tbuckley/cabot-search huggingface dataset:
Exercise-associated DNA methylation change in skeletal muscle and the importance of imprinted genes: a bioinformatics meta-analysis
Authors: William M Brown
Journal: British Journal of Sports Medicine (2015)

Epigenetics is the study of processes--beyond DNA sequence alteration--producing heritable characteristics. For example, DNA methylation modifies gene expression without altering the nucleotide sequence. A well-studied DNA methylation-based phenomenon is genomic imprinting (ie, genotype-independent parent-of-origin effects).We aimed to elucidate: (1) the effect of exercise on DNA methylation and (2) the role of imprinted genes in skeletal muscle gene networks (ie, gene group functional profiling analyses).Gene ontology (ie, gene product elucidation)/meta-analysis.26 skeletal muscle and 86 imprinted genes were subjected to g:Profiler ontology analysis. Meta-analysis assessed exercise-associated DNA methylation change.g:Profiler found four muscle gene networks with imprinted loci. Meta-analysis identified 16 articles (387 genes/1580 individuals) associated with exercise. Age, method, sample size, sex and tissue variation could elevate effect size bias.Only skeletal muscle gene networks including imprinted genes were reported. Exercise-associated effect sizes were calculated by gene. Age, method, sample size, sex and tissue variation were moderators.Six imprinted loci (RB1, MEG3, UBE3A, PLAGL1, SGCE, INS) were important for muscle gene networks, while meta-analysis uncovered five exercise-associated imprinted loci (KCNQ1, MEG3, GRB10, L3MBTL1, PLAGL1). DNA methylation decreased with exercise (60% of loci). Exercise-associated DNA methylation change was stronger among older people (ie, age accounted for 30% of the variation). Among older people, genes exhibiting DNA methylation decreases were part of a microRNA-regulated gene network functioning to suppress cancer.Imprinted genes were identified in skeletal muscle gene networks and exercise-associated DNA methylation change. Exercise-associated DNA methylation modification could rewind the 'epigenetic clock' as we age.CRD42014009800.
Closure of a post-pneumonectomy bronchopleural fistula with fibrin sealant (Tisseel).
Authors: R T Onotera, H W Unruh
Journal: Thorax (1988)

A persistent post-pneumonectomy bronchopleural fistula and empyema were successfully treated by draining and cleansing the empyema cavity and then occluding the fistula with fibrin sealant.
Local application of advanced glycation end products and intimal hyperplasia in the rabbit collared carotid artery
Authors: H Crauwels
Journal: Cardiovascular Research (2000)

Objective: Accumulation of advanced glycation end products (AGEs) in the vessel wall has been implicated in atherogenesis. The aim of our study was to examine the effects of local application of glycated bovine serum albumin (AGE-BSA) on collar-induced intimal hyperplasia in a diabetes-free setting. Methods: Intimal thickening was induced by placing a collar around the carotid artery of rabbits. Via a catheter attached to an osmotic minipump, control BSA or AGE-BSA was administered locally to the vessel wall in a dose of 1.5 or 15 μg h−1 during 14 days. Vessels receiving phosphate buffered saline (PBS, 5 μl h−1) were used as controls. Results: Infusion of AGE-BSA 15 μg h−1 significantly enhanced intimal thickening as compared to control BSA or PBS. Positive remodelling, measured as an increase in the area comprised by the external elastic lamina and preservation of lumen size, was only significant after treatment with the higher dose of AGE-BSA. In all other groups, intimal thickening was accompanied by a decrease of the lumen without outward displacement. Infusion of control BSA or AGE-BSA changed the cell composition of the neointima, with a significant enhancement in the number of T-lymphocytes and macrophages and a reduction in the percentage of intimal area occupied by smooth muscle cells. These effects were however similar for control BSA as well as AGE-BSA. Conclusions: It is concluded that infusion of control BSA or AGE-BSA may aggravate collar-induced intimal thickening by evoking an inflammatory response. This supports the concept that inflammation contributes to atherogenesis. Further, the significant enhancement in intimal hyperplasia by AGE-BSA suggests that glycated proteins provide an additional stimulus for the development of atherosclerotic lesions.
Analysis of Integrin β4 Expression in Human Breast Cancer: Association with Basal-like Tumors and Prognostic Significance
Authors: Shaolei Lu, Karl Simin, Ashraf Khan, Arthur M. Mercurio
Journal: Clinical Cancer Research (2008)

The beta4 integrin has been implicated in functions associated with the genesis and progression of carcinomas based on data obtained from cell lines and mouse models. Data on its expression and relevance to human carcinomas, however, are relatively scant. The aim of this study was to assess its expression and prognostic significance in human breast carcinomas.We integrated data on beta4 expression from multiple gene profiling studies of breast tumors of known clinical outcome with immunohistochemical analysis of 105 breast carcinomas, and we identified genes whose expression correlates with that of beta4.The expression of both beta4 mRNA and protein is not homogeneous in breast cancer and it associates most significantly with the "basal-like" subtype of breast tumors (P = 0.008). No association between beta4 and HER2 expression was evident from either gene profiling or immunohistochemical analysis. To gain insight into the relevance of beta4 expression to human breast carcinomas, we generated a 65-gene "beta4 signature" based on integration of four published gene profiling studies that included the top 0.1% of genes that correlated with beta4, either positively or negatively. This beta4 signature predicted decreased time to tumor recurrence and survival of patients when applied to four data sets including two independent ones.These observations indicate that beta4 expression in human breast cancer is restricted and associated with basal-like cancers, and they support the hypothesis that beta4 may function in concert with a discrete set of proteins to facilitate the aggressive behavior of a subset of tumors.
Mortality of adults with asthma: a prospective cohort study
Authors: E. Huovinen, J. Kaprio, E. Vesterinen, M. Koskenvuo
Journal: Thorax (1997)

Few studies have been published on the overall survival of adult patients with asthma. A cohort study was performed to assess the mortality from all causes, from chronic obstructive pulmonary disease, and from lung cancer among adult asthmatic subjects.A population of 31,110 Finnish adult women and men, mostly twins, was studied to compare the 16 year mortality rates among asthmatic (n = 471) and non-asthmatic persons. A further 293 twin pairs, discordant for asthma, were also studied to determine whether the mortality of patients with asthma differs from that of their age matched siblings.Mortality from all causes was increased among asthmatic adults (age adjusted hazard ratios 1.49, 95% CI 1.09 to 2.05 for men and 1.53, 95% CI 1.10 to 2.13 for women), and mortality due to chronic obstructive pulmonary diseases was also significantly increased in asthmatic subjects. The risk of death due to lung cancer was increased in men with asthma (hazard ratio adjusted for smoking 3.19, 95% CI 1.39 to 7.31). The risk ratios found among twins discordant for asthma corresponded to those found in the whole cohort.Survival in adults with asthma is worse than in those without asthma. The excess deaths due to chronic obstructive pulmonary disease may explain some part of the increased mortality rates, but not all of it.
Atopic cough: little evidence to support a new clinical entity
Authors: L McGarvey
Journal: Thorax (2003)

A cough is by far the most common reason for a patient to seek medical advice.1 Most of these consultations are for acute cough caused by a myriad of respiratory viruses. In practice, we do not attempt to differentiate rhinovirus infection from adenovirus because no important consequence arises from this diagnostic precision. In chronic cough numerous studies have shown that the overwhelming majority of patients are suffering from one of three conditions—a form of asthma, gastro-oesophageal reflux, or rhinitis.2 The question is whether any further subdivision is justified or merely muddies the water.

In their recent paper published in Thorax Fujimura and colleagues, by inventing a diagnosis of “atopic cough”, have succeeded in adding further unnecessary complexity to the area.3 There are many aspects of this paper which cannot be left unchallenged and we have outlined these below.

The evidence to support a new clinical entity “atopic cough” is tenuous and is further hampered by the extremely vague term “probable atopic cough”. This point is well illustrated in their table 2 which outlines a variety of diagnostic permutations possible after interpretation of a series of investigations. We suspect the authors have, in a significant number of these “probable” patients, merely described atopic individuals with cough predominant asthma. Certainly the demonstration of bronchial hyperreactivity (BHR) in 15 such patients (median PC20 2.5 mg/ml, range 1.25–5.0), many of whom had airway eosinophilia and all of whom appear atopic, is suggestive. Such diagnostic imprecision may yet have therapeutic consequences, but the authors do not provide sufficient information in the paper to conclude that these patients failed to respond to steroids, and have indicated that response to bronchodilators was tested in neither a randomised nor a controlled way.

The authors have relied heavily on the “absence of transformation to typical …
Bilateral pulmonary artery aneurysms in Behcet's disease
Authors: Y Almog, G Polliack, M Dranitzki Elhalel, M Shalit, E Rosenmann
Journal: European Respiratory Journal (1993)

A patient presented with fever, haemoptysis and large bilateral perihilar masses. Histology proved that these were pulmonary artery aneurysms due to pulmonary vasculitis, as a manifestation of Behcet's disease. It is suggested that a routine dynamic computed tomographic (CT) scan should be performed in the evaluation of such cases.
VEGF administration in chronic myocardial ischemia in pigs
Authors: John J Lopez, Roger J. Laham, Alon Stamler, Justin D Pearlman, Stuart Bunting, Aaron Kaplan, Joseph P Carrozza, Frank W Sellke, Michael Simons
Journal: Cardiovascular Research (1998)

Objective: Previous investigations have shown the effectiveness of sustained intra- or extravascular administration of vascular endothelial growth factor (VEGF) in chronic myocardial ischemia in improvement of left ventricular function. The present investigations were undertaken in order to evaluate efficacy of a single bolus or local intracoronary delivery. Methods: Yorkshire pigs underwent placement of a left circumflex artery ameroid occluder. Three weeks later the animals were randomized to treatment with VEGF (20 μg) accomplished by local intracoronary delivery system (InfusaSleeve™, n=10), intracoronary bolus infusion (n=7) or by epicardial implantation of an osmotic delivery system (n=7). An additional group of animals received intracoronary administration of saline and served as a control (n=9). Three weeks after initiation of therapy, the animals were evaluated with regard to myocardial perfusion and global as well as regional ventricular function. Results: All three VEGF treatment groups but not the control animals demonstrated a significant increase in the left-to-left (but not right-to-left) collateral index, myocardial blood flow (pre-therapy LCX vs. LAD (average of all groups): 0.76±0.35 vs. 0.96±0.38 ml*min−1*g−1, p=0.03; post-therapy: LCX vs. LAD: 1.16±0.39 vs. 1.15±0.28 ml*min−1*g−1, p=NS) and coronary vasodilatory reserve 3 weeks after growth factor administration. The observed increase in VEGF-induced perfusion correlated with improvement in regional ventricular function in all VEGF-treated groups (pre-therapy vs. post-therapy: i.c. VEGF 20±5.1 vs. 33±4.8; local VEGF 16±2.8 vs. 33.6; pump VEGF 17±3.8 vs. 34±4.9 p<0.05 for all) but not control animals (21±3.3 vs. 27±5.8, p=NS). Conclusion: Single intracoronary delivery (intravascular bolus or local delivery) of VEGF is effective in stimulating physiologically significant angiogenesis in porcine model of chronic myocardial ischemia.
Hereditary Breast-Ovarian Cancer at the Bedside: Role of the Medical Oncologist
Authors: Henry T. Lynch, Carrie L. Snyder, Jane F. Lynch, Bronson D. Riley, Wendy S. Rubinstein
Journal: Journal of Clinical Oncology (2003)

Purpose: To provide practical considerations for diagnosing, counseling, and managing patients at high risk for hereditary breast cancer. Design: We have studied 98 extended hereditary breast cancer (HBC)/hereditary breast-ovarian cancer (HBOC) families with BRCA1/2 germline mutations. From these families, 1,315 individuals were counseled and sampled for DNA testing. Herein, 716 of these individuals received their DNA test results in concert with genetic counseling. Several challenging pedigrees were selected from Creighton University’s hereditary cancer family registry, as well as one family from Evanston/Northwestern Healthcare, to be discussed in this present report. Results: Many obstacles were identified in diagnosis, counseling, and managing patients at high risk for HBC/HBOC. These obstacles were early noncancer death of key relatives, perception of insurance or employment discrimination, fear, anxiety, apprehension, reduced gene penetrance, and poor compliance. Other important issues such as physician culpability and malpractice implications for failure to collect or act on the cancer family history were identified. Conclusion: When clinical gene testing emerged for BRCA1 and BRCA2, little was known about the efficacy of medical interventions. Potential barriers to uptake of testing were largely unexplored. Identification and referral of high-risk patients and families to genetic counseling can greatly enhance the care of the population at the highest risk for cancer. However, because premonitory physical stigmata are absent in most of these syndromes, an HBOC diagnosis may be missed unless a careful family history of cancer of the breast, ovary, or several integrally associated cancers is obtained.
Localization of collagenase in the growth plate of rachitic rats.
Authors: D D Dean, O E Muniz, I Berman, J C Pita, M R Carreno, J F Woessner, D S Howell
Journal: Journal of Clinical Investigation (1985)

In the transition from proliferation to hypertrophic cell zones in the growth plate, there is an increase in chondrocyte volume and a corresponding decrease in collagen content to accommodate the enlarging cells. It is postulated that collagenase accounts for this collagen loss. To test this hypothesis, tibial growth plates were obtained from normal rats, rachitic rats deficient in vitamin D and phosphate, and rats after 48 and 72 h of healing from rickets. Collagenase was quantitated by a pellet assay based on the release of solubilized collagen from the endogenous insoluble collagen in the tissue homogenates. A fourfold greater collagen release and a concomitant sixfold greater hypertrophic cell volume were measured in rachitic growth plates compared with normal age-matched controls. During healing of rickets, collagenase activity and hypertrophic cell volume returned almost to control levels. Rachitic growth plates were dissected into the juxtaepiphyseal 1/3 and the juxtametaphyseal 2/3. The latter portion contained greater than 95% of the hypertrophic cells and 86% of the collagenase. The collagen-degrading activity was extracted from this region and was shown to be a true collagenase by its production of typical A fragments of tropocollagen produced by collagenase action. The enzyme was activated by aminophenylmercuric acetate and trypsin and was inhibited by EDTA, 1,10-phenanthroline, and a tissue inhibitor of metalloproteinases from human articular cartilage. Inhibitors of aspartic, cysteine, and serine proteases had no effect. Micropuncture fluids aspirated from rachitic cartilage contained latent collagenase activity, indicating an extracellular localization. Negative tests for hemoglobin in the rachitic cartilage samples indicated that there was no contamination by capillaries and that this was not a source of collagenase. It is concluded that extracellular collagenase accounts for the loss of cartilage matrix in the hypertrophic zone, and that this process may be distinct from that of capillary invasion.
Thromboembolism following removal of femoral venous apheresis catheters in patients with breast cancer
Authors: M.W. Saif, S.F. Leitman, G. Cusack, M. Horne, A. Freifeld, D. Venzon, A. PremKumar, K.H. Cowan, R.E. Gress, J. Zujewski, C. Kasten-Sportes
Journal: Annals of Oncology (2004)
Radiolabeled Peptides: Valuable Tools for the Detection and Treatment of Cancer
Authors: M. Fani, H. R. Maecke, S. M. Okarvi
Journal: Theranostics (2012)

Human cancer cells overexpress many peptide receptors as molecular targets.Radiolabeled peptides that bind with high affinity and specificity to the receptors on tumor cells hold great potential for both diagnostic imaging and targeted radionuclide therapy.The advantage of solid-phase peptide synthesis, the availability of different chelating agents and prosthetic groups and bioconjugation techniques permit the facile preparation of a wide variety of peptide-based targeting molecules with diverse biological and tumor targeting properties.Some of these peptides, including somatostatin, bombesin, vasoactive intestinal peptide, gastrin, neurotensin, exendin and RGD are currently under investigation.It is anticipated that in the near future many of these peptides may find applications in nuclear oncology.This article presents recent developments in the field of small peptides, and their applications in the diagnosis and treatment of cancer.
Contrasting effects of circulating nitric oxide and nitrergic transmission on exocrine pancreatic secretion in rats
Authors: E Vaquero, X Molero, V Puig-Diví, J-R Malagelada
Journal: Gut (1998)

Background —Nitric oxide (NO) blockade by l -nitroarginine methyl ester ( l -NAME) inhibits pancreatic secretion in vivo and aggravates caerulein induced pancreatitis. Nitric oxide synthase (NOS) is present in pancreatic islets, endothelium, and nerve fibres. l -NAME blocks all known NOS isoforms. Aim —To investigate the source of NO blocked by l -NAME that inhibits amylase secretion. Methods —Amylase output was measured in rats in response to caerulein (0.1–50 μg/kg) alone or with indazole. Baseline secretion and the response to supramaximal caerulein were also examined after administration of indazole, l -NAME, haemoglobin, or aminoguanidine under continuous blood pressure measurement. In separate experiments, pancreatic secretion was measured after blockade of afferent nerve fibres by either systemic or local capsaicin. The effect of neural NOS inhibition on caerulein induced pancreatitis was also investigated. Results — l -NAME, haemoglobin, and supramaximal caerulein (10 μg/kg) increased blood pressure, whereas indazole and suboptimal caerulein (0.1 μg/kg) did not. Indazole and capsaicin decreased basal amylase output. l -NAME and haemoglobin reduced basal amylase output to a lesser extent and potentiated the inhibitory response to supramaximal caerulein. In contrast, full neural NOS inhibition by l -NAME partially reversed the expected caerulein induced suppression of amylase output. This effect was reproduced by indazole and capsaicin. Indazole did not alter responses to either optimal (0.25 μg/kg) or suboptimal (0.1 μg/kg) caerulein, nor, in contrast with l -NAME, aggravate the outcome of caerulein induced pancreatitis. Conclusions —Reduction of circulating NO availability, probably of endothelial origin, is responsible for the decrease in amylase secretion observed in the early response to l -NAME. Nitrergic neurotransmission plays an important role in the control of pancreatic secretion and may induce opposite effects to endothelial NOS activity.
P<scp>HYSIOLOGIC</scp> D<scp>ETERMINANTS OF THE</scp> A<scp>NOREXIA OF</scp> A<scp>GING</scp>: Insights from Animal Studies
Authors: Barbara A. Horwitz, Cynthia A. Blanton, Roger B. McDonald
Journal: Annual Review of Nutrition (2002)

The anorexia of aging is a syndrome characterized by unexplained losses in food intake and body weight that occur near the end of life. Proposed etiologies cover a wide range of biological and psychological conditions. The observation of this phenomenon in older laboratory animals suggests that physiological changes play a significant causal role. Research on the neurochemical control of energy balance has received much attention in recent years, and age-related alterations in the neuropeptidergic effectors of food intake have been implicated in the anorexia of aging. This review provides an update on putative mechanisms underlying this dysregulation of feeding during advanced age.
Personality, lifestyle, and risk of cardiovascular disease and cancer: follow-up of population based cohort
Authors: Til Stürmer, Petra Hasselbach, Manfred Amelang
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objective</b> To study the relation between measures of personality and risk of cardiovascular disease and cancer in a large cohort. <b>Design</b> Follow-up of population based cohort. <b>Setting</b> Heidelberg, Germany. <b>Participants</b> 5114 women and men aged 40-65 in 1992-5. <b>Main outcome measures</b> Psychological traits assessed by several standardised personality questionnaires in 1992-5, related to cause of death (to 2002-3) or reported incidence of cardiovascular diseases and cancer (validated by treating doctors). Relative risks (and 95% confidence intervals) for combined morbidity and mortality according to five important personality traits were estimated using multivariable Cox proportional hazards models. <b>Results</b> During median follow-up of 8.5 years, 257 participants died and 72 were diagnosed with a heart attack, 62 with stroke, and 240 with cancer (morbidity and mortality combined). A high internal locus of control over disease was associated with a decreased risk of myocardial infarction (adjusted relative risk for an increase of 1 SD = 0.75; 95% confidence interval 0.58 to 0.96). An increase of 1 SD in time urgency was associated with a decreased risk of cancer (adjusted relative risk 0.83; 0.73 to 0.95). Other major personality traits—anger control, psychoticism, and symptoms of depression—were not consistently associated with myocardial infarction, stroke, or cancer. <b>Conclusion</b> Internal locus of control over disease and time urgency seem to be associated with reduced risk for common chronic diseases, probably by affecting unmeasured health related behaviour. The other personality traits assessed had no major impact on cardiovascular disease and cancer.