tbuckley/cabot-search huggingface dataset:
Structural basis for reduced glomerular filtration capacity in nephrotic humans.
Authors: M C Drumond, B Kristal, B D Myers, W M Deen
Journal: Journal of Clinical Investigation (1994)

Previous studies have established that in a variety of human glomerulopathies the reduced glomerular filtration rate (GFR) is due to a marked lowering of the ultrafiltration coefficient (Kf). To identify the factors which lower Kf, we measured the filtering surface area per glomerulus, filtration slit frequency, basement membrane thickness, and GFR and its determinants in patients with minimal change and membraneous nephropathies and in age-matched healthy controls. Overall values of Kf for the two kidneys were calculated from GFR, renal plasma flow rate, systemic colloid osmotic pressure, and three assumed values for the transcapillary pressure difference. "Experimental" values of the glomerular hydraulic permeability (kexp) were then calculated from Kf, glomerular filtering surface area, and estimates of the total number of nephrons of the two kidneys. Independent estimates of the glomerular hydraulic permeability (kmodel) were obtained using a recent mathematical model that is based on analyses of viscous flow through the various structural components of the glomerular capillary wall. Individual values of basement membrane thickness and filtration slit frequency were used as inputs in this model. The results indicate that the reductions of Kf in both nephropathies can be attributed entirely to reduced glomerular hydraulic permeability. The mean values of kexp and kmodel were very similar in both disorders and much smaller in the nephrotic groups than in healthy controls. There was good agreement between kexp and kmodel for any given group of subjects. It was shown that, in both groups of nephrotics, filtration slit frequency was a more important determinant of the water flow resistance than was basement membrane thickness. The decrease in filtration slit frequency observed in both disorders caused the average path length for the filtrate to increase, thereby explaining the decreased hydraulic permeability.
Damaged epithelia regenerated by bone marrow–derived cells in the human gastrointestinal tract
Authors: Ryuichi Okamoto, Tomoharu Yajima, Motomi Yamazaki, Takanori Kanai, Makio Mukai, Shinichiro Okamoto, Yasuo Ikeda, Toshifumi Hibi, Johji Inazawa, Mamoru Watanabe
Journal: Nature Medicine (2002)
Five facts and five concepts for rehabilitation of mechanical low back pain
Authors: Mark E Batt, Cheralynne Todd
Journal: British Journal of Sports Medicine (2000)

Background-Sudden death in sport is rare, but when it occurs the eVects are devastating.There have not been any reports to date describing the frequency and causes of sudden death in sport in the Republic of Ireland.Aim-To describe the incidence, possible causes, associated factors, and pathological findings in people who died while exercising in the Republic of Ireland in the 10 year period from January 1987 to December 1996.Methods-All 49 regional coroners in the Republic of Ireland were approached and details on all cases of sudden death in sport from 1 January 1987 to 31 December 1996 were requested.A questionnaire was used to document age, sex, participating sport, previous symptoms, previous medical investigations, circumstances of death, and main pathological finding in all reported cases.Results-Of the 49 coroners surveyed, 45 replied.A total of 51 cases of sudden death in sport were identified.The median age was 48 (range 15-78).Fifty of the deaths were of men.Golf was the most popular participating sport.In 42 cases, the pathological cause of death was atherosclerotic coronary artery disease.Conclusions-This is the first time the incidence of sudden death in sport in the Republic of Ireland has been described.The main cause of death in all age groups was atherosclerotic coronary artery disease.
Smoking Wastes a Good Parisienne
Authors: Per Björntorp
Journal: JAMA (1989)

<h3>To the Editor. —</h3> Shimokata et al<sup>1</sup>observed that smoking increases the waist-hip ratio in men. In some crosssectional studies in Swedish men we observed similar associations.<sup>2,3</sup> Waist-hip ratio is presumed to be an indicator of accumulation of visceral (or intra-abdominal) adipose tissue.<sup>4</sup>With computed tomography, the amount of visceral adipose tissue can be calculated from abdominal scans. We selected 23 men from a healthy population (N = 200) aged 25 to 50 years living in Gothenburg, Sweden. They were selected to cover a maximal range of waist-hip ratios and body mass indexes. Computed tomographic scans were taken at L4/L5 and adipose tissue areas were calculated at a range of — 30 to — 190 Hounsfield units. Table 2 shows that smokers had similar body mass indexes and no significantly different subcutaneous and total fat areas compared with men who never smoked. The visceral fat area, however, was almost
Twelve Months' Experience with the GAP Classification of Childhood Disorders
Authors: JULES R. BEMPORAD, CARL M. PFEIFER, WALLACE BLOOM
Journal: American Journal of Psychiatry (1970)

The authors describe their assessment of the value of the new GAP classification of childhood disorders, which took place after this system had been in use in their facility for a year, during which time 310 children were seen. They also compare the GAP classification with DSM-I and DSM-II. While they express overall satisfaction with the GAP classification, they believe that certain changes (which they outline) are warranted.
Abstract 4164: Regulatory mechanism for Ras degradation and its role in the suppression of cellular transformation and tumorigenesis
Authors: Woo-Jeong Jeong, Kang-Yell Choi
Journal: Cancer Research (2012)

Abstract Ras is a well-characterized proto-oncogene, and its various mutations contribute to transformation and tumorigenesis in a wide variety of human cancers. Although the GTP/GDP loading switch is known as a major regulatory mechanism of Ras, other mechanisms affecting Ras activity, especially those related to cancer, are poorly understood. Here, we report a novel regulatory mechanism for Ras degradation and its role in suppression of cellular transformation and tumors induced by Ras mutations. We show that the negative regulators of Wnt/β-catenin signaling are associated with polyubiquitin-dependent degradation of Ras following phosphorylation and subsequent recruitment of α-TrCP-E3 ligase. The interaction of Ras with the WD40 domain of α-TrCP targeted Ras for polyubiquitination and degradation. This process stimulated by Axin or adenomatous polyposis coli (Apc) and was inhibited by Wnt3a via modulating the phosphorylation status of Ras. Ras-mediated cellular transformation was also inhibited by the expression of α-TrCP and/or Axin. In vivo regulation of Ras stability by Wnt/β-catenin signaling was indicated via measurements of the status of Ras in the intestines of mice stimulated with recombinant Wnt3a by intravenous tail vein injection. The Ras deregulation by negative Wnt/β-catenin signaling was also revealed in human cancers such as colorectal cancer and HCCs etc. Together, our results indicate an essential role for phosphorylation and degradation of Ras and suppression of Ras-induced transformation via the Wnt/β-catenin pathway and provide insight into the role of this novel regulatory mechanism for Ras in colorectal tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4164. doi:1538-7445.AM2012-4164
Incidence of intimal proliferation and apoptosis following balloon angioplasty in an atherosclerotic rabbit model
Authors: J Kamenz
Journal: Cardiovascular Research (2000)

The aim of this study was to determine the occurrence of apoptosis in relation to the proliferative response in the intimal layer after experimental balloon angioplasty of a pre-existing plaque.After induction of an intimal plaque in the right carotid artery by electrical stimulation, 26 rabbits underwent balloon angioplasty. Twelve animals served as a control group without performance of angioplasty after plaque induction. To study the time course of intimal apoptosis and cell proliferation the vessels were excised on day 7, 14 and 28 after balloon angioplasty. For in situ detection of apoptosis, the TUNEL-technique (TdT-mediated d-UTP fluorescein nick end labeling) was used. In addition, bromodeoxyuridine labeling in all animals allowed the determination of the percentage of cells undergoing DNA synthesis in the neointimal area. Additionally, smooth muscle cells were detected by immunostaining of alpha-actin and macrophages by a specific antibody (RAM 11).Within 28 days of balloon angioplasty, the number of cells undergoing apoptosis remained at a very low level and was not significantly different to the control group without interventional treatment (controls: 0.1 +/- 0.15%; 7 days: 0.44 +/- 0.68%; 14 days: 0.13 +/- 0.11%; 28 days: 0.1 +/- 0.1%). In contrast, the number of cells undergoing DNA synthesis was significantly increased at day 7 after angioplasty (3.72 +/- 2.0% vs. 0.51 +/- 0.29% in controls), resulting in an increase of the total intimal area from 0.088 +/- 0.037 mm2 in the control animals up to 0.256 +/- 0.172 mm2 at day 28 following balloon dilatation.Our data showed that significant changes in the occurrence of apoptosis are not involved in the regulation of cellular turnover during the examined time period after vessel wall injury. The lacking up-regulation of apoptosis in comparison to the increased cell proliferation in order to maintain the tissue balance is perhaps an important regulatory mechanism leading to intimal hyperplasia after vascular injury in this animal model. Overall, we suggest that there may be a delicate balance between cell proliferation and apoptosis in smooth muscle cells of the vessel wall, and only small shifts in this balance could account for both cellular accumulation in restenotic lesions as well as cell death in mature atheroma.
Uncritical Thinking in Medicine
Authors: Michael H. M. Dykes
Journal: JAMA (1974)

NO ONE involved in providing health care, whether a professional or a patient, would disagree that the primary goal of the system is maintenance of the health of the patient. A corollary of this position is the assertion that ideally every prophylactic or therapeutic maneuver should have a greater chance of improving rather than of worsening the health of the patient. While it is easy to make this assertion, a number of factors have ensured that in practice it may be extremely difficult for a physician to be certain that a specific clinical maneuver is indeed indicated for a specific patient. Ingelfinger<sup>1</sup>has succinctly defined the ingredients that distinguish the good physician as "the exercise of well based and independent clinical judgment." Although this communication will address itself to a discussion of problems inherent in deciding what is or is not a well-based therapeutic maneuver, it is not intended
A Survey of Medication Treatment for Hyperactive/Inattentive Students
Authors: Daniel J. Safer, John M. Krager
Journal: JAMA (1988)

Since 1971, the Baltimore County Health Department has conducted nine biannual surveys of school nurses in all of the county's public and private schools to determine the prevalence of medication treatment for hyperactivity/inattentiveness among students. The results reveal a consistent doubling of the rate of medication treatment for hyperactive/inattentive students every four to seven years such that in 1987,5.96% of all public elementary school students were receiving such treatment. Related trends from 1971 to 1987 have been that stimulants increased from 76% to 99% of the medication prescribed; methylphenidate hydrochloride rose from 40% to 93% of the total; the male-female ratio dropped from an average of 8:1 to 5:1; the rate of medication treatment for hyperactive/inattentive students rose faster in secondary than in elementary schools; and 25% of students receiving stimulant medication in 1987 were in special education classes or schools. (<i>JAMA</i>1988;260:2256-2258)
In the idiopathic inflammatory myopathies (IIM), do reactive oxygen species (ROS) contribute to muscle weakness?
Authors: Adam P Lightfoot, Anne McArdle, Malcolm J Jackson, Robert G Cooper
Journal: Annals of the Rheumatic Diseases (2015)

The idiopathic inflammatory myopathies (IIMs) are a group of rare autoimmune disorders, collectively known as myositis. Affected patients present with proximal muscle weakness, which usually improves following treatment with immunosuppressants, but often incompletely so, thus many patients remain weak. IIMs are characterised histologically by inflammatory cell infiltrates into skeletal muscle and overexpression of major histocompatibility complex I on muscle cell surfaces. Although inflammatory cell infiltrates represent a major feature of myositis there is growing evidence that muscle weakness correlates only poorly with the degree of cellular infiltration, while weakness may in fact precede such infiltrations. The mechanisms underpinning such non-immune cell mediated weakness in IIM are poorly understood. Activation of the endoplasmic reticulum stress pathways appears to be a potential contributor. Data from non-muscle cells indicate that endoplasmic reticulum stress results in altered redox homeostasis capable of causing oxidative damage. In myopathological situations other than IIM, as seen in ageing and sepsis, evidence supports an important role for reactive oxygen species (ROS). Modified ROS generation is associated with mitochondrial dysfunction, depressed force generation and activation of muscle catabolic and autophagy pathways. Despite the growing evidence demonstrating a key role for ROS in skeletal muscle dysfunction in myopathologies other than IIM, no research has yet investigated the role of modified generation of ROS in inducing the weakness characteristic of IIM. This article reviews current knowledge regarding muscle weakness in the absence of immune cells in IIM, and provides a background to the potential role of modified ROS generation as a mechanism of muscle dysfunction. The authors suggest that ROS-mediated mechanisms are potentially involved in non-immune cell mediated weakness seen in IIM and outline how these mechanisms might be investigated in this context. This appears a timely strategy, given recent developments in targeted therapies which specifically modify ROS generation.
Obama champions new targets for treating and preventing HIV and AIDS
Authors: Z. Kmietowicz
Journal: BMJ (2011)

The US president, Barack Obama, has announced new expanded targets for the country’s programme for combating HIV and AIDS around the world, by promising to support more than six million people on antiretroviral treatment by the end of 2013, two million more than previously planned.

Speaking to mark world AIDS day on 1 December at George Washington University, Washington, DC, President Obama said that the President’s Emergency Plan for AIDS Relief (PEPFAR) would also, over the next two years, provide antiretrovirals to 1.5 million HIV positive women, support more than 4.7 million voluntary male circumcisions in eastern and southern Africa, and distribute more than a billion condoms.

PEPFAR, …
Differential effects of hydroxyurea and INC424 on mutant allele burden and myeloproliferative phenotype in a JAK2-V617F polycythemia vera mouse model
Authors: Lucia Kubovcakova, Pontus Lundberg, Jean Grisouard, Hui Hao-Shen, Vincent Romanet, Rita Andraos, Masato Murakami, Stephan Dirnhofer, Kay-Uwe Wagner, Thomas Radimerski, Radek C. Skoda
Journal: Blood (2012)
Lower Mortality From Coronary Heart Disease and Stroke at Higher Altitudes in Switzerland
Authors: David Faeh, Felix Gutzwiller, Matthias Bopp
Journal: Circulation (2009)

Background— Studies assessing the effect of altitude on cardiovascular disease have provided conflicting results. Most studies were limited because of the heterogeneity of the population, their ecological design, or both. In addition, effects of place of birth were rarely considered. Here, we examine mortality from coronary heart disease and stroke in relation to the altitude of the place of residence in 1990 and at birth. Methods and Results— Mortality data from 1990 to 2000, sociodemographic information, and places of birth and residence in 1990 (men and women between 40 and 84 years of age living at altitudes of 259 to 1960 m) were obtained from the Swiss National Cohort, a longitudinal, census-based record linkage study. The 1.64 million German Swiss residents born in Switzerland provided 14.5 million person-years. Relative risks were calculated with multivariable Poisson regression. Mortality from coronary heart disease (−22% per 1000 m) and stroke (−12% per 1000 m) significantly decreased with increasing altitude. Being born at altitudes higher or lower than the place of residence was associated with lower or higher risk. Conclusions— The protective effect of living at higher altitude on coronary heart disease and stroke mortality was consistent and became stronger after adjustment for potential confounders. Being born at high altitude had an additional and independent beneficial effect on coronary heart disease mortality. The effect is unlikely to be due to classic cardiovascular disease risk factors and rather could be explained by factors related to climate.
443 HBX-INDUCED REPRESSION OF MIR224 EXPRESSION RELIEVES THE DIRECT INHIBITORY EFFECTS OF MIR224 ON HBV PGRNA TO POTENTIATE HBV REPLICATION
Authors: F. Guerrieri, C. Scisciani, L. Belloni, A. Sbardellati, A. Tramontano, M. Levrero, N. Pediconi
Journal: Journal of Hepatology (2012)
Alterations in endocardial vascular resistance after reperfusion in a low flow, high demand model of ischemia: effects of dipyridamole and WEB-2086, a platelet-activating factor antagonist
Authors: Erwin Schröder, Hubert Pouleur, Henri Van Mechelen, André Keyeux, Juan Raigoso, André Charlier
Journal: Journal of the American College of Cardiology (1990)
Metabolic fate of arachidonic acid in hepatocytes of continuously endotoxemic rats.
Authors: E B Rodriguez de Turco, J A Spitzer
Journal: Journal of Clinical Investigation (1988)

The present experiments were designed to characterize the kinetics of [1-14C]arachidonic acid (AA) metabolism as a function of time in hepatocytes obtained from rats infused continuously for 30 h with a nonlethal dose of Escherichia coli endotoxin (ET). Chronic endotoxemia greatly reduces the ability of hepatocytes to utilize [1-14C]AA, which is reflected from the earliest times of incubation in very low labeling of intermediates in the biosynthetic pathways of glycerolipids (phosphatidic acid and diacylglycerol) and slower removal of [1-14C]AA from the free fatty acid pool as compared with saline-infused rats. At later times of incubation, the labeling of phospholipids (especially phosphatidylethanolamine and phosphatidylinositol [PI]), but not of triacylglycerides is decreased. Analysis of fatty acid composition of individual phospholipids from cells of ET-infused rats reveals that the content of AA is significantly reduced only in PI. Hence an impairment in activation/acylation enzymatic mechanisms could affect the turnover of metabolically active phospholipid pools, i.e., PI, involved in signal transmission processes, and result in increased availability of 20:4 for eicosanoid synthesis, contributing to cellular metabolic perturbations in endotoxicosis.
Preparation of the Parturient Patient.
Authors: Norman Roberts
Journal: JAMA (1905)

Fort Stanton, N. M., Jan. 9, 1905. <h3>To the Editor:</h3> —Why is it that the great majority of obstetricians are so neglectful of surgical cleanliness as applied to the external genitals of women in labor? The gynecologist shaves and scrubs the external genitals for every minor operation, and the surgeon does the same even when his field is in the abdomen six inches from the nearest of the pubic hair. But in a disgracefully large proportion of all deliveries no attempt whatever is made by the obstetrician to clean his field of operation, with the result of thousands of unnecessary deaths every year and an incalculable amount of chronic invalidism and sterility. Location, anatomic conformation and functions of the vulva all combine to favor the accumulation there of a large and varied assortment of putrescible materials and pathogenic bacteria. Yet many an obstetrician allows his sterilized hand to come in
Projection of Diabetes Burden Through 2050
Authors: James P. Boyle, Amanda A. Honeycutt, K.M. Venkat Narayan, Thomas J. Hoerger, Linda S. Geiss, Hong Chen, Theodore J. Thompson
Journal: Diabetes Care (2001)

To project the number of people with diagnosed diabetes in the U.S. through 2050, accounting for changing demography and diabetes prevalence rates.We combined age-, sex-, and race-specific diagnosed diabetes prevalence rates-predicted from 1980-1998 trends in prevalence data from the National Health Interview Survey-with Bureau of Census population demographic projections. Sensitivity analyses were performed by varying both prevalence rate and population projections.The number of Americans with diagnosed diabetes is projected to increase 165%, from 11 million in 2000 (prevalence of 4.0%) to 29 million in 2050 (prevalence of 7.2%). The largest percent increase in diagnosed diabetes will be among those aged > or =75 years (+271% in women and +437% in men). The fastest growing ethnic group with diagnosed diabetes is expected to be black males (+363% from 2000-2050), with black females (+217%), white males (+148%), and white females (+107%) following. Of the projected 18 million increase in the number of cases of diabetes in 2050, 37% are due to changes in demographic composition, 27% are due to population growth, and 36% are due to increasing prevalence rates.If recent trends in diabetes prevalence rates continue linearly over the next 50 years, future changes in the size and demographic characteristics of the U.S. population will lead to dramatic increases in the number of Americans with diagnosed diabetes.
Biliary tract diseases in the elderly: management and outcomes
Authors: JEROME H SIEGEL, FRANKLIN E KASMIN
Journal: Gut (1997)

Elderly people commonly present with biliary tract disease. Gallstone disease is an important cause of recurrent abdominal symptoms, and we advocate an aggressive approach in stable patients not at risk to improve the quality of their lives. Choledocholithiasis is optimally treated by ERCP (98% success) even in patients who are at great risk. Endoscopic intervention often obviates the need for emergency biliary tract surgery in the elderly, is better tolerated, and is associated with significantly less risk and a lower mortality. In contrast, emergency surgery in the elderly is poorly tolerated. Even cholecystitis and biliary pancreatitis (not discussed here) are amenable to endoscopic treatment. Malignant biliary obstruction should not and cannot be treated as aggressively as benign disorders affecting the biliary tree as the long term outlook is poor. Endoscopic palliation usually suffices in maximising treatment and improving the patient's quality of life with few associated complications or postprocedural machinations (drainage bags or tubes). The afflicted population in general and the elderly in particular benefit from minimally invasive endoscopic decompression techniques.
TCT-817 Transcatheter Aortic Valve Replacement with a New Balloon Expandable Percutaneous Heart Valve
Authors: Ronald Binder, Josep Rodes-Cabau, David Wood, Michael Mok, Jonathon Leipsic, Robert De Larochelliere, Stefan Toggweiler, Eric Dumont, Melanie Freeman, Alex Willson, John Webb
Journal: Journal of the American College of Cardiology (2012)