tbuckley/cabot-search huggingface dataset:
Molecular cloning, expression, and chromosomal localization of two isoforms of the AE3 anion exchanger from human heart.
Authors: D Yannoukakos, A Stuart-Tilley, H A Fernandez, P Fey, G Duyk, S L Alper
Journal: Circulation Research (1994)

Cl-/HCO3- exchange contributes to regulation of pHi and [Cl-] in cardiac muscle, with possible effects on excitability and contractility. We have isolated human heart cDNAs, which encode two isoforms of the anion exchanger AE3. These clones share long portions of common sequence but have different 5' ends encoding distinct amino-terminal amino acid sequences. The longer AE3 polypeptide of 1232 amino acids, bAE3, displays nearly 96% amino acid sequence identity to the rat and mouse AE3 "brain isoforms." The shorter cAE3 polypeptide of 1034 amino acids in length corresponds to the rat AE3 "cardiac isoform." The unique N-terminal 73 amino acids of the cAE3 sequence are less well conserved between rat and human. Northern blot analysis with isoform-specific probes revealed the presence of both cAE3 and bAE3 mRNAs in human heart tissue. Both AE3 protein isoforms were overexpressed in Chinese hamster ovary cells and detected by immunoblot with antipeptide antibodies. Immunoblot studies of human cardiac membranes detected only cAE3 polypeptides, which were apparently not susceptible to enzymatic deglycosylation. Injection into Xenopus oocytes of cRNAs encoding either cAE3 or bAE3 produced increased 36Cl- uptake into the oocytes, confirming the ability of both AE3 isoforms to transport Cl-. The human AE3 gene was localized to chromosome 2. AE3 may provide a new pharmacologic target for antiarrhythmic and cardioprotective drugs.
Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review
Authors: F. A Campbell
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To establish whether cannabis is an effective and safe treatment option in the management of pain. <b>Design:</b> Systematic review of randomised controlled trials. <b>Data sources:</b> Electronic databases Medline, Embase, Oxford Pain Database, and Cochrane Library; references from identified papers; hand searches. <b>Study selection:</b> Trials of cannabis given by any route of administration (experimental intervention) with any analgesic or placebo (control intervention) in patients with acute, chronic non-malignant, or cancer pain. Outcomes examined were pain intensity scores, pain relief scores, and adverse effects. Validity of trials was assessed independently with the Oxford score. <b>Data extraction:</b> Independent data extraction; discrepancies resolved by consensus. <b>Data synthesis:</b> 20 randomised controlled trials were identified, 11 of which were excluded. Of the 9 included trials (222 patients), 5 trials related to cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain. No randomised controlled trials evaluated cannabis; all tested active substances were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5-20 mg, an oral synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5-3 mg were about as effective as codeine 50-120 mg, and oral benzopyranoperidine 2-4 mg was less effective than codeine 60-120 mg and no better than placebo. Adverse effects, most often psychotropic, were common. <b>Conclusion:</b> Cannabinoids are no more effective than codeine in controlling pain and have depressant effects on the central nervous system that limit their use. Their widespread introduction into clinical practice for pain management is therefore undesirable. In acute postoperative pain they should not be used. Before cannabinoids can be considered for treating spasticity and neuropathic pain, further valid randomised controlled studies are needed. <h3>What is already known on this topic</h3> Three quarters of British doctors surveyed in 1994 wanted cannabis available on prescription Humans have cannabinoid receptors in the central and peripheral nervous system In animal testing cannabinoids are analgesic and reduce signs of neuropathic pain Some evidence exists that cannabinoids may be analgesic in humans <h3>What this study adds</h3> No studies have been conducted on smoked cannabis Cannabinoids give about the same level of pain relief as codeine in acute postoperative pain They depress the central nervous system
The Effect of Oral Contraceptives on the Liver
Authors: Fenton Schaffner
Journal: JAMA (1966)

With world-wide use of oral contraceptive agents, increasing numbers of reports of jaundice following the use of these medications have appeared.<sup>1-14</sup>An attempt to assess the significance of this adverse reaction should take into account existing knowledge of hepatic drug reactions in general. <h3>General Considerations</h3> In evaluating the effects of any drug upon the liver, one must first define the "no effect level" to be accepted. Most drugs are metabolized by the liver, and their continued administration causes adaptive cellular and enzymatic changes consisting primarily of an increase in the smooth endoplasmic reticulum and its detoxifying enzymes.<sup>15,16</sup>Usually there is an associated hypertrophy or hyperplasia of the liver, so that hepatomegaly may become apparent. However, since the results of liver function tests remain normal and the enlargement of the liver when it occurs is not hazardous, it should not be considered an adverse reaction. Adaptive hypertrophy of the
PPAR Activators as Antiinflammatory Mediators in Human T Lymphocytes
Authors: Nikolaus Marx, Bettina Kehrle, Klaus Kohlhammer, Miriam Grüb, Wolfgang Koenig, Vinzenz Hombach, Peter Libby, Jorge Plutzky
Journal: Circulation Research (2002)

Abstract— Activation of T lymphocytes and their ensuing elaboration of proinflammatory cytokines, such as interferon (IFN)-γ, represent a critical step in atherogenesis and arteriosclerosis. IFNγ pathways also appear integral to the development of transplantation-associated arteriosclerosis (Tx-AA), limiting long-term cardiac allograft survival. Although disruption of these IFNγ signaling pathways limits atherosclerosis and Tx-AA in animals, little is known about inhibitory regulation of proinflammatory cytokine production in humans. The present study investigated whether activators of peroxisome proliferator-activated receptor (PPAR)α and PPARγ, with their known antiinflammatory effects, might regulate the expression of proinflammatory cytokines in human CD4-positive T cells. Isolated human CD4-positive T cells express PPARα and PPARγ mRNA and protein. Activation of CD4-positive T cells by anti-CD3 monoclonal antibodies significantly increased IFNγ protein secretion from 0 to 504±168 pg/mL, as determined by ELISA. Pretreatment of cells with well-established PPARα (WY14643 or fenofibrate) or PPARγ (BRL49653/rosiglitazone or pioglitazone) activators reduced anti-CD3-induced IFNγ secretion in a concentration-dependent manner. PPAR activators also inhibited TNFα and interleukin-2 protein expression. In addition, PPAR activators markedly reduced cytokine mRNA expression in these cells. Such antiinflammatory actions were also evident in cell-cell interactions with medium conditioned by PPAR activator-treated T cells attenuating human monocyte CD64 expression and human endothelial cell major histocompatibility complex class II induction. Thus, activation of PPARα and PPARγ in human CD4-positive T cells limits the expression of proinflammatory cytokines, such as IFNγ, yielding potential therapeutic benefits in pathological processes, such as atherosclerosis and Tx-AA.
ErbB2 enhances mammary tumorigenesis, oncogene-independent recurrence and metastasis in a model of IGF-IR-mediated mammary tumorigenesis
Authors: Craig I Campbell, James J Petrik, Roger A Moorehead
Journal: Molecular Cancer (2010)

Abstract Background The type I insulin-like growth factor receptor (IGF-IR) and ErbB2 (Her-2) are receptor tyrosine kinases implicated in human breast cancer. Both proteins are currently the subject of targeted therapeutics that are used in the treatment of breast cancer or which are in clinical trials. The focus of this study was to utilize our inducible model of IGF-IR overexpression to explore the interaction of these two potent oncogenes. Results ErbB2 was overexpressed in our RM11A cell line, a murine tumor cell line that overexpresses human IGF-IR in an inducible manner. ErbB2 conferred an accelerated tumor onset and increased tumor incidence after injection of RM11A cells into the mammary glands of syngeneic wild type mice. This was associated with increased proliferation immediately after tumor cell colonization of the mammary gland; however, this effect was lost after tumor establishment. ErbB2 overexpression also impaired the regression of established RM11A tumors following IGF-IR downregulation and enhanced their metastatic potential. Conclusion This study has revealed that even in the presence of vast IGF-IR overexpression, a modest increase in ErbB2 can augment tumor establishment in vivo , mediate resistance to IGF-IR downregulation and facilitate metastasis. This supports the growing evidence suggesting a possible advantage of using IGF-IR and ErbB2-directed therapies concurrently in the treatment of breast cancer.
Can mind affect body defenses against disease? Nascent specialty offers a host of tantalizing clues
Authors: D. E. Riesenberg
Journal: JAMA (1986)

PSYCHONEUROIMMUNOLOGY, the synthesis of data from psychiatry and immunology, provides an interesting perspective on human illness. Investigators hope that it also may uncover clues to the pathogenesis of acquired immunodeficiency syndrome (AIDS).  This field of behavioral immunology is one of the most exciting developments in recent years and promises to yield great insight into the relationships between psychological factors... and the disease process, says Steven F. Maier, PhD, professor and chair of experimental psychology at the University of Colorado, Boulder. Maier and coworkers have performed animal experiments that suggest a link between stress and immune function and indicate the importance of the subject's sense of control in a stressful situation.  In one experiment, three groups of laboratory rats were given a series of inescapable electric shocks, escapable shocks, or no shocks, respectively ( Science 1983;221:568-570). Lymphocyte proliferation, in response to phytohemagglutinin and concanavalin A (in vitro stimuli), was then measured. Those
Echocardiographic parameters of ventricular dyssynchrony validation in patients with heart failure using sequential biventricular pacing
Authors: Pierre Bordachar, Stephane Lafitte, Sylvain Reuter, Prashanthan Sanders, Pierre Jaïs, Michel Haïssaguerre, Raymond Roudaut, Stephane Garrigue, Jacques Clementy
Journal: Journal of the American College of Cardiology (2004)
Substrate-induced changes in the lipid content of ischemic and reperfused myocardium. Its relation to hemodynamic recovery.
Authors: M J de Groot, W A Coumans, P H Willemsen, G J van der Vusse
Journal: Circulation Research (1993)

To investigate the effect of lactate, pyruvate, and glucose on the endogenous levels of lipids in the normoxic, ischemic, and reperfused myocardium, isolated working rat hearts were exposed to various grades of ischemic insult (15, 30, or 45 minutes). Glucose was present as the basal substrate in the perfusion medium, and lactate (5 mM) or pyruvate (5 mM) was added as the cosubstrate. Lipid metabolism was evaluated by fatty acid accumulation, triacylglycerol turnover, and phospholipid homeostasis. Exogenous lactate significantly increased fatty acid content above preischemic levels after 45 minutes of ischemia. In glucose-perfused hearts, fatty acid levels were even slightly higher than in lactate-perfused hearts, whereas pyruvate-perfused hearts demonstrated less accumulation of fatty acids. By reperfusion, fatty acid levels in glucose-perfused hearts returned to control values. In lactate- and pyruvate-perfused hearts, fatty acid accumulation was further enhanced by reperfusion. When the fatty acid content exceeded 400 nmol/g dry wt during reperfusion, hemodynamic function was impaired, whereas fatty acid levels below 400 nmol/g dry wt did not correlate with hemodynamic recovery. The total triacylglycerol content did not change during ischemia and reperfusion. However, accumulation of glycerol was remarkable during the first 15 minutes of ischemia in all hearts, and release of glycerol by reperfusion was considerable in lactate-perfused hearts after 30 minutes of ischemia and in all groups of hearts after 45 minutes of ischemia. Release of glycerol in association with maintained levels of triacylglycerols suggests turnover of the triacylglycerol pool. The rate of triacylglycerol cycling correlated poorly with hemodynamic recovery. Accumulation of arachidonic acid revealed disturbances in phospholipid turnover. Arachidonic acid accumulation during reperfusion demonstrated a strong relation with impairment of cardiac function. Hence, derangements in phospholipid homeostasis during reperfusion might be involved in myocardial damage, which is influenced by the substrates available.
Agonist-mediated tissue factor expression in cultured vascular smooth muscle cells. Role of Ca2+ mobilization and protein kinase C activation.
Authors: M B Taubman, J D Marmur, C L Rosenfield, A Guha, S Nichtberger, Y Nemerson
Journal: Journal of Clinical Investigation (1993)

Tissue factor (TF) is a low molecular weight glycoprotein that initiates the clotting cascade and is considered to be a major regulator of coagulation, hemostasis, and thrombosis. TF is not expressed in the intima or media of normal adult blood vessels. Accordingly, it has been hypothesized that the initiation of intravascular coagulation may require the "induced" expression of TF in the vessel wall. We report that TF mRNA and protein are rapidly and markedly induced in early and late passaged vascular smooth muscle cells (VSMC) by growth factors (serum, platelet-derived growth factor, epidermal growth factor), vasoactive agonists (angiotensin II), and a clotting factor (alpha-thrombin). The induction of TF mRNA by these agents is dependent upon mobilization of intracellular Ca2+ and is blocked by Ca2+ chelation. In contrast to other growth factor-responsive genes, such as KC and c-fos, downregulation of protein kinase C activity by prolonged treatment with phorbol esters fails to block agonist-mediated TF induction. This raises the possibility that protein kinase C activation may not be necessary for TF mRNA induction in VSMC. VSMC may play a role in the generation or propagation of thrombus through the induction of TF, particularly in settings, such as those associated with acute vessel injury, where the endothelium is denuded and the VSMC are exposed to circulating blood.
Allergy Consultation and Skin Testing Benefits Significantly the Selection of the Antibiotic for Antibacterial Prophylaxis Preoperatively (ABPPO) in Patients Who Report Allergy to Penicillin (PRAP)
Authors: E. Frigas, P.J. Markus, B.J. Narr, D.R. Danielson, P.A. Park, K.A. Bachman, P.A. Harris, M.M. O'Byrne, K.E. Kloos, G.W. Volcheck, H. Kita, D.R. Schroeder
Journal: Journal of Allergy and Clinical Immunology (2006)
Hybrid T cell receptor genes formed by interlocus recombination in normal and ataxia-telangiectasis lymphocytes.
Authors: S Lipkowitz, M H Stern, I R Kirsch
Journal: The Journal of Experimental Medicine (1990)

In this paper, using polymerase chain reaction (PCR), we demonstrated the occurrence of hybrid genes formed by interlocus recombination between T cell receptor gamma (TCR-gamma) variable (V) regions and TCR-beta joining (J) regions in the peripheral blood lymphocytes (PBL) from normal individuals and patients with ataxia-telangiectasia (AT). Sequence analysis of the PCR-derived hybrid genes confirmed that site-specific V gamma-J beta recombination had occurred and showed that 10 of 23 genomic hybrid genes maintained a correct open reading frame. By dilution analysis, the frequency of these hybrid genes was 8 +/- 1/10(5) cells in normal PBL and 587 +/- 195/10(5) cells in AT PBL. These frequencies and the approximately 70-fold difference between the normal and AT samples are consistent with previous cytogenetic data examining the occurrence of an inversion of chromosome 7 in normal and AT PBL. We also demonstrated expression of these hybrid genes by PCR analysis of first-strand cDNA prepared from both normal and AT PBL. Sequence analysis of the PCR-amplified transcripts showed that, in contrast to the genomic hybrid genes, 19 of 22 expressed genes maintained a correct open reading frame at the V-J junction and correctly spliced the hybrid V-J exon to a TCR-beta constant region, thus allowing translation into a potentially functional hybrid TCR protein. Another type of hybrid TCR transcript was found in a which a rearranged TCR-gamma V-J exon was correctly spliced to a TCR-beta constant region. This form of hybrid gene may be formed by trans-splicing. These hybrid TCR genes may serve to increase the repertoire of the immune response. In addition, studies of their mechanism of formation and its misregulation in AT may provide insight into the nature of the chromosomal instability syndrome associated with AT. The mechanism underlying hybrid gene formation may be analogous to the mechanism underlying rearrangements between putative growth-affecting genes and the antigen receptor loci, which are associated with AT lymphocyte clones and lymphoid malignancies.
Serum lactate dehydrogenase and creatine kinase during marathon training.
Authors: A G Rumley, A R Pettigrew, M E Colgan, R Taylor, S Grant, A Manzie, I Findlay, H Dargie, A Elliott
Journal: British Journal of Sports Medicine (1985)

Serum total creatine kinase (CK) and the lactate dehydrogenase (LDH) isoenzymes were studied in 38 sedentary middle-aged men (aged 35-50 yrs) during a 30 week marathon training programme. Basal CK activity rose by 33% after 15 weeks but a significant rise (27%) in LDH activity took 30 weeks to occur. Post-exercise (maximum test on a bicycle ergometer) CK and LDH activities were higher than pre-exercise levels but the increment in enzyme activity following exercise did not change. LDH1 and LDH2 isoenzyme activity increased by 2.5% and 4% of total LDH respectively while LDH3 and LDH5 decreased by 3.9% and 2.4% respectively over 30 weeks. Post marathon total CK did not correlate with finishing time at 30 mins or 30 hrs post race. The range of CK MB isoenzyme activity at 30 mins post race was 1.8-9.8% of total CK with 11 subjects having a value above 6%. The training programme appears not to have affected muscle CK and LDH release during exercise but isoenzyme distribution changes reflect the adaptations known to occur in muscle during endurance training. Unfortunately only 16 subjects were available for all the investigations, and it is these upon whom most of the data were obtained.
Early Olfactory Processing in <i>Drosophila</i>: Mechanisms and Principles
Authors: Rachel I. Wilson
Journal: Annual Review of Neuroscience (2013)

In the olfactory system of Drosophila melanogaster, it is relatively straightforward to target in vivo measurements of neural activity to specific processing channels. This, together with the numerical simplicity of the Drosophila olfactory system, has produced rapid gains in our understanding of Drosophila olfaction. This review summarizes the neurophysiology of the first two layers of this system: the peripheral olfactory receptor neurons and their postsynaptic targets in the antennal lobe. We now understand in some detail the cellular and synaptic mechanisms that shape odor representations in these neurons. Together, these mechanisms imply that interesting neural adaptations to environmental statistics have occurred. These mechanisms also place some fundamental constraints on early sensory processing that pose challenges for higher brain regions. These findings suggest some general principles with broad relevance to early sensory processing in other modalities.
Airway microbiota and bronchial hyperresponsiveness in patients with suboptimally controlled asthma
Authors: Yvonne J. Huang, Craig E. Nelson, Eoin L. Brodie, Todd Z. DeSantis, Marshall S. Baek, Jane Liu, Tanja Woyke, Martin Allgaier, Jim Bristow, Jeanine P. Wiener-Kronish, E. Rand Sutherland, Tonya S. King, Nikolina Icitovic, Richard J. Martin, William J. Calhoun, Mario Castro, Loren C. Denlinger, Emily DiMango, Monica Kraft, Stephen P. Peters, Stephen I. Wasserman, Michael E. Wechsler, Homer A. Boushey, Susan V. Lynch
Journal: Journal of Allergy and Clinical Immunology (2010)
Social class gradients and serum uric acid in males and females
Authors: R. M. Acheson
Journal: BMJ (1969)

The relation between serum uric acid and social class is examined by sex among 910 persons in Wensleydale, Yorkshire, 321 persons in Watford, Hertfordshire, and 1,213 persons in New Haven, Connecticut, all of whom were drawn from the general population. Among the men of Wensleydale there is a tendency of marginal significance at the 5% level for serum uric acid to increase with decreasing social class; in the New Haven women this same trend is significant at the 2.5% level; no trend was found among any of the other four sex-specific groups. Age did not account for the patterns observed. The difference between these findings and those of several studies from the United States is consistent with the view that both serum uric acid levels and gout are under multifactorial control.
Inhaled corticosteroids in COPD: the case against
Authors: S. Suissa, P. J. Barnes
Journal: European Respiratory Journal (2009)

Chronic obstructive pulmonary disease (COPD), a disease that encompasses emphysema, chronic obstructive bronchitis and small airway obstruction and that is characterised by largely irreversible airflow obstruction, now affects around 10% of the population over the age of 40 yrs 1. The sixth commonest global cause of death in 1990, currently fourth in developed countries, it is expected rise to third place globally by 2020 2. This increase is linked to the trends of its foremost risk factor, tobacco consumption during the twentieth century, and will track the worldwide smoking trends of this century. Besides smoking cessation and pulmonary rehabilitation, the treatment of COPD has previously consisted of bronchodilators early in the disease and oxygen in the late stages. However, because of the presence of inflammation in COPD, short courses of systemic corticosteroids have been used for decades in the treatment of exacerbations, often along with antibiotics. Their side-effects, however, made them unsuitable for the long-term treatment of stable COPD.

In the early 1980s, inhaled formulations of corticosteroids were shown to be highly effective for the treatment of asthma and were readily adopted in COPD with no scientific evidence of their benefit in this indication. This transition from asthma to COPD was so natural to prescribers that a Canadian survey conducted in 1994 found that one-third of patients admitted to hospital for COPD were already using inhaled corticosteroids (ICS) 3, despite the fact that no randomised controlled trials had evaluated their effectiveness in COPD. Today, market research studies estimate that the use of these drugs has increased to the point that they are used by >70% of patients with COPD in the USA and Europe, and are currently given as initial therapy to >50% of patients newly diagnosed with COPD, mostly in combination with a long-acting β-agonist (LABA) 4 …