tbuckley/cabot-search huggingface dataset:
Effects of Intensive Versus Moderate Lipid-Lowering Therapy on Myocardial Ischemia in Older Patients With Coronary Heart Disease
Authors: Prakash Deedwania, Peter H. Stone, C. Noel Bairey Merz, Juan Cosin-Aguilar, Nevres Koylan, Don Luo, Pamela Ouyang, Ryszard Piotrowicz, Karin Schenck-Gustafsson, Philippe Sellier, James H. Stein, Peter L. Thompson, Dan Tzivoni
Journal: Circulation (2007)

Clinical trials have demonstrated that, compared with placebo, intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease. However, no studies to date have assessed intensive versus moderate statin therapy in older patients with stable coronary syndromes.A total of 893 ambulatory coronary artery disease patients (30% women) 65 to 85 years of age with > or = 1 episode of myocardial ischemia that lasted > or = 3 minutes during 48-hour ambulatory ECG at screening were randomized to atorvastatin 80 mg/d or pravastatin 40 mg/d and followed up for 12 months. The primary efficacy parameter (absolute change from baseline in total duration of ischemia at month 12) was significantly reduced in both groups at month 3 and month 12 (both P<0.001 for each treatment group) with no significant difference between the treatment groups. Atorvastatin-treated patients experienced greater low-density lipoprotein cholesterol reductions than did pravastatin-treated patients, a trend toward fewer major acute cardiovascular events (hazard ratio, 0.71; 95% confidence interval, 0.46, 1.09; P=0.114), and a significantly greater reduction in all-cause death (hazard ratio, 0.33; 95% confidence interval, 0.13, 0.83; P=0.014).Compared with moderate pravastatin therapy, intensive atorvastatin therapy was associated with reductions in cholesterol, major acute cardiovascular events, and death in addition to the reductions in ischemia observed with both therapies. The contrast between the therapies' differing efficacy for major acute cardiovascular events and death and their nonsignificant difference in efficacy for reduction of ischemia suggests that low-density lipoprotein cholesterol-lowering thresholds for ischemia and major acute cardiovascular events may differ. The Study Assessing Goals in the Elderly (SAGE) demonstrates that older men and women with coronary artery disease benefit from intensive statin therapy.
The efficacy and the risk of immunogenicity of FIX Padua (R338L) in hemophilia B dogs treated by AAV muscle gene therapy
Authors: Jonathan D. Finn, Timothy C. Nichols, Nikolaos Svoronos, Elizabeth P. Merricks, Dwight A. Bellenger, Shangshen Zhou, Paolo Simioni, Katherine A. High, Valder R. Arruda
Journal: Blood (2012)
Low-Tar Cigarettes Come Under Fire
Authors: Paul Cotton
Journal: JAMA (1993)

THE ILLUSION that low-tar brands are safer than regular cigarettes is all smoke and mirrors. A new population-based study has confirmed laboratory evidence that tar and nicotine levels do not predict smokers' exposure to carbon monoxide or the tobacco metabolite cotinine (<i>Am Rev Respir Dis</i>. 1993;148:435-440). The Coalition on Smoking and Health is hoping the new evidence moves the Food and Drug Administration (FDA) and Federal Trade Commission (FTC) to acknowledge that the so-called low-yield cigarettes are being deceptively marketed as though they are less of a health hazard than regular cigarettes, and therefore are subject to regulation as drugs under the Food, Drug, and Cosmetic Act. The tobacco industry insists that it does not promote low-yield brands as healthier. "The only health claims on any pack of cigarettes or any cigarette advertisements are those made by the Surgeon General's warning," says Phillip Morris spokesperson Sheila Banks-McKenzie. RJ Reynolds' public
Reporting and Methods in Clinical Prediction Research: A Systematic Review
Authors: Walter Bouwmeester, Nicolaas P. A. Zuithoff, Susan Mallett, Mirjam I. Geerlings, Yvonne Vergouwe, Ewout W. Steyerberg, Douglas G. Altman, Karel G. M. Moons
Journal: PLoS Medicine (2012)

Walter Bouwmeester and colleagues investigated the reporting and methods of prediction studies in 2008, in six high-impact general medical journals, and found that the majority of prediction studies do not follow current methodological recommendations.
Expression of ryanodine receptor type 3 and TRP channels in endothelial cells: comparison of in situ and cultured human endothelial cells
Authors: R Köhler
Journal: Cardiovascular Research (2001)

Objective: Ca2+ mobilization plays an important role in endothelial function by stimulating Ca2+-dependent synthesis of vasodilating factors. In addition to inositol-1,4,5-trisphosphate (InsP3) mediated Ca2+ mobilization, Ca2+ release from ryanodine-sensitive pools and Ca2+-influx through TRP channels have been suggested to be important in endothelial Ca2+-signaling. However, the function and molecular identity of TRP channels and ryanodine receptors in human endothelium in situ are still elusive. We hypothesized that expression of ryanodine-receptors (RyR) and TRP channels differs between human endothelium in situ and in cultured cells. Methods: By combining single-cell RT-PCR and patch-clamp techniques, expression of RyR and TRP channels was determined in situ in endothelial cells of human mesenteric artery (HMAECs) obtained from patients undergoing bowel resection and in the endothelial cell line EA.hy926. Results: At the single cell level, expression of RyR 3 was detected in 25 and 5% of HMAECs and EA.hy926 samples, respectively. Expression of the RyR 1 and 2 was not detected in either HMAECs or EA.hy926. In patch-clamp experiments in HMAECs, applications of caffeine (0.5 mM) induced sustained hyperpolarization mediated by activation of Ca2+-activated K channels. In EA.hy926, caffeine-induced hyperpolarization was not detected. Single HMAECs expressed the TRP genes, TRP1 and TRP3, but not TRP 4 and 6. The TRP1 was the predominantly expressed TRP gene in HMAECs in situ whereas TRP3 expression was rarely detected. EA.hy926 expressed only TRP1. In patch clamp experiments in HMAECs, Ca2+-store depletion activated non-selective cation currents leading to Ca2+ entry. Conclusions: Our findings suggest that, in addition to InsP3 mediated Ca2+ release, Ca2+ release from ryanodine-sensitive stores mediated by RyR3 and Ca2+ entry through TRP1 might represent important components of endothelial Ca2+ signaling in situ and thereby of endothelial function in intact human blood vessels.
The molecular genetic analysis of the expanding pachyonychia congenita case collection
Authors: N.J. Wilson, E.A. O'Toole, L.M. Milstone, C.D. Hansen, A.A. Shepherd, E. Al‐Asadi, M.E. Schwartz, W.H.I. McLean, E. Sprecher, F.J.D. Smith
Journal: British Journal of Dermatology (2014)

Pachyonychia congenita (PC) is a rare autosomal dominant keratinizing disorder characterized by severe, painful, palmoplantar keratoderma and nail dystrophy, often accompanied by oral leucokeratosis, cysts and follicular keratosis. It is caused by mutations in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16 or KRT17.To identify mutations in 84 new families with a clinical diagnosis of PC, recruited by the International Pachyonychia Congenita Research Registry during the last few years.Genomic DNA isolated from saliva or peripheral blood leucocytes was amplified using primers specific for the PC-associated keratin genes and polymerase chain reaction products were directly sequenced.Mutations were identified in 84 families in the PC-associated keratin genes, comprising 46 distinct keratin mutations. Fourteen were previously unreported mutations, bringing the total number of different keratin mutations associated with PC to 105.By identifying mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17, this study has confirmed, at the molecular level, the clinical diagnosis of PC in these families.
Vascular Effects of Improving Metabolic Control With Metformin or Rosiglitazone in Type 2 Diabetes
Authors: Andrea Natali, Stephanie Baldeweg, Elena Toschi, Brunella Capaldo, Daniele Barbaro, Amalia Gastaldelli, John S. Yudkin, Ele Ferrannini
Journal: Diabetes Care (2004)

OBJECTIVE—The aim of this study was to test whether vascular reactivity is modified by improving metabolic control and peripheral insulin resistance in type 2 diabetes. RESEARCH DESIGN AND METHODS—In a randomized, double-blind design, we assigned 74 type 2 diabetic patients to rosiglitazone (8 mg/day), metformin (1,500 mg/day), or placebo treatment for 16 weeks and measured insulin sensitivity (euglycemic insulin clamp), ambulatory blood pressure, and forearm blood flow response to 1) intra-arterial acetylcholine (ACh), 2) intra-arterial nitroprusside, 3) the clamp, and 4) blockade of nitric oxide (NO) synthase. RESULTS—Compared with 25 nondiabetic subjects, patients had reduced insulin sensitivity (30 ± 1 vs. 41 ± 3 μmol · min−1 · kg fat-free mass−1; P &amp;lt; 0.001) and reduced maximal response to ACh (586 ± 42 vs. 883 ± 81%; P &amp;lt; 0.001). Relative to placebo, 16 weeks of rosiglitazone and metformin similarly reduced fasting glucose (−2.3 ± 0.5 and −2.3 ± 0.5 mmol/l) and HbA1c (−1.2 ± 0.3 and −1.6 ± 0.3%). Insulin sensitivity increased with rosiglitazone (+6 ± 3 μmol · min−1 · kg fat-free mass−1; P &amp;lt; 0.01) but not with metformin or placebo. Ambulatory diastolic blood pressure fell consistently (−2 ± 1 mmHg; P &amp;lt; 0.05) only in the rosiglitazone group. Nitroprusside dose response, clamp-induced vasodilatation, and NO blockade were not affected by either treatment. In contrast, the slope of the ACh dose response improved with rosiglitazone (+40% versus baseline, P &amp;lt; 0.05, +70% versus placebo, P &amp;lt; 0.005) but did not change with either metformin or placebo. This improvement in endothelium-dependent vasodilatation was accompanied by decrements in circulating levels of free fatty acids and tumor necrosis factor-α. CONCLUSIONS—At equivalent glycemic control, rosiglitazone, but not metformin, improves endothelium dependent vasodilatation and insulin sensitivity in type 2 diabetes.
Firearm Homicide Among Black Teenage Males in Metropolitan Counties
Authors: Lois A. Fingerhut
Journal: JAMA (1992)

<h3>Objective.</h3> —To identify US counties (1) that had either significantly high or significantly low firearm homicide rates among black males 15 through 19 years of age in 1983 through 1985 and in 1987 through 1989, and/or (2) that experienced a significant increase in the firearm homicide rate between 1983 through 1985 and 1987 through 1989. <h3>Design.</h3> —Using the Compressed Mortality File, a county-level mortality and population database maintained by the National Center for Health Statistics, Centers for Disease Control, Hyattsville, Md, county-level firearm homicide rates are analyzed. <h3>Setting.</h3> —Eighty counties with a population of at least 10 000 black males 15 through 19 years of age in 1987 through 1989. <h3>Subjects.</h3> —Black males 15 through 19 years of age whose underlying cause of death was classified as firearm homicide (E965.0 through E965.4, or E970) in the<i>ICD-9 (International Statistical Classification of Diseases, Injuries, and Causes of Death, Ninth Revision).</i> <h3>Main Outcome Measure.</h3> —County-specific firearm homicide rate. <h3>Results.</h3> —In 1983 through 1985 and in 1987 through 1989, seven and 13 counties, respectively, were identified that had significantly high firearm homicide rates. Firearm homicide rates were significantly high in both time periods in the following counties: Los Angeles, California; Wayne, Michigan; Kings, New York; St Louis City, Missouri; and Baltimore City, Maryland. Firearm homicide rates increased significantly between 1983 through 1985 and 1987 through 1989 in 34 of the 80 counties. Twenty counties had significantly low rates in both time periods. Several counties with low rates in 1983 through 1985 experienced significant increases and by 1987 through 1989 were among those with high rates. <h3>Conclusions.</h3> —Surveillance of firearm homicide rates at the county level in counties with high and with low rates is a necessary first step in the development of successful violence prevention programs. Those counties where rates are high and increasing are the counties that are in greatest need for intervention strategies. Knowledge of the incidence of nonfatal firearm injuries is also needed. (<i>JAMA</i>. 1992;267:3054-3058)
A Practice-Related Educational Program
Authors: Francis L. Bowler
Journal: JAMA (1977)

A Practice-Related Educational Program has been developed to help the physician in primary practice meet the mounting pressures for continuing medical education. Based on analysis of his practice, the physician tests himself to identify areas of potential improvement. Learning resources appropriate to his educational needs are then made available to him at his home base. A follow-up test determines if the person's learning has been effective, and where further emphasis may be placed. (<i>JAMA</i>237:1346-1349, 1977)
DIPHTHERIA CONTROL IN CHICAGO
Authors: HERMAN N. BUNDESEN
Journal: JAMA (1933)

Experiences in New York State and in Detroit and other cities during the past nine years seem to indicate that if certain fractions of the child population were immunized against diphtheria, epidemics would not occur.<sup>1</sup>It is usually stated that if 35 per cent of the preschool children and 50 per cent of the school children were immunized, outbreaks of diphtheria in a community would not be possible.<sup>2</sup> It is generally agreed that the most satisfactory method of active diphtheria immunization at the present time is with toxoid. Of a series of 100 infants, aged from 4 days to 2 years, given two injections of ordinary toxoid at intervals of either one or three weeks apart, 98 became Schick negative within three months.<sup>3</sup> Recently, the alum toxoid first described in 1931,<sup>4</sup>and afterward perfected by Park,<sup>5</sup>has been shown to be even more efficient. In
Endocytoscopic imaging and tattooing: a caveat
Authors: A. Fasoli, V. Pugliese, B. Gatteschi, M. Truini, E. Meroni
Journal: Endoscopy (2009)

When precise anatomical location of a lesion is essential for endoscopic follow-up after resection, the colonic mucosa is commonly tattooed by submucosal injection of India ink [1] [2] [3]. Our early experience [4] seems to suggest a role of endocytoscopy (ECS) for improving detection of early recurrences of high risk and/or malignant adenomas. However, potential imaging artifacts induced by previous tattooing led us to investigate limitations, if any, of ECS under these circumstances.
EXPERIMENTAL EPIDEMIOLOGY OF TUBERCULOSIS
Authors: Max B. Lurie
Journal: The Journal of Experimental Medicine (1930)

1. Guinea pigs living in the same room but not in the same cage with tuberculous animals acquire tuberculosis, characterized by a chronic course, a marked involvement of the lungs, often with cavity formation and a massive tuberculosis of the tracheobronchial nodes; the mesenteric and cervical nodes are slightly or not at all affected. 2. The route of infection in these guinea pigs is almost always the respiratory tract. 3. Of 103 guinea pigs exposed for a period of up to 32 months 15 or 14.5 per cent developed tuberculosis. The shortest period of exposure leading to fatal tuberculosis was 8 months. 4. The incidence of this tuberculosis acquired by air-borne contagion increases with the duration and intensity of the exposure up to a certain point. 5. A large percentage of the guinea pigs weathered a continuous exposure to the tubercle bacillus for 32 months without becoming tuberculous. This may be due to an innate natural resistance against tuberculosis, or to an acquired immunity resulting from the continuous exposure to the contagion.
Has a New Start—Open Access
Authors: Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2012)

We are now presenting to our readers the first issue of Volume 10 of Genomics, Proteomics & Bioinformatics (GPB).It is also the first issue for the new status.GPB was founded in 2003 and published in English, focusing on research advancement in the fields of omics and bioinformatics.To ensure an international presence, GPB has its 30-50% editorial board members from outside China.From 2006, GPB has been co
Knowing and knowing about
Authors: Ed Peile
Journal: BMJ (2006)

The intracellular signaling mediator TRAF6 is critical for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). Recently we have reported that TRAF6 in DCs is important to maintenance of intestinal immune tolerance through balanced induction of regulatory T cells versus Th2 immunity. In addition, we found a clue that loss of TRAF6ΔDC mucosal tolerance requires the presence of commensal microbiota in a manner that appears independent of the Myd88 pathway. However, which environmental factors induce abnormal Th2 immunity and disease phenotype in TRAF6ΔDC mice remains unclear. Here we suggest that spontaneous gut inflammation occurred in TRAF6ΔDC mice is strongly associated to dietary antigens as well as microbiota.
The Repetitive Ventricular Response in Man
Authors: H. Leon Greene, Philip R. Reid, Allen H. Schaeffer
Journal: New England Journal of Medicine (1978)

We examined the value of cardiac pacing for assessing ventricular electrical instability and for predicting ventricular tachycardia and sudden death in 50 patients with refractory symptomatic ventricular tachycardia, 12 normal patients, and 48 survivors of a recent myocardial infarction. The repetitive ventricular response (two or more ventricular premature beats produced by a single ventricular pacing stimulus during control of heart rate with atrial pacing) was absent in all 12 normal patients but was present in 44 of the 50 patients (88 per cent) with recurrent ventricular tachycardia (P<0.001). Of the 48 survivors of myocardial infarction, 19 had repetitive ventricular responses. During the next 12 months 15 of these patients (79 per cent) had symptomatic ventricular tachycardia or sudden death, or both, as compared with four of 29 patients (14 per cent) who did not have repetitive ventricular responses (P<0.001). The repetitive ventricular response identifies patients with life-threatening ventricular instability, but it is still an investigational technic that should be used only with due precautions. (N Engl J Med 299:729–734, 1978)
The U.S. federal framework for research on endocrine disruptors and an analysis of research programs supported during fiscal year 1996.
Authors: L W Reiter, C DeRosa, R J Kavlock, G Lucier, M J Mac, J Melillo, R L Melnick, T Sinks, B T Walton
Journal: Environmental Health Perspectives (1998)

The potential health and ecological effects of endocrine disrupting chemicals has become a high visibility environmental issue. The 1990s have witnessed a growing concern, both on the part of the scientific community and the public, that environmental chemicals may be causing widespread effects in humans and in a variety of fish and wildlife species. This growing concern led the Committee on the Environment and Natural Resources (CENR) of the National Science and Technology Council to identify the endocrine disruptor issue as a major research initiative in early 1995 and subsequently establish an ad hoc Working Group on Endocrine Disruptors. The objectives of the working group are to 1) develop a planning framework for federal research related to human and ecological health effects of endocrine disrupting chemicals; 2) conduct an inventory of ongoing federal research programs; and 3) identify research gaps and develop a coordinated interagency plan to address priority research needs. This communication summarizes the activities of the federal government in defining a common framework for planning an endocrine disruptor research program and in assessing the status of the current effort. After developing the research framework and compiling an inventory of active research projects supported by the federal government in fiscal year 1996, the CENR working group evaluated the current federal effort by comparing the ongoing activities with the research needs identified in the framework. The analysis showed that the federal government supports considerable research on human health effects, ecological effects, and exposure assessment, with a predominance of activity occurring under human health effects. The analysis also indicates that studies on reproductive development and carcinogenesis are more prevalent than studies on neurotoxicity and immunotoxicity, that mammals (mostly laboratory animals) are the main species under study, and that chlorinated dibenzodioxins and polychlorinated biphenyls are the most commonly studied chemical classes. Comparison of the inventory with the research needs should allow identification of underrepresented research areas in need of attention.
Abstract 4061: A novel CXCR4-mediated mechanism of docetaxel resistance in prostate cancer cells.
Authors: Arun Bhardwaj, Sanjeev K. Srivastava, Sumit Arora, Stephen J. Hyde, Joel F. Andrews, Steven McClellan, Seema Singh, Ajay P. Singh
Journal: Cancer Research (2013)

Abstract Docetaxel (DTX), a semi-synthetic analog of paclitaxel, has emerged as the standard of care for chemotherapy of hormone-resistant prostate cancer. DTX confers its anti-neoplastic activity by inhibiting microtubule depolymerization, which leads to G2/M cell cycle arrest and subsequent apoptosis. However, most patients treated with DTX ultimately develop resistance to the drug and succumb to the disease. Therefore, understanding the mechanisms underlying DTX resistance is a priority area in prostate cancer research. Increasingly, it is being suggested that cancer cells may use common pathways for disease aggressiveness/metastatic spread and chemotherapeutic resistance. Therefore, we investigated the role of CXCL12/CXCR4 signaling, which is known to promote invasion and metastasis, in DTX-resistance of prostate cancer cells. Our data demonstrated that CXCL12 treatment rescued the prostate cancer cells from DTX-induced cytotoxicity and G2/M mitotic arrest. Furthermore, the cytoprotective effect of CXCL12 was abolished upon pretreatment of prostate cancer cells with AMD3100 (a small molecule antagonist of CXCR4) or siRNA-mediated silencing of CXCR4, thus confirming the role of CXCR4 in DTX-resistance. Immunofluorescence analyses revealed enhanced polymerization of microtubules in DTX-treated prostate cancer cells. In accordance with this, immunoblot analyses demonstrated increased levels of detyrosinated (glu-) and acetylated (ace-) tubulins, specific markers of the polymerized tubulin, in prostate cancer cells treated with DTX. Co-treatment of CXCL12 abrogated DTX-induced stabilization of microtubules in the prostate cancer cells, an effect that was diminished when the cells were pre-treated with AMD3100. Altogether, these initial findings demonstrate the role of CXCL12/CXCR4 signaling axis in DTX-resistance of prostate cancer cells and thus could be an attractive target for therapeutic enhancement of DTX. Citation Format: Arun Bhardwaj, Sanjeev K. Srivastava, Sumit Arora, Stephen J. Hyde, Joel F. Andrews, Steven McClellan, Seema Singh, Ajay P. Singh. A novel CXCR4-mediated mechanism of docetaxel resistance in prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4061. doi:10.1158/1538-7445.AM2013-4061