tbuckley/cabot-search huggingface dataset:
Failure of nitroglycerin and diltiazem to reduce platelet-mediated vasoconstriction in dogs with coronary artery stenosis and endothelial injury: Further evidence for thromboxane A2 and serotonin as mediators of coronary artery vasoconstriction in vivo
Authors: Paolo Golino, L. Maximilian Buja, Yao Sheng-Kun, Janice McNatt, James T. Willerson
Journal: Journal of the American College of Cardiology (1990)
Stoichiometry of the T cell antigen receptor (TCR) complex: each TCR/CD3 complex contains one TCR alpha, one TCR beta, and two CD3 epsilon chains.
Authors: J A Punt, J L Roberts, K P Kearse, A Singer
Journal: The Journal of Experimental Medicine (1994)

The stoichiometry of the subunits that comprise the T cell antigen receptor (TCR) complex is not completely known. In particular, it is uncertain whether TCR alpha and TCR beta proteins are present in the TCR complex as one or multiple heterodimeric pairs. In this study we have used mice transgenic for two different TCR alpha and two different TCR beta proteins to determine the number of TCR alpha and TCR beta chains in a single TCR complex. Individual thymocytes and splenic T cells from double TCR transgenic mice simultaneously expressed all four transgenic TCR proteins on their surfaces. Because the individual TCR alpha and individual TCR beta proteins were biochemically distinguishable, we were able to examine association among the transgenic TCR products. We found that each TCR alpha chain paired with each TCR beta chain, but that each TCR complex contained only one TCR alpha and one TCR beta protein. Furthermore, quantitative immunofluorescence revealed that T cells expressed twice as many CD3 epsilon as TCR beta proteins. These findings demonstrate that there are precisely one TCR alpha, one TCR beta, and two CD3 epsilon chains in each TCR/CD3 complex expressed on the surfaces of both thymocytes and mature T cells.
Hospital Sterile Supplies
Authors: J. H. Bowie, F. J. Gillingham, I. D. Campbell, A. R. Gordon
Journal: BMJ (1963)

In well-run institutions, intestinal hospital infection and contact hospital infection are things of the past.However, the present high rates of pyogenic aerial infection cause great concern and must influence the design, method of ventilation, and system of supply for special centres such as operating rooms and intensive-care units.Certain principles of hygiene have proved safe guides for those concerned with the design not only of theatre suites but of the several new forms of special isolation and treatment centres now recognized as essential for the safe- guard of patients-for example, artificial kidney, kidney transplant, and assisted respiration units, and resuscitation and post-operative recovery suites.Experience has shown that any compromise which evades these principles leads to disappointing results for all concerned.Modern teams of surgeons, physicians, and nurses, backed by basic scientists and first-class hospital laboratory services, can often tide the dangerously ill patient over the critical phase immediately threatening life.Thereafter the main risk to these highly susceptible patients is serious hospital infection.In designing surgical suites and certain special treatment centres, therefore, no compromise circumventing the environmental requirements of asepsis should be accepted by either doctors or nurses.Some of the Principles Concerned Instruments, apparatus, materials, etc., can be rendered safe for surgical use by being either sterilized or sanitized -whichever is appropriate for a particular item.Sterilization renders the object totally free from all living micro- organisms, while sanitization means that the object has BRnmi
Effects of Escherichia coli hemolysin on human monocytes. Cytocidal action and stimulation of interleukin 1 release.
Authors: S Bhakdi, M Muhly, S Korom, G Schmidt
Journal: Journal of Clinical Investigation (1990)

This study reports on the potent cytocidal and interleukin-1 releasing properties of Escherichia coli hemolysin (ECH) on human monocytes. Nanomolar concentrations of purified ECH (250-2,000 ng/ml) caused rapid and irreversible depletion of cellular ATP to levels below 20% of controls within 60 min. Subcytocidal doses (10-200 ng/ml) of ECH induced rapid release within 60-120 min of large amounts of interleukin 1 beta (IL-1 beta) from cultured monocytes. IL-1 beta release occurred in the presence of actinomycin D and cycloheximide, and was thus probably due to processing and export of intracellular IL-1 beta precursor. Incubation of toxin-producing E. coli at ratios of only 0.3-3 colony-forming units per monocyte evoked approximately 50% depletion of total cellular ATP within 90 min. Toxin producers also stimulated synthesis and release of large amounts of interleukin 1, but not of tumor necrosis factor within the same time span. In contrast, non-toxin producers caused neither cell death nor rapid interleukin 1 release. Stimulation of rapid interleukin 1 release coupled with potent cytocidal effects on cells of monocytic origin may represent pathogenetically significant events incurred by bacterial strains that produce ECH and related cytolysins.
Is quantitative real time polymerase chain reaction MCAM transcript assay really suitable for prognostic and predictive management of melanoma patients?
Authors: E. Capoluongo, C. Paolillo, F. Vendittelli
Journal: British Journal of Dermatology (2014)

Funding sources: no external funding. Conflicts of interest: none declared. Dear Editor, We have read with great interest the paper ‘Markers of circulating tumour cells in the peripheral blood of patients with melanoma correlate with disease recurrence and progression’, in which Reid et al.1 tried to establish the molecular phenotype of circulating melanoma cells (mCTCs) in order to identify possible biomarkers useful for disease staging, recurrence and prognosis. Although we agree with these authors regarding the use of a multimarker panel for the quantitative real‐time polymerase chain reaction (qRT‐PCR) analysis of the mCTC phenotype, above all when used in the context of laboratory clinical diagnostics, we would like to focus on the need of a stringent validation of each molecular biomarker before its inclusion in a panel for diagnostic purposes. In particular, we focused on the MCAM transcript because it is already known both as a marker of melanoma progression2 and as a more accurate prognostic marker compared with overall clinicopathological characteristics.3 4 In this context, we underline that the most interesting findings provided by Reid et al.1 are in relation to the correlation between MCAM expression and increased tumour burden: these data seem to suggest that MCAM is a suitable marker for monitoring response to therapy, being a surrogate marker of ineffective eradication of circulating melanoma cells and, subsequently, of negative outcome. For these reasons, the authors speculate that MCAM expression could be useful for: (i) monitoring treatment resistance or risk of relapse; (ii) identifying a subset of patients with metastatic disease who respond poorly to conventional systemic treatments and may benefit from an alternative treatment regimen.1
Immunomodulatory treatment trial for paraneoplastic neurological disorders
Authors: Steven Vernino, Brian Patrick O'Neill, Randolph S. Marks, Judith R. O'Fallon, David W. Kimmel
Journal: Neuro-Oncology (2004)

Paraneoplastic neurological disorders are devastating remote effects of malignancy. Despite compelling evidence of an autoimmune pathogenesis, empiric immunomodulatory treatment of these disorders is often ineffective. However, very few systematic studies have been conducted, and the treatment of patients without active malignancy has not been addressed. We conducted a prospective open-label treatment study of plasma exchange plus conventional cancer chemotherapy (10 patients) or plasma exchange plus continuous oral cyclophosphamide (10 patients). All patients had progressive symptoms and at least moderate disability at enrollment (mean Rankin score, 3.4). Patients who had experienced symptoms for more than 12 months were excluded (mean duration of symptoms at enrollment, 3.6 months). The primary outcome measure was change in quantitative disability measures (Rankin and Barthel scores) after 6 months of treatment; a positive response was defined as stability or improvement in disability. Overall, 50% of patients had a positive response at 6 months (6 patients had improved by at least 1 Rankin grade). Patients with good outcome tended to be those with less disability at time of enrollment. Hematologic toxicity was common among those receiving cyclophosphamide. Aggressive immunosuppression early in the clinical course should be considered in patients who have paraneoplastic neurological disorders, even when there is no evidence of active malignancy.
Evidence for More Benefits of Cholesterol-Lowering Drugs
Authors: Andrew A. Skolnick
Journal: JAMA (1997)

CLINICAL STUDIES have shown that cholesterol-lowering drugs—such as the statin class of pharmaceuticals—can dramatically reduce the risks of myocardial infarction (MI) and mortality from heart disease. Accumulating evidence suggests that these agents do more than just lower cholesterol to protect patients at risk for coronary artery disease. The evidence suggests the drugs may help reduce inflammation at the site of the plaque, reduce the risk of thrombosis, help normalize endothelial function, and improve the vessels' vasodilatory function. Speaking at the "Summit on Cholesterol and Coronary Disease: The 2nd National Conference on Lipids in the Elimination and Prevention of Coronary Artery Disease," in Lake Buena Vista, Fla, B. Greg Brown, MD, PhD, professor of medicine and cardiology and director of the University of Washington School of Medicine's Atherosclerosis Research Laboratory, in Seattle, described some of these mechanisms that may lie behind the drugs' ability to protect coronary arteries. <h3>Lipid Depletion</h3> By
Evidence for a differential expression of the FcεRIγ chain in dendritic cells of atopic and nonatopic donors
Authors: Natalija Novak, Carmen Tepel, Susanne Koch, Klaudia Brix, Thomas Bieber, Stefan Kraft
Journal: Journal of Clinical Investigation (2003)

While mast cells and basophils constitutively express the high-affinity IgE receptor (FcεRI), it is absent or weakly expressed on APCs from normal donors. FcεRI is strongly upregulated on APCs from atopic donors and involved in the pathophysiology of atopic diseases. Despite its clinical relevance, data about FcεRI regulation on APCs are scarce. We show that in all donors intracellular α chain of the FcεRI (FcεRIα) accumulates during DC differentiation from monocytes. However, expression of γ chains of the FcεRI (FcεRIγ), mandatory for surface expression, is downregulated. It is low or negative in DCs from normal donors lacking surface FcεRI (FcεRIneg DCs). In contrast, DCs from atopics express surface FcεRI (FcεRIpos DCs) and show significant FcεRIγ expression, which can be coprecipitated with FcεRIα. In FcεRIneg DCs lacking FcεRIγ, immature and core glycosylated FcεRIα accumulates in the endoplasmic reticulum. In FcεRIpos DCs expressing FcεRIγ, an additional mature form of FcεRIα exhibiting complex glycosylation colocalizes with FcεRIγ in the Golgi compartment. IgE binding sustains surface-expressed FcεRI on DCs from atopic donors dependent on baseline protein synthesis and transport and enhances their IgE-dependent APC function. We propose that enhanced FcεRI on DCs from atopic donors is driven by enhanced expression of otherwise limiting amounts of FcεRIγ and is preserved by increased IgE levels.
Clinically Suspected Deep Venous Thrombosis of the Lower Extremities
Authors: Kenneth M. Moser
Journal: JAMA (1977)

To define the utility of new diagnostic approaches in patients with clinically suspected deep venous thrombosis of the lower extremities, 42 legs of 33 patients were studied by fibrinogen labeled with radioactivie iodine (125I) impedance plethysmography (IPG), and contrast venography. The clinical diagnosis was confirmed in approximately two thirds of the legs and patients. In venogram-positive legs, fibrinogen 125I was positive in 70%, IPG in 61%, and one of the two in 78%. In venogram-negative legs, fibrinogen 125I was positive in four (21%) and IPG was negative in all. It was found that the size, age, and location of the thrombus, collateral vein development, heparin sodium therapy, and technical-interpretive choices can influence both IPG and fibrinogen 125I results. The data demonstrate that the fibrinogen 125I and IPG procedures can assist physicians in the diagnosis of clinically suspected deep venous thrombosis of the lower extremities.
Sirtuin mediated neuroprotection and its association with autophagy and apoptosis: Studies employing transgenic C. elegans model
Authors: Aamir Nazir, Pooja Jadiya
Journal: Molecular Neurodegeneration (2013)

Background Sirtuins, NAD+-dependent protein deacetylases, are well known for their role in longevity. Aging is the major known risk factor for the onset of Parkinson’s disease (PD). In our previous studies, SIRT1 induction by calorie restriction (CR) diet regimen has been shown to protect against dopaminergic neurodegeneration via sir-2.1 mediated pathway. Taking the studies forward, we endeavoured to understand the role of nicotinamide adenine dinucleotide activated protein deacetylase Sir2p/Sirt1 in calorie restriction mediated prevention of Parkinsonism employing transgenic Caenorhabditis elegans expressing human alpha synuclein.
PHENOMENON OF LOCAL SKIN REACTIVITY TO BACILLUS TUBERCULOSIS
Authors: Gregory Shwartzman
Journal: The Journal of Experimental Medicine (1935)

New toxic substances in certain tuberculin, O.T., and B. typhosus culture filtrates are described. These substances are capable of eliciting the hemorrhagic necrosis characteristic of the phenomenon of local skin reactivity provided heterologous bacterial filtrates of high potency are used either for the intradermal or the intravenous injection. The toxic substances apparently have no relationship to the tuberculin substances proper. The experiments with inactive preparations also demonstrate in rabbits a state of hypersensitiveness to tuberculin, O.T., and bacteria-free culture filtrates in the absence of tuberculous foci. The reactions are elicited provided the tissues are rendered vulnerable through contact with certain soluble bacterial factors capable of eliciting the phenomenon of local skin reactivity to bacterial filtrates, and provided the tuberculin or the tuberculous culture filtrates are injected intravenously into immunized rabbits.
Asymmetry among Hering primaries thwarts the Inverted spectrum argument
Authors: Robert E. MacLaury
Journal: Behavioral and Brain Sciences (1999)

Purest points of Hering's six primary colors reside at different levels of lightness such that inversion of each hue pair would be detectable in subjects' choice of foci on the Munsell array. An inverted spectrum would not impose the isomorphism constraint on a contrast of red-green or yellow-blue, whatever we conclude about inference in functionalism.
Using telephones in primary care
Authors: P. D Toon
Journal: BMJ (2002)

NHS Direct, the United Kingdom's open access telephone advice system, which is staffed by nurses supported by computer decision software, has been the subject of a long and often bitter debate. Is it value for money; is this system the most effective; how should it relate to other services; and what is its effect on them? But this concentration on one particular initiative ignores wider questions about telephone consultation in primary care. What is its role? Who should do it? What background and training do its providers need?

The telephone has been around for more than a century, but the literature on these questions is scanty. A recent Medline search on telephone consultation found only 77 references on its use in primary care over 35 years. Most of these references were reviews, commentaries, or case studies, with only a handful of controlled trials.

Just as the recent debate has centred on NHS Direct, so the literature focuses on use of the telephone out …
Tests of Ovarian Function
Authors: Jürgen Plotz
Journal: JAMA (1969)

The ovary has two principal functions: (1) the production of ova, and (2) the secretion of sex hormones. Both functions are intimately interrelated and directed toward successful fertilization, migration of the fertilized ovum to the uterus, implantation of the blastocyst in the endometrium, and early development of the embryo. Disturbances of these functions are clinically reflected in menstrual disorders and infertility. The clinical evaluation of ovarian function is based on the cyclic phenomena elicited by the ovarian hormones on target organs and the direct measurements of these hormones or their metabolites or both in body fluids. This is also true for the diagnosis and detection of ovulation in sterile patients and in women practicing the rhythm method of birth control. In the opinion of some authors the recovery of the ovum in the genital tract or the establishment of pregnancy is the only valid and certain method of diagnosing ovulation.
Idiotypic markers of polyclonal B cell activation. Public idiotypes shared by monoclonal antibodies derived from patients with systemic lupus erythematosus or leprosy.
Authors: C Mackworth-Young, J Sabbaga, R S Schwartz
Journal: Journal of Clinical Investigation (1987)

We investigated idiotypic markers of monoclonal antibodies derived from patients with polyclonal B-cell activation. Four monoclonal antibodies with different ligand binding specificities derived from a patient with lepromatous leprosy and three monoclonal anti-DNA antibodies from two patients with SLE were studied. Three new public idiotopes, which were common to monoclonal antibodies from all three patients, were defined by five polyclonal rabbit antiidiotypes, two monoclonal mouse antiidiotopes, and a monoclonal mouse antibody against a synthetic peptide that contains residues of the heavy chain CDR-1 of a monoclonal lupus anti-DNA antibody. The antibody against the synthetic idiotype was found to react with native immunoglobulins in solution. One idiotope was found to be consistently immunogenic in all animals tested. Since the three patients are of different ethnic origins, these shared idiotypes are probably encoded by germline V genes. These genes may be recurrently expressed in states of polyclonal B-cell activation, regardless of etiology. The results suggest that some autoantibodies arise by expansion of a pool of precursors in the normal antibody repertoire.
Somatic cell gene mutations in humans: biomarkers for genotoxicity.
Authors: R J Albertini, J A Nicklas, J P O'Neill
Journal: Environmental Health Perspectives (1993)

Somatic cell gene mutations arising in vivo in humans provide biomarkers for genotoxicity. Four assays, each measuring changes in a different "recorder" gene, are available for detecting mutations of the hemoglobin (Hb) and glycophorin A (gpa) genes in red blood cells and the hypoxanthine-guanine phosphoribosyltransferase (hprt) and HLA genes in T-lymphocytes. Mean adult background mutant frequencies have been established; i.e., approximately 4 x 10(-8) (Hb), 5-10 x 10(-6) (hprt), 10-20 x 10(-6) (gpa) and 30 x 10(-6) (HLA). All the assays have now been used in studies of individuals exposed to physical and/or chemical genotoxic agents, and all have shown elevated values following exposures; examples are presented. In addition to quantitation, the lymphocyte assays allow molecular analyses of in vivo mutations, the definition of background and induced mutational spectra, and the search for unique changes for characterizing specific mutagens. The HPRT system currently has the largest database in this regard. Approximately 15% of adult background hprt mutations are due to gross structural alterations (primarily deletions) having random breakpoints; 85% result from "point" changes detected only by sequencing. In contrast, a specific intragenic deletion due to DNA cleavage at specific sites characterizes fetal hprt mutations, implicating a developmental mistake in their genesis. (This kind of developmental mistake in other genes is frequently observed in lymphoid malignancies.) Mutational spectra are just beginning to be defined for induced hprt mutations, e.g., ionizing radiation produces large deletions.(ABSTRACT TRUNCATED AT 250 WORDS)
LKB1 Regulates Pancreatic β Cell Size, Polarity, and Function
Authors: Zvi Granot, Avital Swisa, Judith Magenheim, Miri Stolovich-Rain, Wakako Fujimoto, Elisabetta Manduchi, Takashi Miki, Jochen K. Lennerz, Christian J. Stoeckert, Oded Meyuhas, Susumu Seino, M. Alan Permutt, Helen Piwnica-Worms, Nabeel Bardeesy, Yuval Dor
Journal: Cell Metabolism (2009)
Adenosine and A1 selective agonists offer minimal protection against ischaemic injury to isolated rat cardiomyocytes
Authors: C. E Ganote, S. Armstrong, J. M Downey
Journal: Cardiovascular Research (1993)

The aim was to determine if isolated rat cardiomyocytes could be protected from ischaemic cell death by preincubation with adenosine or adenosine agonists.Cardiomyocytes isolated from rat hearts were preincubated in the presence of adenosine, CCPA (2-chloro-N6-cyclopentyladenosine), or carbachol prior to concentration into an ischaemic slurry. Effects of glycolysis and of isoprenaline were determined by addition of iodoacetic acid or isoprenaline to the ischaemic incubates and by exclusion of glucose from all media. Rates of ischaemic contracture were determined and survival of the myocytes versus paired control preparations was determined after various times of ischaemia, following resuspension of the cells in isotonic or hypotonic media.Adenosine and CCPA produced only a small reduction of the rates of contracture and death of isolated myocytes. Carbachol gave no significant protection. Neither the degree of injury of control cells nor the amount of protection by CCPA was altered in the presence of added isoprenaline. Protection was abolished by the A1 receptor blocker sulphophenyl theophylline, iodoacetic acid, and exclusion of glucose.Adenosine and adenosine agonists afford a minimal degree of protection to ischaemic isolated myocytes by a glucose dependent mechanism. This protection does not appear to account for the larger degree of protection seen in intact hearts, following similar preconditioning protocols. The failure of adenosine to protect may be related to the quiescent state of isolated cardiomyocytes, or be species specific in that adenosine may not be the trigger for preconditioning in rats.
Development and validation of challenge materials for double-blind, placebo-controlled food challenges in children☆
Authors: Berber J. Vlieg-Boerstra, Charles M.A. Bijleveld, Sicco van der Heide, Berta J. Beusekamp, Saskia A.A. Wolt-Plompen, Jeanet Kukler, Joep. Brinkman, Eric J. Duiverman, Anthony E.J. Dubois
Journal: Journal of Allergy and Clinical Immunology (2004)
Defining Influenza A Virus Hemagglutinin Antigenic Drift by Sequential Monoclonal Antibody Selection
Authors: Suman R. Das, Scott E. Hensley, William L. Ince, Christopher B. Brooke, Anju Subba, Mark G. Delboy, Gustav Russ, James S. Gibbs, Jack R. Bennink, Jonathan W. Yewdell
Journal: Cell Host & Microbe (2013)