tbuckley/cabot-search huggingface dataset:
Checkpoints that control B cell development
Authors: Fritz Melchers
Journal: Journal of Clinical Investigation (2015)

B cells differentiate from pluripotent hematopoietic stem cells (pHSCs) in a series of distinct stages. During early embryonic development, pHSCs migrate into the fetal liver, where they develop and mature to B cells in a transient wave, which preferentially populates epithelia and lung as well as gut-associated lymphoid tissues. This is followed by continuous B cell development throughout life in the bone marrow to immature B cells that migrate to secondary lymphoid tissues, where they mature. At early stages of development, before B cell maturation, the gene loci encoding the heavy and light chains of immunoglobulin that determine the B cell receptor composition undergo stepwise rearrangements of variable region-encoding gene segments. Throughout life, these gene rearrangements continuously generate B cell repertoires capable of recognizing a plethora of self-antigens and non–self-antigens. The microenvironment in which these B cell repertoires develop provide signaling molecules that play critical roles in promoting gene rearrangements, proliferation, survival, or apoptosis, and that help to distinguish self-reactive from non–self-reactive B cells at four distinct checkpoints. This refinement of the B cell repertoire directly contributes to immunity, and defects in the process contribute to autoimmune disease.
The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction
Authors: Jeanna C. Perman, Pontus Boström, Malin Lindbom, Ulf Lidberg, Marcus StÅhlman, Daniel Hägg, Henrik Lindskog, Margareta Scharin Täng, Elmir Omerovic, Lillemor Mattsson Hultén, Anders Jeppsson, Petur Petursson, Johan Herlitz, Gunilla Olivecrona, Dudley K. Strickland, Kim Ekroos, Sven-Olof Olofsson, Jan Borén
Journal: Journal of Clinical Investigation (2011)

Impaired cardiac function is associated with myocardial triglyceride accumulation, but it is not clear how the lipids accumulate or whether this accumulation is detrimental. Here we show that hypoxia/ischemia-induced accumulation of lipids in HL-1 cardiomyocytes and mouse hearts is dependent on expression of the VLDL receptor (VLDLR). Hypoxia-induced VLDLR expression in HL-1 cells was dependent on HIF-1α through its interaction with a hypoxia-responsive element in the Vldlr promoter, and VLDLR promoted the endocytosis of lipoproteins. Furthermore, VLDLR expression was higher in ischemic compared with nonischemic left ventricles from human hearts and was correlated with the total lipid droplet area in the cardiomyocytes. Importantly, Vldlr-/- mice showed improved survival and decreased infarct area following an induced myocardial infarction. ER stress, which leads to apoptosis, is known to be involved in ischemic heart disease. We found that ischemia-induced ER stress and apoptosis in mouse hearts were reduced in Vldlr-/- mice and in mice treated with antibodies specific for VLDLR. These findings suggest that VLDLR-induced lipid accumulation in the ischemic heart worsens survival by increasing ER stress and apoptosis.
Intracellular Crystals in Synovial Fluid Anticoagulated with Oxalate
Authors: H. Ralph Schumacher
Journal: New England Journal of Medicine (1966)

MICBOSCOPICAL examination of synovial fluid for identification of crystals is frequently performed for the diagnosis of gout or pseudogout (chondrocalcinosis). Problems may arise in the differentiation of the sodium urafe from calcium pyrophosphate crystals1 or in distinguishing cholesterol crystals that may be seen in rheumatoid arthritis2 and fibrillar cartilage material in degenerative arthritis.3 Crystals formed from oxalate used as an anticoagulant for the synovial fluid can also be a source of confusion, as noted by Gatter and McCarty4 in a paper published in England, but this possibility has not been widely recognized. This report describes the detection of such oxalate . . .
Long QT interval syndrome. A new look at an old electrocardiographic measurement--the power of the computer.
Authors: M M Laks
Journal: Circulation (1990)

Because clinical studies frequently include only a marginal number of patients, these relatively new, robust statistical techniques will have increased use. The utilization of ROC curves will be more commonplace because they permit the comprehension of the data in a more dynamic mode than merely the reporting of sensitivities and specificities.
Drugs and Behavior
Authors: Thomas T. Tourlentes
Journal: JAMA (1982)

This is a fascinating book with a wealth of interesting and useful information. It brings to life the pharmacology of psychoactive drugs in a way that is meaningful to every practicing physician, regardless of style or type of practice. It also is the sort of book that should be on everyone's reading list of basic texts and standard reference works. Professor Fred Leavitt, the author, has searched the literature thoroughly to augment his own considerable knowledge in the field. Presenting pharmacological facts behaviorally adds greatly to the readability and relevance of a subject ordinarily viewed as dull and esoteric by many clinicians. The organization of topics is logical and lucid, and there is something of immediate interest and importance on every page. This book is almost encyclopedic in its scope, but it also has the added virtue of cohesiveness and brevity. Psychopharmacology is a rapidly changing and often confusing field.
Referral to hospital: can we do better?
Authors: M. Marinker, D. Wilkin, D. H. Metcalfe
Journal: BMJ (1988)

The variation in rates of referral to hospital in general practice-is such that questions about quality and cost can no longer be avoided.In considering referral to hospital the government has now declared that family practitioner committees and the health authorities "should act to ensure that the use of hospital facilities achieves the maximum benefit for patients and services are used to ensure quality of care in a cost effective way."'No definition of benefit is vouchsafed.Benefits might be finding disease, altering the outcome of the disease, or reducing anxiety.In this paper we consider four broad strategies that could be envisaged: adopting norms, rationing, management incentives, and performance review. Adopting normsThe search for economies is most likely to be expressed as a drive to improve the specificity of the decision to refer-that is, to reduce unnecessary referrals.Doctors referring many patients would be encouraged to reduce their referral rates on the assumption that many of the patients they refer do not benefit from, or may be harmed by, referral.Little if anything will be done to increase the sensitivity of the doctor's decision to refer-that is, to increase the number of appropriate referrals.If the Department of Health and Social Security were to make an analogy with its use of data on prescribing regional medical officers might visit the deviants and endeavour to effect a regression to the mean.One problem in drawing an analogy with data on prescribing is that the variance in rates of referral to hospital is much larger than that in prescribing rates.A recent study showed a 25-fold difference between the outliers and a fourfold difference between doctors in the top and bottom fifths for referrals (figure).2The number of general practitioners with high referral rates MSD Foundation, London
Immunoidiopathic or Immunogenic Thrombocytopenic Purpura
Authors: Robert Handin, Arnold L. Smith
Journal: New England Journal of Medicine (1972)

Two decades ago Harrington demonstrated the presence of a humoral antiplatelet factor in patients with idiopathic thrombocytopenic purpura (ITP). Infusion of plasma from patients with ITP into normal persons caused a precipitous fall in the recipient's platelet count.1 Subsequent infusion studies demonstrated that the antiplatelet factor is species specific, has the physicochemical characteristics of an immunoglobulin, and can be adsorbed by autologous or homologous platelets. Although Harrington's studies established that ITP had an immunologic basis, further characterization of the immunologic mechanisms was hindered by the lack of sensitive, specific and reliable methods to detect antiplatelet antibody.Recently, some progress has . . .
Reactive Arthritis and Strongyloides
Authors: G. Forzy
Journal: JAMA (1988)

<h3>To the Editor.</h3> —Reactive arthritis induced by parasitic infestation is rare,<sup>1,2</sup>but this condition has to be kept in mind since a specific antiparasitic treatment is effective. We describe herein a patient with reactive arthritis caused by<i>Strongyloides stercoralis</i>. <h3>Report of a Case.</h3> —A 31-year-old dental hygienist had an unremarkable medical or surgical history, except for a trip to Mexico three months before seeing us. He consulted us following the recent acute appearance of arthritis. The symptoms were polyarticular and symmetrical and principally involved the distal joints. The onset of arthritis had been accompanied by fever (temperature, 39.5°C) and asthenia. His condition improved following treatment with aspirin (acetylsalicylic acid) (3 g/d for three days) and at that time signs of arthritis were restricted to the right shoulder and knee. His erythrocyte sedimentation rate remained elevated; he had leukocytosis (18.0 × 10<sup>9</sup>cells per liter [18 000/mm<sup>3</sup>]) and
Direct comparison of inhaled nitric oxide and aerosolized prostacyclin in acute respiratory distress syndrome.
Authors: D Walmrath, T Schneider, R Schermuly, H Olschewski, F Grimminger, W Seeger
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Inhalation of NO and aerosolization of PGI2 have been suggested to achieve selective pulmonary vasodilation and improvement of arterial oxygenation in patients with ARDS. We directly compared these two modes of transbronchial vasodilator therapy in 16 ARDS patients mechanically ventilated (mean lung injury score [1] 2.75 +/- 0.05). Patients were randomized to receive either first NO and then PGI2, or vice versa. Each drug was individually titrated to find the maximum improvement of arterial oxygenation. Gas exchange variables, including data from the multiple inert gas elimination technique (MIGET), and hemodynamics under application of NO/PGI2 were compared with pre- and post-challenge values. NO (17.8 +/- 2.7 ppm) increased Pa O2/FI O2 from 115 +/- 12 to 144 +/- 15 mm Hg (p<0.01) and reduced the shunt-flow from 33.1 +/- 3.6 to 26.6 +/- 4.5% (p<0.05). Aerosolized PGI2 (7.5 +/- 2.5 ng/kg min) augmented Pa O2/FI O2 from 114 +/- 12 to 135 +/- 12 mm Hg (p<0.01), and decreased shunt from 33.5 +/- 3.8 to 26.0 +/- 3.9% (p<0.05). In 10 patients, both NO and PGI2 caused an increase in Pa O2/FI O2 by at least 10 mm Hg. Two further patients displayed an improvement of arterial oxygenation in response to either NO or PGI2. NO decreased mean pulmonary artery pressure from 34.8 +/- 2.2 to 33.0 +/- 1.8 mm Hg, and PGI2 from 35.0 +/- 2.2 to 31.9 +/- 1.7 mm Hg (p<0.05). We conclude that individually titrated doses of inhaled NO and aerosolized PGI2 effect selective pulmonary vasodilation and redistribute blood-flow from shunt-areas to well-ventilated regions with nearly identical efficacy profiles.
THE EVOLUTIONARY ASPECT OF INFECTIOUS DISEASES, WITH ESPECIAL REFERENCE TO THE LOCAL VENEREAL DISEASES.
Authors: G. FRANK LYDSTON
Journal: JAMA (1902)

The evidence of evolution in general and of infectious micro-organisms in particular, has been so overwhelming during the last decade that it is surprising that teachers of science who renounce the doctrine of evolution can still be found. A few weeks since, however, I heard a distinguished teacher of physiology say that the theory of evolution was untenable and unscientific, and that Darwin was not a scientist. This despite the facts that manifold and indubitable proofs of organic evolution exist, and that evolutionary law controls and binds together all the natural sciences and is the very cornerstone of sociology, and indeed, all else of human interest. But the experimental and laboratory craze is upon us and we are worshipping the new gods instead of weighing their potentialities and assigning to each its proper place in scientific medicine. Experimental facts are valuable in so far as they lead to a more
Abstract 2903: High grade dysplastic polyps: Does size matter
Authors: Martin Tobi, Jeffrey Easler, Fadi Antaki, Edi Levi, Mary Ann Rambus, Michael Lawson
Journal: Cancer Research (2010)

Abstract Adenomas with high-grade dysplasia (HGD) are recognized to be harbingers of future neoplastic lesions and colonoscopy is repeated in a year. There is little data regarding the neoplastic potential of the colon bearing such lesions. We postulated that lesions &amp;gt;1cm, in contrast to their smaller counterparts, would progress through an adenoma-carcinoma sequence. Conversely, smaller sized lesions might have a greater propensity for recurrence since there may be a priori more biological aggressiveness. Methods: We used the Adnab-9 monoclonal anti-adenoma risk marker to investigate high risk patients with HGD adenomas. Immunohistochemistry on normal-appearing colonic mucosa, ELISA of effluent acquired during colonoscopy and fecal Western blotting and ELISA, the stool collected prospectively was performed. Results: 23 patients with HGD adenomas, the majority found on the index colonoscopy were evaluated (table). A trend existed for increased NSAID intake in the large HGD group 5/7 (71%) compared to 2/7 (29%) in the small (p=0.28) and for increased numbers of metachronous adenomas in the small HGD group. More had symptoms in the large HGD group (67%) compared to 40% in small (NSS). No small HGD lesion was associated with a field effect (FE) in contrast to 100% in those patients with large lesion HGD (p&amp;lt;0.01). Concurrence with location of FE with synchronous adenomas was 5/6 (83%) and 2/5 (40%) with metachronous polyps in those with large HGD (p=0.24). Conclusions: Small HGD lesions appear to progress by pathways beyond the purview of the adenoma carcinoma sequence characterized by the significant lack of a field effect. They arise in a colon that may be destined for greater than usual risk for CRN even than that seen with larger HGD lesions. Larger prospective studies should be undertaken to confirm these preliminary findings and determine the tumorigenic pathway but in the interim surveillance for smaller lesions should not be limited to a single 1 year of follow-up.ParameterLarge HGDSmall HGDAll HGDN131023Age x±sd (years)65.5±10.064.7±8.765.2±9.3%Race AA53.93043.5BMI30.3±7.127.9±6.229.3±6.6%Left-sided76.97073.9%TA/TVA/VA69.2/23.1/7.760/40/063/32.7/4.3Size x±sd (mm)21.5±13.76.7±3.115.1±12.8Follow-up yrs3.6±2.15.3±2.7(p=0.15)4.2±2.4Synchronous adenomas1.8±3.3 6/14 46.2%1.4±1.5 5/10 50%1.5±2.7 11/24 45.8%Metachronous adenomas1.3±1; 7/10 70%2.1±2.34* 4/7 57% (p=0.6)1.3±1.7 11/17 64.7%%Ad-9 WB+12.528.620FecalAdnab-92/8 (25%)2/7(28.6%)4/15(26.7%)Effluent Elisa+4/9(44.4%)2/7(28.6%)p=.66/16(38%)%Field Effect6/6 (100)**0/5 (0%)6/11(55.5%)**OR 0.007:CI 0.0001-.415;p=0.0022; *p=0.3 Note: F/U time NSS Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2903.
Pancreatic Fat Content and β-Cell Function in Men With and Without Type 2 Diabetes
Authors: Maarten E. Tushuizen, Mathijs C. Bunck, Petra J. Pouwels, Saskia Bontemps, Jan Hein T. van Waesberghe, Roger K. Schindhelm, Andrea Mari, Robert J. Heine, Michaela Diamant
Journal: Diabetes Care (2007)

Insulin resistance, associated with increased lipolysis, results in a high exposure of nonadipose tissue to lipids. Experimental data indicate that fatty infiltration of pancreatic islets may also contribute to beta-cell dysfunction, but whether this occurs in humans in vivo is unknown.Using proton magnetic resonance spectroscopy and oral glucose tolerance tests, we studied the association of pancreatic lipid accumulation in vivo and various aspects of beta-cell function in 12 insulin-naive type 2 diabetic and 24 age- and BMI-matched nondiabetic men.Patients versus control subjects had higher A1C, fasting plasma glucose, and insulin and triglyceride levels and lower HDL cholesterol, but similar waist circumference. Median (interquartile range) pancreatic fat content in patients and control subjects was 20.4% (13.4-43.6) and 9.7% (7.0-20.2), respectively (P = 0.032). Pancreatic fat correlated negatively with beta-cell function parameters, including the insulinogenic index adjusted for insulin resistance, early glucose-stimulated insulin secretion, beta-cell glucose sensitivity, and rate sensitivity (all P < 0.05), but not potentiation. However, these associations were significantly affected by the diabetic state, such that a significant association of pancreatic fat with beta-cell dysfunction was only present in the nondiabetic group (all P < 0.01), suggesting that once diabetes occurs, factors additional to pancreatic fat account for further beta-cell function decline. In control subjects, the association of pancreatic fat and beta-cell function remained significant after correction for BMI, fasting plasma glucose, and triglycerides (P = 0.006).These findings indicate that pancreatic lipid content may contribute to beta-cell dysfunction and possibly to the subsequent development of type 2 diabetes in susceptible humans.
The Threat to Sign Out Against Medical Advice
Authors: HARRY D. ALBERT
Journal: Annals of Internal Medicine (1973)

Twenty-eight patients were studied who had threatened to sign out of the hospital against medical advice. The threat to leave was usually the last ot a progression of behavioral changes that had not provoked sufficient action by the nursing staff. Threatening to leave was the patients' way to communicate their feelings. There were three reasons for the threat: overwhelming fear, anger, or psychotic reactions. Contributing factors were unrecognized transference reactions, impasses with the staff, intense unmet dependency needs, and family difficulties. Ideally, management should include early recognition of the problem; dispassionate investigation of the circumstances, including the physician's own role; and a review of the problem with the entire staff. Most patients who leave against medical advice return if allowed.
Pathogenesis of Diabetic Ketoacidosis: A Reappraisal
Authors: David S Schade, R P Eaton
Journal: Diabetes Care (1979)

This study reviews the pathogenic hormonal abnormalities (insulin deficiency and stress hormone excess) in diabetic ketoacidosis. The data both supporting and negating a primary role for insulin deficiency in the pathogenesis of diabetic ketoacidosis are examined. Evidence implicating excess stress hormone secretion as a necessary event in the development of severe metabolic decompensation is discussed. The data suggest that diabetic ketoacidosis may be prevented by correcting either the relative deficiency of insulin or the excess secreation of one or a combination of the stress hormones. Studies supporting a primary role for insulin deficiency in the pathogenesis of diabetic ketoacidosis include the beneficial therapeutic response to insulin administration in ketoacidosis, development of ketoacidosis; and (3) stress hormone excess is necessary for fulminant ketoacidosis to be manifested.s following insulin withdrawal from diabetic man and animals, and hypoglycemic and hypoketonemic effects of insulin. Studies negating a primary role for insulin deficiency in ketoacidosis include the “normal” plasma insulin concentration in the majority of ketoacidotic cases, delayed onset of ketoacidosis after insulin withdrawal from diabetic man, and lack of hypolipolytic and hypoketonemic effect of insulin without prior stress hormone adipocyte and hepatocyte stimulation. Evidence that stress hormones (glucagon, catecholamines, cortisol, and growth hormone) contribute to the metabolic decompensation of ketoacidosis includes: (1) in all cases of ketoacidosis, at least one stress hormone is always elevated; (2) pharmacologic blockade of each of the stress hormones reduces the rate and/or frequency of metabolic decompensation in diabetic man; (3) removal of the pituitary and/or the adrenal gland in diabetic animals completely prevents the development of ketoacidosis after insulin withdrawal; and (4) administration of each of the four stress hormones under appropriate conditions induces metabolic decompensation in diabetic man with “normal” circulating levels of plasma insulin concentration. From these studies, the following conclusions are supported: (1) absolute insulin deficiency is an unusual cause of ketoacidosis; (2) the presence of relative insulin deficiency is necessary for the development of ketoacidosis; and (3) stress hormone excess is necessary for fulminant ketoacidosis to be manifested.
Efficacy of propranolol in the control of exercise-induced or augmented ventricular ectopic activity.
Authors: J V Nixon, W Pennington, W Ritter, W Shapiro
Journal: Circulation (1978)

The effect of propranolol on exercise-induced or augmented ventricular ectopy was studied in sixteen male patients, six of whom had documented coronary artery disease. Fifteen patients were exercised after two weeks of oral therapy, fourteen after single oral therapy and eight patients after intravenous therapy. Propranolol dosage was titrated to produce maximal beta-adrenergic blockade. Effective reduction of exercise-induced ventricular ectopy occurred in ten of fifteen patients (P less than 0.001), and in five of six patients with coronary disease (P less than 0.02). Propranolol therapy abolished ventricular couplets in eight of twelve patients and ventricular tachycardia in four of the patients. Single oral and intravenous therapy had similar or greater effects. Plasma propranolol levels following different routes of administration did not correlate with exercise-induced maximal heart rates or percent reduction in ventricular ectopy. When compared to exercise in eleven patients, ambulatory monitoring underestimated the severity, particularly the highest grades, of ventricular ectopy.