tbuckley/cabot-search huggingface dataset:
Effects of Autonomic Blockade on the Baroreflex in Man at Rest and During Exercise
Authors: T. G. PICKERING, B. GRIBBIN, E. Strange PETERSEN, D. J.C. CUNNINGHAM, P. SLEIGHT
Journal: Circulation Research (1972)

The reflex bradycardia produced by a transient phenylephrine-induced rise of arterial pressure was investigated in man during rest and supine exercise, before and after autonomic blockade of the heart. Reflex bradycardia diminished proportionally to the tachycardia of exercise. Propranolol slowed the heart at rest and during exercise, but increased the reflex response only at rest, having no effect during exercise. Atropine, or atropine with propranolol, blocked the reflex during rest and exercise. The tachycardia following hypotension induced by amyl nitrite was similarly affected by the two drugs. Tachycardia induced by standing up and by isoprenaline also diminished the reflex bradycardia. It is concluded that reflex heart rate changes following sudden changes of arterial pressure are predominantly parasympathetic, and diminish during exercise in parallel with the decrease of parasympathetic tone. The reflex response is determined partly by the interaction of parasympathetic and sympathetic impulses at the sinoatrial node, shown by the effects of peripheral sympathetic stimulation and blockade at rest. During exercise central depression of the reflex may also occur.
Sensitization and Asthma Severity in Inner City African Americans (AA) and Latino Americans (LA) in a Large Community Based Cohort
Authors: R. Kumar, C. Saltoun, G. Mosnaim, L.C. Grammer, R. Durazo-Arvizu, L. Stierman, J. Shannon, K.B. Weiss
Journal: Journal of Allergy and Clinical Immunology (2006)
High density gene expression microarrays and gene ontology analysis for identifying processes in implanted tissue engineering constructs
Authors: Gerwen Lammers, Christian Gilissen, Suzan T.M. Nillesen, Peter J.E. Uijtdewilligen, Ronnie G. Wismans, Joris A. Veltman, Willeke F. Daamen, Toin H. van Kuppevelt
Journal: Biomaterials (2010)
Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs.
Authors: F Miedema, A J Petit, F G Terpstra, J K Schattenkerk, F de Wolf, B J Al, M Roos, J M Lange, S A Danner, J Goudsmit
Journal: Journal of Clinical Investigation (1988)

To investigate the effect of persistent HIV infection on the immune system, we studied leukocyte functions in 14 asymptomatic homosexual men (CDC group II/III) who were at least two years seropositive, but who still had normal numbers of circulating CD4+ T cells. Compared with age-matched heterosexual men and HIV-negative homosexual men, the CD4+ and CD8+ T cells from seropositive men showed decreased proliferation to anti-CD3 monoclonal antibody and decreased CD4+ T-helper activity on PWM-driven differentiation of normal donor B cells. Monocytes of HIV-infected homosexual men showed decreased accessory function on normal T cell proliferation induced by CD3 monoclonal antibody. The most striking defect in leukocyte functional activities was observed in the B cells of HIV-infected men. B cells of 13 out of 14 seropositive men failed to produce Ig in response to PWM in the presence of adequate allogeneic T-helper activity. These findings suggest that HIV induces severe immunological abnormalities in T cells, B cells, and antigen-presenting cells early in infection before CD4+ T cell numbers start to decline. Impaired immunological function in subclinically HIV-infected patients may have clinical implications for vaccination strategies, in particular the use of live vaccines in groups with a high prevalence of HIV seropositivity.
Hypertrophic Cardiomyopathy in Cardiac Myosin Binding Protein-C Knockout Mice
Authors: Samantha P. Harris, Christopher R. Bartley, Timothy A. Hacker, Kerry S. McDonald, Pamela S. Douglas, Marion L. Greaser, Patricia A. Powers, Richard L. Moss
Journal: Circulation Research (2002)

Familial hypertrophic cardiomyopathy (FHC) is an inherited autosomal dominant disease caused by mutations in sarcomeric proteins. Among these, mutations that affect myosin binding protein-C (MyBP-C), an abundant component of the thick filaments, account for 20% to 30% of all mutations linked to FHC. However, the mechanisms by which MyBP-C mutations cause disease and the function of MyBP-C are not well understood. Therefore, to assess deficits due to elimination of MyBP-C, we used gene targeting to produce a knockout mouse that lacks MyBP-C in the heart. Knockout mice were produced by deletion of exons 3 to 10 from the endogenous cardiac (c) MyBP-C gene in murine embryonic stem (ES) cells and subsequent breeding of chimeric founder mice to obtain mice heterozygous (+/−) and homozygous (−/−) for the knockout allele. Wild-type (+/+), cMyBP-C +/− , and cMyBP-C −/− mice were born in accordance with Mendelian inheritance ratios, survived into adulthood, and were fertile. Western blot analyses confirmed that cMyBP-C was absent in hearts of homozygous knockout mice. Whereas cMyBP-C +/− mice were indistinguishable from wild-type littermates, cMyBP-C −/− mice exhibited significant cardiac hypertrophy. Cardiac function, assessed using 2-dimensionally guided M-mode echocardiography, showed significantly depressed indices of diastolic and systolic function only in cMyBP-C −/− mice. Ca 2+ sensitivity of tension, measured in single skinned myocytes, was reduced in cMyBP-C −/− but not cMyBP-C +/− mice. These results establish that cMyBP-C is not essential for cardiac development but that the absence of cMyBP-C results in profound cardiac hypertrophy and impaired contractile function.
856-4 Randomized comparison of intra-aortic balloon support versus a percutaneous left ventricular assist device in patients with acute myocardial infarction complicated by cardiogenic shock
Authors: Holger Thiele, Enno Boudriot, Peter Sick, Josef Niebauer, Klaus-Werner Diederich, Rainer Hambrecht, Gerhard Schuler
Journal: Journal of the American College of Cardiology (2004)
The athlete's heart: is big beautiful?
Authors: R J Shephard
Journal: British Journal of Sports Medicine (1996)

Development of the concept of "athlete's heart" is traced through early clinical and radiographic studies to modern echocardiography and magnetic resonance imaging. It is noted that the lower limits of criteria for the diagnosis of a "pathological" enlargement of the heart have frequently been revised in an upward direction, as the prevalence of large hearts has been recognised in both endurance and power sports competitors who are in good health. Belief that hypertrophic cardiomyopathy is the commonest cause of sports related death in young adults is traced to weak diagnostic criteria and frequent republication of a very small group of cases. Although the existence of a congenital myocardial dystrophy is now well established, this condition is extremely rare, and has no particular predilection for athletes. Genetically based screening tests may become available in the future, but the exclusion of young adults from sports participation on echocardiographic criteria appears costly and ineffective. For most people, the development of a large heart is not a pathological sign--rather, it is a desirable outcome that will enhance performance on the sports field, and will allow longer independence in old age.
Functional Implications of Altered Subcellular Localization of PELP1 in Breast Cancer Cells
Authors: Ratna K. Vadlamudi, Bramanandam Manavathi, Seetharaman Balasenthil, Sujit S. Nair, Zhibo Yang, Aysegul A. Sahin, Rakesh Kumar
Journal: Cancer Research (2005)

Abstract It is increasingly accepted that steroidal receptor coregulators may also function in the cytoplasmic compartment. Proline-, glutamic acid–, and leucine-rich protein-1 (PELP1) is a novel coregulator that plays a role in both the genomic and extranuclear actions of estrogen receptors (ER) in hormonally responsive tissues. In this study using breast tumor arrays, we found that PELP1 was localized only in the cytoplasm in 58% of the PELP1-positive breast tumors. To help explain the significance of the cytoplasmic localization of PELP1 in human breast tumors, we created a mutant protein that was expressed only in the cytoplasm (PELP1-cyto) and then generated a model system wherein MCF-7 breast cancer cells were engineered to specifically express this mutant. We found that PELP1-cyto cells were hypersensitive to estrogen but resistant to tamoxifen. PELP1-cyto cells, but not parental MCF-7 cells, formed xenograft tumors in nude mice. In addition, PELP1-cyto cells exhibited increased association of PELP1 with Src, enhanced mitogen-activated protein kinase (MAPK) activation, and constitutive activation of AKT. The altered localization of PELP1 was sufficient to trigger the interaction of PELP1 with the p85 subunit of phosphatidylinositol-3-kinase (PI3K), leading to PI3K activation. In addition, PELP1 interacted with epidermal growth factor receptors and participated in growth factor–mediated ER transactivation functions. Our results suggest that the altered localization of PELP1 modulates sensitivity to antiestrogens, potentiates tumorigenicity, presumably via the stimulation of extranuclear estrogen responses, such as the activation of MAPK and AKT, and also enhance cross-regulation of ER transactivation activity by growth factors.
Efficacy of a nicotine mouth spray in smoking cessation: a randomised, double-blind trial
Authors: Philip Tønnesen, Hans Lauri, Roland Perfekt, Karl Mann, Anil Batra
Journal: European Respiratory Journal (2012)

A nicotine mouth spray has advantages over other acute forms of nicotine replacement therapy, such as a faster uptake of nicotine and faster relief of craving. This multicentre, randomised (2:1), double-blind, placebo-controlled efficacy and safety study evaluated self-reported, carbon monoxide-verified continuous abstinence from smoking from week 2 until weeks 6, 24, and 52 in 479 smokers (≥1 cigarette per day) who were treated with either active (n=318) or placebo (n=161) spray for 12 weeks and low-intensity counselling at three smoking cessation clinics in Denmark and Germany. Active treatment yielded significantly higher continuous abstinence rates than placebo from week 2 until week 6 (26.1% <i>versus</i> 16.1%; relative success rate (RR) 1.62, 95% CI 1.09–2.41), week 24 (15.7% <i>versus</i> 6.8%; RR 2.30, 95% CI 1.23–4.30), and week 52 (13.8% <i>versus</i> 5.6%; RR 2.48, 95% CI 1.24–4.94). Most adverse events were mild to moderate, and 9.1% of subjects on active spray withdrew due to adverse events, compared to 7.5% on placebo. The overall rate of treatment-related adverse events was 87.4% with active spray <i>versus</i> 71.4% with placebo spray. Nicotine mouth spray delivered significantly higher 6-, 24- and 52-week continuous abstinence rates than placebo.
Clinical importance of the Step 3 choice in asthma
Authors: M L Barnes
Journal: Thorax (2006)

We read with interest the meta-analysis by Masoli et al 1 which aimed to further guide clinicians in their choice between addition of long acting β2 agonists (LABA) or use of higher doses of inhaled corticosteroids (ICS) in patients with symptomatic asthma. The pooled odds of at least one moderate or severe exacerbation was 1.35 times higher in those receiving a higher dose of ICS than in those treated with LABA.

Unfortunately, it is difficult to draw any meaningful conclusion as to the clinical relevance of these findings or to compare at a glance the results with those of the previous MIASMA study2 because of differences in the summary statistics presented. For clinicians to understand the clinical context of these two studies, it is helpful to calculate the number needed to treat (NNT), as was done in the original MIASMA study.

Of the 2312 patients randomised to LABA treatment included in the newer study, 184 …
Montelukast as add-on therapy to -agonists and late airway response
Authors: M. Rosewich, M. A. Rose, O. Eickmeier, M. Travaci, R. Kitz, S. Zielen
Journal: European Respiratory Journal (2007)

The present study investigated whether single-dose oral leukotriene receptor antagonists as add-on therapy to short-acting beta-agonists, immediately after allergen challenge, block the late-phase airway response. In total, 35 mild asthmatics (mean age 24 yrs, 19 males) sensitised for house dust mites underwent two courses of bronchial allergen challenge. After the early allergic response (EAR), subjects received salbutamol once and were randomly assigned to either 10 mg of montelukast or placebo (double-blind crossover). To identify a late allergic response, forced expiratory volume in one second (FEV(1)) was monitored over the following 8 h. Baseline exhaled nitric oxide (NO) was determined ahead of each allergen challenge. Baseline NO levels differed significantly depending on the reaction to allergen challenge. In total, 12 subjects showed no significant response, 11 only showed an EAR, and 12 had a dual response and underwent further analysis. The area under the FEV(1) time-response curve 3-8 h after bronchial allergen challenge was -0.77+/-1.68 from the pre-challenge values on montelukast compared with -2.47+/-1.32 on placebo. The baseline exhaled NO fraction of subjects without an EAR was significantly lower than of those presenting a dual response. The results of the present study demonstrate that single-dose leukotriene receptor antagonists given orally right after the early allergic response can significantly inhibit the late allergic response after bronchial allergen challenge.
Direct measurement of acid permeation into rat oesophagus
Authors: S Tanaka
Journal: Gut (2003)

<b>Background and aims:</b> The early responses of the oesophageal mucosa to acid perfusion may predict subsequent pathology. Mucosal responses to luminal acid may result either from acid permeating through the mucosa or from other unknown transduction mechanisms. In order to better understand the dynamics of acid permeation into the oesophageal mucosa, we measured interstitial pH (pH<sub>int</sub>) of the oesophageal basal epithelial layer, pre-epithelial layer thickness, and blood flow in rats in vivo during luminal acid challenge. A novel confocal microscopic technique was used in vitro to measure pH<sub>int</sub> from defined cellular sites in response to luminal and basolateral acidification. <b>Methods:</b> 5-(and-6)-Carboxyfluorescein (CF) and carboxy-seminapthorhodofluor-1 (SNARF-1) fluorescence was used to measure pH<sub>int</sub> by conventional and confocal microscopy, respectively, in urethane anaesthetised rats. Pre-epithelial layer thickness was measured optically with carbon particles as markers. Blood flow was measured with laser Doppler flowmetry. <b>Results:</b> Luminal acidification failed to alter pH<sub>int</sub> in vivo and in vitro, but pH<sub>int</sub> was lowered by modest serosal acidification. Pre-epithelial layer thickness and blood flow increased significantly during luminal surface acid perfusion. Indomethacin had no effect on any acid related response. <b>Conclusion:</b> In this first dynamic measurement of oesophageal acid permeation and pre-epithelial layer thickness, pH<sub>int</sub> was preserved in spite of high luminal acidity by two complementary techniques. Despite the apparent permeability barrier to acid permeation, oesophageal blood flow and thickness responded to luminal acid perfusion.
Differential Expression of Gap Junction Proteins in the Canine Sinus Node
Authors: King F. Kwong, Richard B. Schuessler, Karen G. Green, James G. Laing, Eric C. Beyer, John P. Boineau, Jeffrey E. Saffitz
Journal: Circulation Research (1998)

Electrical coupling of pacemaker cells at gap junctions appears to play an important role in sinus node function. Although the major cardiac gap junction protein, connexin43 (Cx43), is expressed abundantly in atrial and ventricular muscle, its expression in the sinus node has been a subject of controversy. The objectives of the present study were to determine whether Cx43 is expressed by sinus node myocytes, to characterize the spectrum of connexin expression phenotypes in sinus node pacemaker cells, and to define the spatial distribution of different connexin phenotypes in the intact sinus node. To fulfill these objectives, we performed high-resolution immunohistochemical analysis of disaggregated adult canine sinus node preparations. Using enhanced tissue preservation and antigen retrieval techniques, we also performed immunohistochemical studies on sections of intact canine sinus node tissue. Analysis of disaggregated sinus node preparations revealed three populations of pacemaker cells distinguished on the basis of connexin immunohistochemical phenotype: approximately 55% of cells expressed only connexin40 (Cx40); 30% to 35% of cells expressed Cx43, connexin45 (Cx45), and Cx40; and the remaining cells had no detectable connexin expression. In immunostained sections of intact sinus node, Cx43- and Cx45-positive cells were limited in their distribution and were observed in discrete bundles that appeared to abut atrial myocytes. In contrast, Cx40 immunoreactive signal was widely distributed in the sinus node region. These results indicate that subsets of pacemaker cells express distinct connexin phenotypes. Differential expression of connexins could create regions within the sinus node with different conduction properties, thereby contributing to the nonuniform conduction properties seen in this tissue.
On the Intraoperative Molecular Status of Renal Allografts after Vascular Reperfusion and Clinical Outcomes
Authors: Yingyos Avihingsanon, Naili Ma, Martha Pavlakis, James W. Chon, Marc E. Uknis, Anthony P. Monaco, Christiane Ferran, Isaac Stillman, Asher D. Schachter, Christina Mottley, Xin Xiao Zheng, Terry B. Strom
Journal: Journal of the American Society of Nephrology (2005)

Many hypothesize that subtle inflammation and immune activity detected in the intraoperative period are linked to adverse postkidney transplant clinical outcomes. To this end, renal allografts were analyzed for expression of pro-inflammatory, inflammation-induced adhesion molecules, immune activation as well as anti-apoptotic genes expressed 15 min after vascular reperfusion (zero-hour) to determine whether this analysis can aid in predicting the occurrence of delayed graft function (DGF), acute rejection (AR), and the quality of graft function at 6 mo. Intraoperative biopsies were obtained from 75 consecutively performed renal allografts in which consent was obtained 15 min after vascular reperfusion. These biopsies were analyzed by quantitative real-time PCR for transcription of 15 select genes and by standard histopathology. Posttransplant clinical outcomes were also analyzed in respect to intraoperative transcriptional profiles and clinical parameters available at the time of transplantation. This study demonstrates that a limited and hypothesis-driven PCR-based transcriptional profile of the zero-hour kidney biopsy predicts posttransplant clinical outcomes including DGF, early AR, and the quality of renal function 6 mo posttransplantation. For some clinical endpoints, the combined use of molecular analysis and established clinical indicators available at the time of transplantation further enhances the quality of prognosis. The transcriptional profiling data provide absolutely essential data to the predictive models, particularly with respect to AR and renal function 6 mo posttransplantation.
From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology
Authors: Kanwal Pratap Singh Raghav, Sminil Mahajan, James C. Yao, Brian P. Hobbs, Donald A. Berry, Rebecca D. Pentz, Alda Tam, Waun K. Hong, Lee M. Ellis, James Abbruzzese, Michael J. Overman
Journal: Journal of Clinical Oncology (2015)

Purpose The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. Methods We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. Results A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P &lt; .001). Twenty-eight studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials reported a total of 52 unplanned analyses involving primary end points and 33 unplanned analyses involving nonprimary end points, respectively. Studies reported positive unplanned end points and unplanned analyses more frequently than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P = .002; unplanned analyses odd ratio, 8.4; P = .007). Conclusion Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting.
Virus-replicating T cells in the immune response of mice. I. Virus plaque assay of the lymphocytes reactive to sheep erythrocytes.
Authors: N Minato, Y Katsura
Journal: The Journal of Experimental Medicine (1977)

Virus plaque-forming cell assay with vesicular stomatitis virus (VSV), which had been originally introduced by Bloom and his colleagues as a tool for the enumeration of activated lymphocytes, was first applied to the immune response of mice to a widely used antigen, i.e. sheep red blood cells (SRBC). When spleen cells taken from mice previously primed with SRBC were cultured in the presence of the antigen, lymphocytes capable of replicating VSV (antigen-induced virus plaque-forming cells, Ag-V-PFC) were generated in the culture. They seemed to appear as early as 1 day of culture, and the peak was attained by the 2nd day. Most of Ag-V-PFC belonged to T-cell population, since 80-90% of Ag-V-PFC was killed by the treatment of cultured cells with anti-thymocyte serum plus complement. In vitro generation of Ag-V-PFC seemed to be highly cross-reactive (about 40%) with a related antigen (horse red blood cells). Ag-V-PFC detected in the present experiment may not represent helper T cells, effector T cells, or their precursors because of the following: (a) The generation of Ag-V-PFC was completely suppressed by the addition of anti-SRBC mouse serum in the culture, though the helper activity was apparently augmented by the same treatment. (b) Development of Ag-V-PFC was almost completely suppressed by the pretreatment of mice with cyclophosphamide 2 days before immunization, by which delayed-type hypersensitivity (DTH) was markedly augmented. (c) After the immunization of mice, Ag-V-PFC began to develop just when the level of DTH declined, at which point helper activity of the spleen cells also diminished. A possible role of Ag-V-PFC in the immune response was discussed.