tbuckley/cabot-search huggingface dataset:
Primary Care Management of Chronic Stable Angina and Asymptomatic Suspected or Known Coronary Artery Disease: A Clinical Practice Guideline from the American College of Physicians
Authors: Vincenza Snow, Patricia Barry, Stephan D. Fihn, Raymond J. Gibbons, Douglas K. Owens, Sankey V. Williams, Christel Mottur-Pilson, Kevin B. Weiss
Journal: Annals of Internal Medicine (2004)

In 1999, the American College of Physicians (ACP), then the American College of Physicians–American Society of Internal Medicine, and the American College of Cardiology/American Heart Association (ACC/AHA) developed joint guidelines on the management of patients with chronic stable angina. The ACC/AHA then published an updated guideline in 2002, which ACP recognized as a scientifically valid review of the evidence and background paper. This ACP guideline summarizes the recommendations of the 2002 ACC/AHA updated guideline and underscores the recommendations most likely to be important to physicians seeing patients in the primary care setting. This guideline is the second of 2 that provide guidance on the management of patients with chronic stable angina. This document covers treatment and follow-up of symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months. Sections addressing asymptomatic patients are also included. Asymptomatic refers to patients with known or suspected coronary disease based on a history or electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. A previous guideline covered diagnosis and risk stratification for symptomatic patients who have not had an acute myocardial infarction or revascularization procedure in the previous 6 months and asymptomatic patients with known or suspected coronary disease based on a history or electrocardiographic evidence of previous myocardial infarction, coronary angiography, or abnormal results on noninvasive tests. *This paper, written by Vincenza Snow, MD; Patricia Barry, MD, MPH; Stephan D. Fihn, MD, MPH; Raymond J. Gibbons, MD; Douglas K. Owens, MD; Sankey V. Williams, MD; Christel Mottur-Pilson, PhD; and Kevin B. Weiss, MD, MPH, for the American College of Physicians/American College of Cardiology Chronic Stable Angina Panel, was developed for the Clinical Efficacy Assessment Subcommittee of the American College of Physicians (ACP): Kevin B. Weiss, MD, MPH (Chair); Mark Aronson, MD; Patricia Barry, MD, MPH; Donald E. Casey Jr., MD, MPH, MBA; Thomas Cross Jr., MD, MPH; Nick Fitterman, MD; E. Rodney Hornbake, MD; Douglas K. Owens, MD; and Katherine D. Sherif, MD. Approved by the ACP Board of Regents in April 2004.
Targeting of B and T lymphocyte associated (BTLA) prevents graft-versus-host disease without global immunosuppression
Authors: Jörn C. Albring, Michelle M. Sandau, Aaron S. Rapaport, Brian T. Edelson, Ansuman Satpathy, Mona Mashayekhi, Stephanie K. Lathrop, Chyi-Song Hsieh, Matthias Stelljes, Marco Colonna, Theresa L. Murphy, Kenneth M. Murphy
Journal: The Journal of Experimental Medicine (2010)

Graft-versus-host disease (GVHD) causes significant morbidity and mortality in allogeneic hematopoietic stem cell transplantation (aHSCT), preventing its broader application to non-life-threatening diseases. We show that a single administration of a nondepleting monoclonal antibody specific for the coinhibitory immunoglobulin receptor, B and T lymphocyte associated (BTLA), permanently prevented GVHD when administered at the time of aHSCT. Once GVHD was established, anti-BTLA treatment was unable to reverse disease, suggesting that its mechanism occurs early after aHSCT. Anti-BTLA treatment prevented GVHD independently of its ligand, the costimulatory tumor necrosis factor receptor herpesvirus entry mediator (HVEM), and required BTLA expression by donor-derived T cells. Furthermore, anti-BTLA treatment led to the relative inhibition of CD4(+) forkhead box P3(-) (Foxp3(-)) effector T cell (T eff cell) expansion compared with precommitted naturally occurring donor-derived CD4(+) Foxp3(+) regulatory T cell (T reg cell) and allowed for graft-versus-tumor (GVT) effects as well as robust responses to pathogens. These results suggest that BTLA agonism rebalances T cell expansion in lymphopenic hosts after aHSCT, thereby preventing GVHD without global immunosuppression. Thus, targeting BTLA with a monoclonal antibody at the initiation of aHSCT therapy might reduce limitations imposed by histocompatibility and allow broader application to treatment of non-life-threatening diseases.
Certain beta-blockers can decrease beta-adrenergic receptor number: I. Acute reduction in receptor number by tertatolol and bopindolol.
Authors: A De Blasi, M Fratelli, O Marasco
Journal: Circulation Research (1988)

We have previously reported that a potent new beta-blocker, tertatolol, when given at therapeutic doses to healthy volunteers, rapidly reduced the number of human mononuclear leukocyte beta-receptors. In the present study, the mechanism of receptor regulation by beta-antagonists incubated with target cells in vitro was investigated. Two different cell types (human mononuclear leukocytes and S49 murine lymphoma cells) were used, and beta-adrenergic receptors were measured using either the hydrophilic ligand 3H-CGP 12177 (specific for surface receptors) or lipophilic 125I-pindolol (which measures total receptors). In a comparison between beta-blockers, tertatolol and bopindolol, but not propranolol and pindolol, were found to rapidly (1 hour at 37 degrees C) reduce the number of beta-adrenergic receptors. This was paralleled by a reduction in isoproterenol-stimulated cyclic AMP accumulation. The reduction in receptors was the same whether surface or total receptors were measured; thus, it was not due to receptor sequestration. This effect was not caused by partial agonist activity (bopindolol is a weak partial agonist); in parallel experiments, tertatolol and bopindolol, but not pindolol (potent partial agonist) and isoproterenol (full agonist), reduced beta-adrenergic receptors. Finally, this effect was not due to irreversible binding: the receptor reduction induced by the irreversible blocker bromo-acetyl-alprenolol-methane (BAAM) was stable for several hours, while the effect of tertatolol and bopindolol was slowly reversed over the same time course. We suggest that tertatolol and bopindolol have two effects on beta-adrenergic receptors: they bind competitively, and then they modify the receptors so that they are no longer available for binding by ligands or catecholamines.(ABSTRACT TRUNCATED AT 250 WORDS)
Fc receptor modulation in mononuclear phagocytes maintained on immobilized immune complexes occurs by diffusion of the receptor molecule.
Authors: J Michl, M M Pieczonka, J C Unkeless, G I Bell, S C Silverstein
Journal: The Journal of Experimental Medicine (1983)

We describe a method for synchronously assembling antigen-antibody complexes underneath macrophages adherent to an antigen-coated surface. We have used this method to study the mechanism of Fc receptor (FcR) disappearance that occurs when resident and thioglycollate-elicited mouse macrophages are cultured on immune complex-coated surfaces. Erythrocytes opsonized with IgG (E(IgG) and a monoclonal antibody (2.4G2 IgG) directed against the trypsin-resistant FcR (FcRII) were used as indicators of the presence and distribution of FcRII molecules on the macrophage plasma membrane. Inhibitors of aerobic (NaCN) and anerobic (2-deoxyglucose, NaF) glycolysis and pinocytosis, of protein biosynthesis (cycloheximide), and of cytoskeletal function (cytochalasin B and D, colchicine, podophyllotoxin, taxol) did not reduce the rate or extent of FcRII modulation. Moreover, treatment of the macrophages with 0.1-0.5% formaldehyde did not reduce the extent of FcRII modulation as measured by the disappearance of E(IgG) binding sites. FcRII modulation was markedly slowed when the temperature was decreased to 2-4 degrees C. These results prove that FcRII modulation is governed by diffusion of the receptor in the plasma membrane. From the speed of FcRII disappearance from the macrophage's upper surface we calculate that the receptor has a diffusion coefficient at 37 degrees C of 2.5 X 10(-9) cm2/s. This finding indicates that FcRII, in its unligated form, is not linked to the macrophage's cytoskeleton, and that the receptor is capable of accommodating spatially to any distribution of ligands on a particle's surface.
Cardiomyocytes can be generated from marrow stromal cells in vitro
Authors: Shinji Makino, Keiichi Fukuda, Shunichirou Miyoshi, Fusako Konishi, Hiroaki Kodama, Jing Pan, Motoaki Sano, Toshiyuki Takahashi, Shingo Hori, Hitoshi Abe, Jun-ichi Hata, Akihiro Umezawa, Satoshi Ogawa
Journal: Journal of Clinical Investigation (1999)

We have isolated a cardiomyogenic cell line (CMG) from murine bone marrow stromal cells. Stromal cells were immortalized, treated with 5-azacytidine, and spontaneously beating cells were repeatedly screened. The cells showed a fibroblast-like morphology, but the morphology changed after 5-azacytidine treatment in ∼30% of the cells; they connected with adjoining cells after one week, formed myotube-like structures, began spontaneously beating after two weeks, and beat synchronously after three weeks. They expressed atrial natriuretic peptide and brain natriuretic peptide and were stained with anti-myosin, anti-desmin, and anti-actinin antibodies. Electron microscopy revealed a cardiomyocyte-like ultrastructure, including typical sarcomeres, a centrally positioned nucleus, and atrial granules. These cells had several types of action potentials, such as sinus node–like and ventricular cell–like action potentials. All cells had a long action potential duration or plateau, a relatively shallow resting membrane potential, and a pacemaker-like late diastolic slow depolarization. Analysis of the isoform of contractile protein genes, such as myosin heavy chain, myosin light chain, and α-actin, indicated that their muscle phenotype was similar to that of fetal ventricular cardiomyocytes. These cells expressed Nkx2.5/Csx, GATA4, TEF-1, and MEF-2C mRNA before 5-azacytidine treatment and expressed MEF-2A and MEF-2D after treatment. This new cell line provides a powerful model for the study of cardiomyocyte differentiation.
Cardiovascular Disease After Hodgkin Lymphoma Treatment
Authors: Frederika A. van Nimwegen, Michael Schaapveld, Cécile P. M. Janus, Augustinus D. G. Krol, Eefke J. Petersen, John M. M. Raemaekers, Wouter E. M. Kok, Berthe M. P. Aleman, Flora E. van Leeuwen
Journal: JAMA Internal Medicine (2015)

Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular diseases. It is unclear, however, how long the increased risk persists and what the risk factors are for various cardiovascular diseases.To examine relative and absolute excess risk up to 40 years since HL treatment compared with cardiovascular disease incidence in the general population and to study treatment-related risk factors for different cardiovascular diseases.This retrospective cohort study included 2524 Dutch patients diagnosed as having HL at younger than 51 years (median age, 27.3 years) who had been treated from January 1, 1965, through December 31, 1995, and had survived for 5 years since their diagnosis.Treatment for HL, including prescribed mediastinal radiotherapy dose and anthracycline dose.Data were collected from medical records and general practitioners. Cardiovascular events, including coronary heart disease (CHD), valvular heart disease (VHD), and cardiomyopathy and congestive heart failure (HF), were graded according to the Common Terminology Criteria for Adverse Events, version 4.0.After a median follow-up of 20 years, we identified 1713 cardiovascular events in 797 patients. After 35 years or more, patients still had a 4- to 6-fold increased standardized incidence ratio of CHD or HF compared with the general population, corresponding to 857 excess events per 10,000 person-years. Highest relative risks were seen in patients treated before 25 years of age, but substantial absolute excess risks were also observed for patients treated at older ages. Within the cohort, the 40-year cumulative incidence of cardiovascular diseases was 50% (95% CI, 47%-52%). Fifty-one percent of patients with a cardiovascular disease developed multiple events. For patients treated before 25 years of age, cumulative incidences at 60 years or older were 20%, 31%, and 11% for CHD, VHD, and HF as first events, respectively. Mediastinal radiotherapy increased the risks of CHD (hazard ratio [HR], 2.7; 95% CI, 2.0-3.7), VHD (HR, 6.6; 95% CI, 4.0-10.8), and HF (HR, 2.7; 95% CI, 1.6-4.8), and anthracycline-containing chemotherapy increased the risks of VHD (HR, 1.5; 95% CI, 1.1-2.1) and HF (HR, 3.0; 95% CI, 1.9-4.7) as first events compared with patients not treated with mediastinal radiotherapy or anthracyclines, respectively. Joint effects of mediastinal radiotherapy, anthracyclines, and smoking appeared to be additive.Throughout their lives, HL survivors treated at adolescence or adulthood are at high risk for various cardiovascular diseases. Physicians and patients should be aware of this persistently increased risk.
Management of patients with cirrhosis awaiting liver transplantation
Authors: A. Cardenas, P. Gines
Journal: Gut (2010)

The demand for OLT continues to be on the rise with patients spending a long time on the waiting list; this not only increases the risk of developing further decompensation but also mortality. The complications discussed above may not only lead to removal from the waiting list in some cases but also a poorer outcome following transplantation. Therefore the appropriate prevention, recognition and treatment of the above-mentioned complications of cirrhosis will have a positive impact on the outcome before and after liver transplantation.
Identification of children at very low risk of clinically-important brain injuries after head trauma: a prospective cohort study
Authors: Nathan Kuppermann, James F Holmes, Peter S Dayan, John D Hoyle, Shireen M Atabaki, Richard Holubkov, Frances M Nadel, David Monroe, Rachel M Stanley, Dominic A Borgialli, Mohamed K Badawy, Jeff E Schunk, Kimberly S Quayle, Prashant Mahajan, Richard Lichenstein, Kathleen A Lillis, Michael G Tunik, Elizabeth S Jacobs, James M Callahan, Marc H Gorelick, Todd F Glass, Lois K Lee, Michael C Bachman, Arthur Cooper, Elizabeth C Powell, Michael J Gerardi, Kraig A Melville, J Paul Muizelaar, David H Wisner, Sally Jo Zuspan, J Michael Dean, Sandra L Wootton-Gorges
Journal: The Lancet (2009)
Periprocedural Stroke and Cardiac Catheterization
Authors: Martial Hamon, Jean-Claude Baron, Fausto Viader, Michèle Hamon
Journal: Circulation (2008)

During cardiac catheterization, a 65-year-old man suddenly complained of nuchal pain, vertigo, and nausea and rapidly became unconscious, presumably from a stroke.The operator was unsure what type of imaging and management should be undertaken in this infrequent clinical setting.He paged the neurologist, asking him to urgently provide a strategy for diagnosis and management.
Hormonal Regulation of the Differentiation of Cultured Ovarian Granulosa Cells*
Authors: AARON J. W. HSUEH, E. Y. ADASHI, PHILLIP B. C. JONES, THOMAS H. WELSH
Journal: Endocrine Reviews (1984)

In 1672, Regnier de Graaf first described the differentiation of ovarian follicles into the corpus luteum. He stated that "age and coitus cause very great changes in eggs (follicles). In young animals, they are very small and in more developed ones they are larger. After coitus, they (the follicles) so alter as to resemble the globules (the corpora lutea) …, being one or more according as the animal will produce one or more fetuses." (1) Follicles as the functional unit: Ovarian follicles have since been shown to be the basic functional unit of the ovary and consist of an outer layer of theca interna cells which encircle inner layers of granulosa cells. Granulosa cells, in turn, surround the innermost oocyte-cumulus cell complex. The maturation of ovarian follicles and their transformation into corpora lutea is regulated by a specific set of hormones and has been a major research area for ovarian physiologists for several hundred years.
Leucocyte elastase-mediated release of von Willebrand factor from cultured endothelial cells
Authors: M Chignard, V Balloy, P Renesto
Journal: European Respiratory Journal (1993)

The aim of this study was to investigate a possible activation of human endothelial cells in monolayer culture by a purified neutrophil-derived proteinase, i.e. elastase. Cells were isolated from human umbilical cord veins, and incubated either in primary culture or after two passages, in the presence of various concentrations of this proteinase. Although a lack of prostacyclin formation was noted, elastase induced a large release of von Willebrand factor (vWf) in a concentration-dependent manner. Thus, upon incubation with 1 microgram.ml-1 elastase for 30 min, 70 mU.ml-1 vWf were detected in the incubation medium, as compared to 5 mU.ml-1 for control. Using cells in primary culture, a fivefold higher concentration of vWf was recovered following incubation with 10 micrograms.ml-1 elastase than with 0.5 IU.ml-1 thrombin. This effect was linked to the enzymatic activity of elastase and not to its cationic charge, as deduced from the inhibition by eglin C, and the lack of effect of the phenylmethylsulphonyl fluoride (PMSF) treated proteinase. We conclude that vWf release was not due to cell activation, since cytoplasmic calcium mobilization was absent, and inhibition of protein kinase C did not modify the response. In fact, this release was the consequence of cell damage, since concentrations of vWf recovered correlated with cell lysis. These results support the hypothesis that the high level of plasma vWf in patients with sepsis or adult respiratory distress syndrome could result from damage to the endothelial cells by elastase released from activated neutrophils.
Neurotrophins promote revascularization by local recruitment of TrkB+ endothelial cells and systemic mobilization of hematopoietic progenitors
Authors: Pouneh Kermani, Dahlia Rafii, David K. Jin, Paul Whitlock, Wendy Schaffer, Anne Chiang, Loic Vincent, Matthias Friedrich, Koji Shido, Neil R. Hackett, Ronald G. Crystal, Shahin Rafii, Barbara L. Hempstead
Journal: Journal of Clinical Investigation (2005)

The neurotrophin brain-derived neurotrophic factor (BDNF) is required for the maintenance of cardiac vessel wall stability during embryonic development through direct angiogenic actions on endothelial cells expressing the tropomysin receptor kinase B (TrkB). However, the role of BDNF and a related neurotrophin ligand, neurotrophin-4 (NT-4), in the regulation of revascularization of the adult tissues is unknown. To study the potential angiogenic capacity of BDNF in mediating the neovascularization of ischemic and non-ischemic adult mouse tissues, we utilized a hindlimb ischemia and a subcutaneous Matrigel model. Recruitment of endothelial cells and promotion of channel formation within the Matrigel plug by BDNF and NT-4 was comparable to that induced by VEGF-A. The introduction of BDNF into non-ischemic ears or ischemic limbs induced neoangiogenesis, with a 2-fold increase in the capillary density. Remarkably, treatment with BDNF progressively increased blood flow in the ischemic limb over 21 days, similar to treatment with VEGF-A. The mechanism by which BDNF enhances capillary formation is mediated in part through local activation of the TrkB receptor and also by recruitment of Sca-1+CD11b+ pro-angiogenic hematopoietic cells. BDNF induces a potent direct chemokinetic action on subsets of marrow-derived Sca-1+ hematopoietic cells co-expressing TrkB. These studies suggest that local regional delivery of BDNF may provide a novel mechanism for inducing neoangiogenesis through both direct actions on local TrkB-expressing endothelial cells in skeletal muscle and recruitment of specific subsets of TrkB+ bone marrow–derived hematopoietic cells to provide peri-endothelial support for the newly formed vessels.
Beclomethasone/formoterol versus budesonide/formoterol combination therapy in asthma
Authors: A. Papi, P. L. Paggiaro, G. Nicolini, A. M. Vignola, L. M. Fabbri
Journal: European Respiratory Journal (2006)

The present study was designed to compare the fixed combination of beclomethasone and formoterol in a hydrofluoroalkane Modulite® (Chiesi Farmaceutici, Parma, Italy) pressurised metered-dose inhaler (pMDI), with a combination of budesonide and formoterol administered via a Turbuhaler® (AstraZeneca, Lund, Sweden) dry powder inhaler (DPI). This was a phase III, multinational, multicentre, double-blind, double-dummy, randomised, two-arm parallel groups, controlled study design. After a 2-week run-in period, 219 patients with moderate-to-severe asthma were randomised to a 12-week treatment with beclomethasone 200 μg plus formoterol 12 μg b.i.d. delivered via a pMDI or budesonide 400 μg plus formoterol 12 μg b.i.d. delivered via a DPI. The analysis of noninferiority on primary outcome, morning peak expiratory flow in the last 2 weeks of treatment, showed no difference between groups. A statistically significant improvement from baseline in lung function, symptoms and rescue medication use was observed in both groups at all time-points. No differences were observed between treatments in either rate of asthma exacerbations or frequency of adverse events. The new fixed combination of beclomethasone and formoterol in hydrofluoroalkane Modulite® pressurised metered-dose inhaler is equivalent to the marketed combination of budesonide and formoterol in terms of efficacy and tolerability profile.
Risk of testicular cancer in subfertile men: case-control study
Authors: H. Moller, N. E Skakkebak
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To evaluate the association between subfertility in men and the subsequent risk of testicular cancer. <b>Design:</b> Population based case-control study. <b>Setting:</b> The Danish population. <b>Participants:</b> Cases were identified in the Danish Cancer Registry; controls were randomly selected from the Danish population with the computerised Danish Central Population Register. Men were interviewed by telephone; 514men with cancer and 720controls participated. <b>Outcome measure:</b> Occurrence of testicular cancer. <b>Results:</b> A reduced risk of testicular cancer was associated with paternity (relative risk 0.63; 95% confidence interval 0.47 to 0.85). In men who before the diagnosis of testicular cancer had a lower number of children than expected on the basis of their age, the relative risk was 1.98(1.43to 2.75). There was no corresponding protective effect associated with a higher number of children than expected. The associations were similar for seminoma and non-seminomaand were not influenced by adjustment for potential confounding factors. <b>Conclusion:</b> These data are consistent with the hypothesis that male subfertility and testicular cancer share important aetiological factors.