  5. Methylation profiling of 48 candidate genes in tumor and matched normal tissues from breast cancer patients.

    Science.gov (United States)

    Li, Zibo; Guo, Xinwu; Wu, Yepeng; Li, Shengyun; Yan, Jinhua; Peng, Limin; Xiao, Zhi; Wang, Shouman; Deng, Zhongping; Dai, Lizhong; Yi, Wenjun; Xia, Kun; Tang, Lili; Wang, Jun

    2015-02-01

    Gene-specific methylation alterations in breast cancer have been suggested to occur early in tumorigenesis and have the potential to be used for early detection and prevention. The continuous increase in worldwide breast cancer incidences emphasizes the urgent need for identification of methylation biomarkers for early cancer detection and patient stratification. Using microfluidic PCR-based target enrichment and next-generation bisulfite sequencing technology, we analyzed methylation status of 48 candidate genes in paired tumor and normal tissues from 180 Chinese breast cancer patients. Analysis of the sequencing results showed 37 genes differentially methylated between tumor and matched normal tissues. Breast cancer samples with different clinicopathologic characteristics demonstrated distinct profiles of gene methylation. The methylation levels were significantly different between breast cancer subtypes, with basal-like and luminal B tumors having the lowest and the highest methylation levels, respectively. Six genes (ACADL, ADAMTSL1, CAV1, NPY, PTGS2, and RUNX3) showed significant differential methylation among the 4 breast cancer subtypes and also between the ER +/ER- tumors. Using unsupervised hierarchical clustering analysis, we identified a panel of 13 hypermethylated genes as candidate biomarkers that performed a high level of efficiency for cancer prediction. These 13 genes included CST6, DBC1, EGFR, GREM1, GSTP1, IGFBP3, PDGFRB, PPM1E, SFRP1, SFRP2, SOX17, TNFRSF10D, and WRN. Our results provide evidence that well-defined DNA methylation profiles enable breast cancer prediction and patient stratification. The novel gene panel might be a valuable biomarker for early detection of breast cancer.

  6. Radiobiological Determination of Dose Escalation and Normal Tissue Toxicity in Definitive Chemoradiation Therapy for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Warren, Samantha, E-mail: Samantha.warren@oncology.ox.ac.uk [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Partridge, Mike [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom); Carrington, Rhys [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hurt, Chris [Wales Cancer Trials Unit, School of Medicine, Heath Park, Cardiff (United Kingdom); Crosby, Thomas [Velindre Cancer Centre, Velindre Hospital, Cardiff (United Kingdom); Hawkins, Maria A. [Department of Oncology, Gray Institute of Radiation Oncology and Biology, University of Oxford, Oxford (United Kingdom)

    2014-10-01

    Purpose: This study investigated the trade-off in tumor coverage and organ-at-risk sparing when applying dose escalation for concurrent chemoradiation therapy (CRT) of mid-esophageal cancer, using radiobiological modeling to estimate local control and normal tissue toxicity. Methods and Materials: Twenty-one patients with mid-esophageal cancer were selected from the SCOPE1 database (International Standard Randomised Controlled Trials number 47718479), with a mean planning target volume (PTV) of 327 cm{sup 3}. A boost volume, PTV2 (GTV + 0.5 cm margin), was created. Radiobiological modeling of tumor control probability (TCP) estimated the dose required for a clinically significant (+20%) increase in local control as 62.5 Gy/25 fractions. A RapidArc (RA) plan with a simultaneously integrated boost (SIB) to PTV2 (RA{sub 62.5}) was compared to a standard dose plan of 50 Gy/25 fractions (RA{sub 50}). Dose-volume metrics and estimates of normal tissue complication probability (NTCP) for heart and lungs were compared. Results: Clinically acceptable dose escalation was feasible for 16 of 21 patients, with significant gains (>18%) in tumor control from 38.2% (RA{sub 50}) to 56.3% (RA{sub 62.5}), and only a small increase in predicted toxicity: median heart NTCP 4.4% (RA{sub 50}) versus 5.6% (RA{sub 62.5}) P<.001 and median lung NTCP 6.5% (RA{sub 50}) versus 7.5% (RA{sub 62.5}) P<.001. Conclusions: Dose escalation to the GTV to improve local control is possible when overlap between PTV and organ-at-risk (<8% heart volume and <2.5% lung volume overlap for this study) generates only negligible increase in lung or heart toxicity. These predictions from radiobiological modeling should be tested in future clinical trials.

  7. Influence of daily imaging on plan quality and normal tissue toxicity for prostate cancer radiotherapy.

    Science.gov (United States)

    Bell, Katharina; Heitfeld, Marina; Licht, Norbert; Rübe, Christian; Dzierma, Yvonne

    2017-01-10

    Modern radiotherapy offers various possibilities for image guided verification of patient positioning. Different clinically relevant IGRT (image guided radiotherapy) scenarios were considered with regard to their influence on dosimetric plan quality and normal tissue complication probability (NTCP). This study is based on treatment plans of 50 prostate patients. We evaluate the clinically performed IGRT and simulate the influence of different daily IGRT scenarios on plan quality. Imaging doses of planar and cone-beam-CT (CBCT) images for three different energies (6 MV, 1 MV and 121 kV) were added to the treatment plans. The plan quality of the different scenarios was assessed by a visual inspection of the dose distribution and dose-volume-histogram (DVH) and a statistical analysis of DVH criteria. In addition, an assessment of the normal tissue complication probability was performed. Daily 1MV-CBCTs result in undesirable high dose regions in the target volume. The DVH shows that the scenarios with actual imaging performed, daily kV-CBCT and daily 6MV imaging (1x CBCT, 4x planar images per week) do not differ exceedingly from the original plan; especially imaging with daily kV-CBCT has little influence to the sparing of organs at risk. In contrast, daily 1MV- CBCT entails an additional dose of up to two fraction doses. Due to the additional dose amount some DVH constraints for plan acceptability could no longer be satisfied, especially for the daily 1MV-CBCT scenario. This scenario also shows increased NTCP for the rectum. Daily kV-CBCT has negligible influence on plan quality and is commendable for the clinical routine. If no kV-modality is available, a daily IGRT scenario with one CBCT per week and planar axial images on the other days should be preferred over daily MV-CBCT.

  8. Biomechanics and histology of bovine claw suspensory tissue in early acute laminitis.

    Science.gov (United States)

    Danscher, A M; Toelboell, T H; Wattle, O

    2010-01-01

    Weakening of the suspensory tissue supporting the pedal bone is the central issue in the theory of acute bovine laminitis, but this aspect has never been tested. The objective of this study was to investigate the effect of laminitis on the suspensory tissue. The hypothesis was that clinical and histological signs of acute laminitis are associated with decreased strength of the suspensory tissue of the bovine claw. Nonpregnant dairy heifers (n=10) received oral oligofructose overload (17 g/kg of body weight) and were killed 24 (n=4) and 72h (n=6) after overload. Control heifers (n=6) received tap water and were killed at 72 or 96h. Clinical, orthopedic, and histological examinations were carried out to confirm the occurrence of laminitis. After euthanasia, 2 adjacent tissue samples including the horn wall, lamellar layer, dermis, and pedal bone were cut from the dorso-abaxial aspect of each claw. Tissue samples were kept on ice until mounted on a mechanical testing frame, fixed by horn and bone, and loaded to failure. A stress displacement curve was generated and measurements of physiological support (force needed to displace 1mm beyond first resistance) and maximal support (force needed to break the tissue) were recorded. Heifers treated with oligofructose developed clinical signs consistent with ruminal and systemic acidosis after treatment as well as acute laminitis, characterized by weight shifting (35% of observations vs. 6% in controls), moderate lameness (100 vs. 17%, score of 3 out of 5 at 72h), and reaction to hoof testing (30 and 50% at 48 and 72h, respectively, vs. 0% in controls). Histological examination of claws from heifers killed 72h after overload showed changes consistent with acute laminitis, including stretched lamellae, wider basal cells with low chromatin density, and a thick, wavy, and blurry appearance of the basement membrane. Biomechanical results showed no effect of oligofructose overload on physiological support of the suspensory tissue

  9. Quantitative differentiation of normal and scarred tissues using second-harmonic generation microscopy.

    Science.gov (United States)

    Yildirim, Murat; Quinn, Kyle P; Kobler, James B; Zeitels, Steven M; Georgakoudi, Irene; Ben-Yakar, Adela

    2016-11-01

    The aim of this study was to differentiate normal and scarred hamster cheek pouch samples by applying a quantitative image analysis technique for determining collagen fiber direction and density in second-harmonic generation microscopy images. This paper presents a collagen tissue analysis of scarred cheek pouches of four adult male Golden Syrian hamsters as an animal model for vocal fold scarring. One cheek pouch was scarred using an electrocautery unit and the other cheek was used as a control for each hamster. A home-built upright microscope and a compact ultrafast fiber laser were used to acquire depth resolved epi-collected second-harmonic generation images of collagen fibers. To quantify the average fiber direction and fiber density in each image, we applied two-dimensional Fourier analysis and intensity thresholding at five different locations for each control and scarred tissue sample, respectively. The resultant depth-resolved average fiber direction variance for scarred hamster cheek pouches (0.61 ± 0.03) was significantly lower (p tissue (0.73 ± 0.04), indicating increased fiber alignment within the scar. Depth-resolved average voxel density measurements indicated scarred tissues contained greater (p image analysis of both fiber alignment and density from depth-resolved second-harmonic generation images in epi-detection mode enabled the quantification of the increased collagen fiber deposition and alignment typically observed in fibrosis. The epi-detection geometry is the only viable method for in vivo imaging as well as imaging thick turbid tissues. These quantitative endpoints, clearly differentiating between control and scarred hamster cheek pouches, provide an objective means to characterize the extent of vocal fold scarring in vivo in preclinical and clinical research. In particular, this non-invasive method offers advantages for monitoring scar treatments in live animals and following the effects of scarring-related treatments such as

  10. Classification between normal and tumor tissues based on the pair-wise gene expression ratio

    Directory of Open Access Journals (Sweden)

    Wong YC

    2004-10-01

    Full Text Available Abstract Background 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. Method 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. Results 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

  11. Effect of decellularized tissue powders on a rat model of acute myocardial infarction.

    Science.gov (United States)

    Tabuchi, Masaki; Negishi, Jun; Yamashita, Akitatsu; Higami, Tetsuya; Kishida, Akio; Funamoto, Seiichi

    2015-11-01

    Many research groups are currently investigating new treatment modalities for myocardial infarction. Numerous aspects need to be considered for the clinical application of these therapies, such as low cell integration and engraftment rates of cell injection techniques. Decellularized tissues are considered good materials for promoting regeneration of traumatic tissues. The properties of the decellularized tissues are sustained after processing to powder form. In this study, we examined the use of decellularized tissue powder in a rat model of acute myocardial infarction. The decellularized tissue powders, especially liver powder, promoted cell integration and neovascularization both in vitro and in vivo. Decellularized liver powder induced neovascularization in the infarct area, resulting in the suppression of myocardial necrosis. The results of this study suggest that decellularized liver powder has good potential for application as a blood supply material for the treatment of myocardial infarction.

  12. 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.

  13. Atypical locations of retropharyngeal abscess: beware of the normal lateral soft tissue neck X-ray.

    LENUS (Irish Health Repository)

    Uzomefuna, Vincent

    2012-02-01

    Retropharyngeal abscesses (RPA) are uncommon but potentially lethal deep neck space infections, over 95% of which occur in children under six years of age. Without a high index of suspicion, early recognition and prompt intervention, catastrophic consequences can ensue, and mortality can be as high as 60% if jugular vein thrombosis or mediastinitis occurs. While older children may have specific complaints referable to the pharynx, infants and young children may present with vague symptoms. To date, a lot of emphasis continues to be placed on the importance of lateral soft tissue neck X-ray in the diagnosis and management of patients with suspected retropharyngeal abscesses; and lateral neck X-ray has been cited as the most useful radiological view of the laryngopharynx. While we recognise the role of lateral neck X-rays in retropharyngeal and other upper airway pathologies, we present three case series in which lateral neck X-rays were normal and diagnosis was made only after CT scanning. These three cases were unusual as the abscesses were located high in the naso-pharynx making them impossible to detect on the lateral soft tissue neck X-rays and this underscores the need for high index of suspicion and prompt CT or MRI scanning, in any child with symptoms or signs suggestive of a possible retropharyngeal abscess.

  14. The Function of Steroid Receptor Coactivator-1 in Normal Tissues and Cancer

    Directory of Open Access Journals (Sweden)

    Claire A. Walsh, Li Qin, Jean Ching-Yi Tien, Leonie S. Young, Jianming Xu

    2012-01-01

    Full Text Available In 1995, the steroid receptor coactivator-1 (SRC-1 was identified as the first authentic steroid receptor coactivator. Since then, the SRC proteins have remained at the epicenter of coregulator biology, molecular endocrinology and endocrine-related cancer. Cumulative works on SRC-1 have shown that it is primarily a nuclear receptor coregulator and functions to construct highly specific enzymatic protein complexes which can execute efficient and successful transcriptional activation of designated target genes. The versatile nature of SRC-1 enables it to respond to steroid dependent and steroid independent stimulation, allowing it to bind across many families of transcription factors to orchestrate and regulate complex physiological reactions. This review highlights the multiple functions of SRC-1 in the development and maintenance of normal tissue functions as well as its major role in mediating hormone receptor responsiveness. Insights from genetically manipulated mouse models and clinical data suggest SRC-1 is significantly overexpressed in many cancers, in particular, cancers of the reproductive tissues. SRC-1 has been associated with cellular proliferation and tumor growth but its major tumorigenic contributions are promotion and execution of breast cancer metastasis and mediation of resistance to endocrine therapies. The ability of SRC-1 to coordinate multiple signaling pathways makes it an important player in tumor cells' escape of targeted therapy.

  15. Automatic segmentation of histological structures in normal and neoplastic mammary gland tissue sections

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam K.; Malladi, Ravi; Ortiz de Solorzano, Carlos

    2003-01-18

    In this paper we present a scheme for real time segmentation of histological structures in microscopic images of normal and neoplastic mammary gland sections. Paraffin embedded or frozen tissue blocks are sliced, and sections are stained with hematoxylin and eosin (H&E). The sections are then imaged using conventional bright field microscopy. The background of the images is corrected by arithmetic manipulation using a ''phantom.'' Then we use the fast marching method with a speed function that depends on the brightness gradient of the image to obtain a preliminary approximation to the boundaries of the structures of interest within a region of interest (ROI) of the entire section manually selected by the user. We use the result of the fast marching method as the initial condition for the level set motion equation. We run this last method for a few steps and obtain the final result of the segmentation. These results can be connected from section to section to build a three-dimensional reconstruction of the entire tissue block that we are studying.

  16. [Normal connective tissue in penis and its changes in patients with erectile dysfunction and Peyronie's disease].

    Science.gov (United States)

    Neĭmark, A I; Klimachev, V V; Gerval'd, V Ia; Bobrov, I P; Avdalian, A M; Muzalevskaia, N I; Gerval'd, I V; Aliev, R T; Kazymov, M A

    2009-01-01

    The aim of this study was to examine the connective tissue of penis in normal individuals and in patients with erectile dysfunction (ED) and Peyronie's disease (PD) using computer methods of image analysis. Penis tissues were obtained from 20 males aged 20-40 years who died in accidents, penis biopsies were taken from 23 patients with ED and 9 patients with PD (average age: 51 +/- 11.5 years). In both groups of patients, the volumetric fraction of collagen fibers in the tunica albuginea and corpora cavernosa was increased, while that one of elastic fibers was decreased. At the same time, the changes of elastic fibers were noted: the fibers become thinner and formed "rods". The reduction of the amplitude and the wavelength in the collagen fibers of the tunica albuginea in patients with ED and the presence of fibrous plaques in corpora cavernosa in in patients with PD were registered. The methods of computer image analysis may improve the morphologic diagnosis of ED and PD.

  17. Worldwide reported use of IV tissue plasminogen activator for acute ischemic stroke.

    Science.gov (United States)

    Berkowitz, Aaron L; Mittal, Manoj K; McLane, Hannah C; Shen, Gordon C; Muralidharan, Rajanandini; Lyons, Jennifer L; Shinohara, Russell T; Shuaib, Ashfaq; Mateen, Farrah J

    2014-04-01

    Intravenous tissue plasminogen activator is the most effective treatment for acute ischemic stroke, and its use may therefore serve as an indicator of the available level of acute stroke care. The greatest burden of stroke is in low- and middle-income countries, but the extent to which intravenous tissue plasminogen activator is used in these countries is unreported. A systematic review was performed searching each country name AND 'stroke' OR 'tissue plasminogen activator' OR 'thrombolysis' using PubMed, Embase, Global Health, African Index Medicus, and abstracts published in the International Journal of Stroke (Jan. 1, 1996-Oct. 1, 2012). The reported use of intravenous tissue plasminogen activator was then analyzed according to country-level income status, total expenditure on health per capita, and mortality and disability-adjusted life years due to stroke. There were 118,780 citations reviewed. Of 214 countries and independent territories, 64 (30%) reported use of intravenous tissue plasminogen activator for acute ischemic stroke in the medical literature: 3% (1/36) low-income, 19% (10/54) lower-middle-income, 33% (18/54) upper-middle-income, and 50% (35/70) high-income-countries (test for trend, P acute ischemic stroke, total healthcare expenditure per capita (odds ratio 3.3 per 1000 international dollar increase, 95% confidence interval 1.4-9.9, P = 0.02) and reported mortality rate from cerebrovascular disease (odds ratio 1.02, 95% confidence interval 0.99-1.06, P = 0.02) were significant, but reported disability-adjusted life years from cerebrovascular diseases and gross national income per capita were not (P > 0.05). Of the 10 countries with the highest disability-adjusted life years due to stroke, only one reported intravenous tissue plasminogen activator use. By reported use, intravenous tissue plasminogen activator for acute ischemic stroke is available to some patients in approximately one-third of countries. Access to advanced acute

  18. Effect of triiodothyronine on adiponectin expression and leptin release by white adipose tissue of normal rats.

    Science.gov (United States)

    Cabanelas, A; Cordeiro, A; Santos Almeida, N A dos; Monteiro de Paula, G S; Coelho, V M; Ortiga-Carvalho, T M; Pazos-Moura, C C

    2010-04-01

    Previous studies have shown that alterations in thyroid status may lead to changes in serum leptin and adiponectin, both in humans and rodents. The mechanisms, especially for adiponectin, are unclear. In the present study, we investigated the effect of triiodothyronine (T3) on the expression of adiponectin mRNA and the release of leptin and adiponectin by white adipose tissue (WAT) explants obtained from epididymal (visceral) or inguinal (subcutaneous) depots from normal rats. We also analyzed the effects of other known regulators of adiponectin and leptin release, such as rosiglitazone and dexamethasone. T3 acted directly at rat WAT explants in a depot-specific manner and in a unique fashion to each hormone. T3 was able to inhibit leptin release only by epididymal explants, and to reduce adiponectin mRNA expression only in inguinal explants. However, T3 was incapable of modifying adiponectin release by both explants. Additionally, rosiglitazone exhibited an inhibitory effect on adiponectin release by both WAT explants, even though adiponectin mRNA was importantly upregulated only in inguinal explants. Rosiglitazone acted as an inhibitor of leptin release by both studied fat depots, while only epididymal explants responded to the stimulatory effect of dexamethasone on leptin release. Therefore, the present model of isolated rat white adipose tissue explants highlights the fact that the regulation of hormonal production by white adipose tissue depends on the type of depot and its anatomical location. In this context, our results show for the first time a potential inhibitory effect of T3 on adiponectin mRNA expression specifically on WAT from a subcutaneous depot. Georg Thieme Verlag KG Stuttgart New York.

  19. Comparative Proteome Analysis of Breast Cancer and Adjacent Normal Breast Tissues in Human

    Institute of Scientific and Technical Information of China (English)

    Shi-Shan Deng; Tian-Yong Xing; Hong-Ying Zhou; Ruo-Hong Xiong; You-Guang Lu; Bin Wen; Shang-Qing Liu; Hui-Jun Yang

    2006-01-01

    Two-dimensional polyacryiamide gel electrophoresis (2D-PAGE) and matrixassisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS), incorporated with online database searching, were performed to investigate differential proteins of breast cancer and adjacent normal breast tissues. Considering that serum albumin is abundantly presented in normal control samples, 15 differential spots detected in 11 out of 12 (91.7%) breast cancer samples were identified by online SIENA-2DPAGE database searching and MALDI-TOF/TOF-MS analysis. The results indicate that pathological changes of breast cancer are concerned with augmentation of substance metabolism, promotion of proteolytic activity, decline of activity of some inhibitors of enzymes, and so on. Some important proteins involved in the pathological process of breast cancer with changed expression may be useful biomarkers, such as alpha-1-antitrypsin, EF1-beta, cathepsin D, TCTP, SMT3A, RPS12, and PSMA1, among which SMT3A,RPS12, and PSMA1 were first reported for breast cancer in this study.

  20. Estimate of normal tissue damage in treatment planning for stereotactic radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Benassi, M. (Laboratorio Fisica Medica e Sistemi Esperti, C.R.S., Ist. Regina Elena, Rome (Italy)); Begnozzi, L. (Laboratorio Fisica Medica e Sistemi Esperti, C.R.S., Ist. Regina Elena, Rome (Italy)); Gentile, F.P. (Laboratorio Fisica Medica e Sistemi Esperti, C.R.S., Ist. Regina Elena, Rome (Italy)); Chiatti, L. (Laboratorio Fisica Medica e Sistemi Esperti, C.R.S., Ist. Regina Elena, Rome (Italy)); Carpino, S. (Laboratorio Fisica Medica e Sistemi Esperti, C.R.S., Ist. Regina Elena, Rome (Italy))

    1993-10-01

    A personal computer (PC) system was developed to perform treatment planning for radiosurgery and stereotactic radiotherapy. These techniques of irradiation of the brain may be accomplished with a linear accelerator by performing several non-coplanar arcs of a highly collimated beam focused at a fixed point. The PC system allows the acquisition, reconstruction and the visualization of the target volume from CT or MR images, and then it permits to calculate a three-dimensional (3-D) dose distribution due to small photon beams and to visualize it. The software calculates not only total dose distribution, administered fractionated or in single fraction, but also in NTD2 (normalized total dose) predicted to have a biological effect equivalent to the single irradiation. The choice of the best technique is supported by the dose volume histograms (DVH) calculation and by an estimate of complication probability to the brain normal tissue (NTCP). The algorithm for NTCP calculation is based on two models: The linear quadratic and the logistic. A comparison of three different dose calculations for a typical cerebral target volume is presented to demonstrate the system performances. (orig.)

  1. [Tyrosine-protein kinase activity in breast neoplasm. Comparison with activity obtained in benign diseases and in normal tissues].

    Science.gov (United States)

    Pierart, J; Oñate, E; Klaassen, R; Cid, L; Gutierrez, S; Talbot, E; Ross, E; Zambrano, C; Burmeister, R; Puchi, M

    1995-02-01

    Tyrosine protein kinase (TPK) activity is associated to malignant cellular transformation. This work compares TPK activity in 27 surgical biopsy samples of mammary carcinoma, 10 samples of fibroadenomas, 13 samples of fibrocystic breast disease and 27 samples of normal mammary tissue. TPK activity was determined in tissue homogenates using (Val5) angiotensin II as exogenous substrate. In samples of mammary carcinoma, TPK activity was 33.86 +/- 31.98 pmol P32/mg protein/30 min. This value was significantly higher that those observed in fibrocystic disease (3.92 +/- 2.35), fibroadenomas (13.86 +/- 10.9) and normal tissue (3.56 +/- 3.02).

  2. MRI in the assessment of the supportive soft tissues of the cervical spine in acute trauma in children

    Energy Technology Data Exchange (ETDEWEB)

    Keiper, M.D.; Zimmerman, R.A.; Bilaniuk, L.T. [Department of Radiology, Children`s Hospital of Philadelphia, PA (United States)

    1998-06-01

    We carried out a retrospective analysis of imaging and clinical findings in 52 children with a history of cervical spinal trauma. No patient had evidence of a fracture on plain films or CT. All had MRI at 1.5 T because of persistent or delayed symptoms, unexplained findings of injury or instability, or as further assessment of the extent of soft-tissue injury. Clinical follow-up ranged from 6 months to 3.5 years. MRI was evaluated for its influence on therapy and outcome. MRI was positive in 16 (31 %) of 52 patients. Posterior soft-tissue or ligamentous injury was the most common finding in the 10 patients with mild to moderate trauma, while acute disc bulges and longitudinal ligament disruption, each seen in one case, were uncommon. MRI was superior to CT for assessment of the extent of soft-tissue injury and for identification of spinal cord injuries and intracanalicular hemorrhage in the six patients with more severe trauma. MRI specifically influenced the management of all four patients requiring surgery by extending the level of posterior stabilization. No patients with normal MRI or any of the 10 with radiographically stable soft-tissue injury on MRI, developed delayed clinical or radiographic evidence of instability or deformity. (orig.) With 2 figs., 2 tabs., 24 refs.

  3. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus L., protects rat tissues against oxidative damage after acute ethanol administration

    Directory of Open Access Journals (Sweden)

    Carmen Pinto

    2014-01-01

    Full Text Available Ethanol-mediated free radical generation is directly involved in alcoholic liver disease. In addition, chronic alcohol bingeing also induces pathological changes and dysfunction in multi-organs. In the present study, the protective effect of xanthohumol (XN on ethanol-induced damage was evaluated by determining antioxidative parameters and stress oxidative markers in liver, kidney, lung, heart and brain of rats. An acute treatment (4 g/kg b.w. of ethanol resulted in the depletion of superoxide dismutase, catalase and glutathione S-transferase activities and reduced glutathione content. This effect was accompanied by the increased activity of tissue damage marker enzymes (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and lactate dehydrogenase and a significant increase in lipid peroxidation and hydrogen peroxide concentrations. Pre-treatment with XN protected rat tissues from ethanol-induced oxidative imbalance and partially mitigated the levels to nearly normal levels in all tissues checked. This effect was dose dependent, suggesting that XN reduces stress oxidative and protects rat tissues from alcohol-induced injury.

  4. Glucose transporter Glut-1 is detectable in peri-necrotic regions in many human tumor types but not normal tissues: Study using tissue microarrays.

    Science.gov (United States)

    Airley, Rachel; Evans, Andrew; Mobasheri, Ali; Hewitt, Stephen M

    2010-05-20

    The hypoxic tumor microenvironment is associated with malignant progression and poor treatment response. The glucose transporter Glut-1 is a prognostic factor and putative hypoxia marker. So far, studies of Glut-1 in cancer have utilized conventional immunohistochemical analysis in a series of individual biopsy or surgical specimens. Tissue microarrays, however, provide a rapid, inexpensive means of profiling biomarker expression. To evaluate hypoxia markers, tissue cores must show the architectural features of hypoxia; i.e. viable tissue surrounding necrotic regions. Glut-1 may be a useful biomarker to validate tissue microarrays for use in studies of hypoxia-regulated genes in cancer. In this study, we carried out immunohistochemical detection of Glut-1 protein in many tumor and normal tissue types in a range of tissue microarrays. Glut-1 was frequently found in peri-necrotic regions, occurring in 9/34 lymphomas, 6/12 melanomas, and 5/16 glioblastomas; and in 43/54 lung, 22/84 colon, and 23/60 ovarian tumors. Expression was rare in breast (6/40) and prostate (1/57) tumors, and in normal tissue, was restricted to spleen, tongue, and CNS endothelium. In conclusion, tissue microarrays enable the observation of Glut-1 expression in peri-necrotic regions, which may be linked to hypoxia, and reflect previous studies showing differential Glut-1 expression across tumor types and non-malignant tissue.

  5. Comparative Study on Antioxidative System in Normal and Vitrified Shoots of Populus suaveolens in Tissue Culture

    Institute of Scientific and Technical Information of China (English)

    Lin Shanzhi; Zhang Zhiyi; Lin Yuanzhen; Liu Wenfeng; Guo Huan; Zhang Wei; Zhang Chong

    2004-01-01

    To explore the physiological and biochemical mechanism of the occurrence of vitrified shoots of Populus suaveolens in tissue culture, the changes in water, chlorphyll, lignin, H2O2, phenylalanine ammonialyase (PAL), malonaldehyde (MDA), protective enzymatic systems, and some key enzymes involved in the ascorbate- glutathione cycle were comparatively studied in both normal and vitrified shoots of P. Suaveolens. The results show that the lower activities of peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX), dehydroascorbate reductase (DHAR), glutathione reductase (GR) and PAL, and the less contents of chlorphyll, lignin, ascorbate (ASA) and reduced glutathione (GSH) as well as the lower ratios of ASA / DHA and GSH / GSSG are observed in vitrified shoots than in normal ones during the whole culture period. While in comparison with normal shoots, the higher activity of superoxide dismutase (SOD) and the more concentrations of water, H2O2, MDA, dehydroascorbate (DHA) and oxidized glutathione (GSSG) are found in vitrified shoots. Statistical analysis indicates that the enhanced activity of SOD and the decreased activities of CAT and POD as well as some enzymes involved in the ascorbate-glutathione cycle might be closely correlated to the accumulation of H2O2. The less regeneration of ASA and GSH and the lower capacity of the ascorbate-glutathione cycle observed in vitrified shoots might be due to a significant decrease in APX, MDAR, DHAR and GR activities and a decline in redox status of ASA and GSH. The decreases in chlorphyll content might result in a decline in photosynthesis. The lower activities of POD and PAL could result in the decrease of lignin synthesis and cell wall ligination, which might be the key factor leading to the increase in water content. It is concluded that the deficiency of detoxification capacity caused by the lower capacity of the ascorbate-glutathione pathway and the decreased activity of protective enzymatic system might lead to the

  6. Calcium Imaging of AM Dyes Following Prolonged Incubation in Acute Neuronal Tissue.

    Science.gov (United States)

    Cameron, Morven; Kékesi, Orsolya; Morley, John W; Tapson, Jonathan; Breen, Paul P; van Schaik, André; Buskila, Yossi

    2016-01-01

    Calcium-imaging is a sensitive method for monitoring calcium dynamics during neuronal activity. As intracellular calcium concentration is correlated to physiological and pathophysiological activity of neurons, calcium imaging with fluorescent indicators is one of the most commonly used techniques in neuroscience today. Current methodologies for loading calcium dyes into the tissue require prolonged incubation time (45-150 min), in addition to dissection and recovery time after the slicing procedure. This prolonged incubation curtails experimental time, as tissue is typically maintained for 6-8 hours after slicing. Using a recently introduced recovery chamber that extends the viability of acute brain slices to more than 24 hours, we tested the effectiveness of calcium AM staining following long incubation periods post cell loading and its impact on the functional properties of calcium signals in acute brain slices and wholemount retinae. We show that calcium dyes remain within cells and are fully functional >24 hours after loading. Moreover, the calcium dynamics recorded >24 hrs were similar to the calcium signals recorded in fresh tissue that was incubated for 24hrs after dissection. These methods will not only extend experimental time for those using acute neuronal tissue, but also may reduce the number of animals required to complete experimental goals.

  7. Application of Small Angle X-ray Scattering (SAXS for Differentiation between Normal and Cancerous Breast Tissue

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Introduction: Small angle, between 3° and 10°, X ray scattering is predominantly coherent giving rise to diffraction effects that can be observed as constructive and destructive interferences. These interferences carry information about the molecular structure of the tissue and hence can be used to identify changes that occur due to cancer. Method: In this study an energy dispersive X-ray diffraction method was used. The optimum scattering angle, determined from a series of measurements on adipose breast tissue at several angles from 4 to 7.3 degrees, was found to be 6.5°. Once optimized the system was used to measure the diffraction profiles (corrected scattered intensity versus momentum transfer of a total of 99 breast tissue samples. The samples were both normal and tumour samples. Results: Adipose tissue showed a sharp, high intensity peak at low momentum transfer values of approximately 1.1nm-1. Adipose tissue, mixed tissue (adipose & fibroglandular and tumor have peaks at different values of momentum transfer that can be used to identify the tissue. Benign and malignant breast tissues can also be differentiated by both peak positions and peak heights. It was also observed that the results were reproducible even after the tissue had been preserved at liquid nitrogen temperatures. Conclusion: We were able to differentiate between normal, benign and malignant breast tissues by using energy dispersive small angle x-ray scattering.

  8. Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML.

    NARCIS (Netherlands)

    Hollink, I.H.; Zwaan, C.M.; Zimmermann, M.; Arentsen-Peters, T.C.; Pieters, R.; Cloos, J.; Kaspers, G.J.L.; Graaf, S.S.N. de; Harbott, J.; Creutzig, U.; Reinhardt, D.; Heuvel-Eibrink, M.M. van den; Thiede, C.

    2009-01-01

    Nucleophosmin (NPM1) mutations occur frequently in adult cytogenetically normal acute myeloid leukemia (CN-AML) and confer favorable outcome. We investigated the frequency and prognostic significance of NPM1 mutations in childhood AML (n=298), specifically focusing on the CN-AML subgroup (n=100). Mu

  9. Residual Disease in a Novel Xenograft Model of RUNX1-Mutated, Cytogenetically Normal Acute Myeloid Leukemia.

    Directory of Open Access Journals (Sweden)

    Umayal Sivagnanalingam

    Full Text Available Cytogenetically normal acute myeloid leukemia (CN-AML patients harboring RUNX1 mutations have a dismal prognosis with anthracycline/cytarabine-based chemotherapy. We aimed to develop an in vivo model of RUNX1-mutated, CN-AML in which the nature of residual disease in this molecular disease subset could be explored. We utilized a well-characterized patient-derived, RUNX1-mutated CN-AML line (CG-SH. Tail vein injection of CG-SH into NOD scid gamma mice led to leukemic engraftment in the bone marrow, spleen, and peripheral blood within 6 weeks. Treatment of leukemic mice with anthracycline/cytarabine-based chemotherapy resulted in clearance of disease from the spleen and peripheral blood, but persistence of disease in the bone marrow as assessed by flow cytometry and secondary transplantation. Whole exome sequencing of CG-SH revealed mutations in ASXL1, CEBPA, GATA2, and SETBP1, not previously reported. We conclude that CG-SH xenografts are a robust, reproducible in vivo model of CN-AML in which to explore mechanisms of chemotherapy resistance and novel therapeutic approaches.

  10. Molecular prognostic markers for adult acute myeloid leukemia with normal cytogenetics

    Directory of Open Access Journals (Sweden)

    Gregory Tara K

    2009-06-01

    Full Text Available Abstract Acute myeloid leukemia (AML is a heterogenous disorder that results from a block in the differentiation of hematopoietic progenitor cells along with uncontrolled proliferation. In approximately 60% of cases, specific recurrent chromosomal aberrations can be identified by modern cytogenetic techniques. This cytogenetic information is the single most important tool to classify patients at their initial diagnosis into three prognostic categories: favorable, intermediate, and poor risk. Currently, favorable risk AML patients are usually treated with contemporary chemotherapy while poor risk AML patients receive allogeneic stem cell transplantation if suitable stem cell donors exist. The largest subgroup of AML patients (~40% have no identifiable cytogenetic abnormalities and are classified as intermediate risk. The optimal therapeutic strategies for these patients are still largely unclear. Recently, it is becoming increasingly evident that it is possible to identify a subgroup of poorer risk patients among those with normal cytogenic AML (NC-AML. Molecular risk stratification for NC-AML patients may be possible due to mutations of NPM1, FLT3, MLL, and CEBPα as well as alterations in expression levels of BAALC, MN1, ERG, and AF1q. Further prospective studies are needed to confirm if poorer risk NC-AML patients have improved clinical outcomes after more aggressive therapy.

  11. Molecular Mutations and Their Cooccurrences in Cytogenetically Normal Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Mengning Wang

    2017-01-01

    Full Text Available Adult acute myeloid leukemia (AML clinically is a disparate disease that requires intensive treatments ranging from chemotherapy alone to allogeneic hematopoietic cell transplantation (allo-HCT. Historically, cytogenetic analysis has been a useful prognostic tool to classify patients into favorable, intermediate, and unfavorable prognostic risk groups. However, the intermediate-risk group, consisting predominantly of cytogenetically normal AML (CN-AML, itself exhibits diverse clinical outcomes and requires further characterization to allow for more optimal treatment decision-making. The recent advances in clinical genomics have led to the recategorization of CN-AML into favorable or unfavorable subgroups. The relapsing nature of AML is thought to be due to clonal heterogeneity that includes founder or driver mutations present in the leukemic stem cell population. In this article, we summarize the clinical outcomes of relevant molecular mutations and their cooccurrences in CN-AML, including NPM1, FLT3ITD, DNMT3A, NRAS, TET2, RUNX1, MLLPTD, ASXL1, BCOR, PHF6, CEBPAbiallelic, IDH1, IDH2R140, and IDH2R170, with an emphasis on their relevance to the leukemic stem cell compartment. We have reviewed the available literature and TCGA AML databases (2013 to highlight the potential role of stem cell regulating factor mutations on outcome within newly defined AML molecular subgroups.

  12. Mitochondrial cytochrome c oxidase subunit II variations predict adverse prognosis in cytogenetically normal acute myeloid leukaemia.

    Science.gov (United States)

    Silkjaer, Trine; Nyvold, Charlotte Guldborg; Juhl-Christensen, Caroline; Hokland, Peter; Nørgaard, Jan Maxwell

    2013-10-01

    Alterations in the two catalytic genes cytochrome c oxidase subunits I and II (COI and COII) have recently been suggested to have an adverse impact on prognosis in patients with acute myeloid leukaemia (AML). In order to explore this in further detail, we sequenced these two mitochondrial genes in diagnostic bone marrow or blood samples in 235 patients with AML. In 37 (16%) patients, a non-synonymous variation in either COI or COII could be demonstrated. No patients harboured both COI and COII non-synonymous variations. Twenty-four (10%) patients had non-synonymous variations in COI, whereas 13 (6%) patients had non-synonymous variations in COII. The COI and COII are essential subunits of cytochrome c oxidase that is the terminal enzyme in the oxidative phosphorylation complexes. In terms of disease course, we observed that in patients with a normal cytogenetic analysis at disease presentation (CN-AML) treated with curative intent, the presence of a non-synonymous variation in the COII was an adverse prognostic marker for both overall survival and disease-free survival (DFS) in both univariate (DFS; hazard ratio (HR) 4.4, P = 0.006) and multivariate analyses (DFS; HR 7.2, P = 0.001). This is the first demonstration of a mitochondrial aberration playing an adverse prognostic role in adult AML, and we argue that its role as a potentially novel adverse prognostic marker in the subset of CN-AML should be explored further.

  13. Wilms Tumor 1 Gene Mutations in Patients with Cytogenetically Normal Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Salah Aref

    2014-03-01

    Full Text Available OBJECTIVE: This study aimed to assess the prognostic impact of Wilms tumor 1 (WT1 mutations in cytogenetically normal acute myeloid leukemia (CN-AML among Egyptian patients. METHODS: Exons 1, 2, 3, 7, 8, and 9 of WT1 were screened for mutations in samples from 82 CNAML patients out of 203 newly diagnosed AML patients, of age ranging from 21 to 74 years, using high-resolution capillary electrophoresis. RESULTS: Eleven patients out of 82 (13.41% harbored WT1 mutations. Mutations were detected in exon 7 (n=7, exon 9 (n=2, exon 8 (n=1, and exon 3 (n=1, but not in exons 1 or 2. There was no statistically significant difference between the WT1 mutants and wild types as regards age, sex, French-American-British subtypes, and the prevalence of success of induction remission therapy (p=0.966; 28.6% vs. 29.3%. Patients with WT1 mutations had overall survival lower than patients with the wild type (HR=1.38; 95% CI 4.79-6.86; p=0.004. CONCLUSION: CN-AML patients with WT1 mutations have poor clinical outcome. We recommend molecular testing for WT1 mutations in patients with CN-AML at diagnosis in order to improve risk stratification of those patients.

  14. Mutation patterns of 16 genes in primary and secondary acute myeloid leukemia (AML with normal cytogenetics.

    Directory of Open Access Journals (Sweden)

    Marta Fernandez-Mercado

    Full Text Available Acute myeloid leukemia patients with normal cytogenetics (CN-AML account for almost half of AML cases. We aimed to study the frequency and relationship of a wide range of genes previously reported as mutated in AML (ASXL1, NPM1, FLT3, TET2, IDH1/2, RUNX1, DNMT3A, NRAS, JAK2, WT1, CBL, SF3B1, TP53, KRAS and MPL in a series of 84 CN-AML cases. The most frequently mutated genes in primary cases were NPM1 (60.8% and FLT3 (50.0%, and in secondary cases ASXL1 (48.5% and TET2 (30.3%. We showed that 85% of CN-AML patients have mutations in at least one of ASXL1, NPM1, FLT3, TET2, IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations; seventeen cases presented mutations of at least one of these genes. However, there was no consistent pattern in mutation acquisition during disease progression. This report concerns the analysis of the largest number of gene mutations in CN-AML studied to date, and provides insight into the mutational profile of CN-AML.

  15. Lack of noncanonical RAS mutations in cytogenetically normal acute myeloid leukemia.

    Science.gov (United States)

    Reuter, Christoph W M; Krauter, Jürgen; Onono, Fredrick O; Bunke, Tania; Damm, Frederik; Thol, Felicitas; Wagner, Katharina; Göhring, Gudrun; Schlegelberger, Brigitte; Heuser, Michael; Ganser, Arnold; Morgan, Michael A

    2014-06-01

    Transforming mutations in RAS genes are commonly found in human malignancies, including myeloid leukemias. To investigate the incidence, spectrum, and distribution of activating K- and N-RAS mutations in cytogenetically normal acute myeloid leukemia (CN-AML) patients, 204 CN-AML patients were screened. Activating K- and N-RAS mutations were detected in 3 of 204 (1.5 %) and 22 of 204 (10.8 %) CN-AML samples, respectively. RAS mutated patients presented with a lower percentage of bone marrow blasts (65 vs 80 %, P = 0.022). RAS mutations tended to occur with nucleophosmin-1 (NPM1) mutations (P = 0.079), and all three samples containing K-RAS mutations had concomitant NPM1 mutations. There was no significant overlap between K-RAS mutations and N-RAS, FLT3, CEBPA, IDH1/2, WT1 or MLL mutations. RAS mutation status did not impact relapse-free or overall survival of CN-AML patients. In contrast to reports of noncanonical RAS mutations in other cancers, including some leukemia subtypes, we only observed K- and N-RAS mutations in codons 12, 13, or 61 in CN-AML samples. Our findings suggest that while K-RAS mutations are infrequent in CN-AML, activating K-RAS mutations may cooperate with mutated NPM1 to induce leukemia.

  16. Mutation patterns of 16 genes in primary and secondary acute myeloid leukemia (AML) with normal cytogenetics.

    Science.gov (United States)

    Fernandez-Mercado, Marta; Yip, Bon Ham; Pellagatti, Andrea; Davies, Carwyn; Larrayoz, María José; Kondo, Toshinori; Pérez, Cristina; Killick, Sally; McDonald, Emma-Jane; Odero, María Dolores; Agirre, Xabier; Prósper, Felipe; Calasanz, María José; Wainscoat, James S; Boultwood, Jacqueline

    2012-01-01

    Acute myeloid leukemia patients with normal cytogenetics (CN-AML) account for almost half of AML cases. We aimed to study the frequency and relationship of a wide range of genes previously reported as mutated in AML (ASXL1, NPM1, FLT3, TET2, IDH1/2, RUNX1, DNMT3A, NRAS, JAK2, WT1, CBL, SF3B1, TP53, KRAS and MPL) in a series of 84 CN-AML cases. The most frequently mutated genes in primary cases were NPM1 (60.8%) and FLT3 (50.0%), and in secondary cases ASXL1 (48.5%) and TET2 (30.3%). We showed that 85% of CN-AML patients have mutations in at least one of ASXL1, NPM1, FLT3, TET2, IDH1/2 and/or RUNX1. Serial samples from 19 MDS/CMML cases that progressed to AML were analyzed for ASXL1/TET2/IDH1/2 mutations; seventeen cases presented mutations of at least one of these genes. However, there was no consistent pattern in mutation acquisition during disease progression. This report concerns the analysis of the largest number of gene mutations in CN-AML studied to date, and provides insight into the mutational profile of CN-AML.

  17. Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture.

    Science.gov (United States)

    Conte, N; Varela, I; Grove, C; Manes, N; Yusa, K; Moreno, T; Segonds-Pichon, A; Bench, A; Gudgin, E; Herman, B; Bolli, N; Ellis, P; Haddad, D; Costeas, P; Rad, R; Scott, M; Huntly, B; Bradley, A; Vassiliou, G S

    2013-09-01

    Advances in sequencing technologies are giving unprecedented insights into the spectrum of somatic mutations underlying acute myeloid leukaemia with a normal karyotype (AML-NK). It is clear that the prognosis of individual patients is strongly influenced by the combination of mutations in their leukaemia and that many leukaemias are composed of multiple subclones, with differential susceptibilities to treatment. Here, we describe a method, employing targeted capture coupled with next-generation sequencing and tailored bioinformatic analysis, for the simultaneous study of 24 genes recurrently mutated in AML-NK. Mutational analysis was performed using open source software and an in-house script (Mutation Identification and Analysis Software), which identified dominant clone mutations with 100% specificity. In each of seven cases of AML-NK studied, we identified and verified mutations in 2-4 genes in the main leukaemic clone. Additionally, high sequencing depth enabled us to identify putative subclonal mutations and detect leukaemia-specific mutations in DNA from remission marrow. Finally, we used normalised read depths to detect copy number changes and identified and subsequently verified a tandem duplication of exons 2-9 of MLL and at least one deletion involving PTEN. This methodology reliably detects sequence and copy number mutations, and can thus greatly facilitate the classification, clinical research, diagnosis and management of AML-NK.

  18. Investigation of scattering coefficients and anisotropy factors of human cancerous and normal prostate tissues using Mie theory

    Science.gov (United States)

    Pu, Yang; Chen, Jun; Wang, Wubao

    2014-02-01

    The scattering coefficient, μs, the anisotropy factor, g, the scattering phase function, p(θ), and the angular dependence of scattering intensity distributions of human cancerous and normal prostate tissues were systematically investigated as a function of wavelength, scattering angle and scattering particle size using Mie theory and experimental parameters. The Matlab-based codes using Mie theory for both spherical and cylindrical models were developed and applied for studying the light propagation and the key scattering properties of the prostate tissues. The optical and structural parameters of tissue such as the index of refraction of cytoplasm, size of nuclei, and the diameter of the nucleoli for cancerous and normal human prostate tissues obtained from the previous biological, biomedical and bio-optic studies were used for Mie theory simulation and calculation. The wavelength dependence of scattering coefficient and anisotropy factor were investigated in the wide spectral range from 300 nm to 1200 nm. The scattering particle size dependence of μs, g, and scattering angular distributions were studied for cancerous and normal prostate tissues. The results show that cancerous prostate tissue containing larger size scattering particles has more contribution to the forward scattering in comparison with the normal prostate tissue. In addition to the conventional simulation model that approximately considers the scattering particle as sphere, the cylinder model which is more suitable for fiber-like tissue frame components such as collagen and elastin was used for developing a computation code to study angular dependence of scattering in prostate tissues. To the best of our knowledge, this is the first study to deal with both spherical and cylindrical scattering particles in prostate tissues.

  19. Wide-field imaging of fluorescent deoxy-glucose in ex vivo malignant and normal breast tissue

    Science.gov (United States)

    Langsner, R. J.; Middleton, L. P.; Sun, J.; Meric-Bernstam, F.; Hunt, K. K.; Drezek, R. A.; Yu, T. K.

    2011-01-01

    Rapid in situ determination of surgical resection margins during breast cancer surgery would reduce patient time under anesthesia. We present preliminary data supporting the use of a fluorescent glucose analog (2-NBDG) as an optical contrast agent to differentiate freshly excised breast tissue containing cancerous cells from normal breast tissue. Multi-spectral images of 14 breast cancer specimens acquired before and after incubation with 2-NBDG demonstrated increased fluorescent signal in all of the malignant tissue due to increased 2-NBDG consumption. We demonstrate that 2-NBDG has potential as an optical contrast agent to differentiate cancerous from non-cancerous tissue. PMID:21698015

  20. Electroporation-assisted penetration of zinc oxide nanoparticles in ex vivo normal and cancerous human colon tissue

    Science.gov (United States)

    Zhou, L. P.; Wu, G. Y.; Wei, H. J.; Guo, Z. Y.; Yang, H. Q.; He, Y. H.; Xie, S. S.

    2015-11-01

    In this study, we presented the research of the penetration of zinc oxide nanoparticles (ZnO NPs) (30 and 90 nm), and electroporation (EP) assisted penetration of the ZnO NPs in the human normal colon (NC) and adenomatous colon (AC) tissues studied with optical coherence tomography (OCT) and diffuse reflectance (DR) measurement. The results have shown that the attenuation coefficient of colon tissue after the application of 30 or 90 nm ZnO NPs alone decreased approximately by 28% and 14% for NC tissue, 35% and 22% for AC tissue, respectively; while the attenuation coefficient of colon tissue after combined application of 30 or 90 nm ZnO NPs/EP decreased approximately by 46% and 30% for NC tissue, and 53% and 42% for AC tissue, respectively. The results illustrate EP can significantly increase the penetration of ZnO NPs in the colon tissue, especially in AC tissue. Through the analysis of attenuation coefficient and reflectance intensity of the colon tissue, we find that the accumulation of the ZnO NPs in the colon tissue greatly influenced the tissue optical properties.

  1. Differential expression of Nogo-B in preeclampsia placental tissue and normal placental tissue and its correlation with illness-related molecule expression

    Institute of Scientific and Technical Information of China (English)

    Fu-Rong Xu; Hai-Yan Wang

    2016-01-01

    Objective:To study the differential expression of Nogo-B in preeclampsia placental tissue and normal placental tissue and its correlation with illness-related molecule expression.Methods:Placental tissue of preeclampsia puerperas and normal pregnancy puerperas was collected, PCR method was used to detect mRNA contents of Nogo-B and apoptosis genes (Fas, Caspase-3 and Caspase-9) and Elisa was used to detect protein contents of inflammatory factors (TNF-α, IL-1β, IL-6, IL-8, CD40L and VCAM-1) and endothelial injury molecules (LOX-1, ox-LDL, PTX3 and ADM).Results:mRNA content of Nogo-B in preeclampsia placental tissue was significantly higher than that in normal placental tissue and the more severe the disease, the higher the mRNA content of Nogo-B; mRNA contents of Fas, Caspase-3 and Caspase-9 as well as protein contents of TNF-α, IL-1β, IL-6, IL-8, CD40L, VCAM-1, LOX-1, ox-LDL, PTX3 and ADM in preeclampsia placental tissue were significantly higher than those in normal placental tissue; mRNA content of Nogo-B was positively correlated with mRNA contents of Fas, Caspase-3 and Caspase-9 as well as protein contents of TNF-α, IL-1β, IL-6, IL-8, CD40L, VCAM-1, LOX-1, ox-LDL, PTX3 and ADM.Conclusions:Nogo-B expression in preeclampsia placental tissue significantly increases, and the molecule can regulate the generation of apoptosis genes, inflammatory factors and endothelial injury molecules to be involved in the occurrence of preeclampsia.

  2. The Expression and Change of the β3 Integrin Subunit and Fibronectin in Normal Human Oviductal Tissue and Tubal Ectopic Pregnant Tissue

    Institute of Scientific and Technical Information of China (English)

    Chun-jie MA; Wei-jie ZHU; Hai-yan JIN; Guang-yu JIANG; Hong SHEN; Hong LI; Ming-han XIA

    2003-01-01

    Objective To investigate the expression and change of the β3 integrin subunit and fibronectin in normal human oviductal tissue during various phases of the menstrual cycle and tubal ectopic pregnant tissue Methods Samples of normal ( n=29 ) and pregnant fallopian tube ( n=22 ) tissues were obtained from women who had normal cycle and history of normal pregnancy. Normal oviductal tissue samples were divided into 4 groups based on their menstrual cycle.Both expression and distribution of the β3 subunit and fibronectin were determined with the immunohistochemical method and the image analysis.Results The β3 subunit was expressed in the cytoplasm of ciliated cells. The expression level of the β3 subunit was higher after ovulation than that before ovulation in isthmus epithelium (P <0.001), and declined significantly after ovulation in ampullae epithelium (P<0. 001). In umbrella epithelium within 4 days after ovulation, the expression level of the β3 subunit was observed at rather higher level among other phases (P <0.001). The ciliated and secretory cells of the epithelium except for where the pregnancy occurred in tubal pregnancy expressed the β3 subunit, and no significant relationship was found between the normal tubal tissue of the secretory phase and tubal ectopic pregnant tissue (P>0. 05). Fibronectin was expressed in the basement membrane of human oviductal epithelium and matrix. The expression level of fibronectin was higher in the hyperplastic phase than that in the secretory one (P <0. 001). And it was lower in normal tubal tissue of the secretory phase than that in tubal ectopic pregnant tissue (P <0.001).Conclusion The β3 integrin subunit was expressed in the ciliated cells of human oviductal epithelium, and fibronectin was expressed in the basement membrane of human oviductal epithelium and matrix. Their expression and change in oviductal tissue is based on different phases of menstrual cycle. Theβ3 subunit could not related to the

  3. Pulsed Doppler Tissue Imaging for Assessment of Left Ventricular Systolic and Diastolic Synchronicity in Normal Subjects

    Institute of Scientific and Technical Information of China (English)

    Yang Li; Wu Wei; Wang Jingfeng; Zhang Xiaoling

    2006-01-01

    Objectives To quantitatively analyze the longitudinal myocardial systolic and diastolic velocities and time intervals of the left ventricle in normal subjects, and to explore the value of pulsed Doppler tissue imaging (DTI) for the assessment of left ventricular systolic and diastolic synchronicity.Methods Twenty and six healthy subjects were studied by pulsed DTI. The septal and lateral, anterior and inferior walls of the left ventricle were displayed respectively, and basal and middle segments of each wall were selected for myocardial motion spectrum sampling. DTI parameters were: peak systolic myocardial velocity (s), regional pre-ejection period (PEP), time to the peak of s wave (Ts), regional ejection time (ET); peak early diastolic velocity (e),peak late diastolic velocity (a), e/a ratio, time to the beginning of e wave (QE), time to the peak of e wave (Te) and regional isovolumic relaxation time (IVRT).Results The e and e/a were significantly different among basal segments, and s and e/a were significantly different among middle segments, with the highest value in lateral segments and the lowest value in septal segments. The s, e and a were all significantly higher in basal segments than middle segments. None of the systolic time intervals (PEP, Ts and ET) and diastolic time intervals (QE, Te and IVRT) were significantly different among basal segments and middle segments,neither were they when basal segment was compared with middle segment. Conclusions In normal subjects, the longitudinal myocardial systolic and diastolic velocities of the left ventricle are not homogeneous, but the contraction and relaxation are highly synchronized. Pulsed DTI can be used to quantitatively analyze the systolic and diastolic synchronicity of the heart.

  4. 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.

  5. Developing Multivariable Normal Tissue Complication Probability Model to Predict the Incidence of Symptomatic Radiation Pneumonitis among Breast Cancer Patients.

    Directory of Open Access Journals (Sweden)

    Tsair-Fwu Lee

    Full Text Available Symptomatic radiation pneumonitis (SRP, which decreases quality of life (QoL, is the most common pulmonary complication in patients receiving breast irradiation. If it occurs, acute SRP usually develops 4-12 weeks after completion of radiotherapy and presents as a dry cough, dyspnea and low-grade fever. If the incidence of SRP is reduced, not only the QoL but also the compliance of breast cancer patients may be improved. Therefore, we investigated the incidence SRP in breast cancer patients after hybrid intensity modulated radiotherapy (IMRT to find the risk factors, which may have important effects on the risk of radiation-induced complications.In total, 93 patients with breast cancer were evaluated. The final endpoint for acute SRP was defined as those who had density changes together with symptoms, as measured using computed tomography. The risk factors for a multivariate normal tissue complication probability model of SRP were determined using the least absolute shrinkage and selection operator (LASSO technique.Five risk factors were selected using LASSO: the percentage of the ipsilateral lung volume that received more than 20-Gy (IV20, energy, age, body mass index (BMI and T stage. Positive associations were demonstrated among the incidence of SRP, IV20, and patient age. Energy, BMI and T stage showed a negative association with the incidence of SRP. Our analyses indicate that the risk of SPR following hybrid IMRT in elderly or low-BMI breast cancer patients is increased once the percentage of the ipsilateral lung volume receiving more than 20-Gy is controlled below a limitation.We suggest to define a dose-volume percentage constraint of IV20< 37% (or AIV20< 310cc for the irradiated ipsilateral lung in radiation therapy treatment planning to maintain the incidence of SPR below 20%, and pay attention to the sequelae especially in elderly or low-BMI breast cancer patients. (AIV20: the absolute ipsilateral lung volume that received more than

  6. Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation

    DEFF Research Database (Denmark)

    Rittig, Nikolaj; Bach, Ermina; Thomsen, Henrik Holm;

    2016-01-01

    = 0.001) compared with Placebo. These effects were associated with increased phosphorylation of hormone sensitive lipase (pHSL) at ser650 in adipose tissue (p = 0.03), a trend towards elevated pHSL at ser552 (p = 0.09) and cAMP-dependent protein kinase A (PKA) phosphorylation of perilipin 1 (PLIN1) (p...... lipolysis in adipose tissue and is associated with increased pHSL and signs of increased PLIN1 phosphorylation combined with a trend toward decreased insulin signaling. The combination of these mechanisms appear to be the driving forces behind the increased lipolysis observed in the early stages of acute...

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

    Energy Technology Data Exchange (ETDEWEB)

    Keus, R.; Boer, R. de; Lebesque, J. (Nederlands Kanker Inst. ' Antoni van Leeuwenhoekhuis' , Amsterdam (Netherlands)); Noach, P. (Medisch Spectrum Twente, Enschede (Netherlands). Department of Radiotherapy)

    1991-07-01

    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.

  8. Comparative proteomic analysis of normal and tumor stromal cells by tissue on chip based mass spectrometry (toc-MS

    Directory of Open Access Journals (Sweden)

    Friedrich Karlheinz

    2010-01-01

    Full Text Available Abstract In carcinoma tissues, genetic and metabolic changes not only occur at the tumor cell level, but also in the surrounding stroma. This carcinoma-reactive stromal tissue is heterogeneous and consists e.g. of non-epithelial cells such as fibroblasts or fibrocytes, inflammatory cells and vasculature-related cells, which promote carcinoma growth and progression of carcinomas. Nevertheless, there is just little knowledge about the proteomic changes from normal connective tissue to tumor stroma. In the present study, we acquired and analysed specific protein patterns of small stromal sections surrounding head and neck cell complexes in comparison to normal subepithelial connective tissue. To gain defined stromal areas we used laser-based tissue microdissection. Because these stromal areas are limited in size we established the highly sensitive 'tissue on chip based mass spectrometry' (toc-MS. Therefore, the dissected areas were directly transferred to chromatographic arrays and the proteomic profiles were subsequently analysed with mass spectrometry. At least 100 cells were needed for an adequate spectrum. The locating of differentially expressed proteins enables a precise separation of normal and tumor stroma. The newly described toc-MS technology allows an initial insight into proteomic differences between small numbers of exactly defined cells from normal and tumor stroma.

  9. 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].

  10. Metabolic aspects of acute tissue hypoxia during extracorporeal circulation and their modification induced by L-carnitine treatment.

    Science.gov (United States)

    Corbucci, G G; Menichetti, A; Cogliatti, A; Nicoli, P; Ruvolo, C

    1992-01-01

    In this study the authors examine the effects of acute hypoxia due to extracorporeal circulation (ECC) and the role played by L-carnitine treatment on some plasmatic metabolites linked to glycolytic cellular metabolism. To obtain biochemical data, 120 patients in extracorporeal circulation during aortopulmonary bypass surgery were evaluated. The patients received either sodium bicarbonate (40 patients), or L-carnitine during ECC (40 patients) or before and during ECC (40 patients), and plasma samples were collected before ECC, during ECC and after ECC. The levels of lactate and pyruvate showed significant alterations in sodium bicarbonate-treated patients, and there was also a considerable imbalance in the succinate/fumarate ratio. This means that tissue hypoxia due to ECC leads to cellular oxidative damage and to a considerable decrease in the intracellular energy pools. The use of L-carnitine antagonizes the oxidative stress, as is well documented by the levels of plasmatic metabolites which remain confined to normal amounts.

  11. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    Science.gov (United States)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM 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 the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert 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.

  12. 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.

  13. 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.

  14. 3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

    Science.gov (United States)

    Goodwin, Thomas J.

    2013-01-01

    Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

  15. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): An Introduction to the Scientific Issues

    Science.gov (United States)

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

    2012-01-01

    Advances in dose/volume/outcome (or normal tissue complication probability, NTCP) modeling since the seminal Emami paper from 1991 are reviewed. There has been some progress with an increasing number of studies on large patient samples with three-dimensional dosimetry. Nevertheless, NTCP models are not ideal. Issues related to the grading of side effects, selection of appropriate statistical methods, testing of internal and external model validity, and quantification of predictive power and statistical uncertainty, all limit the usefulness of much of the published literature. Synthesis (meta-analysis) of data from multiple studies is often impossible due to sub-optimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge-base includes the need for more data on the effect of patient-related co-factors, interactions between dose-distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to non-uniform dose distributions. Research priorities for the next 5 to 10 years are proposed. PMID:20171515

  16. Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues.

    Science.gov (United States)

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

    2010-03-01

    Advances in dose-volume/outcome (or normal tissue complication probability, NTCP) modeling since the seminal Emami paper from 1991 are reviewed. There has been some progress with an increasing number of studies on large patient samples with three-dimensional dosimetry. Nevertheless, NTCP models are not ideal. Issues related to the grading of side effects, selection of appropriate statistical methods, testing of internal and external model validity, and quantification of predictive power and statistical uncertainty, all limit the usefulness of much of the published literature. Synthesis (meta-analysis) of data from multiple studies is often impossible because of suboptimal primary analysis, insufficient reporting and variations in the models and predictors analyzed. Clinical limitations to the current knowledge base include the need for more data on the effect of patient-related cofactors, interactions between dose distribution and cytotoxic or molecular targeted agents, and the effect of dose fractions and overall treatment time in relation to nonuniform dose distributions. Research priorities for the next 5-10 years are proposed.

  17. PSCs and GLP-1R: occurrence in normal pancreas, acute/chronic pancreatitis and effect of their activation by a GLP-1R agonist.

    Science.gov (United States)

    Nakamura, Taichi; Ito, Tetsuhide; Uchida, Masahiko; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Jensen, Robert T; Takayanagi, Ryoichi

    2014-01-01

    There is increasing concern about the development of pancreatitis in patients with diabetes mellitus who received long-term glucagon-like peptide-1 (GLP-1) analog treatment. Its pathogenesis is unknown. The effects of GLP-1 agonists on pancreatic endocrine cells are well studied; however, there is little information on effects on other pancreatic tissues that might be involved in inflammatory processes. Pancreatic stellate cells (PSCs) can have an important role in pancreatitis, secreting various inflammatory cytokines/chemokines, as well as collagen. In this study, we investigated GLP-1R occurrence in normal pancreas, acute pancreatitis (AP)/chronic pancreatitis (CP), and the effects of GLP-1 analog on normal PSCs, their ability to stimulate inflammatory mediator secretion or proliferation. GLP-1 receptor (GLP-1R) expression/localization in normal pancreas and pancreatitis (AP/CP) tissues were evaluated with histological/immunohistochemical analysis. PSCs were isolated from male Wistar rats. GLP-1R expression and effects of GLP-1 analog on activated PSCs was examined with real-time PCR, MTS assays and western blotting. In normal pancreas, pancreatic β cells expressed GLP-1R, with only low expression in acinar cells, whereas in AP or CP, acinar cells, ductal cells and activated PSCs expressed GLP-1R. With activation of normal PSCs, GLP-1R is markedly increased, as is multiple other incretin-related receptors. The GLP-1 analog, liraglutide, did not induce inflammatory genes expression in activated PSCs, but induced proliferation. Liraglutide activated multiple signaling cascades in PSCs, and the extracellular signal-regulated kinase pathway mediated the PSCs proliferation. GLP-1Rs are expressed in normal pancreas and there is marked enhanced expression in AP/CP. GLP-1-agonist induced cell proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest chronic treatment with GLP-1R agonists could lead to proliferation

  18. Spectral characterization and unmixing of intrinsic contrast in intact normal and diseased gastric tissues using hyperspectral two-photon microscopy.

    Directory of Open Access Journals (Sweden)

    Lauren E Grosberg

    Full Text Available BACKGROUND: Living tissues contain a range of intrinsic fluorophores and sources of second harmonic generation which provide contrast that can be exploited for fresh tissue imaging. Microscopic imaging of fresh tissue samples can circumvent the cost and time associated with conventional histology. Further, intrinsic contrast can provide rich information about a tissue's composition, structure and function, and opens the potential for in-vivo imaging without the need for contrast agents. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used hyperspectral two-photon microscopy to explore the characteristics of both normal and diseased gastrointestinal (GI tissues, relying only on their endogenous fluorescence and second harmonic generation to provide contrast. We obtained hyperspectral data at subcellular resolution by acquiring images over a range of two-photon excitation wavelengths, and found excitation spectral signatures of specific tissue types based on our ability to clearly visualize morphology. We present the two-photon excitation spectral properties of four major tissue types that are present throughout the GI tract: epithelium, lamina propria, collagen, and lymphatic tissue. Using these four excitation signatures as basis spectra, linear unmixing strategies were applied to hyperspectral data sets of both normal and neoplastic tissue acquired in the colon and small intestine. Our results show that hyperspectral unmixing with excitation spectra allows segmentation, showing promise for blind identification of tissue types within a field of view, analogous to specific staining in conventional histology. The intrinsic spectral signatures of these tissue types provide information relating to their biochemical composition. CONCLUSIONS/SIGNIFICANCE: These results suggest hyperspectral two-photon microscopy could provide an alternative to conventional histology either for in-situ imaging, or intraoperative 'instant histology' of fresh tissue

  19. Acute pseudo-obstruction of the large bowel with caecal perforation following normal vaginal delivery: a case report

    Directory of Open Access Journals (Sweden)

    Seenath Marlon

    2010-04-01

    Full Text Available Abstract Introduction Acute pseudo-obstruction of the large bowel following normal vaginal delivery is an extremely rare complication of normal vaginal delivery. It can be fatal if not recognized early. Only one previous report has been found in the English literature. Case presentation A 36-year old Caucasian, normally fit woman presented with abdominal distension and vomiting five days post-normal vaginal delivery at term. Localised peritonitis in the right iliac fossa developed in the next few days, and caecal perforation was found at laparotomy, without evidence of appendicitis or colitis. Conclusion Although very rare, Ogilvie's syndrome should be considered by obstetricians, general surgeons and general practitioners as a potential cause of vomiting and abdominal pain following normal vaginal delivery. Early recognition and management are essential to minimize the possibility of developing serious complications.

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

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Q; Lei, Y; Zheng, D; Zhu, X; Wahl, A; Lin, C; Zhou, S; Zhen, W [University of Nebraska Medical Center, Omaha, NE (United States)

    2015-06-15

    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.

  1. Tissue specific DNA methylation of CpG islands in normal human adult somatic tissues distinguishes neural from non-neural tissues.

    Science.gov (United States)

    Ghosh, Srimoyee; Yates, Allan J; Frühwald, Michael C; Miecznikowski, Jeffrey C; Plass, Christoph; Smiraglia, Dominic

    2010-08-16

    Although most CpG islands are generally thought to remain unmethylated in all adult somatic tissues, recent genome-wide approaches have found that some CpG islands have distinct methylation patterns in various tissues, with most differences being seen between germ cells and somatic tissues. Few studies have addressed this among human somatic tissues and fewer still have studied the same sets of tissues from multiple individuals. In the current study, we used Restriction Landmark Genomic Scanning to study tissue specific methylation patterns in a set of twelve human tissues collected from multiple individuals. We identified 34 differentially methylated CpG islands among these tissues, many of which showed consistent patterns in multiple individuals. Of particular interest were striking differences in CpG island methylation, not only among brain regions, but also between white and grey matter of the same region. These findings were confirmed for selected loci by quantitative bisulfite sequencing. Cluster analysis of the RLGS data indicated that several tissues clustered together, but the strongest clustering was in brain. Tissues from different brain regions clustered together, and, as a group, brain tissues were distinct from either mesoderm or endoderm derived tissues which demonstrated limited clustering. These data demonstrate consistent tissue specific methylation for certain CpG islands, with clear differences between white and grey matter of the brain. Furthermore, there was an overall pattern of tissue specifically methylated CpG islands that distinguished neural tissues from non-neural.

  2. 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.

  3. TET2 mutations in cytogenetically normal acute myeloid leukemia: clinical implications and evolutionary patterns.

    Science.gov (United States)

    Damm, Frederik; Markus, Birgit; Thol, Felicitas; Morgan, Michael; Göhring, Gudrun; Schlegelberger, Brigitte; Krauter, Jürgen; Heuser, Michael; Bernard, Olivier A; Ganser, Arnold

    2014-10-01

    Mutations of the Ten-Eleven-Translocation 2 (TET2) gene have been identified in patients with various myeloid neoplasms, but the clinical relevance of these mutations and their timing during disease development in cytogenetically normal acute myeloid leukemia (CN-AML) remain unclear. The total coding region of TET2 was analyzed by direct sequencing in 215 CN-AML patients younger than 60 years from multicenter treatment trials AML-SHG 0199 (ClinicalTrials Identifier NCT00209833) and 0295. Associations were analyzed in the context of other molecular markers, such as CEBPA, DNMT3A, NMP1, FLT3, IDH1/2, RAS, and WT1. To investigate the order of appearance of TET2 and concomitant mutations, targeted deep resequencing was performed in six patients. At least one sequence variation with impact on TET2 protein sequence was found in 13 of the 215 CN-AML patients (6%). Patients with TET2 mutations tended to be older (P = 0.078) and had higher platelet counts (P = 0.041). TET2-mutated patients were more likely to have concomitant NPM1 (11 of 13; P = 0.047) and DNMT3A (10 of 13; P = 0.001) mutations but were mutually exclusive to partial tandem duplication of the MLL gene (MLL-PTD) and IDH1/2 mutations. TET2 mutations were identified as subclones in four of the six investigated patients by deep sequencing. Progenitor-derived colony assays suggest a stepwise acquisition of mutations during disease development, TET2 mutation being later than NPM1 and DNMT3A. The TET2 mutation status did not influence overall or relapse-free survival.

  4. Analysis of Normal Hematopoietic Stem and Progenitor Cell Contents in Childhood Acute Leukemia Bone Marrow.

    Science.gov (United States)

    Balandrán, Juan Carlos; Vadillo, Eduardo; Dozal, David; Reyes-López, Alfonso; Sandoval-Cabrera, Antonio; Laffont-Ortiz, Merle Denisse; Prieto-Chávez, Jessica L; Vilchis-Ordoñez, Armando; Quintela-Nuñez Del Prado, Henry; Mayani, Héctor; Núñez-Enríquez, Juan Carlos; Mejía-Aranguré, Juan Manuel; López-Martínez, Briceida; Jiménez-Hernández, Elva; Pelayo, Rosana

    2016-11-01

    Childhood acute leukemias (AL) are characterized by the excessive production of malignant precursor cells at the expense of effective blood cell development. The dominance of leukemic cells over normal progenitors may result in either direct suppression of functional hematopoiesis or remodeling of microenvironmental niches, contributing to BM failure and AL-associated mortality. We undertook this study to investigate the contents and functional activity of hematopoietic stem/progenitor cells (HSPC) and their relationship to immune cell production and risk status in AL pediatric patients. Multiparametric flow cytometry of BM aspirates was performed to classify AL on the basis of lineage and differentiation stages and to analyze HSPC and immune cell frequencies. Controlled co-culture systems were conducted to evaluate functional lineage potentials of primitive cells. Statistical correlations and inter-group significant differences were established. Among 113 AL BM aspirates, 26.5% corresponded to ProB, 19.5% to PreB and 32% contain ProB and PreB differentiation stages, whereas nearly 9% of the cases were T- and 13% myeloid-lineage leukemias. We identified ProB-ALL as the subtype endowed with the highest relative contents of HSPC, whereas T-ALL and PreB-ALL showed a critically reduced size of both HSC and MLP compartments. Notably, lower cell frequencies of HSPC in ProB-ALL correlated to high-risk prognosis at disease debut. HSPC abundance at initial diagnosis may aid to predict the clinical course of ALL and to identify high-risk patients. A clearer understanding of their population dynamics and functional properties in the leukemia setting will potentially pave the way for targeted therapies. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  5. 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

  6. Identification of optimal reference genes for gene expression normalization in a wide cohort of endometrioid endometrial carcinoma tissues.

    Directory of Open Access Journals (Sweden)

    Chiara Romani

    Full Text Available Accurate normalization is a primary component of a reliable gene expression analysis based on qRT-PCR technique. While the use of one or more reference genes as internal controls is commonly accepted as the most appropriate normalization strategy, many qPCR-based published studies still contain data poorly normalized and reference genes arbitrarily chosen irrespective of the particular tissue and the specific experimental design. To date, no validated reference genes have been identified for endometrial cancer tissues. In this study, 10 normalization genes (GAPDH, B2M, ACTB, POLR2A, UBC, PPIA, HPRT1, GUSB, TBP, H3F3A belonging to different functional and abundance classes in various tissues and used in different studies, were analyzed to determine their applicability. In total, 100 endometrioid endometrial cancer samples, which were carefully balanced according to their tumor grade, and 29 normal endometrial tissues were examined using SYBR Green Real-Time RT-PCR. The expression stability of candidate reference genes was determined and compared by means of geNorm and NormFinder softwares. Both algorithms were in agreement in identifying GAPDH, H3F3A, PPIA, and HPRT1 as the most stably expressed genes, only differing in their ranking order. Analysis performed on the expression levels of all candidate genes confirm HPRT1 and PPIA as the most stably expressed in the study groups regardless of sample type, to be used alone or better in combination. As the stable expression of HPRT1 and PPIA between normal and tumor endometrial samples fulfill the basic requirement of a reference gene to be used for normalization purposes, HPRT1 expression showed significant differences between samples from low-grade and high-grade tumors. In conclusion, our results recommend the use of PPIA as a single reference gene to be considered for improved reliability of normalization in gene expression studies involving endometrial tumor samples at different tumor degrees.

  7. Impact of different IMRT techniques to improve conformity and normal tissue sparing in upper esophageal cancer

    Directory of Open Access Journals (Sweden)

    Amin E Amin

    2015-03-01

    Full Text Available Purpose: Intensity modulated radiotherapy (IMRT for cervical esophageal cancer is challenging. Although IMRT techniques using inverse planning algorithms are facilitating the treatment planning process, the irradiation dose to the normal tissues can be a critical issue. This study was performed to investigate the effect of beam numbers and their directions and local optimization on: (1 dose conformity and homogeneity to the planning target volume (PTV and (2 dose to the organ at risks (OARs.Methods: Four upper esophageal cancer cases were randomly selected for this treatment planning study. Eight IMRT plans were generated for each case with the same dose-volume constraints but with different beam numbers and arrangements. Local optimization using regular structures drawn automatically around the PTV with margins from 0.5-1.5 cm was performed. IMRT plans were evaluated with respect to isodose distributions, dose-volume histograms (DVHs parameters, homogeneity index (HI, and conformity index (CI. The statistical comparison between the types of plans was done using the One Way ANOVA test.Results: The results showed that IMRT using three or five beams was not sufficient to obtain good dose optimization. The seven field plans showed the best coverage for the PTV with tolerable doses for the OARs, and the beam orientation was very critical. Increasing beams (Bs number from 7 to 13 did not show significant differences in the PTV coverage, while the mean lung dose was increased. The PTV coverage were 95.1, 95.1, 98.1, 97.3, 97.3, 97.3, 97.0, and 97.0% for 3Bs, 5Bs, 7Bs, 9Bs, 13Bs, 7Bs(30, 7Bs(60 (beam angles were changed from 0o to 30o and 60o, and 7Bs(R (seven IMRT plans with ring, respectively. The mean heart dose did not exceed 0.36 Gy with p < 0.05. For lung doses, the best plan was the one with 9Bs which reduced lung volume doses V20Gy (% and V30Gy (%, and reduced mean lung dose from 5.4 to 4.5 Gy with p < 0.05 for 7Bs(R plans. IMRT improved the

  8. Aldehyde dehydrogenase 3B1 (ALDH3B1): immunohistochemical tissue distribution and cellular-specific localization in normal and cancerous human tissues.

    Science.gov (United States)

    Marchitti, Satori A; Orlicky, David J; Brocker, Chad; Vasiliou, Vasilis

    2010-09-01

    Aldehyde dehydrogenase (ALDH) enzymes are critical in the detoxification of endogenous and exogenous aldehydes. Our previous findings indicate that the ALDH3B1 enzyme is expressed in several mouse tissues and is catalytically active toward aldehydes derived from lipid peroxidation, suggesting a potential role against oxidative stress. The aim of this study was to elucidate by immunohistochemistry the tissue, cellular, and subcellular distribution of ALDH3B1 in normal human tissues and in tumors of human lung, colon, breast, and ovary. Our results indicate that ALDH3B1 is expressed in a tissue-specific manner and in a limited number of cell types, including hepatocytes, proximal convoluted tubule cells, cerebellar astrocytes, bronchiole ciliated cells, testis efferent ductule ciliated cells, and histiocytes. ALDH3B1 expression was upregulated in a high percentage of human tumors (lung > breast = ovarian > colon). Increased ALDH3B1 expression in tumor cells may confer a growth advantage or be the result of an induction mechanism mediated by increased oxidative stress. Subcellular localization of ALDH3B1 was predominantly cytosolic in tissues, with the exception of normal human lung and testis, in which localization appeared membrane-bound or membrane-associated. The specificity of ALDH3B1 distribution may prove to be directly related to the functional role of this enzyme in human tissues.

  9. Texture analysis in quantitative MR imaging. Tissue characterisation of normal brain and intracranial tumours at 1.5 T

    DEFF Research Database (Denmark)

    Kjaer, L; Ring, P; Thomsen, C

    1995-01-01

    of common first-order and second-order grey level statistics. Tissue differentiation in the images was estimated by the presence or absence of significant differences between tissue types. A fine discrimination was obtained between white matter, cortical grey matter, and cerebrospinal fluid in the normal...... brain, and white matter was readily separated from the tumour lesions. Moreover, separation of solid tumour tissue and peritumoural oedema was suggested for some tumour types. Mutual comparison of all tumour types revealed extensive differences, and even specific tumour differentiation turned out...

  10. 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.; Rao, J. S.; Rayford, A. R.; Reddy, B. R.; Sears, J.; Thielke, R.; Ulm, M.; Vanderby, R.

    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.

  11. Volume effects of late term normal tissue toxicity in prostate cancer radiotherapy

    Science.gov (United States)

    Bonta, Dacian Viorel

    Modeling of volume effects for treatment toxicity is paramount for optimization of radiation therapy. This thesis proposes a new model for calculating volume effects in gastro-intestinal and genito-urinary normal tissue complication probability (NTCP) following radiation therapy for prostate carcinoma. The radiobiological and the pathological basis for this model and its relationship to other models are detailed. A review of the radiobiological experiments and published clinical data identified salient features and specific properties a biologically adequate model has to conform to. The new model was fit to a set of actual clinical data. In order to verify the goodness of fit, two established NTCP models and a non-NTCP measure for complication risk were fitted to the same clinical data. The method of fit for the model parameters was maximum likelihood estimation. Within the framework of the maximum likelihood approach I estimated the parameter uncertainties for each complication prediction model. The quality-of-fit was determined using the Aikaike Information Criterion. Based on the model that provided the best fit, I identified the volume effects for both types of toxicities. Computer-based bootstrap resampling of the original dataset was used to estimate the bias and variance for the fitted parameter values. Computer simulation was also used to estimate the population size that generates a specific uncertainty level (3%) in the value of predicted complication probability. The same method was used to estimate the size of the patient population needed for accurate choice of the model underlying the NTCP. The results indicate that, depending on the number of parameters of a specific NTCP model, 100 (for two parameter models) and 500 patients (for three parameter models) are needed for accurate parameter fit. Correlation of complication occurrence in patients was also investigated. The results suggest that complication outcomes are correlated in a patient, although

  12. 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.

  13. Validation of Normal Tissue Complication Probability Predictions in Individual Patient: Late Rectal Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Semenenko, Vladimir A., E-mail: vsemenenko@LandauerMP.com [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Tarima, Sergey S. [Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Devisetty, Kiran [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Pelizzari, Charles A.; Liauw, Stanley L. [Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, Illinois (United States)

    2013-03-15

    Purpose: To perform validation of risk predictions for late rectal toxicity (LRT) in prostate cancer obtained using a new approach to synthesize published normal tissue complication data. Methods and Materials: A published study survey was performed to identify the dose-response relationships for LRT derived from nonoverlapping patient populations. To avoid mixing models based on different symptoms, the emphasis was placed on rectal bleeding. The selected models were used to compute the risk estimates of grade 2+ and grade 3+ LRT for an independent validation cohort composed of 269 prostate cancer patients with known toxicity outcomes. Risk estimates from single studies were combined to produce consolidated risk estimates. An agreement between the actuarial toxicity incidence 3 years after radiation therapy completion and single-study or consolidated risk estimates was evaluated using the concordance correlation coefficient. Goodness of fit for the consolidated risk estimates was assessed using the Hosmer-Lemeshow test. Results: A total of 16 studies of grade 2+ and 5 studies of grade 3+ LRT met the inclusion criteria. The consolidated risk estimates of grade 2+ and 3+ LRT were constructed using 3 studies each. For grade 2+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.537 compared with 0.431 for the best-fit single study. For grade 3+ LRT, the concordance correlation coefficient for the consolidated risk estimates was 0.477 compared with 0.448 for the best-fit single study. No evidence was found for a lack of fit for the consolidated risk estimates using the Hosmer-Lemeshow test (P=.531 and P=.397 for grade 2+ and 3+ LRT, respectively). Conclusions: In a large cohort of prostate cancer patients, selected sets of consolidated risk estimates were found to be more accurate predictors of LRT than risk estimates derived from any single study.

  14. Changes of inducible protein-10 and regulated upon activation, normal T cell expressed and secreted protein in acute rejection of pancreas transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    Jun Zhu; Ze-Kuan Xu; Yi Miao; Xun-Liang Liu; Hong Zhang

    2006-01-01

    AIM: To investigate the role of IFN-γ inducible protein -10 (Ip-10) and regulated upon activation, normal T cell expressed and secreted (RANTES) protein in acute pancreatic allograft rejection in rats.METHODS: An experimental pancreas transplantation model was established using diabetic SD rats as the recipient, induced by applying streptozocin (STZ).Pancreas transplantation was performed with a physiologic method of portal venous and enteric drainage. Rats were divided into two groups, isograft group (group A, n = 24) and allograft group (group B, n = 24) in which either healthy SD rats or Wistar rats served as donors, respectively. Twelve diabetic or healthy SD rats were used as controls. At d 1, 4, 7, and 10 post transplantation, serum IP-10 and RANTES were assessed by ELISA and their expression in the allografts was determined by immunohistochemistry.RESULTS: In group B (allograft group), the development of acute rejection was significantly correlated with increased serum concentration and tissue expression of IP-10 and RANTES, with a peak level at d 7 post transplantation. In contrast, there was no obvious change before and after transplantation in group A (isograft group).CONCLUSION: Our study suggests a possible role of IP-10 and RANTES in acute rejection and early monitoring of chemokines may be helpful in predicting the outcome of pancreas transplantation.

  15. 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.

  16. Value of Quantitative Tissue Velocity Imaging in the Detection of Regional Myocardial Function in Dogs with Acute Subendocardial Ischemia

    Institute of Scientific and Technical Information of China (English)

    Qinyyang ZHANG; Youbin DENG; Yani LIU; Haoyi YANG; Bingbing LIU; Weihui SHENTU; Peng LI

    2008-01-01

    This study evaluated the application of quantitative tissue velocity imaging (QTVI) in assessing regional myocardial systolic and diastolic functions in dogs with acute subendocardial ischemia. Animal models of subendocardial ischemia were established by injecting microspheres (about 300 μm in diameter) into the proximal end of left circumflex coronary artery in 11 hybrid dogs through cannulation. Before and after embolization, two-dimensional echocardiography, QTVI and real-time myocardial contrast echocardiography (RT-MCE) via intravenous infusion of self-made microbubbles, were performed, respectively. The systolic segmental wall thickening and subendocardial myocardial longitudinal velocities of risk segments before and after embolization were compared by using paired t analysis. The regional myocardial video intensity versus contrast time could be fitted to an exponential function: y=A-(1-exp-β-t), in which the product of A and β provides a measure of myocardial blood flow. RT-MCE showed that subendocardial normalized A.β was decreased markedly from 0.99±0.19 to 0.35±0.11 (P0.05), the longitudinal peak systolic velocities (Vs) and early-diastolic peak velocities (Ve) recorded by QTVI were declined significantly (P<0.05). Moreover, the subendocardial velocity curves during isovolumic relaxation predominantly showed positive waves, whereas they mainly showed negative waves before the embolization. This study demonstrates that QTVI can more sensitively and accurately detect abnormal regional myocardial function and post-systolic systole causedby acute subendocardial ischemia.

  17. Analysis of normal-tumour tissue interaction in tumours: prediction of prostate cancer features from the molecular profile of adjacent normal cells.

    Directory of Open Access Journals (Sweden)

    Victor Trevino

    Full Text Available Statistical modelling, in combination with genome-wide expression profiling techniques, has demonstrated that the molecular state of the tumour is sufficient to infer its pathological state. These studies have been extremely important in diagnostics and have contributed to improving our understanding of tumour biology. However, their importance in in-depth understanding of cancer patho-physiology may be limited since they do not explicitly take into consideration the fundamental role of the tissue microenvironment in specifying tumour physiology. Because of the importance of normal cells in shaping the tissue microenvironment we formulate the hypothesis that molecular components of the profile of normal epithelial cells adjacent the tumour are predictive of tumour physiology. We addressed this hypothesis by developing statistical models that link gene expression profiles representing the molecular state of adjacent normal epithelial cells to tumour features in prostate cancer. Furthermore, network analysis showed that predictive genes are linked to the activity of important secreted factors, which have the potential to influence tumor biology, such as IL1, IGF1, PDGF BB, AGT, and TGFβ.

  18. External validation of a normal tissue complication probability model for radiation-induced hypothyroidism in an independent cohort

    DEFF Research Database (Denmark)

    Rønjom, Marianne F; Brink, Carsten; Bentzen, Søren M

    2015-01-01

    BACKGROUND: A normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism (RIHT) was previously derived in patients with squamous cell carcinoma of the head and neck (HNSCC) discerning thyroid volume (Vthyroid), mean thyroid dose (Dmean), and latency as predictive...

  19. The early response of p53-dependent proteins during radiotherapy in human rectal carcinoma and in adjacent normal tissue

    NARCIS (Netherlands)

    Stift, A; Prager, G; Selzer, E; Widder, J; Kandioler, D; Friedl, J; Teleky, B; Herbst, F; Wrba, F; Bergmann, M

    2003-01-01

    The aim of this study was to investigate the activation of the p53 pathway and the induction of apoptosis during preoperative radiotherapy in normal human rectal tissue and in rectal carcinoma. Twelve patients with rectal cancer of the lower third were enrolled in this study. Tumor specimens and adj

  20. Gene and protein expression of p53 and p21 in fibroadenomas and adjacent normal mammary tissue.

    Science.gov (United States)

    Schneider, Lolita; Branchini, Gisele; Cericatto, Rodrigo; Capp, Edison; Brum, Ilma Simoni

    2009-02-01

    The aim of this study was to compare p53 and p21 mRNA, and proteins levels between fibroadenomas and adjacent normal mammary tissue of women in reproductive age. A transversal study was performed. Fourteen patients who attended the Breast Service of the Hospital de Clínicas de Porto Alegre were assessed and submitted to surgical resection of fibroadenomas. Fragments of the central area of the fibroadenoma and adjacent normal mammary tissue were obtained. mRNA expression for genes p53 and p21 was evaluated by RT-PCR, and protein expression by the western blot. Paired analyses showed higher gene expression of p53 (P = 0.017) and p21 (P = 0.003), and a higher protein expression of p53 (P = 0.001) in fibroadenomas as compared to normal breast tissue. p21 protein expression was not different (P = 0.97) between the fibroadenoma and the adjacent normal mammary tissue samples. These results suggest the participation of p53 in the formation of fibroadenomas. The role of p21 in fibroadenomas remains to be defined.

  1. Discrimination of prostate cancer from normal peripheral zone and central gland tissue by using dynamic contrast-enhanced MR imaging.

    NARCIS (Netherlands)

    Engelbrecht, M.R.W.; Huisman, H.J.; Laheij, R.J.F.; Jager, G.J.; Leenders, G.J.L.H. van; Hulsbergen-van de Kaa, C.A.; Rosette, J.J.M.H.C. de la; Blickman, J.G.; Barentsz, J.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, pat

  2. Dermatan sulfate domains defined by the novel antibody GD3A12, in normal tissues and ovarian adenocarcinomas.

    NARCIS (Netherlands)

    Dam, G.B. ten; Yamada, S.; Kobayashi, F.; Purushothaman, A.; Westerlo, E.M.A. van de; Bulten, J.; Malmstrom, A.; Sugahara, K.; Massuger, L.F.A.G.; Kuppevelt, A.H.M.S.M. van

    2009-01-01

    Dermatan sulfate (DS) expression in normal tissue and ovarian cancer was investigated using the novel, phage display-derived antibody GD3A12 that was selected against embryonic glycosaminoglycans (GAGs). Antibody GD3A12 was especially reactive with DS rich in IdoA-GalNAc4S disaccharide units. IdoA

  3. Pancreatic stellate cells and CX3CR1: occurrence in normal pancreas and acute and chronic pancreatitis and effect of their activation by a CX3CR1 agonist.

    Science.gov (United States)

    Uchida, Masahiko; Ito, Tetsuhide; Nakamura, Taichi; Hijioka, Masayuki; Igarashi, Hisato; Oono, Takamasa; Kato, Masaki; Nakamura, Kazuhiko; Suzuki, Koichi; Takayanagi, Ryoichi; Jensen, Robert T

    2014-07-01

    Numerous studies suggest important roles of the chemokine, fractalkine (CX3CL1), in acute/chronic pancreatitis; however, the possible mechanisms of the effects are unclear. Pancreatic stellate cells (PSCs) can play important roles in pancreatitis, secreting inflammatory cytokines/chemokines, as well as proliferation. Therefore, we investigated CX3CL1 receptor (CX3CR1) occurrence in normal pancreas and pancreatitis (acute/chronic) tissues and the effects of CX3CL1 on activated PSCs. CX3CR1 expression/localization in normal pancreas and pancreatitis (acute/chronic) tissues was evaluated with immunohistochemical analysis. CX3CR1 expression and effects of CX3CL1 on activated PSCs were examined with real-time polymerase chain reaction, BrdU (5-bromo-2-deoxyuridine) assays, and Western blotting. In normal pancreas, acinar cells expressed CX3CR1 within granule-like formations in the cytoplasm, whereas in acute/chronic pancreatitis, acinar, ductal, and activated PSCs expressed CX3CR1 on cell membranes. With activation of normal PSCs, CX3CR1 is increased. CX3CL1 activated multiple signaling cascades in PSCs. CX3CL1 did not induce inflammatory genes expression in activated PSCs, but induced proliferation. CX3CR1s are expressed in normal pancreas. Expression is increased in acute/chronic pancreatitis, and the CX3CR1s are activated. CX3CL1 induces proliferation of activated PSCs without increasing release of inflammatory mediators. These results suggest that CX3CR1 activation of PSCs could be important in their effects in pancreatitis, especially to PSC proliferation in pancreatitis where CX3CL1 levels are elevated.

  4. Identification of the boundary between normal brain tissue and ischemia region using two-photon excitation fluorescence microscopy

    Science.gov (United States)

    Du, Huiping; Wang, Shu; Wang, Xingfu; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2016-10-01

    Ischemic stroke is one of the common neurological diseases, and it is becoming the leading causes of death and permanent disability around the world. Early and accurate identification of the potentially salvageable boundary region of ischemia brain tissues may enable selection of the most appropriate candidates for early stroke therapies. In this work, TPEF microscopy was used to image the microstructures of normal brain tissues, ischemia regions and the boundary region between normal and ischemia brain tissues. The ischemia brain tissues from Sprague-Dawley (SD) rats were subjected to 6 hours of middle cerebral artery occlusion (MCAO). Our study demonstrates that TPEF microscopy has the ability to not only reveal the morphological changes of the neurons but also identify the boundary between normal brain tissue and ischemia region, which correspond well to the hematoxylin and eosin (H and E) stained images. With the development of miniaturized TPEF microscope imaging devices, TPEF microscopy can be developed into an effectively diagnostic and monitoring tool for cerebral ischemia.

  5. Characterization of acute renal allograft rejection by proteomic analysis of renal tissue in rat.

    Science.gov (United States)

    Chen, Gang; Huang, Jing-Bin; Mi, Jie; He, Yun-Feng; Wu, Xiao-Hou; Luo, Chun-Li; Liang, Si-Min; Li, Jia-Bing; Tang, Ya-Xiong; Li, Jie

    2012-02-01

    Rapid and reliable biomarkers of renal allograft rejection have not been available. This study aimed to investigate biomarkers in renal allograft tissue using proteomic analysis. Orthotopic kidney transplantations were performed using Fisher (F344) or Lewis rats as donors and Lewis rats as recipients. Syngenic control group (Group I) constituted F344-to-F344 orthotopic kidney allo-transplantations (n = 8); and allogenic group (Group II) consisted of F344-to-Lewis orthotopic kidney allo-transplantations (n = 8). Renal tissues were harvested 7 days after transplantation. Samples were analyzed using 2-D electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry. 6 differentially expressed proteins were identified between allogenic group and syngenic control group. A rat model of acute renal allograft rejection was successfully set up. Differentially expressed proteins in renal allograft tissue of rat were detected using proteomic analysis and might serve as novel diagnostic and therapeutic targets in human. Quantitative proteomics, using MALDL-TOF-MS methodology has the potential to provide a profiling and a deeper understanding of acute renal rejection.

  6. Differences in oestrogen receptors in malignant and normal breast tissue as identified by the binding of a new synthetic progestogen.

    OpenAIRE

    Iqbal, M J; Colletta, A. A.; Houmayoun-Valyani, S. D.; Baum, M.

    1986-01-01

    Oestrogen receptor protein (ER) was detected in 9 of 11 samples of malignant breast tissue and 8 of 9 samples of normal breast tissue. Levels of cytosolic ER (ERc) in malignant breast were 21-1102 fmol mg-1 soluble protein (Kd 1.8 X 10(-9)-3.1 X 10(-8) mol l-1) and those of nucleosolic ER (ERn), 13-526 fmol mg-1 soluble protein (Kd 2.1 X 10(-9)-1.4 X 10(-8) mol l-1). In normal breast tissue ERc levels were 33-640 fmol mg-1 soluble protein (Kd 1.3 X 10(-10)-3.2 X 10(-9) mol l-1), ERn was detec...

  7. The use of Compton scattering to differentiate between classifications of normal and diseased breast tissue

    Energy Technology Data Exchange (ETDEWEB)

    Ryan, Elaine A; Farquharson, Michael J; Flinton, David M [School of Allied Health Sciences, City University, Charterhouse Square, London EC1M 6PA (United Kingdom)

    2005-07-21

    This study describes a technique for measuring the electron density of breast tissue utilizing Compton scattered photons. The K{sub {alpha}}{sub 2} line from a tungsten target industrial x-ray tube (57.97 keV) was used and the scattered x-rays collected at an angle of 30{sup 0}. At this angle the Compton and coherent photon peaks can be resolved using an energy dispersive detector and a peak fitting algorithm. The system was calibrated using solutions of known electron density. The results obtained from a pilot study of 22 tissues are presented. The tissue samples investigated comprise four different tissue classifications: adipose, malignancy, fibroadenoma and fibrocystic change (FCC). It is shown that there is a difference between adipose and malignant tissue, to a value of 9.0%, and between adipose and FCC, to a value of 12.7%. These figures are found to be significant by statistical analysis. The differences between adipose and fibroadenoma tissues (2.2%) and between malignancy and FCC (3.4%) are not significant. It is hypothesized that the alteration in glucose uptake within malignant cells may cause these tissues to have an elevated electron density. The fibrotic nature of tissue that has undergone FCC gives the highest measure of all tissue types.

  8. The use of Compton scattering to differentiate between classifications of normal and diseased breast tissue

    Science.gov (United States)

    Ryan, Elaine A.; Farquharson, Michael J.; Flinton, David M.

    2005-07-01

    This study describes a technique for measuring the electron density of breast tissue utilizing Compton scattered photons. The Kα2 line from a tungsten target industrial x-ray tube (57.97 keV) was used and the scattered x-rays collected at an angle of 30°. At this angle the Compton and coherent photon peaks can be resolved using an energy dispersive detector and a peak fitting algorithm. The system was calibrated using solutions of known electron density. The results obtained from a pilot study of 22 tissues are presented. The tissue samples investigated comprise four different tissue classifications: adipose, malignancy, fibroadenoma and fibrocystic change (FCC). It is shown that there is a difference between adipose and malignant tissue, to a value of 9.0%, and between adipose and FCC, to a value of 12.7%. These figures are found to be significant by statistical analysis. The differences between adipose and fibroadenoma tissues (2.2%) and between malignancy and FCC (3.4%) are not significant. It is hypothesized that the alteration in glucose uptake within malignant cells may cause these tissues to have an elevated electron density. The fibrotic nature of tissue that has undergone FCC gives the highest measure of all tissue types.

  9. 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%.

  10. Normalization of gene expression measurement of tissue samples obtained by transurethral resection of bladder tumors

    Directory of Open Access Journals (Sweden)

    Pop LA

    2016-06-01

    Full Text Available Laura A Pop,1,* Valentina Pileczki,1,2,* Roxana M Cojocneanu-Petric,1 Bogdan Petrut,3,4 Cornelia Braicu,1 Ancuta M Jurj,1 Rares Buiga,5 Patriciu Achimas-Cadariu,6,7 Ioana Berindan-Neagoe1,8 1The Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; 2Department of Analytical Chemistry, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; 3Department of Surgery II – Urology, The Oncology Institute “Prof Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania; 4Department of Urology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Cluj, Romania; 5Department of Pathology, The Oncology Institute “Prof. Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania; 6Department of Surgery, The Oncology Institute “Prof Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania; 7Department of Surgical Oncology and Gynecological Oncology, Iuliu Haţieganu University of Medicine and Pharmacy, 8Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof Dr Ion Chiricuţă”, Cluj-Napoca, Cluj, Romania *These authors contributed equally to this work Background: Sample processing is a crucial step for all types of genomic studies. A major challenge for researchers is to understand and predict how RNA quality affects the identification of transcriptional differences (by introducing either false-positive or false-negative errors. Nanotechnologies help improve the quality and quantity control for gene expression studies. Patients and methods: The study was performed on 14 tumor and matched normal pairs of tissue from patients with bladder urothelial carcinomas. We assessed the RNA quantity by using the NanoDrop spectrophotometer and the quality by nano-microfluidic capillary electrophoresis technology provided by Agilent 2100 Bioanalyzer. We evaluated the amplification status of three

  11. Repair of acutely injured spinal cord through constructing tissue-engineered neural complex in adult rats

    Institute of Scientific and Technical Information of China (English)

    PU Yu; GUO Qing-shan; WANG Ai-min; WU Si-yu; XING Shu-xing; ZHANG Zhong-rong

    2007-01-01

    Objective: To construct tissue-engineered neural complex in vitro and study its effect in repairing acutely injured spinal cord in adult rats. Methods: Neural stem cells were harvested from the spinal cord of embryo rats and propagated in vitro. Then the neural stem cells were seeded into polyglycolic acid scaffolds and co-cultured with extract of embryonic spinal cord in vitro. Immunofluorescence histochemistry and scanning electron microscope were used to observe the microstructure of this complex. Animal model of spine semi-transection was made and tissue-engineered neural complex was implanted by surgical intervention. Six weeks after transplantation, functional evaluation and histochemistry were applied to evaluate the functional recovery and anatomic reconstruction. Results: The tissue-engineered neural complex had a distinct structure, which contained neonatal neurons, oligodendrocytes and astrocytes. After tissue-engineered neural complex was implanted into the injured spinal cord, the cell components such as neurons, astrocytes and oligodendrocytes, could survive and keep on developing. The adult rats suffering from spinal cord injury got an obvious neurological recovery in motor skills. Conclusions: The tissue-engineered neural complex appears to have therapeutic effects on the functional recovery and anatomic reconstruction of the adult rats with spinal cord injury.

  12. Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Kevin L., E-mail: kevinmoore@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Schmidt, Rachel [Department of Physics, Fort Hays State University, Hays, Kansas (United States); Moiseenko, Vitali [Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California (United States); Olsen, Lindsey A.; Tan, Jun [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States); Xiao, Ying; Galvin, James [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Pugh, Stephanie [NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States); Seider, Michael J. [Akron City Hospital, Akron, Ohio (United States); Dicker, Adam P. [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Bosch, Walter; Michalski, Jeff; Mutic, Sasa [Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri (United States)

    2015-06-01

    Purpose: The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol. Methods and Materials: A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH{sub 0126,top10%}). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed “high-quality,” “low-quality,” and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol. Results: Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH{sub 0126,top10%} to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the

  13. Sparing of normal tissues with volumetric arc radiation therapy for glioblastoma: single institution clinical experience.

    Science.gov (United States)

    Briere, Tina Marie; McAleer, Mary Frances; Levy, Lawrence B; Yang, James N

    2017-05-02

    Patients with glioblastoma multiforme (GBM) require radiotherapy as part of definitive management. Our institution has adopted the use of volumetric arc therapy (VMAT) due to superior sparing of the adjacent organs at risk (OARs) compared to intensity modulated radiation therapy (IMRT). Here we report our clinical experience by analyzing target coverage and sparing of OARs for 90 clinical treatment plans. VMAT and IMRT patient cohorts comprising 45 patients each were included in this study. For all patients, the planning target volume (PTV) received 50 Gy in 30 fractions, and the simultaneous integrated boost PTV received 60 Gy. The characteristics of the two patient cohorts were examined for similarity. The doses to target volumes and OARs, including brain, brainstem, hippocampi, optic nerves, eyes, and cochleae were then compared using statistical analysis. Target coverage and normal tissue sparing for six patients with both clinical IMRT and VMAT plans were analyzed. PTV coverage of at least 95% was achieved for all plans, and the median mean dose to the boost PTV differed by only 0.1 Gy between the IMRT and VMAT plans. Superior sparing of the brainstem was found with VMAT, with a median difference in mean dose being 9.4 Gy. The ipsilateral cochlear mean dose was lower by 19.7 Gy, and the contralateral cochlea was lower by 9.5 Gy. The total treatment time was reduced by 5 min. The difference in the ipsilateral hippocampal D100% was 12 Gy, though this is not statistically significant (P = 0.03). VMAT for GBM patients can provide similar target coverage, superior sparing of the brainstem and cochleae, and be delivered in a shorter period of time compared with IMRT. The shorter treatment time may improve clinical efficiency and the quality of the treatment experience. Based on institutional clinical experience, use of VMAT for the treatment of GBMs appears to offer no inferiority in comparison to IMRT and may offer distinct advantages, especially for

  14. Levels of interleukin-6, superoxide dismutase and malondialdehyde in the lung tissue of a rat model of hypoxia-induced acute pulmonary edema

    Science.gov (United States)

    GAO, HENGBO; TIAN, YINGPING; WANG, WEI; YAO, DONGQI; ZHENG, TUOKANG; MENG, QINGBING

    2016-01-01

    The present study aimed to investigate the levels of malondialdehyde (MDA), superoxide dismutase (SOD) and interleukin (IL)-6 in the lung tissue of a rat model of acute pulmonary edema induced by acute hypoxia, and its pathophysiological significance. A total of 48 adult Wistar rats were randomly divided into group A, a normal group; group B, a model of acute pulmonary edema induced by hypoxia for 24 h; group C, a model of acute pulmonary edema induced by hypoxia for 48 h; and group D, a model of acute pulmonary edema induced by hypoxia for 72 h. The rats in groups B-D were intraperitoneally injected with 6% ammonium chloride to establish the model of acute pulmonary edema, and were subsequently sacrificed following successful modeling for 24, 48 and 72 h. The plasma of rats was isolated and the lungs of the rats were removed. Subsequently, a 10% lung homogenate was prepared and the contents and the activities of MDA, SOD and IL-6 in the lung tissue and IL-6 in the plasma were detected by enzyme-linked immunosorbent assay. MDA and IL-6 expression levels increased and SOD activity decreased in the lung tissue in group B as compared with group A; however the difference did not reach significance (P>0.05). MDA, IL-6 and SOD levels in the lung tissue of rats were significantly altered following the increased duration of pulmonary edema in groups C and D, as compared group A (P<0.05). The plasma IL-6 levels of the rats in groups B-D significantly increased, as compared with those in group A (P<0.05). In conclusion, the results of the present study demonstrated that the incidence of acute pulmonary edema may be associated with oxidative stress. Furthermore, decreased antioxidant capacity and increased free radical levels may be associated with pulmonary edema, as in the present study the levels of IL-6, SOD and MDA in the lung tissue were observed to be associated with the pathological changes of the disease. PMID:26998026

  15. The sodium iodide symporter (NIS) and potential regulators in normal, benign and malignant human breast tissue.

    LENUS (Irish Health Repository)

    Ryan, James

    2011-01-01

    The presence, relevance and regulation of the Sodium Iodide Symporter (NIS) in human mammary tissue remains poorly understood. This study aimed to quantify relative expression of NIS and putative regulators in human breast tissue, with relationships observed further investigated in vitro.

  16. Viable group A streptococci in macrophages during acute soft tissue infection.

    Directory of Open Access Journals (Sweden)

    Pontus Thulin

    2006-03-01

    Full Text Available Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells.We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria.This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections

  17. Viable Group A Streptococci in Macrophages during Acute Soft Tissue Infection.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells. METHODS AND FINDINGS: We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria. CONCLUSIONS: This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis

  18. Tissue Doppler echocardiography predicts acute myocardial infarction, heart failure, and cardiovascular death in the general population

    DEFF Research Database (Denmark)

    Mogelvang, Rasmus; Biering-Sørensen, Tor; Jensen, Jan Skov

    2015-01-01

    AIMS: To improve risk prediction of cardiovascular morbidity and mortality, we need sensitive markers of cardiac dysfunction; Echocardiographic Tissue Doppler Imaging (TDI) is feasible and harmless and may be ideal for this purpose. METHODS AND RESULTS: Within the community-based Copenhagen City...... by TDI was associated with increased risk of the combined end point, even in the subgroup of persons with a normal conventional echocardiographic examination [per 1 cm/s decrease: s': HR 1.32 (1.12-1.57), P ... in persons with a normal conventional echocardiographic examination....

  19. Prognostic value of immunophenotyping and gene mutations in elderly patients with acute myeloid leukemia with normal karyotype.

    Science.gov (United States)

    Dang, Harry; Jiang, Allan; Kamel-Reid, Suzanne; Brandwein, Joseph; Chang, Hong

    2013-01-01

    Elderly patients with acute myeloid leukemia generally have a poor prognosis and a highly heterogeneous clinical outcome. Prognostic indicators are required for and aid in patient stratification. However, the prognostic value of genetic mutations and immunophenotypic features in elderly normal karyotype acute myeloid leukemia, the largest cytogenetic risk group, remains unclear. We investigated the genetic mutations NPM1, FLT3-ITD, and FLT3-TKD and expression of the membrane antigens CD7, CD15, CD34, and CD56 in 144 elderly patients with de novo normal karyotype acute myeloid leukemia to retrospectively analyze the prognostic and clinical relevance of these parameters. CD7, CD15, CD34, and CD56 were expressed in 24%, 47%, 52%, and 15% of patients, respectively. NPM1 and FLT3-ITD mutations were detected in 51% and 17% of patients, respectively. Complete remission was obtained in 94 patients (65%), and the median overall survival was 16.5 months. Univariate analysis detected 5 markers with prognostic relevance: high leukocyte count, FLT3-ITD mutations, NPM1 mutations, CD34 expression, and CD56 expression in acute myeloid leukemia blasts. In multivariate analysis, patients with NPM1 predicted a higher complete remission (CR) rate (P = .016), longer event-free survival (P = .008), and longer overall survival (P = .049). FLT3-ITD mutations predicted a shorter event-free survival (P = .002) and shorter overall survival (P acute myeloid leukemia. By combining genetic and immunophenotypic markers, we can divide patients into distinct prognostic groups with important implications for prognostic stratification and risk-adapted therapy.

  20. Acute exercise increases adipose tissue interstitial adiponectin concentration in healthy overweight and lean subjects

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Rosenzweig, Mary; Dela, Flemming

    2007-01-01

    OBJECTIVE: We studied how an acute bout of exercise influences expression and concentration of adiponectin and regulators of adiponectin in adipose tissue and plasma. DESIGN AND METHODS: Eight overweight and eight lean males were examined by large-pore microdialysis in s.c. abdominal adipose tissue...... increased the SCAAT interstitial adiponectin concentration in both overweight and lean subjects and concentrations did not differ between groups. Plasma adiponectin did not increase during exercise and was similar in overweight and lean subjects. Adiponectin mRNA in SCAAT decreased during exercise...... and was similar in overweight and lean subjects. Surprisingly, the interstitial adiponectin concentration in SCAAT was only 20% of the plasma concentration. SCAAT interleukin-6 (IL-6) microdialyzate and plasma concentrations and SCAAT IL-6 mRNA increased during exercise in both groups. Tumor necrosis factor- (TNF...

  1. Comparison of salbutamol with normal saline and salbutamol with magnesium sulphate in the treatment of severe acute asthma.

    Science.gov (United States)

    Ahmed, S; Sutradhar, S R; Miah, A H; Bari, M A; Hasan, M J; Alam, M K; Tariquzzaman, M; Sarker, C N

    2013-01-01

    This study compared the efficacy and safety of nebulized magnesium sulphate with salbutamol to normal saline with salbutamol as the initial treatment of severe acute asthma patients. The present study was designed as a randomized open controlled clinical trial. The study was conducted Mymensingh Medical College Hospital over a period of 11 months from December 2009 to October 2010. Patients admitted with severe acute asthma having inclusion criteria were the study population. Among 120 study population 60 were in salbutamol with magnesium sulphate group and 60 were in salbutamol with normal saline group. The study finding showed that peak flow at baseline was similar in two groups. At 10 minutes after nebulization, the mean±SD percentage increase in peak flow was greater in magnesium sulphate group (20±4%) than in the normal saline salbutamol group (13±3%). At 20 minutes the percentage increase in peak flow was greater in magnesium sulphate group (35±7%) than in the normal saline salbutamol group (24±6%) p value salbutamol group reached PEF near to 60% which is not in saline salbutamol group. There was no significant changed in respiratory rate, pulse rate, systolic, diastolic blood pressure and clinical evidence of unwanted adverse effect.

  2. EXPRESSION OF PEDF mRNA AND PROTEIN IN NORMAL MOUSE RETINA AND EXPERIMENTAL CHOROIDAL NEO-VASCULARIZATION TISSUES

    Institute of Scientific and Technical Information of China (English)

    张雷; 王康孙; 王玲; 张士胜; 石海云

    2004-01-01

    Objective To study the expression of pigment epithelium derived factor ( PEDF) in normal mouse retina and experimental choroidal neovascularization (CNV) tissues. Methods CNV mouse models were induced by diode laser. The expression of PEDF mRNA and protein in normal mouse retina and CNV tissues were detected by in situ hybridization and immunohistochemical study. Results In normal mouse retina,PEDF mRNA was observed in the ganglion cell layer, inner nuclear layer and RPE cell layer, and PEDF protein was observed mainly in the nerve fiber layer, ganglion cell layer, photoreceptor cell layer and RPE cell layer, and lower level expression of PEDF protein was also observed in the inner plexiform layer and outer plexiform layer. In CNV tissues,the expression of PEDF mRNA and protein was also observed. 3d and 1 week after photocoagulation, the expression level of PEDF was relatively lower, and increased following the development of CNV. The level was the highest 2 weeks after photocoagulation, then decreased at 3 weeks. Conclusion PEDF was expressed in different layers of retina and was obviously expressed in the CNV tissues induced by laser photocoagulation. These findings suggest that PEDF may participate and modulate the development of CNV.

  3. Evaluation of discoidin domain receptor-2 (DDR2) expression level in normal, benign, and malignant human prostate tissues.

    Science.gov (United States)

    Azemikhah, Mitra; Ashtiani, Hamidreza Ahmadi; Aghaei, Mahmoud; Rastegar, Hosein

    2015-01-01

    Discoidin domain receptor (DDR) is a new member of the receptor tyrosine kinase family. There are two isoforms of discoidin domain receptor (DDR), DDR1 and DDR2. These receptors play a major role in the adhesion, motility and cell proliferation. Due to the important role of DDR2 in the development of tumor extension, this receptor is pivotal in the field of carcinogenesis. The aim of this study was to investigate the mRNA and protein expression of DDR2, in the malignant, benign prostatic hyperplasia (BPH) and normal tissues of patients with prostate cancer. In this study the gene and protein expression of DDR2 in adjacent normal (n=40), BPH (n=40), and malignant (n=40) prostate tissue were measured using real-time PCR and Western blotting. Then, the correlation of DDR2 gene and protein expression with prognostic factors such as age, tumor grade, tumor stage, lymph node involvement, and serum prostate-specific antigen (PSA) concentration were evaluated. The relative mRNA and protein expression level of DDR2 in malignant and benign prostate tissue was significantly higher than those of adjacent normal tissues (PDDR2 mRNA and protein expression with prognostic factors such as tumor grade, stage, lymph node involvement, and serum PSA concentration. However, significant correlation with age was not observed. These findings suggest that DDR2 is a cancer-related gene associated with the aggressive progression of prostate cancer patients.

  4. 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.

  5. Automated prediction of tissue outcome after acute ischemic stroke in computed tomography perfusion images

    Science.gov (United States)

    Vos, Pieter C.; Bennink, Edwin; de Jong, Hugo; Velthuis, Birgitta K.; Viergever, Max A.; Dankbaar, Jan Willem

    2015-03-01

    Assessment of the extent of cerebral damage on admission in patients with acute ischemic stroke could play an important role in treatment decision making. Computed tomography perfusion (CTP) imaging can be used to determine the extent of damage. However, clinical application is hindered by differences among vendors and used methodology. As a result, threshold based methods and visual assessment of CTP images has not yet shown to be useful in treatment decision making and predicting clinical outcome. Preliminary results in MR studies have shown the benefit of using supervised classifiers for predicting tissue outcome, but this has not been demonstrated for CTP. We present a novel method for the automatic prediction of tissue outcome by combining multi-parametric CTP images into a tissue outcome probability map. A supervised classification scheme was developed to extract absolute and relative perfusion values from processed CTP images that are summarized by a trained classifier into a likelihood of infarction. Training was performed using follow-up CT scans of 20 acute stroke patients with complete recanalization of the vessel that was occluded on admission. Infarcted regions were annotated by expert neuroradiologists. Multiple classifiers were evaluated in a leave-one-patient-out strategy for their discriminating performance using receiver operating characteristic (ROC) statistics. Results showed that a RandomForest classifier performed optimally with an area under the ROC of 0.90 for discriminating infarct tissue. The obtained results are an improvement over existing thresholding methods and are in line with results found in literature where MR perfusion was used.

  6. Interstitial fluid pressure: A novel biomarker to monitor photo-induced drug uptake in tumor and normal tissues.

    Science.gov (United States)

    Cavin, Sabrina; Wang, Xingyu; Zellweger, Matthieu; Gonzalez, Michel; Bensimon, Michaël; Wagnières, Georges; Krueger, Thorsten; Ris, Hans-Beat; Gronchi, Fabrizio; Perentes, Jean Y

    2017-10-01

    Low-dose photodynamic therapy PDT (photoinduction) can modulate tumor vessels and enhance the uptake of liposomal cisplatin (Lipoplatin®) in pleural malignancies. However, the photo-induction conditions must be tightly controlled as overtreatment shuts down tumor vessels and enhances normal tissue drug uptake. In a pleural sarcoma and adenocarcinoma rat model (n = 12/group), we applied photoinduction (0.0625 mg/kg Visudyne®, 10 J/cm(2) ) followed by intravenous Lipoplatin® (5 mg/kg) administration. Tumor and normal tissue IFP were assessed before and up to 1 hour following photoinduction. Lipoplatin® uptake was determined 60 minutes following photoinduction. We then treated the pleura of tumor-free minipigs with high dose photodynamic therapy (PDT) (0.0625 mg/kg Visudyne®, 30 J/cm(2) , n = 5) followed by Lipoplatin (5 mg/kg) administration. In rodents, photoinduction resulted in a significant decrease of IFP (P parabola. In minipigs, high dose photodynamic treatment resulted in pleural IFP increase of some animals which predicted higher Lipoplatin® uptake levels. Normal and tumor vasculatures react differently to PDT. Continuous IFP monitoring in normal and tumor tissues is a promising biomarker of vessel photoinduction. Moderate drop in tumor with no change in normal tissue IFP are predictive of specific Lipoplatin® uptake by cancer following PDT. Lasers Surg. Med. 49:773-780, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Analysis of the Genetic Phylogeny of Multifocal Prostate Cancer Identifies Multiple Independent Clonal Expansions in Neoplastic and Morphologically Normal Prostate Tissue

    OpenAIRE

    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

    2015-01-01

    Whole genome 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 on-going abnormal mutational pr...

  8. Flow cytometric determination of stem/progenitor content in epithelial tissues: an example from nonsmall lung cancer and normal lung.

    Science.gov (United States)

    Donnenberg, Vera S; Landreneau, Rodney J; Pfeifer, Melanie E; Donnenberg, Albert D

    2013-01-01

    Single cell analysis and cell sorting has enabled the study of development, growth, differentiation, repair and maintenance of "liquid" tissues and their cancers. The application of these methods to solid tissues is equally promising, but several unique technical challenges must be addressed. This report illustrates the application of multidimensional flow cytometry to the identification of candidate stem/progenitor populations in non-small cell lung cancer and paired normal lung tissue. Seventeen paired tumor/normal lung samples were collected at the time of surgical excision and processed immediately. Tissues were mechanically and enzymatically dissociated into single cell suspension and stained with a panel of antibodies used for negative gating (CD45, CD14, CD33, glycophorin A), identification of epithelial cells (intracellular cytokeratin), and detection of stem/progenitor markers (CD44, CD90, CD117, CD133). DAPI was added to measure DNA content. Formalin fixed paraffin embedded tissue samples were stained with key markers (cytokeratin, CD117, DAPI) for immunofluorescent tissue localization of populations detected by flow cytometry. Disaggregated tumor and lung preparations contained a high proportion of events that would interfere with analysis, were they not eliminated by logical gating. We demonstrate how inclusion of doublets, events with hypodiploid DNA, and cytokeratin+ events also staining for hematopoietic markers reduces the ability to quantify epithelial cells and their precursors. Using the lung cancer/normal lung data set, we present an approach to multidimensional data analysis that consists of artifact removal, identification of classes of cells to be studied further (classifiers) and the measurement of outcome variables on these cell classes. The results of bivariate analysis show a striking similarity between the expression of stem/progenitor markers on lung tumor and adjacent tumor-free lung.

  9. 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.

  10. Brain-derived neurotrophic factor expression is higher in brain tissue from patients with refractory epilepsy than in normal controls

    Institute of Scientific and Technical Information of China (English)

    Yudan Lv; Jiqing Qiu; Zan Wang; Li Cui; Hongmei Meng; Weihong Lin

    2011-01-01

    The role of the brain-derived neurotrophic factor in epilepsy remains controversial. The present study utilized light and electron microscopy to investigate pathological and ultrastructural changes in brain tissue obtained from the seizure foci of 24 patients with temporal epilepsy. We found that epileptic tissue showed neuronal degeneration, glial cell proliferation, nuclear vacuolization, and neural cell tropism. Immunoelectron microscopy and immunohistochemistry showed that brain-derived neurotrophic factor was expressed at significantly higher levels in patients with refractory temporal epilepsy compared with normal controls, demonstrating that the pathological changes within seizure foci in patients with refractory epilepsy are associated with brain-derived neurotrophic factor expression alterations.

  11. Validation of coded aperture coherent scatter spectral imaging for normal and neoplastic breast tissues via surgical pathology

    Science.gov (United States)

    Morris, R. E.; Albanese, K. E.; Lakshmanan, M. N.; McCall, S. J.; Greenberg, J. A.; Kapadia, A. J.

    2016-03-01

    This study intends to validate the sensitivity and specificity of coded aperture coherent scatter spectral imaging (CACSSI) by comparison to standard histological preparation and pathologic analysis methods used to differentiate normal and neoplastic breast tissues. A composite overlay of the CACSSI rendered image and pathologist interpreted stained sections validate the ability of CACSSI to differentiate normal and neoplastic breast structures ex-vivo. Via comparison to pathologist annotated slides, the CACSSI system may be further optimized to maximize sensitivity and specificity for differentiation of breast carcinomas.

  12. Identification of Patient Benefit From Proton Therapy for Advanced Head and Neck Cancer Patients Based on Individual and Subgroup Normal Tissue Complication Probability Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jakobi, Annika, E-mail: Annika.Jakobi@OncoRay.de [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Bandurska-Luque, Anna [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Department of Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden (Germany); Stützer, Kristin; Haase, Robert; Löck, Steffen [OncoRay-National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Wack, Linda-Jacqueline [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); Mönnich, David [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); German Cancer Research Center, Heidelberg (Germany); German Cancer Consortium, Tübingen (Germany); Thorwarth, Daniela [Section for Biomedical Physics, University Hospital for Radiation Oncology, Eberhard Karls Universät Tübingen (Germany); and others

    2015-08-01

    Purpose: The purpose of this study was to determine, by treatment plan comparison along with normal tissue complication probability (NTCP) modeling, whether a subpopulation of patients with head and neck squamous cell carcinoma (HNSCC) could be identified that would gain substantial benefit from proton therapy in terms of NTCP. Methods and Materials: For 45 HNSCC patients, intensity modulated radiation therapy (IMRT) was compared to intensity modulated proton therapy (IMPT). Physical dose distributions were evaluated as well as the resulting NTCP values, using modern models for acute mucositis, xerostomia, aspiration, dysphagia, laryngeal edema, and trismus. Patient subgroups were defined based on primary tumor location. Results: Generally, IMPT reduced the NTCP values while keeping similar target coverage for all patients. Subgroup analyses revealed a higher individual reduction of swallowing-related side effects by IMPT for patients with tumors in the upper head and neck area, whereas the risk reduction of acute mucositis was more pronounced in patients with tumors in the larynx region. More patients with tumors in the upper head and neck area had a reduction in NTCP of more than 10%. Conclusions: Subgrouping can help to identify patients who may benefit more than others from the use of IMPT and, thus, can be a useful tool for a preselection of patients in the clinic where there are limited PT resources. Because the individual benefit differs within a subgroup, the relative merits should additionally be evaluated by individual treatment plan comparisons.

  13. Morphometric analyses of normal pediatric brachial biceps and quadriceps muscle tissue

    National Research Council Canada - National Science Library

    Sallum, Adriana M E; Varsani, Hemlata; Holton, Janice L; Marie, Suely K N; Wedderburn, Lucy R

    2013-01-01

    Pediatric normal brachial biceps (14 specimens) and quadriceps muscles (14 specimens) were studied by immunohistochemistry to quantify fiber-type, diameter and distribution, capillary density, presence of inflammatory cells...

  14. Signaling proteins are represented in tissue fluid/lymph from soft tissues of normal human legs at concentrations different from serum.

    Science.gov (United States)

    Zaleska, Marzanna; Olszewski, Waldemar L; Durlik, Marek; Miller, Norman E

    2013-12-01

    The mobile intercellular fluid flowing to and in the lymphatics contains filtered plasma products and substances synthesized and excreted by tissue cells. Among them are signaling proteins such as cytokines, chemokines, enzymes, and growth factors. They act locally in autocrine and paracrine systems regulating cell metabolism, proliferation, and formation of the ground matrix. They play an immunoregulatory role in infections, wound healing, and tumor cell growth. In this study we measured the concentration of selected cytokines, chemokines, tissue enzymes, and growth factors in tissue fluid/lymph drained from normal human leg soft tissues. Legs exposed to infections and trauma often result in development of lymphedema. Lymph was drained from superficial calf lymphatics using microsurgical techniques. Our studies showed generally higher concentrations of cytokines, chemokines, enzymes, and growth factors in lymph than in serum. The total protein L/S ratio was 0.22, whereas that of various lymph signaling proteins ranged between 1 and 10. This indicates that in addition to proteins filtered from blood, local cells contribute to lymph concentration by own production, depending on the actual cell requirement. Moreover, there were major individual differences of lymph levels with simultaneous stable serum levels. This suggests existence of a local autonomous regulatory humoral mechanism in tissues, not reflected in serum.

  15. Label-free imaging of basement membranes differentiates normal, precancerous, and cancerous colonic tissues by second-harmonic generation microscopy.

    Science.gov (United States)

    Zhuo, Shuangmu; Yan, Jun; Chen, Gang; Shi, Hong; Zhu, Xiaoqin; Lu, Jianping; Chen, Jianxin; Xie, Shusen

    2012-01-01

    Since changes in the basement membranes are the critical indicators for differentiating normal, precancerous, and cancerous colonic tissues, direct visualization of these warning signs is essential for the early diagnosis and treatment of colonic cancer. Here, we present that second harmonic generation (SHG) microscopy can probe the changes of basement membranes in different colonic cancer stages. Our results also show the capability of using the quantitative analyses of images for quantifying these changes in different cancer stages. These results suggest that SHG microscopy has the potential in label-freely imaging the changes of basement membranes for effectively distinguishing between normal, precancerous, and cancerous colonic tissues. To our knowledge, this is the first demonstration of the dynamics of basement membrane changes in different colonic cancer stages using entirely intrinsic source of contrast.

  16. Defining acute ischemic stroke tissue pathophysiology with whole brain CT perfusion.

    Science.gov (United States)

    Bivard, A; Levi, C; Krishnamurthy, V; Hislop-Jambrich, J; Salazar, P; Jackson, B; Davis, S; Parsons, M

    2014-12-01

    This study aimed to identify and validate whole brain perfusion computed tomography (CTP) thresholds for ischemic core and salvageable penumbra in acute stroke patients and develop a probability based model to increase the accuracy of tissue pathophysiology measurements. One hundred and eighty-three patients underwent multimodal stroke CT using a 320-slice scanner within 6hours of acute stroke onset, followed by 24hour MRI that included diffusion weighted imaging (DWI) and dynamic susceptibility weighted perfusion imaging (PWI). Coregistered acute CTP and 24hour DWI was used to identify the optimum single perfusion parameter thresholds to define penumbra (in patients without reperfusion), and ischemic core (in patients with reperfusion), using a pixel based receiver operator curve analysis. Then, these results were used to develop a sigma curve fitted probability based model incorporating multiple perfusion parameter thresholds. For single perfusion thresholds, a time to peak (TTP) of +5seconds best defined the penumbra (area under the curve, AUC 0.79 CI 0.74-0.83) while a cerebral blood flow (CBF) of acute ischemic core (AUC 0.73, CI 0.69-0.77). The probability model was more accurate at detecting the ischemic core (AUC 0.80 SD 0.75-0.83) and penumbra (0.85 SD 0.83-0.87) and was significantly closer in volume to the corresponding reference DWI (P=0.031). Whole brain CTP can accurately identify penumbra and ischemic core using similar thresholds to previously validated 16 or 64 slice CTP. Additionally, a novel probability based model was closer to defining the ischemic core and penumbra than single thresholds. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Histopathologic changes in soft tissue associated with radiographically normal impacted third molars

    Directory of Open Access Journals (Sweden)

    Kotrashetti Vijayalakshmi

    2010-01-01

    Full Text Available Background: The incidence of impacted or embedded third molars accounts for approximately 98%. Since 1948, there are studies reporting pathological changes in an asymptomatic dental follicle. Controversy still exists for removal of asmptomatic impacted teeth. Hence, this study was performed to histologically evaluate soft tissue pathosis in the pericoronal tissues of impacted third molars with pericoronal radiolucency measuring up to 2.5 mm on orthopantomographs. Materials and Methods: Forty-one asymptomatic impacted third molars with follicular space of up to 2.5 mm on radiographs were included. The disimpacted teeth and the follicular tissues were obtained for histological examination. Results: Age of the patients ranged from 14 to 25 years. Of 41 tissues evaluated, histopathological reports of 18 follicles were suggestive of dentigerous cyst, two follicles showed odontogenic keratocyst, one follicle each of calcifying epithelial odontogenic cyst, ameloblastoma-like proliferation, odontogenic myxoma and odontogenic fibroma. Conclusion: This study showed 58.5% of asymptomatic cases with definite pathological changes. Hence, thorough clinical and radiographic examination should be carried out for all impacted third molars and the dental follicular tissue should be submitted for histopathological evaluation.

  18. Early changes of volume and spatial location in target and normal tissues caused by IMRT for cervical cancer.

    Science.gov (United States)

    Chen, Jianwu; Liu, Ping; Chen, Wenjuan; Bai, Penggang; Li, Jiangshan; Ni, Xiaolei; Chen, Kaiqiang; Li, Qixin

    2016-12-01

    To investigate the early changes of volume and spatial location in target and normal tissues caused by intensity-modulated radiotherapy (IMRT) for cervical cancer. Forty patients with cervical cancer were included in this study and treated by IMRT. Computed tomography (CT) was performed before radiotherapy and when the patient had received 27 Gy in 15 fractions. After image registration, the volume of interest (VOI) for the targets and organs at risk was delineated by clinicians on the CT images. Changes of volume, spatial location and Dice similarity were calculated for all VOIs. There were significant changes in gross tumor volume (GTV) in the primary tumor (GTV-T) with t = 8.304 (p<0.01) and visible pelvic lymph nodes (GTV-N) with t = 4.996 (p<0.01) caused by IMRT. The mean volume differences for GTV-T and GTV-N were 38.64% ± 19.50% (range 3.16%-86.49%) and 42.49% ± 25.68% (range 2.79%-87.42%), respectively. Among the organs at risk, the bladder had the greatest volume change with 55.13% ± 33.40% (range 3.25%-116.01%). The Dice similarity for GTV-T and GTV-N was 0.50 ± 0.18 (range 0.10-0.85) and 0.31 ± 0.20 (range 0.00-0.71), respectively. The rectum had the least Dice similarity among the normal tissues, with a mean value of 0.57 ± 0.14 (range 0.18-0.76). There were significant changes in volume and spatial location of the target and normal tissues after 27 Gy IMRT. In order to maintain the radiation dose to the targets and minimize the radiation to normal tissues, it is necessary to modify the radiotherapy planning.

  19. Expression of a plant-associated human cancer antigen in normal,premalignant and malignant esophageal tissues

    Institute of Scientific and Technical Information of China (English)

    Jun Fu; Ping Qu; Mo Li; Hai-Mei Tian; Zhen-Hai Zheng; Xin-Wen Zheng; Wei Zhang

    2003-01-01

    AIM: To study the relationship between the expression profiles of a plant-associated human cancer antigen and carcinogenesis of esophagus and its significance. METHODS: We analyzed expression of a plant-associated human cancer antigen in biopsy specimens of normal (n=29),mildly hyperplastic (n=29), mildly (n=30), moderately (n=27)and severely dysplastic (n=29) and malignant esophageal (n=30) tissues by immunohistochemistry. RESULTS: The plant-associated human cancer antigen was mainly confined to the cytoplasm and showed diffuse type of staining. Positive staining was absent or weak in normal (0/30) and mildly hyperplastic tissue samples (2/29), while strong staining was observed in severe dysplasia (23/29) and carcinoma in situ (24/30). There was significant difference of its expression between normal mucosa and severely dysplastic tissues (P<0.001) or carcinoma in situ (P<0.001). Significant difference was also observed between mild dysplasia and severe dysplasia (P<0.001) or carcinomain situ (P<0.001). An overall trend toward increased staining intensity with increasing grade of dysplasia was found. There was a linear correlation between grade of lesions and staining intensity (r=0.794,P<0.001). Samples from esophageal cancer showed no higher levels of expression than those in severely dysplastic lesions (P>0.05). CONCLUSION: The abnormal expression of this plantassociated human cancer antigen in esophageal lesions is a frequent and early finding in the normal-dysplasiacarcinoma sequence in esophageal carcinogenesis. It might contribute to the carcinogenesis of esophageal cancer. The abnormal expression of this plant-associated human cancer antigen in esophageal lesion tissues may serve as a potential new biomarker for early identification of esophageal cancer.

  20. Hypoxia-Induced miR-210 Modulates Tissue Response to Acute Peripheral Ischemia

    Science.gov (United States)

    Zaccagnini, Germana; Maimone, Biagina; Di Stefano, Valeria; Fasanaro, Pasquale; Greco, Simona; Perfetti, Alessandra; Capogrossi, Maurizio C.; Gaetano, Carlo

    2014-01-01

    Abstract Aims: Peripheral artery disease is caused by the restriction or occlusion of arteries supplying the leg. Better understanding of the molecular mechanisms underpinning tissue response to ischemia is urgently needed to improve therapeutic options. The aim of this study is to investigate hypoxia-induced miR-210 regulation and its role in a mouse model of hindlimb ischemia. Results: miR-210 expression was induced by femoral artery dissection. To study the role of miR-210, its function was inhibited by the systemic administration of a miR-210 complementary locked nucleic acid (LNA)-oligonucleotide (anti-miR-210). In the ischemic skeletal muscle, anti-miR-210 caused a marked decrease of miR-210 compared with LNA-scramble control, while miR-210 target expression increased accordingly. Histological evaluation of acute tissue damage showed that miR-210 inhibition increased both apoptosis at 1 day and necrosis at 3 days. Capillary density decrease caused by ischemia was significantly more pronounced in anti-miR-210-treated mice; residual limb perfusion decreased accordingly. To investigate the molecular mechanisms underpinning the increased damage triggered by miR-210 blockade, we tested the impact of anti-miR-210 treatment on the transcriptome. Gene expression analysis highlighted the deregulation of mitochondrial function and redox balance. Accordingly, oxidative damage was more severe in the ischemic limb of anti-miR-210-treated mice and miR-210 inhibition increased oxidative metabolism. Further, oxidative-stress resistant p66Shc-null mice displayed decreased tissue damage following ischemia. Innovation: This study identifies miR-210 as a crucial element in the adaptive mechanisms to acute peripheral ischemia. Conclusions: The physiopathological significance of miR-210 is context dependent. In the ischemic skeletal muscle it seems to be cytoprotective, regulating oxidative metabolism and oxidative stress. Antioxid. Redox Signal. 21, 1177–1188. PMID:23931770

  1. Colon cancer releases alpha-tocopherol from its O-glycosides better than normal colon tissue.

    Science.gov (United States)

    Knaś, Małgorzata; Szajda, Sławomir Dariusz; Snarska, Jadwiga; Zalewska-Szajda, Beata; Walejko, Piotr; Borzym-Kluczyk, Malgorzata; Knaś-Karaszewska, Katarzyna; Kepka, Alina; Chojnowska, Sylwia; Waszkiewicz, Napoleon; Zimnoch, Magdalena; Maj, Jadwiga; Hryniewicka, Agnieszka; Dudzik, Danuta; Witkowshi, Stanislaw; Puchalski, Zbigniew; Zwierz, Krzysztof

    2009-01-01

    Free radicals, in a colon, may damage DNA, make difficult DNA repair and change course of post-translational modifications of regulatory proteins, which promote tumor initiation and progression. Therefore risk of colon cancer is closely related to diet and other lifestyle factors. Dietary antioxidants, such as vitamin E, should reduce the levels of harmful oxidation products. However vitamin E is not soluble in water, which decreases its bioavailability. As O-glycosides of alpha-tocopherol are better soluble in water and penetrate to tissues easier than free alpha-tocopherol, the aim of our work was to investigate the rate of release the free tocopherol from its O-glycosides in colon cancer, in comparison to human healthy colon tissue. The activities of enzymes catalysing hydrolysis of alpha-tocopheryl glucoside (1a) and mannoside (1b) as well as p-nitrophenyl beta-glucoside (2a) and mannoside (2b) in cancer and healthy human colon tissues, were determined according to the modified method described by Zwierz et al. The alpha-tocopherol and p-nitrophenol were significantly better released from the respective glucosides and mannosides in cancer tissue than in "healthy" human colon tissues, with p = 0.000947 for la, p = 0.033024 for 1b; p = 0.0028 for 2a, and p = 0.0033 for 2b, respectively. Alpha-tocopherol and p-nitrophenol are released from the O-glycosides of glucose and mannose in significantly higher amount in colon cancer than in healthy tissues. The alpha-tocopherol O-glycosides can be considered as prodrugs in prevention and treatment of the colon cancer.

  2. Lipidomic differentiation between human kidney tumors and surrounding normal tissues using HILIC-HPLC/ESI-MS and multivariate data analysis.

    Science.gov (United States)

    Cífková, Eva; Holčapek, Michal; Lísa, Miroslav; Vrána, David; Melichar, Bohuslav; Študent, Vladimír

    2015-09-01

    The characterization of differences among polar lipid classes in tumors and surrounding normal tissues of 20 kidney cancer patients is performed by hydrophilic interaction liquid chromatography (HILIC) coupled to electrospray ionization mass spectrometry (ESI-MS). The detailed analysis of identified lipid classes using relative abundances of characteristic ions in negative- and positive-ion modes is used for the determination of more than 120 individual lipid species containing attached fatty acyls of different chain length and double bond number. Lipid species are described using relative abundances, providing a better visualization of lipidomic differences between tumor and normal tissues. The multivariate data analysis methods using unsupervised principal component analysis (PCA) and supervised orthogonal partial least square (OPLS) are used for the characterization of statistically significant differences in identified lipid species. Ten most significant up- and down-regulated lipids in OPLS score plots are also displayed by box plots. A notable increase of relative abundances of lipids containing four and more double bonds is detected in tumor compared to normal tissues. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. New tetrachromic VOF stain (Type III-G.S) for normal and pathological fish tissues.

    Science.gov (United States)

    Sarasquete, C; Gutiérrez, M

    2005-01-01

    A new VOF Type III-G.S stain was applied to histological sections of different organs and tissues of healthy and pathological larvae, juvenile and adult fish species (Solea senegalensis; Sparus aurata; Diplodus sargo; Pagrus auriga; Argyrosomus regius and Halobatrachus didactylus). In comparison to the original Gutiérrez VOF stain, more acid dyes of contrasting colours and polychromatic/metachromatic properties were incorporated as essential constituents of the tetrachromic VOF stain. This facilitates the selective staining of different basic tissues and improves the morphological analysis of histochemical approaches of the cell components. The VOF Type III -6.5 stain is composed of a mixture of several dyes of varying size and molecular weight (Orange Gtissues to be selectively differentiated and stained. Muscle fibers, collagen, reticulin and elastin fibers, erythrocytes, cartilage, bone, mucous cells, oocytes and larvae were selectively stained and differentiated. Dyes with small size and molecular weight (i.e Orange G), penetrate all tissue structures rapidly, but are only tightly retained in densely textured tissues (i.e erythrocytes). Methyl Blue is an interesting triarylmethane dye (large size and molecular weight), which is incorporated in this new VOF tetrachrome stain, and acquires histochemical significance when used at acid pH (2.8) because collagen and reticulin fibers, as well basophilic and metachromatic substances (strongly ionized sulphated glycoconjugates) can be identified. Muscle tissues show an evident green colour (Fast Green or Light Green affinities), even those isolated and/or diffuse muscle fibers present in the digestive submucosa layer. Connective tissues showed a specific and strong blue colour (Methyl Blue affinity) or mixed blue-red staining (Methyl Blue and Acid Fucshin affinities). Very noticeable is the staining of the

  4. EMPLOYMENT OF A «SIDE POPULATION» APPROACH TO STEM CELL ISOLATION IN NORMAL AND TUMOR TISSUES

    Directory of Open Access Journals (Sweden)

    O. R. Tsinkalovsky

    2008-01-01

    Full Text Available Abstract. A combination of fluorescent staining with Hoechst 33342 dye, and flow cytometry of murine bone marrow cells may be used for separation of a side population (SP, which is highly enriched for hematopoietic stem cells capable of long-term hematopoietic reconstitution in lethally irradiated recipients. Recently, this approach was also applied to analysis of SP cells in several types of non-hematopoietic tissues, and malignant tumours. In spite of yet poor definition of phenotype and functional potency of SP cells from various tissues, the method of SP isolation may be a useful tool for analysis and pre-enrichment of stem cell-like cells of different origin. Present review article presents a brief description of Hoechst 33342-staining approach, and of recent reports concerning SP studies in various normal and malignant tissues. (Med. Immunol., vol. 10, N 4-5, pp 319-326.

  5. Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Na Zhang; Gen-Yang Cheng; Xian-Zhi Liu; Feng-Jiang Zhang

    2014-01-01

    Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue. Methods:Fourty eight rats were randomly divided into four groups(n=12): sham operation group,30 min ischemia60 min reperfusion group,60 min ischemia60 min reperfusion group, and 120 min ischemia60 min reperfusion group.The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreasedBcl-2 expression, increasedBax expression, upregulated expression ofNF-κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.

  6. Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics.

    Science.gov (United States)

    Perepelyuk, Maryna; Chin, LiKang; Cao, Xuan; van Oosten, Anne; Shenoy, Vivek B; Janmey, Paul A; Wells, Rebecca G

    2016-01-01

    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.

  7. Proteomic Comparison of Two-Dimensional Gel Electrophoresis Pro files from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

    Institute of Scientific and Technical Information of China (English)

    Cui Li; Ping Chen; Jingyun Xie; Songping Liang; Xianquan Zhan; Maoyu Li; Xiaoying Wu; Feng Li; Jianling Li; Zhiqiang Xiao; Zhuchu Chen; Xueping Feng

    2003-01-01

    Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). The results showed that well-resolved, reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-ug protein-load. The average deviation of spot position was 0.733+0.101 mm in IEF direction, and 0.925+0.207 mm in SDS-PAGE direction. For tumor tissue, a total of 1241±88 spots were detected, 987±65 spots were matched with an average matching rate of 79.5%. For control, a total of 1190+72 spots were detected, and 875±48 spots were matched with an average matching rate of 73.5%. A total of 864±34 spots were matched between tumors and controls.Forty-three differential proteins were characterized: some proteins were related to oncogenes, and others involved in the regulation of cell cycle and signal transduction. It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis.These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

  8. Prognostic and biologic significance of long non-coding RNA profiling in younger adults with cytogenetically normal acute myeloid leukemia.

    Science.gov (United States)

    Papaioannou, Dimitrios; Nicolet, Deedra; Volinia, Stefano; Mrózek, Krzysztof; Yan, Pearlly; Bundschuh, Ralf; Carroll, Andrew J; Kohlschmidt, Jessica; Blum, William; Powell, Bayard L; Uy, Geoffrey L; Kolitz, Jonathan E; Wang, Eunice S; Eisfeld, Ann-Kathrin; Orwick, Shelley J; Lucas, David M; Caligiuri, Michael A; Stone, Richard M; Byrd, John C; Garzon, Ramiro; Bloomfield, Clara D

    2017-08-01

    Long non-coding ribonucleic acids (RNAs) are a novel class of RNA molecules, which are increasingly recognized as important molecular players in solid and hematologic malignancies. Herein we investigated whether long non-coding RNA expression is associated with clinical and molecular features, as well as outcome of younger adults (aged <60 years) with de novo cytogenetically normal acute myeloid leukemia. Whole transcriptome profiling was performed in a training (n=263) and a validation set (n=114). Using the training set, we identified 24 long non-coding RNAs associated with event-free survival. Linear combination of the weighted expression values of these transcripts yielded a prognostic score. In the validation set, patients with high scores had shorter disease-free (P<0.001), overall (P=0.002) and event-free survival (P<0.001) than patients with low scores. In multivariable analyses, long non-coding RNA score status was an independent prognostic marker for disease-free (P=0.01) and event-free survival (P=0.002), and showed a trend for overall survival (P=0.06). Among multiple molecular alterations tested, which are prognostic in cytogenetically normal acute myeloid leukemia, only double CEBPA mutations, NPM1 mutations and FLT3-ITD associated with distinct long non-coding RNA signatures. Correlation of the long non-coding RNA scores with messenger RNA and microRNA expression identified enrichment of genes involved in lymphocyte/leukocyte activation, inflammation and apoptosis in patients with high scores. We conclude that long non-coding RNA profiling provides meaningful prognostic information in younger adults with cytogenetically normal acute myeloid leukemia. In addition, expression of prognostic long non-coding RNAs associates with oncogenic molecular pathways in this disease. clinicaltrials.gov Identifier: 00048958 (CALGB-8461), 00899223 (CALGB-9665), and 00900224 (CALGB-20202). Copyright© 2017 Ferrata Storti Foundation.

  9. Thiamine pyrophosphate effect and normalized erythrocyte transketolase activity ratio in Wernicke-Korsakoff patients and acute alcoholics undergoing detoxification.

    Science.gov (United States)

    Rooprai, H K; Pratt, O E; Shaw, G K; Thomson, A D

    1996-09-01

    Thiamine deficiency may be assessed clinically by an abnormally low specific erythrocyte transketolase activity and/or by abnormally large activation by thiamine diphosphate in vitro (or 'TPP effect'). In the present investigation, we report erythrocyte transketolase activation by TPP in acute alcoholics and Wernicke-Korsakoff patients undergoing detoxification. A new age-dependent parameter was used to improve the reliability of transketolase activity as an indicator of marginal thiamine deficiency. Thus normalized transketolase activity ratio (NTKZ), primary activation ratio (PAR) and further activation ratio (FAR) were measured in 29 acute alcoholics and 12 Wernicke-Korsakoff patients upon admission, and also on 47 control subjects. It was possible to follow up 14 of the 29 acute alcoholics after 7 days of treatment. Twenty-one per cent of the acute alcoholics and 33% of the Wernicke-Korsakoff patients, on admission to the detoxification Unit, had NTKZ values beyond the defined critical conditions for thiamine deficiency, whereas 7% of the former and 25% of the latter had PAR values beyond these critical conditions. Furthermore, all three parameters were significantly different in the Wernicke-Korsakoff patients compared to the other groups. The pattern of improvement of the different parameters on follow-up varied considerably and is difficult to explain, as only the NTKZ was statistically significant. Hence, only eight out of 14 acute alcoholics showed improvement in NTKZ, seven showed improvement of PAR and six showed improvement of FAR after treatment. Five patients showed improvement of both NTKZ and PAR and none of the patients showed improvement of all three parameters. We conclude that our findings confirm previous reports and that this modified transketolase activation test improves its reliability as an indicator of marginal thiamine deficiency.

  10. Breast Field Cancerization: Isolation and Comparison of Telomerase-Expressing Cells in Tumor and Tumor Adjacent, Histologically Normal Breast Tissue

    Science.gov (United States)

    Trujillo, Kristina A.; Hines, William C.; Vargas, Keith M.; Jones, Anna C.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K.

    2011-01-01

    Telomerase stabilizes chromosomes by maintaining telomere length, immortalizes mammalian cells, and is expressed in more than 90% of human tumors. However, the expression of human telomerase reverse transcriptase (hTERT) is not restricted to tumor cells. We have previously shown that a subpopulation of human mammary epithelial cells (HMEC) in tumor-adjacent, histologically normal (TAHN) breast tissues expresses hTERT mRNA at levels comparable with levels in breast tumors. In the current study, we first validated a reporter for measuring levels of hTERT promoter activity in early-passage HMECs and then used this reporter to compare hTERT promoter activity in HMECs derived from tumor and paired TAHN tissues 1, 3, and 5 cm from the tumor (TAHN-1, TAHN-3, and TAHN-5, respectively). Cell sorting, quantitative real-time PCR, and microarray analyses showed that the 10% of HMECs with the highest hTERT promoter activity in both tumor and TAHN-1 tissues contain more than 95% of hTERT mRNA and overexpress many genes involved in cell cycle and mitosis. The percentage of HMECs within this subpopulation showing high hTERT promoter activity was significantly reduced or absent in TAHN-3 and TAHN-5 tissues. We conclude that the field of normal tissue proximal to the breast tumors contains a population of HMECs similar in hTERT expression levels and in gene expression to the HMECs within the tumor mass and that this population is significantly reduced in tissues more distal to the tumor. PMID:21775421

  11. Identification of Reference Genes for RT-qPCR Data Normalization in Cannabis sativa Stem Tissues

    Science.gov (United States)

    Mangeot-Peter, Lauralie; Legay, Sylvain; Hausman, Jean-Francois; Esposito, Sergio; Guerriero, Gea

    2016-01-01

    Gene expression profiling via quantitative real-time PCR is a robust technique widely used in the life sciences to compare gene expression patterns in, e.g., different tissues, growth conditions, or after specific treatments. In the field of plant science, real-time PCR is the gold standard to study the dynamics of gene expression and is used to validate the results generated with high throughput techniques, e.g., RNA-Seq. An accurate relative quantification of gene expression relies on the identification of appropriate reference genes, that need to be determined for each experimental set-up used and plant tissue studied. Here, we identify suitable reference genes for expression profiling in stems of textile hemp (Cannabis sativa L.), whose tissues (isolated bast fibres and core) are characterized by remarkable differences in cell wall composition. We additionally validate the reference genes by analysing the expression of putative candidates involved in the non-oxidative phase of the pentose phosphate pathway and in the first step of the shikimate pathway. The goal is to describe the possible regulation pattern of some genes involved in the provision of the precursors needed for lignin biosynthesis in the different hemp stem tissues. The results here shown are useful to design future studies focused on gene expression analyses in hemp. PMID:27649158

  12. Identification of Reference Genes for RT-qPCR Data Normalization in Cannabis sativa Stem Tissues

    Directory of Open Access Journals (Sweden)

    Lauralie Mangeot-Peter

    2016-09-01

    Full Text Available Gene expression profiling via quantitative real-time PCR is a robust technique widely used in the life sciences to compare gene expression patterns in, e.g., different tissues, growth conditions, or after specific treatments. In the field of plant science, real-time PCR is the gold standard to study the dynamics of gene expression and is used to validate the results generated with high throughput techniques, e.g., RNA-Seq. An accurate relative quantification of gene expression relies on the identification of appropriate reference genes, that need to be determined for each experimental set-up used and plant tissue studied. Here, we identify suitable reference genes for expression profiling in stems of textile hemp (Cannabis sativa L., whose tissues (isolated bast fibres and core are characterized by remarkable differences in cell wall composition. We additionally validate the reference genes by analysing the expression of putative candidates involved in the non-oxidative phase of the pentose phosphate pathway and in the first step of the shikimate pathway. The goal is to describe the possible regulation pattern of some genes involved in the provision of the precursors needed for lignin biosynthesis in the different hemp stem tissues. The results here shown are useful to design future studies focused on gene expression analyses in hemp.

  13. Rituximab efficiently depletes B cells in lung tumors and normal lung tissue [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Albane Joly-Battaglini

    2016-01-01

    Full Text Available Rituximab is a monoclonal antibody that targets the CD20 B-cell-specific antigen and is widely used as therapy for B-cell lymphoma. Since rituximab depletes both malignant and normal B cells, it is increasingly being used to treat various conditions in which normal B cells have a pathogenic role, such as rheumatoid arthritis and multiple sclerosis. It is well-established that rituximab efficiently eliminates B cells in blood, lymph nodes, and spleen. In contrast, the effect of rituximab in non-lymphoid tissues remains poorly documented and is debated. Here, we report a rheumatoid arthritis patient who was treated with rituximab before receiving thoracic surgery for non-small cell lung cancer. Using flow cytometry and immunohistochemistry, we show that rituximab efficiently depleted CD20-positive B cells in a primary lung tumor, in lung-associated lymph nodes, and in normal lung tissue. We conclude that rituximab may be very efficient at depleting normal B cells in the lungs. This property of rituximab may potentially be exploited for the treatment of conditions in which pathogenic B cells reside in the lungs. On the other hand, the clearance of lung B cells may provide an explanation for the rare cases of severe non-infectious pulmonary toxicity of rituximab.

  14. Clinical impact of MRI perfusion disturbances and normal diffusion in acute stroke patients

    Energy Technology Data Exchange (ETDEWEB)

    Blondin, D. [Institute of Diagnostic Radiology, University Hospital Duesseldorf (Germany)], E-mail: blondin@med.uni-duesseldorf.de; Seitz, R.J. [Department of Neurology, University Hospital Duesseldorf (Germany); Biomedical Research Centre, Heinrich-Heine-Universitaet Duesseldorf (Germany); Brain Imaging Centre, Research Centre Julich (Germany); Rusch, O.; Janssen, H.; Andersen, K.; Wittsack, H.-J.; Turowski, B. [Institute of Diagnostic Radiology, University Hospital Duesseldorf (Germany)

    2009-07-15

    Purpose: In acute ischemic stroke MR-imaging typically shows diffusion abnormalities surrounded by reduced perfusion signifying the so-called ischemic penumbra. Mismatch between diffusion and perfusion abnormalities gives indication for thrombolysis. But is there an indication for thrombolytic treatment, if there is no diffusion abnormality but pathologic perfusion combined with acute stroke symptoms?. Material and methods: MR-imaging of 1465 patients treated on our Stroke Unit between June 2004 and May 2007 retrospectively are analyzed. 6 patients met the inclusion criteria of severe neurological symptoms, large territorial perfusion disturbances, lack of diffusion abnormalities and complete neurological recovery after treatment. Results: In all six patients MTT measurements showed a significantly depressed perfusion in the symptomatic hemisphere (p < 0.02). Time-to-peak delay correlated with the mean transit time delay (0.949, p < 0.01). Indication for thrombolysis was based on perfusion abnormalities and clinical symptoms. Stroke symptoms could be reversed in all patients without any complication. Conclusion: Whereas diffusion imaging could not reveal any abnormality, perfusion analysis legitimated therapy with systemic thrombolysis in heavily affected patients. This work underlines the importance of multimodal MR imaging for guiding treatment decisions in acute stroke patients.

  15. 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.

  16. The fibrinolytic response in injured animal tissues normally low in fibrinolytic activity

    NARCIS (Netherlands)

    Smokovitis, A.; Astrup, T.

    1980-01-01

    Rabbit skin, normally of low fibrinolytic activity, and guinea-pig skin, of medium activity, after crush injury or after the intradermal or subcutaneous injection of aluminum hydroxide, show a remarkable increase in fibrinolytic activity. The activity is caused by a plasminogen activator and is

  17. Determination of optical properties of normal and adenomatous human colon tissues in vitro using integrating sphere techniques

    Institute of Scientific and Technical Information of China (English)

    Hua-Jiang Wei; Da Xing; Jian-Jun Lu; Huai-Min Gu; Guo-Yong Wu; Ying Jin

    2005-01-01

    AIM: The purpose of the present study is to compare the optical properties of normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion in vitro at 476.5, 488, 496.5, 514.5 and 532 nm. We believe these differences in optical properties should help differential diagnosis of human colon tissues by using optical methods.METHODS: In vitro optical properties were investigated for four kinds of tissues: normal human colon mucosa/submucosa and muscle layer/chorion, and adenomatous human colon mucosa/submucosa and muscle layer/chorion. Tissue samples were taken from 13 human colons (13 adenomatous, 13 normal). From the normal human colons a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion), and from the adenomatous human bladders a total of 26 tissue samples, with a mean thickness of 0.40 mm, were used (13 from mucosa/submucosa and 13 from muscle layer/chorion). The measurements were performed using a double-integratingsphere setup and the optical properties were assessed from these measurements using the adding-doubling method that was considered reliable.RESULTS: The results of measurement showed that there were significant differences in the absorption coefficients and scattering coefficients between normal and adenomatous human colon mucosa/submucosa at the same wavelength,and there were also significant differences in the two optical parameters between both colon muscle layer/chorion at the same wavelength. And there were large differences in the anisotropy factors between both colon mucosa/submucosa at the same wavelength, there were also large differences in the anisotropy factors between both colon muscle layer/chorion at the same wavelength.There were large differences in the value ranges of the absorption coefficients, scattering coefficients and anisotropy factors between both colon mucosa/submucosa,and there

  18. New Tetrachromic VOF Stain (Type III-G.S for Normal and Pathological Fish Tissues

    Directory of Open Access Journals (Sweden)

    C Sarasquete

    2005-06-01

    Full Text Available A new VOF Type III-G.S stain was applied to histological sections of different organs and tissues of healthy and pathological larvae, juvenile and adult fish species (Solea senegalensis; Sparus aurata; Diplodus sargo; Pagrus auriga; Argyrosomus regius and Halobatrachus didactylus. In comparison to the original Gutiérrez´VOF stain, more acid dyes of contrasting colours and polychromatic/metachromatic properties were incorporated as essential constituents of the tetrachromic VOF stain. This facilitates the selective staining of different basic tissues and improves the morphological analysis of histochemical approaches of the cell components. The VOF-Type III G.S stain is composed of a mixture of several dyes of varying size and molecular weight (Orange G< acid Fuchsin< Light green

  19. Evolution of normal and neoplastic tissue stem cells: progress after Robert Hooke.

    Science.gov (United States)

    Weissman, Irving

    2015-10-19

    The appearance of stem cells coincides with the transition from single-celled organisms to metazoans. Stem cells are capable of self-renewal as well as differentiation. Each tissue is maintained by self-renewing tissue-specific stem cells. The accumulation of mutations that lead to preleukaemia are in the blood-forming stem cell, while the transition to leukaemia stem cells occurs in the clone at a progenitor stage. All leukaemia and cancer cells escape being removed by scavenger macrophages by expressing the 'don't eat me' signal CD47. Blocking antibodies to CD47 are therapeutics for all cancers, and are currently being tested in clinical trials in the US and UK. © 2015 The Author(s).

  20. The Proliferative Activity of Mammary Epithelial Cells in Normal Tissue Predicts Breast Cancer Risk in Premenopausal Women.

    Science.gov (United States)

    Huh, Sung Jin; Oh, Hannah; Peterson, Michael A; Almendro, Vanessa; Hu, Rong; Bowden, Michaela; Lis, Rosina L; Cotter, Maura B; Loda, Massimo; Barry, William T; Polyak, Kornelia; Tamimi, Rulla M

    2016-04-01

    The frequency and proliferative activity of tissue-specific stem and progenitor cells are suggested to correlate with cancer risk. In this study, we investigated the association between breast cancer risk and the frequency of mammary epithelial cells expressing p27, estrogen receptor (ER), and Ki67 in normal breast tissue. We performed a nested case-control study of 302 women (69 breast cancer cases, 233 controls) who had been initially diagnosed with benign breast disease according to the Nurses' Health Studies. Immunofluorescence for p27, ER, and Ki67 was performed on tissue microarrays constructed from benign biopsies containing normal mammary epithelium and scored by computational image analysis. We found that the frequency of Ki67(+) cells was positively associated with breast cancer risk among premenopausal women [OR = 10.1, 95% confidence interval (CI) = 2.12-48.0]. Conversely, the frequency of ER(+) or p27(+) cells was inversely, but not significantly, associated with subsequent breast cancer risk (ER(+): OR = 0.70, 95% CI, 0.33-1.50; p27(+): OR = 0.89, 95% CI, 0.45-1.75). Notably, high Ki67(+)/low p27(+) and high Ki67(+)/low ER(+) cell frequencies were significantly associated with a 5-fold higher risk of breast cancer compared with low Ki67(+)/low p27(+) and low Ki67(+)/low ER(+) cell frequencies, respectively, among premenopausal women (Ki67(hi)/p27(lo): OR = 5.08, 95% CI, 1.43-18.1; Ki67(hi)/ER(lo): OR = 4.68, 95% CI, 1.63-13.5). Taken together, our data suggest that the fraction of actively cycling cells in normal breast tissue may represent a marker for breast cancer risk assessment, which may therefore impact the frequency of screening procedures in at-risk women. Cancer Res; 76(7); 1926-34. ©2016 AACR.

  1. Automated characterization of normal and pathologic lung tissue by topological texture analysis of multidetector CT

    Science.gov (United States)

    Boehm, H. F.; Fink, C.; Becker, C.; Reiser, M.

    2007-03-01

    Reliable and accurate methods for objective quantitative assessment of parenchymal alterations in the lung are necessary for diagnosis, treatment and follow-up of pulmonary diseases. Two major types of alterations are pulmonary emphysema and fibrosis, emphysema being characterized by abnormal enlargement of the air spaces distal to the terminal, nonrespiratory bronchiole, accompanied by destructive changes of the alveolar walls. The main characteristic of fibrosis is coursening of the interstitial fibers and compaction of the pulmonary tissue. With the ability to display anatomy free from superimposing structures and greater visual clarity, Multi-Detector-CT has shown to be more sensitive than the chest radiograph in identifying alterations of lung parenchyma. In automated evaluation of pulmonary CT-scans, quantitative image processing techniques are applied for objective evaluation of the data. A number of methods have been proposed in the past, most of which utilize simple densitometric tissue features based on the mean X-ray attenuation coefficients expressed in terms of Hounsfield Units [HU]. Due to partial volume effects, most of the density-based methodologies tend to fail, namely in cases, where emphysema and fibrosis occur within narrow spatial limits. In this study, we propose a methodology based upon the topological assessment of graylevel distribution in the 3D image data of lung tissue which provides a way of improving quantitative CT evaluation. Results are compared to the more established density-based methods.

  2. DNA methylation signatures of the AIRE promoter in thymic epithelial cells, thymomas and normal tissues.

    Science.gov (United States)

    Kont, Vivian; Murumägi, Astrid; Tykocinski, Lars-Oliver; Kinkel, Sarah A; Webster, Kylie E; Kisand, Kai; Tserel, Liina; Pihlap, Maire; Ströbel, Philipp; Scott, Hamish S; Marx, Alexander; Kyewski, Bruno; Peterson, Pärt

    2011-12-01

    Mutations in the AIRE gene cause autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), which is associated with autoimmunity towards several peripheral organs. The AIRE protein is almost exclusively expressed in medullary thymic epithelial cells (mTEC) and CpG methylation in the promoter of the AIRE gene has been suggested to control its tissue-specific expression pattern. We found that in human AIRE-positive medullary and AIRE-negative cortical epithelium, the AIRE promoter is hypomethylated, whereas in thymocytes, the promoter had high level of CpG methylation. Likewise, in mouse mTECs the AIRE promoter was uniformly hypomethylated. In the same vein, the AIRE promoter was hypomethylated in AIRE-negative thymic epithelial tumors (thymomas) and in several peripheral tissues. Our data are compatible with the notion that promoter hypomethylation is necessary but not sufficient for tissue-specific regulation of the AIRE gene. In contrast, a positive correlation between AIRE expression and histone H3 lysine 4 trimethylation, an active chromatin mark, was found in the AIRE promoter in human and mouse TECs. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. The Effect of Full Crown Preparation on Normal and Inflamed Pulp Tissue: An Animal Study

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    Mandana Vardkar

    2013-12-01

    Full Text Available Introduction: Full crown preparation may have adverse effects on pulp tissue. In this study, the effect of full-crown preparation on intact versus inflamed pulp tissue was studied. Methods: Fifteen healthy mature cats were randomly selected for this study. The study was performed on four canine teeth of each cat. Cats were anesthetized and then radiographs were taken from the canine teeth. Class V cavities were prepared in cat canine teeth. Soft decayed dentin was placed on the floor of cavities and sealed. After 1 month, all of the samples prepared for crown fabrication. Before crown preparation, an impression was taken in a custom tray. During crown preparation, the remnants of carious dentin were removed and undercuts were sealed by glass-ionomer. After preparation, self-cured acrylic temporary crowns were fabricated in a direct procedure and cemented permanently by glass-ionomer. One week later, teeth of the opposite jaw were prepared in a similar procedure. After 2 months, vital perfusion performed and the pulp tissue was histologically examined. Results: There was no significant difference between 4 groups, regarding to histologic status of the pulp. In healthy lower jaw, inflammation was the most frequent but in the other groups, necrosis was most frequent. Also, there was no significant difference between the upper jaw and the lower jaw groups regarding to the frequency of necrosis and inflammation. Conclusion: There is no significant difference between intact and inflamed groups regarding the frequency of necrosis and inflammation

  4. The Effect of Full Crown Preparation on Normal and Inflamed Pulp Tissue: An Animal Study

    Directory of Open Access Journals (Sweden)

    Maryam Bidar

    2013-01-01

    Full Text Available Introduction: Full crown preparation may have adverse effects on pulp tissue. In this study, the effect of full-crown preparation on intact versus inflamed pulp tissue was studied. Methods: Fifteen healthy mature cats were randomly selected for this study. The study was performed on four canine teeth of each cat. Cats were anesthetized and then radiographs were taken from the canine teeth. Class V cavities were prepared in cat canine teeth. Soft decayed dentin was placed on the floor of cavities and sealed. After 1 month, all of the samples prepared for crown fabrication. Before crown preparation, an impression was taken in a custom tray. During crown preparation, the remnants of carious dentin were removed and undercuts were sealed by glass-ionomer. After preparation, self-cured acrylic temporary crowns were fabricated in a direct procedure and cemented permanently by glass-ionomer. One week later, teeth of the opposite jaw were prepared in a similar procedure. After 2 months, vital perfusion performed and the pulp tissue was histologically examined. Results: There was no significant difference between 4 groups, regarding to histologic status of the pulp. In healthy lower jaw, inflammation was the most frequent but in the other groups, necrosis was most frequent. Also, there was no significant difference between the upper jaw and the lower jaw groups regarding to the frequency of necrosis and inflammation. Conclusion: There is no significant difference between intact and inflamed groups regarding the frequency of necrosis and inflammation

  5. MicroRNA-150 Expression Induces Myeloid Differentiation of Human Acute Leukemia Cells and Normal Hematopoietic Progenitors

    Science.gov (United States)

    Morris, Valerie A.; Zhang, Ailin; Yang, Taimei; Stirewalt, Derek L.; Ramamurthy, Ranjani; Meshinchi, Soheil; Oehler, Vivian G.

    2013-01-01

    In acute myeloid leukemia (AML) and blast crisis (BC) chronic myeloid leukemia (CML) normal differentiation is impaired. Differentiation of immature stem/progenitor cells is critical for normal blood cell function. MicroRNAs (miRNAs or miRs) are small non-coding RNAs that interfere with gene expression by degrading messenger RNAs (mRNAs) or blocking protein translation. Aberrant miRNA expression is a feature of leukemia and miRNAs also play a significant role in normal hematopoiesis and differentiation. We have identified miRNAs differentially expressed in AML and BC CML and identified a new role for miR-150 in myeloid differentiation. Expression of miR-150 is low or absent in BC CML and AML patient samples and cell lines. We have found that expression of miR-150 in AML cell lines, CD34+ progenitor cells from healthy individuals, and primary BC CML and AML patient samples at levels similar to miR-150 expression in normal bone marrow promotes myeloid differentiation of these cells. MYB is a direct target of miR-150, and we have identified that the observed phenotype is partially mediated by MYB. In AML cell lines, differentiation of miR-150 expressing cells occurs independently of retinoic acid receptor α (RARA) signaling. High-throughput gene expression profiling (GEP) studies of the AML cell lines HL60, PL21, and THP-1 suggest that activation of CEPBA, CEBPE, and cytokines associated with myeloid differentiation in miR-150 expressing cells as compared to control cells contributes to myeloid differentiation. These data suggest that miR-150 promotes myeloid differentiation, a previously uncharacterized role for this miRNA, and that absent or low miR-150 expression contributes to blocked myeloid differentiation in acute leukemia cells. PMID:24086639

  6. MicroRNA-150 expression induces myeloid differentiation of human acute leukemia cells and normal hematopoietic progenitors.

    Directory of Open Access Journals (Sweden)

    Valerie A Morris

    Full Text Available In acute myeloid leukemia (AML and blast crisis (BC chronic myeloid leukemia (CML normal differentiation is impaired. Differentiation of immature stem/progenitor cells is critical for normal blood cell function. MicroRNAs (miRNAs or miRs are small non-coding RNAs that interfere with gene expression by degrading messenger RNAs (mRNAs or blocking protein translation. Aberrant miRNA expression is a feature of leukemia and miRNAs also play a significant role in normal hematopoiesis and differentiation. We have identified miRNAs differentially expressed in AML and BC CML and identified a new role for miR-150 in myeloid differentiation. Expression of miR-150 is low or absent in BC CML and AML patient samples and cell lines. We have found that expression of miR-150 in AML cell lines, CD34+ progenitor cells from healthy individuals, and primary BC CML and AML patient samples at levels similar to miR-150 expression in normal bone marrow promotes myeloid differentiation of these cells. MYB is a direct target of miR-150, and we have identified that the observed phenotype is partially mediated by MYB. In AML cell lines, differentiation of miR-150 expressing cells occurs independently of retinoic acid receptor α (RARA signaling. High-throughput gene expression profiling (GEP studies of the AML cell lines HL60, PL21, and THP-1 suggest that activation of CEPBA, CEBPE, and cytokines associated with myeloid differentiation in miR-150 expressing cells as compared to control cells contributes to myeloid differentiation. These data suggest that miR-150 promotes myeloid differentiation, a previously uncharacterized role for this miRNA, and that absent or low miR-150 expression contributes to blocked myeloid differentiation in acute leukemia cells.

  7. Relation between regional distribution of /sup 201/Tl and myocardial blood flow in normal, acutely ischemic, and infarcted myocardium

    Energy Technology Data Exchange (ETDEWEB)

    Chu, A.; Murdock, R.H. Jr.; Cobb, F.R.

    1982-11-01

    Myocardial localization of /sup 201/Tl was compared with direct measurements of myocardial perfusion in normal, acutely ischemic, and recently infarcted myocardium. Studies were performed in 6 chronically instrumented dogs that were subjected to myocardial infarction by occlusion of the proximal left circumflex coronary artery. Four days after myocardial infarction, /sup 201/Tl and 9 +/- 1 micrometer /sup 95/Nb-labelled microspheres were injected simultaneously after acute left anterior descending coronary arterial occlusion; the animals were killed 5 minutes later and the entire left ventricle was sectioned into 1 to 2 g samples. Regression analyses between /sup 201/Tl activity and regional myocardial blood flow using all myocardial samples demonstrated a very close linear relation in each dog; r values were 0.98 or greater, indicating that the initial localization of /sup 201/Tl in acutely ischemic and recently infarcted myocardium as a function of regional blood flow was essentially identical. Consequently, in each dog the regional distribution of /sup 201/Tl closely approximated myocardial perfusion over a wide range of blood flow and potentially different local metabolic conditions that may be encountered in the clinical use of the isotope.

  8. Histological analysis of the distribution pattern of glandular tissue in normal inferior nasal turbinates

    OpenAIRE

    Millas, Ieda; Liquidato, Bianca Maria; Dolci,José Eduardo Lutaif; Fregnani, José Humberto Tavares Guerreiro; Macéa,José Rafael

    2009-01-01

    Nasal turbinates play an important role in nasal physiology. These functions include the important function of particle filtration by the mucocilliary system. Many nasal mucosal diseases, such as rhinitis and rhinosinusitis, are directly related with structural alterations of the mucosal lining of the turbinates. AIM: To study the distribution pattern of the glandular epithelium of the lamina propria in the normal lower nasal turbinate mucosa of the anterior, medium and posterior portions. MA...

  9. Case report of acute lymphoblastic leukemia with multiple soft tissue mass

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    Jang, Jung Yong; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    A 15-year-old patient, who had been diagnosed and treated as Burkitt cell type acute lymphoblastic leukemia (ALL-L3) already, visited our department. He complained of gingival enlargement and loosening teeth 1 month ago. The clinical examination revealed anterior open bite, gingival enlargement, and non tender swelling particularly in molar regions of both jaws. Deep periodontal pockets and severe mobility was shown on most of the teeth. The panoramic radiographs showed severe bone destruction and extrusion of the molars. The contrast enhanced CT showed multiple enhanced mass and bone marrow obliteration in both jaws. Chemotherapy was done the swelling was subsided at 1 month later. In conclusion, radiologic findings of leukemia with soft tissue mass, known as chloroma or granulocytic sarcoma, mimic those of lymphoma, so blood test may be needed for the final diagnosis.

  10. Identification of reliable reference genes for quantitative gene expression studies in oral squamous cell carcinomas compared to adjacent normal tissues in the F344 rat model.

    Science.gov (United States)

    Peng, Xinjian; McCormick, David L

    2016-08-01

    Oral squamous cell carcinomas (OSCCs) induced in F344 rats by 4-nitroquinoline-1-oxide (4-NQO) demonstrate considerable phenotypic similarity to human oral cancers and the model has been widely used for carcinogenesis and chemoprevention studies. Molecular characterization of this model needs reliable reference genes (RGs) to avoid false- positive and -negative results for proper interpretation of gene expression data between tumor and adjacent normal tissues. Microarray analysis of 11 pairs of OSCC and site-matched phenotypically normal oral tissues from 4-NQO-treated rats identified 10 stably expressed genes in OSCC compared to adjacent normal tissues (p>0.5, CVexpression analysis. We successfully identified Hsp90ab1 as a stable RG in 4-NQO-induced OSCC compared to adjacent normal tissues in F344 rats. The combination of two stably expressed genes may be a better option for gene normalization in tissue samples.

  11. 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.

  12. Diagnostic Role of Hyperechoic Fatty Tissue at Ultrasonography in Women with Acute Pelvic Pain

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    Park, Seong Jin; Yi, Boem Ha; Lee, Hae Kyung; Hong, Hyun Sook [Soonchunhyang University Hospital, Bucheon (Korea, Republic of); Kim, Hyun Cheol [Kyung Hee University East-West Neo-medicine Hospital, Seoul (Korea, Republic of)

    2009-12-15

    The aim of this study was to determine whether hyperechoic fatty tissue (HFT) at transabdominal and transvaginal ultrasonography in women with acute pelvic pain has a diagnostic role. We studied 201 women (mean age, 32 years) with acute pelvic and lower abdominal pain; we performed ultrasonography (US) in all them. Of the 201, 94 with gynecological problems were included., They were divided into two groups: with pelvic inflammatory disease (PID: n = 45) and without PID (n = 49). We evaluated the presence and distribution of HFT and its role in differential diagnosis between PID and non-PID groups. We found, using US, HFT in 36/45 (80%) patients with PID by US. Of the 36, single-center HFT was observed in 12/36 (33.3%) patients and multicentric HFT was detected in 24/36 (66.7%). HFT was present adjacent to inflammatory foci, tuboovarian abscesses or inflamed salpinx in 30 women: HFT was present outside the pelvic cavity in 24. Among the latter 24, HFT was present only in the lower abdomen, and not in the pelvic cavity in 6. In the non-PID group, HFT was found in the lower abdomen and pelvic cavity in 7 women. Four of the seven were misdiagnosed with PID. One of seven women with a hemorrhagic corpus luteal cyst rupture with underlying PID and two with ectopic pregnancy with HFT were correctly diagnosed. The presence of HFT may be a reliable US finding for the diagnosis of PID. HFT distinguishes PID from other acute gynecological problems

  13. Glucose-stimulated calcium dynamics in islets of Langerhans in acute mouse pancreas tissue slices.

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    Andraž Stožer

    Full Text Available In endocrine cells within islets of Langerhans calcium ions couple cell stimulation to hormone secretion. Since the advent of modern fluorimetry, numerous in vitro studies employing primarily isolated mouse islets have investigated the effects of various secretagogues on cytoplasmic calcium, predominantly in insulin-secreting beta cells. Due to technical limitations, insights of these studies are inherently limited to a rather small subpopulation of outermost cells. The results also seem to depend on various factors, like culture conditions and duration, and are not always easily reconcilable with findings in vivo. The main controversies regard the types of calcium oscillations, presence of calcium waves, and the level of synchronized activity. Here, we set out to combine the in situ acute mouse pancreas tissue slice preparation with noninvasive fluorescent calcium labeling and subsequent confocal laser scanning microscopy to shed new light on the existing controversies utilizing an innovative approach enabling the characterization of responses in many cells from all layers of islets. Our experiments reproducibly showed stable fast calcium oscillations on a sustained plateau rather than slow oscillations as the predominant type of response in acute tissue slices, and that calcium waves are the mechanistic substrate for synchronization of oscillations. We also found indirect evidence that even a large amplitude calcium signal was not sufficient and that metabolic activation was necessary to ensure cell synchronization upon stimulation with glucose. Our novel method helped resolve existing controversies and showed the potential to help answer important physiological questions, making it one of the methods of choice for the foreseeable future.

  14. Effect of blood transfusion, dopamine, or normal saline on neurogenic shock secondary to acutely raised intracranial pressure.

    Science.gov (United States)

    Rahimifar, M; Tator, C H; Shanlin, R J; Sole, M J

    1989-06-01

    An experimental model to simulate acutely raised intracranial pressure due to a rapidly expanding intracranial space-occupying lesion was used to produce neurogenic shock. Forty-one rats in neurogenic shock (defined as a mean systemic arterial pressure (SAP) of less than 60 mm Hg) were subjected to various treatments to increase the mean SAP to a level of more than 80 mm Hg. The control group with neurogenic shock received no treatment, and the six treatment groups received infusions of: whole blood, packed cells, plasma, normal saline, dopamine, or a combination of dopamine and saline. Detrimental effects were observed after transfusion of packed cells or whole blood, which caused further deterioration of mean SAP. Although dopamine or the combination of dopamine and saline were both effective (p = 0.0001) for reversing hypotension, the combination was the most effective. If this rat paradigm correlates with human disease, these results indicate that, in the absence of hypovolemia, neurogenic shock due to acute intracranial hypertension should be treated with a combined transfusion of dopamine and normal saline, but not blood since the latter could have a detrimental effect.

  15. Comparision Of The Efficacy Of Nebulized L-Epinephrine, Salbutamoland Normal Saline In Acute Bronchiolitis: A Randomized Clinical Trial

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    H. Mussavi

    2005-08-01

    Full Text Available Background:Acute bronchiolitis is the most common form of lower respiratory tract infection in infancy.There are numerous contradictory reports regarding the efficacy of nebulized bronchodilators in the management of infants with acute bronchiolitis. This study was designed to compare the efficacy of nebulized epinephrine with salbutamol for treatment of the disease.Methods:In a randomized clinical trial, 72 infants with moderately severe bronchiolitis were enrolled in three equal groups. Three doses of epinephrine, salbutamol, and normal saline as a placebo nebulized with oxygen were given at 20 minute intervals. Oxygen saturation, respiratory rate and distress were recorded before intervention and I0 minutes after each dose of the drugs. Results: At the end of the study, pre- and post-treatment mean oxygen saturation values, clinical scores and respiratory rates showed significant differences between the epinephrine and salbutamol groups in comparison with the placebo group. The results were more significant in the epinephrine group than other groups. After the treatment course 66%, 50%, and 25% of patients in epinephrine, salbutamol, and placebo groups respectively showed significant improvement at a degree that they could be sent home. No serious side effects were observed.Conclusion: Both nebulized epinephrine and salbutamol improved oxygenation and decreased respiratory distress better than normal saline. L-epinephrim was more effective in relieving respiratory distress and improving oxygen saturation as well as the need for hospitalization than nebulized salbutamol.

  16. Hospitalization expenses of acute ischemic stroke patients with atrial fibrillation relative to those with normal sinus rhythm.

    Science.gov (United States)

    Li, Jiming; Luo, Weiliang

    2017-02-01

    Atrial fibrillation (AF) is a risk factor for acute ischemic stroke (AIS). In mainland China, little is known of the hospitalization expenses of AIS patients with AF compared to those with normal sinus rhythm (SR). This study compared the itemized expenses of AIS patients with or without AF in a hospital in Huizhou City. Patients hospitalized for AIS from March 2014 to March 2015 were enrolled, including 73 with AF and 751 with normal SR. Stroke severity was scored using the National Institutes of Health Stroke Scale (NIHSS). Non-parametric statistical tests were used to determine differences in hospital expenses between the two groups, of which influencing factors were analyzed using single factor and multiple stepwise linear regression analyses. Medicine was the predominant expense during hospitalization of all AIS patients. Patients with AF incurred significantly higher expenses for medicine, bed, treatments, examinations, laboratory tests, and nursing than patients with normal SR (p expenses of patients at the same stroke level in the two groups were similar. Independent factors influencing the higher costs of AF patients were hospital length of stay, pulmonary infection, urinary-tract infection, NIHSS scoring, gastrointestinal bleeding, and congestive heart failure (p hospital length of stay were NIHSS scoring, pulmonary infection, and urinary-tract infection (p expenses during hospitalization compared with those with normal SR, due to greater stroke severity, higher rates of pulmonary infection and congestive heart failure, and longer hospital stays.

  17. Optical properties of normal and thermally coagulated chicken liver tissue measured ex-vivo with diffuse reflectance

    Science.gov (United States)

    Hafeez-Ullah; Atif, M.; Firdous, S.; Mehmood, M. S.; Hamza, M. Y.; Imran, M.; Hussain, G.; Ikram, M.

    2011-02-01

    The purpose of the present study is to determine the optical properties of normal and thermally coagulated chicken liver at 720, 740, 770, 810, 825 and 840 nm wavelengths of laser irradiation. So, we were able to evaluate these optical properties (absorption and scattering coefficients) with ex-vivo study using Kubelka Munk Model (KMM) from the radial dependence of the diffuse reflectance with femtosecond pulsed laser in near IR region. These coefficients were significantly increased with coagulation. The penetration depths of the diffused light have been reported to a maximum value of 8.12 ± 0.36 mm in normal liver and 2.49 ± 0.17 mm in coagulated liver at 840 nm showing increasing behavior towards IR region. The Monte Carlo simulation was used to check the theoretical validation of measured optical properties of the tissue that showed a good match with our experimental results. We believe that these differences in optical properties will be helpful for the understanding arid optimal use of laser applications in medicine and differential diagnosis of tissues by using different optical methods. Especially for the investigation of biological tissue for photodynamic therapy (PDT), the knowledge of the specific optical properties and their thermo-induced changes is important.

  18. Prognostic impact of Wilms tumor gene mutations in Egyptian patients with acute myeloid leukemia with normal karyotype.

    Science.gov (United States)

    Zidan, Magda Abdel Aziz; Kamal Shaaban, Howyda M; Elghannam, Doaa M

    2014-07-01

    The Wilms' tumor (WT1) gene mutations were detected in patients with most forms of acute leukemia. However, the biological significance and the prognostic impact of WT1 mutation in Egyptian patients with acute myeloid leukemia with normal karyotype (AML-NK) are still uncertain. We aimed to evaluate the incidence and clinical relevance of WT1 gene mutations in acute myeloid leukemia with normal karyotype (AML-NK). Exons 7 and 9 of WT1 were screened in samples from 216 adult NK-AML using polymerase chain reaction single-strand conformation polymorphism techniques. Twenty-three patients (10.6%) harbored WT1 mutations. Younger ages and higher marrow blasts were significantly associated with WT1 mutations (P = 0.006 and 0.003 respectively). Complete remission rates were significantly lower in patients with WT1 mutations than those with WT1 wild-type (P = 0.015). Resistance, relapse, and mortality rates were significantly higher in patients with WT1 mutations than those without (P = 0.041, 0.016, and 0.008 respectively). WT1 mutations were inversely associated with NPM1 mutations (P = 0.007). Patients with WT1 mutations had worse disease-free survival (P mutations independently predicted worse DFS (P mutational status. In conclusion, WT1 mutations are a negative prognostic indicator in intensively treated patients with AML-NK, may be a part of molecularly based risk assessment and risk-adapted treatment stratification of patients with AML-NK.

  19. Differential expression profiling between the relative normal and dystrophic muscle tissues from the same LGMD patient

    Directory of Open Access Journals (Sweden)

    Yang Wei

    2006-12-01

    Full Text Available Abstract Background Limb-girdle muscular dystrophy (LGMD is a group of heterogeneous muscular disorders with autosomal dominant and recessive inheritance, in which the pelvic or shoulder girdle musculature is predominantly or primarily involved. Although analysis of the defective proteins has shed some light onto their functions implicated in the etiology of LGMD, our understanding of the molecular mechanisms underlying muscular dystrophy remains incomplete. Methods To give insight into the molecular mechanisms of AR-LGMD, we have examined the differentially expressed gene profiling between the relative normal and pathological skeletal muscles from the same AR-LGMD patient with the differential display RT-PCR approach. The research subjects came from a Chinese AR-LGMD family with three affected sisters. Results In this report, we have identified 31 known genes and 12 unknown ESTs, which were differentially expressed between the relative normal and dystrophic muscle from the same LGMD patient. The expression of many genes encoding structural proteins of skeletal muscle fibers (such as titin, myosin heavy and light chains, and nebulin were dramatically down-regulated in dystrophic muscles compared to the relative normal muscles. The genes, reticulocalbin 1, kinectin 1, fatty acid desaturase 1, insulin-like growth factor binding protein 5 (IGFBP5, Nedd4 family interacting protein 1 (NDFIP1, SMARCA2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 2, encoding the proteins involved in signal transduction and gene expression regulation were up-regulated in the dystrophic muscles. Conclusion The functional analysis of these expression-altered genes in the pathogenesis of LGMD could provide additional information for understanding possible molecular mechanisms of LGMD development.

  20. Expression and significance of SOCS3 in liver tissue of rats with severe acute pancreatitis complicated by liver injury

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    Bin WANG

    2012-11-01

    Full Text Available Objective  To investigate the expression and mechanism of action of suppressor of cytokine signaling 3 (SOCS3 in liver tissue of rats with experimental severe acute pancreatitis (SAP concurring with liver injury. Methods  The rat model of SAP was reproduced by retrograde injection of 4% sodium taurocholate into the biliopancreatic duct. Thirty-two male SD rats were randomly assigned into 4 groups (8 each: normal control group (NC, SAP 6h, 12h, and 18h groups. The levels of serum amylase (AMY, alanine aminotransferase (ALT and aspartate aminotransferase (AST were measured dynamically. The concentrations of IL -6 and IL -18 were determined by ELISA. The localization and expression of SOCS3 protein in liver were determined by immunohistochemical staining and Western blotting. Results  Compared with NC group, the serum levels of AMY, ALT and AST increased significantly in SAP groups (P < 0.05, and there was significant difference among SAP groups. The serum concentrations of IL-6 and IL-18 increased significantly in the SAP groups than in NC group (P < 0.05, and there was significant difference among SAP groups. Compared with NC group, the concentration of SOCS3 protein increased significantly in SAP groups, and increased gradually along with the increased duration of pancreatitis (P < 0.05. A minor expression of SOCS3 protein was found in NC group. The change in SOCS3 protein concentration was consistent with the severity of liver injury as well as the serum concentrations of IL-6 and IL-18. Conclusions  The inflammatory action induced by SAP concurring with liver injury may induce the expression of SOCS3 in liver tissue, and it may increase in intensity along with the severity of liver injury and inflammatory reaction. The mechanism may be attributed to a negative feedback regulation of the inflammatory action mediated by JAK/STAT pathway.

  1. Correlation between the serum and tissue levels of oxidative stress markers and the extent of inflammation in acute appendicitis

    Science.gov (United States)

    Dumlu, Ersin Gürkan; Tokaç, Mehmet; Bozkurt, Birkan; Yildirim, Murat Baki; Ergin, Merve; Yalçin, Abdussamed; Kiliç, Mehmet

    2014-01-01

    OBJECTIVES: To determine the serum and tissue levels of markers of impaired oxidative metabolism and correlate these levels with the histopathology and Alvarado score of acute appendicitis patients. METHOD: Sixty-five acute appendicitis patients (mean age, 31.4±12.06 years; male/female, 30/35) and 30 healthy control subjects were studied. The Alvarado score was recorded. Serum samples were obtained before surgery and 12 hours postoperatively to examine the total antioxidant status, total oxidant status, paraoxonase, stimulated paraoxonase, arylesterase, catalase, myeloperoxidase, ceruloplasmin, oxidative stress markers (advanced oxidized protein products and total thiol level) and ischemia-modified albumin. Surgical specimens were also evaluated. RESULTS: The diagnoses were acute appendicitis (n = 37), perforated appendicitis (n = 8), phlegmonous appendicitis (n = 12), perforated+phlegmonous appendicitis (n = 4), or no appendicitis (n = 4). The Alvarado score of the acute appendicitis group was significantly lower than that of the perforated+phlegmonous appendicitis group (p = 0.004). The serum total antioxidant status, total thiol level, advanced oxidized protein products, total oxidant status, catalase, arylesterase, and ischemia-modified albumin levels were significantly different between the acute appendicitis and control groups. There was no correlation between the pathological extent of acute appendicitis and the tissue levels of the markers; additionally, there was no correlation between the tissue and serum levels of any of the parameters. CONCLUSIONS: The imbalance of oxidant/antioxidant systems plays a role in the pathogenesis acute appendicitis. The Alvarado score can successfully predict the presence and extent of acute appendicitis. PMID:25518019

  2. Early detection of colorectal cancer relapse by infrared spectroscopy in ``normal'' anastomosis tissue

    Science.gov (United States)

    Salman, Ahmad; Sebbag, Gilbert; Argov, Shmuel; Mordechai, Shaul; Sahu, Ranjit K.

    2015-07-01

    Colorectal cancer is one of the most aggressive cancers usually occurring in people above the age of 50 years. In the United States, colorectal cancer is the third most diagnosed cancer. The American Cancer Society has estimated 96,830 new cases of colon cancer and 40,000 new cases of rectal cancer in 2014 in the United States. According to the literature, up to 55% of colorectal cancer patients experience a recurrence within five years from the time of surgery. Relapse of colorectal cancer has a deep influence on the quality of patient life. Infrared (IR) spectroscopy has been widely used in medicine. It is a noninvasive, nondestructive technique that can detect changes in cells and tissues that are caused by different disorders, such as cancer. Abnormalities in the colonic crypts, which are not detectable using standard histopathological methods, could be determined using IR spectroscopic methods. The IR measurements were performed on formalin-fixed, paraffin-embedded colorectal tissues from eight patients (one control, four local recurrences, three distant recurrences). A total of 128 crypts were measured. Our results showed the possibility of differentiating among control, local, and distant recurrence crypts with more than a 92% success rate using spectra measured from the crypts' middle sites.

  3. Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation

    Directory of Open Access Journals (Sweden)

    Dongdong Liu

    2014-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α, whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

  4. Salmon Thrombin as a Treatment to Attenuate Acute Pain and Promote Tissue Healing by Modulating Local Inflammation

    Science.gov (United States)

    2012-12-01

    trauma and in association with the absence of pain . Early cleavage of PAR1 by thrombin may provide its anti- nociceptive properties. We were very...1-1002 TITLE: Salmon Thrombin as a Treatment to Attenuate Acute Pain and Promote Tissue Healing by Modulating Local Inflammation... Pain and 5a. CONTRACT NUMBER Promote Tissue Healing by Modulating Local Inflammation 5b. GRANT NUMBER W81XWH-10-1-1002 5c. PROGRAM ELEMENT

  5. Improved normal tissue sparing in head and neck radiotherapy using biological cost function based-IMRT.

    Science.gov (United States)

    Anderson, N; Lawford, C; Khoo, V; Rolfo, M; Joon, D L; Wada, M

    2011-12-01

    Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50_Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry.

  6. Normal and abnormal tissue identification system and method for medical images such as digital mammograms

    Science.gov (United States)

    Heine, John J. (Inventor); Clarke, Laurence P. (Inventor); Deans, Stanley R. (Inventor); Stauduhar, Richard Paul (Inventor); Cullers, David Kent (Inventor)

    2001-01-01

    A system and method for analyzing a medical image to determine whether an abnormality is present, for example, in digital mammograms, includes the application of a wavelet expansion to a raw image to obtain subspace images of varying resolution. At least one subspace image is selected that has a resolution commensurate with a desired predetermined detection resolution range. A functional form of a probability distribution function is determined for each selected subspace image, and an optimal statistical normal image region test is determined for each selected subspace image. A threshold level for the probability distribution function is established from the optimal statistical normal image region test for each selected subspace image. A region size comprising at least one sector is defined, and an output image is created that includes a combination of all regions for each selected subspace image. Each region has a first value when the region intensity level is above the threshold and a second value when the region intensity level is below the threshold. This permits the localization of a potential abnormality within the image.

  7. Humoral immunodepression following acute NO/sub 2/ exposure in normal and adrenalectomized mice

    Energy Technology Data Exchange (ETDEWEB)

    Azoulay-Dupuis, E.; Levacher, M.; Muffat-Joly, M.; Pocidalo, J.J.

    1985-01-01

    The effects following 20 ppm NO/sub 2/ exposure on humoral immunity were investigated in C57BI/6 mice after 48, 72, and 96 h exposure. Both spleen plaque-forming cell (PFC) responses and serum hemagglutinins (HA) using sheep red blood cells (SRBC) as antigen were studied. Splenic and thymic weight and cellularity decreased on acute exposure to NO/sub 2/. PFC were markedly depressed after 48 h exposure and continued to decrease as exposure time was lengthened. HA titers were also depressed. The same significant suppression of PFC and HA titers was observed in adrenalectomized mice after 96 h NO/sub 2/ exposure. The depression of humoral immunity in NO/sub 2/-exposed mice was independent of stress-induced endogeneous steroids.

  8. Interleukin-19 mediates tissue damage in murine ischemic acute kidney injury.

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    Yu-Hsiang Hsu

    Full Text Available Inflammation and renal tubular injury are major features of acute kidney injury (AKI. Many cytokines and chemokines are released from injured tubular cells and acts as proinflammatory mediators. However, the role of IL-19 in the pathogenesis of AKI is not defined yet. In bilateral renal ischemia/reperfusion injury (IRI-induced and HgCl2-induced AKI animal models, real-time quantitative (RTQ-PCR showed that the kidneys, livers, and lungs of AKI mice expressed significantly higher IL-19 and its receptors than did sham control mice. Immunohistochemical staining showed that IL-19 and its receptors were strongly stained in the kidney, liver, and lung tissue of AKI mice. In vitro, IL-19 upregulated MCP-1, TGF-β1, and IL-19, and induced mitochondria-dependent apoptosis in murine renal tubular epithelial M-1 cells. IL-19 upregulated TNF-α and IL-10 in cultured HepG2 cells, and it increased IL-1β and TNF-α expression in cultured A549 cells. In vivo, after renal IRI or a nephrotoxic dose of HgCl2 treatment, IL-20R1-deficient mice (the deficiency blocks IL-19 signaling showed lower levels of blood urea nitrogen (BUN in serum and less tubular damage than did wild-type mice. Therefore, we conclude that IL-19 mediates kidney, liver, and lung tissue damage in murine AKI and that blocking IL-19 signaling may provide a potent therapeutic strategy for treating AKI.

  9. Adipose Tissue-Derived Stem Cells Reduce Acute and Chronic Kidney Damage in Mice.

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    Marina Burgos-Silva

    Full Text Available Acute and chronic kidney injuries (AKI and CKI constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs in an experimental model of nephrotoxicity induced by folic acid (FA in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation.

  10. Acute toxicity of silver and carbon nanoaerosols to normal and cystic fibrosis human bronchial epithelial cells.

    Science.gov (United States)

    Jeannet, Natalie; Fierz, Martin; Schneider, Sarah; Künzi, Lisa; Baumlin, Nathalie; Salathe, Matthias; Burtscher, Heinz; Geiser, Marianne

    2016-01-01

    Inhalation of engineered nanoparticles (NP) poses a still unknown risk. Individuals with chronic lung diseases are expected to be more vulnerable to adverse effects of NP than normal subjects, due to altered respiratory structures and functions. Realistic and dose-controlled aerosol exposures were performed using the deposition chamber NACIVT. Well-differentiated normal and cystic fibrosis (CF) human bronchial epithelia (HBE) with established air-liquid interface and the human bronchial epithelial cell line BEAS-2B were exposed to spark-generated silver and carbon nanoaerosols (20 nm diameter) at three different doses. Necrotic and apoptotic cell death, pro-inflammatory response, epithelial function and morphology were assessed within 24 h after aerosol exposure. NP exposure resulted in significantly higher necrosis in CF than normal HBE and BEAS-2B cells. Before and after NP treatment, CF HBE had higher caspase-3 activity and secreted more IL-6 and MCP-1 than normal HBE. Differentiated HBE had higher baseline secretion of IL-8 and less caspase-3 activity and MCP-1 secretion compared to BEAS-2B cells. These biomarkers increased moderately in response to NP exposure, except for MCP-1, which was reduced in HBE after AgNP treatment. No functional and structural alterations of the epithelia were observed in response to NP exposure. Significant differences between cell models suggest that more than one and fully differentiated HBE should be used in future toxicity studies of NP in vitro. Our findings support epidemiologic evidence that subjects with chronic airway diseases are more vulnerable to adverse effects of particulate air pollution. Thus, this sub-population needs to be included in nano-toxicity studies.

  11. Local Tumor Control and Normal Tissue Toxicity of Pulsed Low-Dose Rate Radiotherapy for Recurrent Lung Cancer

    Directory of Open Access Journals (Sweden)

    Peng Zhang

    2015-05-01

    Full Text Available Objectives: This study investigates (1 local tumor control and (2 normal tissue toxicity of pulsed low-dose rate radiotherapy (PLDR for recurrent lung cancer. Methods: For study 1, nude mice were implanted with A549 tumors and divided into the following 3 groups: (1 control (n = 10, (2 conventional radiotherapy (RT; n = 10, and (3 PLDR (n = 10. Tumor-bearing mice received 2 Gy daily dose for 2 consecutive days. Weekly magnetic resonance imaging was used for tumor growth monitoring. For study 2, 20 mice received 8 Gy total body irradiation either continuously (n = 10 or 40 × 0.2 Gy pulses with 3-minute intervals (n = 10. Results: For study 1, both conventional RT and PLDR significantly inhibited the growth of A549 xenografts compared with the control group (>35% difference in the mean tumor volume; P .05. For study 2, the average weight was 20.94 ± 1.68 g and 25.69 ± 1.27 g and the survival time was 8 days and 12 days for mice treated with conventional RT and PLDR (P < .05, respectively. Conclusion: This study showed that PLDR could control A549 tumors as effectively as conventional RT, and PLDR induced much less normal tissue toxicity than conventional RT. Thus, PLDR would be a good modality for recurrent lung cancers. Advances in Knowledge: This article reports our results of an in vivo animal investigation of PLDR for the treatment of recurrent cancers, which may not be eligible for treatment because of the dose limitations on nearby healthy organs that have been irradiated in previous treatments. This was the first in vivo study to quantify the tumor control and normal tissue toxicities of PLDR using mice with implanted tumors, and our findings provided evidence to support the clinical trials that employ PLDR treatment techniques.

  12. Are estrogen receptors alpha detectable in normal and abnormal thyroid tissue?

    Science.gov (United States)

    Vaiman, Michael; Olevson, Youlian; Sandbank, Judith; Habler, Liliana; Zehavi, Sergei; Kessler, Alex

    2010-11-01

    The aims of this study is to evaluate the presence of estrogen receptors alpha (ERα) in thyroid lesions and to assess the practicality of this test in view of numerous disagreements on the subject. Immunohistochemical stains were performed for ERα, for the evaluation of immunoreactivity in 296 pathological thyroid tissue samples. We evaluated the intensity of the nuclear and cytoplasmatic staining and the spread of the stain over the sample. Thirty cases of the breast cancer served as a control group. None of the histological thyroid samples showed immunoreactivity for ERα. No difference was found between the various lesions in regard to this absence. The ERα rate of expression in the breast cancer samples was 60%. The ERα is undetectable in the histological samples of benign and malignant thyroid lesions. Further investigation is necessary in the laboratory immunohistochemical workup in order to exclude a possibility of non-specific staining.

  13. The expression and function of organic anion transporting polypeptides in normal tissues and in cancer.

    Science.gov (United States)

    Obaidat, Amanda; Roth, Megan; Hagenbuch, Bruno

    2012-01-01

    Organic anion transporting polypeptides (OATPs) are members of the SLCO gene superfamily of proteins. The 11 human OATPs are classified into 6 families and subfamilies on the basis of their amino acid sequence similarities. OATPs are expressed in several epithelial tissues throughout the body and transport mainly amphipathic molecules with molecular weights of more than 300 kDa. Members of the OATP1 and OATP2 families are functionally the best-characterized OATPs. Among these are the multispecific OATP1A2, OATP1B1, OATP1B3, and OATP2B1. They transport various endo- and xenobiotics, including hormones and their conjugates as well as numerous drugs such as several anticancer agents. Recent reports demonstrate that some OATPs are up- or downregulated in several cancers and that OATP expression might affect cancer development. On the basis of the findings summarized in this review, we propose that OATPs could be valuable targets for anticancer therapy.

  14. Heterogeneous patterns of DNA methylation-based field effects in histologically normal prostate tissue from cancer patients.

    Science.gov (United States)

    Møller, Mia; Strand, Siri Hundtofte; Mundbjerg, Kamilla; Liang, Gangning; Gill, Inderbir; Haldrup, Christa; Borre, Michael; Høyer, Søren; Ørntoft, Torben Falck; Sørensen, Karina Dalsgaard

    2017-01-13

    Prostate cancer (PC) diagnosis is based on histological evaluation of prostate needle biopsies, which have high false negative rates. Here, we investigated if cancer-associated epigenetic field effects in histologically normal prostate tissue may be used to increase sensitivity for PC. We focused on nine genes (AOX1, CCDC181 (C1orf114), GABRE, GAS6, HAPLN3, KLF8, MOB3B, SLC18A2, and GSTP1) known to be hypermethylated in PC. Using quantitative methylation-specific PCR, we analysed 66 malignant and 134 non-malignant tissue samples from 107 patients, who underwent ultrasound-guided prostate biopsy (67 patients had at least one cancer-positive biopsy, 40 had exclusively cancer-negative biopsies). Hypermethylation was detectable for all genes in malignant needle biopsy samples (AUC: 0.80 to 0.98), confirming previous findings in prostatectomy specimens. Furthermore, we identified a four-gene methylation signature (AOX1xGSTP1xHAPLN3xSLC18A2) that distinguished histologically non-malignant biopsies from patients with vs. without PC in other biopsies (AUC = 0.65; sensitivity = 30.8%; specificity = 100%). This signature was validated in an independent patient set (59 PC, 36 adjacent non-malignant, and 9 normal prostate tissue samples) analysed on Illumina 450 K methylation arrays (AUC = 0.70; sensitivity = 40.6%; specificity = 100%). Our results suggest that a novel four-gene signature may be used to increase sensitivity for PC diagnosis through detection of epigenetic field effects in histologically non-malignant prostate tissue samples.

  15. Selection of Suitable Reference Genes for Quantitative Real-Time PCR Normalization in Three Types of Rat Adipose Tissue.

    Science.gov (United States)

    Zhang, Wan-Xia; Fan, Jie; Ma, Jing; Rao, Yi-Song; Zhang, Li; Yan, You-E

    2016-06-22

    Quantitative real-time PCR (qRT-PCR) is the most classical technique in the field of gene expression study. This method requires an appropriate reference gene to normalize mRNA levels. In this study, the expression stability of four frequently-used reference genes in epididymal white adipose tissue (eWAT), inguinal beige adipose tissue (iBeAT) and brown adipose tissue (BAT) from obese and lean rats were evaluated by geNorm, NormFinder and BestKeeper. Based on the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, the two most stable reference genes were recommended in each type of adipose tissue. Two target genes were applied to test the stability of the reference genes. The geNorm and NormFinder results revealed that GAPDH and 36B4 exhibited the highest expression stabilities in eWAT, while 36B4 and β-actin had the highest expression stabilities in iBeAT and BAT. According to the results of the BestKeeper analysis, 36B4 was the most stable gene in eWAT, iBeAT and BAT, in terms of the coefficient of variance. In terms of the coefficient of correlation, GAPDH, 36B4 and β-actin were the most stable genes in eWAT, iBeAT and BAT, respectively. Additionally, expected results and statistical significance were obtained using a combination of two suitable reference genes for data normalization. In conclusion, 36B4 and GAPDH, in combination, are the best reference genes for eWAT, while 36B4 and β-actin are two most suitable reference genes for both iBeAT and BAT. We recommend using these reference genes accordingly.

  16. 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.

  17. Proteomic Comparison of Two—Dimensional Gel Electrophoresis Profiles from Human Lung Squamous Carcinoma and Normal Bronchial Epithelial Tissues

    Institute of Scientific and Technical Information of China (English)

    CuiLi; XianquanZhan; MaoyuLi; XiaoyingWu; FengLi; JianlingLi; ZhiqiangXiao; ZhuchuChen; XuepingFeng; PingChen; JingyunXie; SongpingLiang

    2003-01-01

    Differential proteome profiles of human lung squamous carcinoma tissue compared to paired tumor-adjacent normal bronchial epithelial tissue were established and analyzed by means of immobilized pH gradient-based two-dimensional polyacrylamide gel electrophoresis(2-D PAGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS).The results showed that well-resolved,reproducible 2-DE patterns of human lung squamous carcinoma and adjacent normal bronchial epithelial tissues were obtained under the condition of 0.75-mg protein-load.The average deviation of spot position was 0.733±0.101 mm in IEF direction,and 0.925±0.207mm in SDS-PAGE direction.For tumor tissue,a total of 1241±88 spots were detected,987±65 spots were matched with an average matching rate of 79.5%.For control,a total of 1190±72 spots were detected,and 875±48 spots were matched with an average matching rate of 73.5%.A total of 864±34 spots were matched between tumors and controls.Forth-three differential proteins were characterized:some proteins were related to oncogenes,and others involved in the regulation of cell cycle and signal transduction.It is suggested that the differential proteomic approach is valuable for mass identification of differentially expressed proteins involved in lung carcinogenesis.These data will be used to establish human lung cancer proteome database to further study human lung squamous carcinoma.

  18. Localization and activity of tissue bound cyclic nucleotide phosphodiesterase in normal and lack of changes in psoriatic human skin.

    Science.gov (United States)

    Mahrle, G; Organos, C E

    1976-12-01

    This study has been undertaken to elucidate the localization and the activity of cyclic nucleotide phosphodiesterase (PDE) in psoriatic epidermis compared to normal. The results showed that the evaluation of cytochemical methods may be difficult because of the various factors which interfere with the reaction and the considerable amount of background staining. Additionally, only the tissue bound particulate enzyme fraction may be demonstrated by cytochemical means. Nevertheless, the method did reveal that the activity of PDE, if any, is localized on the cytoplasmic membranes of the cells, independent of their origin, and not on the cell surface. Moreover, no differences were found between normal and psoriatic skin. It seems, therefore, that the intracellular degradation of cAMP remains unaltered in psoriasis.

  19. Characterization of dermal structural assembly in normal and pathological connective tissues by intrinsic signal multiphoton optical microscopy

    Science.gov (United States)

    Lyubovitsky, Julia G.; Xu, Xiaoman; Sun, Chung-ho; Andersen, Bogi; Krasieva, Tatiana B.; Tromberg, Bruce J.

    2008-02-01

    Employing a reflectance multi-photon microscopy (MPM) technique, we developed novel method to quantitatively study the three-dimensional assembly of structural proteins within bulk of dermal ECMs. Using a structurally simplified model of skin with enzymatically dissected epidermis, we find that low resolution MPM clearly discriminates between normal and pathological dermis. High-resolution images revealed that the backscattered MPM signals are affected by the assembly of collagen fibrils and fibers within this system. Exposure of tissues to high concentrations of potentially denaturing chemicals also resulted in the reduction of SHG signals from structural proteins which coincided with the appearance of aggregated fluorescent structures.

  20. Clinical Study of Ultrasonic Tissue Characterization with Integrated Backscatter and Echo Intensity in the Diagnosis of Acute Myocardial Infarction

    Institute of Scientific and Technical Information of China (English)

    王志刚; 冉海涛; 黄晶; 陈庆伟; 邹建中; 苏海兵; 蒲世玉; 凌智瑜; 陈永新; 何明菊

    2001-01-01

    Objectives The purpose of this study was to determine if the ultrasonic integrated backscatter and echo intensity could be used in clinical diagnosis of acute myocardial infarction. Methods and Results Within 2 weeks after acute myocardial infarction, 35 patients underwent ultrasonic tissue characterization from the papillar