tbuckley/cabot-search huggingface dataset:
Effects of rapamycin on cultured hepatocyte proliferation and gene expression
Authors: Antonio Francavilla, Brian I. Carr, Thomas E. Starzl, Alessandro Azzarone, Giuseppe Carrieri, Qui-Hua Zeng
Journal: Hepatology (1992)

ABSTRPlCT Rapamycin, a potent immunosuppressive drug that disrupts normal signal–transduction processes, inhibited hepatocyte proliferation without evidence of inherent cytotoxicity in rat hepatocytes cultured in conventional medium or in a medium enriched with epidermal growth factor. The antiproliferative effect was dose dependent, uninfluenced by the concentration of epidermal growth factor in the medium and long lasting after a brief exposure. The effect of rapamycin was unaltered by the concomitant presence of FK 506 in the medium, suggesting that different binding affinities of these two drugs or even a separate rapamycin binding site may exist. Hepatocytes harvested 12 and 24 hr after partial hepatectomy were progressively less responsive to the antiproliferative effect of rapamycin. The gene expression of transforming growth factor–β was reduced under in vivo rapamycin treatment, but at the same time the gene expression of albumin and glyceraldehyde–3–phosphate dehydrogenase was unchanged or increased. The experiments confirm that rapamycin has inherent growth–control qualities, and they strengthen the hypothesis that the recently defined immunophilin network is central to many aspects of cellular growth control. (Hepatology 1992;15:871-877).
DNA divergence in and around the alcohol dehydrogenase locus in five closely related species of Hawaiian Drosophila.
Authors: J G Bishop, J A Hunt
Journal: Molecular Biology and Evolution (1988)

The alcohol dehydrogenase (Adh) region from five planitibia subgroup species of Hawaiian picture-wing Drosophila has been cloned. A total of 15 kb of DNA in and around the Adh gene has been compared among the five species. Genetic distances were calculated to determine evolutionary relationships. These distances agree with previous distances determined by protein polymorphism and DNA hybridization techniques and can be interpreted in terms of specific island colonization and speciation (founder) events over the past 5 Myr. Examination of the restriction maps of the cloned Adh region from the five species shows many instances of small deletions, insertion of a transposable element in D. heteroneura, and the existence of a highly variable region on the 3' side of the Adh gene. Clustering relationships and rates of DNA change are calculated and compared with the relationship found for other species of Drosophila.
Sport and active recreation injuries in Australia: evidence from emergency department presentations.
Authors: C Finch, G Valuri, J Ozanne-Smith
Journal: British Journal of Sports Medicine (1998)

Despite the rise in specialist clinical services for the management of sports and active recreation injury, many patients attend hospital emergency departments for treatment. The purpose of this study was to describe sports injury cases presented to selected hospital emergency departments around Australia for the period 1989-1993.Routinely collected emergency department injury presentation data from the Australian National Injury Surveillance Unit were examined. Data on 98,040 sports and active recreation emergency department presentations were analysed. Sports and active recreation activities were ranked according to frequency of presentation. Relative proportions of injury type and body region injured were determined. Data are presented separately for children (<15 years of age) and adults (>15 years of age).Among the 10 activities that most commonly led to a sports or active recreation injury presentation for all ages were cycling, Australian football, basketball, soccer, cricket, netball, and rugby. For children, injuries were also commonly associated with roller skating/blading, skateboarding, and trampolining. Hockey, martial arts, and dancing injuries were frequent in adults. Most sporting injuries occurred during organised competition or practice whereas the active recreation injuries occurred in a variety of settings. Fractures, strains, and sprains, particularly to the lower and upper extremities, were common types of injury.The rich, but nevertheless limited, information available about sports and active recreation injuries from data collected in emergency departments indicates that these activities are a common context for injury at the community level in Australia.
T-cell epitopes of Phl p 1, major pollen allergen of timothy grass (Phleum pratense): Evidence for crossreacting and non-crossreacting T-cell epitopes within grass group I allergens
Authors: Siegfried Schenk, Heimo Breiteneder, Markus Susani, Nader Najafian, Sylvia Laffer, Michael Duchêne, Rudolf Valenta, Gottfried Fischer, Otto Scheiner, Dietrich Kraft, Christof Ebner
Journal: Journal of Allergy and Clinical Immunology (1995)
Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK)
Authors: Lisa M. McShane, Douglas G. Altman, Willi Sauerbrei, Sheila E. Taube, Massimo Gion, Gary M. Clark
Journal: JNCI Journal of the National Cancer Institute (2005)

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often, initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.
Interleukin-1β Regulates Angiopoietin-1 Expression in Human Endothelial Cells
Authors: Fan Fan, Oliver Stoeltzing, Wenbiao Liu, Marya F. McCarty, Young D. Jung, Niels Reinmuth, Lee M. Ellis
Journal: Cancer Research (2004)

Angiopoietin (Ang)-1 is an important regulator of endothelial cell (EC) survival and stabilization. Ang-1 exerts its biological effects by binding to the EC-specific tyrosine kinase receptor Tie-2, and initiates intracellular signaling in ECs. However, regulatory mechanisms for endothelial Ang-1 expression have not been completely elucidated. In this study, we investigated the effects of angiogenic cytokines and growth factors on Ang-1 expression in human umbilical vein ECs (HUVECs). Northern blot analysis was performed after HUVECs were exposed to interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, platelet-derived growth factor-BB, insulin-like growth factor-1, or vascular endothelial growth factor (VEGF). Both IL-1beta and tumor necrosis factor-alpha caused marked down-regulation of Ang-1 mRNA levels at 4 h with a further decrease observed at 24 h. Using signaling inhibitors, we identified the P38 pathway as the pathway that mediates IL-1beta down-regulation of Ang-1. Furthermore, treatment of cells with IL-1beta indirectly (via down-regulation of Ang-1) led to a decrease in Tie-2 autophosphorylation levels in HUVECs. We previously demonstrated that IL-1beta regulates VEGF expression in tumor cells. This observation was confirmed in ECs in the present study. Because pericytes play a role in regulating EC function, we also determined whether IL-1beta would also down-regulate Ang-1 in human vascular smooth muscle cells. Similar to our findings in HUVECs, we found that IL-1beta decreased Ang-1 expression in human vascular smooth muscle cells. Direct effects of IL-1beta on angiogenesis were investigated by use of an in vivo Gelfoam angiogenesis assay in which IL-1beta produced a significant increase in vessel counts (P = 0.0189). These results suggest that IL-1beta indirectly regulates angiogenesis by modulating the expression of Ang-1. IL-1beta may trigger a proangiogenic response by decreasing Ang-1 levels in ECs and pericytes and up-regulating VEGF in ECs and tumor cells.
Should beta‐blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET
Authors: Marco Metra, Christian Torp‐Pedersen, John G.F. Cleland, Andrea Di Lenarda, Michel Komajda, Willem J. Remme, Livio Dei Cas, Philip Spark, Karl Swedberg, Philip A. Poole‐Wilson
Journal: European Journal of Heart Failure (2007)
Racial Disparities in Treatment and Survival of Male Breast Cancer
Authors: Katherine D. Crew, Alfred I. Neugut, Xiaoyan Wang, Judith S. Jacobson, Victor R. Grann, George Raptis, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2007)

Black women with breast cancer have poorer survival than do white women, but little is known about racial disparities in male breast cancer. We analyzed race and other predictors of treatment and survival among men with stage I-III breast cancer.We used the Surveillance, Epidemiology, and End Results (SEER) Medicare database to identify men 65 years of age or older diagnosed with stage I-III breast cancer from 1991 to 2002. Multivariate regression was used to compare those treated with those not treated with either chemotherapy or radiation therapy, adjusting for known clinical and demographic factors. Cox proportional hazards regression models were used to analyze survival.Of 510 male breast cancer cases (456 white, 34 black), 94% underwent mastectomy, 28% received adjuvant chemotherapy, and 29% received radiation therapy. Among those with known hormone receptors, 95% had hormone-sensitive tumors. In a multivariate analysis, chemotherapy was associated with younger age, advanced stage, and hormone receptor-negative tumors. Radiation therapy was associated with younger age and advanced stage. Black men were approximately 50% less likely to undergo consultation with an oncologist and subsequently receive chemotherapy; however, the results did not reach statistical significance. The breast cancer-specific mortality hazard ratio was more than tripled for black versus white men (hazard ratio = 3.29; 95% CI, 1.10 to 9.86).After adjustment for known clinical, demographic, and treatment factors, there was an association of black race with increased male breast cancer-specific mortality. Although male breast cancer is rare, the reasons for these disparities need to be better understood.
It's Almost Over— More Letters on Debbie
Authors: Max Spital
Journal: JAMA (1988)

To the Editor.—  The flood of opinion in the April 8 issue of JAMA  1 confirms my first impression that printing It's Over,  2 provided an important, timely platform for a colloquy on euthanasia. Lundberg 3 defends his position to publish without editorial comment with scholarship and grace. The court now supports his right to withhold the name of the author. The sad part is that he had to defend these editorial privileges at all.  In a COMMENTARY 4 in this same issue, four ethicists of some repute take a position against a fundamental right when they condemnTHE JOURNALfor printing the Debbie piece. They say, What in the world is going on? And so say I. What's going on when learned men who teach what is right and just strike out at the First Amendment? And they do it ad hominem, almost in paroxysmal bursts of hysterical
Renal and systemic hemodynamics in experimental cirrhosis in rats: Relation to hepatic function
Authors: Georg Wensing, Ramzi Sabra, Robert A. Branch
Journal: Hepatology (1990)

The onset of sodium retention in the phenobarbital and carbon tetrachloride model of cirrhosis in the rat is preceded by a linear decrease in hepatic function as measured by the aminopyrine breath test. Sodium retention occurs when liver function decreases below a critical threshold. Changes in systemic hemodynamics may be responsible for initiating the development of renal sodium retention. The objective of this study was to investigate the relationship between hepatic function and systemic and renal hemodynamics of experimental cirrhosis in rats maintained on a constant salt diet. Cirrhosis was induced in phenobarbitaltreated rats by weekly administration of carbon tetrachloride. The aminopyrine breath test served as a measure of hepatic function. Three groups of animals were studied to evaluate the contribution of changes in systemic and renal hemodynamics to the onset of sodium retention: a group with sodium retention and aminopyrine breath test results just below the critical threshold, a group without sodium retention and aminopyrine breath test results just above the critical threshold and a phenobarbital–treated control group. In each group, urinary sodium excretion, renal plasma flow, glomerular filtration rate, mean arterial pressure and arterial and renal venous plasma renin activities were determined. A progressive, significant reduction in mean arterial pressure was seen, comparing controls with the other two groups. No differences in renal plasma flow were observed between the three groups, but glomerular filtration rate and filtration fraction were slightly reduced in the sodium–retaining group compared with the non–retaining group and controls. A trend toward increased renin activity was observed in both groups of cirrhotic animals, but the differences were not statistically significant, compared with controls. A positive, curvilinear relationship was found between aminopyrine breath test results and mean arterial pressure and glomerular filtration rates, and a negative association was found between aminopyrine breath test results and plasma renin activity. Our data demonstrate, that in carbon tetrachloride-induced cirrhosis in the rat, changes in mean arterial pressure, glomerular filtration rate and plasma renin activity are closely related to the impairment in hepatic function. The significant decrease in mean arterial pressure in nonsodium–retaining cirrhotic rats suggests that peripheral vasodilatation is the initial event in the development of salt retention in this model of cirrhosis. These observations suggest the hypothesis that changes in tubular function, rather than changes in renal hemodynamics and glomerular function, are responsible for the onset of sodium retention. (Hepatology 1990;12:13-19).
RNA Protein Interaction in Neurons
Authors: Robert B. Darnell
Journal: Annual Review of Neuroscience (2013)

Neurons have their own systems for regulating RNA. Several multigene families encode RNA binding proteins (RNABPs) that are uniquely expressed in neurons, including the well-known neuron-specific markers ELAV and NeuN and the disease antigen NOVA. New technologies have emerged in recent years to assess the function of these proteins in vivo, and the answers are yielding insights into how and why neurons may regulate RNA in special ways-to increase cellular complexity, to localize messenger RNA (mRNA) spatially, and to regulate their expression in response to synaptic stimuli. The functions of such restricted neuronal proteins are likely to be complemented by more widely expressed RNABPs that may themselves have developed specialized functions in neurons, including Argonaute/microRNAs (miRNAs). Here we review what is known about such RNABPs and explore the potential biologic and neurologic significance of neuronal RNA regulatory systems.
Effects of (−)-Epicatechin on Myocardial Infarct Size and Left Ventricular Remodeling After Permanent Coronary Occlusion
Authors: Katrina Go Yamazaki, Pam R. Taub, Maraliz Barraza-Hidalgo, Maria M. Rivas, Alexander C. Zambon, Guillermo Ceballos, Francisco J. Villarreal
Journal: Journal of the American College of Cardiology (2010)
Is this what the debate on rules was about?
Authors: Ulrike Hahn
Journal: Behavioral and Brain Sciences (2005)

The key weakness of the proposed distinction between rules and similarity is that it effectively converts what was previously seen as a consequence of rule or similarity-based processing, into a definition of rule and similarity themselves – evidence is elevated into a conceptual distinction. This conflicts with fundamental intuitions about processes and erodes the relevance of the debate across cognitive science.
Prediction of Clinical Outcome in Multiple Lung Cancer Cohorts by Integrative Genomics: Implications for Chemotherapy Selection
Authors: Philippe Broët, Sophie Camilleri-Broët, Shenli Zhang, Marco Alifano, Dhinoth Bangarusamy, Maxime Battistella, Yonghui Wu, Marianne Tuefferd, Jean-François Régnard, Elaine Lim, Patrick Tan, Lance D. Miller
Journal: Cancer Research (2009)

Abstract The role of adjuvant chemotherapy in patients with stage IB non–small-cell lung cancer (NSCLC) is controversial. Identifying patient subgroups with the greatest risk of relapse and, consequently, most likely to benefit from adjuvant treatment thus remains an important clinical challenge. Here, we hypothesized that recurrent patterns of genomic amplifications and deletions in lung tumors could be integrated with gene expression information to establish a robust predictor of clinical outcome in stage IB NSCLC. Using high-resolution microarrays, we generated tandem DNA copy number and gene expression profiles for 85 stage IB lung adenocarcinomas/large cell carcinomas. We identified specific copy number alterations linked to relapse-free survival and selected genes within these regions exhibiting copy number–driven expression to construct a novel integrated signature (IS) capable of predicting clinical outcome in this series (P = 0.02). Importantly, the IS also significantly predicted clinical outcome in two other independent stage I NSCLC cohorts (P = 0.003 and P = 0.025), showing its robustness. In contrast, a more conventional molecular predictor based solely on gene expression, while capable of predicting outcome in the initial series, failed to significantly predict outcome in the two independent data sets. Our results suggest that recurrent copy number alterations, when combined with gene expression information, can be successfully used to create robust predictors of clinical outcome in early-stage NSCLC. The utility of the IS in identifying early-stage NSCLC patients as candidates for adjuvant treatment should be further evaluated in a clinical trial. [Cancer Res 2009;69(3):1055–62]
Inhibition of Prostate Cancer Osteoblastic Progression with VEGF121/rGel, a Single Agent Targeting Osteoblasts, Osteoclasts, and Tumor Neovasculature
Authors: Khalid A. Mohamedali, Zhi Gang Li, Michael W. Starbuck, Xinhai Wan, Jun Yang, Sehoon Kim, Wendy Zhang, Michael G. Rosenblum, Nora M. Navone
Journal: Clinical Cancer Research (2011)

Abstract Purpose: A hallmark of prostate cancer (PCa) progression is the development of osteoblastic bone metastases, which respond poorly to available therapies. We previously reported that VEGF121/rGel targets osteoclast precursors and tumor neovasculature. Here we tested the hypothesis that targeting nontumor cells expressing these receptors can inhibit tumor progression in a clinically relevant model of osteoblastic PCa. Experimental Design: Cells from MDA PCa 118b, a PCa xenograft obtained from a bone metastasis in a patient with castrate-resistant PCa, were injected into the femurs of mice. Osteoblastic progression was monitored following systemic administration of VEGF121/rGel. Results: VEGF121/rGel was cytotoxic in vitro to osteoblast precursor cells. This cytotoxicity was specific as VEGF121/rGel internalization into osteoblasts was VEGF121 receptor driven. Furthermore, VEGF121/rGel significantly inhibited PCa-induced bone formation in a mouse calvaria culture assay. In vivo, VEGF121/rGel significantly inhibited the osteoblastic progression of PCa cells in the femurs of nude mice. Microcomputed tomographic analysis revealed that VEGF121/rGel restored the bone volume fraction of tumor-bearing femurs to values similar to those of the contralateral (non–tumor-bearing) femurs. VEGF121/rGel significantly reduced the number of tumor-associated osteoclasts but did not change the numbers of peritumoral osteoblasts. Importantly, VEGF121/rGel-treated mice had significantly less tumor burden than control mice. Our results thus indicate that VEGF121/rGel inhibits osteoblastic tumor progression by targeting angiogenesis, osteoclastogenesis, and bone formation. Conclusions: Targeting VEGF receptor (VEGFR)-1- or VEGFR-2–expressing cells is effective in controlling the osteoblastic progression of PCa in bone. These findings provide the basis for an effective multitargeted approach for metastatic PCa. Clin Cancer Res; 17(8); 2328–38. ©2011 AACR.
Long-term Complications Following Childhood and Adolescent Cancer: Foundations for Providing Risk-based Health Care for Survivors
Authors: K. C. Oeffinger, M. M. Hudson
Journal: CA A Cancer Journal for Clinicians (2004)

Survivors of childhood and adolescent cancer are one of the higher risk populations seen by health care professionals. The curative therapy administered for the cancer also affects growing and developing tissues. Following chemotherapy, radiation therapy, and surgery, many survivors will experience chronic or late-occurring health problems, often not becoming clinically apparent until decades after therapy. Survivors face an increased risk of morbidity, mortality, and diminished quality of life associated with their previous cancer therapy. Risk is further modified by the survivor's genetics, lifestyle habits, and comorbid health conditions. Over their lifetime, survivors will see health care professionals from an array of specialties and disciplines. The aim of this review is threefold: (1) to convey a sense of the risk faced by survivors to clinicians unfamiliar with the population; (2) to provide an up-to-date tool for clinicians, regardless of specialty or discipline, when providing care for a survivor; and (3) to complement the recently completed recommendations for screening, prevention, and management of childhood cancer survivors.
Drowning and Hypothermia
Authors: S. Miles
Journal: British Journal of Sports Medicine (1975)

I DROWNINGDrowning is most frequently the end result of accidents in water and is defined as "to suffocate by submersion - especially in water".It is a continuing process which may result in death (drowned) or recovery if rescue and resuscitation is adequate.The process of drowning commences when the victim is no longer able to remain afloat and the face cannot be kept above water.There are many causes for this e.g.inadequate flotation equipment, fatigue, injury, hypo- thermia etc.When water enters the mouth there is copious swallowing.The desire to breathe lessens and in possibly 20% of subjects, especially those who are fit and less exhausted, a protective laryngeal spasm prevents the entry of water into the lungs.This is DRY drowning and respiratory paralysis and unconsciousness result from an uncomplicated anoxia.The patient suffers little and the loss of consciousness is often preceded by pleasant and colourful recall of previous events.There is no pain and the response to treatment is good and uncomplicated.