Uptake of iodine-123-α-methyl tyrosine by gliomas and non-neoplastic brain lesions

International Nuclear Information System (INIS)

Kuwert, T.; Morgenroth, C.; Woesler, B.; Matheja, P.; Palkovic, S.; Vollet, B.; Samnick, S.; Maasjosthusmann, U.; Lerch, H.; Gildehaus, F.J.; Wassmann, H.; Schober, O.

1996-01-01

Using single-photon emission tomography (SPET), the radiopharmaceutical L-3-iodine-123-α-methyl tyrosine (IMT) has been applied to the imaging of amino acid transport into brain tumours. It was the aim of this study to investigate whether IMT SPET is capable of differentiating between high-grade gliomas, low-grade gliomas and non-neoplastic brain lesions. To this end, IMT uptake was determined in 53 patients using the triple-headed SPET camera MULTISPECT 3. Twenty-eight of these subjects suffered from high-grade gliomas (WHO grade III or IV), 12 from low-grade gliomas (WHO grade II), and 13 from non-neoplastic brain lesions, including lesions after effective therapy of a glioma (five cases), infarctions (four cases), inflammatory lesions (three cases), infarctions (four cases), inflammatory lesions (three cases) and traumatic haematoma (one case). IMT uptake was significantly higher in high-grade gliomas than in low-grade gliomas and non-neoplastic lesions. IMT uptake by low-grade gliomas was not significantly different from that by non-neoplastic lesions. Diagnostic sensitivity and specificity were 71% and 83% for differentiating high-grade from low-grade gliomas, 82% and 100% for distinguishing high-grade gliomas from non-neoplastic lesions, and 50% and 100% for discriminating low-grade gliomas from non-neoplastic lesions. Analogously to positron emission tomography with radioactively labelled amino acids and fluorine-18 deoxyglucose, IMT SPET may aid in differentiating higc-grade gliomas from histologically benign brain tumours and non-neoplastic brain lesions; it is of only limited value in differentiating between non-neoplastic lesions and histologically benign brain tumours. (orig.)

Management of neoplastic meningitis.

Science.gov (United States)

Roth, Patrick; Weller, Michael

2015-06-01

Leptomeningeal dissemination of tumor cells, also referred to as neoplastic meningitis, is most frequently seen in patients with late-stage cancer and mostly associated with a poor prognosis. Basically, neoplastic meningitis may affect all patients with a malignant tumor but is most common in patients affected by lung cancer, breast carcinoma, melanoma or hematologic neoplasms such as lymphoma and leukemia. Controlled clinical trials are largely lacking which results in various non-standardized treatment regimens. The presence of solid tumor manifestations in the CNS as well as the extracranial tumor load defines the most appropriate treatment approach. Radiation therapy, systemic chemotherapy and intrathecal treatment must be considered. For each patient, the individual situation needs to be carefully evaluated to determine the potential benefit as well as putative side effects associated with any therapy. A moderate survival benefit and particularly relief from pain and neurological deficits are the main treatment goals. Here, we summarize the management of patients with neoplastic meningitis and review the available treatment options.

Neoplastic changes in freshwater fishes: Correlation with oil refining

International Nuclear Information System (INIS)

Ostrander, G.K.

1993-01-01

Traditionally, oil pollution has been viewed as single event, large scale disasters such as the Exxon Valdez spill in Alaska. However, it is becoming increasingly apparent that by products and anthropogenic contaminants resulting from oil exploration, extraction, recovery, refining, and the manufacture and use of oil and oil-based products are negatively impacting the environment. Potential problems of freshwater pollution by oil contaminants are increasing in many parts of the world from both active and abandoned oil production facilities. In the USA many ''Superfund'' sites have been designated for cleanup under the Comprehensive Environmental Response, Compensation and Liability Act of 1980; primarily because of waste discharged on to the sites by the oil industry. Pollution of surface and groundwater from these sites has already occurred and in some cases has led to deleterious effects on the complex aquatic and terrestrial ecosystems on and near these sites. The effect of oil and oil related products on aquatic organisms will be reviewed. Specifically, the discussion will focus on preneoplastic and neoplastic changes in fishes with a primary endpoint of cancer. Finally, a summary of current studies of feral fishes residing on and near an abandoned oil refinery in Oklahoma will be presented

KIT polymorphisms and mutations determine responses of neoplastic mast cells to bafetinib (INNO-406).

Science.gov (United States)

Peter, Barbara; Hadzijusufovic, Emir; Blatt, Katharina; Gleixner, Karoline V; Pickl, Winfried F; Thaiwong, Tuddow; Yuzbasiyan-Gurkan, Vilma; Willmann, Michael; Valent, Peter

2010-09-01

Advanced systemic mastocytosis (SM) is characterized by uncontrolled growth of neoplastic mast cells (MC) and drug resistance. The tyrosine kinase receptor KIT is often mutated and activated and thus contributes to malignant growth of MC. Therefore, KIT-targeting drugs are currently tested for their ability to block growth of malignant MC. We determined the effects of the multikinase inhibitor INNO-406 (bafetinib) on primary neoplastic MC, the canine mastocytoma cell line C2, the human MC leukemia cell line HMC-1.1 bearing the KIT mutant V560G, and HMC-1.2 cells harboring KIT V560G and KIT D816V. INNO-406 was found to inhibit proliferation in HMC-1.1 cells (IC(50): 30-40 nM), but not in HMC-1.2 cells or primary neoplastic cells in patients with KIT D816V-positive SM. In canines, growth-inhibitory effects of INNO-406 were seen in C2 cells (IC(50): 50-100 nM) exhibiting a KIT exon 11 internal tandem-duplication and in primary neoplastic MC harboring wild-type exon 11, whereas no effects were seen in MC exhibiting a polymorphism at amino acid 581 in exon 11. INNO-406 was found to block KIT phosphorylation and expression in HMC-1.1 cells and C2 cells, but not in HMC-1.2 cells, whereas Lyn-phosphorylation was blocked by INNO-406 in all types of MC. In neoplastic MC, the major target of INNO-406 appears to be KIT. Drug responses may depend on the presence and type of KIT mutation. In human MC, the KIT D816V mutant introduces resistance, and in canine mastocytomas, an exon 11 polymorphism may be indicative of resistance against INNO-406.

The analysis of health condition and the assessment of the risk of neoplastic diseases among residents of villages

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Anna Lewandowska

2017-06-01

Full Text Available Introduction: Neoplastic diseases have been classified as civilization diseases and are a big problem for modern medicine. According to the data from the International Agency for Research of Cancer, about 10 million people suffer from cancer and a number of deaths due to this disease has exceeded 6 million; until 2020 those numbers may double. In Poland, cancer survivors of five years concern 22% of men and 35% of women suffering from tumours, while in northern and western Europe there is a cure rate of 40% for men and 50% for women. The main reason for the adverse situation in Poland is a low percentage of early diagnosis of cancer. On the one hand this results from insufficient preparation of both family doctors and physicians of other specialties, but on the other, from insufficient dissemination of early diagnosis methods. Objective: The objective of the study is to analyze the health condition and to assess the risk of a neoplastic disease among residents of villages. Material and methods: The research involved 1000 residents of villages in Podkarpackie Voivodeship. The age of the researched ranges from 18 to 30 years, with mean age 26.96±0.84 (range [18;30], median 25.95%CI [18,9;29,01]. The researched group is represented in 43,8% by women in 56,2% by men. In order to obtain the research material, a standardized questionnaire has been applied including interview and physical examination, enabling assessment of symptoms reported during the interview and analysis of symptoms indicating a disease, including cancer. Results: According to the data analysis, during last few months the respondents have suffered from such ailments as cough (8.22% W, 7.12% M, dyspnea (3.2% W, 1.78% M, abdominal pain (13.7% W, 4.27% M, pain (5.48% W, 2.14% M and weakness (14.61% W, 4.98% M. During observations, one female respondent was diagnosed with symptoms of melanoma (0.46%, which has been confirmed in later dermatological test. Conclusions: No changes in

Total gastrectomy for non-neoplastic diseases

DEFF Research Database (Denmark)

Bjorn, Niels; Ainsworth, Alan Patrick; Mortensen, Michael Bau

2017-01-01

Background: The aim of this study was to describe patients who had total gastrectomy for non-neoplastic diseases within a well-defined geographical area. Material and Methods: Retrospective study of patients who had gastrectomy for a non-neoplastic disease at the Department of Surgery, Odense...... University Hospital from 1 January 2005 to 31 December 2014. Results: A total of 268 gastrectomies were performed with the 10-year period. Of these, ten (4%) were done for non-neoplastic diseases. Two were men and eight women with a median age of 51 years (range 31 to 96 years). Six had emergency surgery...... of 10 and 2 of 10, respectively. Histology of the resected specimens showed: Oedema, inflammation and/or necrosis (n=6), Menetrier's disease (n=2) and perforation (n=2). Conclusions: Gastrectomy for non-neoplastic diseases accounts for less than 5% of all gastrectomies. The majority of these cases...

Neoplastic causes of abnormal puberty.

Science.gov (United States)

Wendt, Susanne; Shelso, John; Wright, Karen; Furman, Wayne

2014-04-01

Neoplasm-related precocious puberty (PP) is a rare presenting feature of childhood cancer. Moreover, evaluation of suspected PP in a child is complex, and cancer is often not considered. We characterized the clinicopathologic features of patients presenting with PP at a large pediatric cancer center, reviewed the relevant literature, and developed an algorithm for the diagnostic work-up of these patients. We examined the records of all patients with a neoplasm and concomitant PP treated at St. Jude Children's Research Hospital from January 1975 through October 2011, reviewed the available literature, and analyzed the demographic, clinical, endocrine, and neoplasm-related features. Twenty-four of 13,615 children and adolescents (0.18%) were diagnosed with PP within 60 days of presentation. Primary diagnoses included brain tumor (12), adrenocortical carcinoma (5), hepatoblastoma (4), and others (3). PP was observed 0-48 months before diagnosis of neoplasm; 17 patients had peripheral PP and 7 had central PP. Neoplasm-related PP is rare and takes the form of a paraneoplastic syndrome caused by tumor production of hormones or by alteration of physiologic gonadotropin production. PP can precede diagnosis of malignancy by months or years, and neoplastic causes should be considered early to avoid delayed cancer diagnosis. Treatment of the primary malignancy resolved or diminished PP in surviving patients with an intact hypothalamic-pituitary-gonadal axis. © 2013 Wiley Periodicals, Inc.

Atypical focal non-neoplastic brain changes in neurofibromatosis type 1: mass effect and contrast enhancement

International Nuclear Information System (INIS)

Raininko, R.; Thelin, L.; Eeg-Olofsson, O.

2001-01-01

Abstract Children and young adults with neurofibromatosis type 1 often have small high-signal foci on T2-weighted images of the brain. We describe follow-up of two patients in whom one of the foci had atypical features, commonly regarded as signs of a neoplasm. In the first, one lesion showed temporary contrast enhancement and decreasing mass effect. The second developed an expanding lesion that increased minimally in size over 4.5 year's follow-up. The borderline between neoplastic and non-neoplastic lesions seems to be indistinct. (orig.)

Proposed Terminology and Classification of Pre-Malignant Neoplastic Conditions: A Consensus Proposal

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Peter Valent

2017-12-01

Full Text Available Cancer evolution is a step-wise non-linear process that may start early in life or later in adulthood, and includes pre-malignant (indolent and malignant phases. Early somatic changes may not be detectable or are found by chance in apparently healthy individuals. The same lesions may be detected in pre-malignant clonal conditions. In some patients, these lesions may never become relevant clinically whereas in others, they act together with additional pro-oncogenic hits and thereby contribute to the formation of an overt malignancy. Although some pre-malignant stages of a malignancy have been characterized, no global system to define and to classify these conditions is available. To discuss open issues related to pre-malignant phases of neoplastic disorders, a working conference was organized in Vienna in August 2015. The outcomes of this conference are summarized herein and include a basic proposal for a nomenclature and classification of pre-malignant conditions. This proposal should assist in the communication among patients, physicians and scientists, which is critical as genome-sequencing will soon be offered widely for early cancer-detection.

Promoting effect of bile acids on neoplastic transformation of x-irradiated 10T1/2 cells

International Nuclear Information System (INIS)

Han, A.; Hill, C.K.

1984-01-01

Experimental studies have raised a concern about a role of bile acids in colo-rectal carcinogenesis. Studies in vivo suggest that bile acids may act as tumor promoters. Using 10T1/2 mouse cells as a model system, the authors explored the effects of cholic and cheno-deoxycholic acid on x-ray-induced neoplastic transformation in these cells. Addition of either cheno-deoxycholic acid or cholic acid to 10T1/2 cells, 24 hours after exposure to x-rays (50kv) increases significantly the frequencies of transformation. The compounds were present in the medium throughout the entire postirradiation refeeding period. At the concentrations used (0.5μg/ml), neither acid was cytotoxic and did not have any effect on cell survival. The enhancement of radiation-induced transformation seems to be greater in the presence of cholic acid, as compared to the effect of cheno-deoxycholic acid. Increase in transformation was relatively greater after low compared to high doses of radiation. The effect of bile acids on transformation of 10T1/2 cells is similar to that of a known tumor promoter TPA. The authors' observations support the conclusion that promotional effect of bile acids is not because of their specific effect on colonic epithelium, but rather due to their general properties as tumor promoters

Enteroclysis of non-neoplastic disorders of the small intestine

International Nuclear Information System (INIS)

Nolan, D.J.

2000-01-01

Enteroclysis is now widely used for examining the jejunum and ileum. The technique is ideal for demonstrating the extent and severity of disorders that cause morphological changes to the small intestine. In this review many non-neoplastic small intestinal disorders as demonstrated by enteroclysis are described and illustrated. (orig.)

Morphological spectrum of non‑neoplastic lesions of the uterine ...

African Journals Online (AJOL)

Background: The uterine cervix is a gateway to several non‑neoplastic and neoplastic gynecological lesions. Most of these non‑neoplastic lesions are commonly found in women of reproductive age. These lesions constitute a source of morbidity and mortality in women worldwide hence the need to analyze them to provide ...

Proposed Terminology and Classification of Pre-Malignant Neoplastic Conditions: A Consensus Proposal.

Science.gov (United States)

Valent, Peter; Akin, Cem; Arock, Michel; Bock, Christoph; George, Tracy I; Galli, Stephen J; Gotlib, Jason; Haferlach, Torsten; Hoermann, Gregor; Hermine, Olivier; Jäger, Ulrich; Kenner, Lukas; Kreipe, Hans; Majeti, Ravindra; Metcalfe, Dean D; Orfao, Alberto; Reiter, Andreas; Sperr, Wolfgang R; Staber, Philipp B; Sotlar, Karl; Schiffer, Charles; Superti-Furga, Giulio; Horny, Hans-Peter

2017-12-01

Cancer evolution is a step-wise non-linear process that may start early in life or later in adulthood, and includes pre-malignant (indolent) and malignant phases. Early somatic changes may not be detectable or are found by chance in apparently healthy individuals. The same lesions may be detected in pre-malignant clonal conditions. In some patients, these lesions may never become relevant clinically whereas in others, they act together with additional pro-oncogenic hits and thereby contribute to the formation of an overt malignancy. Although some pre-malignant stages of a malignancy have been characterized, no global system to define and to classify these conditions is available. To discuss open issues related to pre-malignant phases of neoplastic disorders, a working conference was organized in Vienna in August 2015. The outcomes of this conference are summarized herein and include a basic proposal for a nomenclature and classification of pre-malignant conditions. This proposal should assist in the communication among patients, physicians and scientists, which is critical as genome-sequencing will soon be offered widely for early cancer-detection. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Neoplastic pericardial disease. Analysis of 26 patients

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Helena Nogueira Soufen

1999-01-01

Full Text Available PURPOSE: To characterize patients with neoplastic pericardial disease diagnosed by clinical presentation, complementary test findings, and the histological type of tumor. METHODS: Twenty-six patients with neoplastic pericardial disease were retrospectively analyzed. RESULTS: Clinical manifestations and abnormalities in chest roentgenograms and electrocardiograms were frequent, but were not specific. Most patients underwent surgery. There was a high positivity of the pericardial biopsy when associated with the cytological analysis of the pericardial liquid used to determine the histological type of the tumor, particularly when the procedure was performed with the aid of pericardioscopy. CONCLUSION: The correct diagnosis of neoplastic pericardial disease involves suspicious but nonspecific findings during clinical examination and in screen tests. The suspicious findings must be confirmed through more invasive diagnostic approaches, in particular pericardioscopy with biopsy and cytological study.

2-[(aminopropyl)amino]ethanethiol (WR1065) is anti-neoplastic and anti-mutagenic when given during 60Coγ-ray irradiation

International Nuclear Information System (INIS)

Hill, C.K.; Nagy, B.; Peraino, C.; Grdina, D.

1986-01-01

The effect of 2[(aminopropyl)amino]ethanethiol (WR1065) has been studied on the induction of neoplastic transformation using 10T1/2 cells and on mutation of the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus using Chinese hamster V79 cells. The first observations that treatment of 10T1/2 cells with 1 mM WR1065 for a total of 35 min during irradiation with 60 C γ-rays significantly reduces the incidence of neoplastic transformation while having no effect on cell viability are reported. In a similar experiment with V79 cells in which 4mM WR1065 was used, a significant reduction in mutation frequency at the HGPRT locus and significant protection against cell killing was found. These results suggest that WR1965 acts to modulate both acute damage and sub-lethal processes that lead to mutation and neoplastic transformation. Beyond the purely mechanistic approach of these studies, the potential application of these agents to minimizing the long-term neoplastic effects of radiation or chemotherapeutic agents currently in use for treating potentially curable cancer patients should be further investigated. (author)

Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

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Geni NL Camara

2003-10-01

Full Text Available As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using consensus primers MY09 and MY11 followed by identification of isolates by restriction fragment length polymorphism. We detected HPV DNA in 62% of the samples, including HPV-16 in 43.8%, HPV-58 in 12.5%, HPV-31 in 10%, HPV-53 in 6.3%, each of HPV-18 and HPV-33 in 3.8% of the isolates. Other types (HPV-35, -52, -66, -CP8304, -6, -11, and -CP8061 were less frequent (= or < 2.5% each. The prevalence of HPV-58 was relatively higher in this population than in data in South America, but similar to results obtained in other studies in Latin America, Europe, and Eastern Asia. Case-control studies need to be carried out to establish the association between the prevalence of HPV types specially the less frequent high-risk types and cervical cancer.

Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

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Laghi Luigi

2006-04-01

Full Text Available Abstract Background Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver. Methods To address whether epigenetic changes take place in connection to age and/or to the underlying disease, we investigated RASSF1A and NORE1A gene promoter methylation by conventional methylation specific PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia, dysplastic (large regenerative, low and high grade dysplastic nodules and neoplastic (hepatocellular adenoma and carcinoma growths. Results In the hepatitic liver (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC we found widespread RASSF1A gene promoter methylation with a methylation index that increased from regenerative conditions (cirrhosis to hepatocellular nodules (p RASSF1A gene promoter methylation, NORE1A gene was never found epigenetically alterated in both hepatitic and non-hepatitic liver. Conclusion We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A gene is increasingly methylated, that this condition takes place as an age-related phenomenon and that the early setting and spreading over time of an epigenetically methylated hepatocyte subpopulation, might be related to liver tumorigenesis.

DIAGNOSIS OF ENDOCRINE DISEASE: Differentiation of pathologic/neoplastic hypercortisolism (Cushing's syndrome) from physiologic/non-neoplastic hypercortisolism (formerly known as pseudo-Cushing's syndrome).

Science.gov (United States)

Findling, James W; Raff, Hershel

2017-05-01

Endogenous hypercortisolism (Cushing's syndrome) usually implies the presence of a pathologic condition caused by either an ACTH-secreting neoplasm or autonomous cortisol secretion from a benign or malignant adrenal neoplasm. However, sustained or intermittent hypercortisolism may also accompany many medical disorders that stimulate physiologic/non-neoplastic activation of the HPA axis (formerly known as pseudo-Cushing's syndrome); these two entities may share indistinguishable clinical and biochemical features. A thorough history and physical examination is often the best (and sometimes only) way to exclude pathologic/neoplastic hypercortisolism. The presence of alcoholism, renal failure, poorly controlled diabetes and severe neuropsychiatric disorders should always raise suspicion that the presence of hypercortisolism may be related to physiologic/non-neoplastic Cushing's syndrome. As late-night salivary cortisol and low-dose dexamethasone suppression have good sensitivity and negative predictive value, normal studies exclude Cushing's syndrome of any form. However, these tests have imperfect specificity and additional testing over time with clinical follow-up is often needed. When there is persistent diagnostic uncertainty, secondary tests such as the DDAVP stimulation test and the dexamethasone-CRH test may provide evidence for the presence or absence of an ACTH-secreting tumor. This review will define and characterize the numerous causes of physiologic/non-neoplastic hypercortisolism and provide a rational clinical and biochemical approach to distinguish it from pathologic/neoplastic hypercortisolism (true Cushing's syndrome). © 2017 European Society of Endocrinology.

Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

OpenAIRE

Camara, Geni NL; Cerqueira, Daniela M; Oliveira, Ana PG; Silva, Evandro O; Carvalho, Luciano GS; Martins, Cláudia RF

2003-01-01

As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV) types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using c...

Sirtuin 1 stimulates the proliferation and the expression of glycolysis genes in pancreatic neoplastic lesions.

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Pinho, Andreia V; Mawson, Amanda; Gill, Anthony; Arshi, Mehreen; Warmerdam, Max; Giry-Laterriere, Marc; Eling, Nils; Lie, Triyana; Kuster, Evelyne; Camargo, Simone; Biankin, Andrew V; Wu, Jianmin; Rooman, Ilse

2016-11-15

Metabolic reprogramming is a feature of neoplasia and tumor growth. Sirtuin 1 (SIRT1) is a lysine deacetylase of multiple targets including metabolic regulators such as p53. SIRT1 regulates metaplasia in the pancreas. Nevertheless, it is unclear if SIRT1 affects the development of neoplastic lesions and whether metabolic gene expression is altered.To assess neoplastic lesion development, mice with a pancreas-specific loss of Sirt1 (Pdx1-Cre;Sirt1-lox) were bred into a KrasG12D mutant background (KC) that predisposes to the development of pancreatic intra-epithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC). Similar grade PanIN lesions developed in KC and KC;Sirt1-lox mice but specifically early mucinous PanINs occupied 40% less area in the KC;Sirt1-lox line, attributed to reduced proliferation. This was accompanied by reduced expression of proteins in the glycolysis pathway, such as GLUT1 and GAPDH.The stimulatory effect of SIRT1 on proliferation and glycolysis gene expression was confirmed in a human PDAC cell line. In resected PDAC samples, higher proliferation and expression of glycolysis genes correlated with poor patient survival. SIRT1 expression per se was not prognostic but low expression of Cell Cycle and Apoptosis Regulator 2 (CCAR2), a reported SIRT1 inhibitor, corresponded to poor patient survival.These findings open perspectives for novel targeted therapies in pancreatic cancer.

Sirtuin 1 stimulates the proliferation and the expression of glycolysis genes in pancreatic neoplastic lesions

Science.gov (United States)

Pinho, Andreia V.; Mawson, Amanda; Gill, Anthony; Arshi, Mehreen; Warmerdam, Max; Giry-Laterriere, Marc; Eling, Nils; Lie, Triyana; Kuster, Evelyne; Camargo, Simone; Biankin, Andrew V.; Wu, Jianmin; Rooman, Ilse

2016-01-01

Metabolic reprogramming is a feature of neoplasia and tumor growth. Sirtuin 1 (SIRT1) is a lysine deacetylase of multiple targets including metabolic regulators such as p53. SIRT1 regulates metaplasia in the pancreas. Nevertheless, it is unclear if SIRT1 affects the development of neoplastic lesions and whether metabolic gene expression is altered. To assess neoplastic lesion development, mice with a pancreas-specific loss of Sirt1 (Pdx1-Cre;Sirt1-lox) were bred into a KrasG12D mutant background (KC) that predisposes to the development of pancreatic intra-epithelial neoplasia (PanIN) and ductal adenocarcinoma (PDAC). Similar grade PanIN lesions developed in KC and KC;Sirt1-lox mice but specifically early mucinous PanINs occupied 40% less area in the KC;Sirt1-lox line, attributed to reduced proliferation. This was accompanied by reduced expression of proteins in the glycolysis pathway, such as GLUT1 and GAPDH. The stimulatory effect of SIRT1 on proliferation and glycolysis gene expression was confirmed in a human PDAC cell line. In resected PDAC samples, higher proliferation and expression of glycolysis genes correlated with poor patient survival. SIRT1 expression per se was not prognostic but low expression of Cell Cycle and Apoptosis Regulator 2 (CCAR2), a reported SIRT1 inhibitor, corresponded to poor patient survival. These findings open perspectives for novel targeted therapies in pancreatic cancer. PMID:27494892

NEOPLASTIC LESIONS OF THE APPENDIX

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Piotr Bryk

2013-11-01

Full Text Available The aim of the research was to present the clinical observations of neoplastic lesions of the appendix (one carcinoid and two mucous cysts and to discuss various manners of treatment and prognosis. Material and methods: The authors of the following paper present a description of three cases of appendix tumours, two patients with a mucous cyst and a patient with carcinoid, against the background of all the appendectomies performed at the Clinical Department of General, Endocrine and Oncological Surgery of the Provincial Polyclinical Hospital in Kielce in the years 2005–2011. Results : Within the 7-year period, a total of 11 719 surgical operations have been performed, where 834 (7.1% were that of appendectomy. Among all of the removed vermiform appendixes, neoplastic lesions occurred in three cases constituting a mere 0.3% of all of the appendectomies performed within that period. In two of the cases there was a suspicion of mucous cysts before the surgical operation. In none of the above-mentioned cases was is possible to ultimately establish the diagnosis before the operation. The patients were subjected to a simple appendectomy. The patients are in good clinical health, with no signs of relapse. Conclusions : The presented cases of patients with appendix tumours illustrate the difficulty of preoperative detection of a neoplastic lesion. This is mainly due to a scantily symptomatic course or symptoms typical of appendicitis. In light of this, histopathological examination of each appendix should be treated as obligatory.

Non-neoplastic parenchymal changes in kidney cancer and post-partial nephrectomy recovery of renal function.

Science.gov (United States)

Bazzi, Wassim M; Chen, Ling Y; Cordon, Billy H; Mashni, Joseph; Sjoberg, Daniel D; Bernstein, Melanie; Russo, Paul

2015-09-01

To explore the association of non-neoplastic parenchymal changes (nNPC) with patients' health and renal function recovery after partial nephrectomy (PN). This retrospective review identified 800 pT1a patients who underwent PN at Memorial Sloan Kettering Cancer Center from 2007 to 2012. Pathology reports were reviewed for nNPC graded as mild or severe: vascular sclerosis (VS), glomerulosclerosis (GS), and fibrosis/scarring. Correlations between nNPC and known preoperative predictors of renal function [age, sex, African-American race, estimated glomerular filtration rate (eGFR), American Society of Anesthesiologists (ASA) score, body mass index, coronary artery disease, and hypertension (HTN)] were assessed using Spearman's rank correlation (ρ). Multivariable linear regression, adjusted for the described known preoperative risk predictors, was performed to evaluate whether the parenchymal features were able to predict 6-month postoperative eGFR. In this study, 46 % of tumors had benign surrounding parenchyma. We noted statistically significant yet weak associations of VS with age (ρ = 0.19; p < 0.001), ASA (ρ = 0.09; p < 0.001), preoperative eGFR (ρ = -0.14; p < 0.001), and HTN (ρ = 0.14; p < 0.001). GS also significantly correlated with HTN, but the correlation was again small (ρ = 0.12; p < 0.001). After adjusting for known risk predictors, only GS was a significant predictor of 6-month postoperative eGFR. When compared with no GS, mild and severe GS were negatively associated with a decrease of 4.9 and 10.8 mL/min/1.73 m(2) in 6-month postoperative eGFR, respectively. Presence of VS and GS correlated with patients' baseline health, and presence of GS predicted postoperative renal function recovery.

X-ray-induced in vitro neoplastic transformation of human diploid cells

International Nuclear Information System (INIS)

Borek, C.

1980-01-01

Techniques have recently been developed to identify and score quantitatively neoplastic transformation caused by x-rays in cultured cells derived from rodents. The present report describes for the first time the neoplastic transformation in vitro of human diploid cells by x-ray irradiation into cells which can progress in vitro into advanced stages of neoplastic development, namely, to form colonies in agar and give rise to tumors when injected into nude mice

Stokes shift spectroscopy for the early diagnosis of epithelial precancers in DMBA treated mouse skin carcinogenesis

Science.gov (United States)

Jeyasingh, Ebenezar; Singaravelu, Ganesan; Prakasarao, Aruna

2018-02-01

In this study, we aim to characterize the tissue transformation in dimethylbenz(a)anthracene (DMBA) treated mouse skin tumor model using stokes shift spectroscopy (SSS) technique for early detection of the neoplastic changes. Stokes shift (SS) spectra measured by scanning both excitation and emission wavelength simultaneously with a fixed wavelength of interval (Δλ=20 nm) in vivo from 33 DMBA treated animals and 6 control animals. The SS spectra of normal (n=6), hyperplasia (n=10), dysplasia (n=10), and WDSCC (n=13) of mice skin shows the distinct peaks around 300, 350, and 386 nm may be attributed to tryptophan, collagen, and NADH respectively. From the observed spectral differences and the ratio variables that resulted in better classification between groups, it is concluded that tryptophan, collagen, and NADH are the key fluorophores that undergo changes during tissue transformation process and hence they can be targeted as tumor markers for early neoplastic changes.

A nine - year retrospective study of avian neoplastic diseases in ...

African Journals Online (AJOL)

Avian neoplastic diseases have been identified as one of the leading causes of mortality and production losses in commercial chickens in Nigeria. Although available reports described the trend of Marek's disease in Zaria, Kaduna state, they did not take cognizance of other neoplastic diseases of poultry hence the need for ...

Joint approach based on clinical and imaging features to distinguish non-neoplastic from neoplastic pituitary stalk lesions.

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Ji Ye Lee

Full Text Available Distinguishing non-neoplastic pituitary stalk lesions (non-NPSLs from neoplastic pituitary stalk lesions (NPSLs is a major concern in guiding treatment for a thickened pituitary stalk. Our study aimed to aid provide preoperative diagnostic assistance by combining clinical and magnetic resonance imaging (MRI findings to distinguish non-NPSLs from NPSLs.We recruited 158 patients with thickened pituitary stalk lesions visible on MRI. Laboratory findings included hypopituitarism, diabetes insipidus (DI, and hyperprolactinemia. MR images were assessed for anterior-posterior thickness (mm, diffuse pituitary stalk thickening, cystic changes, a high T1 signal, and glandular or extrasellar involvement. A diagnostic model was developed using a recursive partitioning logistic regression analysis. The model was validated in an independent dataset comprising 63 patients, and its diagnostic performance was compared with that of the original radiological reports.A univariate analysis found significant associations of DI (P = 0.006, absence of extrasellar involvement (P = 0.002, and lower stalk thickness (P = 0.031 with non-NPSLs. A diagnostic model was created using the following parameters (in order of priority: 1 lack of extrasellar involvement, 2 stalk thickness < 5.3 mm, and 3 presence of DI. The diagnostic performance (area under the curve; AUC of this model in the independent set was 0.813, representing a significant improvement over the original radiological reports (AUC: 0.713, P = 0.029.The joint diagnostic approach based on clinical and imaging-based factors robustly distinguished non-NPSLs from NPSLs. This approach could guide treatment strategies and prevent unnecessary surgery in patients with non-NPSL.

Depleted uranium induces neoplastic transformation in human lung epithelial cells.

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Xie, Hong; LaCerte, Carolyne; Thompson, W Douglas; Wise, John Pierce

2010-02-15

Depleted uranium (DU) is commonly used in military armor and munitions, and thus, exposure of soldiers and noncombatants is frequent and widespread. Previous studies have shown that DU has both chemical and radiological toxicity and that the primary route of exposure of DU to humans is through inhalation and ingestion. However, there is limited research information on the potential carcinogenicity of DU in human bronchial cells. Accordingly, we determined the neoplastic transforming ability of particulate DU to human bronchial epithelial cells (BEP2D). We observed the loss of contact inhibition and anchorage independent growth in cells exposed to DU after 24 h. We also characterized these DU-induced transformed cell lines and found that 40% of the cell lines exhibit alterations in plating efficiency and no significant changes in the cytotoxic response to DU. Cytogenetic analyses showed that 53% of the DU-transformed cell lines possess a hypodiploid phenotype. These data indicate that human bronchial cells are transformed by DU and exhibit significant chromosome instability consistent with a neoplastic phenotype.

Use of magnetic resonance imaging to detect neoplastic meningitis: Limited use in leukemia and lymphoma but convincing results in solid tumors

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Pauls, Sandra; Fischer, Ann-Cathrin; Brambs, Hans-Jürgen; Fetscher, Sebastian; Höche, Wolfram; Bommer, Martin

2012-01-01

Background: An early diagnosis of meningitis is important to improve patients’ survival. Data about a direct comparison of cerebrospinal fluid cytology (CSF-cytology) and MRI are very limited. Therefore, the aim of this study was to compare these two diagnostic modalities in diagnosing meningitis in patients with hematopoietic and solid malignancies. Methods: In 68 patients suspicious for neoplastic meningitis, cytology and MRI (1.5 T) was performed. The meningeal, pial or intraparenchymal hyperintense signal or contrast enhancement was correlated to the final CNS diagnosis and to cytology. Results: 44 patients (64.7%) had neoplastic meningitis, 21 patients (30.9%) had non-neoplastic meningitis. The sensitivity to diagnose meningeal disease was 49.2% for MRI and 95.4% for cytology (p < 0.001). In patients with neoplastic meningitis, sensitivity was 45.5% for MRI and 93.2% for cytology (p < 0.001). In patients with infectious meningitis, sensitivity was 57.1% for MRI and 100% for cytology (p = 0.0013). In patients with solid tumors, the sensitivity was 84.6% for both diagnostic methods. The sensitivity for MRI was low in patients with leukemia (20.0%) and lymphoma (37.5%). The positive predictive value (PPV) for MRI to differentiate infectious from neoplastic meningitis was high in patients with infectious meningitis (75.0%), in patients with lymphoma (83.3%), and in patients with solid tumors (72.7%). Ppv was low in patients with leukemia (33.3%). Conclusion: Diagnostic value of MRI for diagnosing meningitis is especially limited in patients with hematopoietic malignancies. MRI better detected leptomeningeal involvement caused by solid tumors than by leukemia or lymphoma. The ppv to specify neoplastic meningitis depends on tumor subtype.

Enhanced sensitivity to neoplastic transformation by 137Cs γ-rays of cells in the G2-/M-phase age interval

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Cao, J.; Wells, R.L.; Elkind, M.M.

1992-01-01

C3H mouse 10T1/2 cells, exposed to low doses of fission-spectrum neutrons, have an enhanced frequency of neoplastic transformation if protracted exposures are used (Hill et al. 1982, 1984a, 1985). To explain this anormaly, a biophysical model was proposed (Elkind 1991 a,b). The unique shape and radiobiological properties of cells in and around mitosis, led to the proposal that the sensitive window is mitosis and possible cells just preceding or just following M phase (Elkind 1991a,b). This study was undertaken using 137 Cs γ-rays. The authors found that late G 2- to M-phase 10T1/2 cells have a maximal sensitivity to neoplastic transformation as well as to killing by 137 Cs γ-rays. (author)

Increased radiation-induced transformation in C3H/10T1/2 cells after transfer of an exogenous c-myc gene

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Sorrentino, V.; Drozdoff, V.; Zeitz, L.; Fleissner, E.

1987-01-01

C3H/10T 1/2 cells were infected with a retroviral vector expressing a mouse c-myc oncogene and a drug-selection marker. The resulting cells, morphologically indistinguishable from C3H/10T l/1, displayed a greatly enhanced sensitivity to neoplastic transformation by ionizing radiation or by a chemical carcinogen. Constitutive expression of myc therefore appears to synergize with an initial carcinogenic event, providing a function analogous to a subsequent event that apparently is required for the neoplastic transformation of these cells. This cell system should prove useful in exploring early stages in radiation-induced transformation

Collaborating with the enemy: function of macrophages in the development of neoplastic disease.

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Eljaszewicz, Andrzej; Wiese, Małgorzata; Helmin-Basa, Anna; Jankowski, Michal; Gackowska, Lidia; Kubiszewska, Izabela; Kaszewski, Wojciech; Michalkiewicz, Jacek; Zegarski, Wojciech

2013-01-01

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc.), and support invasion and metastases formation. Tumor-associated macrophages (TAMs), a predominant component of leukocytic infiltrate, "cooperate" with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.

Collaborating with the Enemy: Function of Macrophages in the Development of Neoplastic Disease

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Andrzej Eljaszewicz

2013-01-01

Full Text Available Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc., neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect, induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages dependent, since these cells show proangiogenic properties, attenuate the adaptive response (anergization of naïve T lymphocytes, induction of Treg cell formation, polarization of immune response towards Th2, etc., and support invasion and metastases formation. Tumor-associated macrophages (TAMs, a predominant component of leukocytic infiltrate, “cooperate” with the neoplastic tissue, leading to the intensified proliferation and the immune escape of the latter. This paper characterizes the function of macrophages in the development of neoplastic disease.

Collaborating with the Enemy: Function of Macrophages in the Development of Neoplastic Disease

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Andrzej Eljaszewicz; Małgorzata Wiese; Anna Helmin-Basa; Michal Jankowski; Lidia Gackowska; Izabela Kubiszewska; Wojciech Kaszewski; Jacek Michalkiewicz; Wojciech Zegarski

2013-01-01

Due to the profile of released mediators (such as cytokines, chemokines, growth factors, etc.), neoplastic cells modulate the activity of immune system, directly affecting its components both locally and peripherally. This is reflected by the limited antineoplastic activity of the immune system (immunosuppressive effect), induction of tolerance to neoplastic antigens, and the promotion of processes associated with the proliferation of neoplastic tissue. Most of these responses are macrophages...

X-ray-induced in vitro neoplastic transformation of human diploid cells

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Borek, C.

1980-01-01

The neoplastic transformation, in vitro, of human diploid cells by x-ray irradiation into cells which can progress, in vitro, into advanced stages of neoplastic development is described. The cells are shown to form colonies in agar and to give rise to tumours when injected into nude mice. (U.K.)

Probiotics against neoplastic transformation of gastric mucosa: effects on cell proliferation and polyamine metabolism.

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Russo, Francesco; Linsalata, Michele; Orlando, Antonella

2014-10-07

Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains (probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori, little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines (putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.

Knowledge of nursing students about the care provided to people with neoplastic wounds

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Roseane Ferreira Gomes

2017-05-01

Full Text Available Objective: To investigate the knowledge of nursing students about the care provided to patients with neoplastic wound. Method: This is an exploratory research of a qualitative nature, which was attended by 15 students of the Bachelor's Degree in Nursing from the Center of Education and Health of the Federal University of Campina Grande, campus Cuité - PB, in the period from October to November 2015. For data collection, we used a form for an interview. The data were analyzed through the Technique of Thematic Analysis of Minayo. Results: From the analysis of the empirical material emerged the following thematic categories: Category 1 - Defining neoplastic wounds; Category 2 - Knowledge incipient on ‘neoplastic wounds’ for academic and professional practice; Category 3 - Envisioning the theme "neoplastic wound" in the Academy; Category 4 - Knowledge about methods of evaluation of neoplastic wounds and Category 5 - Knowledge of therapeutic modalities of neoplastic wounds. Conclusions: The academics know the evaluative method of a patient with neoplastic wound as integralizadora unit of care process; recognize palliative care as the best therapeutic modality for these customers, especially when they are in completion and indicate the products contraindicated in the treatment of these lesions; however, do not mention the covers and recommended substances for the control of the signs and symptoms of these injuries. In this context, it is believed that the creation of academic projects of extension, with the aim of creating opportunities for integration between theory and practice, is one of the ways to improve the knowledge.   Keywords: Knowledge; Students of Nursing; Skin Neoplasms.

Mechanisms of chemical modification of neoplastic cell transformation by ionizing radiation

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Yang, T.C.; Tobias, C.A.

1985-01-01

During space travel, astronauts will be continuously exposed to ionizing radiation; therefore, it is necessary to minimize the radiation damage by all possible means. The authors' studies show that DMSO (when present during irradiation) can protect cells from being killed and transformed by X rays and that low concentration of DMSO can reduce the transformation frequency significantly when it is applied to cells, even many days after irradiation. The process of neoplastic cell transformation is a complicated one and includes at least two different stages: induction and expression. DMSO apparently can modify the radiation damage during both stages. There are several possible mechanisms for the DMSO effect: (1) changing the cell membrane structure and properties; (2) inducing cell differentiation by acting on DNA; and (3) scavanging free radicals in the cell. Recent studies with various chemical agents, e.g., 5-azacytidine, dexamethane, rhodamin-123, etc., indicate that the induction of cell differentiation by acting on DNA may be an important mechanism for the suppression of expression of neoplastic cell transformation by DMSO

Postradiotherapeutic changes and their evolution in MRI in children with aggressive soft tissue tumors.

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Jastrzębska, Małgorzata; Bekiesińska-Figatowska, Monika; Romaniuk-Doroszewska, Anna; Brągoszewska, Hanna; Iwanowska, Beata; Uliasz, Maria; Szkudlińska-Pawlak, Sylwia; Mądzik, Jarosław

2010-07-01

Magnetic resonance imaging is a commonly used method of monitoring of soft tissue tumours. The aim of the work was to describe precisely the typical changes within soft tissues and bones occurring after radiotherapy in children treated for sarcomas and other soft tissue tumours. With time, the changes undergo evolution and their characteristics and comparison with previous examinations help in a difficult differentiation between tumour lesions and posttherapeutic changes. Fifteen children and young adolescents (9 boys and 6 girls) aged between 2 and 22 years (mean age of 13.4 years) with diagnosed aggressive soft tissue tumours, were treated with radiotherapy. There were 102 MRI examinations analysed in the period from February 2004 to February 2008. The examinations were performed with a 1.5T MRI scanner in the following sequences: SE T1, SE T1+fatsat, before and after gadolinium administration (Gd), FSE T2 and STIR in three planes, and, in some selected cases, a dynamic gadolinium-enhanced (DCE MRI) examination with FAME sequence. HISTOPATHOLOGICAL EXAMINATIONS SHOWED: rhabdomyosarcoma (RMS) in 8 cases, synovial sarcoma - 3, agressive desmoid fibroma - 3, mesenchymoma mal. - 1. MRI examinations were performed at different postradiotherapeutic stages, several times in one patient (12 times at the most). Every postirradiation stage revealed a typical picture of posttherapeutic changes. We distinguished four stages and described changes in different sequences within soft tissues and bones, as well as features of contrast enhancement and enhancement curves in a dynamic study. The stages included: I stage - early, up to 3 months after rth, II stage - chronic, from 3 months to 12 months after rth, with some differences between the following periods: • 3-9 months; 9-12 months; III stage - late, from 1 to 3 years after rth, IV stage - distant, more than 3 years after rth. In the early stage, there were 2 cases with a suspicious, equivocal image of postradiotherapeutic

Diagnostic accuracy of transabdominal high-resolution US for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with EUS.

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Lee, Jeong Sub; Kim, Jung Hoon; Kim, Yong Jae; Ryu, Ji Kon; Kim, Yong-Tae; Lee, Jae Young; Han, Joon Koo

2017-07-01

To compare the diagnostic accuracy of transabdominal high-resolution ultrasound (HRUS) for staging gallbladder cancer and differential diagnosis of neoplastic polyps compared with endoscopic ultrasound (EUS) and pathology. Among 125 patients who underwent both HRUS and EUS, we included 29 pathologically proven cancers (T1 = 7, T2 = 19, T3 = 3) including 15 polypoid cancers and 50 surgically proven polyps (neoplastic = 30, non-neoplastic = 20). We reviewed formal reports and assessed the accuracy of HRUS and EUS for diagnosing cancer as well as the differential diagnosis of neoplastic polyps. Statistical analyses were performed using chi-square tests. The sensitivity, specificity, PPV, and NPV for gallbladder cancer were 82.7 %, 44.4 %, 82.7 %, and 44 % using HRUS and 86.2 %, 22.2 %, 78.1 %, and 33.3 % using EUS. HRUS and EUS correctly diagnosed the stage in 13 and 12 patients. The sensitivity, specificity, PPV, and NPV for neoplastic polyps were 80 %, 80 %, 86 %, and 73 % using HRUS and 73 %, 85 %, 88 %, and 69 % using EUS. Single polyps (8/20 vs. 21/30), larger (1.0 ± 0.28 cm vs. 1.9 ± 0.85 cm) polyps, and older age (52.5 ± 13.2 vs. 66.1 ± 10.3 years) were common in neoplastic polyps (p diagnostic accuracy for GB cancer compared with EUS. • HRUS and EUS showed similar diagnostic accuracy for differentiating neoplastic polyps. • Single, larger polyps and older age were common in neoplastic polyps. • HRUS is less invasive compared with EUS.

Neoplastic stem cells: current concepts and clinical perspectives.

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Schulenburg, Axel; Brämswig, Kira; Herrmann, Harald; Karlic, Heidrun; Mirkina, Irina; Hubmann, Rainer; Laffer, Sylvia; Marian, Brigitte; Shehata, Medhat; Krepler, Clemens; Pehamberger, Hubert; Grunt, Thomas; Jäger, Ulrich; Zielinski, Christoph C; Valent, Peter

2010-11-01

Neoplastic stem cells have initially been characterized in myeloid leukemias where NOD/SCID mouse-repopulating progenitors supposedly reside within a CD34+/Lin- subset of the malignant clone. These progenitors are considered to be self-renewing cells responsible for the in vivo long-term growth of neoplastic cells in leukemic patients. Therefore, these cells represent an attractive target of therapy. In some lymphoid leukemias, NOD/SCID mouse-repopulating cells were also reported to reside within the CD34+/Lin- subfraction of the clone. More recently, several attempts have been made to transfer the cancer stem cell concept to solid tumors and other non-hematopoietic neoplasms. In several of these tumors, the cell surface antigens AC133 (CD133) and CD44 are considered to indicate the potential of a cell to initiate permanent tumor formation in vivo. However, several questions concerning the phenotype, self-renewal capacity, stroma-dependence, and other properties of cancer- or leukemia-initiating cells remain to be solved. The current article provides a summary of our current knowledge on neoplastic (cancer) stem cells, with special emphasis on clinical implications and therapeutic options as well as a discussion about conceptual and technical limitations. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Pitfalls of improperly procured adjacent non-neoplastic tissue for somatic mutation analysis using next-generation sequencing

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Lei Wei

2016-10-01

Full Text Available Abstract Background The rapid adoption of next-generation sequencing provides an efficient system for detecting somatic alterations in neoplasms. The detection of such alterations requires a matched non-neoplastic sample for adequate filtering of non-somatic events such as germline polymorphisms. Non-neoplastic tissue adjacent to the excised neoplasm is often used for this purpose as it is simultaneously collected and generally contains the same tissue type as the neoplasm. Following NGS analysis, we and others have frequently observed low-level somatic mutations in these non-neoplastic tissues, which may impose additional challenges to somatic mutation detection as it complicates germline variant filtering. Methods We hypothesized that the low-level somatic mutation observed in non-neoplastic tissues may be entirely or partially caused by inadvertent contamination by neoplastic cells during the surgical pathology gross assessment or tissue procurement process. To test this hypothesis, we applied a systematic protocol designed to collect multiple grossly non-neoplastic tissues using different methods surrounding each single neoplasm. The procedure was applied in two breast cancer lumpectomy specimens. In each case, all samples were first sequenced by whole-exome sequencing to identify somatic mutations in the neoplasm and determine their presence in the adjacent non-neoplastic tissues. We then generated ultra-deep coverage using targeted sequencing to assess the levels of contamination in non-neoplastic tissue samples collected under different conditions. Results Contamination levels in non-neoplastic tissues ranged up to 3.5 and 20.9 % respectively in the two cases tested, with consistent pattern correlated with the manner of grossing and procurement. By carefully controlling the conditions of various steps during this process, we were able to eliminate any detectable contamination in both patients. Conclusion The results demonstrated that the

Mesenchymal stromal cells of osteosarcoma patients do not show evidence of neoplastic changes during long-term culture.

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Buddingh, Emilie P; Ruslan, S Eriaty N; Reijnders, Christianne M A; Szuhai, Karoly; Kuijjer, Marieke L; Roelofs, Helene; Hogendoorn, Pancras C W; Maarten Egeler, R; Cleton-Jansen, Anne-Marie; Lankester, Arjan C

2015-01-01

In vitro expanded mesenchymal stromal cells (MSCs) are increasingly used as experimental cellular therapy. However, there have been concerns regarding the safety of their use, particularly with regard to possible oncogenic transformation. MSCs are the hypothesized precursor cells of high-grade osteosarcoma, a tumor with often complex karyotypes occurring mainly in adolescents and young adults. To determine if MSCs from osteosarcoma patients could be predisposed to malignant transformation we cultured MSCs of nine osteosarcoma patients and five healthy donors for an average of 649 days (range 601-679 days). Also, we compared MSCs derived from osteosarcoma patients at diagnosis and from healthy donors using genome wide gene expression profiling. Upon increasing passage, increasing frequencies of binucleate cells were detected, but no increase in proliferation suggestive of malignant transformation occurred in MSCs from either patients or donors. Hematopoietic cell specific Lyn substrate 1 (HLCS1) was differentially expressed (fold change 0.25, P value 0.0005) between MSCs of osteosarcoma patients (n = 14) and healthy donors (n = 9). This study shows that although HCLS1 expression was downregulated in MSCs of osteosarcoma patients and binucleate cells were present in both patient and donor derived MSCs, there was no evidence of neoplastic changes to occur during long-term culture.

Para neoplastic syndromes: Usefulness of 18F-fluoro-deoxy-glucose (F.D.G.) positron emission tomography (PET)

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Banayan, S.; Janier, M.; Guillerma-Zucchi, N.; Billotey, C.; Ninet, J.; Delmas, P.; Thivolet, C.; Pellet, O.

2008-01-01

Background We evaluated the performance of 18 F-fluorodeoxyglucose ( 18 F.D.G.) positron emission tomography (PET) in the diagnosis of underlying malignancy in cases of suspected para neoplastic syndrome (P.S.). Methods 18 F.D.G.-PET was performed in 31 patients, clinically suspected to have P.S.. The P.S. were 34, among which 12 neurological diseases, eight endocrine, seven rheumatological, one dermatological and six vascular. We compared computed tomography (CT), iodine-enhanced most of the time, and 18 F.D.G.-PET reports to clinicians definitive conclusion at the end of the work-up and a follow-up period of, at least, two months. Results We obtained a histological diagnosis of cancer for ten patients, but could only identify the primary site of malignancy for nine of them. 18 F.D.G.-PET showed six primary sites among which three were not seen on CT. CT disclosed four primary sites, among which one was not seen on 18 F.D.G.-PET. In one case, 18 F.D.G.-PET disclosed regional lymph node metastases whereas these were not identified by CT. Eleven non-neoplastic causes were evidenced, among which 18 F.D.G.-PET played a major role in three cases. Ten causes were still undetermined at the end of the study. Conclusion Whole-body 18 F.D.G.-PET study plays an important role in the identification of underlying malignancy in clinically suspected para neoplastic syndromes; either by identifying the primary tumor or by directing biopsy of metastases. Furthermore, it can identify non-neoplastic causes. (authors)

Role of nuclear medicine in pulmonary neoplastic processes

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Waxman, A.D.

1986-01-01

It has been demonstrated that the single most important factor in determining survival in patients with bronchogenic carcinoma is the extent of spread of metastasis from the primary lesion. This explains the extensive efforts in developing accurate staging tests for pulmonary tumors, both primary and metastatic, with special emphasis on the determination of pulmonary hilar and mediastinal spread of disease. Continued improvements in nuclear medicine instrumentation along with the development of tumor specific radiopharmaceuticals, as well as agents that have the capability of tracking tumor viability, have changed the orientation of scintigraphic techniques in the evaluation of pulmonary neoplastic processes. Gallium scintigraphy is no longer considered as a primary imaging modality in the staging of pulmonary tumors, and in most institutions has been replaced by computed tomography (CT) for this purpose. It has been demonstrated that gallium, relative to other imaging modalities, is a sensitive indicator of hilar spread of tumor. However, because of the normally high background activity within the sternum and spine, mediastinal abnormalities are poorly detected. Since most pulmonary tumors metastasize via regional nodes to the pulmonary hilum and then to the mediastinum, the high sensitivity for the detection of pulmonary hilar abnormalities and the high specificity for mediastinal lesion detection suggest that gallium scintigraphy is a valuable adjunctive test when used appropriately. Thallium 201 as a tumor agent is being studied by several institutions. Preliminary results indicate a high degree of sensitivity for the detection of pulmonary hilar and mediastinal lesions and there are early indications that thallium is a promising agent to evaluate tumor viability. 52 references

Neoplastic lesions of the temporomandibular joint (TMJ): diagnosis, differential diagnosis and intervention

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Vogl, T.J.; Abolmaali, N.; Schedel, H.; Bergh, B.

2001-01-01

Purpose. To evaluate the effectiveness of diagnostic and interventional radiological techniques for neoplastic lesions of the temporomandibular joint (TMJ). Material and methods. Modern diagnosis of the TMJ is based on the clinical use of conventional X-ray techniques, computed tomography (CT), magnetic resonance imaging (MRI) and interventional techniques like biopsies, vascular occlusion and ablation. Results. Conventional X-ray still forms the basic diagnostic procedure applied in open and closed mouth position. CT improves the diagnostic information and serves as the standard diagnostical instrument for cartaliganeous or osseous neoplastic lesions. MRI evaluates soft tissue infiltration in multiplanar techniques and high spatial resolution. Interventional vascular and ablative techniques improve the treatment of neoplastic disorders. (orig.) [de

Treatment of non-neoplastic renal hemorrhage with segmental embolization of renal artery

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Zhu Bing

2007-01-01

Objective: To explore the value of segmental embolization of renal artery in dealing with non- neoplastic renal hemorrhage. Methods: Four cases of non-neoplastic hemorrhage, including 2 with bleeding after renal acupuncture biopsy, 2 with bleeding after nephrolithotomy and 1 with congenital renal arteriovenous malformation, were treated with superselective segmental embolization of renal artery. 2 were embolized with coil, 1 with alcohol plus coil and 1 with PVA parcels. Results: Hematuria disappeared in 1-3 days. There was no recurrence in 7-45 months follow up and no complications induced by embolization. Conclusion: It is a safe and reliable therapy to treat non-neoplastic renal hemorrhage with segmental embolization of renal artery. (authors)

Detection of immune complexes in sera of dogs with rheumatic and neoplastic diseases by 125I-Clq binding test

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Terman, D.S.; Moore, D.; Collins, J.; Johnston, B.; Person, D.; Templeton, J.; Poser, R.; Quinby, F.

1979-01-01

Some canine rheumatic and neoplastic diseases bear a striking clinical and serological resemblance to their counterparts in man. In the present study, human 125 I-Clq was employed in a radioimmunoassay for detection of immune complexes in sera of normal dogs and those with rheumatic and neoplastic diseases. Human 125 I-Clq showed binding of 16.7 +- 5.73% in a group of normal dog sera with binding of 32.5 +- 17.3% and 43.0 +- 16.0% in sera of dogs with rheumatic and neoplastic diseases. respectively. Human 125 I-Clq bound similar quantities of heat-aggregated canine and human gamma-globulin over a broad range of concentrations and human 125 I-Clq binding in canine sera was effectively inhibited by similar quantities of heat aggregated canine and human gamma-globulin. Seven of 12 dogs with elevated levels of Clq binding had active clinical and serological rheumatic disease (SLE or rheumatoid arthritis), while none of 7 dogs with values within the normal range had active clinical disease. All 5 dogs with widespread osteogenic sarcoma and all 4 dogs with high grade adenocarcinoma of the mammary gland had elevated Clq binding values while 2 animals with low grade malignancies without evident metastases did not. Thus, it appears that human 125 I-Clq may be employed to assay immune complexes in canine sera and may be a valuable technique for the study of dogs with various rheumatic and neoplastic diseases. (author)

Diffusion tensor imaging in inflammatory and neoplastic intramedullary spinal cord lesions: Focusing on fiber tracking

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Kim, Hyo Jin; Lee, Joon Woo; Lee, Eugene; Kim, Sung Gon; Kang, Yu Suhn; Ahn, Joong Mo; Kang, Heung Sik [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

2017-02-15

Inflammatory and neoplastic intramedullary spinal cord lesions have overlapping clinical features, and it is occasionally difficult to distinguish one from the other on conventional magnetic resonance imaging. We aimed to compare diffusion tensor imaging findings between inflammatory and neoplastic intramedullary spinal cord lesions, with a specific focus on patterns of fiber tracking. Diffusion tensor imaging was performed in patients with either inflammatory or neoplastic intramedullary spinal cord lesions. The fiber tracking patterns (categorized as “intact,” “displaced,” or “interrupted”) were compared between these two groups. Eight patients were included in the study: 5 patients with pathologically or clinically confirmed inflammatory lesions and 3 patients with pathologically or clinically confirmed neoplastic lesions. Among the 5 patients with inflammatory lesions, 2 patients exhibited the displaced pattern and 3 patients exhibited the intact pattern. Among the 3 patients with neoplastic lesions, 1 patient exhibited the intact pattern, 1 patient exhibited the displaced pattern, and 1 patient exhibited the interrupted pattern. In this study, inflammatory and neoplastic intramedullary spinal cord lesions were not clearly differentiated by fiber tracking; both conditions can present with overlapping features such as displaced fibers. The exclusion of inflammatory conditions based on the presence of displaced fibers in fiber tracking images should be avoided.

Prenatal exposure to BPA alters the epigenome of the rat mammary gland and increases the propensity to neoplastic development.

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Eugen Dhimolea

Full Text Available Exposure to environmental estrogens (xenoestrogens may play a causal role in the increased breast cancer incidence which has been observed in Europe and the US over the last 50 years. The xenoestrogen bisphenol A (BPA leaches from plastic food/beverage containers and dental materials. Fetal exposure to BPA induces preneoplastic and neoplastic lesions in the adult rat mammary gland. Previous results suggest that BPA acts through the estrogen receptors which are detected exclusively in the mesenchyme during the exposure period by directly altering gene expression, leading to alterations of the reciprocal interactions between mesenchyme and epithelium. This initiates a long sequence of altered morphogenetic events leading to neoplastic transformation. Additionally, BPA induces epigenetic changes in some tissues. To explore this mechanism in the mammary gland, Wistar-Furth rats were exposed subcutaneously via osmotic pumps to vehicle or 250 µg BPA/kg BW/day, a dose that induced ductal carcinomas in situ. Females exposed from gestational day 9 to postnatal day (PND 1 were sacrificed at PND4, PND21 and at first estrus after PND50. Genomic DNA (gDNA was isolated from the mammary tissue and immuno-precipitated using anti-5-methylcytosine antibodies. Detection and quantification of gDNA methylation status using the Nimblegen ChIP array revealed 7412 differentially methylated gDNA segments (out of 58207 segments, with the majority of changes occurring at PND21. Transcriptomal analysis revealed that the majority of gene expression differences between BPA- and vehicle-treated animals were observed later (PND50. BPA exposure resulted in higher levels of pro-activation histone H3K4 trimethylation at the transcriptional initiation site of the alpha-lactalbumin gene at PND4, concomitantly enhancing mRNA expression of this gene. These results show that fetal BPA exposure triggers changes in the postnatal and adult mammary gland epigenome and alters gene

Perfusion abnormalities in congenital and neoplastic pulmonary disease: comparison of MR perfusion and multislice CT imaging

International Nuclear Information System (INIS)

Boll, Daniel T.; Lewin, Jonathan S.; Young, Philip; Gilkeson, Robert C.; Siwik, Ernest S.

2005-01-01

The aim of this work was to assess magnetic resonance (MR) perfusion patterns of chronic, nonembolic pulmonary diseases of congenital and neoplastic origin and to compare the findings with results obtained with pulmonary, contrast-enhanced multislice computed tomography (CT) imaging to prove that congenital and neoplastic pulmonary conditions require MR imaging over the pulmonary perfusion cycle to successfully and directly detect changes in lung perfusion patterns. Twenty-five patients underwent concurrent CT and MR evaluation of chronic pulmonary diseases of congenital (n=15) or neoplastic (n=10) origin. Analysis of MR perfusion and contrast-enhanced CT datasets was realized by defining pulmonary and vascular regions of interest in corresponding positions. MR perfusion calculated time-to-peak enhancement, maximal enhancement and the area under the perfusion curve. CT datasets provided pulmonary signal-to-noise ratio measurements. Vessel centerlines of bronchial arteries were determined. Underlying perfusion type, such as pulmonary arterial or systemic arterial supply, as well as regions with significant variations in perfusion were determined statistically. Analysis of the pulmonary perfusion pattern detected pulmonary arterial supply in 19 patients; six patients showed systemic arterial supply. In pulmonary arterial perfusion, MR and multislice CT imaging consistently detected the perfusion type and regions with altered perfusion patterns. In bronchial arterial supply, MR perfusion and CT imaging showed significant perfusion differences. Patients with bronchial arterial supply had bronchial arteries ranging from 2.0 to 3.6 mm compared with submillimeter diameters in pulmonary arterial perfusion. Dynamic MR imaging of congenital and neoplastic pulmonary conditions allowed characterization of the pulmonary perfusion type. CT imaging suggested the presence of systemic arterial perfusion by visualizing hypertrophied bronchial arteries. (orig.)

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry.

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Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student'st test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Marolla, Ana Paula Cleto [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Waisberg, Jaques [Hospital do Servidor Público Estadual, São Paulo, SP (Brazil); Faculdade de Medicina do ABC, Santo André, SP (Brazil); Saba, Gabriela Tognini [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Waisberg, Daniel Reis [Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP (Brazil); Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva [Faculdade de Medicina do ABC, Santo André, SP (Brazil)

2015-07-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

International Nuclear Information System (INIS)

Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues

The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

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Sun, Yu; Wong, Nicholas; Guan, Yinghui; Salamanca, Clara M.; Cheng, Jung Chien; Lee, Jonathan M.; Gray, Joe W.; Auersperg, Nelly

2008-04-25

Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We defined the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.

Nanoscale changes in chromatin organization represent the initial steps of tumorigenesis: a transmission electron microscopy study

International Nuclear Information System (INIS)

Cherkezyan, Lusik; Backman, Vadim; Stypula-Cyrus, Yolanda; Subramanian, Hariharan; White, Craig; Dela Cruz, Mart; Wali, Ramesh K; Goldberg, Michael J; Bianchi, Laura K; Roy, Hemant K

2014-01-01

Nuclear alterations are a well-known manifestation of cancer. However, little is known about the early, microscopically-undetectable stages of malignant transformation. Based on the phenomenon of field cancerization, the tissue in the field of a tumor can be used to identify and study the initiating events of carcinogenesis. Morphological changes in nuclear organization have been implicated in the field of colorectal cancer (CRC), and we hypothesize that characterization of chromatin alterations in the early stages of CRC will provide insight into cancer progression, as well as serve as a biomarker for early detection, risk stratification and prevention. For this study we used transmission electron microscopy (TEM) images of nuclei harboring pre-neoplastic CRC alterations in two models: a carcinogen-treated animal model of early CRC, and microscopically normal-appearing tissue in the field of human CRC. We quantify the chromatin arrangement using approaches with two levels of complexity: 1) binary, where chromatin is separated into areas of dense heterochromatin and loose euchromatin, and 2) grey-scale, where the statistics of continuous mass-density distribution within the nucleus is quantified by its spatial correlation function. We established an increase in heterochromatin content and clump size, as well as a loss of its characteristic peripheral positioning in microscopically normal pre-neoplastic cell nuclei. Additionally, the analysis of chromatin density showed that its spatial distribution is altered from a fractal to a stretched exponential. We characterize quantitatively and qualitatively the nanoscale structural alterations preceding cancer development, which may allow for the establishment of promising new biomarkers for cancer risk stratification and diagnosis. The findings of this study confirm that ultrastructural changes of chromatin in field carcinogenesis represent early neoplastic events leading to the development of well

A HISTOPATHOLOGICAL STUDY OF NEOPLASTIC LESIONS OF UTERINE CERVIX OF PERI AND POSTMENOPAUSAL WOMEN

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Jogesh Kakati

2017-03-01

Full Text Available BACKGROUND Neoplastic lesions of uterine cervix is one of the most common malignant neoplasms in women. The tremendous success in giving a confirmed diagnosis of the disease by doing histopathological examination is of prime importance in giving the most appropriate treatment and to understand the prognosis. The aim of the study is to study the incidence and age-wise distribution of the neoplastic lesions of the uterine cervix in peri and postmenopausal women by doing histopathological examination of neoplastic lesions and by doing correlation of clinical findings with histopathological examination. MATERIALS AND METHODS The study included 803 cases of total cervical specimens, out of which 180 cases of neoplastic cervical lesions were found, out of which 150 cases were found in the peri and postmenopausal age groups, i.e. above 40 years of age. The study was done in Gauhati Medical College and Hospital, Guwahati, from the period 1 st June, 2013, to 1 st June, 2014. The specimens that were included in the study were punch biopsies, hysterectomies and polypectomies and cervical specimens were studied by doing histopathological examinations. RESULTS Out of the 150 cases of neoplastic lesions in the peri and postmenopausal women, the most common neoplastic lesion was cervical intraepithelial neoplasia, i.e. CIN (8.3% of the cervix, followed by malignant (5.6% and benign (4.7% lesions of the cervix in this study group of patients. CONCLUSION Histopathological examination of the cervix is an effective method of giving a confirmed diagnosis of all the noncancerous, precancerous and cancerous lesions of uterine cervix, which helps in giving the most appropriate treatment and also helps in understanding the prognosis.

[Carcinogenesis and its mechanism of mutant-type[12Asp]K-ras4B gene].

Science.gov (United States)

Gui, Li-ming; Wei, Li-hui; Zhang, Ying-mei; Wang, Jian-liu; Wang, Ying; Chen, Ying; Ma, Da-long

2002-01-01

Ras gene plays an important role in the extra- and intra-cellular signal transduction pathway. It mediates series cascade reactions, and eventually actives transcriptional factors in nucleus. It is unknown on the mechanism of carcinogenesis of Ras gene in endometrial carcinoma, though K-ras mutant is very common in endometrial atypical hyperplasia and carcinoma. On basis of discovering the mutation in 12th codon of K-ras in endometrial carcinoma cell line, HEC-1A, we explored the carcinogenesis and molecular mechanism of mutant-type [12Asp] K-ras4B gene. (1) Full-length [12Asp]K-ras4B cDNA was amplified with RT-PCR, then inserted into pcDI eukaryotic expressive vector. (2) Morphological change, growth kinetics in vitro and tumorigencity in nude mice in vivo after-before transfection were observed. (3) To test the cell growth kinetics by methyl thiazolium tetrazolium (MTT) and [3H]thymidine incorporation method. (1) The authors have successfully constructed eukaryotic expression plasmid pcDI-[12Asp] K-ras4B; (2) To confirm that [12Asp] K-ras4B mutant can trigger the neoplastic transformation of NIH3T3 cells by test in vitro and in vivo. (3) After pMCV-RasN17 plasmid, a Ras mutant were transfected into pcDI-[12Asp] K-ras4B cells, the growth of this cell were restrained significantly in comparison with control group. (4) These findings indicate the expression of RafS621A resulted in remarkable inhibition in proliferation of pcDI-[12Asp]K-ras4B cell (P ras4B cell growth (P ras4B gene alone is able to cause neoplastic transformation in NIH3T3 cells in vitro and in vivo. (2) [12Asp]K-ras4B-induced NIH3T3 cells neoplastic transformation required Raf signaling pathway.

Quantitative evaluation of RASSF1A methylation in the non-lesional, regenerative and neoplastic liver

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Di Gioia, Sonia; Bianchi, Paolo; Destro, Annarita; Grizzi, Fabio; Malesci, Alberto; Laghi, Luigi; Levrero, Massimo; Morabito, Alberto; Roncalli, Massimo

2006-01-01

Background Epigenetic changes during ageing and their relationship with cancer are under the focus of intense research. RASSF1A and NORE1A are novel genes acting in concert in the proapoptotic pathway of the RAS signalling. While NORE1A has not been previously investigated in the human liver, recent reports have suggested that RASSF1A is frequently epigenetically methylated not only in HCC but also in the cirrhotic liver. Methods To address whether epigenetic changes take place in connection to age and/or to the underlying disease, we investigated RASSF1A and NORE1A gene promoter methylation by conventional methylation specific PCR and Real-Time MSP in a series of hepatitic and non-hepatitic livers harboring regenerative/hyperplastic (cirrhosis/focal nodular hyperplasia), dysplastic (large regenerative, low and high grade dysplastic nodules) and neoplastic (hepatocellular adenoma and carcinoma) growths. Results In the hepatitic liver (chronic hepatitic/cirrhosis, hepatocellular nodules and HCC) we found widespread RASSF1A gene promoter methylation with a methylation index that increased from regenerative conditions (cirrhosis) to hepatocellular nodules (p < 0.01) to HCC (p < 0.001). In the non-hepatitic liver a consistent pattern of gene methylation was also found in both lesional (focal nodular hyperplasia and hepatocellular adenoma) and non-lesional tissue. Specifically, hepatocellular adenomas (HA) showed a methylation index significantly higher than that detected in focal nodular hyperplasia (FNH) (p < 0.01) and in non-lesional tissue (p < 0.001). In non-lesional liver also the methylation index gradually increased by ageing (p = 0.002), suggesting a progressive spreading of methylated cells over time. As opposed to RASSF1A gene promoter methylation, NORE1A gene was never found epigenetically alterated in both hepatitic and non-hepatitic liver. Conclusion We have shown that in non-lesional, regenerative and neoplastic liver the RASSF1A gene is increasingly

Serum amyloid A protein in amyloidosis, rheumatic, and neoplastic diseases

International Nuclear Information System (INIS)

Benson, M.D.; Cohen, A.S.

1979-01-01

Serum levels of amyloid protein A (SAA) have been shown to be elevated in different types of amyloidosis and in rheumatic diseases by radioimmunoassay using 125 iodine labeled AA and anti-AA. SAA levels were elevated in both primary and secondary amyloidosis, but there were highly significant differences between these levels. In heredofamilial amyloid, SAA levels were within normal limits. While the mean SAA level was elevated in persons over 70 years, the fact that some persons in this age group had normal levels suggested that marked elevation after age 70 may be due to occult inflammatory or neoplastic disease. High SAA levels in patients with rheumatoid arthritis correlated, in most cases, with physician evaluation of disease activity and Westergren ESR. SAA levels in patients with systemic lupus erythematosus were lower than those in patients with rheumatoid arthritis, and most patients with degenerative joint disease had normal levels. Very high levels of SAA were found in patients with neoplastic diseases. Patients with carcinoma of the lung and bowel had much higher levels than patients with carcinoma of the breast. Determination of SAA levels may be of value in evaluating different forms of systemic amyloidosis, assessing the activity of rheumatic disease, and screening for occult inflammatory or neoplastic disease

Trisomy of the Dscr1 gene suppresses early progression of pancreatic intraepithelial neoplasia driven by oncogenic Kras

International Nuclear Information System (INIS)

Lee, Jang Choon; Shin, Jimin; Baek, Kwan-Hyuck

2013-01-01

Highlights: •A single extra copy of Dscr1 restrains progression of PanIN-1A to PanIN-1B lesions. •Dscr1 trisomy attenuates calcineurin–NFAT pathway in neoplastic ductal epithelium. •Dscr1 trisomy leads to upregulation of p15 INK4b in neoplastic ductal epithelium. •A single extra copy of Dscr1 reduces epithelial proliferation in early PanIN lesions. •Dscr1 trisomy may protect Down syndrome individuals from pancreatic cancer. -- Abstract: Individuals with Down syndrome exhibit remarkably reduced incidence of most solid tumors including pancreatic cancer. Multiple mechanisms arising from the genetic complexity underlying Down syndrome has been suggested to contribute to such a broad cancer protection. In this study, utilizing a genetically engineered mouse model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia-1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN lesions mediated by oncogenic Kras G12D . In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15 Ink4b tumor suppressor and reduction of cell proliferation in early PanIN lesions. Our data suggest that attenuation of calcineurin–NFAT signaling in neoplastic pancreatic ductal epithelium by a single extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN lesions driven by oncogenic Kras, and thus may be a potential mechanism underlying reduced incidence of pancreatic cancer in Down syndrome individuals

Glycaemic adverse drug reactions from anti-neoplastics used in ...

African Journals Online (AJOL)

235625 records ... Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ... Based on the emphasized nine antineoplastic drugs with high hyperglycemic ADR incidence, we found: fluorouracil, sorafenib and pemetrexed with high ADR record of metabolism and nutrition disorders; ...

Value of the biological data in the sonographic diagnosis of neoplastic biliary obstruction

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Ferrari, F; Fagioli Zucchi, A; Rappuoli, G; Guercia, M; Terrosi Vagnoli, P

1988-01-01

The authors' purpose is to demonstrate the possibility of improving US reliability in the diagnosis of neoplastic obstructions of the bile ducts, basing their study on the hematic alkaline phosphates level (AP), wich is an earlier sign of obstruction than bilirubine values. All 368 patients observed had AP levels above the threshold of 270 IU/l. The 34 patients with neoplastic obstruction (including 13 without jaundice) had more than twice the normal level of AP, and presented with at least one dilated bile duct in the biliary tree. Coronal scans of the main bile duct are fundamental in the diagnosis of the level of obstruction. It seems thus possible to affirm that US diagnosis of the biliary obstruction, together with high AP values (more than twice the normal), provides with reliable information as to the neoplastic nature of the biliary obstruction, even if jaundice is not present.

Value of the biological data in the sonographic diagnosis of neoplastic biliary obstruction

International Nuclear Information System (INIS)

Ferrari, F.; Fagioli Zucchi, A.; Rappuoli, G.; Guercia, M.; Terrosi Vagnoli, P.

1988-01-01

The authors' purpose is to demonstrate the possibility of improving US reliability in the diagnosis of neoplastic obstructions of the bile ducts, basing their study on the hematic alkaline phosphates level (AP), wich is an earlier sign of obstruction than bilirubine values. All 368 patients observed had AP levels above the threshold of 270 IU/l. The 34 patients with neoplastic obstruction (including 13 without jaundice) had more than twice the normal level of AP, and presented with at least one dilated bile duct in the biliary tree. Coronal scans of the main bile duct are fundamental in the diagnosis of the level of obstruction. It seems thus possible to affirm that US diagnosis of the biliary obstruction, together with high AP values (more than twice the normal), provides with reliable information as to the neoplastic nature of the biliary obstruction, even if jaundice is not present

Telomere length in normal and neoplastic canine tissues.

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

2007-12-01

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

Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions.

Science.gov (United States)

Beger, Hans G; Schwarz, Michael; Poch, Bertram

2012-11-01

Cystic neoplasms of the pancreas are diagnosed frequently due to early use of abdominal imaging techniques. Intraductal papillary mucinous neoplasm, mucinous cystic neoplasm, and serous pseudopapillary neoplasia are considered pre-cancerous lesions because of frequent transformation to cancer. Complete surgical resection of the benign lesion is a pancreatic cancer preventive treatment. The application for a limited surgical resection for the benign lesions is increasingly used to reduce the surgical trauma with a short- and long-term benefit compared to major surgical procedures. Duodenum-preserving total pancreatic head resection introduced for inflammatory tumors in the pancreatic head transfers to the patient with a benign cystic lesion located in the pancreatic head, the advantages of a minimalized surgical treatment. Based on the experience of 17 patients treated for cystic neoplastic lesions with duodenum-preserving total pancreatic head resection, the surgical technique of total pancreatic head resection for adenoma, borderline tumors, and carcinoma in situ of cystic neoplasm is presented. A segmental resection of the peripapillary duodenum is recommended in case of suspected tissue ischemia of the peripapillary duodenum. In 305 patients, collected from the literature by PubMed search, in about 40% of the patients a segmental resection of the duodenum and 60% a duodenum and common bile duct-preserving total pancreatic head resection has been performed. Hospital mortality of the 17 patients was 0%. In 305 patients collected, the hospital mortality was 0.65%, 13.2% experienced a delay of gastric emptying and a pancreatic fistula in 18.2%. Recurrence of the disease was 1.5%. Thirty-two of 175 patients had carcinoma in situ. Duodenum-preserving total pancreatic head resection for benign cystic neoplastic lesions is a safe surgical procedure with low post-operative morbidity and mortality.

Importance of Absent Neoplastic Epithelium in Patients Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Science.gov (United States)

Enblad, Malin; Birgisson, Helgi; Wanders, Alkwin; Sköldberg, Filip; Ghanipour, Lana; Graf, Wilhelm

2016-04-01

The importance of absent neoplastic epithelium in specimens from cytoreductive surgery (CRS) is unknown. This study aimed to investigate the prevalence and prognostic value of histopathology without neoplastic epithelium in patients treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). Data were extracted from medical records and histopathology reports for patients treated with initial CRS and HIPEC at Uppsala University Hospital, Sweden, between 2004 and 2012. Patients with inoperable disease and patients undergoing palliative non-CRS surgery were excluded from the study. Patients lacking neoplastic epithelium in surgical specimens from CRS, with or without mucin, were classified as "neoplastic epithelium absent" (NEA), and patients with neoplastic epithelium were classified as "neoplastic epithelium present" (NEP). The study observed NEA in 78 of 353 patients (22 %). Mucin was found in 28 of the patients with NEA. For low-grade appendiceal mucinous neoplasms and adenomas, the 5-year overall survival rate was 100 % for NEA and 84 % for NEP, and the 5-year recurrence-free survival rate was 100 % for NEA and 59 % for NEP. For appendiceal/colorectal adenocarcinomas (including tumors of the small intestine), the 5-year overall survival rate was 61 % for NEA and 38 % for NEP, and the 5-year recurrence-free survival rate was 60 % for NEA and 14 % for NEP. Carcinoembryonic antigen level, peritoneal cancer index, and completeness of the cytoreduction score were lower in patients with NEA. A substantial proportion of patients undergoing CRS and HIPEC have NEA. These patients have a favorable prognosis and a decreased risk of recurrence. Differences in patient selection can affect the proportion of NEA and hence explain differences in survival rates between reported series.

Biomarkers for screening of lung cancer and pre-neoplastic lesions in a high risk Chilean population

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Marta I Adonis

2014-01-01

Full Text Available BACKGROUND: The mortality of lung cancer (LC, increases each year in the world, in spite of any advances, in development of new drugs to advance stages of LC. The high incidence of LC has been associated with smoking habit, genetic diversity and environmental pollution. Antofagasta region has been reported to have the highest LC mortality rate in Chile and its inhabitants were exposed to arsenic in their drinking water in concentrations as high as 870 μg/L. Non-invasive techniques such as biomarkers (Automatic Quantitative Cytometry: AQC and DR70 and Auto Fluorescence Bronchoscopy (AFB might be potentially useful as a supplementary diagnostic approach and early detection. Early detection is one of the most important factors to intervene and prevent cancer progression in LC. This is a work of an ongoing prospective bimodality cancer surveillance study in high risk LC volunteers. Enrolment was done in subjects from Antofagasta and Metropolitan regions. In addition, we enrolled subjects who were suspected of having lung cancer. AQC, DR70 and AFB were used as tools in the detection of pre-neoplastic (PNL and neoplastic lesions (NL. RESULTS: Half of the samples, classified as suspicious by AFB, were confirmed as metaplasia or dysplasia by histopathology. For LC, DR70 showed a higher sensitivity (95.8% and specificity (91.9% than AQC. However, for PNL AQC showed a higher sensitivity (91.9% than DR70 (27.3%, although both with low PPV values. As a pre screener, both biomarkers might be employed as complementary tools to detect LC, especially as serially combined tests, with a sensitivity of 60% and a PPV of 65.2%. Additionally, the use of parallel combined tests might support the detection of PNL (sensitivity 91.2%; PPV 49.1%. CONCLUSION: This work adds information on cellular and molecular biomarkers to complement imaging techniques for early detection of LC in Latin America that might contribute to formulate policies concerning screening of LC

Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

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Patrícia F. Castro

2016-01-01

Full Text Available Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates.

Prevalence of Neoplastic Diseases in Pet Birds Referred for Surgical Procedures

Science.gov (United States)

Castro, Patrícia F.; Fantoni, Denise T.; Miranda, Bruna C.; Matera, Julia M.

2016-01-01

Neoplastic disease is common in pet birds, particularly in psittacines, and treatment should be primarily aimed at tumor eradication. Nineteen cases of pet birds submitted to diagnostic and/or therapeutic surgical procedures due to neoplastic disease characterized by the presence of visible masses were retrospectively analyzed; affected species, types of neoplasms and respective locations, and outcomes of surgical procedures were determined. All birds undergoing surgery belonged to the order Psittaciformes; the Blue-fronted parrot (Amazona aestiva) was the prevalent species. Lipoma was the most frequent neoplasm in the sample studied. Most neoplasms affected the integumentary system, particularly the pericloacal area. Tumor resection was the most common surgical procedure performed, with high resolution and low recurrence rates. PMID:26981315

Non-neoplastic surgical diseases of the lung and pleura

International Nuclear Information System (INIS)

Walter, P.A.

1987-01-01

Non-neoplastic diseases of the bronchi, pulmonary parenchyma, mediastinum, and pleura that are amenable to surgical management represent a wide range of unrelated etiopathogenic conditions that usually have a focal distribution. The author discusses the presurgical clinical, radiographic, and laboratory assessment and prognoses, and addresses therapeutic recommendations

[Non-neoplastic enlargement of salivary glands: clinico-histologic analysis].

Science.gov (United States)

González Guevara, Martha Beatriz; Torres Tejero, Marco Antonio; Martínez Mata, Guillermo

2005-01-01

We carried out a retrospective study on non-neoplastic enlargement of the salivary glands at the Oral Histopathology Diagnostic Center of the Autonomous Metropolitan University at Xochimilco (UAM-Xochimilco) in Mexico during a period of 24 years (1979-2003). From 5,625 biopsies received and analyzed, a total of 461 (8.2%) were non-neoplastic enlargement of the salivary glands; for each case, we registered demographic data as well as clinic characteristics. These lesions were characterized as a heterogeneous group of pathologic entities among which we included local, obstructive, infectious, and immunopathologic lesions. The most frequent lesion was the extravasation cyst in 341 (74%) cases, followed by chronic sialoadenitis and Sjögren's syndrome with 54 (11.7%) and 41 (8.8%) cases, respectively, and at a lesser percentage mucous retention cyst, sialosis, benign lymphoepithelial lesions and those related with sialolytes. Females were affected more frequently; mean age was second to third life decades. These lesions were most frequently localized on inferior labial mucosa.

Perceived Behavioral Changes in Early Multiple Sclerosis

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Fabiana Souza Lima

2007-01-01

Full Text Available Acquired behavioral changes have essentially been described in advanced multiple sclerosis (MS. The present study was designed to determine whether behavioral modifications specifically related to the MS pathological process could be identified in the initial phase of the disease, as compared to control patients with chronic, relapsing and progressive inflammatory disorders not involving the central nervous system (CNS. Eighty-eight early MS patients (Expanded Disability Status Scale score ≤ 2.5 and 48 controls were tested. Perceived changes by informants in behavioral control, goal-directed behavior, decision making, emotional expression, insight and interpersonal relationships were assessed using the Iowa Scale of Personality Change (ISPC. Executive behavioral disturbances were screened using the Dysexecutive Questionnaire (DEX. The mean change between the premorbid and postmorbid ISPC ratings was similar in the MS [12.2 (SD 15.6] and in the control [11.5 (SD 15.1] group. The perceived behavioral changes (PBCs most frequently reported in both groups were lack of stamina, lability/moodiness, anxiety, vulnerability to stress and irritability. Pathological scores in the DEX were also similar in both groups. Correlations between PBCs and DEX scores were different in MS and control groups. MS patients with cognitive impairment had a marginally higher number of PBCs than control patients (p = 0.056 and a significantly higher DEXp score (p = 0.04. These results suggest that (1 PBCs occurring in early MS patients were not different from those induced by comparable chronic non-CNS disorders, (2 qualitative differences in the relationship between behavioral symptoms and executive-behavioral changes may exist between MS and control groups, and (3 behavioral symptoms seem associated with cognitive deficits in MS. We further plan to assess these observations longitudinally.

Trisomy of the Dscr1 gene suppresses early progression of pancreatic intraepithelial neoplasia driven by oncogenic Kras

Energy Technology Data Exchange (ETDEWEB)

Lee, Jang Choon; Shin, Jimin; Baek, Kwan-Hyuck, E-mail: khbaek@skku.edu

2013-10-11

Highlights: •A single extra copy of Dscr1 restrains progression of PanIN-1A to PanIN-1B lesions. •Dscr1 trisomy attenuates calcineurin–NFAT pathway in neoplastic ductal epithelium. •Dscr1 trisomy leads to upregulation of p15{sup INK4b} in neoplastic ductal epithelium. •A single extra copy of Dscr1 reduces epithelial proliferation in early PanIN lesions. •Dscr1 trisomy may protect Down syndrome individuals from pancreatic cancer. -- Abstract: Individuals with Down syndrome exhibit remarkably reduced incidence of most solid tumors including pancreatic cancer. Multiple mechanisms arising from the genetic complexity underlying Down syndrome has been suggested to contribute to such a broad cancer protection. In this study, utilizing a genetically engineered mouse model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia-1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN lesions mediated by oncogenic Kras{sup G12D}. In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15{sup Ink4b} tumor suppressor and reduction of cell proliferation in early PanIN lesions. Our data suggest that attenuation of calcineurin–NFAT signaling in neoplastic pancreatic ductal epithelium by a single extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN lesions driven by oncogenic Kras, and thus may be a potential mechanism underlying reduced incidence of pancreatic cancer in Down syndrome individuals.

Selenium, selenoenzymes, oxidative stress and risk of neoplastic progression from Barrett's esophagus: results from biomarkers and genetic variants.

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Yumie Takata

Full Text Available Clinical trials have suggested a protective effect of selenium supplementation on the risk of esophageal cancer, which may be mediated through the antioxidant activity of selenoenzymes. We investigated whether serum selenium concentrations, selenoenzyme activity, oxidative stress and genetic variation in selenoenzymes were associated with the risk of neoplastic progression to esophageal adenocarcinoma (EA and two intermediate endpoints, aneuploidy and tetraploidy. In this prospective cohort study, during an average follow-up of 7.3 years, 47 EA cases, 41 aneuploidy cases and 51 tetraploidy cases accrued among 361 participants from the Seattle Barrett's Esophagus Research Study who were free of EA at the time of blood draw and had at least one follow-up visit. Development to EA was assessed histologically and aneuploidy and tetraploidy by DNA content flow cytometry. Serum selenium concentrations were measured using atomic absorption spectrometry, activity of glutathione peroxidase (GPX 1 and GPX3 by substrate-specific coupled test procedures, selenoprotein P (SEPP1 concentrations and protein carbonyl content by ELISA method and malondialdehyde concentrations by HPLC. Genetic variants in GPX1-4 and SEPP1 were genotyped. Serum selenium was not associated with the risk of neoplastic progression to EA, aneuploidy or tetraploidy (P for trend = 0.25 to 0.85. SEPP1 concentrations were positively associated with the risk of EA [hazard ratio (HR = 3.95, 95% confidence intervals (CI = 1.42-10.97 comparing the third tertile with the first] and with aneuploidy (HR = 6.53, 95% CI = 1.31-32.58, but not selenoenzyme activity or oxidative stress markers. No genetic variants, overall, were associated with the risk of neoplastic progression to EA (global p = 0.12-0.69. Our results do not support a protective effect of selenium on risk of neoplastic progression to EA. Our study is the first to report positive associations of plasma SEPP1

In vitro early changes in intercellular junctions by treatment with a chemical carcinogen.

Science.gov (United States)

Tachikawa, T; Kohno, Y; Matsui, Y; Yoshiki, S

1986-06-01

To examine early intercellular junction changes caused by treatment with 9,10-dimethyl-1,2-benzanthracene (DMBA), rat lingual epithelium was cultivated in isolation and observed by electrophysiological, freeze-fracture and whole-mount electron microscopy. Electrophysiological measurements showed a transient decrease in membrane potential of -10.2 mV 6 h after the treatment. It returned to almost the same level as that of the control group 1 day later. Six hours after treatment, input resistance decreased rapidly to 5.3 M omega but increased to 18.0 M omega 12 h after treatment. Transient reduction of input resistance and membrane potential occurred prior to the decrease in the coupling ratio 6 h after treatment with DMBA. In freeze-fracture replicas, the number of gap junctions decreased by approximately 45% of the control value 6 h after treatment with DMBA. At 12 h and thereafter, the number and area of gap junctions subsequently decreased by 60-80% of the control value. Alterations in the number and area of desmosomes were similar to those of the gap junctions. The formation of epithelial cytoskeletons, partially devoid of the 2-4 and 5-8 nm filaments was also observed. A decrease in the density of filament networks beneath the plasma membranes was especially apparent. Treatment with a carcinogen brought about morphological cellular changes as early as 6 h after treatment, and such early changes might trigger metabolic cellular abnormalities. Affected cells appear to move away from normal cells in a process of repeated destruction and revision of intercellular junctions, and cytoskeletons.

DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

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Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

2018-06-08

Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

Chronic Trichuris muris infection causes neoplastic change in the intestine and exacerbates tumour formation in APC min/+ mice.

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Kelly S Hayes

2017-06-01

Full Text Available Incidences of infection-related cancers are on the rise in developing countries where the prevalence of intestinal nematode worm infections are also high. Trichuris muris (T. muris is a murine gut-dwelling nematode that is the direct model for human T. trichiura, one of the major soil-transmitted helminth infections of humans. In order to assess whether chronic infection with T. muris does indeed influence the development of cancer hallmarks, both wild type mice and colon cancer model (APC min/+ mice were infected with this parasite. Parasite infection in wild type mice led to the development of neoplastic change similar to that seen in mice that had been treated with the carcinogen azoxymethane. Additionally, both chronic and acute infection in the APCmin/+ mice led to an enhanced tumour development that was distinct to the site of infection suggesting systemic control. By blocking the parasite induced T regulatory response in these mice, the increase in the number of tumours following infection was abrogated. Thus T. muris infection alone causes an increase in gut pathologies that are known to be markers of cancer but also increases the incidence of tumour formation in a colon cancer model. The influence of parasitic worm infection on the development of cancer may therefore be significant.

Big Five personality stability, change, and codevelopment across adolescence and early adulthood.

Science.gov (United States)

Borghuis, Jeroen; Denissen, Jaap J A; Oberski, Daniel; Sijtsma, Klaas; Meeus, Wim H J; Branje, Susan; Koot, Hans M; Bleidorn, Wiebke

2017-10-01

Using data from 2 large and overlapping cohorts of Dutch adolescents, containing up to 7 waves of longitudinal data each (N = 2,230), the present study examined Big Five personality trait stability, change, and codevelopment in friendship and sibling dyads from age 12 to 22. Four findings stand out. First, the 1-year rank-order stability of personality traits was already substantial at age 12, increased strongly from early through middle adolescence, and remained rather stable during late adolescence and early adulthood. Second, we found linear mean-level increases in girls' conscientiousness, in both genders' agreeableness, and in boys' openness. We also found temporal dips (i.e., U-shaped mean-level change) in boys' conscientiousness and in girls' emotional stability and extraversion. We did not find a mean-level change in boys' emotional stability and extraversion, and we found an increase followed by a decrease in girls' openness. Third, adolescents showed substantial individual differences in the degree and direction of personality trait changes, especially with respect to conscientiousness, extraversion, and emotional stability. Fourth, we found no evidence for personality trait convergence, for correlated change, or for time-lagged partner effects in dyadic friendship and sibling relationships. This lack of evidence for dyadic codevelopment suggests that adolescent friends and siblings tend to change independently from each other and that their shared experiences do not have uniform influences on their personality traits. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

DNA measurements on cell nuclei of normal, proliferating and neoplastic thyroid tissues in rats

International Nuclear Information System (INIS)

Christov, K.; Thomas, C.; Sandritter, W.

1975-01-01

Nuclear DNA content was measured in 3 normal, 9 hyperplastic and 16 neoplastic rat thyroid glands. Thyroid hyperplasia and tumor growth were induced after treatment of the animals with X rays and methylthiouracil. In the control animals only diploid thyroid epithelial cells were observed. In stages of diffuse and nodular thyroid hyperplasia, the total DNA content per nucleus indicated that most chromosomes were diploid; only a few cells were hyperdiploid. In thyroid adenomas and carcinomas scattering of the diploid region and an increased number of hyperdiploid cells were found. Among the various types of thyroid tumors neither a difference in the number of hyperdiploid cells, nor the typical pattern of the distribution of these cells in a histogram was found. The increased number of hyperdiploid cells in hyperplastic and neoplastic thyroids only suggested an increase in the proportion of cells entering the cell cycle and not an appearance of a neoplastic strain. (author)

DNA measurements on cell nuclei of normal, proliferating and neoplastic thyroid tissues in rats

Energy Technology Data Exchange (ETDEWEB)

Christov, K [National Center of Oncology, Academy of Medicine, Sofia-56 (Bulgaria); Thomas, C; Sandritter, W [Freiburg Univ. (F.R. Germany). Pathologisches Inst.

1975-01-01

Nuclear DNA content was measured in 3 normal, 9 hyperplastic and 16 neoplastic rat thyroid glands. Thyroid hyperplasia and tumor growth were induced after treatment of the animals with X rays and methylthiouracil. In the control animals only diploid thyroid epithelial cells were observed. In stages of diffuse and nodular thyroid hyperplasia, the total DNA content per nucleus indicated that most chromosomes were diploid; only a few cells were hyperdiploid. In thyroid adenomas and carcinomas scattering of the diploid region and an increased number of hyperdiploid cells were found. Among the various types of thyroid tumors neither a difference in the number of hyperdiploid cells, nor the typical pattern of the distribution of these cells in a histogram was found. The increased number of hyperdiploid cells in hyperplastic and neoplastic thyroids only suggested an increase in the proportion of cells entering the cell cycle and not an appearance of a neoplastic strain.

A nine-nucleotide deletion and splice variation in the coding region of the interferon induced ISG12 gene

DEFF Research Database (Denmark)

Smidt, Kamille; Hansen, Lise Lotte; Søgaard, T Max M

2003-01-01

distributed between ISG12 and ISG12-S in breast carcinoma cells, in cancer cell lines and in cervical cytobrush material with neoplastic lesions. In addition, we have found a nine-nucleotide deletion situated in exon 4 of the ISG12 gene. This deletion leads to a three-amino-acid deletion (AMA) in the putative...... ISG12 gene products, ISG12Δ and ISG12-SΔ. We have determined the prevalence of the deletion ISG12Δ in normal and neoplastic cells. Homozygosity ISG12(0/0) and ISG12(Δ/Δ), and heterozygosity ISG12(0/Δ) were found, although the ISG12(Δ/Δ) genotype was rare. In heterozygous cells from cytobrush material...

Non-neoplastic conditions presenting as soft-tissue tumours

International Nuclear Information System (INIS)

Crundwell, N.; O'Donnell, P.; Saifuddin, A.

2007-01-01

Review of referrals to our unit over the last 7 years showed that of approximately 750 cases referred as soft-tissue tumours, 132 were subsequently diagnosed as non-neoplastic lesions. The imaging characteristics of these lesions are presented to differentiate them from neoplasms. The most common diagnoses were myositis ossificans, ganglion cyst, abscess/infection, bursitis and synovitis. The imaging features of other rarer conditions will also be discussed

Non-neoplastic conditions presenting as soft-tissue tumours

Energy Technology Data Exchange (ETDEWEB)

Crundwell, N. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom); O' Donnell, P. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom); Saifuddin, A. [Royal National Orthopaedic Hospital, Stanmore, Middlesex (United Kingdom)]. E-mail: asif.saifuddin@rnoh.nhs.uk

2007-01-15

Review of referrals to our unit over the last 7 years showed that of approximately 750 cases referred as soft-tissue tumours, 132 were subsequently diagnosed as non-neoplastic lesions. The imaging characteristics of these lesions are presented to differentiate them from neoplasms. The most common diagnoses were myositis ossificans, ganglion cyst, abscess/infection, bursitis and synovitis. The imaging features of other rarer conditions will also be discussed.

The influence of theosophy on Mondrian's neoplastic work

OpenAIRE

Bris Marino, Pablo

2014-01-01

(ENG)The influence of Theosophy in the symbolist painting of Mondrian (1908-1911) has been unanimously recognized. There is not, however, the same consensus with respect to the influence of theosophy in his neoplastic period. There is a relationship between Mondrian’s theoretical writing and his practical work, but no proportionality. Mondrian’s theoretical discourse is not limited to painting and touches on other arts and disciplines (architecture,...

Differentiation of osteoporotic and neoplastic vertebral fractures by chemical shift {in-phase and out-of phase} MR imaging

International Nuclear Information System (INIS)

Ragab, Yasser; Emad, Yasser; Gheita, Tamer; Mansour, Maged; Abou-Zeid, A.; Ferrari, Serge; Rasker, Johannes J.

2009-01-01

Objective: The objective of this study was to establish the cut-off value of the signal intensity drop on chemical shift magnetic resonance imaging (MRI) with appropriate sensitivity and specificity to differentiate osteoporotic from neoplastic wedging of the spine. Patients and methods: All patients with wedging of vertebral bodies were included consecutively between February 2006 and January 2007. A chemical shift MRI was performed and signal intensity after (in-phase and out-phase) images were obtained. A DXA was performed in all. Results: A total of 40 patients were included, 20 with osteoporotic wedging (group 1) and 20 neoplastic (group 2). They were 21 males and 19 females. Acute vertebral collapse was observed in 15 patients in group 1 and subacute collapse in another 5 patients, while in group 2, 11 patients showed acute collapse and 9 patients (45%) showed subacute vertebral collapse. On the chemical shift MRI a substantial reduction in signal intensity was found in all lesions in both groups. The proportional changes observed in signal intensity of bone marrow lesions on in-phase compared with out-of-phase images showed significant differences in both groups (P < 0.05). At a cut-off value of 35%, the observed sensitivity of out-of-phase images was 95%, specificity was 100%, positive predictive value was 100% and negative predictive value was 95.2%. Conclusion: A chemical shift MRI is useful in order to differentiate patients with vertebral collapse due to underlying osteoporosis or neoplastic process.

Case of a rare type of non-neoplastic mucinous pancreatic cyst – likely new pathological entity?

International Nuclear Information System (INIS)

Hilendarov, A.; Nedeva, M.; Belovejdov, V.; Aleksieva, D.; Sirakov, N.

2013-01-01

Full text:Introduction: The cystic lesions of the pancreas consists of a range of pathologies which may be broadly divided into neoplastic, non- neoplastic and cysts. Recently a new non-neoplastic cystic lesions, called mucinous non-neoplastic cysts, have been described. Materials and Methods: The imaging methods (ultrasound and CT ) were used as well as invasive imaging methods under image control with a view of the histological verification of the diagnosis. A case of pancreatic cystic lesion is described, accidentally detected by ultrasound and CT scan made for different purpose. Results : The finding was a 28/32 mm cyst in the body of the pancreas, apparently communicating with the pancreatic duct . The Endoscopic Retrograde Cholangiopancreatography and laboratory tests of liver function, serum CEA and carbohydrate antigen C19 -9 were within normal limits. After the distal pancreatectomy and splenectomy the lasting histological specimen showed a simple cyst, lined with mucinous epithelium. Conclusion: The presented case guides the imaging diagnosticians and surgeons towards seeking a thorough preoperative clarification of pancreatic cystic lesions. It is recommended that patients diagnosed with 'benign' mucinous neoplasm are closely monitored due to the inability to completely confirm the benign nature of the lesion

The Relationship between Brown Adipose Tissue Activity and Neoplastic Status: an 18F-FDG PET/CT Study in the Tropics

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Huang Yung-Cheng

2011-12-01

Full Text Available Abstract Background Brown adipose tissue (BAT has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG positron emission tomography/computed tomography (PET/CT in people living in the tropics, where the influence of outdoor temperature was low. Methods 18F-FDG PET/CT scans were reviewed and the total metabolic activity (TMA of identified activated BAT quantified. The distribution and TMA of activated BAT were compared between patients with and without a cancer history. The neoplastic status of patients was scored according to their cancer history and 18F-FDG PET/CT findings. We evaluated the relationships between the TMA of BAT and neoplastic status along with other factors: age, body mass index, fasting blood sugar, gender, and outdoor temperature. Results Thirty of 1740 patients had activated BAT. Those with a cancer history had wider BAT distribution (p = 0.043 and a higher TMA (p = 0.028 than those without. A higher neoplastic status score was associated with a higher average TMA. Multivariate analyses showed that neoplastic status was the only factor significantly associated with the TMA of activated BAT (p = 0.016. Conclusions Neoplastic status is a critical determinant of BAT activity in patients living in the tropics. More active neoplastic status was associated with more vigorous TMA of BAT.

Big Five personality stability, change, and co-development across adolescence and early adulthood

OpenAIRE

Borghuis, J.; Denissen, J.J.A.; Oberski, D.L.; Sijtsma, K.; Meeus, W.H.J.; Branje, S; Koot, H.M.; Bleidorn, Wiebke

2017-01-01

Using data from 2 large and overlapping cohorts of Dutch adolescents, containing up to 7 waves of longitudinal data each (N = 2,230), the present study examined Big Five personality trait stability, change, and codevelopment in friendship and sibling dyads from age 12 to 22. Four findings stand out. First, the 1-year rank-order stability of personality traits was already substantial at age 12, increased strongly from early through middle adolescence, and remained rather stable during late ado...

78 FR 76507 - Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases)

Science.gov (United States)

2013-12-17

... include updating the medical terminology in the listings. For example, we would replace the term ``Hodgkin... Revised Medical Criteria for Evaluating Cancer (Malignant Neoplastic Diseases); Proposed Rule #0;#0...

Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using 111In-DTPA ventriculography

International Nuclear Information System (INIS)

Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.

1982-01-01

Cerebrospinal fluid flow dynamics were evaluated by 111 In-diethylenetriamine pentaacetic acid ( 111 In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that 111 In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis

Radiodiagnosis of early radiation intestinal changes

International Nuclear Information System (INIS)

Volodina, G.I.; Abdulkhakova, D.A.

1987-01-01

X-ray examination of the colon in 102 patients and of the small intestine in 62 was performed during combined radiation therapy of cervical cancer and at different time after its discontinuation. Early radiation functional and morphological changes in the ileum and colon were detected. Radiation changes in the ileac mucosa were noted in 52% of the patients, changes of various degree in the rectal, sigmoid and cecal mucosa were noted in 41.2%. Moderate radiation changes in the ascending, descending and horizontal parts of the colon were noted in 10.7%. Early radiation intestinal injuries in the form of erosions and ulcers were revealed in 5.8% of the patients. In most of the patients radiation intestinal changes were without noticeable clinical manifestations. All these patients could be defined as a group at risk of developing late radiation changes

Capsule endoscopy in neoplastic diseases

Science.gov (United States)

Pennazio, Marco; Rondonotti, Emanuele; de Franchis, Roberto

2008-01-01

Until recently, diagnosis and management of small-bowel tumors were delayed by the difficulty of access to the small bowel and the poor diagnostic capabilities of the available diagnostic techniques. An array of new methods has recently been developed, increasing the possibility of detecting these tumors at an earlier stage. Capsule endoscopy (CE) appears to be an ideal tool to recognize the presence of neoplastic lesions along this organ, since it is non-invasive and enables the entire small bowel to be visualized. High-quality images of the small-bowel mucosa may be captured and small and flat lesions recognized, without exposure to radiation. Recent studies on a large population of patients undergoing CE have reported small-bowel tumor frequency only slightly above that reported in previous surgical series (range, 1.6%-2.4%) and have also confirmed that the main clinical indication to CE in patients with small-bowel tumors is obscure gastrointestinal (GI) bleeding. The majority of tumors identified by CE are malignant; many were unsuspected and not found by other methods. However, it remains difficult to identify pathology and tumor type based on the lesion’s endoscopic appearance. Despite its limitations, CE provides crucial information leading in most cases to changes in subsequent patient management. Whether the use of CE in combination with other new diagnostic (MRI or multidetector CT enterography) and therapeutic (Push-and-pull enteroscopy) techniques will lead to earlier diagnosis and treatment of these neoplasms, ultimately resulting in a survival advantage and in cost savings, remains to be determined through carefully-designed studies. PMID:18785274

Socio-economic position early in life, cognitive development and cognitive change from young adulthood to middle age

DEFF Research Database (Denmark)

Osler, Merete; Avlund, Kirsten; Mortensen, Erik Lykke

2013-01-01

BACKGROUND: We examine the influence of social circumstances early in life on changes in cognitive function from young adulthood to middle age, and we explore the impact of birth characteristics, childhood activities, education and adult social class on the expected relationship. METHODS: A cohort...... of 11 532 men born in Copenhagen, Denmark in 1953-7906, 10 246 and 2483 participants-had completed assessments of cognitive function at ages 12, 18 and 57 years, respectively. Linear regression was used to investigate the association of early-life characteristics with cognitive test scores at these ages...... and with score changes from early to mid-adulthood. RESULTS: The cognitive scores at age 57 years had high correlations with scores at ages 12 (r = 0.67) and 18 years (r = 0.70), and these two scores also showed bivariate correlation (r = 0.69). Having a father from the working class at birth was associated...

FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders

International Nuclear Information System (INIS)

Chiappetta, Gennaro; Pierantoni, Giovanna Maria; Fusco, Alfredo; Ferraro, Angelo; Botti, Gerardo; Monaco, Mario; Pasquinelli, Rosa; Vuttariello, Emilia; Arnaldi, Liliane; Di Bonito, Maurizio; D'Aiuto, Giuseppe

2007-01-01

Fos-related antigen 1 (FRA-1) is an immediate early gene encoding a member of AP-1 family of transcription factors involved in cell proliferation, differentiation, apoptosis, and other biological processes. fra-1 gene overexpression has an important role in the process of cellular transformation, and our previous studies suggest FRA-1 protein detection as a useful tool for the diagnosis of thyroid neoplasias. Here we investigate the expression of the FRA-1 protein in benign and malignant breast tissues by immunohistochemistry, Western blot, RT-PCR and qPCR analysis, to evaluate its possible help in the diagnosis and prognosis of breast neoplastic diseases. We investigate the expression of the FRA-1 protein in 70 breast carcinomas and 30 benign breast diseases by immunohistochemistry, Western blot, RT-PCR and qPCR analysis. FRA-1 protein was present in all of the carcinoma samples with an intense staining in the nucleus. Positive staining was also found in most of fibroadenomas, but in this case the staining was present both in the nucleus and cytoplasm, and the number of positive cells was lower than in carcinomas. Similar results were obtained from the analysis of breast hyperplasias, with no differences in FRA-1 expression level between typical and atypical breast lesions; however the FRA-1 protein localization is mainly nuclear in the atypical hyperplasias. In situ breast carcinomas showed a pattern of FRA-1 protein expression very similar to that observed in atypical hyperplasias. Conversely, no FRA-1 protein was detectable in 6 normal breast tissue samples used as controls. RT-PCR and qPCR analysis confirmed these results. Similar results were obtained analysing FRA-1 expression in fine needle aspiration biopsy (FNAB) samples. The data shown here suggest that FRA-1 expression, including its intracellular localization, may be considered a useful marker for hyperplastic and neoplastic proliferative breast disorders

Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state.

Science.gov (United States)

Hanning, Jennifer E; Saini, Harpreet K; Murray, Matthew J; Caffarel, Maria M; van Dongen, Stijn; Ward, Dawn; Barker, Emily M; Scarpini, Cinzia G; Groves, Ian J; Stanley, Margaret A; Enright, Anton J; Pett, Mark R; Coleman, Nicholas

2013-11-01

In cervical carcinomas, high-risk human papillomavirus (HR-HPV) may be integrated into host chromosomes or remain extra-chromosomal (episomal). We used the W12 cervical keratinocyte model to investigate the effects of HPV16 early gene depletion on in vitro cervical carcinogenesis pathways, particularly effects shared by cells with episomal versus integrated HPV16 DNA. Importantly, we were able to study the specific cellular consequences of viral gene depletion by using short interfering RNAs known not to cause phenotypic or transcriptional off-target effects in keratinocytes. We found that while cervical neoplastic progression in vitro was characterized by dynamic changes in HPV16 transcript levels, viral early gene expression was required for cell survival at all stages of carcinogenesis, regardless of viral physical state, levels of early gene expression or histology in organotypic tissue culture. Moreover, HPV16 early gene depletion induced changes in host gene expression that were common to both episome-containing and integrant-containing cells. In particular, we observed up-regulation of autophagy genes, associated with enrichment of senescence and innate immune-response pathways, including the senescence-associated secretory phenotype (SASP). In keeping with these observations, HPV16 early gene depletion induced autophagy in both episome-containing and integrant-containing W12 cells, as evidenced by the appearance of autophagosomes, punctate expression of the autophagy marker LC3, conversion of LC3B-I to LC3B-II, and reduced levels of the autophagy substrate p62. Consistent with the reported association between autophagy and senescence pathways, HPV16 early gene depletion induced expression of the senescence marker beta-galactosidase and increased secretion of the SASP-related protein IGFBP3. Together, these data indicate that depleting HR-HPV early genes would be of potential therapeutic benefit in all cervical carcinogenesis pathways, regardless of viral

Expression of a fms-related oncogene in carcinogen-induced neoplastic epithelial cells

International Nuclear Information System (INIS)

Walker, C.; Nettesheim, P.; Barrett, J.C.; Gilmer, T.M.

1987-01-01

Following carcinogen exposure in vitro, normal rat tracheal epithelial cells are transformed in a multistage process in which the cultured cells become immortal and ultimately, neoplastic. Five cell lines derived from tumors produced by neoplastically transformed rat tracheal epithelial cells were examined for the expression of 11 cellular oncogenes previously implicated in pulmonary or epithelial carcinogenesis. RNA homologous to fms was expressed at a level 5-19 times higher than normal tracheal epithelial cells in three of five of the tumor-derived lines. All three lines expressing high levels of fms-related RNA gave rise to invasive tumors of epithelial origin when injected into nude mice. Increased expression of the fms-related mRNA was not due to gene amplification, and no gene rearrangement was detected by Southern analyses. RNA blot analysis using a 3' v-fms probe detected a 9.5-kilobase message in the three tumor-derived lines, whereas both normal rat aveolar macrophages and the human choriocarcinoma line BeWo expressed a fms transcript of ≅ 4 kilobases. The authors conclude from these data that the gene expressed as a 9.5-kilobase transcript in these neoplastic epithelial cells is a member of a fms-related gene family but may be distinct from the gene that encodes the macrophage colony-stimulating factor (CSF-1) receptor

Mechanisms of radiation-induced neoplastic cell transformation

Energy Technology Data Exchange (ETDEWEB)

Yang, T.C.H.; Tobias, C.A.

1984-04-01

Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table.

Mechanisms of radiation-induced neoplastic cell transformation

International Nuclear Information System (INIS)

Yang, T.C.H.; Tobias, C.A.

1984-04-01

Studies with cultured mammalian cells demonstrated clearly that radiation can transform cells directly and can enhance the cell transformation by oncogenic DNA viruses. In general, high-LET heavy-ion radiation can be more effective than X and gamma rays in inducing neoplastic cell transformation. Various experimental results indicate that radiation-induced DNA damage, most likely double-strand breaks, is important for both the initiation of cell transformation and for the enhancement of viral transformation. Some of the transformation and enhancement lesions can be repaired properly in the cell, and the amount of irrepairable lesions produced by a given dose depends on the quality of radiation. An inhibition of repair processes with chemical agents can increase the transformation frequency of cells exposed to radiation and/or oncogenic viruses, suggesting that repair mechanisms may play an important role in the radiation transformation. The progression of radiation-transformed cells appears to be a long and complicated process that can be modulated by some nonmutagenic chemical agents, e.g., DMSO. Normal cells can inhibit the expression of transforming properties of tumorigenic cells through an as yet unknown mechanism. The progression and expression of transformation may involve some epigenetic changes in the irradiated cells. 38 references, 15 figures, 1 table

Neoplastic and proliferative disorders of the perinephric space

International Nuclear Information System (INIS)

Heller, M.T.; Haarer, K.A.; Thomas, E.; Thaete, F.L.

2012-01-01

The perinephric space is a well-marginated central compartment of the retroperitoneum, located between the anterior and posterior pararenal spaces. Various neoplastic and proliferative disorders can affect the perinephric space, and there is a wide array of imaging findings. Although many perinephric lesions may extend directly from the kidney and adrenal gland, other lesions occur in the perinephric space due to haematogenous spread, as part of a systemic disease, or by extension from an adjacent retroperitoneal compartment. Imaging plays a pivotal role in the diagnosis of perinephric diseases, as many of the disease processes affecting this space will not result in clinical signs or symptoms until the disease is at an advanced stage. Despite the often shared non-specific clinical and imaging findings among these disease processes, application of a categorical differential diagnosis based on the imaging characteristics will serve to narrow the differential diagnosis and direct further evaluation and treatment. In this article, the lesions have been categorized as soft-tissue rind [nephroblastomatosis, fibrosis, Erdheim–Chester disease (ECD), extramedullary haematopoiesis, lymphoma, infiltrating metastases], focal solid lesions (extension of renal or adrenal malignancies, melanoma metastases, treated lymphoma), fat-containing lesions (angiomyolipoma, liposarcoma, myelolipoma), and cystic lesions (lymphangiomas, abscesses). The aim of this article is to demonstrate and describe the key imaging features of several neoplastic and proliferative disorders that affect the perinephric space.

Imaging of demyelinating and neoplastic diseases of the spinal cord; Bildgebung bei demyelinisierenden und tumoroesen Erkrankungen des Rueckenmarks

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Mueller-Mang, C. [Institut fuer CT und MRT Gaenserndorf, Gaenserndorf (Austria)

2010-12-15

The clinical symptoms of myelopathy are variable and non-specific. Demyelinating as well as neoplastic spinal cord diseases can cause paresthesia, progressive sensomotoric deficits and bowel and bladder dysfunction. Imaging of the spine, especially with magnetic resonance imaging (MRI), is an essential component in the diagnostic assessment of myelopathy and makes a substantial contribution to achieving the correct diagnosis. Although intramedullary neoplasms are far less common than demyelinating spinal cord diseases, radiologists should be familiar with the three most common entities, astrocytoma, ependymoma and hemangioblastoma, which represent over 70% of all spinal cord neoplasms. An early diagnosis and therapy is essential with neoplastic and demyelinating spinal cord diseases to hold residual neurological deficits as low as possible. (orig.) [German] Die klinische Symptomatik von Myelopathien ist aeusserst variabel und unspezifisch. Sowohl demyelinisierende als auch tumoroese Rueckenmarkerkrankungen koennen Paraesthesien, progrediente sensomotorische Ausfaelle und eine Sphinkterdysfunktion hervorrufen. Bildgebende Untersuchungen, und hier allen voran die MRT, sind ein unerlaesslicher Bestandteil zur Abklaerung von Myelopathien und tragen wesentlich zur korrekten Diagnose bei. Intramedullaere Tumoren sind zwar weitaus seltener als demyelinisierende Rueckenmarkerkrankungen, dennoch sollte der Radiologe mit den Bildmerkmalen der 3 haeufigsten Tumorarten, dem Astrozytom, Ependymom und Haemangioblastom vertraut sein, die ueber 70% aller Rueckenmarktumoren verursachen. Eine moeglichst fruehe Diagnostik und Therapie sind bei tumoroesen und demyelinisierenden Rueckenmarkerkrankungen essenziell, um bleibende neurologische Defizite moeglichst gering zu halten. (orig.)

Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma

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Spyros Darmanis

2017-10-01

Full Text Available Summary: Glioblastoma (GBM is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor’s genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration. Additionally, in investigating the immunological response to the tumors, we found transcriptionally distinct myeloid cell populations residing in the tumor core and the surrounding peritumoral space. Our data provide a detailed dissection of GBM cell types, revealing an abundance of information about tumor formation and migration. : Darmanis et al. perform single-cell transcriptomic analyses of neoplastic and stromal cells within and proximal to primary glioblastomas. The authors describe a population of neoplastic-infiltrating glioblastoma cells as well as a putative role of tumor-infiltrating immune cells in supporting tumor growth. Keywords: single cell, RNA-seq, glioma, glioblastoma, GBM, brain, heterogeneity, infiltrating, diffuse, checkpoint

Understanding Early Educators' Readiness to Change

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Peterson, Shira M.

2012-01-01

Researchers in the fields of humanistic psychology, counseling, organizational change, and implementation science have been asking a question that is at the heart of today's early care and education quality improvement efforts: When it comes to changing one's behavior, what makes a person ready to change? Although the concept of readiness to…

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

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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.

Feeding variations and shape changes of a temperate reef clingfish during its early ontogeny

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Valentina Bernal-Durán

2017-06-01

Full Text Available The majority of rocky reef fishes have complex life cycles, involving transition from a pelagic to a benthic environment. This means that as they grow, their morphology, behaviour and feeding habits must change. Therefore, shape changes occurring during early development of these fishes will be related to diet changes. The clingfish Sicyases sanguineus was selected for this study, because it displays a noticeable variation in shape from pelagic larvae to juvenile stage, and it is expected that diet composition will change as well. The pattern of shape changes was studied using geometric morphometrics. A set of 9 landmarks were digitized in 159 larval and juvenile fish and the same specimens were used for gut content analysis. Allometric growth was most prominent early in the ontogeny, from 4 to 12 mm. Morphology changed from a thin and hydrodynamic shape to a more robust and deeper body prior to settlement. The diet of the clingfish during larval stages showed preferences for a variety of copepod stages. As individual grows the ingested prey volume increases, but not the number and width of prey. A partial least square analysis showed low covariance between shape changes and diet composition changes in prey number and volume, suggesting that the two processes were temporally decoupled. The biggest shape changes, a lengthening of the visceral cavity and a flattening of the head, occurred up to 12 mm standard length, while the largest feeding differentiation, shifting from copepods to microalgae, occurred after 16 mm. Results suggest that shape changes precede trophic changes in this clingfish species during the transition from a pelagic to a benthic habitat.

The role of dynamic susceptibility contrast-enhanced perfusion MR imaging in differentiating between infectious and neoplastic focal brain lesions: results from a cohort of 100 consecutive patients.

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Valdeci Hélio Floriano

Full Text Available BACKGROUND AND PURPOSE: Differentiating between infectious and neoplastic focal brain lesions that are detected by conventional structural magnetic resonance imaging (MRI may be a challenge in routine practice. Brain perfusion-weighted MRI (PWI may be employed as a complementary non-invasive tool, providing relevant data on hemodynamic parameters, such as the degree of angiogenesis of lesions. We aimed to employ dynamic susceptibility contrast-enhanced perfusion MR imaging (DSC-MRI to differentiate between infectious and neoplastic brain lesions by investigating brain microcirculation changes. MATERIALS AND METHODS: DSC-MRI perfusion studies of one hundred consecutive patients with non-cortical neoplastic (n = 54 and infectious (n = 46 lesions were retrospectively assessed. MRI examinations were performed using a 1.5-T scanner. A preload of paramagnetic contrast agent (gadolinium was administered 30 seconds before acquisition of dynamic images, followed by a standard dose 10 seconds after starting imaging acquisitions. The relative cerebral blood volume (rCBV values were determined by calculating the regional cerebral blood volume in the solid areas of lesions, normalized to that of the contralateral normal-appearing white matter. Discriminant analyses were performed to determine the cutoff point of rCBV values that would allow the differentiation of neoplastic from infectious lesions and to assess the corresponding diagnostic performance of rCBV when using this cutoff value. RESULTS: Neoplastic lesions had higher rCBV values (4.28±2.11 than infectious lesions (0.63±0.49 (p<0.001. When using an rCBV value <1.3 as the parameter to define infectious lesions, the sensitivity of the method was 97.8% and the specificity was 92.6%, with a positive predictive value of 91.8%, a negative predictive value of 98.0%, and an accuracy of 95.0%. CONCLUSION: PWI is a useful complementary tool in distinguishing between infectious and neoplastic brain

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

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Carvalho, Filomena M; Zaganelli, Fabricia L; Almeida, Bernardo G L; Goes, Joao Carlos Sampaio; Baracat, Edmund C; Carvalho, Jesus P

2010-01-01

OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2‐40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6%) cases, with 29/31 (93.5%) of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node‐positive cases was lower than that of node‐negative (18.9% vs. 22.6%, respectively). Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8%) cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively), although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host‐tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas. PMID:21340215

Prognostic value of podoplanin expression in intratumoral stroma and neoplastic cells of uterine cervical carcinomas

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Filomena M Carvalho

2010-01-01

Full Text Available OBJECTIVE: To investigate the clinicopathological significance of podoplanin expression in the intratumoral stroma and neoplastic cells of early stage uterine cervical cancer. MATERIALS AND METHODS: A total of 143 patients with clinical stage I and IIA uterine cervical carcinomas underwent surgery between 2000 and 2007. Clinicopathological data and slides associated with these cases were retrospectively reviewed. Immunodetection of podoplanin expression in histologic sections of tissue microarray blocks was performed using the monoclonal antibody D2-40. RESULTS: Expression of podoplanin was detected in neoplastic cells in 31/143 (21.6% cases, with 29/31 (93.5% of these cases diagnosed as squamous carcinoma. For all of the cases examined, the strongest signal for podoplanin expression was observed at the proliferating edge of the tumor nests. The rate of positive podoplanin expression for node-positive cases was lower than that of node-negative (18.9% vs. 22.6%, respectively. Furthermore, the rate of positive podoplanin expression in fatal cases was 10.5% vs. 21.6%, respectively. In 27/143 (18.8% cases, podoplanin expression was detected in fibroblasts of the intratumoral stroma, and this expression did not correlate with patient age, clinical stage, tumor size, histologic type, depth of infiltration, or vascular involvement. Moreover, expression of podoplanin in intratumoral stroma fibroblasts was only negatively associated with nodal metastasis. A greater number of fatal cases was observed among negative intratumoral stroma fibroblasts (15.5% vs. 3.7%, respectively, although this difference was not significant. CONCLUSIONS: These preliminary results suggest that podoplanin may have a role in host-tumor interactions and, as a result, may represent a favorable prognostic factor for squamous cervical carcinomas.

Immunogenetical study of the atomic-bombed patients of neoplastic diseases

International Nuclear Information System (INIS)

Hirota, Masaki; Miyazaki, Takashige; Tomonaga, Akimitsu; Hara, Kohei; Hirose, Takeshi

1978-01-01

The immunogenetical backgrounds of 30 patients with neoplastic diseases (group I) and 30 with non-neoplastic diseases (group II) who were exposed to the A-bomb within 30 km of the center of explosion were studied using human leucocyte antigen (HLA), whose gene combines with Ir-gene, as an index. Eighty-four healthy, non-exposed persons (group III) were selected as controls. Regarding phenotype and genotype frequency, type A9 showed Aw24 and type A10 showed A26 in all cases. Except for Bw40, there was no significant difference among the groups (frequency of A9, I>II; that of A10, II< III). Bw40 was frequently observed in group I although it had racial specificity. There were 16 cases of Bw40 in group I (53.3%), 10 cases in group II (33.3%), and 23 cases in group III (27.3%). Further analysis of Bw40 revealed that Bw40.1 and Bw40.2 were more frequent in group I than in the control group. Bw40.3 was not observed in any of the groups. (Tsunoda, M.)

Changes in insomnia subtypes in early Parkinson disease.

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Tholfsen, Lena K; Larsen, Jan P; Schulz, Jörn; Tysnes, Ole-Bjørn; Gjerstad, Michaela D

2017-01-24

To examine the development of factors associated with insomnia in a cohort of originally drug-naive patients with incident Parkinson disease (PD) during the first 5 years after diagnosis. One hundred eighty-two drug-naive patients with PD derived from a population-based incident cohort and 202 control participants were assessed for insomnia before treatment initiation and were repeatedly examined after 1, 3, and 5 years. Insomnia was diagnosed according to the Stavanger Sleepiness Questionnaire. The Parkinson's Disease Sleep Scale was used to differentiate sleep initiation problems from problems of sleep maintenance. Generalized estimating equation models were applied for statistical measures. The prevalence of insomnia in general was not higher in patients with PD compared to controls at the 5-year follow-up. There were changes in the prevalence of the different insomnia subtypes over the 5-year follow-up. The prevalence of solitary problems in sleep maintenance increased from 31% (n = 18) in the drug-naive patients at baseline to 49% (n = 29) after 1 year and were associated with the use of dopamine agonists and higher Montgomery-Åsberg Depression Rating Scale scores. The prevalence of solitary sleep initiation problems decreased continuously from 21% (n = 12) at baseline to 7.4% (n = 4) after 5 years; these were associated with less daytime sleepiness. The prevalence rates of the different insomnia subtypes changed notably in patients with early PD. The frequency of sleep maintenance problems increased, and these problems were associated with dopamine agonist use and depressive symptoms, while the total number of patients with insomnia remained stable. Our findings reflect the need for early individual assessments of insomnia subtypes and raise the possibility of intervention to reduce these symptoms in patients with early PD. © 2016 American Academy of Neurology.

Osteogenic tumour in Australopithecus sediba: Earliest hominin evidence for neoplastic disease

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Patrick S. Randolph-Quinney

2016-07-01

Full Text Available We describe the earliest evidence for neoplastic disease in the hominin lineage. This is reported from the type specimen of the extinct hominin Australopithecus sediba from Malapa, South Africa, dated to 1.98 million years ago. The affected individual was male and developmentally equivalent to a human child of 12 to 13 years of age. A penetrating lytic lesion affected the sixth thoracic vertebra. The lesion was macroscopically evaluated and internally imaged through phase-contrast X-ray synchrotron microtomography. A comprehensive differential diagnosis was undertaken based on gross- and micro-morphology of the lesion, leading to a probable diagnosis of osteoid osteoma. These neoplasms are solitary, benign, osteoid and bone-forming tumours, formed from well-vascularised connective tissue within which there is active production of osteoid and woven bone. Tumours of any kind are rare in archaeological populations, and are all but unknown in the hominin record, highlighting the importance of this discovery. The presence of this disease at Malapa predates the earliest evidence of malignant neoplasia in the hominin fossil record by perhaps 200 000 years.

Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis

International Nuclear Information System (INIS)

Pogribny, Igor P.; Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.; Muskhelishvili, Levan; Rodriguez-Juarez, Rocio; Kovalchuk, Olga; Han Tao; Fuscoe, James C.; Ross, Sharon A.; Beland, Frederick A.

2007-01-01

Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce non-alcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. In the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G 1 to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen

Influence on intraocular pressure of the postural change and daily activities in the early morning in suspected glaucoma patients

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Ting Chen

2014-05-01

Full Text Available AIM:To evaluate the influence on intraocular pressure(IOPof the postural change and daily activities in the early morning in suspected glaucoma patients.METHODS:The supine and sitting IOP were measured and analyzed on 51 suspected glaucoma patients(100 eyeswith Icare rebound tonometer before and after getting up and daily activities in the early morning. RESULTS: The mean of sitting IOP of 51 patients was 17.12±4.53mmHg, which was significantly lower than the mean of supine IOP(19.14±5.51mmHg. The mean of IOP before and after daily activity of 51 patients were 17.12±4.53mmHg and 14.44±3.90mmHg respectively, which showed significantly difference. CONCLUSION:Postural change and daily activities can result in significant changes of IOP in suspected glaucoma patients.

Genetic biomarkers for neoplastic colorectal cancer in peripheral lymphocytes.

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Ionescu, Mirela; Ciocirlan, Mihai; Ionescu, Cristina; Becheanu, Gabriel; Gologan, Serban; Teiusanu, Adriana; Arbanas, Tudor; Mircea, Diculescu

2011-04-01

Loss of genomic stability appears as a key step in colorectal carcinogenesis. Micronucleus (MN) designates a chromosome fragment or an entire chromosme which lags behind mitosis. MN may be noticed as an additional nucleus within the cytoplasm cell during the intermediate mitosis phases. We tested the hypothesis that MN and its related anomalies may be associated with the presence of neoplastic colorectal lesions. Peripheral blood lymphocytes were cultured and microscopically examined. The frequency of micronuclei (FMN) and the presence of nucleoplasmic bridges (NPB) in binucleated cells were compared in patients with of without colorectal neoplastic lesions. We included 45 patients undergoing colonoscopy, 23 males and 22 females, with a median age of 59. 17 patients had polyps, 11 colorectal cancer (CRC) and 17 had a normal colonoscopy. The FMN was significantly higher in women than in men (8.14 vs 4.17, p=0.008); NPB were significantly less frequent in patients with advanced adenomas (>10mm or vilous) or CRC (p=0.044) when compared with patients with normal colonoscopy, hiperplastic polyps or non-advanced adenomas. Micronuclei are more frequent in women, but its frequency was not significantly different in patients with advanced adenomas or CRC. Null or low frequency values for nucleoplasmic bridges presence in peripheral lymphocyte may be predictive for advanced adenomas and colorectal cancer.

Adaptive Response Against Spontaneous Neoplastic Transformation In Vitro Induced by Ionizing Radiation

International Nuclear Information System (INIS)

Redpath, J. Leslie

2003-01-01

The goal of this project was to establish a dose response curve for radiation-induced neoplastic transformation of HeLa x skin fibroblast human hybrid cells in vitro under experimental conditions were an adaptive response, if it were induced, would have an opportunity to be expressed. During the first two years of the grant an exhaustive series of experiments were performed and the resulting data were reported at the 2000 Annual Meeting of the Radiation Research Society and then Subsequently published. The data showed that an adaptive response against spontaneous neoplastic transformation was seen up to doses of 10cGy of Cs-137 gamma rays. At dose of 30, 50 and 100 cGy the transformation frequencies were above background. This indicated that for this system, under the specific experimental conditions used, there was a threshold of somewhere between 10 and 30 cGy. The results also indicated some unexpected, though very interesting, correlations with relative risk estimates made from human epidemiologic studies

Chondroblastoma and chondromyxoid fibroma : disentangling the neoplastic chondrogenesis of two rare cartilaginous tumours

NARCIS (Netherlands)

Romeo, Salvatore

2010-01-01

The scope of this study was to disentangle neoplastic chondrogenesis in two rare cartilaginous tumours: chondroblastoma and chondromyxoid fibroma. It was addressed: 1 The spectrum of phenotypic differentiation in chondroblastoma and chondromyxoid fibroma, 2 The signalling pathways driving

Assessing early communication skills at 12 months: a retrospective study of Autism Spectrum Disorder.

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Swain, Nathaniel Robert; Eadie, Patricia Ann; Prior, Margot Ruth; Reilly, Sheena

2015-07-01

Early identification of Autism Spectrum Disorder (ASD) is currently limited by the absence of reliable biological markers for the disorder, as well as the reliability of screening and assessment tools for children aged between 6 and 18 months. Ongoing research has demonstrated the importance of early social communication skills in differentiating children later diagnosed with ASD from their typically developing (TD) peers, but researchers have not yet investigated whether these differences can be detected using community-ascertained systematic observation data as early as 12 months. To investigate whether differences in early social communication skills can be detected at 12 months of age, comparing children later diagnosed with ASD, and TD peers; and to determine whether differences remain when groupings are based on age of subsequent ASD diagnosis. From a prospective community-ascertained sample, we collected data on children in early life, then conducted retrospective analyses for those children who were later diagnosed with ASD by the age of 7 years, compared with matched TD peers. We analysed standardized observational data of early communication skills, collected using the Communication and Symbolic Behavior Scales-Developmental Profile (CSBS-DP) Behavior Sample, when participants were 12 months of age. Children in the ASD group exhibited significantly lower social communication skills than the TD group, including on the Total score and Social and Symbolic Composite scores of the CSBS-DP Behavior Sample. Differences on the Total score and Social Composite were also detected for both early and late ASD diagnosis groups when compared with the TD group. These findings give further support for the importance of social communication in assessing children at risk of ASD as early as 12 months of age. Future research could evaluate the sensitivity and specificity of direct observation of these early communication skills as diagnostic indicators for ASD at 12 months

Early resistance change and stress/electromigrationmodeling in aluminium interconnects

NARCIS (Netherlands)

Petrescu, V.; Mouthaan, A.J.; Schoenmaker, W.

1997-01-01

A complete description for early resistance change and two dimensional simulation of mechanical stress evolution in confined Al interconnects, related to the electromigration, is given in this paper. The model, combines the stress/ vacancy concentration evolution with the early resistance change of

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Differential diagnosis of well-differentiated squamous cell carcinoma from non-neoplastic oral mucosal lesions: New cytopathologic evaluation method dependent on keratinization-related parameters but not nuclear atypism.

Science.gov (United States)

Hara, Hitoshi; Misawa, Tsuneo; Ishii, Eri; Nakagawa, Miki; Koshiishi, Saki; Amemiya, Kenji; Oyama, Toshio; Tominaga, Kazuya; Cheng, Jun; Tanaka, Akio; Saku, Takashi

2017-05-01

The cytology of oral squamous cell carcinoma (SCC) is challenging because oral SCC cells tend to be well differentiated and lack nuclear atypia, often resulting in a false negative diagnosis. The purpose of this study was to establish practical cytological parameters specific to oral SCCs. We reviewed 123 cases of malignancy and 53 of non-neoplastic lesions of the oral mucosa, which had been diagnosed using both cytology and histopathology specimens. From those, we selected 12 SCC and 4 CIS cases that had initially been categorized as NILM to ASC-H with the Bethesda system, as well as 4 non-neoplastic samples categorized as LSIL or ASC-H as controls, and compared their characteristic findings. After careful examinations, we highlighted five cytological parameters, as described in Results. Those 20 cytology samples were then reevaluated by 4 independent examiners using the Bethesda system as well as the 5 parameters. Five cytological features, (i) concentric arrangement of orangeophilic cells (indicating keratin pearls), (ii) large number of orangeophilic cells, (iii) bizarre-shaped orangeophilic cells without nuclear atypia, (iv) keratoglobules, and (v) uneven filamentous cytoplasm, were found to be significant parameters. All malignant cases contained at least one of those parameters, while none were observed in the four non-neoplastic cases with nuclear atypia. In reevaluations, the Bethesda system did not help the screeners distinguish oral SCCs from non-neoplastic lesions, while use of the five parameters enabled them to make a diagnosis of SCC. Recognition of the present five parameters is useful for oral SCC cytology. Diagn. Cytopathol. 2017;45:406-417. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Early transcriptional changes in cardiac mitochondria during chronic doxorubicin exposure and mitigation by dexrazoxane in mice

Energy Technology Data Exchange (ETDEWEB)

Vijay, Vikrant; Moland, Carrie L.; Han, Tao; Fuscoe, James C. [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lee, Taewon [Department of Mathematics, Korea University, Sejong (Korea, Republic of); Herman, Eugene H. [Toxicology and Pharmacology Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, The National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850-9734 (United States); Jenkins, G. Ronald [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Lewis, Sherry M. [Office of Scientific Coordination, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Cummings, Connie A. [UltraPath Imaging, 2228 Page Road, Durham, NC 27703 (United States); Gao, Yuan; Cao, Zhijun; Yu, Li-Rong [Biomarkers and Alternative Models Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States); Desai, Varsha G., E-mail: varsha.desai@fda.hhs.gov [Personalized Medicine Branch, Division of Systems Biology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079 (United States)

2016-03-15

Identification of early biomarkers of cardiotoxicity could help initiate means to ameliorate the cardiotoxic actions of clinically useful drugs such as doxorubicin (DOX). Since DOX has been shown to target mitochondria, transcriptional levels of mitochondria-related genes were evaluated to identify early candidate biomarkers in hearts of male B6C3F{sub 1} mice given a weekly intravenous dose of 3 mg/kg DOX or saline (SAL) for 2, 3, 4, 6, or 8 weeks (6, 9, 12, 18, or 24 mg/kg cumulative DOX doses, respectively). Also, a group of mice was pretreated (intraperitoneally) with the cardio-protectant, dexrazoxane (DXZ; 60 mg/kg) 30 min before each weekly dose of DOX or SAL. At necropsy a week after the last dose, increased plasma concentrations of cardiac troponin T (cTnT) were detected at 18 and 24 mg/kg cumulative DOX doses, whereas myocardial alterations were observed only at the 24 mg/kg dose. Of 1019 genes interrogated, 185, 109, 140, 184, and 451 genes were differentially expressed at 6, 9, 12, 18, and 24 mg/kg cumulative DOX doses, respectively, compared to concurrent SAL-treated controls. Of these, expression of 61 genes associated with energy metabolism and apoptosis was significantly altered before and after occurrence of myocardial injury, suggesting these as early genomics markers of cardiotoxicity. Much of these DOX-induced transcriptional changes were attenuated by pretreatment of mice with DXZ. Also, DXZ treatment significantly reduced plasma cTnT concentration and completely ameliorated cardiac alterations induced by 24 mg/kg cumulative DOX. This information on early transcriptional changes during DOX treatment may be useful in designing cardioprotective strategies targeting mitochondria. - Highlights: • Altered mitochondria-related gene expression before heart injury by doxorubicin • Dexrazoxane mitigated doxorubicin-induced early expression changes in mitochondria. • Dexrazoxane completely ameliorated doxorubicin-induced pathology in mouse heart.

Degradation of type IV collagen by neoplastic human skin fibroblasts

International Nuclear Information System (INIS)

Sheela, S.; Barrett, J.C.

1985-01-01

An assay for the degradation of type IV (basement membrane) collagen was developed as a biochemical marker for neoplastic cells from chemically transformed human skin fibroblasts. Type IV collagen was isolated from basement membrane of Syrian hamster lung and type I collagen was isolated from rat tails; the collagens were radioactively labelled by reductive alkylation. The abilities of normal (KD) and chemically transformed (Hut-11A) human skin fibroblasts to degrade the collagens were studied. A cell-associated assay was performed by growing either normal or transformed cells in the presence of radioactively labelled type IV collagen and measuring the released soluble peptides in the medium. This assay also demonstrated that KD cells failed to synthesize an activity capable of degrading type IV collagen whereas Hut-11A cells degraded type IV collagen in a linear manner for up to 4 h. Human serum at very low concentrations, EDTA and L-cysteine inhibited the enzyme activity, whereas protease inhibitors like phenylmethyl sulfonyl fluoride, N-ethyl maleimide or soybean trypsin inhibitor did not inhibit the enzyme from Hut-11A cells. These results suggest that the ability to degrade specifically type IV collagen may be an important marker for neoplastic human fibroblasts and supports a role for this collagenase in tumor cell invasion

Differentiation of osteoporotic and neoplastic vertebral fractures by chemical shift {l_brace}in-phase and out-of phase{r_brace} MR imaging

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Ragab, Yasser [Radiology Department, Faculty of Medicine, Cairo University (Egypt); Radiology Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: yragab61@hotmail.com; Emad, Yasser [Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University (Egypt); Rheumatology and Rehabilitation Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: yasseremad68@yahoo.com; Gheita, Tamer [Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University (Egypt)], E-mail: gheitamer@yahoo.com; Mansour, Maged [Oncology Department, Faculty of Medicine, Cairo University (Egypt); Oncology Department, Dr Erfan and Bagedo General Hospital (Saudi Arabia)], E-mail: magedmansour@yahoo.com; Abou-Zeid, A. [Public Health Department, Faculty of Medicine, Cairo University, Cairo (Egypt)], E-mail: alaabouzeid@yahoo.com; Ferrari, Serge [Division of Bone Diseases, Department of Rehabilitation and Geriatrics, and WHO, Collaborating Center for Osteoporosis Prevention, Geneva University Hospital (Switzerland)], E-mail: serge.ferrari@medecine.unige.ch; Rasker, Johannes J. [Rheumatologist University of Twente, Enschede (Netherlands)], E-mail: j.j.rasker@utwente.nl

2009-10-15

Objective: The objective of this study was to establish the cut-off value of the signal intensity drop on chemical shift magnetic resonance imaging (MRI) with appropriate sensitivity and specificity to differentiate osteoporotic from neoplastic wedging of the spine. Patients and methods: All patients with wedging of vertebral bodies were included consecutively between February 2006 and January 2007. A chemical shift MRI was performed and signal intensity after (in-phase and out-phase) images were obtained. A DXA was performed in all. Results: A total of 40 patients were included, 20 with osteoporotic wedging (group 1) and 20 neoplastic (group 2). They were 21 males and 19 females. Acute vertebral collapse was observed in 15 patients in group 1 and subacute collapse in another 5 patients, while in group 2, 11 patients showed acute collapse and 9 patients (45%) showed subacute vertebral collapse. On the chemical shift MRI a substantial reduction in signal intensity was found in all lesions in both groups. The proportional changes observed in signal intensity of bone marrow lesions on in-phase compared with out-of-phase images showed significant differences in both groups (P < 0.05). At a cut-off value of 35%, the observed sensitivity of out-of-phase images was 95%, specificity was 100%, positive predictive value was 100% and negative predictive value was 95.2%. Conclusion: A chemical shift MRI is useful in order to differentiate patients with vertebral collapse due to underlying osteoporosis or neoplastic process.

An in vitro model demonstrates the potential of neoplastic human germ cells to influence the tumour microenvironment.

Science.gov (United States)

Klein, B; Schuppe, H-C; Bergmann, M; Hedger, M P; Loveland, B E; Loveland, K L

2017-07-01

Testicular germ cell tumours (TGCT) typically contain high numbers of infiltrating immune cells, yet the functional nature and consequences of interactions between GCNIS (germ cell neoplasia in situ) or seminoma cells and immune cells remain unknown. A co-culture model using the seminoma-derived TCam-2 cell line and peripheral blood mononuclear cells (PBMC, n = 7 healthy donors) was established to investigate how tumour and immune cells each contribute to the cytokine microenvironment associated with TGCT. Three different co-culture approaches were employed: direct contact during culture to simulate in situ cellular interactions occurring within seminomas (n = 9); indirect contact using well inserts to mimic GCNIS, in which a basement membrane separates the neoplastic germ cells and immune cells (n = 3); and PBMC stimulation prior to direct contact during culture to overcome the potential lack of immune cell activation (n = 3). Transcript levels for key cytokines in PBMC and TCam-2 cell fractions were determined using RT-qPCR. TCam-2 cell fractions showed an immediate increase (within 24 h) in several cytokine mRNAs after direct contact with PBMC, whereas immune cell fractions did not. The high levels of interleukin-6 (IL6) mRNA and protein associated with TCam-2 cells implicate this cytokine as important to seminoma physiology. Use of PBMCs from different donors revealed a robust, repeatable pattern of changes in TCam-2 and PBMC cytokine mRNAs, independent of potential inter-donor variation in immune cell responsiveness. This in vitro model recapitulated previous data from clinical TGCT biopsies, revealing similar cytokine expression profiles and indicating its suitability for exploring the in vivo circumstances of TGCT. Despite the limitations of using a cell line to mimic in vivo events, these results indicate how neoplastic germ cells can directly shape the surrounding tumour microenvironment, including by influencing local immune responses. IL6

M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells.

Directory of Open Access Journals (Sweden)

Yasushi Hara

Full Text Available Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs, acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt pathway and the signal transducer and activator of transcription 5 (STAT5 but only on endolysosomes and on the endoplasmic reticulum (ER, respectively. Here, we show a strategy for inhibition of the Kit-PI3K-Akt pathway in neoplastic mast cells by M-COPA (2-methylcoprophilinamide, an inhibitor of this secretory pathway. In M-COPA-treated cells, Kit localization in the ER is significantly increased, whereas endolysosomal Kit disappears, indicating that M-COPA blocks the biosynthetic transport of Kit from the ER. The drug greatly inhibits oncogenic Akt activation without affecting the association of Kit with PI3K, indicating that ER-localized Kit-PI3K complex is unable to activate Akt. Importantly, M-COPA but not imatinib suppresses neoplastic mast cell proliferation through inhibiting anti-apoptotic Akt activation. Results of our M-COPA treatment assay show that Kit can activate Erk not only on the ER but also on other compartments. Furthermore, Tyr568/570, Tyr703, Tyr721, and Tyr936 in Kit are phosphorylated on the ER, indicating that these five tyrosine residues are all phosphorylated before mutant Kit reaches the plasma membrane (PM. Our study provides evidence that Kit is tyrosine-phosphorylated soon after synthesis on the ER but is

M-COPA suppresses endolysosomal Kit-Akt oncogenic signalling through inhibiting the secretory pathway in neoplastic mast cells.

Science.gov (United States)

Hara, Yasushi; Obata, Yuuki; Horikawa, Keita; Tasaki, Yasutaka; Suzuki, Kyohei; Murata, Takatsugu; Shiina, Isamu; Abe, Ryo

2017-01-01

Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib. Recently, we showed that in neoplastic mast cells that endogenously express an imatinib-resistant Kit mutant, Kit causes oncogenic activation of the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the signal transducer and activator of transcription 5 (STAT5) but only on endolysosomes and on the endoplasmic reticulum (ER), respectively. Here, we show a strategy for inhibition of the Kit-PI3K-Akt pathway in neoplastic mast cells by M-COPA (2-methylcoprophilinamide), an inhibitor of this secretory pathway. In M-COPA-treated cells, Kit localization in the ER is significantly increased, whereas endolysosomal Kit disappears, indicating that M-COPA blocks the biosynthetic transport of Kit from the ER. The drug greatly inhibits oncogenic Akt activation without affecting the association of Kit with PI3K, indicating that ER-localized Kit-PI3K complex is unable to activate Akt. Importantly, M-COPA but not imatinib suppresses neoplastic mast cell proliferation through inhibiting anti-apoptotic Akt activation. Results of our M-COPA treatment assay show that Kit can activate Erk not only on the ER but also on other compartments. Furthermore, Tyr568/570, Tyr703, Tyr721, and Tyr936 in Kit are phosphorylated on the ER, indicating that these five tyrosine residues are all phosphorylated before mutant Kit reaches the plasma membrane (PM). Our study provides evidence that Kit is tyrosine-phosphorylated soon after synthesis on the ER but is unable to

Neoplastic meningitis: a retrospective review of clinical presentations, radiological and cerebrospinal fluid findings.

Science.gov (United States)

Jearanaisilp, Sorrawit; Sangruji, Tumthip; Danchaivijitr, Chotipat; Danchaivijitr, Nasuda

2014-08-01

To review the clinical, radiological, and laboratory presentations of patients with neoplastic meningitis. Patients with neoplastic meningitis were recruited by a retrospective search of cerebrospinal fluid (CSF) cytopathological report database of Siriraj Hospital between 1997 and 2006. Clinical information and CSF result of these patients were extracted from their medical records. Neuroimagings were reviewed by a neuroradiologist. The present study revealed 40 cases of neoplastic meningitis, which comprised of 17 cases with carcinomatous meningitis (CM) and 23 lymphoma/leukemia meningitis (LM) cases. In patients with CM, the majority (70%) had adenocarcinoma of lung or breast. Three of 17 cases with unknown primary tumor had carcinomatous meningitis as an initial presentation. In LM most of the cases (70%) were diagnosed with acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The most common symptom among patients with CM and LM was headache follow by cranial nerve palsy. In CM cases, CSF cytology was positive in the first specimen in 15 cases (82.35%) and in 22 from 23 cases (95.7%) in LM cases. Overall CSF showed pleocytosis in 36 cases (90%), most of which were lymphocyte predominant. The most common findings from brain imagings were leptomeningeal enhancement and hydrocephalus. The common primary sites were lung and breast cancer in the CM group and ALL and NHL in the LM group. The common symptoms were headache and cranial nerve palsy. Routine CSF examination was abnormal in virtually all cases. Positive CSF cytology was a gold standard for a diagnosis of leptomeningeal metastasis. High index of suspicious and awareness were required to avoid miss diagnosis.

Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease

Science.gov (United States)

Borner, Roseane; Bento-Torres, João; Souza, Diego RV; Sadala, Danyelle B; Trevia, Nonata; Farias, José Augusto; Lins, Nara; Passos, Aline; Quintairos, Amanda; Diniz, José Antônio; Perry, Victor Hugh; Vasconcelos, Pedro Fernando; Cunningham, Colm

2011-01-01

Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression. PMID:21862877

Nuclear Division Index may Predict Neoplastic Colorectal Lesions.

Science.gov (United States)

Ionescu, Mirela E; Ciocirlan, Mihai; Becheanu, Gabriel; Nicolaie, Tudor; Ditescu, Cristina; Teiusanu, Adriana G; Gologan, Serban I; Arbanas, Tudor; Diculescu, Mircea M

2011-07-01

Colorectal cancer (CRC) develops by accumulation of multiple genetic damages leading to genetic instability that can be evaluated by cytogenetic methods. In the current study we used Cytokinesis-Blocked Micronucleus Assay (CBMN) technique to assess the behavior of Nuclear Division Index(NDI) in peripheral lymphocytes of patients with CRC and polyps versus patients with normal colonoscopy. Blood samples were collected from patients after informed consent. By CBMN technique we assessed the proportion of mono-nucleated, bi-nucleated, tri-nucleated and tetra-nucleated cells/500 cells, to calculate NDI. Data were statistically analyzed using the SPSS 11.0 package. 45 patients were available for analysis, 23 men and 22 women, with a mean age of 58.7±13.5. 17 had normal colonoscopy, 17 colonic polyps and 11 CRC. The mean NDI values were significantly smaller for patients with CRC or polyps than in patients with normal colonoscopy (1.57 vs 1.73, p=0.013). The difference persisted for patients with neoplastic lesions (adenomas and carcinomas) when compared with patients with normal colonoscopy or non neoplastic (hyperplastic) polyps (1.56 vs.1.71, p=0.018). The NDI cut-off value to predict the presence of adenomas or carcinomas was equal to 1.55 with a 54.2% sensitivity and 81% specificity of lower values (p=0.019). The NDI cut off value to predict the presence of advanced adenomas or cancer was 1.525 for a sensitivity of 56.3% and a specificity of 82.8% (p=0.048). NDI may be useful in screening strategies for colorectal cancer as simple, noninvasive, inexpensive cytogenetic biomarker.

Adenocarcinoma of the rete testis with prominent papillary structure and clear neoplastic cells: Morphologic and immunohistochemical findings and differential diagnosis

Directory of Open Access Journals (Sweden)

Pei-Wen Huang

2015-01-01

Full Text Available Adenocarcinoma of the rete testis is rare, and its etiology is unknown. The definite diagnosis merely depends on the exclusion of other tumors and histological features. We first describe a 38-year-old man with a carcinoma arising in the rete testis. The tumor was characterized by clear neoplastic cells and branching papillary growth. Focal stromal invasion and transition of normal rete epithelium to neoplastic cells were seen. The neoplastic cells were positive for epithelial membrane antigen, Ber-Ep4, vimentin, renal cell carcinoma marker, and CD10, while negative for Wilms′ tumor 1, thyroid transcription factor-1, estrogen receptor, prostate specific antigen, placental alkaline phosphate, CD117, and alpha-1-fetoprotein. According to the above features, we diagnosed this tumor as adenocarcinoma of the rete testis. To our best knowledge, this is the first reported case of adenocarcinoma of the rete testis with prominently papillary structure and clear neoplastic cells. The rarity of adenocarcinoma of the rete testis and the unique features in our case cause diagnostic pitfalls. A complete clinicopathological study and thorough differential diagnosis are crucial for the correct result.

EVALUATION OF EARLY ISCHEMIC CHANGES IN STROKE PATIENTS TREATED WITH THROMBOLYTIC THERAPY

OpenAIRE

Kolevski Goran; Korneti-Pekevska Kostandina

2016-01-01

Introduction:The aim of this study is to evaluate early brain ischemic changes on CT scan in stroke patients in correlation with the clinical outcome, as well as to evaluate if there is prognostic and predictive features that can be used. Patients and methods: We examined 20 patients with acute ischemic stroke, from which 12 were male and 8 were female, at the age from 47 to 76 years. Results: The hyperdense medial artery (HMA) sign was present in 10 (50%) patients. Concerning the ASPECTS s...

Possible error-prone repair of neoplastic transformation induced by fission-spectrum neutrons

Energy Technology Data Exchange (ETDEWEB)

Hill, C K; Han, A; Elkind, M M

1948-01-01

An examination was made of the effect of fission-spectrum neutrons from the JANUS reactor at Argonne National Laboratory, delivered either as acute or protracted irradiation, on the incidence of neoplastic transformation in the C3H 10T1/2 mouse embryo cell line. Acute exposures were delivered at 10-38 cGy min/sup -1/, protracted exposures at 0.086 or 0.43 cGy min/sup -1/. The total doses for both ranged from 2.4 to 350 cGy. In the low dose region (2.4-80 cGy), there was a large enhancement in transformation frequency when the neutrons were delivered at the low dose rates compared with the high dose rates, but the survival of the cells was not significantly different between the two exposures conditions. Analysis of the intial parts of the curves shows that the regression line for protracted doses is about 9 times steeper than that for single acute exposures. Finally, the possibility is discussed that an ''error-prone'' repair process may be causing the enhanced transformation frequency by protracted neutron exposures.

Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage

International Nuclear Information System (INIS)

Ganapathi, Ramya; Manda, Kailash

2017-01-01

Purpose: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Methods and Materials: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Results: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significant changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Conclusion: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.

Later Life Changes in Hippocampal Neurogenesis and Behavioral Functions After Low-Dose Prenatal Irradiation at Early Organogenesis Stage

Energy Technology Data Exchange (ETDEWEB)

Ganapathi, Ramya; Manda, Kailash, E-mail: kailashmanda@gmail.com

2017-05-01

Purpose: To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Methods and Materials: Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Results: Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significant changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Conclusion: Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female.

Gastric diffuse large B cell lymphoma presenting as para neoplastic cerebellar degeneration: Case report and review of literature

International Nuclear Information System (INIS)

Lakshmaiah, K.C.; Viveka, B.K.; Kumar, N.A.; Saini, M.L.; Sinha, S.; Saini, K.S.

2013-01-01

Para neoplastic cerebellar degeneration (PCD) is a type of para neoplastic neurological disorder (PND) that is associated with many solid tumors, Hodgkins lymphoma (HL) and very rarely with non-Hodgkin lymphoma (NHL). We report a case of PCD associated with gastric diffuse large B-cell lymphoma (DLBCL) in a patient who presented with acute onset of giddiness and double vision and had complete remission of the gastric lesion and marked improvement of cerebellar syndrome with rituximab-based combination chemotherapy. A brief review of the literature is also presented.

Matrix Metalloproteinases in Non-Neoplastic Disorders

Science.gov (United States)

Tokito, Akinori; Jougasaki, Michihisa

2016-01-01

The matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. There are at least 23 members of MMPs ever reported in human, and they and their substrates are widely expressed in many tissues. Recent growing evidence has established that MMP not only can degrade a variety of components of extracellular matrix, but also can cleave and activate various non-matrix proteins, including cytokines, chemokines and growth factors, contributing to both physiological and pathological processes. In normal conditions, MMP expression and activity are tightly regulated via interactions between their activators and inhibitors. Imbalance among these factors, however, results in dysregulated MMP activity, which causes tissue destruction and functional alteration or local inflammation, leading to the development of diverse diseases, such as cardiovascular disease, arthritis, neurodegenerative disease, as well as cancer. This article focuses on the accumulated evidence supporting a wide range of roles of MMPs in various non-neoplastic diseases and provides an outlook on the therapeutic potential of inhibiting MMP action. PMID:27455234

Early weight loss predicts weight loss treatment response regardless of binge-eating disorder status and pretreatment weight change.

Science.gov (United States)

Barnes, Rachel D; Ivezaj, Valentina; Pittman, Brian P; Grilo, Carlos M

2018-04-10

Individuals seeking weight loss treatment have diverse pretreatment weight trajectories, and once enrolled, individuals' response to weight loss treatments also varies greatly and may be influenced by the presence of binge-eating disorder (BED). Reported average weight losses may obscure these considerable differences. This study examined whether BED status and different weight-related change variables are associated with successful weight loss treatment outcomes in a controlled treatment study. Participants (N = 89) with overweight/obesity, with and without BED, participated in a 3-month weight loss trial in primary care with 3- and 12-month follow-ups. We tested the prognostic significance of four weight-related change variables (the last supper, early weight loss, pretreatment weight trajectory, weight suppression) on outcomes (weight loss-overall, weight loss-"subsequent," weight loss during second half of treatment). Early weight loss was positively associated with weight loss-overall at post-treatment, and at 3-month and 12-month follow-up. Early weight loss was positively associated with weight loss-subsequent at post-treatment only. No other weight-related variables were significantly associated with weight loss. Models including BED status and treatment condition were not significant. Participants with early weight loss were more likely to continue losing weight, regardless of BED status or treatment condition. The results highlight the importance of early dedication to weight loss treatment to increase the likelihood of positive outcomes. © 2018 Wiley Periodicals, Inc.

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.

Early extracellular matrix changes are associated with later development of bronchiolitis obliterans syndrome after lung transplantation

DEFF Research Database (Denmark)

Müller, Catharina; Andersson-Sjöland, Annika; Schultz, Hans Henrik

2017-01-01

are largely unknown. The aim of this study was to identify potential early changes in the extracellular matrix (ECM) in different compartments of the transplanted lung prior to the development of BOS. Methods: Transbronchial biopsies from a cohort of 58 lung transplantation patients at the Copenhagen...... and immunohistochemistry. Results: A time-specific and compartment-specific pattern of ECM changes was detected. Alveolar total collagen (p=0.0190) and small airway biglycan (p=0.0199) increased between 3 and 12 months after transplantation in patients developing BOS, while collagen type IV (p=0.0124) increased...... in patients without BOS. Patients with early-onset BOS mirrored this increase. Patients developing grade 3 BOS showed distinct ECM changes already at 3 months. Patients with BOS with treated acute rejections displayed reduced alveolar total collagen (p=0.0501) and small airway biglycan (p=0.0485) at 3 months...

Non-neoplastic cystic and cystic-like lesions of the pancreas: may mimic pancreatic cystic neoplasms.

Science.gov (United States)

Goh, Brian K P; Tan, Yu-Meng; Chung, Yaw-Fui A; Chow, Pierce K H; Ong, Hock-Soo; Lim, Dennis T H; Wong, Wai-Keong; Ooi, London L P J

2006-05-01

Cystic lesions of the pancreas consist of a broad range of pathological entities. With the exception of the pancreatic pseudocyst, these are usually caused by pancreatic cystic neoplasms. Non-neoplastic pancreatic cystic and cystic-like lesions are extremely rare. In the present article, the surgical experience with these unusual entities over a 14-year period is reported. Between 1991 and 2004, all patients who underwent surgical exploration for a cystic lesion of the pancreas were retrospectively reviewed. Patients with a pancreatic pseudocyst were excluded. There were 106 patients of whom 8 (7.5%) had a final pathological diagnosis consistent with a non-neoplastic pancreatic cystic or cystic-like lesion, including 3 patients with a benign epithelial cyst, 2 with a pancreatic abscess (one tuberculous and one foreign body), 2 with mucous retention cysts and 1 with a mucinous non-neoplastic cyst. These eight patients are the focus of this study. There were six female and two male patients with a median age of 61.5 years (range, 41-71 years). All the patients were of Asian origin including seven Chinese and one Indian. Four of the patients were asymptomatic and their pancreatic cysts were discovered incidentally on radiological imaging for other indications. All the patients underwent preoperative radiological investigations, including ultrasonography, computed tomography or magnetic resonance imaging, which showed a cystic lesion of the pancreas. Three patients, all of whom were symptomatic, were diagnosed preoperatively with a malignant cystic neoplasm on the basis of radiological imaging. Two patients were eventually found to have a pancreatic abscess, one tuberculous and the other, secondary to foreign body perforation. The third patient was found on final histology to have chronic pancreatitis with retention cysts. The remaining five patients had a preoperative diagnosis of an indeterminate cyst; on pathological examination, they were found to have a benign

Biological Characteristics of Caspase-14 and Its Expression in Neoplastic Diseases in the View of Translational Medicine

Directory of Open Access Journals (Sweden)

Kang-sheng LIU

2016-06-01

Full Text Available Caspase-14, a member of caspase family, only exists in mammals. As the most divergent member in the family of mammalian caspases, caspase-14 displays a variety of unique characteristics. It is expressed in a limited number of tissues and has the shortest amino acid sequence within the caspase protein family. At present, it has been found that caspase-14 is functionally different from the inflammatory reaction group of typical caspase family members. It exerts a certain effect in the promotion of final differentiation of epidermal cells and hydration of stratum corneum so as to maintain the steady state of skin barrier. In recent years, caspase-14 expression has been discovered in neoplastic diseases. Translational medicine integrates experimental research results and clinical guidance into the optimal implementation criteria for promoting the prediction, prevention and treatment of diseases. Via human genomics and molecular biology, translational medicine offers a possibility of screening molecular markers so that it can be used to diagnose the neoplastic diseases. In this article, the biological characteristics and substrates of caspase-14 as well as its expression in embryonic period and neoplastic diseases were reviewed.

Neoplastic Meningitis from Solid Tumors: A Prospective Clinical Study in Lombardia and a Literature Review on Therapeutic Approaches

Directory of Open Access Journals (Sweden)

A. Silvani

2013-01-01

Full Text Available Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC and liposomal antitumor agents (liposomal AraC. Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

Arising podosomal structures are associated with neoplastic cell morphological phenotype induced by the microenvironment

Czech Academy of Sciences Publication Activity Database

Veselý, Pavel; Blase, C.; Matoušková, Eva; Bereiter-Hahn, J.

2006-01-01

Roč. 26, - (2006), s. 967-972 ISSN 0250-7005 R&D Projects: GA MZd(CZ) NR8145 Institutional research plan: CEZ:AV0Z50520514 Keywords : podosomes * neoplastic cell morphotype * phenotypic plasticity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.479, year: 2006

Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells.

Science.gov (United States)

Granger, D L; Lehninger, A L

1982-11-01

Previous work has shown that injury of neoplastic cells by cytotoxic macrophages (CM) in cell culture is accompanied by inhibition of mitochondrial respiration. We have investigated the nature of this inhibition by studying mitochondrial respiration in CM-injured leukemia L1210 cells permeabilized with digitonin. CM-induced injury affects the mitochondrial respiratory chain proper. Complex I (NADH-coenzyme Q reductase) and complex II (succinate-coenzyme Q reductase) are markedly inhibited. In addition a minor inhibition of cytochrome oxidase was found. Electron transport from alpha-glycerophosphate through the respiratory chain to oxygen is unaffected and permeabilized CM-injured L1210 cells oxidizing this substrate exhibit acceptor control. However, glycerophosphate shuttle activity was found not to occur within CM-injured or uninjured L1210 cells in culture hence, alpha-glycerophosphate is apparently unavailable for mitochondrial oxidation in the intact cell. It is concluded that the failure of respiration of intact neoplastic cells injured by CM is caused by the nearly complete inhibition of complexes I and II of the mitochondrial electron transport chain. The time courses of CM-induced electron transport inhibition and arrest of L1210 cell division are examined and the possible relationship between these phenomena is discussed.

Gallium SPECT detection of neoplastic intravascular obstruction of the superior vena cava

International Nuclear Information System (INIS)

Swayne, L.C.; Kaplan, I.L.

1989-01-01

A rare case of an intravascular neoplastic obstruction of the superior vena cava is discussed. The lesion was detected with gallium single photon emission computed tomography (SPECT) despite a normal appearance on a concurrent radiographic CT study. A computer-generated composite SPECT-CT image confirmed the intravascular localization of the radioisotope, and a subsequent CT-guided transthoracic needle biopsy revealed a poorly differentiated adenocarcinoma

Rheological changes of polyamide 12 under oscillatory shear

Science.gov (United States)

Mielicki, C.; Gronhoff, B.; Wortberg, J.

2014-05-01

Changes in material properties as well as process deviation prevent Laser Sintering (LS) technology from manufacturing of quality assured parts in a series production. In this context, the viscosity of Polyamide 12 (PA12) is assumed to possess the most significant influence, as it determines the sintering velocity, the resistance towards melt formation and the bonding strength of sintered layers. Moreover, the viscosity is directly related to the structure of the molten polymer. In particular, it has been recently reported that LS process conditions lead to structural changes of PA12 affecting viscosity and coalescence of adjacent polymer particles, i.e. melt formation significantly. Structural change of PA12 was understood as a post condensation. Its influence on viscosity was described by a time and temperature depending rheological model whereas time dependence was considered by a novel structural change shift factor which was derived from melt volume rate data. In combination with process data that was recorded using online thermal imaging, the model is suitable to control the viscosity (processability of the material) as result of material and process properties. However, as soon as laser energy is exposed to the powder bed PA12 undergoes a phase transition from solid to molten state. Above the melting point, structural change is expected to occur faster due to a higher kinetic energy and free volume of the molten polymer. Oscillatory shear results were used to study the influence of aging time and for validation of the novel structural change shift factor and its model parameters which were calibrated based on LS processing condition.

Near-infrared Raman spectroscopy for estimating biochemical changes associated with different pathological conditions of cervix

Science.gov (United States)

Daniel, Amuthachelvi; Prakasarao, Aruna; Ganesan, Singaravelu

2018-02-01

The molecular level changes associated with oncogenesis precede the morphological changes in cells and tissues. Hence molecular level diagnosis would promote early diagnosis of the disease. Raman spectroscopy is capable of providing specific spectral signature of various biomolecules present in the cells and tissues under various pathological conditions. The aim of this work is to develop a non-linear multi-class statistical methodology for discrimination of normal, neoplastic and malignant cells/tissues. The tissues were classified as normal, pre-malignant and malignant by employing Principal Component Analysis followed by Artificial Neural Network (PC-ANN). The overall accuracy achieved was 99%. Further, to get an insight into the quantitative biochemical composition of the normal, neoplastic and malignant tissues, a linear combination of the major biochemicals by non-negative least squares technique was fit to the measured Raman spectra of the tissues. This technique confirms the changes in the major biomolecules such as lipids, nucleic acids, actin, glycogen and collagen associated with the different pathological conditions. To study the efficacy of this technique in comparison with histopathology, we have utilized Principal Component followed by Linear Discriminant Analysis (PC-LDA) to discriminate the well differentiated, moderately differentiated and poorly differentiated squamous cell carcinoma with an accuracy of 94.0%. And the results demonstrated that Raman spectroscopy has the potential to complement the good old technique of histopathology.

Early characteristic radiographic changes in mucolipidosis II

Energy Technology Data Exchange (ETDEWEB)

Lai, Lillian M. [Lucile Packard Children' s Hospital and Stanford University, Pediatric Radiology, Palo Alto, CA (United States); Lachman, Ralph S. [Lucile Packard Children' s Hospital and Stanford University, Pediatric Radiology, Palo Alto, CA (United States); University of California, International Skeletal Dysplasia Registry, Los Angeles, CA (United States)

2016-11-15

Although mucolipidosis type II has similar metabolic abnormalities to those found in all the mucopolysaccharidoses and mucolipidoses, there are distinctive diagnostic radiographic changes of mucolipidosis II in the perinatal/newborn/infant period. To describe the early characteristic radiographic changes of mucolipidosis II and to document when these changes manifest and resolve. We retrospectively reviewed radiographs and clinical records of 19 cases of mucolipidosis II from the International Skeletal Dysplasia Registry (1971-present; fetal age to 21/2 years). A radiologist with special expertise in skeletal dysplasias evaluated the radiographs. The most common abnormalities were increased vertebral body height (80%, nonspecific), talocalcaneal stippling (86%), periosteal cloaking (74%) and vertebral body rounding (50%). Unreported findings included sacrococcygeal sclerosis (54%) and vertebral body sclerosis (13%). Rickets and hyperparathyroidism-like (pseudohyperparathyroidism) changes (rarely reported) were found in 33% of cases. These changes invariably started in the newborn period and resolved by 1 year of age. The conversion from these early infantile radiographic features to dysostosis multiplex changes occurred in 41% of cases, and within the first year after birth. Several findings strongly suggest the diagnosis of mucolipidosis II, including cloaking in combination with one or more of the following radiographic criteria: talocalcaneal stippling, sacrococcygeal or generalized vertebral body sclerosis, vertebral body rounding, or rickets/hyperparathyroidism-like changes in the perinatal/newborn/infancy period. These findings are not found in the other two forms of mucolipidosis nor in any of the mucopolysaccharidoses. (orig.)

Early characteristic radiographic changes in mucolipidosis II

International Nuclear Information System (INIS)

Lai, Lillian M.; Lachman, Ralph S.

2016-01-01

Although mucolipidosis type II has similar metabolic abnormalities to those found in all the mucopolysaccharidoses and mucolipidoses, there are distinctive diagnostic radiographic changes of mucolipidosis II in the perinatal/newborn/infant period. To describe the early characteristic radiographic changes of mucolipidosis II and to document when these changes manifest and resolve. We retrospectively reviewed radiographs and clinical records of 19 cases of mucolipidosis II from the International Skeletal Dysplasia Registry (1971-present; fetal age to 21/2 years). A radiologist with special expertise in skeletal dysplasias evaluated the radiographs. The most common abnormalities were increased vertebral body height (80%, nonspecific), talocalcaneal stippling (86%), periosteal cloaking (74%) and vertebral body rounding (50%). Unreported findings included sacrococcygeal sclerosis (54%) and vertebral body sclerosis (13%). Rickets and hyperparathyroidism-like (pseudohyperparathyroidism) changes (rarely reported) were found in 33% of cases. These changes invariably started in the newborn period and resolved by 1 year of age. The conversion from these early infantile radiographic features to dysostosis multiplex changes occurred in 41% of cases, and within the first year after birth. Several findings strongly suggest the diagnosis of mucolipidosis II, including cloaking in combination with one or more of the following radiographic criteria: talocalcaneal stippling, sacrococcygeal or generalized vertebral body sclerosis, vertebral body rounding, or rickets/hyperparathyroidism-like changes in the perinatal/newborn/infancy period. These findings are not found in the other two forms of mucolipidosis nor in any of the mucopolysaccharidoses. (orig.)

Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease.

Science.gov (United States)

Stout, Julie C; Jones, Rebecca; Labuschagne, Izelle; O'Regan, Alison M; Say, Miranda J; Dumas, Eve M; Queller, Sarah; Justo, Damian; Santos, Rachelle Dar; Coleman, Allison; Hart, Ellen P; Dürr, Alexandra; Leavitt, Blair R; Roos, Raymund A; Langbehn, Doug R; Tabrizi, Sarah J; Frost, Chris

2012-07-01

Deterioration of cognitive functioning is a debilitating symptom in many neurodegenerative diseases, such as Huntington's disease (HD). To date, there are no effective treatments for the cognitive problems associated with HD. Cognitive assessment outcomes will have a central role in the efforts to develop treatments to delay onset or slow the progression of the disease. The TRACK-HD study was designed to build a rational basis for the selection of cognitive outcomes for HD clinical trials. There were a total of 349 participants, including controls (n=116), premanifest HD (n=117) and early HD (n=116). A standardised cognitive assessment battery (including nine cognitive tests comprising 12 outcome measures) was administered at baseline, and at 12 and 24 months, and consisted of a combination of paper and pencil and computerised tasks selected to be sensitive to cortical-striatal damage or HD. Each cognitive outcome was analysed separately using a generalised least squares regression model. Results are expressed as effect sizes to permit comparisons between tasks. 10 of the 12 cognitive outcomes showed evidence of deterioration in the early HD group, relative to controls, over 24 months, with greatest sensitivity in Symbol Digit, Circle Tracing direct and indirect, and Stroop word reading. In contrast, there was very little evidence of deterioration in the premanifest HD group relative to controls. The findings describe tests that are sensitive to longitudinal cognitive change in HD and elucidate important considerations for selecting cognitive outcomes for clinical trials of compounds aimed at ameliorating cognitive decline in HD.

Hormone Receptor Expression Analyses in Neoplastic and Non-Neoplastic Canine Mammary Tissue by a Bead Based Multiplex Branched DNA Assay: A Gene Expression Study in Fresh Frozen and Formalin-Fixed, Paraffin-Embedded Samples.

Directory of Open Access Journals (Sweden)

Annika Mohr

Full Text Available Immunohistochemistry (IHC is currently considered the method of choice for steroid hormone receptor status evaluation in human breast cancer and, therefore, it is commonly utilized for assessing canine mammary tumors. In case of low hormone receptor expression, IHC is limited and thus is complemented by molecular analyses. In the present study, a multiplex bDNA assay was evaluated as a method for hormone receptor gene expression detection in canine mammary tissues. Estrogen receptor (ESR1, progesterone receptor (PGR, prolactin receptor (PRLR and growth hormone receptor (GHR gene expressions were evaluated in neoplastic and non-neoplastic canine mammary tissues. A set of 119 fresh frozen and 180 formalin-fixed, paraffin-embedded (FFPE was comparatively analyzed and used for assay evaluation. Furthermore, a possible association between the hormone receptor expression in different histological subtypes of canine malignant mammary tumors and the castration status, breed and invasive growth of the tumor were analyzed. The multiplex bDNA assay proved to be more sensitive for fresh frozen specimens. Hormone receptor expression found was significantly decreased in malignant mammary tumors in comparison to non-neoplastic tissue and benign mammary tumors. Among the histological subtypes the lowest gene expression levels of ESR1, PGR and PRLR were found in solid, anaplastic and ductal carcinomas. In summary, the evaluation showed that the measurement of hormone receptors with the multiplex bDNA assay represents a practicable method for obtaining detailed quantitative information about gene expression in canine mammary tissue for future studies. Still, comparison with IHC or quantitative real-time PCR is needed for further validation of the present method.

Early resistance change and stress/electromigration evolution in near bamboo interconnects

NARCIS (Netherlands)

Petrescu, V.; Mouthaan, A.J.; Dima, G.; Govoreanu, B.; Mitrea, O.; Profirescu, M.

1997-01-01

A complete description for early resistance change and mechanical stress evolution in near-bamboo interconnects, related to the electromigration, is given in this paper. The proposed model, for the first time, combines the stress/vacancy concentration evolution with the early resistance change of

Topical Collection: Climate-change research by early-career hydrogeologists

Science.gov (United States)

Re, Viviana; Maldaner, Carlos H.; Gurdak, Jason J.; Leblanc, Marc; Resende, Tales Carvalho; Stigter, Tibor Y.

2018-05-01

Scientific outreach, international networking, collaboration and adequate courses are needed in both developed and developing countries to enable early-career hydrogeologists to promote long-term multidisciplinary approaches to cope with climate-change issues and emphasize the importance of groundwater in a global strategy for adaptation. One such collaboration has involved the Early Career Hydrogeologists' Network of the International Association of Hydrogeologists (ECHN-IAH) and the UNESCO International Hydrological Programme's (IHP) Groundwater Resources Assessment under the Pressures of Humanity and Climate Changes (GRAPHIC) project. This collaboration seeks to foster the education and involvement of the future generation of water leaders in the debate over groundwater and climate change.

Experimental control of neoplastic progression in cell populations: Foulds' rules revisited.

OpenAIRE

Rubin, H

1994-01-01

Foulds introduced six rules of tumor progression based on his observations of spontaneous mammary cancer in mice and generalized them to all forms of neoplasia [Foulds, L. (1954) Cancer Res. 14, 327-339 and Foulds, L. (1969) Neoplastic Development (Academic, New York), Vol. 1, preface and pp. 72-74.] Rules III, IV, and V are considered controversial, and research in animals seems inadequate to resolve the controversies. A subline of NIH 3T3 cells undergoes progressive transformation to produc...

Changes in various metabolic parameters in blood and milk during experimental Escherichia coli mastitis for primiparous Holstein dairy cows during early lactation

DEFF Research Database (Denmark)

Moyes, Kasey M; Larsen, Torben; Sørensen, Peter

2014-01-01

BackgroundThe objective of this study was to characterize the changes in various metabolic parameters in blood and milk during IMI challenge with Escherichia coli (E. coli) for dairy cows during early lactation. Thirty, healthy primiparous Holstein cows were infused (h = 0) with ~20-40 cfu of live...... the effect of IMI challenge on metabolic responses of cows during early lactation.ResultsBy 12 h, E. coli was recovered from challenged quarters and shedding continued through 72 h. Rectal temperature peaked by 12 h post-challenge and returned to pre-challenge values by 36 h post-IMI challenge. Daily feed...... intake and milk yield decreased (P mastitis challenge. Plasma BHBA decreased (12 h; P

Change in Physical Attraction in Early Romantic Relationships

OpenAIRE

Victor Karandashev; Brittany Fata

2014-01-01

The goal of our research was to study the changes in physical attraction during the early stages of romantic relationships. The longitudinal study explored the personality characteristics of a partner and relationship events affecting physical attraction of early (within the first year) romantic relationships. Participants completed an eight-week longitudinal rating of their attraction toward their romantic partner. Factor analysis revealed behavioral, cognitive, emotional, and physiological ...

Resilience in Change: Positive Perspectives on the Dynamics of Change in Early Childhood Systems

Science.gov (United States)

Douglass, Anne

2016-01-01

Change is a central feature of the early care and education landscape today. Much of the research on educational change focuses on the negative or challenging aspects of change. This study employed a critical theory framework from the organizational sciences field, positive organizational scholarship, to offer a new way of thinking about change in…

Reduced temperature (22 degrees C) results in enhancement of cell killing and neoplastic transformation in noncycling HeLa x skin fibroblast human hybrid cells irradiated with low-dose-rate gamma radiation

International Nuclear Information System (INIS)

Redpath, J.L.; Antoniono, R.J.

1995-01-01

The effect of reduced temperature (22 degrees C) or serum deprivation during low-dose-rate (0.66 cGy/min) γ irradiation on cell killing and neoplastic transformation has been examined using the HeLa x skin fibroblast human hybrid cell system. The reduced temperature stops progression of these cells through the cell cycle while serum deprivation slows down cell turnover markedly. The data demonstrate an enhancement in both of the end points when cells are held at 22 degrees C compared to parallel experiments done at 37 degrees C. In operational terms, the decreased survival and increased neoplastic transformation are consistent with our earlier hypothesis of a higher probability of misrepair at reduced temperature. The interpretation that this damage enhancement was associated with the reduced temperature, and not the fact that the cells were noncycling, was supported by the results of experiments performed with cells cultured at 37 degrees C in serum-free medium for 35 h prior to and then during the 12.24 h low-dose-rate radiation exposure. Under these conditions, cell cycle progression, as shown by reduction in growth rate and dual-parameter flow cytometric analysis, was considerable inhibited (cell cycle time increased from 20 h to 40 h), and there was no significant enhancement of cell killing or neoplastic transformation. 23 refs., 2 figs., 1 tab

Limbic grey matter changes in early Parkinson's disease.

Science.gov (United States)

Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

2017-05-02

The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The

Early Life Factors and Adult Leisure Time Physical Inactivity Stability and Change.

Science.gov (United States)

Pinto Pereira, Snehal M; Li, Leah; Power, Chris

2015-09-01

Physical inactivity has a high prevalence and associated disease burden. A better understanding of influences on sustaining and changing inactive lifestyles is needed. We aimed to establish whether leisure time inactivity was stable in midadulthood and whether early life factors were associated with inactivity patterns. In the 1958 British birth cohort (n = 12,271), leisure time inactivity (frequency, less than once a week) assessed at 33 and 50 yr was categorized as "never inactive," "persistently inactive," "deteriorating," or "improving." Early life factors (birth to 16 yr) were categorized into three (physical, social, and behavioral) domains. Using multinomial logistic regression, we assessed associations with inactivity persistence and change of factors within each early life domain and the three domains combined with and without adjustment for adult factors. Inactivity prevalence was similar at 33 and 50 yr (approximately 31%), but 17% deteriorated and 18% improved with age. In models adjusted for all domains simultaneously, factors associated with inactivity persistence versus never inactive were prepubertal stature (8% lower risk/height SD), poor hand control/coordination (17% higher risk/increase on four-point scale), cognition (16% lower/SD in ability) (physical); parental divorce (25% higher), class at birth (7% higher/reduction on four-point scale), minimal parental education (16% higher), household amenities (2% higher/increase in 19-point score (high = poor)) (social); and inactivity (22% higher/reduction in activity on four-point scale), low sports aptitude (47% higher), smoking (30% higher) (behavioral). All except stature, parental education, sports aptitude, and smoking were associated also with inactivity deterioration. Poor hand control/coordination was the only factor associated with improved status (13% lower/increase on four-point scale) versus persistently inactive. Adult leisure time inactivity is moderately stable. Early life factors are

Immunohistochemistry expression of TCF4 protein on carcinoma, adenoma and non neoplastic colorectal mucosa

Directory of Open Access Journals (Sweden)

Leonardo Huber Tauil

2014-01-01

Full Text Available Purpose: To detect and quantify the immunoreactivity of TCF4 protein in colorectal carci- noma, colorectal adenoma and non-neoplasic colorectal epithelium. Methods: We studied 129 individuals: 40 with colorectal cancer, 52 with colorectal ad- enoma and 37 with non-neoplastic colorectal epithelium. The colorectal adenoma and carcinoma samples were obtained from patients who underwent surgical procedures, and colonoscopies and samples of non-neoplastic colorectal epithelium were taken from patients who died from cardiovascular diseases, without diseases of the large intestine. Samples of different tissues were included in paraffin blocks, and the immunohistochem- ical expression of protein TCF4 was analyzed using the technique of tissue microarray (TMA with polyclonal antibody TCF4. The immunoreactivity was analyzed and classified as positive and negative. Results: The immunohistochemical expression of TCF4 protein was significantly higher (p < 0.01 in colorectal carcinoma than in the non-neoplastic colorectal epithelium and adenoma. There was no difference (p = 0.76 between TCF4 protein immunohistochemical expression in colorectal adenoma and non-neoplastic colorectal tissue. Conclusions: TCF4 protein showed a more intense expression in colorectal carcinoma than in non-neoplastic colorectal epithelium and adenoma, indicating that this protein is in- volved in colorectal carcinogenesis. Resumo: Objetivos: Detectar e quantificar a imunoexpressão da proteína TCF4 no carcinoma e no adenoma colorretal e no epitélio colorretal não neoplásico. Método: Foram estudados 129 indivíduos: 40 com carcinoma colorretal, 52 com adenoma colorretal e 37 com epitélio colorretal não neoplásico. Os tecidos de adenoma e carcinoma colorretais foram representados por amostras da lesão retirada de doentes submetidos a procedimentos cirúrgicos e colonoscópicos, e as amostras de epitélio colorretal não neo- plásico foram retiradas de doentes falecidos por

Study of morphological alterations of the adrenal glands in the neoplastic cachexia
Estudo das alterações morfológicas da glândula adrenal na caquexia neoplásica

OpenAIRE

Tânia Longo Mazzuco; Karina Garcia Cotrim; Alexandre Yukio Saito; Marcelo Abbá Macioszek; Eveline Aparecida Isquierdo Fonseca

2009-01-01

Advanced cancer occurs with nutritional and metabolic alterations that characterize neoplastic cachexia. When homeostasis is compromised, the adrenal glands have a fundamental role in the neuroendocrine response. Our purpose in this research was to study morphological alterations of the adrenal glands in the development of cancer associated to cachexia. Cachexia experimental model induced by Walker 256 tumor in Wistar rats, was used. Animals were sacrificed 12 days after tumor cells inoculati...

Diagnostic Accuracy of CT in Paediatric Intracranial Neoplastic Lesions - Radiologic and Pathologic Correlation

International Nuclear Information System (INIS)

Qureshi, A.

2011-01-01

The frequency of paediatric tumours in developing countries could be attributed to the increased percentage (39% of total population of children) in the overall population. Therefore, extensive researches should be under taken in the field of Paediatric Oncology in the third world. Objective: This study was conducted to determine the diagnostic accuracy of CT by comparing the pre-operative radiological findings of paediatric brain tumours with post-operative histopathological findings on the basis of characteristic radiological features of various tumours. Materials and Methods: This was a hospital based prospective, cross-sectional and descriptive study carried out in Radiology Dept, KEMU / Mayo Hospital, Lahore. Study was conducted over a period of 3 years from June 2005 till June 2008 and comprised of 100 cases of paediatric brain tumours up to 12 years of age. Cases were also collected from Mayo and Children Hospital, Lahore. Results: Topographically, supratentorial tumours were found more than infratentorial 55 : 45. Low grade were more common than high grade 73 : 27. The most common tumour was astrocytoma with 52 cases. Medulloblastoma ranked the second with 16 cases followed by craniopharyngioma with 12 cases. Conclusion: The diagnostic accuracy of CT scan was found to be 83% when correlated with histopathology. CT proved fairly accurate in detection of paediatric intracranial neoplastic lesions. As CT is relatively commonly available inexpensive modality than MRI so it can be used as non invasive imaging modality. (author)

Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study

NARCIS (Netherlands)

Haycock, P.C.; Burgess, S.; Nounu, A.; Zheng, J.; Okoli, G.N.; Bowden, J.; Wade, K.H.; Timpson, N.J.; Evans, D.M.; Willeit, P.; Aviv, A.; Gaunt, T.R.; Hemani, G.; Mangino, M.; Ellis, H.P.; Kurian, K.M.; Pooley, K.A.; Eeles, R.A.; Lee, J.E.; Fang, S.; Chen, W.V.; Law, M.H.; Bowdler, L.M.; Iles, M.M.; Yang, Q.; Worrall, B.B.; Markus, H.S.; Hung, R.J.; Amos, C.I.; Spurdle, A.B.; Thompson, D.J.; O'Mara, T.A.; Wolpin, B.; Amundadottir, L.; Stolzenberg-Solomon, R.; Trichopoulou, A.; Onland-Moret, N.C.; Lund, E.; Duell, E.J.; Canzian, F.; Severi, G.; Overvad, K.; Gunter, M.J.; Tumino, R.; Svenson, U.; Rij, A. van; Baas, A.F.; Bown, M.J.; Samani, N.J.; t'Hof, F.N.G. van; Tromp, G.; Jones, G.T.; Kuivaniemi, H.; Elmore, J.R.; Johansson, M.; McKay, J.; Scelo, G.; Carreras-Torres, R.; Gaborieau, V.; Brennan, P.; Bracci, P.M.; Neale, R.E.; Olson, S.H.; Gallinger, S.; Li, D.; Petersen, G.M.; Risch, H.A.; Klein, A.P.; Han, J.; Abnet, C.C.; Freedman, N.D.; Taylor, P.R.; Maris, J.M.; Aben, K.K.H.; Kiemeney, L.A.; Vermeulen, S.H.; Wiencke, J.K.; Walsh, K.M.; Wrensch, M.; Rice, T.; Turnbull, C.; Litchfield, K.; Paternoster, L.; Standl, M.; Abecasis, G.R.; SanGiovanni, J.P.; Li, Y.; Mijatovic, V.; Sapkota, Y.; Low, S.K.; Zondervan, K.T.; Montgomery, G.W.; Nyholt, D.R.; Heel, D.A. van; Hunt, K.; Arking, D.E.; Ashar, F.N.; Sotoodehnia, N.; Woo, D.; et al.,

2017-01-01

Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study,

Casein kinase II is elevated in solid human tumours and rapidly proliferating non-neoplastic tissue

DEFF Research Database (Denmark)

Münstermann, U; Fritz, G; Seitz, G

1990-01-01

Protein kinase CKII (i.e. casein kinase II, CKII, NII) is expressed at a higher level in rapidly proliferating tissues and in solid human tumours (e.g. colorectal carcinomas) when compared to the corresponding non-neoplastic colorectal mucosa. This could be shown by (a) Western blotting of cellular...

Biomarkers for Early Detection of Malignant Mesothelioma: Diagnostic and Therapeutic Application

Energy Technology Data Exchange (ETDEWEB)

Tomasetti, Marco, E-mail: m.tomasetti@univpm.it; Santarelli, Lory [Department of Molecular Pathology and Innovative Therapies, Occupational Medicine, Polytechnic University of Marche, via Tronto 10/A Torrette 60020, Ancona (Italy)

2010-04-14

Malignant mesothelioma (MM) is a rare and aggressive tumour of the serosal cavities linked to asbestos exposure. Improved detection methods for diagnosing this type of neoplastic disease are essential for an early and reliable diagnosis and treatment. Thus, focus has been placed on finding tumour markers for the non-invasive detection of MM. Recently, some blood biomarkers have been described as potential indicators of early and advanced MM cancers. The identification of tumour biomarkers alone or in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos, a common phenomenon in several areas of western countries.

The claudin gene family: expression in normal and neoplastic tissues

International Nuclear Information System (INIS)

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

2006-01-01

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

Computed tomography in neoplastic diseases of the skull base and adjacent areas using EMI scanner CT-1000

International Nuclear Information System (INIS)

Ono, Yoshimi; Ohtake, Eiji; Asakura, Koichi; Tanohata, Kazunori; Ito, Otomasa

1980-01-01

CT-findings of 145 patients with and without neoplastic diseases of the skull base were evaluated using EMI CT-1000. Analysis of 64 patients without any lesion at the skull base showed more artifacts compared with that of higher slices, so that good or fair images were obtained only in 64% of this groups of patients. The most important factor in producing artifacts are considered to be caused by patient's movement. We also evaluated the tumor extension to the skull base in 81 patients. They were 24 brain tumors, 21 pituitary adenomas, and 36 nasopharyngeal and paranasal cancers. Four out of 24 brain tumors showed extracranial extension, 12 pituitary adenomas infiltrating outside of the sella turcica, and 10 cases of nasopharyngeal cancers showed intracranial extension. It was concluded that CT presented an excellent information in evaluating the degree of extension of neoplasms which invading to the skull base. (author)

CBT for eating disorders: The impact of early changes in eating pathology on later changes in personality pathology, anxiety and depression.

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Turner, Hannah; Marshall, Emily; Wood, Francesca; Stopa, Lusia; Waller, Glenn

2016-02-01

Whilst studies have consistently identified early symptom reduction as an important predictor of treatment outcome, the impact of early change on common comorbid features has not been investigated. This study of CBT for eating disorders explored patterns of early change in eating pathology and longer-term change in personality pathology, anxiety and depression. It also explored the impact of early change in eating pathology on overall change in personality pathology, anxiety and depression. Participants were 179 adults diagnosed with eating disorders who were offered a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment and following the 6th session. They also completed measures of personality disorder cognitions, anxiety and depression at the start and end of treatment. There were significant changes in eating pathology over the first six sessions of treatment. Significant improvements were also seen in personality disorder pathology, anxiety and depression by the end of therapy. Effect sizes were medium to large for both completer and intention to treat analyses. Early changes in eating pathology were associated with later changes in common comorbid features, with early reduction in restraint being a key predictor. These findings demonstrate that early symptom change can be achieved in CBT for eating disorders when delivered in routine clinical practice. Such change has long-term benefits that go beyond the domain of eating pathology, enhancing change in personality pathology, anxiety and depression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Responsiveness of fetal rat brain cells to glia maturation factor during neoplastic transformation in cell culture

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Haugen, A; Laerum, O D; Bock, E

1981-01-01

of gestation. The brains of the treated fetuses were transferred to cell culture and underwent neoplastic transformation with a characteristic sequence of phenotypic alterations which could be divided into five different stages. During the first 40 days after explantation (stage I & II) BE induced...

Distribution and quantitative changes in amounts of aquaporin 1, 5 and 9 in the pig uterus during the estrous cycle and early pregnancy

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Skowronski Mariusz T

2010-09-01

Full Text Available Abstract Background Aquaporins (AQPs are a family of membrane channel proteins that facilitate bulk water transport. To date, 11 isoforms of AQPs have been reported to be expressed in the female and male reproductive systems. The purpose of our study was to determine the localization and quantitative changes in the expression of AQP1, 5 and 9 within the pig uterus during different stages of the estrous cycle and early pregnancy. Methods Immunoperoxidase and semi-quantitative immunoblotting techniques were used to examine the distribution and changes in amounts of AQP1, AQP5 and AQP9 in uteral cells of pigs at the early (Days 2-4, middle (10-12, late (14-16 stage of the luteal phase and late (18-20 stage of the follicular phase of the estrous cycle as well as on Days 14-16 and 30-32 of gestation (the onset and the end of implantation process. Results The results demonstrated that AQP1, 5, and 9 were clearly detected in all studied stages of the estrous cycle and pregnancy. AQP1 was localized within uterine blood vessels. In cyclic gilts, endometrial and myometrial expression of AQP1 protein did not change significantly but increased during gestation. AQP5 was localized in smooth muscle cells and uterine epithelial cells. Endometrial expression of AQP5 protein did not change significantly between Days 2-4 and 10-12 of the estrous cycle but increased on Days 14-16 and 18-20 as well as during early pregnancy. Myometrial expression of AQP5 did not differ significantly during the estrous cycle but increased in the pregnancy. The anti-AQP9 antibody labeled uterine epithelial cells of uterus. Endometrial expression of AQP9 did not change significantly between Days 2-4 and 10-12 of the estrous cycle but increased on Days 14-16 and 18-20 as well as during early pregnancy. Conclusions The results suggest that a functional and distinctive collaboration exists among diverse AQPs in water handling during the different uterine phases in the estrous cycle and

Microstructural Changes of the Human Brain from Early to Mid-Adulthood

OpenAIRE

Tian, Lixia; Ma, Lin

2017-01-01

Despite numerous studies on the microstructural changes of the human brain throughout life, we have indeed little direct knowledge about the changes from early to mid-adulthood. The aim of this study was to investigate the microstructural changes of the human brain from early to mid-adulthood. We performed two sets of analyses based on the diffusion tensor imaging (DTI) data of 111 adults aged 18–55 years. Specifically, we first correlated age with skeletonized fractional anisotropy (FA), mea...

Organizational change, psychosocial work environment, and non-disability early retirement

DEFF Research Database (Denmark)

Breinegaard, Nina; Jensen, Johan Høy; Bonde, Jens Peter

2017-01-01

Objective: This study examines the impact of organizational change and psychosocial work environment on non-disability early retirement among senior public service employees. Methods: In January and February 2011, Danish senior public service employees aged 58–64 years (N=3254) from the Capital...... psychosocial work environment contribute to non-disability early retirement among senior public service employees, measured at work-unit level....... Region of Denmark responded to a survey assessing psychosocial work environment (ie, social capital, organizational justice, and quality of management). Work-unit organizational changes (ie, change of management, merging, demerging, and relocation) were recorded from January 2009 to March 2011. Weekly...

Early Change in Stroke Size Performs Best in Predicting Response to Therapy.

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Simpkins, Alexis Nétis; Dias, Christian; Norato, Gina; Kim, Eunhee; Leigh, Richard

2017-01-01

Reliable imaging biomarkers of response to therapy in acute stroke are needed. The final infarct volume and percent of early reperfusion have been used for this purpose. Early fluctuation in stroke size is a recognized phenomenon, but its utility as a biomarker for response to therapy has not been established. This study examined the clinical relevance of early change in stroke volume and compared it with the final infarct volume and percent of early reperfusion in identifying early neurologic improvement (ENI). Acute stroke patients, enrolled between 2013 and 2014 with serial magnetic resonance imaging (MRI) scans (pretreatment baseline, 2 h post, and 24 h post), who received thrombolysis were included in the analysis. Early change in stroke volume, infarct volume at 24 h on diffusion, and percent of early reperfusion were calculated from the baseline and 2 h MRI scans were compared. ENI was defined as ≥4 point decrease in National Institutes of Health Stroke Scales within 24 h. Logistic regression models and receiver operator characteristics analysis were used to compare the efficacy of 3 imaging biomarkers. Serial MRIs of 58 acute stroke patients were analyzed. Early change in stroke volume was significantly associated with ENI by logistic regression analysis (OR 0.93, p = 0.048) and remained significant after controlling for stroke size and severity (OR 0.90, p = 0.032). Thus, for every 1 mL increase in stroke volume, there was a 10% decrease in the odds of ENI, while for every 1 mL decrease in stroke volume, there was a 10% increase in the odds of ENI. Neither infarct volume at 24 h nor percent of early reperfusion were significantly associated with ENI by logistic regression. Receiver-operator characteristic analysis identified early change in stroke volume as the only biomarker of the 3 that performed significantly different than chance (p = 0.03). Early fluctuations in stroke size may represent a more reliable biomarker for response to therapy than the

Epigenetic changes in solid and hematopoietic tumors.

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Toyota, Minoru; Issa, Jean-Pierre J

2005-10-01

There are three connected molecular mechanisms of epigenetic cellular memory in mammalian cells: DNA methylation, histone modifications, and RNA interference. The first two have now been firmly linked to neoplastic transformation. Hypermethylation of CpG-rich promoters triggers local histone code modifications resulting in a cellular camouflage mechanism that sequesters gene promoters away from transcription factors and results in stable silencing. This normally restricted mechanism is ubiquitously used in cancer to silence hundreds of genes, among which some critically contribute to the neoplastic phenotype. Virtually every pathway important to cancer formation is affected by this process. Methylation profiling of human cancers reveals tissue-specific epigenetic signatures, as well as tumor-specific signatures, reflecting in particular the presence of epigenetic instability in a subset of cancers affected by the CpG island methylator phenotype. Generally, methylation patterns can be traced to a tissue-specific, proliferation-dependent accumulation of aberrant promoter methylation in aging tissues, a process that can be accelerated by chronic inflammation and less well-defined mechanisms including, possibly, diet and genetic predisposition. The epigenetic machinery can also be altered in cancer by specific lesions in epigenetic effector genes, or by aberrant recruitment of these genes by mutant transcription factors and coactivators. Epigenetic patterns are proving clinically useful in human oncology via risk assessment, early detection, and prognostic classification. Pharmacologic manipulation of these patterns-epigenetic therapy-is also poised to change the way we treat cancer in the clinic.

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

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Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Brandenburg, Sytze [KVI Center for Advanced Radiation Research, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Coppes, Robert P. [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Luijk, Peter van, E-mail: p.van.luijk@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed the dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late

HPV genotype distribution and anomalous association of HPV33 to cervical neoplastic lesions in San Luis Potosí, Mexico.

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DelaRosa-Martínez, Raúl; Sánchez-Garza, Mireya; López-Revilla, Rubén

2016-01-01

The association of human papillomavirus (HPV) types to neoplastic lesions increase as a function of their oncogenicity and the duration of the infection since lesion severity progresses from low-grade to high-grade and cancer. In an outbreak, the prevalence of the HPV type involved would increase and the proportion of the associated low-grade lesions would predominate over severe lesions. In this study, the prevalence of HPV types and their association to neoplastic lesions was determined in women subjected to colposcopy in San Luis Potosí, Mexico. DNA from high-risk (HR) and low-risk (LR) HPV types was identified by E6 nested multiplex PCR in cervical scrapes from 700 women with normal cytology, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial lesions (HSIL) or invasive cervical cancer (CC). Overall HPV-DNA prevalence was 67.7 %, that of HR-HPV was 63.1 %, and that of LR-HPV was 21.3 %. The highest prevalence (78.2 %) occurred in the 15-24 year group, whereas that of single infections was 52 % and that of multiple infections (i.e., by 2-6 HPV types) was 48 %. The most prevalent HR types were HPV33 (33.1 %), HPV16 (16.6 %), HPV18 and HPV51 (6.7 % each). HR-HPV prevalence was 29.6 % in normal cytology, 26.7 % in ASCUS, 63.3 % in LSIL, 68.2 % in HSIL, and 90.5 % in CC. Three prevalence trends for HR-HPV types were found in neoplastic lesions of increasing severity: increasing (LSIL  CC) for HPV33. Two-thirds of the women subjected to colposcopy from 2007 to 2010 in San Luis Potosí have HPV infections which predominate in the 15-24 years group. Around half of the infections are by one viral type and the rest by 2-6 types. HPV33 is the most prevalent type, followed by HPV16. Overall HR-HPV prevalence increases with the severity of neoplastic lesions. HPV33 prevalence is highest in LSIL and its U-shaped trend with progressing neoplastic lesions

Alcohol consumption and the neoplastic progression in Barrett's esophagus: a systematic review and meta-analysis.

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Zhifeng Lou

Full Text Available PURPOSE: In the developed countries, the incidence of esophageal adenocarcinoma (EAC is increasing over recent decades. The purpose of this meta-analysis was to arrive at quantitative conclusions about the contribution of alcohol intakes and the progression of Barrett's esophagus. METHODS: A comprehensive, systematic bibliographic search of medical literature published up to Oct 2013 was conducted to identify relevant studies. A meta-analysis was conducted for alcohol consumption on the Barrett's esophagus progression. RESULTS: A total of 882 cases in 6,867 individuals from 14 observational studies were indemnified in this meta-analysis. The result of this current meta-analysis, including 10 case-control and 4 cohort studies, indicated that alcohol consumption was not associated with the neoplastic progression in Barrett's esophagus (RR, 1.17; 95% CI, 0.93-1.48. When stratified by the study designs, no significant association was detected in either high vs low group or ever vs never group. CONCLUSIONS: Alcohol drinking is not associated with risk of neoplastic progression in Barrett's esophagus. Further well designed studies are needed in this area.

The FDA approved PI3K inhibitor GDC-0941 enhances in vitro the anti-neoplastic efficacy of Axitinib against c-myc-amplified high-risk medulloblastoma.

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Ehrhardt, Michael; Craveiro, Rogerio B; Velz, Julia; Olschewski, Martin; Casati, Anna; Schönberger, Stefan; Pietsch, Torsten; Dilloo, Dagmar

2018-04-01

Aberrant receptor kinase signalling and tumour neovascularization are hallmarks of medulloblastoma development and are both considered valuable therapeutic targets. In addition to VEGFR1/2, expression of PDGFR α/β in particular has been documented as characteristic of metastatic disease correlating with poor prognosis. Therefore, we have been suggested that the clinically approved multi-kinase angiogenesis inhibitor Axitinib, which specifically targets these kinases, might constitute a promising option for medulloblastoma treatment. Indeed, our results delineate anti-neoplastic activity of Axitinib in medulloblastoma cell lines modelling the most aggressive c-myc-amplified Non-WNT/Non-SHH and SHH-TP53-mutated tumours. Exposure of medulloblastoma cell lines to Axitinib results in marked inhibition of proliferation and profound induction of cell death. The differential efficacy of Axitinib is in line with target expression of medulloblastoma cells identifying VEGFR 1/2, PDGFR α/β and c-kit as potential markers for drug application. The high specificity of Axitinib and the consequential low impact on the haematopoietic and immune system render this drug ideal multi-modal treatment approaches. In this context, we demonstrate that the clinically available PI3K inhibitor GDC-0941 enhances the anti-neoplastic efficacy of Axitinib against c-myc-amplified medulloblastoma. Our findings provide a rational to further evaluate Axitinib alone and in combination with other therapeutic agents for the treatment of most aggressive medulloblastoma subtypes. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Total and regional body-composition changes in early postmenopausal women

DEFF Research Database (Denmark)

Wang, Q; Hassager, C; Ravn, Pernille

1994-01-01

Total and regional body composition were measured in 373 early postmenopausal women aged 49-60 y by dual-energy x-ray absorptiometry to evaluate whether the changes in body composition in the early postmenopausal years are related to menopause itself or merely to age. Both fat mass and fat...

Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC.

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Scarpa, Marco; Scarpa, Melania; Castagliuolo, Ignazio; Erroi, Francesca; Kotsafti, Andromachi; Basato, Silvia; Brun, Paola; D'Incà, Renata; Rugge, Massimo; Angriman, Imerio; Castoro, Carlo

2016-03-01

BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. The expression of Dnmts 1 and 3A was significantly increased in UC-related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance.

Motivation, Work Satisfaction, and Teacher Change among Early Childhood Teachers

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Wagner, Brigid Daly; French, Lucia

2010-01-01

This study tests the explanatory power of Deci and Ryan's (1985) self-determination theory as a framework for describing how interactions between early childhood teachers and the systems within which their work is embedded influence motivation for professional growth and change in teaching practice. Fifty-four early childhood teachers and teacher…

Reduced Pms2 expression in non-neoplastic flat mucosa from patients with colon cancer correlates with reduced apoptosis competence.

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Bernstein, Harris; Prasad, Anil; Holubec, Hana; Bernstein, Carol; Payne, Claire M; Ramsey, Lois; Dvorakova, Katerina; Wilson, Megan; Warneke, James A; Garewal, Harinder

2006-06-01

Pms2 protein is a component of the DNA mismatch repair complex responsible both for post-replication correction of DNA nucleotide mispairs and for early steps in apoptosis. Germline mutations in DNA mismatch repair genes give rise to hereditary non-polyposis colon cancer, which accounts for about 4% of colon cancers. However, little is known about the expression of mismatch repair proteins in relation to sporadic colon cancer, which accounts for the great majority of colon cancers. Multiple samples were taken from the non-neoplastic flat mucosa of colon resections from patients with no colonic neoplasia, a tubulovillous adenoma, or an adenocarcinoma. Expression of Pms2 was assessed using semiquantitative immunohistochemistry. Apoptosis was assessed in polychrome-stained epoxy sections using morphologic criteria. Samples from patients without colonic neoplasia had moderate to strong staining for Pms2 in cell nuclei at the base of crypts, while samples from 2 of the 3 colons with a tubulovillous adenoma, and from 6 of the 10 colons with adenocarcinomas, showed reduced Pms2 expression. Samples from patients with an adenocarcinoma that had reduced Pms2 expression also exhibited reduced apoptosis capability in nearby tissue samples, evidenced when this paired tissue was stressed ex vivo with bile acid. Reduced Pms2 expression in the colonic mucosa may be an early step in progression to colon cancer. This reduction may cause decreased mismatch repair, increased genetic instability, and/or reduced apoptotic capability. Immunohistochemical determination of reduced Pms2 expression, upon further testing, may prove to be a promising early biomarker of risk of progression to malignancy.

Radiotherapy-induced Early ECG Changes and Their Comparison with Echocardiography in Patients with Early-stage Breast Cancer.

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Tuohinen, Suvi Sirkku; Keski-Pukkila, Konsta; Skyttä, Tanja; Huhtala, Heini; Virtanen, Vesa; Kellokumpu-Lehtinen, Pirkko-Liisa; Raatikainen, Pekka; Nikus, Kjell

2018-04-01

Early electrocardiogram (ECG) changes after breast cancer radiotherapy (RT) have been reported, but their characteristics and associated factors are largely unknown. This study aimed to explore early RT-induced ECG changes and to compare them with echocardiography changes. Sixty eligible patients with chemotherapy-naïve left-sided and 20 with right-sided breast cancer were evaluated with echocardiography, blood samples and ECG before and after RT. RT-induced ECG changes in the anterior leads. T-Wave changes were most frequent. T-Wave decline was associated independently with patient age (β=-0.245, p=0.005), mean heart radiation dose (β=1.252, p=0.001) and global systolic strain rate change (β=7.943, p=0.002). T-Wave inversion was associated independently with mean heart radiation dose (β=0.143, pECG changes were prevalent and associated with functional and structural changes in echocardiography. ECG could be used for post-RT cardiac screening. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Developmental Changes in Sleep Oscillations during Early Childhood

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Eckehard Olbrich

2017-01-01

Full Text Available Although quantitative analysis of the sleep electroencephalogram (EEG has uncovered important aspects of brain activity during sleep in adolescents and adults, similar findings from preschool-age children remain scarce. This study utilized our time-frequency method to examine sleep oscillations as characteristic features of human sleep EEG. Data were collected from a longitudinal sample of young children (n=8; 3 males at ages 2, 3, and 5 years. Following sleep stage scoring, we detected and characterized oscillatory events across age and examined how their features corresponded to spectral changes in the sleep EEG. Results indicated a developmental decrease in the incidence of delta and theta oscillations. Spindle oscillations, however, were almost absent at 2 years but pronounced at 5 years. All oscillatory event changes were stronger during light sleep than slow-wave sleep. Large interindividual differences in sleep oscillations and their characteristics (e.g., “ultrafast” spindle-like oscillations, theta oscillation incidence/frequency also existed. Changes in delta and spindle oscillations across early childhood may indicate early maturation of the thalamocortical system. Our analytic approach holds promise for revealing novel types of sleep oscillatory events that are specific to periods of rapid normal development across the lifespan and during other times of aberrant changes in neurobehavioral function.

Impact of Major Pulmonary Resections on Right Ventricular Function: Early Postoperative Changes.

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Elrakhawy, Hany M; Alassal, Mohamed A; Shaalan, Ayman M; Awad, Ahmed A; Sayed, Sameh; Saffan, Mohammad M

2018-01-15

Right ventricular (RV) dysfunction after pulmonary resection in the early postoperative period is documented by reduced RV ejection fraction and increased RV end-diastolic volume index. Supraventricular arrhythmia, particularly atrial fibrillation, is common after pulmonary resection. RV assessment can be done by non-invasive methods and/or invasive approaches such as right cardiac catheterization. Incorporation of a rapid response thermistor to pulmonary artery catheter permits continuous measurements of cardiac output, right ventricular ejection fraction, and right ventricular end-diastolic volume. It can also be used for right atrial and right ventricular pacing, and for measuring right-sided pressures, including pulmonary capillary wedge pressure. This study included 178 patients who underwent major pulmonary resections, 36 who underwent pneumonectomy assigned as group (I) and 142 who underwent lobectomy assigned as group (II). The study was conducted at the cardiothoracic surgery department of Benha University hospital in Egypt; patients enrolled were operated on from February 2012 to February 2016. A rapid response thermistor pulmonary artery catheter was inserted via the right internal jugular vein. Preoperatively the following was recorded: central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac output, right ventricular ejection fraction and volumes. The same parameters were collected in fixed time intervals after 3 hours, 6 hours, 12 hours, 24 hours, and 48 hours postoperatively. For group (I): There were no statistically significant changes between the preoperative and postoperative records in the central venous pressure and mean arterial pressure; there were no statistically significant changes in the preoperative and 12, 24, and 48 hour postoperative records for cardiac index; 3 and 6 hours postoperative showed significant changes. There were statistically significant changes between the preoperative and

Extracellular matrix in tumours as a source of additional neoplastic lesions - a review

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Madej Janusz A.

2014-03-01

Full Text Available The review describes the role of cells of extracellular matrix (ECM as a source of neoplastic outgrowths additional to the original tumour. The cells undergo a spontaneous transformation or stimulation by the original tumour through intercellular signals, e.g. through Shh protein (sonic hedgehog. Additionally, cells of an inflammatory infiltrate, which frequently accompany malignant tumours and particularly carcinomas, may regulate tumour cell behaviour. This is either by restricting tumour proliferation or, inversely, by induction and stimulation of the proliferation of another tumour cell type, e.g. mesenchymal cells. The latter type of tumour may involve formation of histologically differentiated stromal tumours (GIST, which probably originate from interstitial cells of Cajal in the alimentary tract. Occasionally, e.g. in gastric carcinoma, proliferation involves lymphoid follicles and lymphocytes of GALT (gut-associated lymphoid tissue, which gives rise to lymphoma. The process is preceded by the earlier stage of intestinal metaplasia, or is induced by gastritis alone. This is an example of primary involvement of inflammatory infiltrate cells in neoplastic progression. Despite the numerous histogenetic classifications of tumours (zygotoma benignum et zygotoma malignum, or mesenchymomata maligna et mesenchymomata benigna, currently in oncological diagnosis the view prevails that the direction of tumour differentiation and its degree of histologic malignancy (grading are more important factors than the histogenesis of the tumour.

Cerebellar hemangioblastomas: A study of the immunoprofile of neoplastic stromal component

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Tasić Desanka

2004-01-01

Full Text Available Background. Central nervous system hemangioblastomas (HBs are uncommon highly vascularized tumors that are predominantly found in the cerebellum. They occur sporadically or in association with von Hippel-Lindau (VHL disease. HBs are of unknown histogenesis, and the origin of stromal cells is still a subject of debate. The aim of this study was to investigate the immunoprofile of neoplastic stromal component, and to determine whether the profile of the expression of immunomarkers used can contribute to the elucidation of the histogenesis of HBs. Methods. A series of eight cerebellar HBs were histochemically examined for the detection of mast cells and immunohistochemically for the expression of factor VIII-related antigen (FVIII-RAg, CD34, vimentin, factor XIIIa (FXIIIa, S-100 protein, glial fibrillary acidic protein (GFAP, neuron-specific enolase (NSE neurofilaments (NF, synaptophysin, chromogranin, and somatostatin. Results. Mast cells were present in all hemangioblastomas, and were particularly abundant in one tumor. Immunohistochemically, intense reactivity for vimentin and NSE in the stromal cells was constantly seen. Immunoreactivity with S-100 protein and FXIIIa was variable, but generally many HBs stromal cells were negative for these markers. However, stromal cells were uniformly negative for FVIII-RAg in all HBs investigated. They were negative for CD34 GFAP, NF, synaptophysin, chromogranin, as well as somatostatin. GFAP-positivity of the occasional stromal type cells, located only peripherally, was interpreted as "pseudopositivity". Conclusion. The immunoprofile of neoplastic stromal component in this study suggested a possible origin from undifferentiated multipotential mesenchymal cells. High expression of NSE (glycolytic and hypoxia-inducible enzyme in the HBs stromal cells might be related to the loss of the VHL protein function.

Changes in gene expression and cellular architecture in an ovarian cancer progression model.

Directory of Open Access Journals (Sweden)

Amy L Creekmore

Full Text Available BACKGROUND: Ovarian cancer is the fifth leading cause of cancer deaths among women. Early stage disease often remains undetected due the lack of symptoms and reliable biomarkers. The identification of early genetic changes could provide insights into novel signaling pathways that may be exploited for early detection and treatment. METHODOLOGY/PRINCIPAL FINDINGS: Mouse ovarian surface epithelial (MOSE cells were used to identify stage-dependent changes in gene expression levels and signal transduction pathways by mouse whole genome microarray analyses and gene ontology. These cells have undergone spontaneous transformation in cell culture and transitioned from non-tumorigenic to intermediate and aggressive, malignant phenotypes. Significantly changed genes were overrepresented in a number of pathways, most notably the cytoskeleton functional category. Concurrent with gene expression changes, the cytoskeletal architecture became progressively disorganized, resulting in aberrant expression or subcellular distribution of key cytoskeletal regulatory proteins (focal adhesion kinase, α-actinin, and vinculin. The cytoskeletal disorganization was accompanied by altered patterns of serine and tyrosine phosphorylation as well as changed expression and subcellular localization of integral signaling intermediates APC and PKCβII. CONCLUSIONS/SIGNIFICANCE: Our studies have identified genes that are aberrantly expressed during MOSE cell neoplastic progression. We show that early stage dysregulation of actin microfilaments is followed by progressive disorganization of microtubules and intermediate filaments at later stages. These stage-specific, step-wise changes provide further insights into the time and spatial sequence of events that lead to the fully transformed state since these changes are also observed in aggressive human ovarian cancer cell lines independent of their histological type. Moreover, our studies support a link between aberrant cytoskeleton

HLA‐G modulates the radiosensitivity of human neoplastic cells

International Nuclear Information System (INIS)

Michelin, Severino; Gallegos, Cristina; Baffa Trasci, Sofía; Dubner, Diana; Favier, B.; Carosella, E.D.

2011-01-01

Tumor cells show a very broad range of radiosensitivities. The differential radiosensitivity may depend on many factors, being the efficiency to recognize and/or repair the DNA lesion, and the cell cycle control mechanisms, the most important (Jeggo and Lavin, 2009; Kumala et al., 2003). Human leukocyte antigen‐G (HLA‐G) is a non‐classical HLA class I molecule involved in fetus protection form the maternal immune system, transplant tolerance, and viral and tumoral immune escape (Carosella et al., 2008). It has been determined that gamma radiation modulates HLA‐G expression at the plasma membrane of human melanoma cells. However, its role in tumoral radiosensitivity has not been demonstrated yet. The objective of this work was to determine if the radiosensitivity of human neoplastic cell lines cultured in vitro was mediated by HLA‐G expression. (authors)

Changing Policy, Changing Culture: Steps toward Early Learning Quality Improvement in Australia

Science.gov (United States)

Tayler, Collette

2011-01-01

Across Australia a combined government effort is underway to reform early childhood education and care (ECEC) provision. A National Law Bill passed in 2010 heralds a new legal, regulatory and accountability framework that embraces all types ECEC provision. As a result, service providers face rapid change to address a new orientation and higher…

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

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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%.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

12 CFR 1710.18 - Change of audit partner.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Change of audit partner. 1710.18 Section 1710.18 Banks and Banking OFFICE OF FEDERAL HOUSING ENTERPRISE OVERSIGHT, DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT SAFETY AND SOUNDNESS CORPORATE GOVERNANCE Corporate Practices and Procedures § 1710.18 Change of...

Early Self-Regulation, Early Self-Regulatory Change, and Their Longitudinal Relations to Adolescents' Academic, Health, and Mental Well-Being Outcomes.

Science.gov (United States)

Howard, Steven J; Williams, Kate E

2018-05-16

To evaluate the extent to which early self-regulation and early changes in self-regulation are associated with adolescents' academic, health, and mental well-being outcomes. Data were collected from 1 of the cohorts in a large dual-cohort cross-sequential study of Australian children. This cohort consisted of a nationally representative data set of 4983 Australian children assessed at 4 to 5 years of age, who were followed longitudinally to 14 to 15 years of age. Using regression within a path analysis framework, we first sought to investigate associations of early self-regulation (at 4-5 years and 6-7 years of age) with a broad range of academic, health, and mental well-being outcomes in adolescence (at 14-15 years). We next investigated the extent to which an early change in self-regulation (from 4 to 7 years of age) predicted these adolescents' outcomes. Early self-regulation predicted the full range of adolescents' outcomes considered such that a 1-SD increase in self-regulation problems was associated with a 1.5- to 2.5-times greater risk of more-negative outcomes. An early positive change in self-regulation was associated with a reduced risk of these negative outcomes for 11 of the 13 outcomes considered. These results suggest the potential of early self-regulation interventions, in particular, in influencing long-term academic, health, and well-being trajectories.

Evaluation of early changes of cartilage biomarkers following ...

African Journals Online (AJOL)

Evaluation of early changes of cartilage biomarkers following arthroscopic meniscectomy in young Egyptian adults. ... Asked Questions about PDFs. Alternatively, you can download the PDF file directly to your computer, from where it can be opened using a PDF reader. To download the PDF, click the Download link above.

The relationship between early changes in the HAMD-17 anxiety/somatization factor items and treatment outcome among depressed outpatients.

Science.gov (United States)

Farabaugh, Amy; Mischoulon, David; Fava, Maurizio; Wu, Shirley L; Mascarini, Alessandra; Tossani, Eliana; Alpert, Jonathan E

2005-03-01

The 17-item Hamilton Rating Scale for Depression (HAMD-17) Anxiety/Somatization factor includes six items: Anxiety (psychic), Anxiety (somatic), Somatic Symptoms (gastrointestinal), Somatic Symptoms (general), Hypochondriasis and Insight. This study examines the relationship between early changes (defined as those observed between baseline and week 1) in these HAMD-17 Anxiety/Somatization Factor items and treatment outcome among major depressive disorder (MDD) patients who participated in a study comparing the antidepressant efficacy of a standardized extract of hypericum with both placebo and fluoxetine. Following a 1-week, single-blind washout, patients with MDD diagnosed by the Structured Clinical Interview for DSM-IV (SCID) were randomized to 12 weeks of double-blind treatment with hypericum extract (900 mg/day), fluoxetine (20 mg/day) or placebo. The relationship between early changes in HAMD-17 anxiety/somatization factor items and treatment outcome was assessed separately for patients who received study treatment (hypericum or fluoxetine) versus placebo with a logistic regression method. One hundred and thirty-five patients (female 57%, mean age=37.3+/-11.0 years; mean baseline HAMD-17=19.7+/-3.2 years) were randomized to double-blind treatment and were included in the intent-to-treat (ITT) analyses. After adjusting for baseline HAMD-17 scores and for multiple comparisons with the Bonferroni correction, patients who remitted (HAMD-17 score Somatic Symptoms (General) scores than non-remitters. No other significant differences in early changes were noted for the remaining items between remitters versus non-remitters who received active treatment. For patients treated with placebo, early change was not predictive of remission for any of the items after Bonferroni correction. In conclusion, the presence of early improvement on the HAMD-17 item concerning fatigue and general somatic symptoms is significantly predictive of achieving remission at endpoint with

12/15-lipoxygenase is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice.

Directory of Open Access Journals (Sweden)

Dorothy D Sears

2009-09-01

Full Text Available Recent understanding that insulin resistance is an inflammatory condition necessitates searching for genes that regulate inflammation in insulin sensitive tissues. 12/15-lipoxygenase (12/15LO regulates the expression of proinflammatory cytokines and chemokines and is implicated in the early development of diet-induced atherosclerosis. Thus, we tested the hypothesis that 12/15LO is involved in the onset of high fat diet (HFD-induced insulin resistance.Cells over-expressing 12/15LO secreted two potent chemokines, MCP-1 and osteopontin, implicated in the development of insulin resistance. We assessed adipose tissue inflammation and whole body insulin resistance in wild type (WT and 12/15LO knockout (KO mice after 2-4 weeks on HFD. In adipose tissue from WT mice, HFD resulted in recruitment of CD11b(+, F4/80(+ macrophages and elevated protein levels of the inflammatory markers IL-1beta, IL-6, IL-10, IL-12, IFNgamma, Cxcl1 and TNFalpha. Remarkably, adipose tissue from HFD-fed 12/15LO KO mice was not infiltrated by macrophages and did not display any increase in the inflammatory markers compared to adipose tissue from normal chow-fed mice. WT mice developed severe whole body (hepatic and skeletal muscle insulin resistance after HFD, as measured by hyperinsulinemic euglycemic clamp. In contrast, 12/15LO KO mice exhibited no HFD-induced change in insulin-stimulated glucose disposal rate or hepatic glucose output during clamp studies. Insulin-stimulated Akt phosphorylation in muscle tissue from HFD-fed mice was significantly greater in 12/15LO KO mice than in WT mice.These results demonstrate that 12/15LO mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding.

Radiation induced early onset of neuro-cognitive changes

International Nuclear Information System (INIS)

Kumar, Mayank; Haridas, Seenu; Gupta, Mamta; Trivedi, Richa; Khushu, Subhash; Manda, Kailash

2012-01-01

Exposure to ionizing radiations has been shown to cause many detrimental effects. Primarily, the effects observed are broadly classified into hematopoietic syndrome at lower doses, gastrointestinal syndrome and central nervous system dysfunctions at high doses. However, recent studies reported that even at lower doses, there is an effect seen on the nervous system which can be observed as a decline in cognitive abilities. This has been reported in patients undergoing radiotherapy. The cognitive decline, especially in young patients affects development and has been shown to persist for years after the therapy. Thus, the aim of this study was to study and consolidate the early effects of radiation exposure which result in behavioural alterations and cognitive decline. Since, radiation-induced early changes in behavioural functions are poorly understood, therefore, the present investigation aimed to conceptualize and design behavioural test batteries in order to systematically study the immediate alterations in behavioural function following irradiation with a-rays. The behavioural alterations were correlated to changes in the different area of brain like hippocampus, thalamus, hypothalamus and corpus callosum using Diffusion Tensor Imaging (DTI) studies. Present study reported profound changes in behaviour, as well as alterations in the morphology of the brain tissue as perceived by DTI, 48 hours after exposure to ionizing radiations. These changes need to be correlated and clarified further to understand the mechanisms behind the cognitive dysfunctions occurring immediately after radiation exposure as well as to find out a therapeutic window to counteract or reduce the effect of long term cognitive changes following irradiation. (author)

Changes in nucleosome repeat lengths precede replication in the early replicating metallothionein II gene region of cells synchronized in early S phase

International Nuclear Information System (INIS)

D'Anna, J.A.; Tobey, R.A.

1989-01-01

Previous investigations showed that inhibition of DNA synthesis by hydroxyurea, aphidicolin, or 5-fluorodeoxyuridine produced large changes in the composition and nucleosome repeat lengths of bulk chromatin. There the authors report results of investigations to determine whether the changes in nucleosome repeat lengths might be localized in the initiated replicons, as postulated. In most experiments, Chinese hamster (line CHO) cells were synchronized in G1, or they were synchronized in early S phase by allowing G1 cells to enter S phase in medium containing 1 mM hydroxyurea or 5 μg mL -1 aphidicolin, a procedure believed to produce an accumulation of initiated replicons that arise from normally early replicating DNA. Measurements of nucleosome repeat lengths of bulk chromatin, the early replicating unexpressed metallothionein II (MTII) gene region, and a later replicating repeated sequence indicate that the changes in repeat lengths occur preferentially in the early replicating MTII gene region as G1 cells enter and become synchronized in early S phase. During that time, the MTII gene region is not replicated nor is there any evidence for induction of MTII messenger RNA. Thus, the results are consistent with the hypothesis that changes in chromatin structure occur preferentially in the early replicating (presumably initiated) replicons at initiation or that changes in chromatin structure can precede replication during inhibition of DNA synthesis. The shortened repeat lengths that precede MTII replication are, potentially, reversible, because they become elongated when the synchronized early S-phase cells are released to resume cell cycle progression

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

Science.gov (United States)

Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

2014-06-01

Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Is there an association with constitutional structural chromosomal abnormalities and hematologic neoplastic process? A short review.

Science.gov (United States)

Panani, Anna D

2009-04-01

The occasional observation of constitutional chromosomal abnormalities in patients with a malignant disease has led to a number of studies on their potential role in cancer development. Investigations of families with hereditary cancers and constitutional chromosomal abnormalities have been key observations leading to the molecular identification of specific genes implicated in tumorigenesis. Large studies have been reported on the incidence of constitutional chromosomal aberrations in patients with hematologic malignancies, but they could not confirm an increased risk for hematologic malignancy among carriers of structural chromosomal changes. However, it is of particular interest that constitutional structural aberrations with breakpoints similar to leukemia-associated specific breakpoints have been reported in patients with hematologic malignancies. Because of insufficient data, it remains still unclear if these aberrations represent random events or are associated with malignancy. There has been a substantial discussion about mechanisms involved in constitutional structural chromosomal changes in the literature. The documentation of more patients with constitutional structural chromosomal changes could be of major importance. Most importantly, the molecular investigation of chromosomal regions involved in rearrangements could give useful information on the genetic events underlying constitutional anomalies, contributing to isolation of genes important in the development of the neoplastic process. Regarding constitutional anomalies in patients with hematologic disorders, a survey of the cytogenetic data of our cytogenetics unit is herein also presented.

Mexican-Origin Youth's Cultural Orientations and Adjustment: Changes from Early to Late Adolescence

Science.gov (United States)

Updegraff, Kimberly A.; Umaña-Taylor, Adriana J.; McHale, Susan M.; Wheeler, Lorey A.; Perez-Brena, Norma

2013-01-01

Drawing from developmental and cultural adaptation perspectives and using a longitudinal design, this study examined: (a) mean-level changes in Mexican-origin adolescents’ cultural orientations and adjustment from early to late adolescence; and (b) bidirectional associations between cultural orientations and adjustment using a cross-lag panel model. Participants included 246 Mexican-origin, predominantly immigrant families that participated in home interviews and a series of nightly phone calls when target adolescents were 12 years and 18 years of age. Girls exhibited more pronounced declines in traditional gender role attitudes than did boys, and all youth declined in familism values, time spent with family, and involvement in Mexican culture. Bidirectional relations between cultural orientations and adjustment emerged, and some associations were moderated by adolescent nativity and gender. PMID:22966929

Infant pain-related negative affect at 12 months of age: early infant and caregiver predictors.

Science.gov (United States)

Din Osmun, Laila; Pillai Riddell, Rebecca; Flora, David B

2014-01-01

To examine the predictive relationships of early infant and caregiver variables on expressed pain-related negative affect duration at the 12-month immunization. Infants and their caregivers (N = 255) were followed during immunization appointments over the first year of life. Latent growth curve modeling in a structural equation modeling context was used. Higher levels of initial infant pain reactivity at 2 months and caregiver emotional availability averaged across 2, 4, and 6 months of age were related to larger decreases in the duration of infant negative affect over the first 6 months of life. Longer duration of infant negative affect at 2 months and poorer regulation of infant negative affect over the first 6 months of life predicted longer durations of infant negative affect by 12 months. Infant negative affect at 12 months was a function of both infant factors and the quality of caregiver interactive behaviors (emotional availability) in early infancy.

Neoplastic lesions of the temporomandibular joint (TMJ): diagnosis, differential diagnosis and intervention; Neoplasien des Temporomandibulargelenks (TMG). Diagnostik, Differenzialdiagnostik und Intervention

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Vogl, T.J.; Abolmaali, N.; Schedel, H.; Bergh, B. [Frankfurt Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Maeurer, J. [Radiologische Praxis am Prinzregentenplatz, Muenchen (Germany)

2001-09-01

Purpose. To evaluate the effectiveness of diagnostic and interventional radiological techniques for neoplastic lesions of the temporomandibular joint (TMJ). Material and methods. Modern diagnosis of the TMJ is based on the clinical use of conventional X-ray techniques, computed tomography (CT), magnetic resonance imaging (MRI) and interventional techniques like biopsies, vascular occlusion and ablation. Results. Conventional X-ray still forms the basic diagnostic procedure applied in open and closed mouth position. CT improves the diagnostic information and serves as the standard diagnostical instrument for cartaliganeous or osseous neoplastic lesions. MRI evaluates soft tissue infiltration in multiplanar techniques and high spatial resolution. Interventional vascular and ablative techniques improve the treatment of neoplastic disorders. (orig.) [German] Zielsetzung. Vorstellung der Wertigkeit bildgebender Verfahren fuer die diagnostische und interventionelle Radiologie des Temporomandibulargelenks (TMG). Material und Methodik. Die moderne Radiologie des TMG basiert auf dem Einsatz der konventionellen Roentgendiagnostik, der Computertomographie (CT) und der Magnetresonanztomographie (MRT), sowie interventioneller Verfahren wie der Biopsie, vaskulaerer Embolisationsverfahren und tumorablativer Verfahren. Ergebnisse. Als Basisdiagnostik dient die konventionelle Diagnostik in offener und geschlossener Mundposition der Erfassung von Funktionsstoerungen sowie ossaerer Destruktionen. Die CT erweitert das diagnostische Spektrum und verbessert die Differenzialdiagnostik fuer ossifizierende Prozesse. Der Einsatz der MRT erlaubt die Erfassung der Weichteilinfiltration sowie der Gelenkstrukturen. Vaskulaere interventionelle Verfahren dienen der praetherapeutischen Okklusion bzw. der palliativen Tumortherapie in Form der okklusiven Embolisation, der Chemoembolisation, oder auch der Tumorablation. (orig.)

Epstein-Barr virus load in transplant patients: Early detection of post-transplant lymphoproliferative disorders.

Science.gov (United States)

Fellner, María Dolores; Durand, Karina A; Solernou, Veronica; Bosaleh, Andrea; Balbarrey, Ziomara; García de Dávila, María T; Rodríguez, Marcelo; Irazu, Lucía; Alonio, Lidia V; Picconi, María A

2016-01-01

High levels of circulating EBV load are used as a marker of post-transplant lymphoproliferative disorders (PTLD). There is no consensus regarding the threshold level indicative of an increase in peripheral EBV DNA. The aim of the study was to clinically validate a developed EBV quantification assay for early PTLD detection. Transversal study: paired peripheral blood mononuclear cells (PBMC), plasma and oropharyngeal lymphoid tissue (OLT) from children undergoing a solid organ transplant with (n=58) and without (n=47) PTLD. Retrospective follow-up: 71 paired PBMC and plasma from recipients with (n=6) and without (n=6) PTLD history. EBV load was determined by real-time PCR. The diagnostic ability to detect all PTLD (categories 1-4), advanced PTLD (categories 2-4) or neoplastic PTLD (categories 3 and 4) was estimated by analyzing the test performance at different cut-off values or with a load variation greater than 0.5log units. The higher diagnostic performance for identifying all, advanced or neoplastic PTLD, was achieved with cut-off values of 1.08; 1.60 and 2.47log EBVgEq/10(5) PBMC or 2.30; 2.60; 4.47loggEq/10(5) OLT cells, respectively. EBV DNA detection in plasma showed high specificity but low (all categories) or high (advanced/neoplastic categories) sensitivity for PTLD identification. Diagnostic performance was greater when: (1) a load variation in PBMC or plasma was identified; (2) combining the measure of EBV load in PBMC and plasma. The best diagnostic ability to identify early PTLD stages was achieved by monitoring EBV load in PBMC and plasma simultaneously; an algorithm was proposed. Copyright © 2016 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State

KAUST Repository

Li, Yulin; Choi, Peter  S.; Casey, Stephanie  C.; Dill, David  L.; Felsher, Dean  W.

2014-01-01

The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

MYC through miR-17-92 Suppresses Specific Target Genes to Maintain Survival, Autonomous Proliferation, and a Neoplastic State

KAUST Repository

Li, Yulin

2014-08-01

The MYC oncogene regulates gene expression through multiple mechanisms, and its overexpression culminates in tumorigenesis. MYC inactivation reverses turmorigenesis through the loss of distinguishing features of cancer, including autonomous proliferation and survival. Here we report that MYC via miR-17-92 maintains a neoplastic state through the suppression of chromatin regulatory genes Sin3b, Hbp1, Suv420h1, and Btg1, as well as the apoptosis regulator Bim. The enforced expression of miR-17-92 prevents MYC suppression from inducing proliferative arrest, senescence, and apoptosis and abrogates sustained tumor regression. Knockdown of the five miR-17-92 target genes blocks senescence and apoptosis while it modestly delays proliferative arrest, thus partially recapitulating miR-17-92 function. We conclude that MYC, via miR-17-92, maintains a neoplastic state by suppressing specific target genes.

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

Science.gov (United States)

Lange, Marie; Heutte, Natacha; Noal, Sabine; Rigal, Olivier; Kurtz, Jean-Emmanuel; Lévy, Christelle; Allouache, Djelila; Rieux, Chantal; Lefel, Johan; Clarisse, Bénédicte; Leconte, Alexandra; Veyret, Corinne; Barthélémy, Philippe; Longato, Nadine; Tron, Laure; Castel, Hélène; Eustache, Francis; Giffard, Bénédicte; Joly, Florence

2018-06-22

Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. The sample consisted of women newly diagnosed with EBC ( n  = 118) and healthy controls ( n  = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( p  = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. The Oncologist IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced

From early stress to 12-month development in very preterm infants: Preliminary findings on epigenetic mechanisms and brain growth.

Science.gov (United States)

Fumagalli, Monica; Provenzi, Livio; De Carli, Pietro; Dessimone, Francesca; Sirgiovanni, Ida; Giorda, Roberto; Cinnante, Claudia; Squarcina, Letizia; Pozzoli, Uberto; Triulzi, Fabio; Brambilla, Paolo; Borgatti, Renato; Mosca, Fabio; Montirosso, Rosario

2018-01-01

Very preterm (VPT) infants admitted to Neonatal Intensive Care Unit (NICU) are at risk for altered brain growth and less-than-optimal socio-emotional development. Recent research suggests that early NICU-related stress contributes to socio-emotional impairments in VPT infants at 3 months through epigenetic regulation (i.e., DNA methylation) of the serotonin transporter gene (SLC6A4). In the present longitudinal study we assessed: (a) the effects of NICU-related stress and SLC6A4 methylation variations from birth to discharge on brain development at term equivalent age (TEA); (b) the association between brain volume at TEA and socio-emotional development (i.e., Personal-Social scale of Griffith Mental Development Scales, GMDS) at 12 months corrected age (CA). Twenty-four infants had complete data at 12-month-age. SLC6A4 methylation was measured at a specific CpG previously associated with NICU-related stress and socio-emotional stress. Findings confirmed that higher NICU-related stress associated with greater increase of SLC6A4 methylation at NICU discharge. Moreover, higher SLC6A4 discharge methylation was associated with reduced anterior temporal lobe (ATL) volume at TEA, which in turn was significantly associated with less-than-optimal GMDS Personal-Social scale score at 12 months CA. The reduced ATL volume at TEA mediated the pathway linking stress-related increase in SLC6A4 methylation at NICU discharge and socio-emotional development at 12 months CA. These findings suggest that early adversity-related epigenetic changes might contribute to the long-lasting programming of socio-emotional development in VPT infants through epigenetic regulation and structural modifications of the developing brain.

Development of a method for the accurate measurement of protein turnover in neoplastic cells grown in culture

International Nuclear Information System (INIS)

Silverman, J.A.

1984-01-01

In this study, it was shown that standard techniques for cell recovery and sample preparation for liquid scintillation counting led to underestimation of the radioactivity present in cell proteins by 20-40%. These techniques involved labeling with 3 He leucine or 14 C leucine, scraping the cells from the dish in a buffer, TCA precipitation of the cell proteins, solubilization in NaOH and counting in a liquid scintillation counter. Hydrolysis of the proteins with HCl or Pronase significantly increased the recovery of the labeled proteins. Also, solubilization in situ with NaOH or hydrolysis in situ with Pronase recovered 5-10% additional labeled proteins. The techniques developed here allow the accurate measurement of radioactivity in cell proteins. In addition, these techniques were used to study protein turnover in rat hepatoma cells grown in culture. These cells regulated their growth rate through changes in the protein synthesis rate as opposed to changes in the protein degradation rate. These data support the hypothesis that neoplastic cells, unlike normal cells, do not regulate proteolysis in growth control; normal cells under similar conditions have been shown to activate lysosomal proteolysis as they reach confluence. The physiologic implications of this observation are discussed

Limited scleroderma and early detection of visceral changes

International Nuclear Information System (INIS)

Kalyuzhnaya, L.D.; Potsibina, V.V.; Stychinskaya, L.P.; Turik, N.V.

1989-01-01

The state of liver, kidneys, osteoarticular apparatus at the early stages of development of limited scleroderma and with the exclusion of visceral changes on the basis of clinical-laboratory studies is investigated. 11 patients with scleroderma in the age of 7-18 years were examined. Osteoscintigraphy with 99m TC-phosphone and dynamic scintigraphy of kidneys without additional introduction of RF, and hepatocholecyctoscintigraphy with 99m tc-HIPA of the patients were realized. The conclusion is made that radionuclide investigation methods permit to reveal various visceral changes, which are not recognizable by clinical methods

Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults.

Science.gov (United States)

Pfeifer, M; Verhovec, R; Zizek, B; Prezelj, J; Poredos, P; Clayton, R N

1999-02-01

Hypopituitary patients have increased mortality from vascular disease, and in these patients, early markers of atherosclerosis [increased carotid artery intima-media thickness (IMT) and reduced distensibility] are more prevalent. As GH replacement can reverse some risk factors of atherosclerosis, the present study examined the effect of GH treatment on morphological and functional changes in the carotid and brachial arteries of GH-deficient (GHD) adults. Eleven GHD hypopituitary men (24-49 yr old) were treated with recombinant human GH (0.018 U/kg BW x day) for 18 months. IMT of the common carotid artery (CCA) and the carotid bifurcation (CB), and flow-mediated endothelium-dependent dilation (EDD) of the brachial artery were measured by B mode ultrasound before and at 3, 6, 12, and 18 months of treatment, and values were compared with those in 12 age-matched control men. Serum concentrations of lipids, lipoprotein(a), insulin-like growth factor I (IGF-I), and IGF-binding protein-3 (IGFBP-3) were also measured. In GHD men before treatment the IMTs of the CCA [mean(SD), 0.67(0.05) mm] and CB [0.75(0.04) mm] were significantly greater (P < 0.001) than those in control men [0.52(0.07) and 0.65(0.07) mm, respectively]. GH treatment normalized the IMT of the CCA by 6 months [0.53(0.04) mm] and that of the CB by 3 months [0.68(0.05) mm]. The IMT of the carotid artery (CCA and CB) was negatively correlated with serum IGF-I (r = -0.53; P < 0.0001). There was a significant improvement in flow-mediated EDD of the brachial artery at 3 months, which was sustained at 6 and 18 months of GH treatment (P < 0.05). GH treatment increased high density lipoprotein cholesterol at 3 and 6 months, but did not reduce total or low density lipoprotein cholesterol and was without effect on lipoprotein(a). There was no correlation between plasma lipids and changes in IMT or EDD of the arteries examined. In conclusion, GH treatment of hypopituitary GHD men reverses early morphological and

Network contact changes in early and later postseparation years

NARCIS (Netherlands)

Terhell, E.L.; Broese Van Groenou, M.I.; van Tilburg, T.G.

2007-01-01

This study explains changes in contact frequency in relationships of the preseparation personal network in the early and later years after partners separate. The explanation includes general and separation-related characteristics of the network relationship and the individual. Personal interviews

Early versus delayed invasive strategy for intermediate- and high-risk acute coronary syndromes managed without P2Y12 receptor inhibitor pretreatment: Design and rationale of the EARLY randomized trial.

Science.gov (United States)

Lemesle, Gilles; Laine, Marc; Pankert, Mathieu; Puymirat, Etienne; Cuisset, Thomas; Boueri, Ziad; Maillard, Luc; Armero, Sébastien; Cayla, Guillaume; Bali, Laurent; Motreff, Pascal; Peyre, Jean-Pascal; Paganelli, Franck; Kerbaul, François; Roch, Antoine; Michelet, Pierre; Baumstarck, Karine; Bonello, Laurent

2018-01-01

According to recent literature, pretreatment with a P2Y 12 ADP receptor antagonist before coronary angiography appears no longer suitable in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) due to an unfavorable risk-benefit ratio. Optimal delay of the invasive strategy in this specific context is unknown. We hypothesize that without P2Y 12 ADP receptor antagonist pretreatment, a very early invasive strategy may be beneficial. The EARLY trial (Early or Delayed Revascularization for Intermediate- and High-Risk Non-ST-Segment Elevation Acute Coronary Syndromes?) is a prospective, multicenter, randomized, controlled, open-label, 2-parallel-group study that plans to enroll 740 patients. Patients are eligible if the diagnosis of intermediate- or high-risk NSTE-ACS is made and an invasive strategy intended. Patients are randomized in a 1:1 ratio. In the control group, a delayed strategy is adopted, with the coronary angiography taking place between 12 and 72 hours after randomization. In the experimental group, a very early invasive strategy is performed within 2 hours. A loading dose of a P2Y 12 ADP receptor antagonist is given at the time of intervention in both groups. Recruitment began in September 2016 (n = 558 patients as of October 2017). The primary endpoint is the composite of cardiovascular death and recurrent ischemic events at 1 month. The EARLY trial aims to demonstrate the superiority of a very early invasive strategy compared with a delayed strategy in intermediate- and high-risk NSTE-ACS patients managed without P2Y 12 ADP receptor antagonist pretreatment. © 2018 Wiley Periodicals, Inc.

IMAGING OF INTRACRANIAL SPACE OCCUPYING LESIONS- A PROSPECTIVE STUDY IN A TERTIARY CARE CENTRE- GGH, KAKINADA, A.P.

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Radha Rani Kaki

2017-02-01

Full Text Available BACKGROUND The high morbidity and mortality associated with ICSOLs necessitates their early diagnosis so as to plan the required intervention. An analysis of 50 cases of Intracranial Space Occupying Lesions (ICSOL including neoplastic and non-neoplastic masses diagnosed and treated at GGH, Kakinada, over a period of one year is presented. CT scan and MRI were used for the diagnosis. MATERIALS AND METHODS In this prospective cohort study, 50 patients with ICSOL were studied predominantly by MRI and also by CT and MRS (wherever necessary. Imaging findings were evaluated, tabulated and correlated with histopathological findings and also clinical findings (wherever available. The findings were statistically analysed. RESULTS Most patients were in age range of 50-60 years. Male:female ratio was 2:3. Most common presenting symptom was headache associated with vomiting. Predominantly, solitary lesions were present in 47 patients (94% and multiple lesions in three patients (6%. 39 cases were supratentorial, 10 cases were infratentorial and one lesion was both supra and infratentorial in location. 40 patients were having neoplastic lesions (80% and 10 had non-neoplastic lesions (20%. In our study, meningiomas were the most common neoplastic lesion while among non-neoplastic lesions, arachnoid cysts were the most common. Of the neoplastic cases, 12 cases (30% were malignant and 28 (70% cases were benign mass effect was the most common associated imaging finding. For neoplastic lesions, the imaging sensitivity was 92.5%, specificity was 70%, accuracy was 88%, positive predictive value was 92.5% and negative predictive value was 70%. While for the non-neoplastic lesions, imaging sensitivity was 70%, specificity was 92.5% and accuracy was 88%. CONCLUSION Neuroimaging in combination with clinical findings can be helpful in early diagnosis and localisation of ICSOL and for proper management of the patient. The neurosurgeon, neuroradiologist and

40 CFR 600.507-12 - Running change data requirements.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Running change data requirements. 600... Passenger Automobiles)-Procedures for Determining Manufacturer's Average Fuel Economy § 600.507-12 Running... shall submit additional running change fuel economy and carbon-related exhaust emissions data as...

12 CFR 250.180 - Reports of changes in control of management.

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Reports of changes in control of management... FEDERAL RESERVE SYSTEM MISCELLANEOUS INTERPRETATIONS Interpretations § 250.180 Reports of changes in control of management. (a) Under a statute enacted September 12, 1964 (Pub. L. 88-593; 78 Stat. 940) all...

12 CFR 714.8 - Are the early payment provisions, or interest rate provisions, applicable in leasing arrangements?

Science.gov (United States)

2010-01-01

... provisions, or interest rate provisions, applicable in leasing arrangements? You are not subject to the early... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Are the early payment provisions, or interest rate provisions, applicable in leasing arrangements? 714.8 Section 714.8 Banks and Banking NATIONAL...

A study on early microstructural changes in the rabbit gallbladder induced by shock waves

Energy Technology Data Exchange (ETDEWEB)

Oh, Eun Oak [Hong-Sung Koryo Hospital, Hongsung (Korea, Republic of); Shim, Hyung Jin; Kim, Kun Sang; Ryo, Dae Sik; Choi, Yun Sun; Song, In Sup; Kim, Young Koo [College of Medicine, Chung Ang University, Seoul (Korea, Republic of)

1994-05-15

In order to evaluate microstructural changes after shock wave exposure, gross, light microscopic and transmission electron microscopic findings were analyzed with rabbit gallbladders. A preliminary study(2 rabbits) was performed to determine the dosage intensity of shock waves needed to inflict damage, using a EDAP LT 01 piezoelectric extracorporeal shock wave lothotriptor. The Gallbladders of three different groups of rabbits were given shock waves of various intensity. A storage value of 100, 50, 25 at rate of 20/sec under 80% power were given to group I (4 rabbits), group II (4 rabbits), and group III (3 rabbits), respectively. The rabbits were sacrificed 6-12 hours later. The observed pathologic changes in the transmission electron microscopy were vaculization of cytoplasm and swelling of epithelial cells with dilatation and structural alteration of intracellular organelles, especially endoplasmic reticulum. Cell membrane rupture and necrosis were observed at the markedly affected area. The structural changes of intracellular organelles were minimally found at a storage value of 25. However, above pathologic changes with dilatation and structural alterations of endoplasmic reticulums were more profound at value of 100. Early histologic changes induced by shocked waves are dose dependent and findings of cellular damage caused by ESWL might be explained as above.

Microstructural Changes of the Human Brain from Early to Mid-Adulthood

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Lixia Tian

2017-08-01

Full Text Available Despite numerous studies on the microstructural changes of the human brain throughout life, we have indeed little direct knowledge about the changes from early to mid-adulthood. The aim of this study was to investigate the microstructural changes of the human brain from early to mid-adulthood. We performed two sets of analyses based on the diffusion tensor imaging (DTI data of 111 adults aged 18–55 years. Specifically, we first correlated age with skeletonized fractional anisotropy (FA, mean diffusivity (MD, axial diffusivity (AD and radial diffusivity (RD at global and regional level, and then estimated individuals’ ages based on each DTI metric using elastic net, a kind of multivariate pattern analysis (MVPA method that aims at selecting the model that achieves the best trade-off between goodness of fit and model complexity. We observed statistically significant negative age-vs-FA correlations and relatively less changes of MD. The negative age-vs-FA correlations were associated with negative age-vs-AD and positive age-vs-RD correlations. Regional negative age-vs-FA correlations were observed in the bilateral genu of the corpus callosum (CCg, the corticospinal tract (CST, the fornix and several other tracts, and these negative correlations may indicate the earlier changes of the fibers with aging. In brain age estimation, the chronological-vs-estimated-age correlations based on FA, MD, AD and RD were R = 0.62, 0.44, 0.63 and 0.69 (P = 0.002, 0.008, 0.002 and 0.002 based on 500 permutations, respectively, and these results indicate that even the microstructural changes from early to mid-adulthood alone are sufficiently specific to decode individuals’ ages. Overall, the current results not only demonstrated statistically significant FA decreases from early to mid-adulthood and clarified the driving factors of the FA decreases (RD increases and AD decreases, in contrast to increases of both measures in late-adulthood, but highlighted the

Microstructural Changes of the Human Brain from Early to Mid-Adulthood.

Science.gov (United States)

Tian, Lixia; Ma, Lin

2017-01-01

Despite numerous studies on the microstructural changes of the human brain throughout life, we have indeed little direct knowledge about the changes from early to mid-adulthood. The aim of this study was to investigate the microstructural changes of the human brain from early to mid-adulthood. We performed two sets of analyses based on the diffusion tensor imaging (DTI) data of 111 adults aged 18-55 years. Specifically, we first correlated age with skeletonized fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) at global and regional level, and then estimated individuals' ages based on each DTI metric using elastic net, a kind of multivariate pattern analysis (MVPA) method that aims at selecting the model that achieves the best trade-off between goodness of fit and model complexity. We observed statistically significant negative age-vs-FA correlations and relatively less changes of MD. The negative age-vs-FA correlations were associated with negative age-vs-AD and positive age-vs-RD correlations. Regional negative age-vs-FA correlations were observed in the bilateral genu of the corpus callosum (CCg), the corticospinal tract (CST), the fornix and several other tracts, and these negative correlations may indicate the earlier changes of the fibers with aging. In brain age estimation, the chronological-vs-estimated-age correlations based on FA, MD, AD and RD were R = 0.62, 0.44, 0.63 and 0.69 ( P = 0.002, 0.008, 0.002 and 0.002 based on 500 permutations), respectively, and these results indicate that even the microstructural changes from early to mid-adulthood alone are sufficiently specific to decode individuals' ages. Overall, the current results not only demonstrated statistically significant FA decreases from early to mid-adulthood and clarified the driving factors of the FA decreases (RD increases and AD decreases, in contrast to increases of both measures in late-adulthood), but highlighted the necessity of

Change in Physical Attraction in Early Romantic Relationships

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Victor Karandashev

2014-12-01

Full Text Available The goal of our research was to study the changes in physical attraction during the early stages of romantic relationships. The longitudinal study explored the personality characteristics of a partner and relationship events affecting physical attraction of early (within the first year romantic relationships. Participants completed an eight-week longitudinal rating of their attraction toward their romantic partner. Factor analysis revealed behavioral, cognitive, emotional, and physiological dimensions. The behavioral and emotional dimensions play the largest role in attraction among both genders, with cognitive dimension also affecting attraction in women. Personality characteristics of one’s partner are significant predictors of physical attraction for both men and women. However, events occurring in the relationship seem to be only reliable predictors for a women’s attraction.

Early Cretaceous climate change (Hauterivian - Early Aptian): Learning from the past to prevent modern reefs decline

Science.gov (United States)

Godet, Alexis; Bodin, Stéphane; Adatte, Thierry; Föllmi, Karl B.

2010-05-01

In the last decades, the anthropogenic increase pCO2atm has been considered as one of the main contributors for the decline of modern coral reefs, and nearly 60% of these marine ecosystems are presently threatened (Bryant et al., 1998). Interactions between anthropogenic change and reef growth can, however, not be reduced to a single factor, and it is essential to look at the Earth's history to understand and counterbalance. During the Early Cretaceous, enhanced pCO2atm may have been responsible, at least in part, for the demise of the carbonate platform along the northern margin of the Tethys through climatic feedback mechanisms. From the Hauterivian to the Early Aptian, increased rainfalls are documented from the clay-mineral association, by a change from a smectite-dominated (most of the Hauterivian), to a kaolinite-dominated assemblage (latest Hauterivian up to the early Late Barremian). This switch is dated to the Pseudothurmannia ohmi ammonozone in the Vocontian Trough of southeastern France (Angles section, Godet et al., 2008). It is immediately followed in time by major nutrient input, as is illustrated by the substantial increase in phosphorus accumulation rates (PAR), not only in this section, but also in the Ultrahelvetic area of Switzerland and in the Umbria-Marche basin of Italy (Bodin et al., 2006). On the other hand, the remainder of the Hauterivian is characterized by PAR mean values characteristic of mesotrophic conditions, whereas the Late Barremian witnesses the return to oligotrophic environments (lower PAR values). Synchronously, these perturbations are mirrored on the platform by changes in the type of carbonate ecosystems. Indeed, a stronger continental runoff, and a subsequent input in the oceanic domain of nutrients (e.g., phosphorus) and clastic material modified marine palaeoenvironmental conditions and triggered changes in ecosystems. A unique archive of the Early Cretaceous carbonate platform is preserved in the Helvetic Alps, where the

Maturity-associated variation in change of direction and dribbling speed in early pubertal years and 5-year developmental changes in young soccer players.

Science.gov (United States)

Valente-Dos-Santos, J; Coelho-E-Silva, M J; Vaz, V; Figueiredo, A J; Capranica, L; Sherar, L B; Elferink-Gemser, M T; Malina, R M

2014-06-01

The purpose of the current study was to assess the developmental changes in change of direction and dribbling speed in youth soccer players taking into account skeletal age (SA), maturity status, body size, estimated fat mass, aerobic endurance, lower limb explosive strength and annual volume of training. Eighty-three male soccer players aged 10-15 years (SA) at baseline were annually followed over 5 years, resulting in an average 4.4 observations per player. After testing for multicollinearity, multi-level regression modeling was used to examine the longitudinal developmental changes on change of direction and dribbling speed. Maturity-associated variability was significant in change of direction and also dribbling speed among young soccer players aged 12-14 years with better scores being performed by late maturers. Moreover, the predicted longitudinal scores for change of direction and dribbling speed improved with SA (Psoccer-specific skill, dibbling speed, was also explained by annual volume of training (Pperformances with and without the ball possession at early ages of participation in competitive soccer. The effects tend to persist across ages combined with longitudinal changes in body composition and functional fitness. In the particular case of the ball test, annual volume of training was also a longitudinal performance predictor.

Cranial thickness changes in early childhood

Science.gov (United States)

Gajawelli, Niharika; Deoni, Sean; Shi, Jie; Dirks, Holly; Linguraru, Marius George; Nelson, Marvin D.; Wang, Yalin; Lepore, Natasha

2017-11-01

The neurocranium changes rapidly in early childhood to accommodate the developing brain. However, developmental disorders may cause abnormal growth of the neurocranium, the most common one being craniosynostosis, affecting about 1 in 2000 children. It is important to understand how the brain and neurocranium develop together to understand the role of the neurocranium in neurodevelopmental outcomes. However, the neurocranium is not as well studied as the human brain in early childhood, due to a lack of imaging data. CT is typically employed to investigate the cranium, but, due to ionizing radiation, may only be used for clinical cases. However, the neurocranium is also visible on magnetic resonance imaging (MRI). Here, we used a large dataset of MRI images from healthy children in the age range of 1 to 2 years old and extracted the neurocranium. A conformal geometry based analysis pipeline is implemented to determine a set of statistical atlases of the neurocranium. A growth model of the neurocranium will help us understand cranial bone and suture development with respect to the brain, which will in turn inform better treatment strategies for neurocranial disorders.

Cool Science: K-12 Climate Change Art Displayed on Buses

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Chen, R. F.; Lustick, D. S.; Lohmeier, J.; Thompson, S. R.

2015-12-01

Cool science is an art contest where K12 students create placards (7" x 22") to educate the public about climate change. Students are prompted to create their artwork in response to questions such as: What is the evidence for climate change? How does climate change impact your local community? What can you do to reduce the impacts of climate change? In each of three years, 500-600 student entrees have been submitted from more than 12 school districts across Massachusetts. A panel of judges including scientists, artists, rapid transit representatives, and educators chooses elementary, middle, and high school winners. Winners (6), runners-up (6), and honorable mentions (12) and their families and teachers are invited to an annual Cool Science Award Ceremony to be recognized and view winning artwork. All winning artwork is posted on the Cool Science website. The winning artwork (2 per grade band) is converted into placards (11" x 28") and posters (2.5' x 12') that are placed on the inside (placards) and outside (posters) of buses. Posters are displayed for one month. So far, Cool Science was implemented in Lowell, MA where over 5000 public viewers see the posters daily on the sides of Lowell Rapid Transit Authority (LRTA) buses, making approximately 1,000,000 impressions per year. Cool Science acts to increase climate literacy in children as well as the public, and as such promotes intergenerational learning. Using art in conjunction with science learning about climate change appears to be effective at engaging not just traditionally high achieving science students, but also those interested in the creative arts. Hearing winners' stories about how they created their artwork and what this contest meant to them supports the idea that Cool Science attracts a wide diversity of students. Parents discuss climate change with their children. Multiple press releases announcing the winners further promotes the awareness of climate change throughout school districts and their

Early and phasic cortical metabolic changes in vestibular neuritis onset.

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Marco Alessandrini

Full Text Available Functional brain activation studies described the presence of separate cortical areas responsible for central processing of peripheral vestibular information and reported their activation and interactions with other sensory modalities and the changes of this network associated to strategic peripheral or central vestibular lesions. It is already known that cortical changes induced by acute unilateral vestibular failure (UVF are various and undergo variations over time, revealing different cortical involved areas at the onset and recovery from symptoms. The present study aimed at reporting the earliest change in cortical metabolic activity during a paradigmatic form of UVF such as vestibular neuritis (VN, that is, a purely peripheral lesion of the vestibular system, that offers the opportunity to study the cortical response to altered vestibular processing. This research reports [(18F]fluorodeoxyglucose positron emission tomography brain scan data concerning the early cortical metabolic activity associated to symptoms onset in a group of eight patients suffering from VN. VN patients' cortical metabolic activity during the first two days from symptoms onset was compared to that recorded one month later and to a control healthy group. Beside the known cortical response in the sensorimotor network associated to vestibular deafferentation, we show for the first time the involvement of Entorhinal (BAs 28, 34 and Temporal (BA 38 cortices in early phases of symptomatology onset. We interpret these findings as the cortical counterparts of the attempt to reorient oneself in space counteracting the vertigo symptom (Bas 28, 34 and of the emotional response to the new pathologic condition (BA 38 respectively. These interpretations were further supported by changes in patients' subjective ratings in balance, anxiety, and depersonalization/derealization scores when tested at illness onset and one month later. The present findings contribute in expanding

Neural changes underlying early stages of L2 vocabulary acquisition.

Science.gov (United States)

Pu, He; Holcomb, Phillip J; Midgley, Katherine J

2016-11-01

Research has shown neural changes following second language (L2) acquisition after weeks or months of instruction. But are such changes detectable even earlier than previously shown? The present study examines the electrophysiological changes underlying the earliest stages of second language vocabulary acquisition by recording event-related potentials (ERPs) within the first week of learning. Adult native English speakers with no previous Spanish experience completed less than four hours of Spanish vocabulary training, with pre- and post-training ERPs recorded to a backward translation task. Results indicate that beginning L2 learners show rapid neural changes following learning, manifested in changes to the N400 - an ERP component sensitive to lexicosemantic processing and degree of L2 proficiency. Specifically, learners in early stages of L2 acquisition show growth in N400 amplitude to L2 words following learning as well as a backward translation N400 priming effect that was absent pre-training. These results were shown within days of minimal L2 training, suggesting that the neural changes captured during adult second language acquisition are more rapid than previously shown. Such findings are consistent with models of early stages of bilingualism in adult learners of L2 ( e.g. Kroll and Stewart's RHM) and reinforce the use of ERP measures to assess L2 learning.

Climate Change Decouples Drought from Early Wine Grape Harvests in France

Science.gov (United States)

Cook, Benjamin I.; Wolkovich, Elizabeth M.

2016-01-01

Across the world, wine grape phenology has advanced in recent decades, in step with climate-change-induced trends in temperature - the main driver of fruit maturation - and drought. Fully understanding how climate change contributes to changes in harvest dates, however, requires analysing wine grape phenology and its relationship to climate over a longer-term context, including data predating anthropogenic interference in the climate system. Here, we investigate the climatic controls of wine grape harvest dates from 1600-2007 in France and Switzerland using historical harvest and climate data. Early harvests occur with warmer temperatures (minus 6 days per degree Centigrade) and are delayed by wet conditions (plus 0.07 days per millimeter; plus 1.68 days per PDSI (Palmer drought severity index)) during spring and summer. In recent decades (1981-2007), however, the relationship between harvest timing and drought has broken down. Historically, high summer temperatures in Western Europe, which would hasten fruit maturation, required drought conditions to generate extreme heat. The relationship between drought and temperature in this region, however, has weakened in recent decades and enhanced warming from anthropogenic greenhouse gases can generate the high temperatures needed for early harvests without drought. Our results suggest that climate change has fundamentally altered the climatic drivers of early wine grape harvests in France, with possible ramifications for viticulture management and wine quality.

Forests and Phenology: Designing the Early Warning System to Understand Forest Change

Science.gov (United States)

Pierce, T.; Phillips, M. B.; Hargrove, W. W.; Dobson, G.; Hicks, J.; Hutchins, M.; Lichtenstein, K.

2010-12-01

Vegetative phenology is the study of plant development and changes with the seasons, such as the greening-up and browning-down of forests, and how these events are influenced by variations in climate. A National Phenology Data Set, based on Moderate Resolution Imaging Spectroradiometer satellite images covering 2002 through 2009, is now available from work by NASA, the US Forest Service, and Oak Ridge National Laboratory. This new data set provides an easily interpretable product useful for detecting changes to the landscape due to long-term factors such as climate change, as well as finding areas affected by short-term forest threats such as insects or disease. The Early Warning System (EWS) is a toolset being developed by the US Forest Service and the University of North Carolina-Asheville to support distribution and use of the National Phenology Data Set. The Early Warning System will help research scientists, US Forest Service personnel, forest and natural resources managers, decision makers, and the public in the use of phenology data to better understand unexpected change within our nation’s forests. These changes could have multiple natural sources such as insects, disease, or storm damage, or may be due to human-induced events, like thinning, harvest, forest conversion to agriculture, or residential and commercial use. The primary goal of the Early Warning System is to provide a seamless integration between monitoring, detection, early warning and prediction of these forest disturbances as observed through phenological data. The system consists of PC and web-based components that are structured to support four user stages of increasing knowledge and data sophistication. Building Literacy: This stage of the Early Warning System educates potential users about the system, why the system should be used, and the fundamentals about the data the system uses. The channels for this education include a website, interactive tutorials, pamphlets, and other technology

Psychometric evaluation of the general health questionnaire-12 and Rosenberg self-esteem scale in Hungarian and Slovak early adolescents

NARCIS (Netherlands)

Sarkova, M.; Nagyova, I.; Katreniakova, Z.; Geckova, A.M.; Orosova, O.; Middel, B.; van Dijk, J.P.; van den Heuvel, W.

2006-01-01

The reliability and factor structure of the General Health Questionnaire-12 (GHQ-12) and the Rosenberg Self-Esteem scale (RSE) were evaluated in samples of Hungarian and Slovak early adolescents. The principal component analyses support the two-factor solution for GHQ-12 with subscales

Speeding through cell cycle roadblocks: Nuclear cyclin D1-dependent kinase and neoplastic transformation

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Diehl J Alan

2008-09-01

Full Text Available Abstract Mitogenic induction of cyclin D1, the allosteric regulator of CDK4/6, is a key regulatory event contributing to G1 phase progression. Following the G1/S transition, cyclin D1 activation is antagonized by GSK3β-dependent threonine-286 (Thr-286 phosphorylation, triggering nuclear export and subsequent cytoplasmic degradation mediated by the SCFFbx4-αBcrystallin E3 ubiquitin ligase. Although cyclin D1 overexpression occurs in numerous malignancies, overexpression of cyclin D1 alone is insufficient to drive transformation. In contrast, cyclin D1 mutants refractory to phosphorylation-dependent nuclear export and degradation are acutely transforming. This raises the question of whether overexpression of cyclin D1 is a significant contributor to tumorigenesis or an effect of neoplastic transformation. Significantly, recent work strongly supports a model wherein nuclear accumulation of cyclin D1-dependent kinase during S-phase is a critical event with regard to transformation. The identification of mutations within SCFFbx4-αBcrystallin ligase in primary tumors provides mechanistic insight into cyclin D1 accumulation in human cancer. Furthermore, analysis of mouse models expressing cyclin D1 mutants refractory to degradation indicate that nuclear cyclin D1/CDK4 kinase triggers DNA re-replication and genomic instability. Collectively, these new findings provide a mechanism whereby aberrations in post-translational regulation of cyclin D1 establish a cellular environment conducive to mutations that favor neoplastic growth.

3D quantitative analysis of early decomposition changes of the human face.

Science.gov (United States)

Caplova, Zuzana; Gibelli, Daniele Maria; Poppa, Pasquale; Cummaudo, Marco; Obertova, Zuzana; Sforza, Chiarella; Cattaneo, Cristina

2018-03-01

Decomposition of the human body and human face is influenced, among other things, by environmental conditions. The early decomposition changes that modify the appearance of the face may hamper the recognition and identification of the deceased. Quantitative assessment of those changes may provide important information for forensic identification. This report presents a pilot 3D quantitative approach of tracking early decomposition changes of a single cadaver in controlled environmental conditions by summarizing the change with weekly morphological descriptions. The root mean square (RMS) value was used to evaluate the changes of the face after death. The results showed a high correlation (r = 0.863) between the measured RMS and the time since death. RMS values of each scan are presented, as well as the average weekly RMS values. The quantification of decomposition changes could improve the accuracy of antemortem facial approximation and potentially could allow the direct comparisons of antemortem and postmortem 3D scans.

Temperature dependence of 1H NMR relaxation time, T2, for intact and neoplastic plant tissues

Science.gov (United States)

Lewa, Czesław J.; Lewa, Maria

Temperature dependences of the spin-spin proton relaxation time, T2, have been shown for normal and tumorous tissues collected from kalus culture Nicotiana tabacum and from the plant Kalanchoe daigremontiana. For neoplastic plant tissues, time T2 was increased compared to that for intact plants, a finding similar to that for animal and human tissues. The temperature dependences obtained were compared to analogous relations observed with animal tissues.

Correlation between standardized uptake value and apparent diffusion coefficient of neoplastic lesions evaluated with whole-body simultaneous hybrid PET/MRI.

Science.gov (United States)

Rakheja, Rajan; Chandarana, Hersh; DeMello, Linda; Jackson, Kimberly; Geppert, Christian; Faul, David; Glielmi, Christopher; Friedman, Kent P

2013-11-01

The purpose of this study was to assess the correlation between standardized uptake value (SUV) and apparent diffusion coefficient (ADC) of neoplastic lesions in the use of a simultaneous PET/MRI hybrid system. Twenty-four patients with known primary malignancies underwent FDG PET/CT. They then underwent whole-body PET/MRI. Diffusion-weighted imaging was performed with free breathing and a single-shot spin-echo echo-planar imaging sequence with b values of 0, 350, and 750 s/mm(2). Regions of interest were manually drawn along the contours of neoplastic lesions larger than 1 cm, which were clearly identified on PET and diffusion-weighted images. Maximum SUV (SUVmax) on PET/MRI and PET/CT images, mean SUV (SUVmean), minimum ADC (ADCmin), and mean ADC (ADCmean) were recorded on PET/MR images for each FDG-avid neoplastic soft-tissue lesion with a maximum of three lesions per patient. Pearson correlation coefficient was used to asses the following relations: SUVmax versus ADCmin on PET/MR and PET/CT images, SUVmean versus ADCmean, and ratio of SUVmax to mean liver SUV (SUV ratio) versus ADCmin. A subanalysis of patients with progressive disease versus partial treatment response was performed with the ratio of SUVmax to ADCmin for the most metabolically active lesion. Sixty-nine neoplastic lesions (52 nonosseous lesions, 17 bone metastatic lesions) were evaluated. The mean SUVmax from PET/MRI was 7.0 ± 6.0; SUVmean, 5.6 ± 4.6; mean ADCmin, 1.10 ± 0.58; and mean ADCmean, 1.48 ± 0.72. A significant inverse Pearson correlation coefficient was found between PET/MRI SUVmax and ADCmin (r = -0.21, p = 0.04), between SUVmean and ADCmean (r = -0.18, p = 0.07), and between SUV ratio and ADCmin (r = -0.27, p = 0.01). A similar inverse Pearson correlation coefficient was found between the PET/CT SUVmax and ADCmin. Twenty of 24 patients had previously undergone PET/CT; five patients had a partial treatment response, and six had progressive disease according to Response Evaluation

Transmembrane potential of GlyCl-expressing instructor cells induces a neoplastic-like conversion of melanocytes via a serotonergic pathway

Directory of Open Access Journals (Sweden)

Douglas Blackiston

2011-01-01

Understanding the mechanisms that coordinate stem cell behavior within the host is a high priority for developmental biology, regenerative medicine and oncology. Endogenous ion currents and voltage gradients function alongside biochemical cues during pattern formation and tumor suppression, but it is not known whether bioelectrical signals are involved in the control of stem cell progeny in vivo. We studied Xenopus laevis neural crest, an embryonic stem cell population that gives rise to many cell types, including melanocytes, and contributes to the morphogenesis of the face, heart and other complex structures. To investigate how depolarization of transmembrane potential of cells in the neural crest’s environment influences its function in vivo, we manipulated the activity of the native glycine receptor chloride channel (GlyCl. Molecular-genetic depolarization of a sparse, widely distributed set of GlyCl-expressing cells non-cell-autonomously induces a neoplastic-like phenotype in melanocytes: they overproliferate, acquire an arborized cell shape and migrate inappropriately, colonizing numerous tissues in a metalloprotease-dependent fashion. A similar effect was observed in human melanocytes in culture. Depolarization of GlyCl-expressing cells induces these drastic changes in melanocyte behavior via a serotonin-transporter-dependent increase of extracellular serotonin (5-HT. These data reveal GlyCl as a molecular marker of a sparse and heretofore unknown cell population with the ability to specifically instruct neural crest derivatives, suggest transmembrane potential as a tractable signaling modality by which somatic cells can control stem cell behavior at considerable distance, identify a new biophysical aspect of the environment that confers a neoplastic-like phenotype upon stem cell progeny, reveal a pre-neural role for serotonin and its transporter, and suggest a novel strategy for manipulating stem cell behavior.

EVALUATION OF EARLY ISCHEMIC CHANGES IN STROKE PATIENTS TREATED WITH THROMBOLYTIC THERAPY

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Kolevski Goran

2016-07-01

Full Text Available Introduction:The aim of this study is to evaluate early brain ischemic changes on CT scan in stroke patients in correlation with the clinical outcome, as well as to evaluate if there is prognostic and predictive features that can be used. Patients and methods: We examined 20 patients with acute ischemic stroke, from which 12 were male and 8 were female, at the age from 47 to 76 years. Results: The hyperdense medial artery (HMA sign was present in 10 (50% patients. Concerning the ASPECTS score, 5 patients (25% had normal score of 10 points, while 7 patients (35% had score of 7 points. 12 patients (60% had unfavorable outcome, while 8 patients (40% had favorable outcome. Our statistical analysis shows that age of more than 65 years, presence of 2 or more risk-factors, ASPECTS score of 7 and presence of HMA sign were all statistically significant predictors of unfavorable outcome in examined patients (p<0.05 each. The presence of the hyperdense medial artery sign was the most significant single predictor for unfavorable clinical outcome (p=0.0042, p<0.05. Conclusion:The presence of HMA sign is the most significant single predictor for unfavorable clinical outcome.

Age and Spatial Peculiarities of Non-neoplastic Diseases of the Skin and Subcutaneous Tissue in Kazakhstan, 2003-2015.

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Igissinov, Nurbek; Kulmirzayeva, Dariyana; Bilyalova, Zarina; Akpolatova, Gulnur; Mamyrbayeva, Marzya; Zhumagaliyeva, Galina

2017-11-01

Arrangement of effective management aimed at improving dermatological services and consistent care of patients with skin diseases depends on understanding the epidemiological situation. This retrospective study presents an epidemiological assessment of non-neoplastic skin and subcutaneous tissue diseases in Kazakhstan registered in 2003-2015. The yearly incidence rate of the diseases among the whole population was in average 3,341.8±121.1 per 100000 population. This represents 4835.0±156.1 for children, 5503.2±141.8 for adolescents and 2646.6±106.7 for adults per 100000 inhabitants. Space and time incidence rate was evaluated according to the administrative division. The overall trend decreased to 3.5% in children to 2.8% in adolescents to 1.9%, and in adults to 3.9%. Considerable variation in rates was seen across the country, with highest rates in East Kazakhstan, Mangystau and Aktobe regions, the lowest - in Atyrau and South-Kazakhstan regions. Non-neoplastic diseases of skin and subcutaneous tissue continue to be an urgent public health problem, especially among children in many regions of Kazakhstan.

Sensitivity to radiation of human normal, hyperthyroid, and neoplastic thyroid epithelial cells in primary culture

International Nuclear Information System (INIS)

Miller, R.C.; Hiraoka, Toshio; Kopecky, K.J.; Nakamura, Nori; Jones, M.P.; Ito, Toshio; Clifton, K.H.

1986-09-01

Samples of thyroid tissue removed surgically from 63 patients were cultured in vitro and X-irradiated to investigate the radiosensitivities of various types of thyroid epithelial cells. A total of 76 samples were obtained, including neoplastic cells from patients with papillary carcinoma (PC) or follicular adenoma (FA), cells from hyperthyroidism (HY) patients, and normal cells from the surgical margins of PC and FA patients. Culturing of the cells was performed in a manner which has been shown to yield a predominance of epithelial cells. Results of colony formation assays indicated that cells from HY and FA patients were the least radiosensitive: when adjusted to the overall geometric mean plating efficiency of 5.5 %, the average mean lethal dose D 0 was 97.6 cGy for HY cells, and 96.7 cGy and 94.3 cGy, respectively, for neoplastic and normal cells from FA patients. Cells from PC patients were more radiosensitive, normal cells having an adjusted average D 0 of 85.0 cGy and PC cells a significantly (p = .001) lower average D 0 of 74.4 cGy. After allowing for this variation by cell type, in vitro radiosensitivity was not significantly related to age at surgery (p = .82) or sex (p = .10). These results suggest that malignant thyroid cells may be especially radiosensitive. (author)

Does early change predict long-term (6 months) improvements in subjects who receive manual therapy for low back pain?

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Cook, Chad; Petersen, Shannon; Donaldson, Megan; Wilhelm, Mark; Learman, Ken

2017-09-01

Early change is commonly assessed for manual therapy interventions and has been used to determine treatment appropriateness. However, current studies have only explored the relationship of between or within-session changes and short-/medium-term outcomes. The goal of this study was to determine whether pain changes after two weeks of pragmatic manual therapy could predict those participants with chronic low back pain who demonstrate continued improvements at 6-month follow-up. This study was a retrospective observational design. Univariate logistic regression analyses were performed using a 33% and a 50% pain change to predict improvement. Those who experienced a ≥33% pain reduction by 2 weeks had 6.98 (95% CI = 1.29, 37.53) times higher odds of 50% improvement on the GRoC and 4.74 (95% CI = 1.31, 17.17) times higher odds of 50% improvement on the ODI (at 6 months). Subjects who reported a ≥50% pain reduction at 2 weeks had 5.98 (95% CI = 1.56, 22.88) times higher odds of a 50% improvement in the GRoC and 3.99 (95% CI = 1.23, 12.88) times higher odds of a 50% improvement in the ODI (at 6 months). Future studies may investigate whether a change in plan of care is beneficial for patients who are not showing early improvement predictive of a good long-term outcome.

Effects of Training and Feedback on Accuracy of Predicting Rectosigmoid Neoplastic Lesions and Selection of Surveillance Intervals by Endoscopists Performing Optical Diagnosis of Diminutive Polyps.

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Vleugels, Jasper L A; Dijkgraaf, Marcel G W; Hazewinkel, Yark; Wanders, Linda K; Fockens, Paul; Dekker, Evelien

2018-05-01

Real-time differentiation of diminutive polyps (1-5 mm) during endoscopy could replace histopathology analysis. According to guidelines, implementation of optical diagnosis into routine practice would require it to identify rectosigmoid neoplastic lesions with a negative predictive value (NPV) of more than 90%, using histologic findings as a reference, and agreement with histology-based surveillance intervals for more than 90% of cases. We performed a prospective study with 39 endoscopists accredited to perform colonoscopies on participants with positive results from fecal immunochemical tests in the Bowel Cancer Screening Program at 13 centers in the Netherlands. Endoscopists were trained in optical diagnosis using a validated module (Workgroup serrAted polypS and Polyposis). After meeting predefined performance thresholds in the training program, the endoscopists started a 1-year program (continuation phase) in which they performed narrow band imaging analyses during colonoscopies of participants in the screening program and predicted histological findings with confidence levels. The endoscopists were randomly assigned to groups that received feedback or no feedback on the accuracy of their predictions. Primary outcome measures were endoscopists' abilities to identify rectosigmoid neoplastic lesions (using histology as a reference) with NPVs of 90% or more, and selecting surveillance intervals that agreed with those determined by histology for at least 90% of cases. Of 39 endoscopists initially trained, 27 (69%) completed the training program. During the continuation phase, these 27 endoscopists performed 3144 colonoscopies in which 4504 diminutive polyps were removed. The endoscopists identified neoplastic lesions with a pooled NPV of 90.8% (95% confidence interval 88.6-92.6); their proposed surveillance intervals agreed with those determined by histologic analysis for 95.4% of cases (95% confidence interval 94.0-96.6). Findings did not differ between the group

Sea-level change and demography during the last glacial termination and early Holocene across the Australian continent

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Williams, Alan N.; Ulm, Sean; Sapienza, Tom; Lewis, Stephen; Turney, Chris S. M.

2018-02-01

Future changes in sea-level are projected to have significant environmental and social impacts, but we have limited understanding of comparable rates of change in the past. Using comprehensive palaeoenvironmental and archaeological datasets, we report the first quantitative model of the timing, spatial extent and pace of sea-level change in the Sahul region between 35-8 ka, and explore its effects on hunter-gatherer populations. Results show that the continental landmass (excluding New Guinea) increased to 9.80 million km2 during the Last Glacial Maximum (LGM), before a reduction of 2.12 million km2 (or ∼21.6%) to the early Holocene (8 ka). Almost 90% of this inundation occurs during and immediately following Meltwater Pulse (MWP) 1a between 14.6 and 8 ka. The location of coastlines changed on average by 139 km between the LGM and early Holocene, with some areas >300 km, and at a rate of up to 23.7 m per year (∼0.6 km land lost every 25-year generation). Spatially, inundation was highly variable, with greatest impacts across the northern half of Australia, while large parts of the east, south and west coastal margins were relatively unaffected. Hunter-gatherer populations remained low throughout (hypothesis that late Pleistocene coastal populations were low, with use of coastal resources embedded in broad-ranging foraging strategies, and which would have been severely disrupted in some regions and at some time periods by sea-level change outpacing tolerances of mangals and other near-shore ecological communities.

Detection of occult cancer with [18F]-FDG scintigraphy in case of limbic encephalitis, a rare neurologic para neoplastic syndrome

International Nuclear Information System (INIS)

Kerrou, K.; Aide, N.; Montravers, F.; Grahek, D.; Younsi-Pourtau, N.; Petegnief, Y.; Colombet-Lamau, C.; Beco, V. de; Talbot, J.N.

2003-01-01

Limbic encephalitis is a rare neurologic para-neoplastic syndrome due to the production of anti-neuronal antibodies induced by the presence of a malignant tumour, most frequently a small cell lung cancer: The discovery and the resection of the malignant tissue allows a stabilisation of the neurological syndrome, a complete recovery being impossible when irreversible lesions are present. ( 18 F)-FDG PET may play a determinant role when the cancer is still occult after conventional imaging work-up. We report here on a such patient with evolving limbic encephalitis and no detectable cancer with conventional imaging modalities. ( 18 F)-FDG CDET successfully localised neoplastic small cell lung cancer tissue in the lung. The malignant tumour was not even detectable at surgery and was only confirmed at post surgical histology exactly exactly where it has been spotted by CDET. After surgery, the neurologic syndrome is now steady. (authors)

Active Early: one-year policy intervention to increase physical activity among early care and education programs in Wisconsin

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Tara L. LaRowe

2016-07-01

Full Text Available Abstract Background Early childcare and education (ECE is a prime setting for obesity prevention and the establishment of healthy behaviors. The objective of this quasi-experimental study was to examine the efficacy of the Active Early guide, which includes evidenced-based approaches, provider resources, and training, to improve physical activity opportunities through structured (i.e. teacher-led activity and environmental changes thereby increasing physical activity among children, ages 2–5 years, in the ECE setting. Methods Twenty ECE programs in Wisconsin, 7 family and 13 group, were included. An 80-page guide, Active Early, was developed by experts and statewide partners in the fields of ECE, public health, and physical activity and was revised by ECE providers prior to implementation. Over 12 months, ECE programs received on-site training and technical assistance to implement the strategies and resources provided in the Active Early guide. Main outcome measures included observed minutes of teacher-led physical activity, physical activity environment measured by the Environment and Policy Assessment and Observation (EPAO instrument, and child physical activity levels via accelerometry. All measures were collected at baseline, 6 months, and 12 months and were analyzed for changes over time. Results Observed teacher-led physical activity significantly increased from 30.9 ± 22.7 min at baseline to 82.3 ± 41.3 min at 12 months. The change in percent time children spent in sedentary activity decreased significantly after 12 months (−4.4 ± 14.2 % time, −29.2 ± 2.6 min, p < 0.02. Additionally, as teacher led-activity increased, percent time children were sedentary decreased (r = −0.37, p < 0.05 and percent time spent in light physical activity increased (r = 0.35, p < 0.05. Among all ECE programs, the physical activity environment improved significantly as indicated by multiple sub-scales of

Isolation of transformation-defective, replication-nondefective early region 1B mutants of adenovirus 12

International Nuclear Information System (INIS)

Fukui, Y.; Saito, I.; Shiroki, K.; Shimojo, H.

1984-01-01

The authors isolated three adenovirus 12 early region 1B mutants (in205B, in205C, and dl205) by ligation of the cleaved DNA-protein complex and transfection of human embryo kidney cells with the ligation products. These mutants could replicate efficiently in human embryo kidney or KB cells but showed markedly reduced transforming capacities both in vitro and in vivo. In cells infected with the mutants, the early region 1B gene was transcribed efficiently. In cells infected with in205B, the products corresponding to the early region 1B-coded 19,000-molecular-weight polypeptide was detected by in vitro translation but not immunoprecipitated extract of labeled cells. In cells infected with in205C or dl205, the products corresponding to the same polypeptide were not detected by either in vitro translation or immunoprecipitation of labeled cell extracts. The results suggest that the 19,000-molecular-weight polypeptide encoded by early region 1B is required for cell transformation but not for viral propagation

Knowledge and beliefs concerning early childhood caries from mothers of children ages zero to 12 months.

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Azevedo, Marina Sousa; Romano, Ana Regina; Dos Santos, Iná da Silva; Cenci, Maximiliano Sergio

2014-01-01

This study's purpose was to assess mothers' knowledge and beliefs about early childhood caries (ECC) etiology and prevention. This cross-sectional study targeted mothers (N=277) of zero- to 12-month-olds visiting 12 public health care centers in Pelotas, Rio Grande do Sul, Brazil. Information on causes of and recommendations to prevent ECC, as well as socioeconomic and demographic variables, was collected. Chi-square, univariate, and multiple logistic regression analyses were performed (Pinfluence caries in their children. None reported the role of micro-organisms and lack of fluoride in the caries etiology. These findings highlight the importance of providing preventive orientation to the mothers regarding early childhood caries. Information on age of first dental visit should be emphasized, especially among mothers with more than one child and low-income families.

Developmental Changes in Sleep Spindle Characteristics and Sigma Power across Early Childhood

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Ian J. McClain

2016-01-01

Full Text Available Sleep spindles, a prominent feature of the non-rapid eye movement (NREM sleep electroencephalogram (EEG, are linked to cognitive abilities. Early childhood is a time of rapid cognitive and neurophysiological maturation; however, little is known about developmental changes in sleep spindles. In this study, we longitudinally examined trajectories of multiple sleep spindle characteristics (i.e., spindle duration, frequency, integrated spindle amplitude, and density and power in the sigma frequency range (10–16 Hz across ages 2, 3, and 5 years (n=8; 3 males. At each time point, nocturnal sleep EEG was recorded in-home after 13-h of prior wakefulness. Spindle duration, integrated spindle amplitude, and sigma power increased with age across all EEG derivations (C3A2, C4A1, O2A1, and O1A2; all ps < 0.05. We also found a developmental decrease in mean spindle frequency (p<0.05 but no change in spindle density with increasing age. Thus, sleep spindles increased in duration and amplitude but decreased in frequency across early childhood. Our data characterize early developmental changes in sleep spindles, which may advance understanding of thalamocortical brain connectivity and associated lifelong disease processes. These findings also provide unique insights into spindle ontogenesis in early childhood and may help identify electrophysiological features related to healthy and aberrant brain maturation.

Early diagnosis of autism spectrum disorder: stability and change in clinical diagnosis and symptom presentation.

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Guthrie, Whitney; Swineford, Lauren B; Nottke, Charly; Wetherby, Amy M

2013-05-01

Although a diagnosis of autism spectrum disorder (ASD) appears to be stable in children as young as age three, few studies have explored stability of a diagnosis in younger children. Predictive value of diagnostic tools for toddlers and patterns of symptom change are important considerations for clinicians making early diagnoses. Most findings come from high-risk samples, but reports on children screened in community settings are also needed. Stability of diagnosis and Autism Diagnostic Observation Schedule – Toddler Module (ADOS-T) classifications and scores was examined across two time points in a sample of 82 children identified through the FIRST WORDS Project.Children received two comprehensive diagnostic evaluations at average ages of 19.39 (SD = 2.12) and 36.89 (SD = 3.85) months. Stability was 100% when confirming and ruling out a diagnosis of ASD based on a comprehensive diagnostic evaluation that included clinic and home observations,although diagnosis was initially deferred for 17% of the sample. Receiver Operating Characteristic curves revealed excellent sensitivity and acceptable specificity for the ADOS-T compared to concurrent diagnosis. Logistic regressions indicated good predictive value of initial ADOS-T scores for follow-up diagnosis. Finally, both ASD and Non-ASD children demonstrated a decrease in Social Affect scores (i.e.,improvement), whereas children with ASD demonstrated an increase in Restricted and Repetitive Behavior scores (i.e., worsening), changes that were accounted for by nonverbal developmental level in mixed model analyses. Short-term stability was documented for children diagnosed at 19 months on average, although a minority of children initially showed unclear diagnostic presentations.Findings highlight utility of the ADOS-T in making early diagnoses and predicting follow-up diagnoses. Children with ASD demonstrated improvement in social communication behaviors and unfolding of repetitive behaviors, suggesting that certain

Time-course of exercise and its association with 12-month bone changes

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Vainionpää Aki

2009-11-01

Full Text Available Abstract Background Exercise has been shown to have positive effects on bone density and strength. However, knowledge of the time-course of exercise and bone changes is scarce due to lack of methods to quantify and qualify daily physical activity in long-term. The aim was to evaluate the association between exercise intensity at 3, 6 and 12 month intervals and 12-month changes in upper femur areal bone mineral density (aBMD and mid-femur geometry in healthy premenopausal women. Methods Physical activity was continuously assessed with a waist-worn accelerometer in 35 healthy women (35-40 years participating in progressive high-impact training. To describe exercise intensity, individual average daily numbers of impacts were calculated at five acceleration levels (range 0.3-9.2 g during time intervals of 0-3, 0-6, and 0-12 months. Proximal femur aBMD was measured with dual x-ray absorptiometry and mid-femur geometry was evaluated with quantitative computed tomography at the baseline and after 12 months. Physical activity data were correlated with yearly changes in bone density and geometry, and adjusted for confounding factors and impacts at later months of the trial using multivariate analysis. Results Femoral neck aBMD changes were significantly correlated with 6 and 12 months' impact activity at high intensity levels (> 3.9 g, r being up to 0.42. Trochanteric aBMD changes were associated even with first three months of exercise exceeding 1.1 g (r = 0.39-0.59, p r = 0.38-0.52, p Conclusion The number of high acceleration impacts during 6 months of training was positively associated with 12-month bone changes at the femoral neck, trochanter and mid-femur. These results can be utilized when designing feasible training programs to prevent bone loss in premenopausal women. Trial registration Clinical trials.gov NCT00697957

Determination of minimal clinically important change in early and advanced Parkinson's disease.

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Hauser, Robert A; Auinger, Peggy

2011-04-01

Two common primary efficacy outcome measures in Parkinson's disease (PD) are change in Unified Parkinson's Disease Rating Scale (UPDRS) scores in early PD and change in "off" time in patients with motor fluctuations. Defining the minimal clinically important change (MCIC) in these outcome measures is important to interpret the clinical relevance of changes observed in clinical trials and other situations. We analyzed data from 2 multicenter, placebo-controlled, randomized clinical trials of rasagiline; TEMPO studied 404 early PD subjects, and PRESTO studied 472 levodopa-treated subjects with motor fluctuations. An anchor-based approach using clinical global impression of improvement (CGI-I) was used to determine MCIC for UPDRS scores and daily "off" time. MCIC was defined as mean change in actively treated subjects rated minimally improved on CGI-I. Receiver operating characteristic (ROC) curves defined optimal cutoffs discriminating between changed and unchanged subjects. MCIC for improvement in total UPDRS score (parts I-III) in early PD was determined to be -3.5 points based on mean scores and -3.0 points based on ROC curves. In addition, we found an MCIC for reduction in "off" time of 1.0 hours as defined by mean reduction in "off" time in active treated subjects self-rated as minimally improved on CGI-I minus mean reduction in "off" time in placebo-treated subjects self-rated as unchanged (1.9-0.9 hours). We hypothesize that many methodological factors can influence determination of the MCIC, and a range of values is likely to emerge from multiple studies. Copyright © 2011 Movement Disorder Society.

Low dose CT in early lung cancer diagnosis: prevalence data

International Nuclear Information System (INIS)

Cardinale, Luciano; Cortese, Giancarlo; Ferraris, Fabrizio; Perotto, Fabio; Fava, Cesare; Borasio, Piero; Dogliotti, Luigi; Novello, Silvia; Scagliotti, Giorgio

2005-01-01

Purpose. Lung cancer has a high mortality rate and its prognosis largely depends on early detection. We report the prevalence data of the study on early detection of lung cancer with low-dose spiral CT underway at our hospital. Materials and methods. Since the beginning of 2001, 519 asymptomatic volunteers have undergone annual blood tests, sputum tests, urinalyses and low-dose spiral CT. The inclusion criteria were age (55 years old), a history of cigarette smoking and a negative history for previous neoplastic disease. The diagnostic workup varied depending on the size and CT features of the nodules detected. Results. At baseline, the CT scan detected nodules> 5 mm in 22% of subjects; the nodules were single in 42 and multiple in 71. In 53% of cases the findings were completely negative, while in 122 (23.4%) nodules with a diameter [it

Expression of the α2-macroglobulin receptor on human neoplastic fibroblastoid cells

International Nuclear Information System (INIS)

Grofova, M.; Matoska, J.; Bies, J.; Bizik, J.; Vaheri, A.

1995-01-01

The α 2 -macroglobulin membrane-associated receptor ( α 2 MR) has been previously detected on hepatocytes, fibroblast, macrophages, syncytiotrophoblasts and recently on human malignant blood cells of myelomonocytic leukemia. In cells growing in vitro from human germ cell tumors α 2 MR mRNA was detected by Northern blotting. Endocytosis of α 2 MR from culture medium was detected in these cells by indirect immunofluorescence. In cell extracts α 2 MR and its degradation products were detected by immunoblotting. The cells expressing α 2 MR and internalizing α 2 MR were identified as fibroblast both by their morphology and expression of vimentin intermediate filaments. The role and function of α 2 MR receptor in the analyzed neoplastic cells of teratomatous origin is discussed. (author)

Atypical B12 Deficiency with Nonresolving Paraesthesia

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S. Haider

2013-01-01

Full Text Available Vitamin B12 deficiency can present with various hematological, gastrointestinal and neurological manifestations. We report a case of elderly female who presented with neuropathy and vitamin B12 deficiency where the final work-up revealed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS. This case suggests that, although POEMS syndrome is a rare entity, it can present with vitamin-B12 deficiency and thus specific work up for early diagnosis of POEMS should be considered in patients with B12 deficiency unresponsive to therapy.

Immunoelectron microscopic localisation of keratin and luminal epithelial antigens in normal and neoplastic urothelium.

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Wilson, P D; Nathrath, W B; Trejdosiewicz, L K

1982-01-01

Immunoelectron microscope cytochemistry was carried out on 2% paraformaldehyde fixed, 50 mu sections of normal urothelium and bladder carcinoma cells in culture using antisera raised in rabbits to human 40-63 000 MW epidermal "broad spectrum" keratin and calf urothelial "luminal epithelial antigen" (aLEA) Both the unconjugated and indirect immunoperoxidase-DAB techniques were used before routine embedding. The localisation of both keratin and luminal epithelial antigen (LEA) was similar in normal and neoplastic cells and reaction product was associated not only with tonofilaments but also lining membrane vesicles and on fine filaments in the cytoplasmic ground substance.

Climate change implications and use of early warning systems for global dust storms

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Harriman, Lindsey M.

2014-01-01

With increased changes in land cover and global climate, early detection and warning of dust storms in conjunction with effective and widespread information broadcasts will be essential to the prevention and mitigation of future risks and impacts. Human activities, seasonal variations and long-term climatic patterns influence dust storms. More research is needed to analyse these factors of dust mobilisation to create more certainty for the fate of vulnerable populations and ecosystems in the future. Early warning and communication systems, when in place and effectively implemented, can offer some relief to these vulnerable areas. As an issue that affects many regions of the world, there is a profound need to understand the potential changes and ultimately create better early warning systems for dust storms.

Longitudinal Associations Between Microstructural Changes and Microperimetry in the Early Stages of Age-Related Macular Degeneration.

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Wu, Zhichao; Cunefare, David; Chiu, Elizabeth; Luu, Chi D; Ayton, Lauren N; Toth, Cynthia A; Farsiu, Sina; Guymer, Robyn H

2016-07-01

To determine whether longitudinal changes in mesopic visual function on microperimetry occurred independent of its associations with microstructural parameters on spectral-domain optical coherence tomography (SD-OCT) in the early stages of AMD. Forty-one AMD eyes underwent microperimetry testing and SD-OCT scans over a 12-month period at 6-month intervals. Microstructural parameters analyzed include the retinal pigment epithelium-drusen complex (RPEDC) layer thickness, number of hyperreflective foci (HF) and their inner retinal migration (represented by a weighted axial distribution score; AxD), and the number of atrophic areas. Microperimetric sensitivity was 0.29 dB (95% confidence interval [CI] = -0.38 to -0.20 dB, P < 0.001) and 0.13 dB (95% CI = -0.22 to -0.03 dB, P = 0.008) lower in each sector for every 10-μm higher RPEDC layer thickness and 1-HF present, but was not associated with the AxD score or the number of atrophic areas present (P ≤ 0.464). However, each 10-μm greater RPEDC layer thickness and 1-HF present was not independently associated with a further decline in sensitivity (-0.08 dB/year, 95% CI = -0.24 to 0.07 dB/year, P = 0.288 and 0.09 dB/year, 95% CI = -0.06 to 0.24 dB/year, P = 0.242, respectively) over time when accounting for the association between RPEDC layer thickness and number of HF with microperimetric sensitivity. Longitudinal changes in mesopic visual function measured on microperimetry paralleled changes in the microstructural changes over a 12-month time frame, without any changes occurring independent of the associations between structure and function alone.

Early changes in plasma glucagon and growth hormone response to oral glucose in experimental hyperthyroidism.

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Tosi, F; Moghetti, P; Castello, R; Negri, C; Bonora, E; Muggeo, M

1996-08-01

The mechanisms underlying deterioration of glucose tolerance associated with hyperthyroidism are not completely understood. Increases in glucagon and growth hormone (GH) secretion have been previously found in hyperthyroid subjects, and could play a crucial role in this phenomenon. However, studies have not yet established the time sequence of changes in plasma glucose on the one hand and glucagon and GH on the other. To assess the early effects of thyroid hormone excess on glucose tolerance and plasma concentrations of the main glucoregulatory hormones, 12 nondiabetic euthyroid subjects underwent an oral glucose tolerance test (OGTT) before and after triiodothyronine ([T3] 120 micrograms/d) was administered for 10 days. Plasma levels of glucose, insulin, glucagon, and GH were determined at fasting and after the glucose load. T3 administration caused a marked increase in serum T3 (8.8 +/- 0.6 v 2.0 +/- 0.1 nmol/L), with clinical and biochemical signs of thyrotoxicosis. During the treatment, plasma glucose significantly increased both at fasting and after the glucose load (basal, 5.3 +/- 0.1 v 4.9 +/- 0.2 mmol/L, P hormone excess rapidly impairs glucose tolerance. Altered secretion of GH is an early event in thyrotoxicosis accompanying the onset of hyperglycemia, whereas plasma glucagon is appropriately suppressed by the increased plasma glucose levels. Thus, GH but not glucagon may contribute to the early hyperglycemic effect of thyrotoxicosis.

HPV16 early gene E5 specifically reduces miRNA-196a in cervical cancer cells

OpenAIRE

Liu, Chanzhen; Lin, Jianfei; Li, Lianqin; Zhang, Yonggang; Chen, Weiling; Cao, Zeyi; Zuo, Huancong; Chen, Chunling; Kee, Kehkooi

2015-01-01

High-risk human papillomavirus (HPV) type 16, which is responsible for greater than 50% of cervical cancer cases, is the most prevalent and lethal HPV type. However, the molecular mechanisms of cervical carcinogenesis remain elusive, particularly the early steps of HPV infection that may transform normal cervical epithelium into a pre-neoplastic state. Here, we report that a group of microRNAs (microRNAs) were aberrantly decreased in HPV16-positive normal cervical tissues, and these groups of...

Does the Brief Observation of Social Communication Change Help Moving Forward in Measuring Change in Early Autism Intervention Studies?

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Pijl, Mirjam K. J.; Rommelse, Nanda N. J.; Hendriks, Monica; De Korte, Manon W. P.; Buitelaar, Jan K.; Oosterling, Iris J.

2018-01-01

The field of early autism research is in dire need of outcome measures that adequately reflect subtle changes in core autistic behaviors. This article compares the ability of a newly developed measure, the Brief Observation of Social Communication Change (BOSCC), and the Autism Diagnostic Observation Schedule (ADOS) to detect changes in core…

Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes.

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Xu, Ning; Chua, Angela K; Jiang, Hong; Liu, Ning-Ai; Goodarzi, Mark O

2014-08-01

Androgen excess is a central feature of polycystic ovary syndrome (PCOS), which affects 6% to 10% of young women. Mammals exposed to elevated androgens in utero develop PCOS-like phenotypes in adulthood, suggesting fetal origins of PCOS. We hypothesize that excess androgen exposure during early embryonic development may disturb the epigenome and disrupt metabolism in exposed and unexposed subsequent generations. Zebrafish were used to study the underlying mechanism of fetal origins. Embryos were exposed to androgens (testosterone and dihydrotestosterone) early at 26 to 56 hours post fertilization or late at 21 to 28 days post fertilization. Exposed zebrafish (F0) were grown to adults and crossed to generate unexposed offspring (F1). For both generations, global DNA methylation levels were examined in ovaries using a luminometric methylation assay, and fasting and postprandial blood glucose levels were measured. We found that early but not late androgen exposure induced changes in global methylation and glucose homeostasis in both generations. In general, F0 adult zebrafish exhibited altered global methylation levels in the ovary; F1 zebrafish had global hypomethylation. Fasting blood glucose levels were decreased in F0 but increased in F1; postprandial glucose levels were elevated in both F0 and F1. This androgenized zebrafish study suggests that transient excess androgen exposure during early development can result in transgenerational alterations in the ovarian epigenome and glucose homeostasis. Current data cannot establish a causal relationship between epigenetic changes and altered glucose homeostasis. Whether transgenerational epigenetic alteration induced by prenatal androgen exposure plays a role in the development of PCOS in humans deserves study.

Vitamin B-12 supplementation during pregnancy and early lactation increases maternal, breast milk, and infant measures of vitamin B-12 status.

Science.gov (United States)

Duggan, Christopher; Srinivasan, Krishnamachari; Thomas, Tinku; Samuel, Tinu; Rajendran, Ramya; Muthayya, Sumithra; Finkelstein, Julia L; Lukose, Ammu; Fawzi, Wafaie; Allen, Lindsay H; Bosch, Ronald J; Kurpad, Anura V

2014-05-01

Pregnant women in resource-poor areas are at risk of multiple micronutrient deficiencies, and indicators of low vitamin B-12 status have been associated with adverse pregnancy outcomes, including anemia, low birth weight, and intrauterine growth retardation. To evaluate whether daily oral vitamin B-12 supplementation during pregnancy increases maternal and infant measures of vitamin B-12 status, we performed a randomized, placebo-controlled clinical trial. Pregnant women vitamin B-12 (50 μg) or placebo through 6 wk postpartum. All women were administered iron and folic acid supplements throughout pregnancy. One hundred eighty-three women were randomly assigned to receive vitamin B-12 and 183 to receive placebo. Compared with placebo recipients, vitamin B-12-supplemented women had significantly higher plasma vitamin B-12 concentrations at both the second (median vitamin B-12 concentration: 216 vs. 111 pmol/L, P vitamin B-12 concentration was 136 pmol/L in vitamin B-12-supplemented women vs. 87 pmol/L in the placebo group (P vitamin B-12-supplemented women, the incidence of delivering an infant with intrauterine growth retardation was 33 of 131 (25%) vs. 43 of 125 (34%) in those administered placebo (P = 0.11). In a subset of infants tested at 6 wk of age, median plasma vitamin B-12 concentration was 199 pmol/L in those born to supplemented women vs. 139 pmol/L in the placebo group (P = 0.01). Infant plasma methylmalonic acid and homocysteine concentrations were significantly lower in the vitamin B-12 group as well. Oral supplementation of urban Indian women with vitamin B-12 throughout pregnancy and early lactation significantly increases vitamin B-12 status of mothers and infants. It is important to determine whether there are correlations between these findings and neurologic and metabolic functions. This trial was registered at clinicaltrials.gov as NCT00641862.

Changes in early-successional hardwood forest area in four bird conservation regions across four decades

Science.gov (United States)

Sonja N. Oswalt; Kathleen E. Franzreb; David A. Buehler

2012-01-01

Early successional hardwood forests constitute important breeding habitat for many migratory songbirds. Declines in populations of these species suggest changes in habitat availability either on the species’ wintering grounds or on their early successional breeding grounds. We used Forest Inventory and Analysis data from 11 states across four decades to examine changes...

Moderate beer consumption does not change early or mature atherosclerosis in mice

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Blanco-Vaca Francisco

2004-01-01

Full Text Available Abstract Background Although the consumption of wine in particular has been associated with a lower risk of atherothrombotic cardiovascular disease, systematic reviews differ as to the relative protective effect of beer, wine and spirits. Two previous studies showed that red wine reduces fatty streak formation (early atherosclerosis but not mature atherosclerosis in apolipoprotein (apo E-deficient (apoE-/- mice. Aim of the study To determine whether a moderate beer intake would affect early and mature atherosclerotic lesion formation using control C57BL/6 and apoE-/- mice, respectively, as models. Methods Control C57BL/6 and apoE-/- mice were randomized to receive either water, ethanol, mild beer, dark beer or ethanol-free beer. The level of beer was designed to approximate the alcohol intake currently believed to be beneficial in reducing human vascular risk. Control C57BL/6 mice were fed a Western diet for 24 weeks, and apoE-/- mice a chow diet for 12 weeks. At the end of the trial period, mice were euthanized and atherosclerotic lesions quantified. Plasma lipid concentrations were also measured. Results The amount of atherosclerosis and average number of lesions in the proximal aortic region did not differ among groups in control C57BL/6 mice (p = 0.32 and p = 0.29, respectively and apoE-/- mice (p = 0.19 and p = 0.59, respectively. No consistent differences were observed in plasma lipid and lipoprotein concentrations among water, ethanol and beer groups. Conclusions Moderate beer consumption does not change the development of early or mature atherosclerosis in mice. Our findings do not support the hypothesis of an anti-atherogenic effect of beer. Other potential protective actions of moderate beer consumption such as plaque stabilization, a reduction in plaque intrinsic thrombogenicity, or a reduction in the systemic propensity to thrombosis, remain to be studied.

Interobserver agreement for the spine instability neoplastic score varies according to the experience of the evaluator

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William Gemio Jacobsen Teixeira

2013-01-01

Full Text Available OBJECTIVES: To evaluate the interobserver agreement for the Neoplastic Spine Instability Score (SINS among spine surgeons with or without experience in vertebral metastasis treatment and physicians in other specialties. METHODS: Case descriptions were produced based on the medical records of 40 patients with vertebral metastases. The descriptions were then published online. Physicians were invited to evaluate the descriptions by answering questions according to the Neoplastic Spine Instability Score (SINS. The agreement among physicians was calculated using the kappa coefficient. RESULTS: Seventeen physicians agreed to participate: three highly experienced spine surgeons, seven less-experienced spine surgeons, three surgeons of other specialties, and four general practitioners (n = 17. The agreement for the final SINS score among all participants was fair, and it varied according to the SINS component. The agreement was substantial for the spine location only. The agreement was higher among experienced surgeons. The agreement was nearly perfect for spinal location among the spine surgeons who were highly experienced in vertebral metastases. CONCLUSIONS: This study demonstrates that the experience of the evaluator has an impact on SINS scale classification. The interobserver agreement was only fair among physicians who were not spine surgeons and among spine surgeons who were not experienced in the treatment of vertebral metastases, which may limit the use of the SINS scale for the screening of unstable lesions by less-experienced evaluators.

Activated Hepatic Stellate Cells Induce Tumor Progression of Neoplastic Hepatocytes in a TGF-β Dependent Fashion

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MIKULA, M.; PROELL, V.; FISCHER, A.N.M.; MIKULITS, W.

2010-01-01

The development of hepatocellular carcinomas from malignant hepatocytes is frequently associated with intra- and peritumoral accumulation of connective tissue arising from activated hepatic stellate cells. For both tumorigenesis and hepatic fibrogenesis, transforming growth factor (TGF)-β signaling executes key roles and therefore is considered as a hallmark of these pathological events. By employing cellular transplantation we show that the interaction of neoplastic MIM-R hepatocytes with the tumor microenvironment, containing either activated hepatic stellate cells (M1-4HSCs) or myofibroblasts derived thereof (M-HTs), induces progression in malignancy. Cotransplantation of MIM-R hepatocytes with M-HTs yielded strongest MIM-R generated tumor formation accompanied by nuclear localization of Smad2/3 as well as of β-catenin. Genetic interference with TGF-β signaling by gain of antagonistic Smad7 in MIM-R hepatocytes diminished epithelial dedifferentiation and tumor progression upon interaction with M1-4HSCs or M-HTs. Further analysis showed that tumors harboring disrupted Smad signaling are devoid of nuclear β-catenin accumulation, indicating a crosstalk between TGF-β and β-catenin signaling. Together, these data demonstrate that activated HSCs and myofibroblasts directly govern hepatocarcinogenesis in a TGF-β dependent fashion by inducing autocrine TGF-β signaling and nuclear β-catenin accumulation in neoplastic hepatocytes. These results indicate that intervention with TGF-β signaling is highly promising in liver cancer therapy. PMID:16883581

Comparison of the circadian variation in cell proliferation in normal and neoplastic colonic epithelial cells.

Science.gov (United States)

Kennedy, M F; Tutton, P J; Barkla, D H

1985-09-15

Circadian variations in cell proliferation in normal tissues have been recognised for many years but comparable phenomena in neoplastic tissues appear not to have been reported. Adenomas and carcinomas were induced in mouse colon by injection of dimethylhydrazine (DMH) and cell proliferation in these tumors was measured stathmokinetically. In normal intestine cell proliferation is fastest at night whereas in both adenomas and carcinomas it was found to be slower at night than in the middle of the day. Chemical sympathectomy was found to abolish the circadian variation in tumor cell proliferation.

Neoplastic transformation of hamster embryo cells irradiated in utero and assayed in vitro

International Nuclear Information System (INIS)

Borek, C.; Pain, C.; Mason, H.

1977-01-01

It is stated that induction of neoplastic transformation in vitro by x-rays and neutrons has been reported, and the authors had previously found that transformation by x-rays could be detected at doses as low as 1 R and the rate of transformation increased with dose, reaching a peak of 1% between 150 and 300 R. This frequency of neoplastic transformation in vitro is much higher than the frequency of radiation induced tumors observed after exposing animals to similar doses of radiation. Studies are here reported showing that malignant transformed cells can be obtained from embryos irradiated in utero and assayed in vitro, and that the frequency of transformation is at least tenfold lower than when the irradiations are performed in vitro, and thus closer to the incidence in animals. Hamster embryo cells were used for the studies. Questions that arise are as follows: does the host mediate in modulating transformation by radiation; is there a repair of transforming events before they can be expressed; and how significant is the state of cells during irradiation in determining the rate of transformation. It is known from in vitro studies that cell replication is required for fixation of the transformation. With the in vitro technique cells are seeded as single cells with ample opportunity to divide. In addition they are not in contact with one another, and constitute a mixture of cell types from many tissues. In utero the situation is quite different; the embryonic cells are irradiated as tissues where there is cell to cell contact in tissue-specific arrangements, and where the rate of cell replication varies with the tissue. It remains to be seen which of these factors, if any, is responsible for the lowered yield of transformed cells characteristic of in utero as opposed to in vitro irradiation. (U.K.)

In vitro study of the influence of alpha particles irradiation on the pre-neoplastic transformation of rat trachea epithelial cells

International Nuclear Information System (INIS)

Kugel, C.

2001-12-01

Intern contamination by actinide oxide inhalation is potentially one health hazard during the nuclear fuel fabrication process. The aerosol particles can induce pulmonary lesions, such as epithelial cancers in particular. Their toxicity is mainly due to radiotoxicity of α irradiation. The aim of this work was to contribute, by an in vitro model, to the study of the apparition of pre-neoplastic states on epithelial cells after high LET irradiation. Primary cultures of rat tracheal epithelial cells were used. Two rat strain cells, SD TR for Sprague Dawley rats and WF TR for Wistar Furth I Fischer F344 rats, were compared after exposure to a dose range from 0 to 5 Gy. Reproductive cell death, i.e. senescent death, seems to be the main lethal way induced by α and γ irradiations. The nuclear volume of WF TR cells is higher than that of SD TR ones, explaining the higher α radiation-induced lethality of these cells. These WF TR cells are also much sensitive to dose rate and α particles energy. In the same manner, pre-neoplastic transformation rate of the cells seems to depend on the physical parameters of irradiation. But, it mainly varies as a function of cell radiosensitivity, that means cell death. In fact, the transformation rate of sensitive WF TR cells is lower than that of SD TR ones. In term of transformation for SD TR cells, dose-effect relationship fits to a linear and infra linear function after α irradiation, whereas the curve fits to linear and quadratic function after γ irradiation. The Relative Biological Efficiency (RBE) of α particles for lethality and pre-neoplastic transformation were determined for several levels of dose. A constant value of about 3 was found for RBE of lethality whatever the α dose. By contrast, the RBE of transformation has a value of about 10 up to 0.5 Gy and gradually decreases at higher doses to reach a value of 1 at 5 Gy. Similar shapes of dose-effect relationship can be observed for malignant lung tumour induction after

Neoplastic transformation in vitro by low doses of ionizing radiation: Role of adaptive response and bystander effects

International Nuclear Information System (INIS)

Ko, M.; Lao, X.-Y.; Kapadia, R.; Elmore, E.; Redpath, J.L.

2006-01-01

The shape of the dose-response curve for cancer induction by low doses of ionizing radiation is of critical importance to the assessment of cancer risk at such doses. Epidemiologic analyses are limited by sensitivity to doses typically greater than 50-100 mGy for low LET radiation. Laboratory studies allow for the examination of lower doses using cancer-relevant endpoints. One such endpoint is neoplastic transformation in vitro. It is known that this endpoint is responsive to both adaptive response and bystander effects. The relative balance of these processes is likely to play an important role in determining the shape of the dose-response curve at low doses. A factor that may influence this balance is cell density at time of irradiation. The findings reported in this paper indicate that the transformation suppressive effect of low doses previously seen following irradiation of sub-confluent cultures, and attributed to an adaptive response, is reduced for irradiated confluent cultures. However, even under these conditions designed to optimize the role of bystander effects the data do not fit a linear no-threshold model and are still consistent with the notion of a threshold dose for neoplastic transformation in vitro by low LET radiation

The development of functional network organization in early childhood and early adolescence: A resting-state fNIRS study

OpenAIRE

Lin Cai; Qi Dong; Haijing Niu

2018-01-01

Early childhood (7–8 years old) and early adolescence (11–12 years old) constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS) imaging data to examine topological ...

Change in contrast enhancement of HCC on 1-month follow-up CT after local radiotherapy: An early predictor of final treatment response

International Nuclear Information System (INIS)

Kim, Eun Young; Choi, Dongil; Lim, Do Hoon; Lee, Won Jae; Yoo, Byung Chul; Paik, Seung Woon

2009-01-01

Background: The purpose of this study was to evaluate the change in contrast enhancement of HCC on 1-month follow-up CT after local radiotherapy (RT) as an early predictor of final treatment response. Materials: Fifty patients who underwent local RT for HCCs had both pre-RT and post-RT CT scans including 1-month follow-up CT. We assessed the final treatment response by using the change in maximal tumor size on 6-12-month follow-up CT scan after RT. We also evaluated the change in tumor enhancement between pre-RT and 1-month follow-up CT scans. Results: A final treatment response was achieved in 27 (54%) of 50 patients, who showed either a complete response (n = 11) or a partial response (n = 16). Compared with non-responsive patients (n = 23), responsive patients showed a significant decrease in tumor enhancement on 1-month follow-up CT after RT in both objective and subjective analyses (each P < 0.001). Conclusion: The change in contrast enhancement of HCC seen on the 1-month follow-up CT in patients after local RT may be used as an early predictor of final treatment response.

Global situational awareness and early warning of high-consequence climate change.

Energy Technology Data Exchange (ETDEWEB)

Backus, George A.; Carr, Martin J.; Boslough, Mark Bruce Elrick

2009-08-01

Global monitoring systems that have high spatial and temporal resolution, with long observational baselines, are needed to provide situational awareness of the Earth's climate system. Continuous monitoring is required for early warning of high-consequence climate change and to help anticipate and minimize the threat. Global climate has changed abruptly in the past and will almost certainly do so again, even in the absence of anthropogenic interference. It is possible that the Earth's climate could change dramatically and suddenly within a few years. An unexpected loss of climate stability would be equivalent to the failure of an engineered system on a grand scale, and would affect billions of people by causing agricultural, economic, and environmental collapses that would cascade throughout the world. The probability of such an abrupt change happening in the near future may be small, but it is nonzero. Because the consequences would be catastrophic, we argue that the problem should be treated with science-informed engineering conservatism, which focuses on various ways a system can fail and emphasizes inspection and early detection. Such an approach will require high-fidelity continuous global monitoring, informed by scientific modeling.

MR imaging and ultrasonography findings of early myositis ossificans: a case report

International Nuclear Information System (INIS)

Lee, Kyung Ryeol; Park, So Young; Jin, Wook; Won, Kyu Yeoun

2016-01-01

Myositis ossificans (MO) is a benign soft tissue lesion with non-neoplastic heterotopic bone formation. MO in the intermediate and mature stages can be easily diagnosed if characteristic imaging findings such as a peripheral zonal pattern of ossification with variable thickness is observed. However, it is difficult to correctly diagnose early MO because it can mimic malignancy clinically, radiologically, and histopathologically. We report a case of early pseudosarcomatous phase of non-traumatic MO with atypical imaging findings. A 59-year-old woman presented with pain followed by a mass in the left thigh within a week. MR imaging and ultrasonography showed an intramuscular lesion with preserved muscle fascicles in the vastus lateralis muscle. Intralesional ossification or calcification was not seen on ultrasonography. A diagnosis of myositis ossificans was made by ultrasonographically guided biopsy. (orig.)

MR imaging and ultrasonography findings of early myositis ossificans: a case report

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyung Ryeol [Jeju National University Hospital, Department of Radiology, Jeju-si, Jeju Special Self-Governing Province (Korea, Republic of); Park, So Young; Jin, Wook [Kyung Hee University Hospital at Gangdong, Department of Radiology, Seoul (Korea, Republic of); Won, Kyu Yeoun [Kyung Hee University Hospital at Gangdong, Department of Pathology, Seoul (Korea, Republic of)

2016-10-15

Myositis ossificans (MO) is a benign soft tissue lesion with non-neoplastic heterotopic bone formation. MO in the intermediate and mature stages can be easily diagnosed if characteristic imaging findings such as a peripheral zonal pattern of ossification with variable thickness is observed. However, it is difficult to correctly diagnose early MO because it can mimic malignancy clinically, radiologically, and histopathologically. We report a case of early pseudosarcomatous phase of non-traumatic MO with atypical imaging findings. A 59-year-old woman presented with pain followed by a mass in the left thigh within a week. MR imaging and ultrasonography showed an intramuscular lesion with preserved muscle fascicles in the vastus lateralis muscle. Intralesional ossification or calcification was not seen on ultrasonography. A diagnosis of myositis ossificans was made by ultrasonographically guided biopsy. (orig.)

Methylation changes associated with early maturation stages in the Atlantic salmon

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Pérez-Figueroa Andrés

2011-10-01

Full Text Available Abstract Background Early maturation in the Atlantic salmon is an interesting subject for numerous research lines. Prior to sea migration, parr can reach sexual maturation and successfully fertilize adult female eggs during the reproductive season. These individuals are known as precocious parr, mature parr or "sneakers". Reasons for early maturation are unknown and this transitory stage is usually considered to be a threshold trait. Here, we compare methylation patterns between mature and immature salmon parr from two different rivers in order to infer if such methylation differences may be related to their maturation condition. First we analyzed genetic differences between rivers by means of AFLPs. Then, we compared the DNA methylation differences between mature and immature parrs, using a Methylation-Sensitive Amplified Polymorphism (MSAP, which is a modification of the AFLPs method by making use of the differential sensitivity of a pair of restriction enzymes isoschizomeres to cytosine methylation. The tissues essayed included brain, liver and gonads. Results AFLPs statistical analysis showed that there was no significant differentiation between rivers or a significant differentiation between maturation states in each river. MSAP statistical analysis showed that among the three tissues sampled, the gonads had the highest number of significant single-locus variation among populations with 74 loci followed by brain with 70 and finally liver with only 12. Principal components analysis (PCA of the MSAP profiles revealed different profiles among different tissues (liver, brain and testis clearly separating maturation states in the testis tissue when compared to the liver. Conclusions Our results reveal that genetically-similar mature and immature salmon parr present high levels of DNA methylation variation in two of the three analyzed tissues. We hypothesize that early maturation may be mostly mediated by epigenetic processes rather than by

The impact of early symptom change and therapeutic alliance on treatment outcome in cognitive-behavioural therapy for eating disorders.

Science.gov (United States)

Turner, Hannah; Bryant-Waugh, Rachel; Marshall, Emily

2015-10-01

The present study explored the impact of early symptom change (cognitive and behavioural) and the early therapeutic alliance on treatment outcome in cognitive-behavioural therapy (CBT) for the eating disorders. Participants were 94 adults with diagnosed eating disorders who completed a course of CBT in an out-patient community eating disorders service in the UK. Patients completed a measure of eating disorder psychopathology at the start of treatment, following the 6th session and at the end of treatment. They also completed a measure of therapeutic alliance following the 6th session. Greater early reduction in dietary restraint and eating concerns, and smaller levels of change in shape concern, significantly predicted later reduction in global eating pathology. The early therapeutic alliance was strong across the three domains of tasks, goals and bond. Early symptom reduction was a stronger predictor of later reduction in eating pathology than early therapeutic alliance. The early therapeutic alliance did not mediate the relationship between early symptom reduction and later reduction in global eating pathology. Instead, greater early symptom reduction predicted a strong early therapeutic alliance. Early clinical change was the strongest predictor of treatment outcome and this also facilitated the development of a strong early alliance. Clinicians should be encouraged to deliver all aspects of evidence-based CBT, including behavioural change. The findings suggest that this will have a positive impact on both the early therapeutic alliance and later change in eating pathology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mountains as early warning indicators of climate change

Science.gov (United States)

Williams, M. W.

2015-12-01

The panoramic splendor and complexity of mountain environments have inspired and challenged humans for centuries. These areas have been variously perceived as physical structures to be conquered, as sites of spiritual inspiration, and as some of the last untamed natural places on Earth. In our time, the perception that "mountains are forever" may provide solace to those seeking stability in a rapidly changing world. However, changes in the hydrology and in the abundance and species composition of the native flora and fauna of mountain ecosystems are potential bellwethers of global change, because these systems have a propensity to amplify environmental changes within specific portions of this landscape. Mountain areas are thus sentinels of climate change. We are seeing effects today in case histories I present from the Himalaya's, Andes, Alps, and Rocky Mountains. Furthermore, these ecosystem changes are occurring in mountain areas before they occur in downstream ecosystems. Thus, mountains are early warning indicators of perturbations such as climate change. The sensitivity of mountain ecosystems begs for enhanced protection and worldwide protection. Our understanding of the processes that control mountain ecosystems—climate interactions, snowmelt runoff, biotic diversity, nutrient cycling—is much less developed compared to downstream ecosystems where human habitation and development has resulted in large investments in scientific knowledge to sustain health and agriculture. To address these deficiencies, I propose the formation of an international mountain research consortium.

Does the Brief Observation of Social Communication Change help moving forward in measuring change in early autism intervention studies?

NARCIS (Netherlands)

Pijl, M.K.J.; Rommelse, N.N.J.; Hendriks, M.; Korte, M.W.P. de; Buitelaar, J.K.; Oosterling, I.J.

2018-01-01

The field of early autism research is in dire need of outcome measures that adequately reflect subtle changes in core autistic behaviors. This article compares the ability of a newly developed measure, the Brief Observation of Social Communication Change (BOSCC), and the Autism Diagnostic

Externalizing behavior in early childhood and body mass index from age 2 to 12 years: longitudinal analyses of a prospective cohort study

Directory of Open Access Journals (Sweden)

Schoppe-Sullivan Sarah

2010-07-01

Full Text Available Abstract Background Some evidence suggests that obesity and behavior problems are related in children, but studies have been conflicting and have rarely included children under age 4. An association between behavior problems in early childhood and risk for obesity could suggest that a common set of factors contribute to both. Our research objectives were to determine the extent to which externalizing behavior in early childhood is related to body mass index (BMI in early childhood and through age 12, and to evaluate whether these associations differ by sex and race. Methods Data from the NICHD Study of Early Child Care and Youth Development were analyzed. Externalizing behaviors at 24 months were assessed by mothers using the Child Behavior Checklist. BMI was calculated from measured height and weight assessed 7 times between age 2 and 12 years. Linear mixed effects models were used to assess associations between 24 month externalizing behavior and BMI from 2 to 12 years, calculate predicted differences in BMI, and evaluate effect modification. Results Externalizing behavior at 24 months was associated with a higher BMI at 24 months and through age 12. Results from a linear mixed effects model, controlling for confounding variables and internalizing behavior, predicted a difference in BMI of approximately 3/4 of a unit at 24 months of age comparing children with high levels of externalizing behavior to children with low levels of externalizing behavior. There was some evidence of effect modification by race; among white children, the average BMI difference remained stable through age 12, but it doubled to 1.5 BMI units among children who were black or another race. Conclusions Our analyses suggest that externalizing behaviors in early childhood are associated with children's weight status early in childhood and throughout the elementary school years, though the magnitude of the effect is modest.

Diagnostic capabilities of the virtual bronchoscopy at advanced neoplastic process of esophagus with formation of tracheobronchial fistula: Description of a case

Directory of Open Access Journals (Sweden)

M. A. Mitev

2017-09-01

Full Text Available The relevance of the problem is related to the continued increase in the neoplastic processes, and at the same time also to the development and improvement of the endoscopic and CT equipment, and thus expanding the diagnostic capabilities. Purpose: The presented research examines the results of the study of a rare case of ruptured trachea as a result of cancer of the esophagus. Methods: Fiberoptic esophagoscopy (FOE and CT of the chest followed by virtual bronchoscopy on a patient with a ruptured trachea, a 63 year-old man, were performed. Result: Performing MDCT with virtual bronchoscopy, according to this study, is crucial as the sole and complex methodology for the described case in connection with the finding of the trachea-oesophageal fistula and evaluation of the mediastinum and the pulmonary parenchyma. Conclusion: The VB is a successful method equally effective compared to the FB, to diagnose of advanced neoplastic processes.

Comparison of radiosensitivities of human autologous normal and neoplastic thyroid epithelial cells

International Nuclear Information System (INIS)

Miller, R.C.; Kopecky, K.J.; Hiraoka, T.; Ezaki, H.; Clifton, K.H.

1986-01-01

Studies were conducted to examine differences between the radiosensitivities of normal and neoplastic epithelial cells of the human thyroid. Freshly excised thyroid tissues from the tumours of eight patients with papillary carcinoma (PC) and five with follicular adenoma (FA) were cultured in vitro separately from normal thyroid tissue obtained from the surgical margins of the same patients. Plating efficiency of unirradiated control tissue was lower, on average for tumour tissue compared with normal tissue. Radiosensitivity, measured by the 37% inactivation dose D 0 , was greater for carcinoma tissue than for normal tissue in seven out of eight PC cases. Adenomatous tissue was less radiosensitive than normal tissue in four out of five FA cases. This is the first report comparing the radiosensitivity of autologous normal and abnormal epithelial tissue from the human thyroid. (author)

Has growth mixture modeling improved our understanding of how early change predicts psychotherapy outcome?

Science.gov (United States)

Koffmann, Andrew

2017-03-02

Early change in psychotherapy predicts outcome. Seven studies have used growth mixture modeling [GMM; Muthén, B. (2001). Second-generation structural equation modeling with a combination of categorical and continuous latent variables: New opportunities for latent class-latent growth modeling. In L. M. Collins & A. G. Sawyers (Eds.), New methods for the analysis of change (pp. 291-322). Washington, DC: American Psychological Association] to identify patient classes based on early change but have yielded conflicting results. Here, we review the earlier studies and apply GMM to a new data set. In a university-based training clinic, 251 patients were administered the Outcome Questionnaire-45 [Lambert, M. J., Hansen, N. B., Umphress, V., Lunnen, K., Okiishi, J., Burlingame, G., … Reisinger, C. W. (1996). Administration and scoring manual for the Outcome Questionnaire (OQ 45.2). Wilmington, DE: American Professional Credentialing Services] at each psychotherapy session. We used GMM to identify class structure based on change in the first six sessions and examined trajectories as predictors of outcome. The sample was best described as a single class. There was no evidence of autoregressive trends in the data. We achieved better fit to the data by permitting latent variables some degree of kurtosis, rather than to assume multivariate normality. Treatment outcome was predicted by the amount of early improvement, regardless of initial level of distress. The presence of sudden early gains or losses did not further improve outcome prediction. Early improvement is an easily computed, powerful predictor of psychotherapy outcome. The use of GMM to investigate the relationship between change and outcome is technically complex and computationally intensive. To date, it has not been particularly informative.

Prehospital administration of P2Y12 inhibitors and early coronary reperfusion in primary PCI

DEFF Research Database (Denmark)

De Backer, Ole; Ratcovich, Hanna; Biasco, Luigi

2015-01-01

The newer oral P2Y12 inhibitors prasugrel and ticagrelor have been reported to be more potent and faster-acting antiplatelet agents than clopidogrel. This study aimed to investigate whether prehospital loading with prasugrel or ticagrelor improves early coronary reperfusion as compared to prehosp......The newer oral P2Y12 inhibitors prasugrel and ticagrelor have been reported to be more potent and faster-acting antiplatelet agents than clopidogrel. This study aimed to investigate whether prehospital loading with prasugrel or ticagrelor improves early coronary reperfusion as compared...... to prehospital loading with clopidogrel in a real-world ST-elevation myocardial infarction (STEMI) setting. Over a 70-month period, 3497 patients with on-going STEMI of less than 6 hours and without cardiac arrest or cardiogenic shock underwent primary percutaneous coronary intervention (PPCI) at our centre....... The primary endpoint of this study was the proportion of patients who did not meet the criteria for TIMI (Thrombolysis In Myocardial Infarction) flow grade 3 in the infarct-related artery at initial angiography before PPCI. Prehospital loading with prasugrel (n = 883) or ticagrelor (n = 491) did...

Sex differences in depression-like behavior after nerve injury are associated with differential changes in brain-derived neurotrophic factor levels in mice subjected to early life stress.

Science.gov (United States)

Nishinaka, Takashi; Kinoshita, Megumi; Nakamoto, Kazuo; Tokuyama, Shogo

2015-04-10

We recently demonstrated that exposure to early life stress exacerbates nerve injury-induced thermal and mechanical hypersensitivity in adult male and female mice. Accumulating evidence suggests that chronic pain causes emotional dysfunction, such as anxiety and depression. In the present study, we investigated the impact of early life stress on depression-like behavior after nerve injury in mice. In addition, we examined the expression of brain-derived neurotrophic factor (BDNF), which is known to be involved in the pathogenesis of depression. Early life stress was induced by maternal separation between 2 and 3 weeks of age combined with social isolation after weaning (MSSI). At 9 weeks of age, the sciatic nerve was partially ligated to elicit neuropathic pain. Depression-like behavior was evaluated using the forced swim test at 12 weeks of age. Tissue samples from different regions of the brain were collected at the end of maternal separation (3 weeks of age) or after the forced swim test (12 weeks of age). At 12 weeks of age, immobility time in the forced swim test was increased only in MSSI-stressed female mice with nerve injury. BDNF expression was increased in male, but not female, MSSI-stressed mice at 3 weeks of age. However, MSSI stress did not impact BDNF expression in male or female mice at 12 weeks of age. Our findings suggest that exposure to early life stress exacerbates emotional dysfunction induced by neuropathic pain in a sex-dependent manner. Changes in BDNF expression after early life stress may be associated with neuropathic pain-induced depression-like behavior in adulthood. Furthermore, sex differences in BDNF expression after exposure to early life stress may contribute to sex-specific susceptibility to neuropathic pain-induced emotional dysfunction. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Early warning signals of abrupt temperature change in different regions of China over the past 50 years

International Nuclear Information System (INIS)

Tong Ji-Long; Wu Hao; Hou Wei; He Wen-Ping; Zhou Jie

2014-01-01

In this paper, the early warning signals of abrupt temperature change in different regions of China are investigated. Seven regions are divided on the basis of different climate temperature patterns, obtained through the rotated empirical orthogonal function, and the signal-to-noise temperature ratios for each region are then calculated. Based on the concept of critical slowing down, the temperature data that contain noise in the different regions of China are preprocessed to study the early warning signals of abrupt climate change. First, the Mann–Kendall method is used to identify the instant of abrupt climate change in the temperature data. Second, autocorrelation coefficients that can identify critical slowing down are calculated. The results show that the critical slowing down phenomenon appeared in temperature data about 5–10 years before abrupt climate change occurred, which indicates that the critical slowing down phenomenon is a possible early warning signal for abrupt climate change, and that noise has less influence on the detection results of the early warning signals. Accordingly, this demonstrates that the model is reliable in identifying the early warning signals of abrupt climate change based on detecting the critical slowing down phenomenon, which provides an experimental basis for the actual application of the method. (geophysics, astronomy, and astrophysics)

Drought early warning and risk management in a changing environment

Science.gov (United States)

Pulwarty, R. S.

2011-12-01

Drought has long been recognized as falling into the category of incremental but long-term and cumulative environmental changes, also termed slow-onset or creeping events. These event types would include: air and water quality decline, desertification processes, deforestation and forest fragmentation, loss of biodiversity and habitats, and nitrogen overloading, among others. Climate scientists continue to struggle with recognizing the onset of drought and scientists and policy makers continue to debate the basis (i.e., criteria) for declaring an end to a drought. Risk-based management approaches to drought planning at the national and regional levels have been recommended repeatedly over the years but their prototyping, testing and operational implementation have been limited. This presentation will outline two avenues for disaster risk reduction in the context of drought (1) integrated early warning information systems, and (2) linking disaster risk reduction to climate change adaptation strategies. Adaptation involves not only using operational facilities and infrastructure to cope with the immediate problems but also leaving slack or reserve for coping with multiple stress problems that produce extreme impacts and surprise. Increasing the 'anticipatability' of an event, involves both monitoring of key indicators from appropriate baseline data, and observing early warning signs that assumptions in risk management plans are failing and critical transitions are occurring. Illustrative cases will be drawn from the IPCC Special Report on Managing the Risks of Extreme Events and Disasters (2011), the UN Global Assessment of Disaster Risk Reduction (2011) and implementation activities in which the author has been engaged. Most drought early warning systems have tended to focus on the development and use of physical system indicators and forecasts of trends and thresholds. We show that successful early warning systems that meet expectations of risk management also have

Dual-energy CT with iodine quantification in distinguishing between bland and neoplastic portal vein thrombosis in patients with hepatocellular carcinoma.

Science.gov (United States)

Ascenti, G; Sofia, C; Mazziotti, S; Silipigni, S; D'Angelo, T; Pergolizzi, S; Scribano, E

2016-09-01

To investigate the diagnostic accuracy of dual-energy multidetector computed tomography (MDCT) with iodine quantification compared to conventional enhancement measurements in distinguishing bland from neoplastic portal vein thrombosis in patients with hepatocellular carcinoma. Thirty-four patients (26 men, eight women; mean age, 62 years) with hepatocellular carcinoma and portal vein thrombosis underwent contrast-enhanced dual-energy MDCT during the late hepatic arterial phase for the assessment of portal thrombosis (bland, n=21; neoplastic, n=13). Datasets were analysed separately by two different readers. Interobserver correlation and variability were calculated and compared with the Bland-Altman method. Diagnostic accuracy of conventional enhancement measurements and iodine quantification was calculated by setting either histopathology (n=7) or a reference standard based on MDCT imaging criteria and thrombus evolutionary characteristics compared to a previous MDCT examination (n=27). For iodine quantification threshold determination receiver operating characteristic (ROC) curves were drawn. p-Values <0.05 were considered significant. For conventional enhancement measurements and iodine quantification interobserver correlation was 98% and 96%. Enhancement measurement resulted in a sensitivity of 92.3%, specificity of 85.7%, positive predictive value (PPV) of 80%, and negative predictive value (NPV) of 94.7%. An iodine concentration of 0.9 mg/ml optimised discrimination between neoplastic and bland thrombi (area under the ROC [AUC] 0.993) resulting in a sensitivity of 100%, specificity of 95.2%, PPV of 92.9%, and NPV of 100%. The overall diagnostic accuracy of iodine quantification (97%) was significantly better than conventional enhancement measurements (88.2%; p<0.001). Compared to conventional enhancement measurements, iodine quantification improves the characterisation of portal vein thrombi during the late hepatic arterial phase in patients with

Age-Related DNA Methylation Changes and Neoplastic Transformation of the Human Prostate

Science.gov (United States)

2011-07-01

Toyota M, Ho C, Ahuja N, et al. Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification...hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received 12/23/2009; revised 05/07/2010; accepted 05...Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Gonzalez S, Tarafa G, Sidransky D, Meltzer SJ, Baylin SB, Herman JG (2000

Evaluation of early changes of cartilage biomarkers following arthroscopic meniscectomy in young Egyptian adults

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Hamdy Khamis Koryem

2015-09-01

Conclusion: Cartilage volume loss by MRI combined with changes in cartilage matrix turnover detected by molecular biomarkers may reflect the initial changes associated with cartilage degeneration that account for early OA.

EFFECTS OF RUMEN PROTECTED METHIONINE AND VITAMIN B12 ON RBC PARAMETERS OF DAIRY COWS IN EARLY LACTATION

Directory of Open Access Journals (Sweden)

Morteza Safarkhanlou

2016-12-01

Full Text Available To study the effects of rumen-protected methionine and vitamin B12 as well as their interactions on the parameters of red blood cells of dairy cows in early lactation, 16 Holstein cows in early lactation in experiment with randomized complete block design with the 2×2 factorial arrangement used for 42 days. In this experiment, there were four treatments, which in each treatment is placed two cows primi-parous and two cows multi-parous. Treatments included: 1 The group receiving the basal diet, 2 The group receiving the basal diet with vitamin B12 injections, 3 The group receiving the basal diet with rumen-protected methionine, 4 The group receiving the basal diet with vitamin B12 injections and rumen-protected methionine. The results showed that in the use of vitamin B12 and rumen-protected methionine, there is no significant difference between the experimental groups in the number of red blood cells, hemoglobin levels and blood hematocrit. Mean corpuscular (cell volume and mean corpuscular (cell hemoglobin did increase with vitamin B12 supplementation. In a general conclusion, it seems that increasing MCV and MCH may result in improvement in oxygenation and in turn lead to improvement on dry matter intake and milk production.

Environmental change during the Late Berriasian - Early Valanginian: a prelude to the late Early Valanginian carbon-isotope event?

Science.gov (United States)

Morales, Chloé; Schnyder, Johann; Spangenberg, Jorge; Adatte, Thierry; Westermann, Stephane; Föllmi, Karl

2010-05-01

The Valanginian period is well known for a positive excursion in marine and terrestrial δ13C records, which has been interpreted as the consequence of a major perturbation in the global carbon cycle (Lini et al., 1992; Erba et al., 2004). In contrast to the positive δ13C excursions of the Early Aptian and latest Cenomanian, marine organic-rich sediments have only been recognized from a few localities (van de Schootbrugge et al., 2003; Reboulet et al., 2003; Gröcke et al., 2005; Westermann et al., in press). The δ13C excursion began in the late Early Valanginian (campylotoxus ammonite zone) and gradually ended during the Late Valanginian. It is associated with a phase of widespread carbonate-platform drowning on the shelf (Föllmi et al., 1994) and a decline in calcareous nannofossils in the pelagic realm (Erba et al., 2004). As a triggering mechanism, numerous authors invoke the formation of the Parañà-Etendeka flood basalt. The correlation of this episode with the Valanginian δ13C event depends, however, on the absolute ages attributed to the Valanginian stage. The recent geological timescale by Ogg et al. (2008) shows that the major eruptional phase occurred during the Late Valanginian. This may imply that the late Early Valanginian δ13C event resulted from a combination of different factors. Important paleoenvironmental change occurred already in the latest Berriasian and earliest Valanginian, prior to the positive δ13C excursion. An increase in nutrient input near the onset of the δ13C excursion (campylotoxus ammonite zone), which may be considered as a trigger of the carbon cycle perturbation, has been identified in different studies, (Hennig, 2003; Duchamp-Alphonse et al., 2007; Bornemann & Mutterlose, 2008). Heterozoan faunal associations became dominant since the Early Valanginian on the northern Tethyan Helvetic platform and may indicate the beginning of sea-water eutrophication (Föllmi et al., 2007). Clay assemblages in the Tethys and Western

Early Decrease in Respiration and Uncoupling Event Independent of Cytochrome c Release in PC12 Cells Undergoing Apoptosis

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Berghella, Libera; Ferraro, Elisabetta

2012-01-01

Cytochrome c is a key molecule in mitochondria-mediated apoptosis. It also plays a pivotal role in cell respiration. The switch between these two functions occurs at the moment of its release from mitochondria. This process is therefore extremely relevant for the fate of the cell. Since cytochrome c mediates respiration, we studied the changes in respiratory chain activity during the early stages of apoptosis in order to contribute to unravel the mechanisms of cytochrome c release. We found that, during staurosporine (STS)- induced apoptosis in PC12 cells, respiration is affected before the release of cytochrome c, as shown by a decrease in the endogenous uncoupled respiration and an uncoupling event, both occurring independently of cytochrome c release. The decline in the uncoupled respiration occurs also upon Bcl-2 overexpression (which inhibits cytochrome c release), while the uncoupling event is inhibited by Bcl-2. We also observed that the first stage of nuclear condensation during STS-induced apoptosis does not depend on the release of cytochrome c into the cytosol and is a reversibile event. These findings may contribute to understand the mechanisms affecting mitochondria during the early stages of apoptosis and priming them for the release of apoptogenic factors. PMID:22666257

Biogenic amines as regulators of the proliferative activity of normal and neoplastic intestinal epithelial cells (review).

Science.gov (United States)

Tutton, P J; Barkla, D H

1987-01-01

The role of extracellular amines such as noradrenaline and serotonin and their interaction with cyclic nucleotides and intracellular polyamines in the regulation of intestinal epithelial cell proliferation is reviewed with particular reference to the differences between normal and neoplastic cells. In respect to the normal epithelium of the small intestine there is a strong case to support the notion that cell proliferation is controlled by, amongst other things, sympathetic nerves. In colonic carcinomas, antagonists for certain serotonin receptors, for histamine H2 receptors and for dopamine D2 receptors inhibit both cell division and tumour growth. Because of the reproducible variations between tumour lines in the response to these antagonists, this inhibition appears to be due to a direct effect on the tumour cells rather than an indirect effect via the tumour host or stroma. This conclusion is supported by the cytocidal effects of toxic congeners of serotonin on the tumour cells. The most salient difference between the amine responses of normal and neoplastic cells relates to the issue of amine uptake. Proliferation of crypt cells is promoted by amine uptake inhibitors, presumably because they block amine re-uptake by the amine secreting cells--sympathetic neurones and enteroendocrine cells. However, tumour cell proliferation is strongly inhibited by amine uptake inhibitors, suggesting that neoplastic cells can, and need to take up the amine before being stimulated by it. Recent revelations in the field of oncogenes also support an important association between amines, cyclic nucleotides and cell division. The ras oncogenes code for a protein that is a member of a family of molecules which relay information from extracellular regulators, such as biogenic amines, to the intracellular regulators, including cyclic nucleotides. Evidence is presented suggesting that enteroendocrine cells, enterocytes, carcinoid tumour cells and adenocarcinoma cells all have the same

Early auditory change detection implicitly facilitated by ignored concurrent visual change during a Braille reading task.

Science.gov (United States)

Aoyama, Atsushi; Haruyama, Tomohiro; Kuriki, Shinya

2013-09-01

Unconscious monitoring of multimodal stimulus changes enables humans to effectively sense the external environment. Such automatic change detection is thought to be reflected in auditory and visual mismatch negativity (MMN) and mismatch negativity fields (MMFs). These are event-related potentials and magnetic fields, respectively, evoked by deviant stimuli within a sequence of standard stimuli, and both are typically studied during irrelevant visual tasks that cause the stimuli to be ignored. Due to the sensitivity of MMN/MMF to potential effects of explicit attention to vision, however, it is unclear whether multisensory co-occurring changes can purely facilitate early sensory change detection reciprocally across modalities. We adopted a tactile task involving the reading of Braille patterns as a neutral ignore condition, while measuring magnetoencephalographic responses to concurrent audiovisual stimuli that were infrequently deviated either in auditory, visual, or audiovisual dimensions; 1000-Hz standard tones were switched to 1050-Hz deviant tones and/or two-by-two standard check patterns displayed on both sides of visual fields were switched to deviant reversed patterns. The check patterns were set to be faint enough so that the reversals could be easily ignored even during Braille reading. While visual MMFs were virtually undetectable even for visual and audiovisual deviants, significant auditory MMFs were observed for auditory and audiovisual deviants, originating from bilateral supratemporal auditory areas. Notably, auditory MMFs were significantly enhanced for audiovisual deviants from about 100 ms post-stimulus, as compared with the summation responses for auditory and visual deviants or for each of the unisensory deviants recorded in separate sessions. Evidenced by high tactile task performance with unawareness of visual changes, we conclude that Braille reading can successfully suppress explicit attention and that simultaneous multisensory changes can

Early detection of structual changes in random signal

International Nuclear Information System (INIS)

Kuroda, Yoshiteru; Yokota, Katsuhiro

1981-01-01

Early detection of structual changes in observed random signal is very important from the point of system diagnosis. In this paper, the following procedures are applied to this problem and the results are compared. (1) auto-regressive model to random signal to calculate the prediction error, i.e., the defference between observed and predicted values. (2) auto-regressive method to caluculate the sum of the prediction error. (3) a method is based on AIC (Akaike Information Criterion). Simulation is made of these procedures, indicating their merits and demerits as a diagostic tools. (author)

Early development of Calanus hyperboreus nauplii: Response to a changing ocean

DEFF Research Database (Denmark)

Jung-Madsen, Signe; Nielsen, Torkel Gissel; Grønkjær, Peter

2013-01-01

To forecast effects of temperature changes on recruitment and population dynamics of the Arctic copepod Calanus hyperboreus, laboratory experiments investigating temperature and food effects on early development were performed in Disko Bay, western Greenland, in 2009, and ascent rates of C. hyper...

Neoplastic pleural effusion and intrathoracic metastasis of a scapular osteosarcoma in a dog: a multidisciplinary integrated diagnostic approach.

Science.gov (United States)

Mesquita, Luis; Mortier, Jeremy; Ressel, Lorenzo; Finotello, Riccardo; Silvestrini, Paolo; Piviani, Martina

2017-06-01

A 10-year-old, female spayed mixed-breed or cross-bred dog was referred to the Small Animal Teaching Hospital of the University of Liverpool due to tachypnea, dyspnea, and pleural effusion not responding to diuretics and antibiotics. The chest was drained and cytology of the pleural fluid was consistent with a modified transudate with presence of atypical cells initially attributed to mesothelial hyperplasia and dysplasia. Computed tomography detected, in addition to the bilateral pleural effusion, diffuse pleural thickening, multiple pleural and pulmonary nodules, and a mineralized and lytic mass in the left scapula. Imaging findings were suggestive of a primary bone tumor with intrathoracic metastasis. Cytology of the left scapular and pleural masses revealed a malignant neoplasm highly suggestive of osteosarcoma. The diagnosis was confirmed by demonstration of a positive cytochemical reaction for alkaline phosphatase on prestained cytology slides. This finding prompted review of the initial interpretation of the pleural effusion cytology. The presence of neoplastic osteoblasts in the thoracic fluid was identified by a combination of cytochemistry, cell pellet immunohistochemistry, and transmission electron microscopy findings. In this report, a multidisciplinary integrated diagnostic approach was used to diagnose and confirm a neoplastic pleural effusion due to osteosarcoma metastasis in a dog. © 2017 American Society for Veterinary Clinical Pathology.

Confocal laser endomicroscopy and ultrasound endoscopy during the same endoscopic session for diagnosis and staging of gastric neoplastic lesions.

Science.gov (United States)

Gheorghe, C; Iacob, R; Dumbrava, Mona; Becheanu, G; Ionescu, M

2009-01-01

Confocal LASER endomicroscopy (CLE) is a newly developed endoscopic technique which allows subsurface in vivo histological assessment during ongoing endoscopy and targeted biopsies. Ultrasound endoscopy (EUS) is a useful tool in staging upper GI malignant lesions. We describe for the first time the use of both techniques during the same endoscopic session, in a pilot study, in order to increase the diagnostic yield of histological assessment and provide the staging of the gastric neoplastic lesions thus decreasing the time to therapeutic decision. CLE has been performed with the Pentax EG-3870CIK confocal endomicroscope after a 5 ml intravenous 10% fluorescein injection; EUS has been performed subsequently, during the same endoscopic Propofol sedation session, using a standard radial EUS-scope. Eleven patients have been investigated, 4 females, 7 males, mean age 59.7 +/- 12.3 years. The indication of CLE/EUS exploration was the presence of a gastric polypoid lesion in 37% of cases, atypical gastric ulcer in 27% of patients, gastric lymphoma 18%, suspicion of gastric cancer recurrence after resection 9% and infiltrating type gastric cancer 9%. Histological assessment after targeted biopsy has established the diagnosis of gastric adenocarcinoma in 55% of cases, gastric lymphoma in 18% of cases, gastric adenoma, gastric GIST and gastric foveolar hyperplasia in 9% of cases respectively. CLE has allowed targeted biopsies in 81.8% of cases. In 2 patients - one case with suspected recurrent gastric cancer after surgery and one case of gastric lymphoma, CLE has indicated normal gastric mucosa. The EUS evaluation has shown TO lesion in two cases, T1 in 3 cases, T2 in 3 cases, T3 in one case. The EUS evaluation showed in one gastric lymphoma patient a lesion interesting the mucosa and submucosa with regional adenopathy and a submucosal lesion with regional adenopathy in the other gastric lymphoma case. The therapeutic decision was surgery in 73% of cases, chemotherapy and

Onconeuronal and antineuronal antibodies in patients with neoplastic and non-neoplastic pulmonary pathologies and suspected for paraneoplastic neurological syndrome

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Michalak S

2009-12-01

Full Text Available Abstract Objective Onconeuronal antibodies are important diagnostic tool in patients with suspicion of paraneoplastic neurological syndromes (PNS. However, their role in PNS pathophysiology and specificity for particular neurological manifestation remains unclear. The aim of this study was to evaluate onconeuronal and antineuronal antibodies in patients with pulmonary pathologies and suspected for PNS. Materials and methods Twenty one patients with pulmonary pathologies were selected from the database of 525 consecutive patients with suspicion of PNS. Patients' sera were screened for the presence of onconeuronal and antineuronal antibodies by means of indirect immunofluorescence; the presence was confirmed by Western blotting. Clinical data were obtained from medical records, hospital data base, and questionnaire-based direct telephone contact with patients. Results Among 21 patients, aged 54 ± 11, with pulmonary pathologies, the most frequent neurological manifestations were neuropathies. Typical PNS included paraneoplastic cerebellar degeneration (PCD and limbic encephalitis (LE. We found cases with multiple onconeuronal antibodies (anti-Ri and anti-Yo and coexisting PNS (PCD/LE. Well-defined onconeuronal antibodies were identified in 23.8% of patients. Among antineuronal antibodies, the most frequent were anti-MAG (23.8%. ROC curves analysis revealed high sensitivity of onconeuronal and antineuronal antibodies for typical PNS and lower for pulmonary malignancies. Conclusions Tests for antibodies are highly sensitive for the diagnosis of typical paraneoplastic neurological syndromes. Anti-myelin and anti-MAG antibodies are associated with non-neoplastic pulmonary diseases. Patients with well-defined onconeuronal antibodies require careful screening and follow-up, because the PNS diagnosis indicates a high probability of an underlying malignancy.

Compact energy dispersive X-ray microdiffractometer for diagnosis of neoplastic tissues

Science.gov (United States)

Sosa, C.; Malezan, A.; Poletti, M. E.; Perez, R. D.

2017-08-01

An energy dispersive X-ray microdiffractometer with capillary optics has been developed for characterizing breast cancer. The employment of low divergence capillary optics helps to reduce the setup size to a few centimeters, while providing a lateral spatial resolution of 100 μm. The system angular calibration and momentum transfer resolution were assessed by a detailed study of a polycrystalline reference material. The performance of the system was tested by means of the analysis of tissue-equivalent samples previously characterized by conventional X-ray diffraction. In addition, a simplified correction model for an appropriate comparison of the diffraction spectra was developed and validated. Finally, the system was employed to evaluate normal and neoplastic human breast samples, in order to determine their X-ray scatter signatures. The initial results indicate that the use of this compact energy dispersive X-ray microdiffractometer combined with a simplified correction procedure is able to provide additional information to breast cancer diagnosis.

Two Single-Nucleotide Polymorphisms in ADAM12 Gene Are Associated with Early and Late Radiographic Knee Osteoarthritis in Estonian Population

Directory of Open Access Journals (Sweden)

Irina Kerna

2013-01-01

Full Text Available Objectives. To investigate associations of selected single-nucleotide polymorphisms (SNPs in ADAM12 gene with radiographic knee osteoarthritis (rKOA in Estonian population. Methods. The rs3740199, rs1871054, rs1278279, and rs1044122 SNPs in ADAM12 gene were genotyped in 438 subjects (303 women from population-based cohort, aged 32 to 57 (mean 45.4. The rKOA features were evaluated in the tibiofemoral joint (TFJ and patellofemoral joint. Results. The early rKOA was found in 51.4% of investigated subjects (72% women and 12.3% of participants (63% women had advanced stage of diseases. The A allele of synonymous SNP rs1044122 was associated with early rKOA in TFJ, predominantly with the presence of osteophytes in females (OR 1.57; 95% CI 1.08–2.29, . The C allele of intron polymorphism rs1871054 carried risk for advanced rKOA, mostly to osteophyte formation in TFJ in males (OR 3.03; 95% CI 1.11–7.53, . Also the CCAA haplotype of ADAM12 was associated with osteophytosis, again mostly in TFJ in males (. For rs3740199 and rs1278279, no statistically significant associations were observed. Conclusion.  ADAM12 gene variants are related to rKOA risk during the early and late stages of diseases. The genetic risk seems to be predominantly associated with the appearance of osteophytes—a marker of bone remodelling and neochondrogenesis.

Psychometric evaluation of the general health questionnaire-12 and Rosenberg self-esteem scale in Hungarian and Slovak early adolescents

OpenAIRE

Sarkova, M.; Nagyova, I.; Katreniakova, Z.; Geckova, A.M.; Orosova, O.; Middel, B.; van Dijk, J.P.; van den Heuvel, W.

2006-01-01

The reliability and factor structure of the General Health Questionnaire-12 (GHQ-12) and the Rosenberg Self-Esteem scale (RSE) were evaluated in samples of Hungarian and Slovak early adolescents. The principal component analyses support the two-factor solution for GHQ-12 with subscales "depression/anxiety" and "social dysfunction". Similarly, the RSE appears to be an instrument with a two-factor structure with subscales "negative self-esteem" and "positive self-esteem" in both samples. Reliab...

A 12,000 year record of changes in herbivore niche separation and palaeoclimate (Wonderwerk Cave, South Africa)

Science.gov (United States)

Ecker, Michaela; Brink, James; Horwitz, Liora Kolska; Scott, Louis; Lee-Thorp, Julia A.

2018-01-01

The large mammalian fauna of southern Africa is characterised by strong niche separation into grazer and browser species, with few falling into the intermediate mixed-feeder niche. Moreover, the modern fauna is reduced in species diversity compared to the Pleistocene, following the extinction of several specialized grazers in the late Pleistocene and early Holocene. How did this state develop, and how might it be connected to climatic change during the Holocene? To better understand this development, we obtained extensive carbon and oxygen stable light isotope data from herbivore tooth enamel samples from Wonderwerk Cave, South Africa, spanning about 12,000-500 cal. BP. This is a unique dataset since it is the only site in the southern Kalahari with a robust chronometric record and well-preserved faunal remains for the last 12,000 years without significant gaps. Combining the stable isotopes with pollen and micromammal data from Wonderwerk Cave, we have explored shifts in the proportions of C3 and C4 plants and moisture availability. Although climate remained generally semi-arid for much of this period, the results show significant hydrological and vegetation shifts in the sequence, particularly with the strengthening of summer rainfall in the mid-Holocene. The results for the sixteen herbivore species reveal a reinforcement of the grazer-browser niche partitioning through the Holocene and shows how niche specialization follows changes in local vegetation composition. In the light of this reconstruction of the local ecology we discuss grazer extinctions, human adaptations, and the drivers behind climatic changes in the summer rainfall zone of southern Africa.

A Study on BRCA1/2 Mutations, Hormone Status and HER-2 Status in Korean Women with Early-onset Breast Cancer

International Nuclear Information System (INIS)

Choi, Doo Ho; Jin, So Young; Lee, Dong Wha; Kim, Eun Seog; Kim, Yong Ho

2008-01-01

Women with breast cancer diagnosed at an age of 40 years or younger have a greater prevalence of germline BRCA1 and BRCA2 mutations than the prevalence of women with breast cancer diagnosed at older ages. Several immunohistochemical characteristics have been identified in breast cancers from studies of Caucasian women with BRCA1/2 mutations having familial or early-onset breast cancers. The aim of this study is to determine whether early-onset breast cancer in BRCA1 or BRCA2 mutation carriers, who were not selected from a family history, could be distinguished by the use of immunohistochemical methods and could be distinguished from breast cancer in women of a similar age without a germline BRCA1 or BRCA2 mutation. We also analyzed the prognostic difference between BRCA1/2 related and BRCA1/2 non-related patients by the use of univariate and multivariate analysis. Breast cancer tissue specimens from Korean women with early-onset breast cancers were studied using a tumor tissue microarray. Immunohistochemical staining of estrogen receptor (ER), progesterone receptor (PR) and HER-2, as well as the histology and grade of these specimens, were compared. The prognostic impact of immunohistochemical and histological factors as well as the BRCA1/2 mutation status was investigated separately. There were 14 cases and 16 deleterious BRCA1/2 mutations among 101 patients tested. A family history (4/14) and bilateral breast cancers (3/9) were high risk factors for BRCA1/2 mutations. BRCA1/2- associated cancers demonstrated more expression of ER-negative (19.4% versus 5.1%, p=0.038) and HER-2 negative than BRCA1/2 negative tumors, especially for tumors with BRCA1 tumors The BRCA1/2 mutation rate for patients with triple negative tumors (negative expression of ER, PR and HER-2) was 24.2%. Tumor size, nodal status, and HER-2 expression status were significantly associated with disease free survival, as determined by univariate and multivariate analysis, but the BRCA1/2 status was

Changes in nurses' decision making during a 12-h day shift.

Science.gov (United States)

McClelland, L E; Switzer, F S; Pilcher, J J

2013-01-01

Although shift work is necessary in many health-care settings, research suggests that it can have detrimental effects on performance in health-care providers. To determine if a change in decision-making occurred across a 12-h day shift in a sample of registered nurses. The participants were nurses working a 12-h day shift (7 a.m.-7 p.m.) at a large hospital in the south-eastern USA. Participants completed a policy-capturing questionnaire, examining their likelihood of calling a physician in response to specific patient symptoms, at the beginning and end of the shift. They also completed self-report surveys on alertness, stress and sleepiness. Sixty-five nurses completed the study, an overall response rate of 41%. Participants significantly changed their decision-making policies from the beginning to the end of the work shift and also became significantly less alert and more stressed. However, there was no correlation between decision-making and reported alertness and stress. These results suggest that medical judgment in registered nurses changed from the beginning to the end of a 12-h day shift. One possible underlying mechanism responsible for the changes seen across the shift could be the ability to maintain attention, as suggested by the Controlled Attention Model. The current results expand upon previous research, indicating there are a variety of negative outcomes associated with shift work.

The development of functional network organization in early childhood and early adolescence: A resting-state fNIRS study.

Science.gov (United States)

Cai, Lin; Dong, Qi; Niu, Haijing

2018-04-01

Early childhood (7-8 years old) and early adolescence (11-12 years old) constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS) imaging data to examine topological changes in network organization during development from early childhood and early adolescence to adulthood. Our results showed that the properties of small-worldness and modularity were not significantly different across development, demonstrating the developmental maturity of important functional brain organization in early childhood. Intriguingly, young children had a significantly lower global efficiency than early adolescents and adults, which revealed that the integration of the distributed networks strengthens across the developmental stages underlying cognitive development. Moreover, local efficiency of young children and adolescents was significantly lower than that of adults, while there was no difference between these two younger groups. This finding demonstrated that functional segregation remained relatively steady from early childhood to early adolescence, and the brain in these developmental periods possesses no optimal network configuration. Furthermore, we found heterogeneous developmental patterns in the regional nodal properties in various brain regions, such as linear increased nodal properties in the frontal cortex, indicating increasing cognitive capacity over development. Collectively, our results demonstrated that significant topological changes in functional network organization occurred during these two critical developmental stages, and provided a novel insight into elucidating subtle changes in brain functional networks across development. Copyright �

The development of functional network organization in early childhood and early adolescence: A resting-state fNIRS study

Directory of Open Access Journals (Sweden)

Lin Cai

2018-04-01

Full Text Available Early childhood (7–8 years old and early adolescence (11–12 years old constitute two landmark developmental stages that comprise considerable changes in neural cognition. However, very limited information from functional neuroimaging studies exists on the functional topological configuration of the human brain during specific developmental periods. In the present study, we utilized continuous resting-state functional near-infrared spectroscopy (rs-fNIRS imaging data to examine topological changes in network organization during development from early childhood and early adolescence to adulthood. Our results showed that the properties of small-worldness and modularity were not significantly different across development, demonstrating the developmental maturity of important functional brain organization in early childhood. Intriguingly, young children had a significantly lower global efficiency than early adolescents and adults, which revealed that the integration of the distributed networks strengthens across the developmental stages underlying cognitive development. Moreover, local efficiency of young children and adolescents was significantly lower than that of adults, while there was no difference between these two younger groups. This finding demonstrated that functional segregation remained relatively steady from early childhood to early adolescence, and the brain in these developmental periods possesses no optimal network configuration. Furthermore, we found heterogeneous developmental patterns in the regional nodal properties in various brain regions, such as linear increased nodal properties in the frontal cortex, indicating increasing cognitive capacity over development. Collectively, our results demonstrated that significant topological changes in functional network organization occurred during these two critical developmental stages, and provided a novel insight into elucidating subtle changes in brain functional networks across

Frameworks for Change: Four Recurrent Themes for Quality in Early Childhood Curriculum Initiatives

Science.gov (United States)

Burgess, Jennifer; Fleet, Alma

2009-01-01

This paper reports on the first phase of a case study that investigated how early childhood teachers experience organisational change. As one of three levels of quality improvement, State government-funded curriculum initiatives were developed with an aim to promote change. Three curriculum documents, one each focusing on literacy, pedagogy and…

The gene expression program of prostate fibroblast senescence modulates neoplastic epithelial cell proliferation through paracrine mechanisms.

Science.gov (United States)

Bavik, Claes; Coleman, Ilsa; Dean, James P; Knudsen, Beatrice; Plymate, Steven; Nelson, Peter S

2006-01-15

The greatest risk factor for developing carcinoma of the prostate is advanced age. Potential molecular and physiologic contributors to the frequency of cancer occurrence in older individuals include the accumulation of somatic mutations through defects in genome maintenance, epigenetic gene silencing, oxidative stress, loss of immune surveillance, telomere dysfunction, chronic inflammation, and alterations in tissue microenvironment. In this context, the process of prostate carcinogenesis can be influenced through interactions between intrinsic cellular alterations and the extrinsic microenvironment and macroenvironment, both of which change substantially as a consequence of aging. In this study, we sought to characterize the molecular alterations that occur during the process of prostate fibroblast senescence to identify factors in the aged tissue microenvironment capable of promoting the proliferation and potentially the neoplastic progression of prostate epithelium. We evaluated three mechanisms leading to cell senescence: oxidative stress, DNA damage, and replicative exhaustion. We identified a consistent program of gene expression that includes a subset of paracrine factors capable of influencing adjacent prostate epithelial growth. Both direct coculture and conditioned medium from senescent prostate fibroblasts stimulated epithelial cell proliferation, 3-fold and 2-fold, respectively. The paracrine-acting proteins fibroblast growth factor 7, hepatocyte growth factor, and amphiregulin (AREG) were elevated in the extracellular environment of senescent prostate fibroblasts. Exogenous AREG alone stimulated prostate epithelial cell growth, and neutralizing antibodies and small interfering RNA targeting AREG attenuated, but did not completely abrogate the growth-promoting effects of senescent fibroblast conditioned medium. These results support the concept that aging-related changes in the prostate microenvironment may contribute to the progression of prostate

Late neoplastic changes following medical irradiation

International Nuclear Information System (INIS)

Hutchison, G.B.

1976-01-01

New additions since 1968 to the literature on radiation carcinogenesis in man support the earlier conclusion of an approximately linear increase in cancer incidence in a broad intermediate dose range for most sites of cancer. Questions are raised regarding the nature of the dose-response relation at very low and at very high dose exposures. Analyses of some data on exposure to radiation from internal deposits of radioactive material suggest that the dose-response curve at low and intermediate ranges is concave up, implying a smaller effect per unit exposure at very low doses than at intermediate ranges. Data on exposure to the very high but anatomically limited doses of radiation used in cancer therapy give conflicting results, suggesting in one report a continuation of the linear relation into the high-dose range. Other reports suggest a lesser effect per unit dose at high doses than at intermediate doses. Extensive laboratory studies of exposure of experimental animals indicate that over broad dose ranges, exceptions to simple linear relations are the rule, and that factors of dose rate and fractionation also affect the dose-response relation

Low Dose Suppression of Neoplastic Transformation in Vitro

Energy Technology Data Exchange (ETDEWEB)

John Leslie Redpath

2012-05-01

This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

Maternal-child adrenocortical attunement in early childhood: continuity and change.

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Hibel, Leah C; Granger, Douglas A; Blair, Clancy; Finegood, Eric D

2015-01-01

This study evaluated continuity and change in maternal-child hypothalamic-pituitary-adrenal axis attunement in early childhood. Participants were drawn from a prospective study of 1,292 mother-child dyads, which were racially diverse, predominantly low-income, and non-urban. Child focused stress tasks designed to elicit anger, fear, and frustration were administered during early infancy, later infancy, and toddlerhood. Mothers' and children's saliva samples (later assayed for cortisol) were collected before and after the tasks. The strength of mother-child adrenocortical attunement was conserved across infancy and toddlerhood. The magnitude of maternal-child adrenocortical attunement decreased in response to the child-focused stress tasks. Maternal sensitivity and the child's task-related emotional reactivity moderated adrenocortical attunement across the task, with greater maternal sensitivity during a free-play, and lower levels of child emotional reactivity during the stress tasks, stabilizing attunement from pre- to post-task levels. The findings advance our understanding of individual differences in the social regulation of adrenocortical activity in early childhood. © 2014 Wiley Periodicals, Inc.

Effect of age on radiation-induced early changes of rat rectum. A histological time sequence

International Nuclear Information System (INIS)

Olofsen-van Acht, Manouk J.J.; Hooije, Christel M.C. van; Aardweg, Gerard J.M.J. van den; Levendag, Peter C.; Velthuysen, Marie Louise F. van

2001-01-01

Background and purpose: Radiation treatment of the elderly (>75 years) is often modified due to an assumed decrease in normal tissue tolerance in this age group. Since more radiobiological data concerning normal tissue toxicity as a function of age are needed, a histological study of age-related radiation changes of the rectum was performed. Materials and methods: The rectum of young and old female Wistar rats (12 and 78 weeks, respectively) was irradiated with single doses of 22 and 39 Gy. The field size was 1.5x2.0 cm. The animals were sacrificed at 1, 2, 4 and 10 weeks after treatment. To evaluate radiation damage, 12 histological parameters were scored in four areas of the rectum. A total radiation injury score was calculated. The number of proliferative epithelial cells was evaluated by 5-bromo-2'-deoxyuridine labeling. Results: Some age-related histological differences were observed; especially, the incidence of ulceration and vascular occlusion was higher in the older group. In the low dose group of the older animals, 60% showed ulceration, which was 0% for the young low dose animals. Severe vascular changes occurred early and were more extensive in older animals (4 weeks) than in the younger group (10 weeks). In the area adjacent to the treatment field, cell proliferation increased significantly in older rats at 1 week after 22 Gy, which did not occur in the young group. Conclusions: Discrete radiation-induced histological differences were observed between the rectum of young and old Wistar rats, especially in the development of ulceration and vascular changes. Although the survival of these Wistar rats in earlier studies was not affected by age, the impact of the observed histological differences for their importance in the long-term is currently being investigated

Precursors of social emotional functioning among full-term and preterm infants at 12 months: Early infant withdrawal behavior and symptoms of maternal depression.

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Moe, Vibeke; Braarud, Hanne Cecilie; Wentzel-Larsen, Tore; Slinning, Kari; Vannebo, Unni Tranaas; Guedeney, Antoine; Heimann, Mikael; Rostad, Anne Margrethe; Smith, Lars

2016-08-01

This study forms part of a longitudinal investigation of early infant social withdrawal, maternal symptoms of depression and later child social emotional functioning. The sample consisted of a group of full-term infants (N=238) and their mothers, and a group of moderately premature infants (N=64) and their mothers. At 3 months, the infants were observed with the Alarm Distress Baby Scale (ADBB) and the mothers completed the Edinburgh Postnatal Depression Scale (EPDS). At 12 months, the mothers filled out questionnaires about the infants' social emotional functioning (Infant Toddler Social Emotional Assessment and the Ages and Stages Questionnaire-Social Emotional). At 3 months, as we have previously shown, the premature infants had exhibited more withdrawal behavior and their mothers reported elevated maternal depressive symptoms as compared with the full-born group. At 12 months the mothers of the premature infants reported more child internalizing behavior. These data suggest that infant withdrawal behavior as well as maternal depressive mood may serve as sensitive indices of early risk status. Further, the results suggest that early maternal depressive symptoms are a salient predictor of later child social emotional functioning. However, neither early infant withdrawal behavior, nor gestational age, did significantly predict social emotional outcome at 12 months. It should be noted that the differences in strength of the relations between ADBB and EPDS, respectively, to the outcome at 12 months was modest. An implication of the study is that clinicians should be aware of the complex interplay between early infant withdrawal and signs of maternal postpartum depression in planning ports of entry for early intervention. Copyright © 2016 Elsevier Inc. All rights reserved.

Massachusetts Early Warning Indicator System (EWIS). "Technical Descriptions of Risk Model Development": Middle and High School Age Groupings (Grades 7-12)

Science.gov (United States)

Massachusetts Department of Elementary and Secondary Education, 2013

2013-01-01

The Massachusetts Department of Elementary and Secondary Education (Department) created the grades 1-12 Early Warning Indicator System (EWIS) in response to district interest in the Early Warning Indicator Index (EWII) that the Department previously created for rising grade 9 students. Districts shared that the EWII data were helpful, but also…

Modulation of early stress-induced neurobiological changes: a review of behavioural and pharmacological interventions in animal models.

Science.gov (United States)

Harrison, E L; Baune, B T

2014-05-13

Childhood adversity alters the predisposition to psychiatric disorders later in life. Those with psychiatric conditions and a history of early adversity exhibit a higher incidence of treatment resistance compared with individuals with no such history. Modulation of the influence early stress exerts over neurobiology may help to prevent the development of psychiatric disorders in some cases, while attenuating the extent of treatment resistance in those with established psychiatric disorders. This review aims to critically evaluate the ability of behavioural, environmental and pharmacologic interventions to modulate neurobiological changes induced by early stress in animal models. Databases were systematically searched to locate literature relevant to this review. Early adversity was defined as stress that resulted from manipulation of the mother-infant relationship. Analysis was restricted to animal models to enable characterisation of how a given intervention altered specific neurobiological changes induced by early stress. A wide variety of changes in neurobiology due to early stress are amenable to intervention. Behavioural interventions in childhood, exercise in adolescence and administration of epigenetic-modifying drugs throughout life appear to best modulate cellar and behavioural alterations induced by childhood adversity. Other pharmacotherapies, such as endocannabinoid system modulators, anti-inflammatories and antidepressants can also influence these neurobiological and behavioural changes that result from early stress, although findings are less consistent at present and require further investigation. Further work is required to examine the influence that behavioural interventions, exercise and epigenetic-modifying drugs exert over alterations that occur following childhood stress in human studies, before possible translational into clinical practice is possible.

Confocal fluorescence microscopy to evaluate changes in adipocytes in the tumor microenvironment associated with invasive ductal carcinoma and ductal carcinoma in situ.

Science.gov (United States)

Dobbs, Jessica L; Shin, Dongsuk; Krishnamurthy, Savitri; Kuerer, Henry; Yang, Wei; Richards-Kortum, Rebecca

2016-09-01

Adipose tissue is a dynamic organ that provides endocrine, inflammatory and angiogenic factors, which can assist breast carcinoma cells with invasion and metastasis. Previous studies have shown that adipocytes adjacent to carcinoma, known as cancer-associated adipocytes, undergo extensive changes that correspond to an "activated phenotype," such as reduced size relative to adipocytes in non-neoplastic breast tissue. Optical imaging provides a tool that can be used to characterize adipocyte morphology and other features of the tumor microenvironment. In this study, we used confocal fluorescence microscopy to acquire images of freshly excised breast tissue stained topically with proflavine. We developed a computerized algorithm to identify and quantitatively measure phenotypic properties of adipocytes located adjacent to and far from normal collagen, ductal carcinoma in situ and invasive ductal carcinoma. Adipocytes were measured in confocal fluorescence images of fresh breast tissue collected from 22 patients. Results show that adipocytes adjacent to neoplastic tissue margins have significantly smaller area compared to adipocytes far from the margins of neoplastic lesions and compared to adipocytes adjacent to non-neoplastic collagenous stroma. These findings suggest that confocal microscopic images can be utilized to evaluate phenotypic properties of adipocytes in breast stroma which may be useful in defining alterations in microenvironment that may aid in the development and progression of neoplastic lesions. © 2016 UICC.

White spot syndrome virus induces metabolic changes resembling the warburg effect in shrimp hemocytes in the early stage of infection.

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Chen, I-Tung; Aoki, Takashi; Huang, Yun-Tzu; Hirono, Ikuo; Chen, Tsan-Chi; Huang, Jiun-Yan; Chang, Geen-Dong; Lo, Chu-Fang; Wang, Han-Ching

2011-12-01

The Warburg effect is an abnormal glycolysis response that is associated with cancer cells. Here we present evidence that metabolic changes resembling the Warburg effect are induced by a nonmammalian virus. When shrimp were infected with white spot syndrome virus (WSSV), changes were induced in several metabolic pathways related to the mitochondria. At the viral genome replication stage (12 h postinfection [hpi]), glucose consumption and plasma lactate concentration were both increased in WSSV-infected shrimp, and the key enzyme of the pentose phosphate pathway, glucose-6-phosphate dehydrogenase (G6PDH), showed increased activity. We also found that at 12 hpi there was no alteration in the ADP/ATP ratio and that oxidative stress was lower than that in uninfected controls. All of these results are characteristic of the Warburg effect as it is present in mammals. There was also a significant decrease in triglyceride concentration starting at 12 hpi. At the late stage of the infection cycle (24 hpi), hemocytes of WSSV-infected shrimp showed several changes associated with cell death. These included the induction of mitochondrial membrane permeabilization (MMP), increased oxidative stress, decreased glucose consumption, and disrupted energy production. A previous study showed that WSSV infection led to upregulation of the voltage-dependent anion channel (VDAC), which is known to be involved in both the Warburg effect and MMP. Here we show that double-stranded RNA (dsRNA) silencing of the VDAC reduces WSSV-induced mortality and virion copy number. For these results, we hypothesize a model depicting the metabolic changes in host cells at the early and late stages of WSSV infection.

Impacts of Early Summer Eurasian Snow Cover Change on Atmospheric Circulation in Northern Mid-Latitudes

Science.gov (United States)

Nozawa, T.

2016-12-01

Recently, Japan Aerospace Exploration Agency (JAXA) has developed a new long-term snow cover extent (SCE) product using Advanced Very High Resolution Radiometer (AVHRR) and Moderate Resolution Imaging Spectroradiometer (MODIS) data spanning from 1980's to date. This new product (JAXA/SCE) has higher spatial resolution and smaller commission error compared with traditional SCE dataset of National Oceanic and Atmospheric Administration (NOAA/SCE). Continuity of the algorithm is another strong point in JAXA/SCE. According to the new JAXA/SCE dataset, the Eurasian SCE has been significantly retreating since 1980's, especially in late spring and early summer. Here, we investigate impacts of early summer Eurasian snow cover change on atmospheric circulation in Northern mid-latitudes, especially over the East Asia, using the new JAXA/SCE dataset and a few reanalysis data. We will present analyzed results on relationships between early summer SCE anomaly over the Eurasia and changes in atmospheric circulations such as upper level zonal jets (changes in strength, positions, etc.) over the East Asia.

Three-Dimensional Printing as an Interdisciplinary Communication Tool: Preparing for Removal of a Giant Renal Tumor and Atrium Neoplastic Mass.

Science.gov (United States)

Golab, Adam; Slojewski, Marcin; Brykczynski, Miroslaw; Lukowiak, Magdalena; Boehlke, Marek; Matias, Daniel; Smektala, Tomasz

2016-08-22

Three-dimensional (3D) printing involves preparing 3D objects from a digital model. These models can be used to plan and practice surgery. We used 3D printing to plan for a rare complicated surgery involving the removal of a renal tumor and neoplastic mass, which reached the heart atrium. A printed kidney model was an essential element of communication for physicians with different specializations.

Morphologic alterations in normal and neoplastic tissues following hyperthermia treatment

International Nuclear Information System (INIS)

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

1984-01-01

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

Perceived Social Support Change in Patients with Early-stage Breast Cancer and Controls

Science.gov (United States)

Thompson, Tess; Rodebaugh, Thomas L.; Pérez, Maria; Schootman, Mario; Jeffe, Donna B.

2014-01-01

Objective To identify variables associated with levels of and change in social support in a cohort of early-stage breast cancer patients and age-matched controls. Methods Telephone interviews measuring perceived social support and other demographic and psychosocial variables were conducted at 4–6 weeks and 6, 12, and 24 months after surgery (patients) or a normal/benign screening mammogram (controls). A latent trajectory model was used to model the intercept (starting point) and slope (changing) aspects of social support. Results Participants included 542 controls and 541 patients (77% White, 23% African American; mean age 57.7 [SD = 10.6]). Most participants reported high social support. Patients reported significantly higher levels of social support at baseline than controls. For patients, social support had a significant negative slope that significantly varied between individuals; the intercept of social support also varied significantly. Predictors of lower social support intercept in patients included not being married/partnered, being White, having lower perceived general health, and having higher negative affect (modeled as a latent variable defined by anxiety and depression symptom severity). Patients who were African American (vs. White) or had mastectomy (vs. lumpectomy) had steeper social support declines, and participants with both these characteristics had lower starting points as well as steeper declines. Social support among controls did not change significantly. Conclusions Clinicians might consider psychosocial interventions for patients reporting low social support around the time of diagnosis and surgical treatment, and for patients at risk for steeper declines in support, such as African Americans and women undergoing mastectomy. PMID:23477582

Central nervous system complications after liver transplantation.

Science.gov (United States)

Kim, Jeong-Min; Jung, Keun-Hwa; Lee, Soon-Tae; Chu, Kon; Roh, Jae-Kyu

2015-08-01

We investigated the diversity of central nervous system complications after liver transplantation in terms of clinical manifestations and temporal course. Liver transplantation is a lifesaving option for end stage liver disease patients but post-transplantation neurologic complications can hamper recovery. Between 1 January 2001 and 31 December 2010, patients who had undergone liver transplantation at a single tertiary university hospital were included. We reviewed their medical records and brain imaging data and classified central nervous system complications into four categories including vascular, metabolic, infectious and neoplastic. The onset of central nervous system complications was grouped into five post-transplantation intervals including acute (within 1 month), early subacute (1-3 months), late subacute (3-12 months), chronic (1-3 years), and long-term (after 3 years). During follow-up, 65 of 791 patients (8.2%) experienced central nervous system complications, with 30 occurring within 1 month after transplantation. Vascular etiology was the most common (27 patients; 41.5%), followed by metabolic (23; 35.4%), infectious (nine patients; 13.8%), and neoplastic (six patients). Metabolic encephalopathy with altered consciousness was the most common etiology during the acute period, followed by vascular disorders. An initial focal neurologic deficit was detected in vascular and neoplastic complications, whereas metabolic and infectious etiologies presented with non-focal symptoms. Our study shows that the etiology of central nervous system complications after liver transplantation changes over time, and initial symptoms can help to predict etiology. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early changes of parotid density and volume predict modifications at the end of therapy and intensity of acute xerostomia

International Nuclear Information System (INIS)

Belli, Maria Luisa; Broggi, Sara; Scalco, Elisa; Rizzo, Giovanna; Sanguineti, Giuseppe; Fiorino, Claudio; Cattaneo, Giovanni Mauro; Dinapoli, Nicola; Valentini, Vincenzo; Ricchetti, Francesco

2014-01-01

To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer. Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients. A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher ''mean'' acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / 3 /day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia. (orig.) [de

Early motor learning changes in upper-limb dynamics and shoulder complex loading during handrim wheelchair propulsion.

Science.gov (United States)

Vegter, Riemer J K; Hartog, Johanneke; de Groot, Sonja; Lamoth, Claudine J; Bekker, Michel J; van der Scheer, Jan W; van der Woude, Lucas H V; Veeger, Dirkjan H E J

2015-03-10

To propel in an energy-efficient manner, handrim wheelchair users must learn to control the bimanually applied forces onto the rims, preserving both speed and direction of locomotion. Previous studies have found an increase in mechanical efficiency due to motor learning associated with changes in propulsion technique, but it is unclear in what way the propulsion technique impacts the load on the shoulder complex. The purpose of this study was to evaluate mechanical efficiency, propulsion technique and load on the shoulder complex during the initial stage of motor learning. 15 naive able-bodied participants received 12-minutes uninstructed wheelchair practice on a motor driven treadmill, consisting of three 4-minute blocks separated by two minutes rest. Practice was performed at a fixed belt speed (v = 1.1 m/s) and constant low-intensity power output (0.2 W/kg). Energy consumption, kinematics and kinetics of propulsion technique were continuously measured. The Delft Shoulder Model was used to calculate net joint moments, muscle activity and glenohumeral reaction force. With practice mechanical efficiency increased and propulsion technique changed, reflected by a reduced push frequency and increased work per push, performed over a larger contact angle, with more tangentially applied force and reduced power losses before and after each push. Contrary to our expectations, the above mentioned propulsion technique changes were found together with an increased load on the shoulder complex reflected by higher net moments, a higher total muscle power and higher peak and mean glenohumeral reaction forces. It appears that the early stages of motor learning in handrim wheelchair propulsion are indeed associated with improved technique and efficiency due to optimization of the kinematics and dynamics of the upper extremity. This process goes at the cost of an increased muscular effort and mechanical loading of the shoulder complex. This seems to be associated with an

Dual-energy CT with iodine quantification in distinguishing between bland and neoplastic portal vein thrombosis in patients with hepatocellular carcinoma

International Nuclear Information System (INIS)

Ascenti, G.; Sofia, C.; Mazziotti, S.; Silipigni, S.; D'Angelo, T.; Pergolizzi, S.; Scribano, E.

2016-01-01

Aim: To investigate the diagnostic accuracy of dual-energy multidetector computed tomography (MDCT) with iodine quantification compared to conventional enhancement measurements in distinguishing bland from neoplastic portal vein thrombosis in patients with hepatocellular carcinoma. Material and methods: Thirty-four patients (26 men, eight women; mean age, 62 years) with hepatocellular carcinoma and portal vein thrombosis underwent contrast-enhanced dual-energy MDCT during the late hepatic arterial phase for the assessment of portal thrombosis (bland, n=21; neoplastic, n=13). Datasets were analysed separately by two different readers. Interobserver correlation and variability were calculated and compared with the Bland–Altman method. Diagnostic accuracy of conventional enhancement measurements and iodine quantification was calculated by setting either histopathology (n=7) or a reference standard based on MDCT imaging criteria and thrombus evolutionary characteristics compared to a previous MDCT examination (n=27). For iodine quantification threshold determination receiver operating characteristic (ROC) curves were drawn. p-Values <0.05 were considered significant. Results: For conventional enhancement measurements and iodine quantification interobserver correlation was 98% and 96%. Enhancement measurement resulted in a sensitivity of 92.3%, specificity of 85.7%, positive predictive value (PPV) of 80%, and negative predictive value (NPV) of 94.7%. An iodine concentration of 0.9 mg/ml optimised discrimination between neoplastic and bland thrombi (area under the ROC [AUC] 0.993) resulting in a sensitivity of 100%, specificity of 95.2%, PPV of 92.9%, and NPV of 100%. The overall diagnostic accuracy of iodine quantification (97%) was significantly better than conventional enhancement measurements (88.2%; p<0.001). Conclusion: Compared to conventional enhancement measurements, iodine quantification improves the characterisation of portal vein thrombi during the late

Age and Spatial Peculiarities of Non-neoplastic Diseases of the Skin and Subcutaneous Tissue in Kazakhstan, 2003–2015

OpenAIRE

IGISSINOV, Nurbek; KULMIRZAYEVA, Dariyana; BILYALOVA, Zarina; AKPOLATOVA, Gulnur; MAMYRBAYEVA, Marzya; ZHUMAGALIYEVA, Galina

2017-01-01

Background: Arrangement of effective management aimed at improving dermatological services and consistent care of patients with skin diseases depends on understanding the epidemiological situation. Methods: This retrospective study presents an epidemiological assessment of non-neoplastic skin and subcutaneous tissue diseases in Kazakhstan registered in 2003–2015. Results: The yearly incidence rate of the diseases among the whole population was in average 3,341.8±121.1 per 100000 population. T...

Organizational change, psychosocial work environment, and non-disability early retirement: a prospective study among senior public employees.

Science.gov (United States)

Breinegaard, Nina; Jensen, Johan Høy; Bonde, Jens Peter

2017-05-01

Objective This study examines the impact of organizational change and psychosocial work environment on non-disability early retirement among senior public service employees. Methods In January and February 2011, Danish senior public service employees aged 58-64 years (N=3254) from the Capital Region of Denmark responded to a survey assessing psychosocial work environment (ie, social capital, organizational justice, and quality of management). Work-unit organizational changes (ie, change of management, merging, demerging, and relocation) were recorded from January 2009 to March 2011. Weekly data on non-disability early retirement transfer were obtained from the DREAM register database, which holds weekly information about all public benefit payments in Denmark. Hazard ratios (HR) for early retirement following employees' 60 th birthday were estimated with Cox regression adjusted for age, gender, and socioeconomic status. Results Exposure to change of management [HR 1.37, 95% confidence interval (95% CI) 1.13-1.66], mergers (HR 1.23, 95% CI 1.02-1.48), and relocation of work unit (HR 1.24, 95% CI 1.01-1.54) increased rate of non-disability early retirement, while demerging of work unit did not (HR 1.03, 95% CI 0.79-1.33). Work units with lower levels of social capital (HR 1.22, 95% CI 1.05-1.41), organizational justice, (HR 1.18, 95% CI 1.04-1.32), and quality of management (HR 1.14, 95% CI 1.02-1.25) increased rate of early retirement. Conclusion Organizational change and poor psychosocial work environment contribute to non-disability early retirement among senior public service employees, measured at work-unit level.

Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts.

Science.gov (United States)

Carpenter, Lewis; Norton, Sam; Nikiphorou, Elena; Jayakumar, Keeranur; McWilliams, Daniel F; Rennie, Kirsten L; Dixey, Josh; Kiely, Patrick; Walsh, David Andrew; Young, Adam

2017-12-01

To assess the 5-year progression of erosions and joint space narrowing (JSN) and their associations with rheumatoid factor (RF) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years. Radiographic joint damage was recorded using the Sharp/van der Heijde (SHS) method in the Early Rheumatoid Arthritis Study (ERAS), 1986-2001, and the Early Rheumatoid Arthritis Network (ERAN), 2002-2013. Mixed-effects negative binomial regression estimated changes in radiographic damage over 5 years, including erosions and JSN, separately. RF, along with age, sex, and baseline markers of disease activity were controlled for. A total of 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS, ERAN patients had a lower mean total SHS score at baseline (ERAN 6.2 versus ERAS 10.5; P < 0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P < 0.001). Seventy-four percent of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS 3.9 versus ERAN 1.2; P < 0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P < 0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF-positive patients was substantially higher for ERAS (RF positive 8.6 versus RF negative 5.1; P < 0.001), relative to ERAN (RF positive 2.0 versus RF negative 1.9; P = 0.855). Radiographic progression was shown to be significantly reduced between the 2 cohorts, and was associated with lower baseline damage and other factors, including changes in early disease-modifying antirheumatic drug use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment. © 2017, American College of Rheumatology.

Is the global rise of asthma an early impact of anthropogenic climate change?

Directory of Open Access Journals (Sweden)

Paul John Beggs

Full Text Available The increase in asthma incidence, prevalence, and morbidity over recent decades presents a significant challenge to public health. Pollen is an important trigger of some types of asthma, and both pollen quantity and season depend on climatic and meteorological variables. Over the same period as the global rise in asthma, there have been considerable increases in atmospheric carbon dioxide concentration and global average surface temperature. We hypothesize anthropogenic climate change as a plausible contributor to the rise in asthma. Greater concentrations of carbon dioxide and higher temperatures may increase pollen quantity and induce longer pollen seasons. Pollen allergenicity can also increase as a result of these changes in climate. Exposure in early life to a more allergenic environment may also provoke the development of other atopic conditions, such as eczema and allergic rhinitis. Although the etiology of asthma is complex, the recent global rise in asthma could be an early health effect of anthropogenic climate change.

High soluble CD30, CD25 and IL-6 may identify patients with worse survival in CD30+ cutaneous lymphomas and early mycosis fungoides

Science.gov (United States)

Kadin, Marshall E.; Pavlov, Igor; Delgado, Julio C.; Vonderheid, Eric C.

2011-01-01

Histopathology alone cannot predict outcome of patients with CD30+ primary cutaneous lymphoproliferative disorders (CD30CLPD) and early mycosis fungoides (MF). To test the hypothesis that serum cytokines/cytokine receptors provide prognostic information in these disorders, we measured soluble CD30 (sCD30), sCD25, and selected cytokines in cell cultures and sera of 116 patients with CD30CLPD and 96 patients with early MF followed up to 20 years. Significant positive correlation was found between sCD30 levels and sCD25, CD40L, IL-6, and IL-8, suggesting CD30+ neoplastic cells secrete these cytokines, but not Th2 cytokines. In vitro studies confirmed sCD30, sCD25, IL-6 and IL-8 are secreted by CD30CLPD-derived cell lines. CD30CLPD patients with above normal sCD30 and sCD25 had worse overall and disease-related survivals, but only sCD30 retained significance in Cox models that included advanced age. High sCD30 also identified patients with worse survival in early MF. Increased IL-6 and IL-8 correlated with poor disease-related survival in CD30CLPD patients, We conclude that: (1) neoplastic cells of some CD30CLPD patients do not resemble Th2 cells, (2) high serum sCD30, sCD25, IL-6, and perhaps IL-8 levels may provide prognostic information useful for patient management. PMID:22071475

Early segmental changes in ischemic acute tubular necrosis of the rat kidney

DEFF Research Database (Denmark)

Faarup, Poul; Nørgaard, Tove; Hegedüs, Viktor

2004-01-01

The background and mechanisms of ischemic acute tubular necrosis are still essentially unclarified. Therefore a quantitative morphological technique was applied for evaluation of the early structural changes in different fractions of the proximal convoluted tubule in the rat renal cortex. In male...

Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Applying a conceptual model to the results of three workplace surveys

NARCIS (Netherlands)

Kromhout, H.; Hoek, F.; Uitterhoeve, R.; Huijbers, R.; Overmars, R.F.; Anzion, R.; Vermeulen, R.

2000-01-01

Dermal exposure to anti-neoplastic drugs has been suggested as a potentially important route of exposure of hospital workers. Three small-scale workplace surveys were carried out in several hospitals focusing on contamination by leakage from IV infusion systems; contamination by spilled urine of

Focus formation and neoplastic transformation by herpes simplex virus type 2 inactivated intracellularly by 5-bromo-2'-deoxyuridine and near UV light

International Nuclear Information System (INIS)

Manak, M.M.; Aurelian, L.; Ts'o, P.O.

1981-01-01

The induction of focus formation in low serum and of neoplastic transformation of Syrian hamster embryo cells was examined after the expression of herpes simplex virus type 2 functions. Syrian hamster embryo cells infected at a high multiplicity (5 PFU/cell) with 5-bromo-2'-deoxyuridine-labeled herpes simplex virus type 2 (11% substitution of thymidine residues) were exposed to near UV light irradiation at various times postinfection. This procedure specifically inactivated the viral genome, while having little, if any, effect on the unlabeled cellular DNA. Focus formation in 1% serum and neoplastic transformation were observed in cells exposed to virus inactivated before infection, but the frequency was enhanced (15- to 27-fold) in cells in which the virus was inactivated at 4 to 8 h postinfection. Only 2 to 45 independently isolated foci were capable of establishing tumorigenic lines. The established lines exhibited phenotypic alterations characteristic of a transformed state, including reduced serum requirement, anchorage-independent growth, and tumorigenicity. They retained viral DNA sequences and, even at relatively late passage, expressed viral antigens, including ICP 10

Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis.

Science.gov (United States)

Georgopoulou, Antonia-Panagiota; Savva, Athina; Giamarellos-Bourboulis, Evangelos J; Georgitsi, Marianna; Raftogiannis, Maria; Antonakos, Nicolaos; Apostolidou, Efterpi; Carrer, Dionyssia-Pinelopi; Dimopoulos, George; Economou, Aggelos; Efthymiou, George; Galanakis, Nearchos; Galani, Labrini; Gargalianos, Panagiotis; Karaiskos, Ilias; Katsenos, Chrisostomos; Kavatha, Dimitra; Koratzanis, Evangelos; Labropoulos, Panagiotis; Lada, Malvina; Nakos, George; Paggalou, Evgenia; Panoutsopoulos, George; Paraschos, Michael; Pavleas, Ioannis; Pontikis, Konstantinos; Poulakou, Garyfallia; Prekates, Athanassios; Sybardi, Styliani; Theodorakopoulou, Maria; Trakatelli, Christina; Tsiaoussis, Panagiotis; Gogos, Charalambos; Giamarellou, Helen; Armaganidis, Apostolos; Meisner, Michael

2011-06-01

The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials. Copyright © 2011 Elsevier Inc. All rights reserved.

RET/PTC1-Driven Neoplastic Transformation and Proinvasive Phenotype of Human Thyrocytes Involve Met Induction and β-Catenin Nuclear Translocation

Directory of Open Access Journals (Sweden)

Giuliana Cassinelli

2009-01-01

Full Text Available Activation of the RET gene by chromosomal rearrangements generating RET/PTC oncogenes is a frequent, early, and causative event in papillary thyroid carcinoma (PTC. We have previously shown that, in human primary thyrocytes, RET/PTC1 induces a transcriptional program including the MET proto-oncogene. In PTCs, β-catenin is frequently mislocated to the cytoplasm nucleus. We investigated the interplay between Ret/ptc1 signaling and Met in regulating the proinvasive phenotype and β-catenin localization in cellular models of human PTC. Here, we show that Met protein is expressed and is constitutively active in human thyrocytes exogenously expressing RET/PTC1 as well as a mutant (Y451F devoid of the main Ret/ptc1 multidocking site. Both in transformed thyrocytes and in the human PTC cell line TPC-1, Ret/ptc1-Y451-dependent signaling and Met cooperated to promote a proinvasive phenotype. Accordingly, gene/functional silencing of either RET/PTC1 or MET abrogated early branching morphogenesis in TPC-1 cells. The same effect was obtained by blocking the common downstream effector Akt. Y451 of Ret/ptc1 was required to promote proliferation and nuclear translocation of β-catenin, suggesting that these oncogene-driven effects are Met-independent. Pharmacologic inhibition of Ret/ptc1 and Met tyrosine kinases by the multitarget small molecule RPI-1 blocked cell proliferation and invasive ability and dislocated β-catenin from the nucleus. Altogether, these results support that Ret/ptc1 cross talks with Met at transcriptional and signaling levels and promotes β-catenin transcriptional activity to drive thyrocyte neoplastic transformation. Such molecular network, promoting disease initiation and acquisition of a proinvasive phenotype, highlights new options to design multitarget therapeutic strategies for PTCs.

Early and Middle Jurassic climate changes: implications for palaeoceanography and tectonics

DEFF Research Database (Denmark)

Korte, Christoph; Hesselbo, Stephen; Ullmann, Clemens Vinzenz

2014-01-01

The occurrence of ‘ice ages’ within the overall warm Jurassic Period has been the subject of much discussion and not a little controversy. Recently it has been suggested on the basis of occurrence of glendonites in circum-Arctic basins that cold episodes took place in the Jurassic (Price, 1999; R...... by substantial changes in oceanic current patterns which were initiated by a major tectonic uplift that prevented the transport of heat to Polar Regions....... three pronounced oxygen isotope ‘Ice Age’ cycles, and the subsequent well known Toarcian Oceanic Anoxic ‘supergreenhouse’ Event is followed by very warm seawater temperatures in the late Toarcian. Moreover, a very pronounced and effective cooling occurred during the latest Toarcian and early Aalenian...... (Early-Middle Jurassic Boundary Event) resulted in substantial expansion of Arctic climates to palaeolatitudes as low as 45° and in distinctly cooler seawater temperatures in lower latitude European seas. At least the extensive cooling at the Early-Middle Jurassic Boundary Event was most likely driven...

Screening colonoscopy for the detection of neoplastic lesions in asymptomatic HIV-infected subjects.

Science.gov (United States)

Bini, E J; Green, B; Poles, M A

2009-08-01

Although non-AIDS defining malignancies are rapidly increasing as HIV-infected subjects live longer, little is know about the results of screening for colonic neoplasms (adenomatous polyps and adenocarcinomas) in this population. We conducted a screening colonoscopy study to determine the prevalence of colonic neoplasms in 136 asymptomatic HIV-infected subjects >or=50 years of age and 272 asymptomatic uninfected control subjects matched for age, sex, and family history of colorectal cancer. Advanced neoplasms were defined as adenomas >or=10 mm or any adenoma, regardless of size, with villous histology, high-grade dysplasia, or adenocarcinoma. The prevalence of neoplastic lesions was significantly higher in HIV-infected subjects than in control subjects (62.5% vs 41.2%, pscreening colonoscopy should be offered to HIV-infected subjects, but the age of initiation and the optimal frequency of screening require further study.

Early Childhood Development Policy and Programming in India: Critical Issues and Directions for Paradigm Change

Science.gov (United States)

Sharma, Adarsh; Sen, Rekha Sharma; Gulati, Renu

2008-01-01

The critical importance of the early childhood years and the rights perspective to human development has made policy and programming for early childhood development an imperative for every nation. In India, poverty, changing economic and social structures resulting in the breakdown of traditional coping mechanisms and family care systems, and the…

[Early detection of cervical cancer in Chile: time for change].

Science.gov (United States)

Léniz Martelli, Javiera; Van De Wyngard, Vanessa; Lagos, Marcela; Barriga, María Isabel; Puschel Illanes, Klaus; Ferreccio Readi, Catterina

2014-08-01

Mortality rates for cervical cancer (CC) in Chile are higher than those of developed countries and it has an unequal socioeconomic distribution. The recognition of human papilloma virus (HPV) as the causal agent of cervical cancer in the early 80's changed the prevention paradigms. Current goals are to prevent HPV infection by vaccination before the onset of sexual activity and to detect HPV infection in women older than 30 years. This article reviews CC prevention and early detection methods, discusses relevant evidence to support a change in Chile and presents an innovation proposal. A strategy of primary screening based on HPV detection followed by triage of HPV-positive women by colposcopy in primary care or by cytological or molecular reflex testing is proposed. Due to the existence in Chile of a well-organized nationwide CC prevention program, the replacement of a low-sensitivity screening test such as the Papanicolau test with a highly sensitive one such as HPV detection, could quickly improve the effectiveness of the program. The program also has a network of personnel qualified to conduct naked-eye inspections of the cervix, who could easily be trained to perform triage colposcopy. The incorporation of new prevention strategies could reduce the deaths of Chilean women and correct inequities.

Three-dimensional lithographically-defined organotypic tissue arrays for quantitative analysis of morphogenesis and neoplastic progression

Energy Technology Data Exchange (ETDEWEB)

Nelson, Celeste M.; Inman, Jamie L.; Bissell, Mina J.

2008-02-13

Here we describe a simple micromolding method to construct three-dimensional arrays of organotypic epithelial tissue structures that approximate in vivo histology. An elastomeric stamp containing an array of posts of defined geometry and spacing is used to mold microscale cavities into the surface of type I collagen gels. Epithelial cells are seeded into the cavities and covered with a second layer of collagen. The cells reorganize into hollow tissues corresponding to the geometry of the cavities. Patterned tissue arrays can be produced in 3-4 h and will undergo morphogenesis over the following one to three days. The protocol can easily be adapted to study a variety of tissues and aspects of normal and neoplastic development.

Changes in spontaneous brain activity in early Parkinson's disease.

Science.gov (United States)

Yang, Hong; Zhou, Xiaohong Joe; Zhang, Min-Ming; Zheng, Xu-Ning; Zhao, Yi-Lei; Wang, Jue

2013-08-09

Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of pbrain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0.69). These results indicate that the abnormal resting state spontaneous brain activity associated with patients with early PD can be revealed by Reho analysis. Copyright �

Role of MMP-12 on tissue remodeling at early stage of radiation-induced pulmonary injury

International Nuclear Information System (INIS)

Li Ming; Song Liangwen; Diao Ruiying; Wang Shaoxia; Xu Xinping; Luo Qingliang

2008-01-01

Objective: To explore the role of MMP-12 on tissue remodeling at early stage of radiation- induced pulmonary injury. Methods: Wistar rats irradiated by 60 Co γ-rays to the whole lungs were sacrificed at 1, 2, 4 weeks. MMP-12 mRNA expression was detected by RT-PCR. MMP-2, MMP-9, MMP-12 activities were determined by zymography. The degradation and collapse of elastin were determined by tissue elastin particular staining; the 'cross talking' phenomenon between alveolar type II cells and mesenchymal cells was observed under electron microscope; the expression of TGF-β1 and TNF-α in BALF was detected by ELISA. The expression of α-SMA was determined by immunohistochemistry. Results: The mRNA expression of MMP-12 displayed a significant elevation at 1, 2, 4 weeks after irradiation. MMP-12 activity increased at 2, 4 weeks after irradiation. Elastin began to degrade and collapse at 1 week, which became worst 4 weeks after irradiation. The cross talking phenomenon was found under electron microscope. The expression of TGF-β1, TNF-α and α-SMA was increased gradually as time elapse after irradiation. Conclusions: 60 Co γ-ray irradiation can promote pulmonary MMP-12 expression, initiate pulmonary tissue remodeling by degradation of elastin, and make the pulmonary injury develop towards pulmonary fibrosis eventually. (authors)

Interpersonal Development, Stability, and Change in Early Adulthood

Science.gov (United States)

Wright, Aidan G. C.; Pincus, Aaron L.; Lenzenweger, Mark F.

2011-01-01

Objective This goal of this research was to explore the development of the interpersonal system mapped by the interpersonal circumplex in early adulthood (Ages 18-22). Method This study uses the Longitudinal Study of Personality Disorders sample (N = 250; 53% Female). Participants completed the Revised Interpersonal Adjective Scales (Wiggins, Trapnell, & Phillips, 1988) in their freshman, sophomore, and senior years of college. Estimates of structural, rank-order, mean, individual, and ipsative stability were calculated for the broad interpersonal dimensions of Dominance and Affiliation, and also the lower-order octant scales. Additionally, the interpersonal profile parameters of differentiation and prototypicality were calculated at each wave and explored longitudinally, and also used as predictors of interpersonal stability. Results We found excellent structural and high rank-order and ipsative stability in the interpersonal scales over this time period. Mean increases on the Affiliation axis, but not on the Dominance axis, were found to mask differential rates of change among the octant scales, along with significant individual variation in the rates of change. Interpersonal differentiation and prototypicality were related to higher stability in overall interpersonal style. Conclusions Results point to evidence of both stability and nuanced change, illuminating some of the features of the structural variables that can be derived from interpersonal circumplex profiles. PMID:22224462

Early Articular Cartilage MRI T2 Changes After Anterior Cruciate Ligament Reconstruction Correlate With Later Changes in T2 and Cartilage Thickness

Science.gov (United States)

Williams, Ashley; Winalski, Carl S.; Chu, Constance R.

2018-01-01

Anterior cruciate ligament (ACL) injury is a known risk factor for future development of osteoarthritis (OA). This human clinical study seeks to determine if early changes to cartilage MRI T2 maps between baseline and 6 months following ACL reconstruction (ACLR) are associated with changes to cartilage T2 and cartilage thickness between baseline and 2 years after ACLR. Changes to T2 texture metrics and T2 mean values in medial knee cartilage of 17 human subjects 6 months after ACLR were compared to 2-year changes in T2 and in cartilage thickness of the same areas. T2 texture and mean assessments were also compared to that of 11 uninjured controls. In ACLR subjects, six-month changes in mean T2 correlated to 2-year changes in mean T2 (R = 0.80, p = 0.0001), and 6-month changes to T2 texture metrics, but not T2 mean, correlated with 2-year changes in medial femoral cartilage thickness in 9 of the 20 texture features assessed (R = 0.48–0.72, p ≤ 0.05). Both mean T2 and texture differed (p evaluation of T2 map and textural changes may provide early warning of cartilage at risk for progressive degeneration after ACL injury and reconstruction. PMID:27381512

Early evidence (ca. 12,000 B.P.) for feasting at a burial cave in Israel

OpenAIRE

Munro, Natalie D.; Grosman, Leore

2010-01-01

Feasting is one of humanity's most universal and unique social behaviors. Although evidence for feasting is common in the early agricultural societies of the Neolithic, evidence in pre-Neolithic contexts is more elusive. We found clear evidence for feasting on wild cattle and tortoises at Hilazon Tachtit cave, a Late Epipaleolithic (12,000 calibrated years B.P.) burial site in Israel. This includes unusually high densities of butchered tortoise and wild cattle remains in two structures, the u...

microstructure change in 12 % Cr steel during creep

International Nuclear Information System (INIS)

Winatapura, D. S.; Panjaitan, E.; Arslan, A.; Sulistioso, G.S.

1998-01-01

The microstructure change in steel containing of 12% Cr or DIN X20CrMoV 12 1 during creep has been studied by means of optical microscopy and Transmission Electron Microscope (TEM). The creep testing at 650 o C was conducted under constant load of 650 Mpa. The heat treatment of the specimen before creep testing was austenization, followed by tempering for 2 hours. The obtained microstructure was tempered martensitic. This microstructure consisted of the martensite laths, and distributed randomly in the matrix. During tempering, chromium carbide particles of Cr 7 C 6 less than 0,2 μmin-size were precipitated on or and in the subgrain and lath martensite grain boundary. During creep testing those particles transformed and precipitated as chrome carbide precipitates of Cr 23 C 6 . At the secondary creep stage, the void formation occurred, and then it developed into the creep cracks. At tertiary creep stage for 3554 hours, the specimen was failure. The creep cracks were informs of transgranular and intergranular modes which propagated almost perpendicular to the stress axis. From this observation, it is suggested that tempering caused the ductility of martensitic microstructure, which increased the creep resistant or Cr 12% steel

Radiobiological studies on the importance of tumor oxygenation for anti-neoplastic therapy

International Nuclear Information System (INIS)

Grau, C.

1994-01-01

The aim of the twelve studies included in the present thesis was to determine the importance of hypoxia for various anti-neoplastic treatment modalities, and to evaluate possible ways of overcoming the hypoxia problem by combined modality therapy. The murine tumor systems were the C3H mammary carcinoma with 5-12% hypoxic cells, and the SCCVII squamous cell carcinoma with 2% hypoxic cells. The radiation response was significantly improved by the use of hypoxic cell radiosensitizers such as nimorazole or misonidazole, or by allowing the mice to breathe oxygen or carbogen during irradiation. In contrast, the radiation response was significantly impaired by carbon monoxide breathing at a level comparable to what has been observed in heavy smokers. The clamped TCD 50 assay was used to classify cancer chemotherapeutic drugs according to their preferential cytotoxicity towards the different tumor subpopulations. Methotrexate had no effect on hypoxic cells and was only borderline toxic towards aerobic cells. Three drugs had significant effect against oxic cells only (5-fluorouracil, bleomycin and cisplatin). Similarly, three drugs were toxic towards hypoxic cells only (etoposide, carmustine, and mitomycin c). Three drugs were effective towards both cell types (vincristine, adriamycin, cyclophosphamide). Hypoxic cells in areas with insufficient blood supply, poor nutrition and increased acidity is known to be highly sensitive to hyperthermia. In a study where cisplatin, heat and x-rays were given together, the local tumor control was not improved when compared to radiation + heat, apparently due to a lack of enhancement in the killing of hypoxic cells. These studies have demonstrated the influence of tumor oxygenation on tumor response to treatment with drugs, hyperthermia and irradiation. New strategies targeted also against perfusion-limited hypoxia is needed. One of the most important conclusions from the present thesis can be implemented without expensive trials or

IQ at Age 12 Following a History of Institutional Care: Findings from the Bucharest Early Intervention Project

Science.gov (United States)

Almas, Alisa N.; Degnan, Kathryn A.; Nelson, Charles A.; Zeanah, Charles H.; Fox, Nathan A.

2016-01-01

Young children removed from institutions and placed into foster care or adoptive homes have been shown to experience significant gains in IQ relative to children who remain in institutions. Less is known about the long-term impact of severe early deprivation on development in late childhood. Data are presented from a follow-up of children at 12…

A Systematic Review to Define the Speech and Language Benefit of Early (<12 Months) Pediatric Cochlear Implantation.

Science.gov (United States)

Bruijnzeel, Hanneke; Ziylan, Fuat; Stegeman, Inge; Topsakal, Vedat; Grolman, Wilko

2016-01-01

This review aimed to evaluate the additional benefit of pediatric cochlear implantation before 12 months of age considering improved speech and language development and auditory performance. We conducted a search in PubMed, EMBASE and CINAHL databases and included studies comparing groups with different ages at implantation and assessing speech perception and speech production, receptive language and/or auditory performance. We included studies with a high directness of evidence (DoE). We retrieved 3,360 articles. Ten studies with a high DoE were included. Four articles with medium DoE were discussed in addition. Six studies compared infants implanted before 12 months with children implanted between 12 and 24 months. Follow-up ranged from 6 months to 9 years. Cochlear implantation before the age of 2 years is beneficial according to one speech perception score (phonetically balanced kindergarten combined with consonant-nucleus-consonant) but not on Glendonald auditory screening procedure scores. Implantation before 12 months resulted in better speech production (diagnostic evaluation of articulation and phonology and infant-toddler meaningful auditory integration scale), auditory performance (Categories of Auditory Performance-II score) and receptive language scores (2 out of 5; Preschool Language Scale combined with oral and written language skills and Peabody Picture Vocabulary Test). The current best evidence lacks level 1 evidence studies and consists mainly of cohort studies with a moderate to high risk of bias. Included studies showed consistent evidence that cochlear implantation should be performed early in life, but evidence is inconsistent on all speech and language outcome measures regarding the additional benefit of implantation before the age of 12 months. Long-term follow-up studies are necessary to provide insight on additional benefits of early pediatric cochlear implantation. © 2016 S. Karger AG, Basel.

Changes in the welfare state and the ethics of early childhood educators

DEFF Research Database (Denmark)

Hjort, Katrin

2016-01-01

Ethical reflection is more relevant than ever before. As a reaction to both the trend of utilitarianism in early childhood education and the changes in the organisation of welfare sevices in the Nordic countries a professional ethics of virtue must be revitalized. However, it is not an easy path...

Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator

Science.gov (United States)

Zheng, Louise D.; Linarelli, Leah E.; Brooke, Joseph; Smith, Cayleen; Wall, Sarah S.; Greenawald, Mark H.; Seidel, Richard W.; Estabrooks, Paul A.; Almeida, Fabio A.; Cheng, Zhiyong

2016-01-01

Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention. PMID:27298712

Laparoscopic sleeve gastrectomy in patients over 59 years: early recovery and 12-month follow-up.

Science.gov (United States)

Leivonen, Marja Kaarina; Juuti, Anne; Jaser, Nabil; Mustonen, Harri

2011-08-01

Bariatric surgery has shown to be safe for patients over 60 years with good results especially considering resolving of comorbidities. Sleeve gastrectomy is considered to be safer than gastric bypass (GBP) and more effective than gastric banding with less adverse symptoms. Weight loss may be more modest than after GBP, but the effect on vitamins may also be milder. Since 2007, we collected prospectively 12-month follow-up data from 55 sleeve gastrectomy patients of whom 12 were over 59 years of age. Vitamin and calcium supplements were used postoperatively. The recovery from the operation was recorded during hospital stay, at 1- and 12-month follow-up visits using a standard protocol including laboratory tests. The results between patients over and under 59 years were compared. The preoperative weight and weight loss were comparable between the groups. Operation time was shorter and hospital stay was longer for older patients, p = ns. There was no operative mortality. Early major complications were seen more often in the older age group, 42% vs 9% (p = 0.02), but late complications were more common in younger patients, 17% vs 44%, p = ns. Early complications were mostly bleedings, which did not lengthen the hospital stay, neither were re-operations nor endoscopic procedures needed. Excess weight loss and resolving of comorbidities after 12 months was comparable between the groups. However, vitamin deficiencies and hypoalbuminemia were more common in the older age group, 42% and 23% for vitamins and 44% and 29% for proteins, p = ns. The older patients had more adverse effects related to surgery, 25% vs 9%, and younger had more adverse psychiatric effects, p = ns. Sleeve gastrectomy is effective and safe for older bariatric patients. Weight loss is comparable to younger patients and enough to resolve the comorbidities in most of the patients. With standardized nutritional supplementation, the older patients had more often vitamin deficiencies and

California forests show early indications of both range shifts and local persistence under climate change

Science.gov (United States)

Josep M. Serra-Diaz; Janet Franklin; Whalen W. Dillon; Alexandra D. Syphard; Frank W. Davis; Ross K. Meentemeyer

2015-01-01

Aim Forest regeneration data provide an early signal of the persistence and migration of tree species, so we investigated whether species shifts due to climate change exhibit a common signal of response or whether changes vary by species. Location California Floristic Province, United...

The diagnostic value of sacroiliac CT for detecting early changes of ankylosing spondylitis

Energy Technology Data Exchange (ETDEWEB)

Park, Ju Hyun; Park, Ji Seon; Ryu, Kyung Nam [Kyunghee University Medical Center, Seoul (Korea, Republic of); Jin, Wook [East-West Neo Medical Center, Seoul (Korea, Republic of)

2007-02-15

We wanted to evaluate the diagnostic value of the various findings on sacroiliac CT for detecting the early changes of ankylosing spondylitis (AS). Between April 2005 and March 2006, 51 sacroiliac CT images with the clinical suspicion of AS, but no definite evidence of AS on the plain radiograph only, were retrospectively reviewed. Finally, 36 patients (mean age: 28.6 years; 34 males and 2 females), who were clinically diagnosed as AS (AS group, n = 26) or they had no evidence of AS (non-AS group, n = 10), were evaluated. Two musculoskeletal radiologists analyzed the presence of marginal irregularity, bony erosion and subchondral sclerosis. A statistical analysis was performed to evaluate the incidence, sensitivity and specificity of each finding. Marginal irregularity was seen in 21 of 26 AS subjects, and in 8 of 10 non-AS subjects. Bony erosion was only seen in 13 of 26 AS subjects. Subchondral sclerosis was observed in 19 of 26 AS subjects and in 8 of 10 non-AS subjects. The sensitivity/specificity for each findings were 72.4%/28.6%, 100%/43.5% and 70.4%/22.2%, respectively. Except for bony erosions, these results showed no statistical significance ({rho} = .006). Bony erosion on CT is a very sensitive finding for the early changes of AS, whereas marginal irregularity or subchondral sclerosis is not so helpful in differentiating AS from non-AS. Attention to these results may further enhance the accurate diagnosis of the early changes in AS.

RET/PTC1-Driven Neoplastic Transformation and Proinvasive Phenotype of Human Thyrocytes Involve Met Induction and β-Catenin Nuclear Translocation1

Science.gov (United States)

Cassinelli, Giuliana; Favini, Enrica; Degl'Innocenti, Debora; Salvi, Alessandro; De Petro, Giuseppina; Pierotti, Marco A; Zunino, Franco; Borrello, Maria Grazia; Lanzi, Cinzia

2009-01-01

Activation of the RET gene by chromosomal rearrangements generating RET/PTC oncogenes is a frequent, early, and causative event in papillary thyroid carcinoma (PTC). We have previously shown that, in human primary thyrocytes, RET/PTC1 induces a transcriptional program including the MET proto-oncogene. In PTCs, β-catenin is frequently mislocated to the cytoplasm nucleus. We investigated the interplay between Ret/ptc1 signaling and Met in regulating the proinvasive phenotype and β-catenin localization in cellular models of human PTC. Here, we show that Met protein is expressed and is constitutively active in human thyrocytes exogenously expressing RET/PTC1 as well as a mutant (Y451F) devoid of the main Ret/ptc1 multidocking site. Both in transformed thyrocytes and in the human PTC cell line TPC-1, Ret/ptc1-Y451-dependent signaling and Met cooperated to promote a proinvasive phenotype. Accordingly, gene/functional silencing of either RET/PTC1 or MET abrogated early branching morphogenesis in TPC-1 cells. The same effect was obtained by blocking the common downstream effector Akt. Y451 of Ret/ptc1 was required to promote proliferation and nuclear translocation of β-catenin, suggesting that these oncogene-driven effects are Met-independent. Pharmacologic inhibition of Ret/ptc1 and Met tyrosine kinases by the multitarget small molecule RPI-1 blocked cell proliferation and invasive ability and dislocated β-catenin from the nucleus. Altogether, these results support that Ret/ptc1 cross talks with Met at transcriptional and signaling levels and promotes β-catenin transcriptional activity to drive thyrocyte neoplastic transformation. Such molecular network, promoting disease initiation and acquisition of a proinvasive phenotype, highlights new options to design multitarget therapeutic strategies for PTCs. PMID:19107227

How Does Early Feedback in an Online Programming Course Change Problem Solving?

Science.gov (United States)

Ebrahimi, Alireza

2012-01-01

How does early feedback change the programming problem solving in an online environment and help students choose correct approaches? This study was conducted in a sample of students learning programming in an online course entitled Introduction to C++ and OOP (Object Oriented Programming) using the ANGEL learning management system platform. My…

Early changes of parotid density and volume predict modifications at the end of therapy and intensity of acute xerostomia.

Science.gov (United States)

Belli, Maria Luisa; Scalco, Elisa; Sanguineti, Giuseppe; Fiorino, Claudio; Broggi, Sara; Dinapoli, Nicola; Ricchetti, Francesco; Valentini, Vincenzo; Rizzo, Giovanna; Cattaneo, Giovanni Mauro

2014-10-01

To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer. Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients. A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher "mean" acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm(3)/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.

Stroboscopy and imaging in interdisciplinary diagnosis of early stages of carcinoma of the larynx

International Nuclear Information System (INIS)

Bigenzahn, W.; Denk, D.M.; Fruehwald, F.

1998-01-01

The laryngostroboscopy is regarded to be the most important functional investigation in laryngologic and phoniatric diagnostics. She allows an analysis of vocal fold vibrations during phonation. Stroboscopic evaluations permit to early detect infiltrative processes of the vocal folds. Superficial alterations of the mucous membrane that invade into the muscle cause a phonatory 'standstill' of the vocal fold in the stroboscopy, i.e. a complete lack of vibratory motion. If such a phonatory standstill persists for more than 2 or 3 weeks, a biopsy via microlaryngoscopy is indicated for diagnostic purposes. In comparison to stroboscopy, imaging techniques are not of such great significance in early laryngeal cancer. But in case of suspected infiltration of the tumor a further diagnostic evaluation with CT or MRI is necessary to detect possible neoplastic invasion of the laryngeal cartilage or of extralaryngeal structures. In this paper, we present the principle of laryngostroboscopy, the examination procedure and the stroboscopic parameters. Case reports of early laryngeal cancer illustrate the interdisciplinary diagnostic procedure with CT, MRI and stroboscopy. (orig.) [de

STUDY OF OVARIAN CHANGES IN RATS WITH MAMMARY CARCINOMAS

Directory of Open Access Journals (Sweden)

Maja Zečević

2013-03-01

Full Text Available The aim of this study was to estimate ovarian changes in 7,12 dimethylbenz (α anthracene (DMBA induced rat mammary carcinomas. The study was carried out on female virgin albino Wistar rats (n=35, age=35-37days, body mass 120-140g, divided into control (n=10 and experimental group (n=25. Anesthetised animals of experimental group were inoculated with 2 mg mixture (1 mg of DMBA and 1 mg of cholesterol-buffer into the fifth left mammary gland. The animals were sacrificed 90 days after implantation, and ovaries and mammary glands were investigated. Mammary gland carcinomas (in situ and/or invasive were pathohistologically verified in 19 experimental animals. Histological, histochemical, and immunohistochemical (cytokeratin AE1/AE3 and PCNA studies of ovaries were performed.Besides non-neoplastic changes, such as decrease in ovary’s volume, reduction in the rate of follicular development and numerous corpora lutea formation were found in the vicinity of preneoplastic changes: papillomatous epithelial hyperplasia and inclusion cysts, microglandular formations with dysplasia and seromucinous microcystic formation. Intensive diffuse PCNA expression was present in the epithelium of glandlike structures, follicular and inclusion cysts.These morphological changes confirmed that DMBA is a pluripotent carcinogen capable to induce a wide spectrum of preneoplastic lesions in the ovaries. The present dilemma is whether the changes described are the consequence of the direct effects of DMBA or of hormonal activity of the induced breast carcinomas, or both.

SV40 T antigen alone drives karyotype instability that precedes neoplastic transformation of human diploid fibroblasts.

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Ray, F A; Peabody, D S; Cooper, J L; Cram, L S; Kraemer, P M

1990-01-01

To define the role of SV40 large T antigen in the transformation and immortalization of human cells, we have constructed a plasmid lacking most of the unique coding sequences of small t antigen as well as the SV40 origin of replication. The promoter for T antigen, which lies within the origin of replication, was deleted and replaced by the Rous sarcoma virus promoter. This minimal construct was co-electroporated into normal human fibroblasts of neonatal origin along with a plasmid containing the neomycin resistance gene (neo). Three G418-resistant, T antigen-positive clones were expanded and compared to three T antigen-positive clones that received the pSV3neo plasmid (capable of expressing large and small T proteins and having two origins of replication). Autonomous replication of plasmid DNA was observed in all three clones that received pSV3neo but not in any of the three origin minus clones. Immediately after clonal expansion, several parameters of neoplastic transformation were assayed. Low percentages of cells in T antigen-positive populations were anchorage independent or capable of forming colonies in 1% fetal bovine serum. The T antigen-positive clones generally exhibited an extended lifespan in culture but rarely became immortalized. Large numbers of dead cells were continually generated in all T antigen-positive, pre-crisis populations. Ninety-nine percent of all T antigen-positive cells had numerical or structural chromosome aberrations. Control cells that received the neo gene did not have an extended life span, did not have noticeable numbers of dead cells, and did not exhibit karyotype instability. We suggest that the role of T antigen protein in the transformation process is to generate genetic hypervariability, leading to various consequences including neoplastic transformation and cell death.

REPEATED TREATMENTS WITH DOXORUBICIN CAUSES ELECTROCARDIOGRAM (ECG) CHANGES AND INCREASED VENTRICULAR PREMATURE BEATS IN WISTAR-KYOTO (WKY) RATS

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Doxorubicin (DOX) is a widely used anthracycline anti-neoplastic drug used to treat tumors. However it has been implicated in irreversible cardiac toxicity via the generation of a proxidant semiquinone free radical, which often results in cardiomyopathy and changes in the ECG. Ac...

Changes in mediators of inflammation and pro-thrombosis after 12 ...

African Journals Online (AJOL)

Changes in mediators of inflammation and pro-thrombosis after 12 months of dietary modification in adults with metabolic syndrome. S.K. Rahamon, U.A. Fabian, M.A. Charles-Davies, J.A. Olaniyi, A.A. Fasanmade, K.S. Akinlade, O.E. Oyewole, M.O. Owolabi, J.R. Adebusuyi, O.O. Hassan, B.M. Ajobo, M.O. Ebesunun, ...

The efficacy of low-dose helical CT screening as an option for health examination

International Nuclear Information System (INIS)

Kishi, Kazuma; Hara, Shigeko; Kurosaki, Atsuko; Fujii, Takeshi; Yoshimura, Kunihiko

2007-01-01

We retrospectively evaluated the results of low-dose helical CT screening as an option for health examinations. From November 2002 to October 2005, CT screening was performed in 2,306 individuals (men 1,766, women 540, mean age 56.1 years). Among them, 71 individuals (3.1%) were diagnosed as having active thoracic diseases consisting of 14 neoplasms and 57 non-neoplastic diseases. Of 14 patients with neoplastic lesions, 13 had lung cancer, 1 of whom had double primary lung cancer, and 1 had atypical adenomatous hyperplasia. The mean diameter of the 14 lung cancers was 14.4 mm. The histology of these lesions was adenocarcinoma in 13 and squamous cell carcinoma in 1. The pathological stage was IA in 12 patients and IIA in 1. All patients underwent surgical resection. On the other hand, emphysema was diagnosed in 40 asymptomatic individuals based on CT and spirometry, and smoking cessation was strongly implemented for those who were current smokers. CT screening is useful for detecting not only early lung cancer but also non-neoplastic lung diseases. (author)

Coping with a changing environment: The effects of early life stress

DEFF Research Database (Denmark)

Vindas, Marco A.; Madaro, Angelico; Fraser, Thomas W.K.

2016-01-01

to environmental changes is particularly evident at early life stages. We investigated the performance of salmon, previously subjected to an unpredictable chronic stress (UCS) treatment at an early age (10 month old parr), over several months and life stages. The UCS fish showed overall higher specific growth...... rates compared with unstressed controls after smoltification, a particularly challenging life stage, and after seawater transfer. Furthermore, subjecting fish to acute stress at the end of the experiment, we found that UCS groups had an overall lower hypothalamic catecholaminergic and brain stem...... serotonergic response to stress compared with control groups. In addition, serotonergic activity was negatively correlated with final growth rates,which implies that serotonin responsive individuals have growth disadvantages. Altogether, our results may imply that a subduedmonoaminergic response in stressful...

Social change in ‘Phoenicia’ in the late Bronze/early Iron Age transition

OpenAIRE

Boyes, Philip

2013-01-01

This dissertation explores social, cultural and political changes in the region later known as ‘Phoenicia’ during the period of approximately 1300-900 BC. By applying modern approaches to theoretical questions such as the nature of social change, identity, migration and how such phenomena are represented in the archaeological record, this dissertation aims to provide a discussion of Late Bronze/Early Iron Age Phoenicia based on a more solid methodological foundation than has of...

Family Relationships from Adolescence to Early Adulthood: Changes in the Family System following Firstborns' Leaving Home

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Whiteman, Shawn D.; McHale, Susan M.; Crouter, Ann C.

2011-01-01

This study charted the course of parent-child and sibling relationships from early adolescence to early adulthood and examined how these relationships changed following firstborns' departure from their parents' home for the first time. Data were drawn from a 10-year longitudinal study of family relationships. Participants included mothers,…

Network based early warning indicators of vegetation changes in a land–atmosphere model

NARCIS (Netherlands)

Yin, Z.; Dekker, S.C.; Rietkerk, M.; Hurk, B.J.J.M. van den; Dijkstra, H.A.

2016-01-01

Abstract Numerous model studies demonstrate that ecosystems might not shift smoothly with a gradual change in resource concentration. At specific points, vegetation can suddenly shift from one stable state to another. To predict such undesirable shifts, statistical indicators are proposed for early

Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations

OpenAIRE

Irfan Affan Bin; Reichlin Tobias R.; Twerenbold Raphael; Meister Marc; Moehring Berit; Wildi Karin; Bassetti Stefano; Zellweger Christa; Gimenez Maria Rubini; Hoeller Rebeca; Murray Karsten; Sou SeoungMann; Mueller Mira; Mosimann Tamina; Reiter Miriam

2013-01-01

Background: Absolute changes in high sensitivity cardiac troponin T (hs cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high sensitivity cardiac troponin I (hs cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. Methods: In a prospective international multicenter study high sensitivity cardiac troponin (hs cTn) was ...

Photodetection of early cancer by laser-induced fluorescence of a tumor-selective dye: apparatus design and realization

Science.gov (United States)

Wagnieres, Georges A.; Depeursinge, Christian D.; Monnier, Philippe; Savary, Jean-Francois; Cornaz, Piet F.; Chatelain, Andre; van den Bergh, Hubert

1990-07-01

An apparatus is designed and realized to detect "early" cancer at the surface of the hollow organs in the human body by endoscopic means. The tumor is localized by the laser induced fluorescence of a dye (HPD) which concentrates selectively in the neoplastic tissue after intravenous injection. Fluorescence contrast between the tumor and its normal surroundings is enhanced by subtracting the background autofluorescence which occurs in both types of tissue. This is done by means of 2-color digital images manipulation in real-time. Preliminary clinical tests of the apparatus demonstrated the detection of carcinoma in situ in the esophagus.

Loss of a putative tumor suppressor locus after gamma-ray-induced neoplastic transformation of HeLa x Skin fibroblast human cell hybrids

International Nuclear Information System (INIS)

Mendonca, M.S.; Redpath, J.L.; Fasching, C.L.

1995-01-01

The nontumorigenic HeLa x skin fibroblast hybrid cell line, CGL1, can be induced to re-express HeLa tumor-associated cell surface antigen, p75-IAP (intestinal alkaline phosphatase), with resulting neoplastic transformation, by exposure to γ radiation. This has allowed the human hybrid system to be developed into a quantitative in vitro model for radiation-induced neoplastic transformation of human cells. Recently, several γ-ray-induced IAP-expression mutants (GIMs) of the nontumorigenic HeLa x skin fibroblast hybrid CGL1 were isolated and all were tumorigenic when injected subcutaneously into nude mice. Control cell lines which were negative for p75-IAP (CONs) were also isolated from irradiated populations, and none were found to be tumorigenic. We have now begun to investigate the molecular basis of radiation-induced neoplastic transformation in this system by studying the potential genetic linkage between p75/IAP expression, tumorigenicity and damage to a putative tumor suppressor locus on fibroblast chromosome 11. Previous analysis of rare spontaneous segregants has indicated that this locus is involved in the regulation of tumorigenicity and in the expression of the HeLa tumor-associated cell surface marker intestinal alkaline phosphatase (p75-IAP) in this system. Therefore, analysis by restriction fragment length polymorphism and chromosome painting have been performed for chromosome 11, and for chromosome 13 as a control, for the p75/IAP-positive GIM and p75/IAP-negative CON cell lines. We report that in five of eight of the GIMs large-scale damage to the fibroblast chromosome 11's is evident (four GIMs have lost one complete copy of a fibroblast chromosome 11 heavily damaged). None of the CONs, however (0/5), have lost a complete copy of either fibroblast chromosome 11. No large-scale damage to the control chromosome 13's was detected in the GIMs or CONs. 49 refs., 3 figs., 2 tabs

Holo-transcobalamin is an indicator of vitamin B-12 absorption in healthy adults with adequate vitamin B-12 status

DEFF Research Database (Denmark)

von Castel-Roberts, Kristina M; Mørkbak, Anne Louise; Nexo, Ebba

2007-01-01

BACKGROUND: It has been hypothesized that the response of holo-transcobalamin (holo-TC) to oral vitamin B-12 may be used to assess absorption. To develop a reliable clinical absorption test that uses holo-TC, it is necessary to determine the optimal timeline for vitamin B-12 administration...... and postdose assessment. OBJECTIVE: The objective of this study was to assess the magnitude and patterns of change in the postabsorption response of holo-TC to oral vitamin B-12. DESIGN: Adult (18-49 y) male and female participants (n = 21) with normal vitamin B-12 status were given three 9-mug doses...... of vitamin B-12 at 6-h intervals beginning early morning (baseline) on day 1. Blood was drawn at 17 timed intervals over the course of 3 d for the analysis of holo-TC and other indicators of vitamin B-12 status. RESULTS: Mean holo-TC increased significantly (P

Neoplastic Multifocal Skin Lesions: Biology, Etiology, and Targeted Therapies for Nonmelanoma Skin Cancers.

Science.gov (United States)

Fernandes, Ana R; Santos, Ana C; Sanchez-Lopez, Elena; Kovačević, Andjekla B; Espina, Marta; Calpena, Ana C; Veiga, Francisco J; Garcia, Maria L; Souto, Eliana B

2018-01-01

Neoplastic skin lesions are multifocal, diffuse skin infiltrations of particular relevance in the differential diagnosis of ulcerative, nodular, or crusting skin lesions. Nonmelanoma skin cancers (NMSCs), namely, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and also actinic keratosis (AK), are the most common malignant tumors in humans. BCCs do not proliferate rapidly and most of the times do not metastasize, while SCCs are more infiltrative, metastatic, and destructive. AKs are precursor lesions of cutaneous SCCs. The classical therapy of NMSCs makes use of photodynamic therapy associated with chemotherapeutics. With improved understanding of the pathological mechanisms of tumor initiation, progression, and differentiation, a case is made towards the use of targeted chemotherapy with the intent to reduce the cytotoxicity of classical treatments. The present review aims to describe the current state of the art on the knowledge of NMSC, including its risks factors, oncogenes, and skin carcinogenesis, discussing the classical therapy against new therapeutic options. © 2017 S. Karger AG, Basel.

Epigenetic change in e-cardherin and COX-2 to predict chronic periodontitis

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Wang Min

2010-11-01

Full Text Available Abstract Background DNA methylation of certain genes frequently occurs in neoplastic cells. Although the cause remains unknown, many genes have been identified with such atypical methylation in neoplastic cells. The hypermethylation of E-Cadherin and Cyclooxygenase 2 (COX-2 in chronic inflammation such as chronic periodontitis may demonstrate mild lesion/mutation epigenetic level. This study compares the hypermethylation status of E-Cadherin and COX-2 genes which are often found in breast cancer patients with that in chronic periodontitis. Methods Total DNA was extracted from the blood samples of 108 systemically healthy non-periodontitis subjects, and the gingival tissues and blood samples of 110 chronic periodontitis patient as well as neoplastic tissues of 106 breast cancer patients. Methylation-specific PCR for E-Cadherin and COX-2 was performed on these samples and the PCR products were analyzed on 2% agarose gel. Results Hypermethylation of E-Cadherin and COX-2 was observed in 38% and 35% of the breast cancer samples, respectively. In chronic periodontitis patients the detection rate was 25% and 19% respectively, and none was found in the systemically healthy non-periodontitis control subjects. The hypermethylation status was shown to be correlated among the three groups with statistical significance (p Conclusions This set of data shows that the epigenetic change in E-Cadherin and Cyclooxygenase-2 is associated with chronic periodontitis. The epigenetic changes presented in chronic inflammation patients might demonstrate an irreversible destruction in the tissues or organs similar to the effects of cancer. Chronic periodontitis to some extent might be associated with DNA hypermethylation which is related to cancer risk factors.

Physical and chemical stability of proflavine contrast agent solutions for early detection of oral cancer.

Science.gov (United States)

Kawedia, Jitesh D; Zhang, Yan-Ping; Myers, Alan L; Richards-Kortum, Rebecca R; Kramer, Mark A; Gillenwater, Ann M; Culotta, Kirk S

2016-02-01

Proflavine hemisulfate solution is a fluorescence contrast agent to visualize cell nuclei using high-resolution optical imaging devices such as the high-resolution microendoscope. These devices provide real-time imaging to distinguish between normal versus neoplastic tissue. These images could be helpful for early screening of oral cancer and its precursors and to determine accurate margins of malignant tissue for ablative surgery. Extemporaneous preparation of proflavine solution for these diagnostic procedures requires preparation in batches and long-term storage to improve compounding efficiency in the pharmacy. However, there is a paucity of long-term stability data for proflavine contrast solutions. The physical and chemical stability of 0.01% (10 mg/100 ml) proflavine hemisulfate solutions prepared in sterile water was determined following storage at refrigeration (4-8℃) and room temperature (23℃). Concentrations of proflavine were measured at predetermined time points up to 12 months using a validated stability-indicating high-performance liquid chromatography method. Proflavine solutions stored under refrigeration were physically and chemically stable for at least 12 months with concentrations ranging from 95% to 105% compared to initial concentration. However, in solutions stored at room temperature increased turbidity and particulates were observed in some of the tested vials at 9 months and 12 months with peak particle count reaching 17-fold increase compared to baseline. Solutions stored at room temperature were chemically stable up to six months (94-105%). Proflavine solutions at concentration of 0.01% were chemically and physically stable for at least 12 months under refrigeration. The solution was chemically stable for six months when stored at room temperature. We recommend long-term storage of proflavine solutions under refrigeration prior to diagnostic procedure. © The Author(s) 2014.

Early grey matter changes in structural covariance networks in Huntington's disease.

Science.gov (United States)

Coppen, Emma M; van der Grond, Jeroen; Hafkemeijer, Anne; Rombouts, Serge A R B; Roos, Raymund A C

2016-01-01

Progressive subcortical changes are known to occur in Huntington's disease (HD), a hereditary neurodegenerative disorder. Less is known about the occurrence and cohesion of whole brain grey matter changes in HD. We aimed to detect network integrity changes in grey matter structural covariance networks and examined relationships with clinical assessments. Structural magnetic resonance imaging data of premanifest HD ( n  = 30), HD patients (n = 30) and controls (n = 30) was used to identify ten structural covariance networks based on a novel technique using the co-variation of grey matter with independent component analysis in FSL. Group differences were studied controlling for age and gender. To explore whether our approach is effective in examining grey matter changes, regional voxel-based analysis was additionally performed. Premanifest HD and HD patients showed decreased network integrity in two networks compared to controls. One network included the caudate nucleus, precuneous and anterior cingulate cortex (in HD p  covariance might be a sensitive approach to reveal early grey matter changes, especially for premanifest HD.

The contrasting effects of short-term climate change on the early recruitment of tree species.

Science.gov (United States)

Ibáñez, Inés; Katz, Daniel S W; Lee, Benjamin R

2017-07-01

Predictions of plant responses to climate change are frequently based on organisms' presence in warmer locations, which are then assumed to reflect future performance in cooler areas. However, as plant life stages may be affected differently by environmental changes, there is little empirical evidence that this approach provides reliable estimates of short-term responses to global warming. Under this premise, we analyzed 8 years of early recruitment data, seed production and seedling establishment and survival, collected for two tree species at two latitudes. We quantified recruitment to a wide range of environmental conditions, temperature, soil moisture and light, and simulated recruitment under two forecasted climatic scenarios. Annual demographic transitions were affected by the particular conditions taking place during their onset, but the effects of similar environmental shifts differed among the recruitment stages; seed production was higher in warmer years, while seedling establishment and survival peaked during cold years. Within a species, these effects also varied between latitudes; increasing temperatures at the southern location will have stronger detrimental effects on recruitment than similar changes at the northern locations. Our simulations illustrate that warmer temperatures may increase seed production, but they will have a negative effect on establishment and survival. When the three early recruitment processes were simultaneously considered, simulations showed little change in recruitment dynamics at the northern site and a slight decrease at the southern site. It is only when we considered these three stages that we were able to assess likely changes in early recruitment under the predicted conditions.

Fatal haemorrhage and neoplastic thrombosis in a captive African lion (Panthera leo) with metastatic testicular sex cord-stromal tumour.

Science.gov (United States)

Gonzales-Viera, Omar Antonio; Sánchez-Sarmiento, Angélica María; Fernandes, Natália Coelho Couto de Azevedo; Guerra, Juliana Mariotti; Ressio, Rodrigo Albergaria; Catão-Dias, José Luiz

2017-10-13

The study of neoplasia in wildlife species contributes to the understanding of cancer biology, management practices, and comparative pathology. Higher frequencies of neoplasms among captive non-domestic felids have been reported most commonly in aging individuals. However, testicular tumours have rarely been reported. This report describes a metastatic testicular sex cord-stromal tumour leading to fatal haemorrhage and thrombosis in a captive African lion (Panthera leo). During necropsy of a 16-year-old male African lion, the left testicle and spermatic cord were found to be intra-abdominal (cryptorchid), semi-hard and grossly enlarged with multiple pale-yellow masses. Encapsulated haemorrhage was present in the retroperitoneum around the kidneys. Neoplastic thrombosis was found at the renal veins opening into the caudal vena cava. Metastases were observed in the lungs and mediastinal lymph nodes. Histology revealed a poorly differentiated pleomorphic neoplasm comprised of round to polygonal cells and scattered spindle cells with eosinophilic cytoplasm. An immunohistochemistry panel of inhibin-α, Ki-67, human placental alkaline phosphatase, cytokeratin AE1/AE3, cKit, vimentin and S100 was conducted. Positive cytoplasmic immunolabeling was obtained for vimentin and S100. The gross, microscopic and immunohistochemical findings of the neoplasm were compatible with a poorly differentiated pleomorphic sex cord-stromal tumour. Cause of death was hypovolemic shock from extensive retroperitoneal haemorrhage and neoplastic thrombosis may have contributed to the fatal outcome. To our knowledge, this is the first report of sex cord-stromal tumour in non-domestic felids.

Early 21st century spatially detailed elevation changes of Jammu and Kashmir glaciers (Karakoram–Himalaya)

DEFF Research Database (Denmark)

Vijay, Saurabh; Braun, Matthias

2018-01-01

Although a number of studies indicate the regional heterogeneity of the glacier elevation and mass changes in high-mountain Asia in the early 21st century, little is known about these changes with high spatial detail for some of the regions. In this study we present respective glacier elevation a...

Changes in oscillatory dynamics in the cell cycle of early Xenopus laevis embryos.

Directory of Open Access Journals (Sweden)

Tony Y-C Tsai

2014-02-01

Full Text Available During the early development of Xenopus laevis embryos, the first mitotic cell cycle is long (∼85 min and the subsequent 11 cycles are short (∼30 min and clock-like. Here we address the question of how the Cdk1 cell cycle oscillator changes between these two modes of operation. We found that the change can be attributed to an alteration in the balance between Wee1/Myt1 and Cdc25. The change in balance converts a circuit that acts like a positive-plus-negative feedback oscillator, with spikes of Cdk1 activation, to one that acts like a negative-feedback-only oscillator, with a shorter period and smoothly varying Cdk1 activity. Shortening the first cycle, by treating embryos with the Wee1A/Myt1 inhibitor PD0166285, resulted in a dramatic reduction in embryo viability, and restoring the length of the first cycle in inhibitor-treated embryos with low doses of cycloheximide partially rescued viability. Computations with an experimentally parameterized mathematical model show that modest changes in the Wee1/Cdc25 ratio can account for the observed qualitative changes in the cell cycle. The high ratio in the first cycle allows the period to be long and tunable, and decreasing the ratio in the subsequent cycles allows the oscillator to run at a maximal speed. Thus, the embryo rewires its feedback regulation to meet two different developmental requirements during early development.

Radiation induced early delayed changes in mice brain: a 1h MRS and behavioral evaluation study

International Nuclear Information System (INIS)

Gupta, Mamta; Rana, Poonam; Haridas, Seenu; Manda, Kailash; Hemanth Kumar, B.S.; Khushu, Subash

2014-01-01

Radiation induced CNS injury can be classified as acute, early delayed and late delayed. Most of the studies suggest that acute injury is reversible whereas early delayed and late delayed injury is irreversible leading to metabolic and cognitive impairment. Extensive research has been carried out on cranial radiation induced early and late delayed changes, there are no reports on whole body radiation induced early and delayed changes. The present study was designed to observe early delayed effects of radiation during whole body radiation exposure. A total of 20 C57 male mice were divided in two groups of 10 animals each. One group was exposed to a dose of 5 Gy whole body radiation through Tele 60 Co irradiation facility with source operating at 2.496 Gy/min, while other group served as sham irradiated control. Behavioral and MR spectroscopy was carried out 3 months post irradiation. Behavioral parameters such as locomotor activity and working memory were evaluated first then followed by MR spectroscopy at 7T animal MRI system. For MRS, voxel was localised in the cortex-hippocampus region of mouse brain. MR spectra were acquired using PRESS sequence, FID was processed using LC model for quantitation. The data showed impaired cognitive functions and altered metabolite levels during early delayed phase of whole body radiation induced injury. In behavioural experiments, there was a significant impairment in the cognitive as well as exploratory functions at 3 months post irradiation in irradiated group as compared to controls. MRS results explained changes in mI, glutamine and glx levels in irradiated animals compared to controls. Altered mI level has been found to be associated with reduced cognitive abilities in many brain disorders including MCI and Alzheimer's disease. The findings of this study suggest that whole body radiation exposure may have long lasting effect on the cognitive performance. (author)

Visual Acuity Change over 12 Months in the Prospective Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study: ProgStar Report Number 6.

Science.gov (United States)

Kong, Xiangrong; Strauss, Rupert W; Cideciyan, Artur V; Michaelides, Michel; Sahel, José-Alain; Munoz, Beatriz; Ahmed, Mohamed; Ervin, Ann M; West, Sheila K; Cheetham, Janet K; Scholl, Hendrik P N

2017-11-01

To estimate the yearly rate of change of best-corrected visual acuity (BCVA) and the risk of loss 1 line or more over 1 year and to identify risk factors for BCVA loss in patients with Stargardt disease (STGD1). Multicenter, prospective cohort study. Two hundred fifty-nine patients (489 eyes) with molecularly confirmed STGD1 enrolled at 9 centers in the United States and Europe. Participants were followed up every 6 months, and data at the baseline and 6- and 12-month visits were analyzed. Best-corrected visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Standardized reporting forms were used to collect participants' characteristics and clinical observations. Linear mixed effects models were used to estimate the rate of BCVA loss. Linear models with generalized estimating equations were used to identify risk factors for BCVA loss of 1 line or more over 1 year. Change in BCVA over 1 year. Cross-sectional analysis at baseline showed that earlier symptom onset and longer duration since onset was associated with worse BCVA. Longitudinal analysis showed no overall significant change of BCVA within 12 months, but the rate of BCVA change was significantly different by baseline BCVA (P trials with 1 year's duration. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Early diagnosis of morphologic-functional changes of the airways by a simple method of inhalation scintigraphy

International Nuclear Information System (INIS)

Flierdt, E. van de; Bauer, R.; Laubenbacher, C.; Didic, M.; Langhammer, H.R.; Pabst, H.W.

1992-01-01

In order to validate a method of inhalation scintigraphy with 99m Tc-labeled human serum albumin in the early diagnosis of morphologic-functional changes of the airways 35 volunteers and patients (12 healthy non-smokers and smokers each, 11 patients with bronchitis) were studied. Deposition of the aerosol immediately after inhalation was calculated quantitatively by a ROI technique and qualitatively (scoring of central deposition, homogeneity, and recognizability of lung outline). Additionally, the regional clearance of the inhaled aerosol was determined by continuous lung imaging up to 60 min (mainly regional mucociliary removal rates). Discrimination between healthy volunteers and patients with bronchitis was possible by means of deposition patterns immediately after inhalation. On the other hand, no differences could be recognized in this way between healthy non-smokers and smokers. Regional mucociliary removal was higher in non-smokers than in smokers, but there was no difference between smokers and patients with bronchitis. (orig.) [de

Disruptive cell cycle regulation involving epigenetic downregulation of Cdkn2a (p16Ink4a) in early-stage liver tumor-promotion facilitating liver cell regeneration in rats

International Nuclear Information System (INIS)

Tsuchiya, Takuma; Wang, Liyun; Yafune, Atsunori; Kimura, Masayuki; Ohishi, Takumi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

2012-01-01

Cell cycle aberration was immunohistochemically examined in relation to preneoplastic liver cell foci expressing glutathione S-transferase placental form (GST-P) at early stages of tumor-promotion in rats with thioacetamide (TAA), a hepatocarcinogen facilitating liver cell regeneration. Immunoexpression of p16 Ink4a following exposure to other hepatocarcinogens/promoters and its DNA methylation status were also analyzed during early and late tumor-promotion stages. GST-P + liver cell foci increased cell proliferation and decreased apoptosis when compared with surrounding liver cells. In concordance with GST-P + foci, checkpoint proteins at G 1 /S (p21 Cip1 , p27 Kip1 and p16 Ink4a ) and G 2 /M (phospho-checkpoint kinase 1, Cdc25c and phospho-Wee1) were either up- or downregulated. Cellular distribution within GST-P + foci was either increased or decreased with proteins related to G 2 -M phase or DNA damage (topoisomerase IIα, phospho-histone H2AX, phospho-histone H3 and Cdc2). In particular, p16 Ink4a typically downregulated in GST-P + foci and regenerative nodules at early tumor-promotion stage with hepatocarcinogens facilitating liver cell regeneration and in neoplastic lesions at late tumor-promotion stage with hepatocarcinogens/promoters irrespective of regenerating potential. Hypermethylation at exon 2 of Cdkn2a was detected at both early- and late-stages. Thus, diverse disruptive expression of G 1 /S and G 2 /M proteins, which allows for clonal selection of GST-P + foci, results in the acquisition of multiple aberrant phenotypes to disrupt checkpoint function. Moreover, increased DNA-damage responses within GST-P + foci may be the signature of genetic alterations. Intraexonic hypermethylation may be responsible for p16 Ink4a -downregulation, which facilitates cell cycle progression in early preneoplastic lesions produced by repeated cell regeneration and late-stage neoplastic lesions irrespective of the carcinogenic mechanism.

Neoplastic progression of the human breast cancer cell line G3S1 is associated with elevation of cytoskeletal dynamics and upregulation of MT1-MMP

Czech Academy of Sciences Publication Activity Database

Tolde, O.; Rosel, D.; Mierke, C.T.; Paňková, D.; Folk, P.; Veselý, Pavel; Brabek, J.

2010-01-01

Roč. 36, č. 4 (2010), s. 833-839 ISSN 1019-6439 R&D Projects: GA MŠk(CZ) LC06061 Institutional research plan: CEZ:AV0Z50520514 Keywords : invasiveness * neoplastic progression * cytoskeletal dynamics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.571, year: 2010

Responses of Nucleus Tractus Solitarius (NTS) early and late neurons to blood pressure changes in anesthetized F344 rats.

Science.gov (United States)

Kolpakova, Jenya; Li, Liang; Hatcher, Jeffrey T; Gu, He; Zhang, Xueguo; Chen, Jin; Cheng, Zixi Jack

2017-01-01

Previously, many different types of NTS barosensitive neurons were identified. However, the time course of NTS barosensitive neuronal activity (NA) in response to arterial pressure (AP) changes, and the relationship of NA-AP changes, have not yet been fully quantified. In this study, we made extracellular recordings of single NTS neurons firing in response to AP elevation induced by occlusion of the descending aorta in anesthetized rats. Our findings were that: 1) Thirty-five neurons (from 46 neurons) increased firing, whereas others neurons either decreased firing upon AP elevation, or were biphasic: first decreased firing upon AP elevation and then increased firing during AP decrease. 2) Fourteen neurons with excitatory responses were activated and rapidly increased their firing during the early phase of AP increase (early neurons); whereas 21 neurons did not increase firing until the mean arterial pressure changes (ΔMAP) reached near/after the peak (late neurons). 3) The early neurons had a significantly higher firing rate than late neurons during AP elevation at a similar rate. 4) Early neuron NA-ΔMAP relationship could be well fitted and characterized by the sigmoid logistic function with the maximal gain of 29.3. 5) The increase of early NA correlated linearly with the initial heart rate (HR) reduction. 6) The late neurons did not contribute to the initial HR reduction. However, the late NA could be well correlated with HR reduction during the late phase. Altogether, our study demonstrated that the NTS excitatory neurons could be grouped into early and late neurons based on their firing patterns. The early neurons could be characterized by the sigmoid logistic function, and different neurons may differently contribute to HR regulation. Importantly, the grouping and quantitative methods used in this study may provide a useful tool for future assessment of functional changes of early and late neurons in disease models.

Evaluation of early and late complications in patients with congenital lobar emphysema: A 12 year experience

Directory of Open Access Journals (Sweden)

Nazem Masood

2010-01-01

Full Text Available Background: Congenital lobar emphysema (CLE is characterised by over distension of one lobe and pressure on the adjacent lobe and mediastinum. In this study, we review the pathological results of our paediatric patients with CLE, highlighting the early and late complications that occurred in these patients. Patients and Methods: In a prospective study from 1996 to 2008, we evaluated 30 patients with CLE diagnosis. Variables collected included sex, age at the time of diagnosis, radiological diagnostic method, type of treatment, pathological analysis, surgical findings and early postoperative complications. Parents were asked to refer to our clinic for follow-up and evaluation of late complications. Results: Thirty patients and males accounted for majority of the study population (n = 20, 67%. The mean age of male and female patients (at admission was 7.2 ± 2.3 and 4.7 ± 1.2 months respectively (P = not significant. The main diagnostic method was chest x-ray (CXR in all patients. Abnormal bronchial cartilage was found in 71% of patients. The most affected lobe was left upper lobe (50%. Associated anomalies were seen in four patients. Early postoperative periodhadtwo cases of pneumothoraces. At six month follow up, five (25% males and four females (40% had delayed weight gain. Permanent oxygen dependency was seen in two patients. Twenty- six patients underwent thoracotomy. Mortality rate was 13%. Base deficit at the time of admission was greater in those patients who eventually died, (-8.6 ± 1.2 versus -3.1 ± 0.4 (P = 0.0003. There were two deaths in the bilobar involvement group and two in the unilobar involvement group (P = 0.07, near significant. Conclusion: This study confirms that the number of affected lobes and base deficit at the time of admission were associated with significantly increased mortality.

Early changes in socioeconomic status do not predict changes in body mass in the first decade of life.

Science.gov (United States)

Starkey, Leighann; Revenson, Tracey A

2015-04-01

Many studies link childhood socioeconomic status (SES) to body mass index (BMI), but few account for the impact of socioeconomic mobility throughout the lifespan. This study aims to investigate the impact of socioeconomic mobility on changes in BMI in childhood. Analyses tested whether [1] socioeconomic status influences BMI, [2] changes in socioeconomic status impact changes in BMI, and [3] timing of socioeconomic status mobility impacts BMI. Secondary data spanning birth to age 9 were analyzed. SES and BMI were investigated with gender, birth weight, maternal race/ethnicity, and maternal nativity as covariates. Autoregressive structural equation modeling and latent growth modeling were used. Socioeconomic status in the first year of life predicted body mass index. Child covariates were consistently associated with body mass index. Rate of change in socioeconomic status did not predict change in body mass index. The findings suggest that early socioeconomic status may most influence body mass in later childhood.

Adapt or withdraw? Evidence on technological changes and early retirement using matched worker-firm data

OpenAIRE

Torbjørn Hægeland; Dag Rønningen; Kjell G. Salvanes

2007-01-01

Abstract: Older workers typically possess older vintages of skills than younger workers, and they may suffer more from technological change. Experienced workers may nevertheless have accumulated human capital making them suitable for adopting new technologies. On the other hand, to adjust to new technologies, workers must invest in training. This may not be worthwhile for the oldest workers, and technological change may thus induce early retirement. If technological change occu...

Financialization impedes climate change mitigation: Evidence from the early American solar industry

Science.gov (United States)

Jerneck, Max

2017-01-01

The article investigates how financialization impedes climate change mitigation by examining its effects on the early history of one low-carbon industry, solar photovoltaics in the United States. The industry grew rapidly in the 1970s, as large financial conglomerates acquired independent firms. While providing needed financial support, conglomerates changed the focus from existing markets in consumer applications toward a future utility market that never materialized. Concentration of the industry also left it vulnerable to the corporate restructuring of the 1980s, when the conglomerates were dismantled and solar divisions were pared back or sold off to foreign firms. Both the move toward conglomeration, when corporations became managed as stock portfolios, and its subsequent reversal were the result of increased financial dominance over corporate governance. The American case is contrasted with the more successful case of Japan, where these changes to corporate governance did not occur. Insulated from shareholder pressure and financial turbulence, Japanese photovoltaics manufacturers continued to expand investment throughout the 1980s when their American rivals were cutting back. The study is informed by Joseph Schumpeter’s theory of creative destruction and Hyman Minsky’s theory of financialization, along with economic sociology. By highlighting the tenuous and conflicting relation between finance and production that shaped the early history of the photovoltaics industry, the article raises doubts about the prevailing approach to mitigate climate change through carbon pricing. Given the uncertainty of innovation and the ease of speculation, it will do little to spur low-carbon technology development without financial structures supporting patient capital. PMID:28435862

Financialization impedes climate change mitigation: Evidence from the early American solar industry.

Science.gov (United States)

Jerneck, Max

2017-03-01

The article investigates how financialization impedes climate change mitigation by examining its effects on the early history of one low-carbon industry, solar photovoltaics in the United States. The industry grew rapidly in the 1970s, as large financial conglomerates acquired independent firms. While providing needed financial support, conglomerates changed the focus from existing markets in consumer applications toward a future utility market that never materialized. Concentration of the industry also left it vulnerable to the corporate restructuring of the 1980s, when the conglomerates were dismantled and solar divisions were pared back or sold off to foreign firms. Both the move toward conglomeration, when corporations became managed as stock portfolios, and its subsequent reversal were the result of increased financial dominance over corporate governance. The American case is contrasted with the more successful case of Japan, where these changes to corporate governance did not occur. Insulated from shareholder pressure and financial turbulence, Japanese photovoltaics manufacturers continued to expand investment throughout the 1980s when their American rivals were cutting back. The study is informed by Joseph Schumpeter's theory of creative destruction and Hyman Minsky's theory of financialization, along with economic sociology. By highlighting the tenuous and conflicting relation between finance and production that shaped the early history of the photovoltaics industry, the article raises doubts about the prevailing approach to mitigate climate change through carbon pricing. Given the uncertainty of innovation and the ease of speculation, it will do little to spur low-carbon technology development without financial structures supporting patient capital.

Early changes in left atrial volume after acute myocardial infarction

DEFF Research Database (Denmark)

Bakkestrom, R.; Andersen, Mads J; Ersboll, M.

2016-01-01

. The objective was to assess changes in LA volume early after MI in patients with diastolic dysfunction and the relation to invasive hemodynamics and natriuretic peptides. Methods: 62 patients with left ventricle ejection fraction (LVEF) >= 45%, diastolic E/e' > 8 and LA volume index >34 ml/m(2) within 48 h......Background: Dilatation of left atrium (LA) reflects chronic LA pressure or volume overload that possesses considerable prognostic information. Little is known regarding the interaction between LA remodeling after acute myocardial infarction (MI) and left atrial pressure at rest and during exercise...... of MI were enrolled. After 1 and 4 months blood sampling, echocardiography and right heart catheterization were performed during exercise test. Results: LA remodeling was considered in patients with a change from mild (35-41 ml/m(2)), to severe (>48ml/m(2)) dilatation after 4 months (Found in 22...

Preventability of early vs. late readmissions in an academic medical center.

Directory of Open Access Journals (Sweden)

Kelly L Graham

Full Text Available It is unclear if the 30-day unplanned hospital readmission rate is a plausible accountability metric.Compare preventability of hospital readmissions, between an early period [0-7 days post-discharge] and a late period [8-30 days post-discharge]. Compare causes of readmission, and frequency of markers of clinical instability 24h prior to discharge between early and late readmissions.120 patient readmissions in an academic medical center between 1/1/2009-12/31/2010.Sum-score based on a standard algorithm that assesses preventability of each readmission based on blinded hospitalist review; average causation score for seven types of adverse events; rates of markers of clinical instability within 24h prior to discharge.Readmissions were significantly more preventable in the early compared to the late period [median preventability sum score 8.5 vs. 8.0, p = 0.03]. There were significantly more management errors as causative events for the readmission in the early compared to the late period [mean causation score [scale 1-6, 6 most causal] 2.0 vs. 1.5, p = 0.04], and these errors were significantly more preventable in the early compared to the late period [mean preventability score 1.9 vs 1.5, p = 0.03]. Patients readmitted in the early period were significantly more likely to have mental status changes documented 24h prior to hospital discharge than patients readmitted in the late period [12% vs. 0%, p = 0.01].Readmissions occurring in the early period were significantly more preventable. Early readmissions were associated with more management errors, and mental status changes 24h prior to discharge. Seven-day readmissions may be a better accountability measure.

Melanocytic nevi and non-neoplastic hyperpigmentations.

Science.gov (United States)

Clemente, C

2017-06-01

This is the first of three chapters that will be progressively published on Pathologica as updating activity of the Italian Study Group of Dermatopathology (GISD), Italian Society of Pathology and Cytology (SIAPeC IAP). The first chapter concerns non-neoplastic hyperpigmented skin lesions and nevi, the second will address the topics of dysplastic nevus, borderline and low malignant potential melanocytic proliferations and the third melanoma in its variants and differential diagnoses with a supplement on the immunohistochemistry and molecular support to diagnostic and prognostic definition of nevi and melanomas. Although we believe that great advances were made in the application of ancillary genetic, immunohistochemical and molecular techniques, for the diagnosis and biological characterization of melanocytic tumors the morphology still remains the gold standard. These chapters are not intended as substitutes or even claim to be compared to the numerous and valuable texts that are also recently published, but they want to present, concisely and quickly available, all of those traits that we believe essential to the histopathological evaluation of a melanocytic lesion. No morphological parameter is exclusive and individually sufficient to make the correct diagnosis of nevus or melanoma but to reach a final conclusive and appropriate interpretation a set of morphological characters must be evaluated and compared. I was lucky enough to be able to examine several thousand cases and to draw lessons from each of these increasing my diagnostic experience. I had a great lesson by my teacher and good friend Prof. Martin C. Mihm Jr of Boston, dermato-pathologist with undisputed international reputation, who, with great passion, patience and friendship, transferred me much of his experience and knowledge and for which I always thank him. Special thanks I would like to address Dr. Agostino Crupi, dermatologist, skin-oncologist and brilliant dermatoscopist who taught me how the

Early diagnosis of myocardial infarction using absolute and relative changes in cardiac troponin concentrations.

Science.gov (United States)

Irfan, Affan; Reichlin, Tobias; Twerenbold, Raphael; Meister, Marc; Moehring, Berit; Wildi, Karin; Bassetti, Stefano; Zellweger, Christa; Gimenez, Maria Rubini; Hoeller, Rebeca; Murray, Karsten; Sou, Seoung Mann; Mueller, Mira; Mosimann, Tamina; Reiter, Miriam; Haaf, Philip; Ziller, Ronny; Freidank, Heike; Osswald, Stefan; Mueller, Christian

2013-09-01

Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. The area under the receiver operating characteristic curve for diagnosing acute myocardial infarction was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays (P Siemens, 0.96 [95% CI, 0.93-0.99]) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI assays. Reclassification analysis confirmed the superiority of absolute changes versus relative changes. Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infarction. The combination of absolute and relative changes provides a small added value for hs-cTnT, but not for hs-cTnI. Copyright © 2013 Elsevier Inc. All rights reserved.

Pancreatic endocrine tumor with neoplastic venous thrombus and bilobar liver metastasis. A case report.

Science.gov (United States)

Barbier, L; Turrini, O; Sarran, A; Delpero, J-R

2010-02-01

We report the case of an asymptomatic 56-year-old woman with a metastatic pancreatic endocrine tumor, fortuitously discovered by abdominal imaging. A CT-scan showed a large mass in the pancreatic tail invading the spleen and stomach; in addition, there was neoplastic thrombus within the spleno-mesentericoportal venous confluence and bilobar liver metastases. Surgical resection was performed in two stages. The first procedure was an extended left pancreatectomy with venous thrombectomy and "clearance" of the left hepatic lobe. During the interval, embolization of the right portal vein was carried out. Right hepatectomy and radiofrequency destruction of residual metastases was then performed. On the basis of completeness of the resection and the histopathological data, the patient did not undergo any adjuvant therapy, in accordance with French guidelines. At 1 year of follow-up, there was no evidence of recurrence. (c) 2010 Elsevier Masson SAS. All rights reserved.

Enhanced neoplastic transformation by mammography X rays relative to 200 kVp X rays: indication for a strong dependence on photon energy of the RBE(M) for various end points.

Science.gov (United States)

Frankenberg, D; Kelnhofer, K; Bär, K; Frankenberg-Schwager, M

2002-01-01

The fundamental assumption implicit in the use of the atomic bomb survivor data to derive risk estimates is that the gamma rays of Hiroshima and Nagasaki are considered to have biological efficiencies equal to those of other low-LET radiations up to 10 keV/microm, including mammography X rays. Microdosimetric and radiobiological data contradict this assumption. It is therefore of scientific and public interest to evaluate the efficiency of mammography X rays (25-30 kVp) to induce cancer. In this study, the efficiency of mammography X rays relative to 200 kVp X rays to induce neoplastic cell transformation was evaluated using cells of a human hybrid cell line (CGL1). For both radiations, a linear-quadratic dose-effect relationship was observed for neoplastic transformation of CGL1 cells; there was a strong linear component for the 29 kVp X rays. The RBE(M) of mammography X rays relative to 200 kVp X rays was determined to be about 4 for doses energies of transformation of CGL1 cells. Both the data available in the literature and the results of the present study strongly suggest an increase of RBE(M) for carcinogenesis in animals, neoplastic cell transformation, and clastogenic effects with decreasing photon energy or increasing LET to an RBE(M) approximately 8 for mammography X rays relative to 60Co gamma rays.

Protein kinase C-related kinase 1 and 2 play an essential role in thromboxane-mediated neoplastic responses in prostate cancer

OpenAIRE

O'Sullivan, Aine G.; Mulvaney, Eamon P.; Hyland, Paula B.; Kinsella, B. Therese

2015-01-01

The prostanoid thromboxane (TX) A2 is increasingly implicated in neoplastic progression, including prostate cancer (PCa). Mechanistically, we recently identified protein kinase C-related kinase (PRK) 1 as a functional interactant of both the TP? and TP? isoforms of the human T prostanoid receptor (TP). The interaction with PRK1 was not only essential for TP?/TP?-induced PCa cell migration but also enabled the TXA2-TP axis to induce phosphorylation of histone H3 at Thr11 (H3Thr11), an epigenet...

Changes in friends' and parental influences on cigarette smoking from early through late adolescence.

Science.gov (United States)

Liao, Yue; Huang, Zhaoqing; Huh, Jimi; Pentz, Mary Ann; Chou, Chih-Ping

2013-07-01

This study examined the changes in friends' and parental influences on cigarette smoking across two developmentally distinct social environments for adolescents: junior high school and high school. Longitudinal data consisting of seven repeated measures following 1,001 adolescents from 7th to 12th grade was obtained from the Midwestern Prevention Project. A two-piece Growth Curve Model (GCM) was used to assess the growth trajectory of current cigarette use: one piece for the junior high school period, and the other for the high school period. Perceived friends' and parental cigarette use were each used as a time-varying covariate in separate GCMs. Effects of friends' and parental cigarette use remained significant on adolescent cigarette smoking across the two developmental periods. The magnitude of friends' effect was in general higher during junior high school than high school. The magnitude of the parental effect remained relatively stable between the two periods. However, decreasing trends in both effects were observed from 10th to 12th grade. Gender differences also emerged. Friends' and parental effects were greater for girls in their early high school years, whereas friends' effect decreased in magnitude among girls and increased among boys during high school. The transition from junior high school to high school represents an opportunity for interventions to counteract peer influence given that such influence appeared to be much weaker during this period. However, interventions should continue to target parents as their behavior remains influential through the end of high school. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Changes in Friends’ and Parental Influences on Cigarette Smoking from Early through Late Adolescence

Science.gov (United States)

Liao, Yue; Huang, Zhaoqing; Huh, Jimi; Pentz, Mary Ann; Chou, Chih-Ping

2013-01-01

Purpose This study examined the changes in friends’ and parental influences on cigarette smoking across two developmentally distinct social environments for adolescents: junior high school and high school. Methods Longitudinal data consisting of seven repeated measures following 1,001 adolescents from 7th to 12th grade was obtained from the Midwestern Prevention Project. A two-piece Growth Curve Model (GCM) was used to assess the growth trajectory of current cigarette use: one piece for the junior high school period, and the other for the high school period. Perceived friends’ and parental cigarette use were each used as a time-varying covariate in separate GCMs. Results Effects of friends’ and parental cigarette use remained significant on adolescent cigarette smoking across the two developmental periods. The magnitude of friends’ effect was in general higher during junior high school than high school. The magnitude of the parental effect remained relatively stable between the two periods. However, decreasing trends in both effects were observed from 10th to 12th grade. Gender differences also emerged. Friends’ and parental effects were greater for girls in their early high school years, whereas friends’ effect decreased in magnitude among girls and increased among boys during high school. Conclusions The transition from junior high school to high school represents an opportunity for interventions to counteract peer influence since such influence appeared to be much weaker during this period. However, interventions should continue to target parents as their behavior remains influential through the end of high school. PMID:23583505

Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine.

Science.gov (United States)

Ogino, Shuji; Nishihara, Reiko; VanderWeele, Tyler J; Wang, Molin; Nishi, Akihiro; Lochhead, Paul; Qian, Zhi Rong; Zhang, Xuehong; Wu, Kana; Nan, Hongmei; Yoshida, Kazuki; Milner, Danny A; Chan, Andrew T; Field, Alison E; Camargo, Carlos A; Williams, Michelle A; Giovannucci, Edward L

2016-07-01

Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases, such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical/radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational/systems biology, there are wide open opportunities in MPE to contribute to public

Structural changes in complex steels with 12 % Cr during welding thermal cycle

International Nuclear Information System (INIS)

Ul'yanova, N.V.; Kurnosova, N.D.

1981-01-01

The structural changes in the heat affected zones of welded steam tubes of the 12Kh11V2MF and 18Kh12VMBFR steels, are investigated. A short-time heating of thin samples up to 1300-900 deg C with the aim of imitating the thermal welding cycle permits to determine temperatures of specific region formation in heat affeced zones of 12% Cr steels. The difference in the amounts and structure of σ-ferrite and γ-phase in these regions is established. A ''tongue'' nature of γ-phase grain growth is found in the temperature range of 1150-1100 deg C, while at 1300-1250 deg C σ-ferrite growth with the formation of saw-shape boundaries is observed. It is shown that tensile properties of imitated heat affected zone of 12Kh12VMBFP steel increase with heating temperature with the insignificant plasticity decrease. Impact strength on longitudinal samples decreases but remains higher than that determined by specifications [ru

In vitro of quantitative MR imaging of early degenerative changes in human articular cartilage

International Nuclear Information System (INIS)

Kim, Ok Wha; Lee, Young Jun; Cha, Sung Suk; Hwa, Ryu Ji

2004-01-01

To assess the applicability of quantitative MR microscopy for the detection of glycosaminoglycan (GAG) depletion as an early sign of degeneration in the articular cartilage of humans treated by trypsin. Four cartilage-bone blocks were obtained from the patient who had suffered from osteoarthritis of the knee and underwent a total knee replacement arthroscopy. Each articular cartilage segment was resected as to a round disk shape (8 mm in diameter) with a remnant of subchondral bone 1 mm in thickness. Four different culture solutions were prepared, and these solutions were 0.2 mg/ml of trypsin solution (group 1), 1 mM of Gd (DTPA) 2-mixed trypsin solution (group 2), phosphate buffered saline (PBS) (group 3), and 1 mM of Gd (DTPA) 2-mixed PBS (group 4). The cartilages were cultured and then MR imagings were performed every hour for 5 hrs, and we continued the additional cultures of 24 hrs, 36 hrs and 48 hrs. Three imaging sequences were used: T1-weighted spin echo (TR/TE, 450/22), proton density turbo spin echo with fat suppression (TR/TE, 3000/25), and CPMG (Carr-Purcell-Meiboom-Gill) (TR/TE/TI, 760/21-168, 360). MR imaging data were analyzed with pixel-by-pixel comparisons in all groups. The GAG loss in the articular cartilage was increased proportionately to the culture duration. Mean changes of T1 relaxation time were 1.2% for group 1, -1.9% for group 3, -54.7% for group 2 and -64.2% for group 4 (p< 0.05). When comparing by linear profile on the T1-weighted images, SNR increased and T1 relaxation time decreased for group 2 and 4, as the culture duration increased (p< 0.05). On the correlation analysis, there is significant correlation between GAG loss and Gd (DTPA) 2-enhancement for group 2 (p=0.0431), but there was no significant difference for group 4 (p=0.0918). More enhancement with Gd (DTPA) 2-was noted for group 2 than for group 4. Group 2 showed a diffuse enhancement in all the layers of cartilage, but for group 4, prominent enhancement was noted only in

P2Y12R-Dependent Translocation Mechanisms Gate the Changing Microglial Landscape

Directory of Open Access Journals (Sweden)

Ukpong B. Eyo

2018-04-01

Full Text Available Summary: Microglia are an exquisitely tiled and self-contained population in the CNS that do not receive contributions from circulating monocytes in the periphery. While microglia are long-lived cells, the extent to which their cell bodies are fixed and the molecular mechanisms by which the microglial landscape is regulated have not been determined. Using chronic in vivo two-photon imaging to follow the microglial population in young adult mice, we document a daily rearrangement of the microglial landscape. Furthermore, we show that the microglial landscape can be modulated by severe seizures, acute injury, and sensory deprivation. Finally, we demonstrate a critical role for microglial P2Y12Rs in regulating the microglial landscape through cellular translocation independent of proliferation. These findings suggest that microglial patrol the CNS through both process motility and soma translocation. : Using a chronic in vivo imaging approach, Eyo et al. show that the physical positions of brain microglia change daily and that these changes increase following certain experimental manipulations. The mechanism underlying these changes involves cell translocation controlled by microglial-specific P2Y12 receptors. Keywords: microglia, P2Y12, seizures, epilepsy, whisker trimming, microglial landscape, two photon chronic imaging

AN ASSOCIATION OF CYTOKINE LEVELS WITH DISEASE ACTIVITY, AUTOANTIBODY LEVELS, AND JOINT DESTRUCTIVE CHANGES IN EARLY RHEUMATOID ARTHRITIS

Directory of Open Access Journals (Sweden)

A. S. Avdeeva

2015-01-01

Full Text Available Objective: to assess the association of cytokine profile measures with disease activity, autoantibody levels, and joint destructive changes in patients with early rheumatoid arthritis (RA.Subjects and methods. Forty-five patients, including 35 women, with early RA were examined. Their median age was 53.5 [46; 59.5] years; the duration of the disease – 7.0 [4.0; 11.5] months; DAS28 – 5.8 [4.9; 6.4]; 91 and 96% of the patents were positive for rheumatoid factor (RF and anticyclic citrullinated peptide antibodies, respectively. Serum cytokine concentrations were estimated using the xMAP multiplex technology. The modified Sharp method was employed to quantify radiographic changes.Results and discussion. A group of 30 patients with high disease activity (DAS28 >5.1 had higher levels of interleukin (IL-6 (62.3 [36.1; 127.5] pg/ml and IP-10 (6367.8 [3682.7; 10691.3] pg/ml than 15 patients with moderate/low disease activity (DAS28 ≤5.1 (35.8 [13.4; 64.2] and 3222.6 [1881.0; 5671.9] pg/ml, respectively, p < 0.05. The patients highly positive for IgM RF had higher levels (pg/ml of proinflammatory cytokines, such as IL-1β, IL-2, IL-6, IL-12, IL-15, interferon-γ, and tumor necrosis factor-α; the chemokine monocyte chemotactic protein-1 and the growth factors IL-7 and vascular endothelial growth factor (4.8 [2.8; 19.3], 23.0 [7.1; 55.8], 64.2 [41.6; 170.5], 52.2 [30.9; 126.9], 2.4 [0.2; 11.2], 210.8 [119.9; 584.2], 90.7 [42.7; 307/9], 57.5 [26.1; 93.8], 54.9 [37.1; 123.7], and 143.3 [70.6; 249.6] pg/ml than those who were negative/lowly positive for IgM RF (2.3 [1.9; 3.1], 4.9 [2.9; 16.8], 24.9 [20.4; 45.4], 25.6 [19.9; 57.1], 0.2 [0.01; 1.65], 94.4 [86.3; 138.9], 37.3 [23.6; 47.7], 20.9 [12.3; 33.9], 32.6 [28.1; 37.8], 74.2 [53.5; 147.6], respectively (p < 0.05.Conclusion. There are significant differences in cytokine profile measures in patients with early RA in relation to disease activity and serum autoantibody levels.

Post-radiation changes in oral tissues - An analysis of cancer irradiation cases

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Jay Ashokkumar Pandya

2014-01-01

Full Text Available Introduction: Radiation, commonly employed as neoadjuvant, primary, and adjuvant therapy for head and neck cancer causes numerous epithelial and stromal changes, prominent among which is fibrosis with its early and late consequences. Very little is known about the true nature of the fibrosed tissue and the type of fibers accumulated. Radiotherapy affects the supporting tumor stroma often resulting in a worsening grade of tumor post-radiation. Aim: To study epithelial, neoplastic, stromal, and glandular changes in oral cavity induced by radiation therapy for oral squamous cell carcinoma (OSCC using special stains. Materials and Methods: The study included 27 samples of recurrent OSCC following completion of radiotherapy (recurrence within an average span of 11 months, and 26 non-irradiated cases of OSCC. Patients with a history of combined radiotherapy and chemotherapy were not included in the study. The epithelial changes assessed included epithelial atrophy, apoptosis, necrosis, dysplasia, and neoplasia. The connective tissue was evaluated for amount of fibrosis, quality of fibers (using picrosirius red staining, fibrinous exudate, necrosis, pattern of invasion, vessel wall thickening, and salivary gland changes. The aforementioned changes were assessed using light and polarizing microscopy and tabulated. Statistical Analysis: Epithelial and connective tissue parameters were compared between the irradiated and non-irradiated cases using chi square and t-tests. Results: Epithelial and connective tissue parameters were found to be increased in irradiated patients. Pattern of invasion by tumor cells varied from strands and  cords between the two groups studied. The effect of radiation was seen to reflect on the maturity of fibers and the regularity of their distribution.

The anti-neoplastic activity of Vandetanib against high-risk medulloblastoma variants is profoundly enhanced by additional PI3K inhibition.

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Craveiro, Rogerio B; Ehrhardt, Michael; Velz, Julia; Olschewski, Martin; Goetz, Barbara; Pietsch, Torsten; Dilloo, Dagmar

2017-07-18

Medulloblastoma is comprised of at least four molecular subgroups with distinct clinical outcome (WHO classification 2016). SHH-TP53-mutated as well as MYC-amplified Non-WNT/Non-SHH medulloblastoma show the worst prognosis.Here we present evidence that single application of the multi-kinase inhibitor Vandetanib displays anti-neoplastic efficacy against cell lines derived from high-risk SHH-TP53-mutated and MYC-amplified Non-WNT/Non-SHH medulloblastoma. The narrow target spectrum of Vandetanib along with a favourable toxicity profile renders this drug ideal for multimodal treatment approaches. In this context our investigation documents that Vandetanib in combination with the clinically available PI3K inhibitor GDC-0941 leads to enhanced cytotoxicity against MYC-amplified and SHH-TP53-mutated medulloblastoma. In line with these findings we show for MYC-amplified medulloblastoma a profound reduction in activity of the oncogenes STAT3 and AKT. Furthermore, we document that Vandetanib and the standard chemotherapeutic Etoposide display additive anti-neoplastic efficacy in the investigated medulloblastoma cell lines that could be further enhanced by PI3K inhibition. Of note, the combination of Vandetanib, GDC-0941 and Etoposide results in MYC-amplified and SHH-TP53-mutated cell lines in complete loss of cell viability. Our findings therefore provide a rational to further evaluate Vandetanib in combination with PI3K inhibitors as well as standard chemotherapeutics in vivo for the treatment of most aggressive medulloblastoma variants.

Early blindness and coma during intrathecal chemotherapy for meningeal carcinomatosis.

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Boogerd, W; Moffie, D; Smets, L A

1990-02-01

A 35-year-old woman was treated with intraventricular methotrexate (MTX) with a total dose of 70 mg followed by cytosine arabinoside (Ara-C) with a total dose of 80 mg for meningeal metastasis of breast carcinoma. Radiation therapy was not given. Despite a response of the meningeal tumor the patient developed in the third week of MTX treatment a progressive visual loss and loss of consciousness which worsened during subsequent Ara-C treatment and led to death within 3 weeks. Postmortem examination revealed only minimal neoplastic infiltration of the meninges. Multiple foci of axonal degeneration and demyelination were found in the optic nerves and chiasm, the superficial layers of the brainstem, and spinal cord and to some extent in other cranial nerves and spinal nerve roots. The possible causes of this previously unreported early complication are discussed.

Pedagogical Change at Times of Change in the Higher Education System: An Exploration of Early Career Mentoring, Co-publication and Teaching & Learning Insights

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Bill Boyd

2015-03-01

Full Text Available Universities are at a time of change. Their social, political and economic conditions are under challenge, while technological change challenges curriculum design and implementation, requiring reconsiderations of teaching and learning practices. In this context, and as part of the conference session on Higher education in 2014: threshold, watershed or business as usual?, I reviewed an approach I have been trialing to supporting early- and mid-career academics to navigate through this changing environment. This paper presents an illustrated essay on a human-scale approach to early- and mid-career mentoring through the establishment of small team-based research and writing projects. The essay provides examples of activities that, on the one hand, assist academics to develop the tools they need to navigate the new and evolving environment of higher education, while on the other hand directly addresses key pedagogical issues and provides new insight into teaching and learning in higher education.

Spotlight on daytime napping during early childhood

OpenAIRE

Horváth,Klára; Plunkett,Kim

2018-01-01

Klára Horváth,1 Kim Plunkett2 12nd Department of Pediatrics, Semmelweis University, Budapest, Hungary; 2Department of Experimental Psychology, University of Oxford, Oxford, UK Abstract: Daytime napping undergoes a remarkable change in early childhood, and research regarding its relationship to cognitive development has recently accelerated. In this review, we summarize our current understanding of this relationship focusing on children aged <5 years. First, we eva...

The difficulties of pseudo-Cushing's syndrome (or "non-neoplastic hypercortisolism").

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Chabre, Olivier

2018-06-01

Pseudo-Cushing's syndrome covers different pathological conditions responsible for mild-to-moderate ACTH-dependent hypercortisolism, related not to an ACTH-secreting tumor but rather to CRH and/or AVP hypothalamic secretion through activation of various neural pathways, in patients generally displaying excess central adiposity. It is better termed "non-neoplastic hypercortisolism" (NNH). The main conditions implicated in NNH comprise: neuropsychiatric disorder, alcohol abuse, insulin-resistant obesity, polycystic ovary syndrome, and end-stage kidney disease. Glucocorticoid resistance is one differential diagnosis, as are some cases of primary adrenal disease with incompletely suppressed ACTH. Differentiating between NNH and mild-to-moderate Cushing's disease can be a real challenge. Clinical analysis, based on thorough history taking and screening for catabolic signs is essential; useful explorations include midnight serum or salivary cortisol and Dex/CRH and ddAVP stimulation response. Pituitary MRI suffers from limitations regarding both sensitivity and specificity, while bilateral inferior petrosal sinus sampling cannot distinguish between pituitary ACTH secretion by a tumor or by normal cells stimulated by endogenous CRH. Definitive diagnosis of functional etiology requires demonstrating that treatment of the underlying condition restores normal secretion of ACTH and cortisol, but this is not always possible. Lingering diagnostic uncertainty has to be accepted in certain patients, who will have to be followed up for some time before diagnosis can be considered more or less definitive. Copyright © 2018. Published by Elsevier Masson SAS.

Long-term changes in climatological calendar

International Nuclear Information System (INIS)

Jaagus, J.

1997-01-01

Trends in time series of climatic seasons in Tartu, Estonia, during 1891-1995 are analysed using regression analysis. Two intermediate seasons between autumn and winter (late autumn, early winter), and two ones between winter and spring (late winter and early spring) are determined. The climatic seasons correspond quite well to individual stages of annual cycling of nature. Results of linear regression analysis demonstrate changes in climatological calendar reflecting the influence of global warming. Climatic seasons of spring period have moved to earlier time, and seasons of autumn period to later time. Statistically significant trends were observed for beginning date of early spring (12 days earlier), summer (11 days earlier) and late autumn (8 days later). Beginning date of winter has shifted 12 days later. Duration of summer season has increased by two weeks and duration of winter season has decreased by the same time. (author)

Early anisotropy changes in the corpus callosum of patients with optic neuritis

International Nuclear Information System (INIS)

Bester, M.; Ding, X.Q.; Holst, B.; Fiehler, J.; Heesen, C.; Schippling, S.; Martin, R.

2008-01-01

Optic neuritis (ON) and any other early manifestation of multiple sclerosis (MS) are referred to as clinically isolated syndrome (CIS) as long as MS is suspected. In this prospective study we aimed to determine whether diffusion tensor imaging (DTI) could quantify structural changes in patients with early MS. A total of 24 patients and 15 control subjects were prospectively followed by clinical examinations and MRI. the main inclusion criterion was presentation with ON. Patients underwent serial MRI scans: MRI1 (baseline, n=24), MRI2 (mean 6.6 months, n=24), MRI3 (mean 13.0 months, n=14), MRI4 (mean 39.4 months, n=5). Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were derived from DTI. Four regions of interest (ROIs) were defined in normal-appearing white matter (NAWM). In the temporal course FA decreased in the genu of the callosal body (GCC) from MRI1 to MRI4 (P=0.005) and in the splenium of the callosal body (SCC) (P=0.006). Patients already had lower FA values in the SCC (P<0.01) on MRI1 compared with the controls. Patients had lower FA values in the GCC (P<0.01) starting from MRI2. Patients with definite MS on follow-up (n=9) showed a correlation between FA in the SCC and time (r=-0.40, P=0.004), whereas patients without progression did not. Our findings suggest that the corpus callosum is an early site for development of anisotropy changes in MS patients with ON. There seems to be a primary FA decrease in all patients with ON that only deteriorates in the group developing definite MS. (orig.)

Dynamic changes in the interchromosomal interaction of early histone gene loci during development of sea urchin.

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Matsushita, Masaya; Ochiai, Hiroshi; Suzuki, Ken-Ichi T; Hayashi, Sayaka; Yamamoto, Takashi; Awazu, Akinori; Sakamoto, Naoaki

2017-12-15

The nuclear positioning and chromatin dynamics of eukaryotic genes are closely related to the regulation of gene expression, but they have not been well examined during early development, which is accompanied by rapid cell cycle progression and dynamic changes in nuclear organization, such as nuclear size and chromatin constitution. In this study, we focused on the early development of the sea urchin Hemicentrotus pulcherrimus and performed three-dimensional fluorescence in situ hybridization of gene loci encoding early histones (one of the types of histone in sea urchin). There are two non-allelic early histone gene loci per sea urchin genome. We found that during the morula stage, when the early histone gene expression levels are at their maximum, interchromosomal interactions were often formed between the early histone gene loci on separate chromosomes and that the gene loci were directed to locate to more interior positions. Furthermore, these interactions were associated with the active transcription of the early histone genes. Thus, such dynamic interchromosomal interactions may contribute to the efficient synthesis of early histone mRNA during the morula stage of sea urchin development. © 2017. Published by The Company of Biologists Ltd.

The landscape of PreK-12 engineering online resources for teachers: global trends

OpenAIRE

Bagiati, Aikaterini; Evangelou, Demetra; Magana, Alejandra; Kaloustian, Garene; Zhu, Jiabin; Yoon, So Yoon

2014-01-01

Background: The newly formed discipline of engineering education is addressing the need to (a) enhance STEM education for precollege students and (b) identify optimum ways to introduce engineering content starting, perhaps, from the early ages. Introducing engineering at the Prekindergarten through 12th grade (PreK-12) education level requires significant changes in teacher preparation and support. It highlights the need for developing developmentally appropriate content knowledge and ped...

Early change in coping strategies in responsive treatments for borderline personality disorder: A mediation analysis.

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Kramer, Ueli; Keller, Sabine; Caspar, Franz; de Roten, Yves; Despland, Jean-Nicolas; Kolly, Stéphane

2017-05-01

Difficulty in emotion regulation is a hallmark feature of patients with borderline personality disorder (BPD). Therefore, change in the frequency of certain patients' coping strategies-aiming at emotion regulation-are among the most promising mechanisms of change in treatments for BPD. In parallel, it was highlighted that therapist responsiveness significantly contributed to outcome across treatment approaches (Stiles, 2009). Based on a randomized controlled trial (Kramer et al., 2014), the present process-outcome mediation analysis aims at examining the patient's early change in frequency of coping strategies-in particular the decrease in behavioral forms of coping-as potential mechanism of change in responsive treatments for BPD. A total of 57 patients with BPD were included in the present analysis, out of whom 27 were randomly assigned to a 10-session psychiatric treatment and 30 to a 10-session psychiatric treatment augmented with the responsive intervention of the motive-oriented therapeutic relationship (Caspar, 2007). The 1st, 5th, and 9th session of each therapy were transcribed and analyzed using the Coping Action Pattern Rating Scale (Perry et al., 2005; 171 sessions analyzed in total), a validated observer-rated method for assessing coping strategies in the therapy process. Psychological distress was assessed using the OQ-45 at intake, after Session 5, and after Session 10. The results confirmed a responsiveness effect associated with the motive-oriented therapeutic relationship and showed a significant decrease in frequency of behavioral forms of coping, F(1, 54) = 3.09, p = .05, d = .56, which was not different between the 2 conditions. In addition, we demonstrated that the early decrease in behavioral forms of coping between Sessions 1 and 5 partially mediated the link between the group assignment and the change in psychological distress between Sessions 5 and 10. These results shed light on the centrality of therapist responsiveness in treatments for

[Clinical study of induced abortion of early-early pregnancy: an analysis of 10, 404 cases].

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Kang, Jian; Wang, Xue-fen; Zhang, Li; Liu, Jian-hua

2012-01-03

To evaluate the advantages and disadvantages of early-early pregnancy induced abortion (EPIA). A total of 10 404 cases of EPIA performed at our hospital from January 1993 to December 2003 were retrospectively analyzed and compared with 9434 cases of common induced abortion (CIA). The amount of hemorrhage and operative duration, degree of pain, rate of induced-abortion syndrome, rate of incomplete abortion, menstrual changes and post-operative onset of Asherman's syndrome were observed and compared between 2 groups. The average age, ratio of parous cases, ratio of the cases of first-pregnancy induced abortion were not different between 2 groups (P > 0.05). The amount of hemorrhage bleeding ((4.9 ± 3.2) ml), operative duration ((90.3 ± 12.4) s), degree of pain, rate of induced-abortion syndrome, menstrual changes and the rate of Asherman's syndrome in the EPIA group were all significantly less than those in the CIA group (P abortion (0.44%) in the EPIA group was significantly higher than that (0.21%) in the CIA group (P abortion stays high.

Vitamin D and calcium intake and risk of early menopause12

Science.gov (United States)

Purdue-Smithe, Alexandra C; Whitcomb, Brian W; Szegda, Kathleen L; Boutot, Maegan E; Manson, JoAnn E; Hankinson, Susan E; Rosner, Bernard A; Troy, Lisa M; Michels, Karin B; Bertone-Johnson, Elizabeth R

2017-01-01

Background: Early menopause, defined as the cessation of ovarian function before the age of 45 y, affects ∼10% of women and is associated with higher risk of cardiovascular disease, osteoporosis, and other conditions. Few modifiable risk factors for early menopause have been identified, but emerging data suggest that high vitamin D intake may reduce risk. Objective: We evaluated how intakes of vitamin D and calcium are associated with the incidence of early menopause in the prospective Nurses’ Health Study II (NHS2). Design: Intakes of vitamin D and calcium from foods and supplements were measured every 4 y with the use of a food-frequency questionnaire. Cases of incident early menopause were identified from all participants who were premenopausal at baseline in 1991; over 1.13 million person-years, 2041 women reported having natural menopause before the age of 45 y. We used Cox proportional hazards regression to evaluate relations between intakes of vitamin D and calcium and incident early menopause while accounting for potential confounding factors. Results: After adjustment for age, smoking, and other factors, women with the highest intake of dietary vitamin D (quintile median: 528 IU/d) had a significant 17% lower risk of early menopause than women with the lowest intake [quintile median: 148 IU/d; HR: 0.83 (95% CI: 0.72, 0.95); P-trend = 0.03]. Dietary calcium intake in the highest quintile (median: 1246 mg/d) compared with the lowest (median: 556 mg/d) was associated with a borderline significantly lower risk of early menopause (HR: 0.87; 95% CI: 0.76, 1.00; P-trend = 0.03). Associations were stronger for vitamin D and calcium from dairy sources than from nondairy dietary sources, whereas high supplement use was not associated with lower risk. Conclusions: Findings suggest that high intakes of dietary vitamin D and calcium may be modestly associated with a lower risk of early menopause. Further studies evaluating 25-hydroxyvitamin D concentrations, other

Nail changes secondary to docetaxel chemotherapy : a case report

Directory of Open Access Journals (Sweden)

Ghafoor Qamar

2008-01-01

Full Text Available Abstract Introduction Docetaxel is a chemotherapy agent used in the management of many neoplastic conditions. Various side effects are known. Nail changes are often under-recognised or attributed to other causes. Case presentation We report the case of a 66 year old gentleman who received docetaxel chemotherapy for non-small cell lung cancer. He had nail changes as a complication of the treatment. Conclusion Nail toxicity is a recognised side-effect of taxane chemotherapy agents and can often persist for many months after finishing the treatment. We would like to highlight this problem, so it can be considered as a differential diagnosis in the appropriate population.

Inhibition of Neoplastic Transformation and Chemically-Induced Skin Hyperplasia in Mice by Traditional Chinese Medicinal Formula Si-Wu-Tang

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Mandy M. Liu

2017-03-01

Full Text Available Exploring traditional medicines may lead to the development of low-cost and non-toxic cancer preventive agents. Si-Wu-Tang (SWT, comprising the combination of four herbs, Rehmanniae, Angelica, Chuanxiong, and Paeoniae, is one of the most popular traditional Chinese medicines for women’s diseases. In our previous studies, the antioxidant Nrf2 pathways were strongly induced by SWT in vitro and in vivo. Since Nrf2 activation has been associated with anticarcinogenic effects, the purpose of this study is to evaluate SWT’s activity of cancer prevention. In the Ames test, SWT demonstrated an antimutagenic activity against mutagenicity induced by the chemical carcinogen 7,12-dimethylbenz(aanthracene (DMBA. In JB6 P+ cells, a non-cancerous murine epidermal model for studying tumor promotion, SWT inhibited epidermal growth factor (EGF-induced neoplastic transformation. The luciferase reporter gene assays demonstrated that SWT suppressed EGF-induced AP-1 and TNF-α-induced NF-κB activation, which are essential factors involved in skin carcinogenesis. In a DMBA-induced skin hyperplasia assay in ‘Sensitivity to Carcinogenesis’ (SENCAR mice, both topical and oral SWT inhibited DMBA-induced epidermal hyperplasia, expression of the proliferation marker Proliferating cell nuclear antigen (PCNA, and H-ras mutations. These findings demonstrate, for the first time, that SWT prevents tumor promoter and chemical-induced carcinogenesis in vitro and in vivo, partly by inhibiting DNA damage and blocking the activation of AP-1 and NF-κB.

Early change of thyroid hormone concentration after 131I treatment in patients with solitary toxic adenoma

International Nuclear Information System (INIS)

Pirnat, E.; Fidler, V.; Zaletel, K.; Gaberscek, S.; Hojker, S.

2002-01-01

Aim: In spite of extensive use of 131 I for treatment of hyperthyroidism, the results of early outcome are variable. In our prospective clinical study we tested whether 131 I induced necrosis causing clinical aggravation of hyperthyroidism and increasing the free thyroid hormone concentration in the serum of patients with solitary toxic adenoma not pretreated with antithyroid drugs. Patients and methods: 30 consecutive patients were treated with 925 MBq 131 I. Serum concentration of thyrotropin (TSH), free thyroxine (fT 4 ), free triiodothyronine (fT 3 ), thyroglobulin (Tg), and interleukin-6 (IL-6) were measured before and after application of 131 I. Results: After application of 131 I no clinical worsening was observed. FT 4 and fT 3 concentration did not change significantly within the first five days, whereas both of them significantly decreased after 12 days (p 131 I induced necrosis of thyroid cells was found. Therefore, the application of 131 I may be considered as a safe and effective treatment for patients with hyperthyroidism due to toxic adenoma. (orig.)

Critical role of CCDC6 in the neoplastic growth of testicular germ cell tumors

International Nuclear Information System (INIS)

Staibano, Stefania; Fusco, Alfredo; Chieffi, Paolo; Celetti, Angela; Ilardi, Gennaro; Leone, Vincenza; Luise, Chiara; Merolla, Francesco; Esposito, Francesco; Morra, Francesco; Siano, Maria; Franco, Renato

2013-01-01

DNA damage response has been clearly described as an anti-cancer barrier in early human tumorigenesis. Moreover, interestingly, testicular germ cell tumors (TGCTs) have been reported to lack the DNA Damage Response (DDR) pathway activation. CCDC6 is a pro-apoptotic phosphoprotein substrate of the kinase ataxia telangectasia mutated (ATM) able to sustain DNA damage checkpoint in response to genotoxic stress and is commonly rearranged in malignancies upon fusion with different partners. In our study we sought to determine whether CCDC6 could have a role in the patho-genesis of testicular germ cell tumors. To achieve this aim, analysis for CCDC6 expression has been evaluated on serial sections of the mouse testis by immunohistochemistry and on separate populations of murine testicular cells by western blot. Next, the resistance to DNA damage-induced apoptosis and the production of reactive oxygen species has been investigated in GC1 cells, derived from immortalized type B murine germ cells, following CCDC6 silencing. Finally, the CCDC6 expression in normal human testicular cells, in Intratubular Germ Cell Neoplasia Unclassified (IGCNU), in a large series of male germ cell tumours and in the unique human seminoma TCam2 cell line has been evaluated by immunohistochemistry and by Western Blot analyses. The analysis of the CCDC6 expression revealed its presence in Sertoli cells and in spermatogonial cells. CCDC6 loss was the most consistent feature among the primary tumours and TCam2 cells. Interestingly, following treatment with low doses of H 2 O 2 , the silencing of CCDC6 in GC1 cells caused a decrease in the oxidized form of cytochrome c and low detection of Bad, PARP-1 and Caspase 3 proteins. Moreover, in the silenced cells, upon oxidative damage, the cell viability was protected, the γH2AX activation was impaired and the Reactive Oxygen Species (ROS) release was decreased. Therefore, our results suggest that the loss of CCDC6 could aid the spermatogonial cells to

[Relationship between body weight status in early adulthood and body weight change at middle age in adults and type 2 diabetes mellitus].

Science.gov (United States)

Zhou, Long; Zhao, Liancheng; Li, Ying; Guo, Min; Wu, Yangfeng

2016-03-01

To explore the relationship between weight status in early adulthood and body weight change at middle age in adults and type 2 diabetes mellitus (T2DM). The data of 14 population samples from China Multicenter Collaborative Study of Cardiovascular Epidemiology conducted in 1998 were used. Approximately 1 000 men and women in each sample were surveyed for cardiovascular disease risk factors, including body weight at age 25 years. The body mass index (BMI) at the age 25 years was calculated. The association between body weight in early adulthood and body weight change at middle age and T2DM was examined by using logistic regression model. The incidence of T2DM in low weight group (BMIweight group (BMI: 18.5-23.9 kg/m(2)), overweight group (BMI: 24.0-27.9 kg/m(2)) and obese group (BMI:≥28.0 kg/m(2)) at 25 years old were 2.4%(30/1263), 2.8%(266/9562), 4.0%(70/1739) and 6.4% (7/110), respectively (P value for trendincidence of T2DM for adults with weight change 12.5 kg at middle age were 2.5% (18/712), 1.3%(21/1629), 2.1%(48/2330), 2.3%(59/2585), 3.7%(94/2518), and 4.6% (133/2900) respectively. (P value for trend weight gain were positively correlated with T2DM after adjusted other risk factors (all P values for trend weight gain at middle age were both independently associated with the increased risk of T2DM in middle-aged men and women.

Gray-Matter Volume Estimate Score: A Novel Semi-Automatic Method Measuring Early Ischemic Change on CT

OpenAIRE

Song, Dongbeom; Lee, Kijeong; Kim, Eun Hye; Kim, Young Dae; Lee, Hye Sun; Kim, Jinkwon; Song, Tae-Jin; Ahn, Sung Soo; Nam, Hyo Suk; Heo, Ji Hoe

2015-01-01

Background and Purpose We developed a novel method named Gray-matter Volume Estimate Score (GRAVES), measuring early ischemic changes on Computed Tomography (CT) semi-automatically by computer software. This study aimed to compare GRAVES and Alberta Stroke Program Early CT Score (ASPECTS) with regards to outcome prediction and inter-rater agreement. Methods This was a retrospective cohort study. Among consecutive patients with ischemic stroke in the anterior circulation who received intra-art...

Biochemical aspects of the neoplastic cell in relation to positive indicators

International Nuclear Information System (INIS)

Strom, R.

1975-01-01

In scintigraphic diagnoses with positive indicators, the capacity of these indicators to fix themselves or to selectively concentrate in the neoplastic tissue is utilized. This selectivity could be due to several biochemical peculiarities of the tumor cells in relation to surrounding cells: the presence on the membrane of particular chemical groups which allow these cells to invade adjacent tissue without being subject to contact inhibition; the presence on these same membranes of antigenic determinants which are particular to these cells and which can be revealed with specific antibodies; a high concentration of nucleic acid in tumor cells, with the associated possibility of fixing substances having a particular tropism for nucleic acids or for their chemical constituents; an elevated rate of nucleic acid synthesis, with an associated increase in the incorporation of precursors and also of substances which specifically interfere with this biochemical pathway; in numerous cases, tumor cells produce high quantities of acidic metabolites which must be neutralized by equivalent quantities of anions, the latter entering the cells by active transport phenomena; in tumors which develop particularly rapidly, there is a development of degenerative processes with an accumulation of degradation products; in metastatic tumors, the cells have metabolic and biosynthetic activities which are a function of the original tissue, with the possiblity of a clear metabolic difference in relation to adjacent tissues [fr

Late biological effects of ionizing radiation as influenced by dose, dose rate, age at exposure and genetic sensitivity to neoplastic transformation

International Nuclear Information System (INIS)

Spalding, J.F.; Prine, J.R.; Tietjen, G.L.

1978-01-01

A most comprehensive investigation is in progress at the Los Alamos Scientific Laboratory to study the late biological effects of whole-body exposure to gamma irradiation as they may be influenced by total dose, dose rate, age at exposure and genetic background. Strain C57B1/6J mice of four age groups (newborn, 2, 6 and l5 months) were given five doses (20, 60, 180, 540, and 1620 rads) of gamma rays, with each dose being delivered at six dose rates (0.7, 2.1, 6.3, 18.9, 56.7 rads/day and 25 rads/min). Forty to sixty mice were used in each of the approximately 119 dose/dose-rate and age combinations. The study was done in two replications with an equal number of mice per replicaton. Strain RF/J mice were used in a companion study to investigate the influence of genetic background on the type and magnitude of effect. Results of the first and second replications of the l5-month-old age group and data on the influence of genetic background on biological response have been completed, and the results show no significant life shortening within the dose and dose-rate range used. It was also concluded that radiaton-induced neoplastic transformaton was significantly greater in mice with a known genetic sensitivity to neoplastic disease than in mammals which do not normally have a significant incidence of tumours. (author)

The magnetic epoch-6 carbon shift: a change in the ocean's 13C/12C ratio 6.2 million years ago

International Nuclear Information System (INIS)

Vincent, E.; Killingley, J.S.; Berger, W.H.

1980-01-01

Tropical Indian Ocean planktonic and benthic foraminifera have 13 C/ 12 C ratios which change abruptly within Magnetic Epoch 6 about 6.2 million years ago. All species analyzed in the Late Miocene section of DSDP Site 238 show a shift towards lighter values of delta 13 C by about 0.8 per thousand. The oxygen isotope signal indicates that the pre-shift period is climatically quiet while the post-shift period has strong fluctuations. The authors suggest that the shift reflects a sudden increase in the rate of supply of organic carbon from coastal lowlands and from shelves exposed by regression, as well as a change in deep circulation patterns and ocean fertility. The event marks the transition of the ocean-atmosphere system from a quiet Early and Middle Neogene climate regime toward a Late Neogene regime characterized by climatic amplifying mechanisms (albedo feedback, bottom water production) located around the northern North Atlantic. The beginning of this regime may have been strongly influenced by the isolation of the Mediterranean basin. (Auth.)

Linked color imaging reduces the miss rate of neoplastic lesions in the right colon: a randomized tandem colonoscopy study.

Science.gov (United States)

Paggi, Silvia; Mogavero, Giuseppe; Amato, Arnaldo; Rondonotti, Emanuele; Andrealli, Alida; Imperiali, Gianni; Lenoci, Nicoletta; Mandelli, Giovanna; Terreni, Natalia; Conforti, Francesco Simone; Conte, Dario; Spinzi, Giancarlo; Radaelli, Franco

2018-04-01

 Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI).  Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI-WLI group) and vice versa (WLI-LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate.  Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI-WLI and 24.7 % in WLI-LCI). At per-polyp analysis, double inspection of the right colon in the LCI-WLI and WLI-LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively ( P  one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI - WLI group and in 13 of 300 patients (4.3 %) in the WLI - LCI group ( P  = 0.01).  LCI could reduce the miss rate of neoplastic lesions in the right colon. © Georg Thieme Verlag KG Stuttgart · New York.

A Microbiomic Analysis in African Americans with Colonic Lesions Reveals Streptococcus sp.VT162 as a Marker of Neoplastic Transformation

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Hassan Brim

2017-11-01

Full Text Available Increasing evidence suggests a role of the gut microbiota in colorectal carcinogenesis (CRC. To detect bacterial markers of colorectal cancer in African Americans a metabolomic analysis was performed on fecal water extracts. DNA from stool samples of adenoma and healthy subjects and from colon cancer and matched normal tissues was analyzed to determine the microbiota composition (using 16S rDNA and genomic content (metagenomics. Metagenomic functions with discriminative power between healthy and neoplastic specimens were established. Quantitative Polymerase Chain Reaction (q-PCR using primers and probes specific to Streptococcus sp. VT_162 were used to validate this bacterium association with neoplastic transformation in stool samples from two independent cohorts of African Americans and Chinese patients with colorectal lesions. The metabolomic analysis of adenomas revealed low amino acids content. The microbiota in both cancer vs. normal tissues and adenoma vs. normal stool samples were different at the 16S rRNA gene level. Cross-mapping of metagenomic data led to 9 markers with significant discriminative power between normal and diseased specimens. These markers identified with Streptococcus sp. VT_162. Q-PCR data showed a statistically significant presence of this bacterium in advanced adenoma and cancer samples in an independent cohort of CRC patients. We defined metagenomic functions from Streptococcus sp. VT_162 with discriminative power among cancers vs. matched normal and adenomas vs. healthy subjects’ stools. Streptococcus sp. VT_162 specific 16S rDNA was validated in an independent cohort. These findings might facilitate non-invasive screening for colorectal cancer.

The Relationship between Brown Adipose Tissue Activity and Neoplastic Status: an ¹⁸F-FDG PET/CT Study in the Tropics

OpenAIRE

Huang Yung-Cheng; Chen Tai-Been; Hsu Chien-Chin; Li Shau-Hsuan; Wang Pei-Wen; Lee Bi-Fang; Kuo Ching-Yuan; Chiu Nan-Tsing

2011-01-01

Abstract Background Brown adipose tissue (BAT) has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in people living in the tropics, where the influence of outdoor temperature was low. Methods 18F-FDG PE...

Associations between Grawe's general mechanisms of change and Young's early maladaptive schemas in psychotherapy research: a comparative study of change processes.

Science.gov (United States)

Mander, Johannes V; Jacob, Gitta A; Götz, Lea; Sammet, Isa; Zipfel, Stephan; Teufel, Martin

2015-01-01

The study aimed at analyzing associations between Grawe's general mechanisms of change and Young's early maladaptive schemas (EMS). Therefore, 98 patients completed the Scale for the Multiperspective Assessment of General Change Mechanisms in Psychotherapy (SACiP), the Young Shema Questionnaire-Short Form Revised (YSQ S3R), and diverse outcome measures at the beginning and end of treatment. Our results are important for clinical applications, as we demonstrated strong predictive effects of change mechanisms on schema domains using regression analyses and cross-lagged panel models. Resource activation experiences seem to be especially crucial in fostering alterations in EMS, as this change mechanism demonstrated significant associations with several schema domains. Future research should investigate these aspects in more detail using observer-based micro-process analyses.

Feasibility of using fluorescence in situ hybridization (FISH) to detect early gene changes in sputum cells from uranium miners

Energy Technology Data Exchange (ETDEWEB)

Neft, R.E.; Rogers, J.L.; Belinsky, S.A. [and others

1995-12-01

Epidemiological studies have shown that combined exposure to radon progeny and tobacco smoke produce a greater than additive or synergistic increase in lung cancer risk. Lung cancer results from multiple genetic changes over a long period of time. An early change that occurs in lung cancer is trisomy 7 which is found in 50% of non-small cell lung cancer and in the far margins of resected lung tumors. The 80% mortality associated with lung cancer is in part related to the high proportion of patients who present with an advanced, unresectable tumor. Therefore, early detection of patients at risk for tumor development is critical to improve treatment of this disease. Currently, it is difficult to detect lung cancer early while it is still amendable by surgery. Saccomanno, G. has shown that premalignant cytologic changes in sputum cells collected from uranium miners can be detected by a skilled, highly trained cytopathologist. A more objective alternative for identifying premalignant cells in sputum may be to determine whether an early genetic change such as trisomy 7 is present in these cells. Fluorescence in situ hybridization (FISH) can be used to identify cells with trisomy 7. The results of this investigation indicate that FISH may prove to be an accurate, efficient method to test at-risk individuals for genetic alterations in bronchial epithelial cells from sputum.

Feasibility of using fluorescence in situ hybridization (FISH) to detect early gene changes in sputum cells from uranium miners

International Nuclear Information System (INIS)

Neft, R.E.; Rogers, J.L.; Belinsky, S.A.

1995-01-01

Epidemiological studies have shown that combined exposure to radon progeny and tobacco smoke produce a greater than additive or synergistic increase in lung cancer risk. Lung cancer results from multiple genetic changes over a long period of time. An early change that occurs in lung cancer is trisomy 7 which is found in 50% of non-small cell lung cancer and in the far margins of resected lung tumors. The 80% mortality associated with lung cancer is in part related to the high proportion of patients who present with an advanced, unresectable tumor. Therefore, early detection of patients at risk for tumor development is critical to improve treatment of this disease. Currently, it is difficult to detect lung cancer early while it is still amendable by surgery. Saccomanno, G. has shown that premalignant cytologic changes in sputum cells collected from uranium miners can be detected by a skilled, highly trained cytopathologist. A more objective alternative for identifying premalignant cells in sputum may be to determine whether an early genetic change such as trisomy 7 is present in these cells. Fluorescence in situ hybridization (FISH) can be used to identify cells with trisomy 7. The results of this investigation indicate that FISH may prove to be an accurate, efficient method to test at-risk individuals for genetic alterations in bronchial epithelial cells from sputum

An exploratory analysis of changes in mood, anxiety and craving from pre- to post-single sessions of exercise, over 12 weeks, among patients with alcohol dependence.

Science.gov (United States)

Brown, Richard A; Prince, Mark A; Minami, Haruka; Abrantes, Ana M

2016-10-01

Aerobic exercise is currently being studied as a relapse prevention strategy for individuals with alcohol use disorders. Negative affect and cravings predict relapse. The acute effects of moderate-intensity exercise have been shown to improve mood and reduce craving. The current study examined the acute effects of exercise on changes in mood, anxiety, and craving from pre- to post-exercise at each week of a 12-week moderate intensity exercise intervention with sedentary alcohol dependent adults. Twenty-six participants in the exercise condition of a larger randomized clinical trial (Brown et al., 2014) exercised in small groups at moderate intensity for 20 to 40 minutes per session. Participants rated mood, anxiety, and cravings in the present moment before and after each exercise session over the course of the 12-week intervention. Data analyses focused on effect size and interval estimation. Joinpoint analysis was used to model longitudinal trends. Increases in mood and decreases in anxiety and craving were apparent at every session. Effect size estimates revealed that average change from pre- to post-exercise was in the small to medium range with some individual sessions reaching the large range. Joinpoint analyses revealed that the pre-post exercise changes in mood increased, anxiety remained stable, and craving diminished across the 12 weeks. This study provides provisional support for a change in mood, anxiety and alcohol cravings for the role of exercise in the early recovery period for alcohol dependence. Acute single bouts of moderate-intensity exercise may help individuals with alcohol dependence manage mood, anxiety, and craving thereby reducing relapse risk, but further research is needed with a more rigorous study design.

Trajectories of Change and Relationship between Parent-Adolescent School-Related Conflict and Academic Achievement in Early Adolescence

Science.gov (United States)

Brkovic, Irma; Keresteš, Gordana; Puklek Levpušc?ek, Melita

2014-01-01

The study explored changes in parent-adolescent school-related conflict rate and academic performance over a 5-year period among Croatian early adolescents and gender differences in these changes. Furthermore, it examined the relationship between conflict and achievement. The study was performed by applying an accelerated approach to overlapping…

Nucleoli in human early erythroblasts (K2, K1, K1/2 cells).

Science.gov (United States)

Smetana, K; Jirásková, I; Klamová, H

2005-01-01

Human early erythroid precursors classified according to the nuclear size were studied to provide information on nucleoli in these cells using simple cytochemical procedures for demonstration of RNA and proteins of silver-stained nucleolar organizers. K2 cells with nuclear diameter larger than 13 microm and K1 cells with nuclear diameter larger than 9 microm corresponding to proerythroblasts and macroblasts (large basophilic erythroblasts) mostly possessed large irregularly shaped nucleoli with multiple fibrillar centres representing "active nucleoli". K1/2 cells with nuclear diameter smaller than 9 microm corresponding to small basophilic erythroblasts were usually characterized by the presence of micronucleoli representing "inactive nucleolar types". On the other hand, a few K1/2 cells contained large nucleoli with multiple fibrillar centres similar to those present in K2 cells and thus appeared as "microproerythroblasts". The nucleolar asynchrony expressed by the presence of large irregularly shaped nucleoli with multiple nucleoli (active nucleoli) and ring-shaped nucleoli (resting nucleoli) in one and the same nucleus of K2 or K1 cells was not exceptional and might reflect a larger resistance of these cells to negative factors influencing the erythropoiesis. The intranucleolar translocation of silver-stained nucleolus organized regions was noted in K2 cells and might indicate the premature aging of these cells without further differentiation. More studies, however, are required in this direction.

The influence of melatonin on metabolic changes in female rats induced by continuous irradiation and/or administration of 7,12-dimethylbenz/a/anthracene

International Nuclear Information System (INIS)

Ahlers, I.; Solar, P.; Ahlersova, E.; Kassayova, M.; Smajda, B.

1997-01-01

Metabolic profile is an important biological marker of neoplastic processes not only in the tumor itself but also in the host organism. The neuro-hormone melatonin has been implicated in the experiments as an oncostatic agent. Female Wistar:Han SPF rats (Velaz, Prague, Czech Republic) were irradiated continuously for 15 days using a daily gamma rays dose of 96 mGy. At the end of exposure one group of rats was administered 5 mg/kg b.w. of dimethylbenz/a/anthracene (DMBA) intragastrically. During the period of exposure to ionizing radiation a part of the animals was supplied with melatonin (M) at a concentration of 20 μl/ml in drinking water. Selected parameters of lipid and carbohydrate metabolism and levels of selected hormones were determined 2, 30 and 100 days post-irradiation. The irradiation itself caused only small changes in tissue lipids. The application of a single low dose (subthreshold from the point of view of induction of mammary tumors) of DMBA caused more pronounced changes in nonirradiated animals; of the changes observed an increase in lipids in the liver, triacylglycerol (TG) in the thymus and decrease in myocardial glycogen predominated. The intake (by drinking) of exogenous M prevented the biochemical pattern of fatty liver in animals administered DMBA in both groups, irradiated an nonirradiated. A Prolonged effect of exogenous M, demonstrated by prevention of increase in TG in the thymus and of irradiated animals caused by administration of DMBA, was observed. The mechanism of metabolic effect of M is not known. Additional experiments are needed to explain the relationship between the beneficial effect of M on metabolic changes and its presumable oncostatic effect in rats. (author)

Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness

Science.gov (United States)

Bauer, Corinna M.; Hirsch, Gabriella V.; Zajac, Lauren; Koo, Bang-Bon; Collignon, Olivier

2017-01-01

In the setting of profound ocular blindness, numerous lines of evidence demonstrate the existence of dramatic anatomical and functional changes within the brain. However, previous studies based on a variety of distinct measures have often provided inconsistent findings. To help reconcile this issue, we used a multimodal magnetic resonance (MR)-based imaging approach to provide complementary structural and functional information regarding this neuroplastic reorganization. This included gray matter structural morphometry, high angular resolution diffusion imaging (HARDI) of white matter connectivity and integrity, and resting state functional connectivity MRI (rsfcMRI) analysis. When comparing the brains of early blind individuals to sighted controls, we found evidence of co-occurring decreases in cortical volume and cortical thickness within visual processing areas of the occipital and temporal cortices respectively. Increases in cortical volume in the early blind were evident within regions of parietal cortex. Investigating white matter connections using HARDI revealed patterns of increased and decreased connectivity when comparing both groups. In the blind, increased white matter connectivity (indexed by increased fiber number) was predominantly left-lateralized, including between frontal and temporal areas implicated with language processing. Decreases in structural connectivity were evident involving frontal and somatosensory regions as well as between occipital and cingulate cortices. Differences in white matter integrity (as indexed by quantitative anisotropy, or QA) were also in general agreement with observed pattern changes in the number of white matter fibers. Analysis of resting state sequences showed evidence of both increased and decreased functional connectivity in the blind compared to sighted controls. Specifically, increased connectivity was evident between temporal and inferior frontal areas. Decreases in functional connectivity were observed

Early menarche, nulliparity and the risk for premature and early natural menopause.

Science.gov (United States)

Mishra, Gita D; Pandeya, Nirmala; Dobson, Annette J; Chung, Hsin-Fang; Anderson, Debra; Kuh, Diana; Sandin, Sven; Giles, Graham G; Bruinsma, Fiona; Hayashi, Kunihiko; Lee, Jung Su; Mizunuma, Hideki; Cade, Janet E; Burley, Victoria; Greenwood, Darren C; Goodman, Alissa; Simonsen, Mette Kildevæld; Adami, Hans-Olov; Demakakos, Panayotes; Weiderpass, Elisabete

2017-03-01

Are parity and the timing of menarche associated with premature and early natural menopause? Early menarche (≤11 years) is a risk factor for both premature menopause (final menstrual period, FMP menopause (FMP 40-44 years), a risk that is amplified for nulliparous women. Women with either premature or early menopause face an increased risk of chronic conditions in later life and of early death. Findings from some studies suggest that early menarche and nulliparity are associated with early menopause, however overall the evidence is mixed. Much of the evidence for a direct relationship is hampered by a lack of comparability across studies, failure to adjust for confounding factors and inadequate statistical power. This pooled study comprises 51 450 postmenopausal women from nine observational studies in the UK, Scandinavia, Australia and Japan that contribute to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Age at menarche (categorized as ≤11, 12, 13, 14 and 15 or more years) and parity (categorized as no children, one child and two or more children) were exposures of interest. Age at FMP was confirmed by at least 12 months of cessation of menses where this was not the result of an intervention (such as surgical menopause due to bilateral oophorectomy or hysterectomy) and categorized as premature menopause (FMP before age 40), early menopause (FMP 40-44 years), 45-49 years, 50-51 years, 52-53 years and 54 or more years. We used multivariate multinomial logistic regression models to estimate relative risk ratio (RRR) and 95% CI for associations between menarche, parity and age at FMP adjusting for within-study correlation. The median age at FMP was 50 years (interquartile range 48-53 years), with 2% of the women experiencing premature menopause and 7.6% early menopause. Women with early menarche (≤11 years, compared with 12-13 years) were at higher risk of premature menopause (RRR 1