tbuckley/cabot-search huggingface dataset:
Angiotensin II Signaling Pathways Mediate Expression of Cardiac T-Type Calcium Channels
Authors: Laurent Ferron, Véronique Capuano, Yann Ruchon, Edith Deroubaix, Alain Coulombe, Jean-François Renaud
Journal: Circulation Research (2003)

Recent studies indicate that cardiac T-type Ca2+ current (ICaT) reappears in hypertrophied ventricular cells. The aim of this study was to investigate the role of angiotensin II (Ang II), a major inducer of cardiac hypertrophy, in the reexpression of T-type channel in left ventricular hypertrophied myocytes. We induced cardiac hypertrophy in rats by abdominal aorta stenosis for 12 weeks and thereafter animals were treated for 2 weeks with losartan (12 mg/kg per day), an antagonist of type 1 Ang II receptors (AT1). In hypertrophied myocytes, we showed that the reexpressed ICaT is generated by the CaV3.1 and CaV3.2 subunits. After losartan treatment, ICaT density decreased from 0.40+/-0.05 pA/pF (n=26) to 0.20+/-0.03 pA/pF (n=27, P<0.01), affecting CaV3.1- and CaV3.2-related currents. The amount of CaV3.1 mRNA increased during hypertrophy and retrieved its nonhypertrophic level after losartan treatment, whereas the amount of CaV3.2 mRNA was unaffected by stenosis. In cultured newborn ventricular cells, chronic Ang II application (0.1 micromol/L) also increased ICaT density and CaV3.1 mRNA amount. UO126, a mitogen-activated protein kinase kinase-1/2 (MEK1/2) inhibitor, reduced Ang II-increased ICaT density and CaV3.1 mRNA amount. Bosentan, an endothelin (ET) receptor antagonist, reduced Ang II-increased ICaT density without affecting the amount of CaV3.1 mRNA. Finally, cotreatment with bosentan and UO126 abolished the Ang II-increased ICaT density. Our results show that AT1-activated MEK pathway and autocrine ET-activated independent MEK pathway upregulate T-type channel expression. Ang II-increased of ICaT density observed in hypertrophied myocytes may play a role in the pathogenesis of Ca2+ overload and arrhythmias seen in cardiac pathology.
Neuronal ensembles sufficient for recovery sleep and the sedative actions of α2 adrenergic agonists
Authors: Zhe Zhang, Valentina Ferretti, İlke Güntan, Alessandro Moro, Eleonora A Steinberg, Zhiwen Ye, Anna Y Zecharia, Xiao Yu, Alexei L Vyssotski, Stephen G Brickley, Raquel Yustos, Zoe E Pillidge, Edward C Harding, William Wisden, Nicholas P Franks
Journal: Nature Neuroscience (2015)
A new asthma severity index: a predictor of near-fatal asthma?
Authors: P. Lee, J. Abisheganaden, C.B.E. Chee, Y.T. Wang
Journal: European Respiratory Journal (2001)

Bronchial hyperresponsiveness (BHR), measured as the provocative dose of inhaled histamine or methacholine required to produce a 20% fall in forced expiratory volume in one second (FEV 1 ) (PD 20 ), is widely used as one of the indices of asthma severity. Excessive bronchoconstriction, reflected by the maximal percentage fall in forced vital capacity (FVC) at PD 20 (ΔFVC %) during BHR testing, is considered to be the most important pathophysiological determinant in fatal asthma. The present study hypothesized that an index which combines both the ease of airway narrowing and excessive bronchoconstriction, ΔFVC %/log(PD 20 ), may be better in assessing asthma severity, especially in those at risk of near-fatal attacks. The dose-response curves of 46 asthmatics who underwent methacholine challenge testing were studied. Group 1 (n=14) patients had mild disease, Group 2 (n=21) had moderate disease and Group 3 (n=11) had severe disease, as classified according to the Global Initiative for Asthma. Nine patients had prior intubation for near-fatal asthma. ΔFVC %/log (PD 20 ) was better than ΔFVC % and PD 20 in categorizing patients into the three severity groups (p&lt;0.0001), but more importantly, it was able to discriminate patients with previous intubation from those without (p=0.04). It also correlated better with FEV 1 (% predicted), frequency of symptoms and inhaled steroid requirement than either index alone. It is concluded that the percentage fall in forced vital capacity/log of the provocative dose causing a 20% fall in forced expiratory volume in one second combines information on the ease and excessive degrees of airway narrowing in asthma. This new index may be better at assessing asthma severity and in discriminating those at risk of near-fatal attacks.
Effect of baffle fenestration on outcome of the modified Fontan operation.
Authors: N D Bridges, J E Mayer, J E Lock, R A Jonas, F L Hanley, J F Keane, S B Perry, A R Castaneda
Journal: Circulation (1992)

BACKGROUND The "fenestrated Fontan" (surgical baffle fenestration followed by transcatheter test occlusion and permanent closure after postoperative recovery) was adopted in an effort to reduce perioperative mortality and morbidity. This study assesses the effect of baffle fenestration on outcome. METHODS AND RESULTS Patients having a modified Fontan operation with a cavocaval baffle and cavopulmonary anastomosis were retrospectively selected for study. Those with baffle fenestration (n = 91) were compared with those without baffle fenestration (n = 56) with respect to preoperative risk factors, age, anatomy, surgical date, and presence or absence of a previous bidirectional cavopulmonary anastomosis. Outcome variables were failure (death or take-down) and duration of postoperative pleural effusions and hospitalization. Survival and clinical status after hospital discharge were ascertained. The two groups did not appear to differ with respect to age or anatomic diagnosis. Patients having baffle fenestration were at significantly greater preoperative risk by univariate and multivariate analysis (p &lt; 0.01). Operative failure was low in both groups (11% without and 7% with baffle fenestration, p = NS). Durations of pleural effusions and hospitalization were significantly shorter with baffle fenestration (p &lt; 0.01). Neither date of surgery nor a previous bidirectional cavopulmonary anastomosis appeared to contribute to improved outcome. Patients with baffle fenestration had lower postoperative systemic venous pressure (p &lt; 0.01). There were no late deaths. Functional status in both groups is good (82% in New York Heart Association class I). CONCLUSIONS Baffle fenestration is associated with low mortality, significantly less pleural effusion, and significantly shorter hospitalization among high-risk patients having a modified Fontan operation.
High weekly intravenous doses of desferrioxamine in porphyria cutanea tarda
Authors: E. ROCCHI, M. CASSANELLI, E. VENTURA
Journal: British Journal of Dermatology (1987)

Two elderly patients with sporadic porphyria cutanea tarda (PCT) and severe associated diseases were treated with high weekly intravenous doses of desferrioxamine. This therapy proved more effective than slow subcutaneous desferrioxamine infusion and no adverse effect was recorded. We consider high dose intravenous desferrioxamine a suitable treatment for those PCT patients with severe associated diseases who are unable to apply the technique of subcutaneous desferrioxamine infusion.
The Management of Infectious Diseases in Clinical Practice.
Authors: Phillip K. Peterson
Journal: Annals of Internal Medicine (1983)

The other chapters discuss in much the same way complement, polymorph nuclear leucocytes, lymphocyte populations, macrophages and immunogenetics and their relation to chronic rheumatic disease.This book is really a review for the specialist with an immunological bias engaged in rheumatology research, who requires a very good update in the relevant immunology, rather than a text for practising physicians.My impression is that the rheumatologist, who thinks of the patient as the centre of his attention rather than of immunological explanations, will be bemused, just like renaissance man, when he was informed that Copernicus had proven that the sun no longer moved round the earth.
Distinction of Hereditary Nonpolyposis Colorectal Cancer and Sporadic Microsatellite-Unstable Colorectal Cancer through Quantification of MLH1 Methylation by Real-time PCR
Authors: Marcus Bettstetter, Stephan Dechant, Petra Ruemmele, Monika Grabowski, Gisela Keller, Elke Holinski-Feder, Arndt Hartmann, Ferdinand Hofstaedter, Wolfgang Dietmaier
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Promoter hypermethylation occurs frequently in tumors and leads to silencing of tumor-relevant genes like tumor suppressor genes. In a subset of sporadic colorectal cancers (CRC), inactivation of the mismatch repair gene MLH1 due to promoter methylation causes high level of microsatellite instability (MSI-H). MSI-H is also a hallmark of hereditary nonpolyposis colorectal cancer (HNPCC) in which mismatch repair inactivation results from germ-line mutations. For differentiation of sporadic and hereditary MSI-H tumor patients, MLH1 promoter methylation analysis is a promising tool but is not yet used in daily diagnostics because only qualitative techniques without standardization are available. The aim of this study is to establish a reliable and quantitative MLH1 methylation analysis technique and to define valid MLH1 methylation cutoff values for HNPCC diagnostics. Experimental Design: We developed a new real-time PCR–based technique to detect and quantify methylation of both proximal and distal hMLH1 promoter regions. We established and validated this technique in a cohort of 108 CRCs [94 MSI-H and 16 microsatellite stable (MSS) cases] comprising a reference (n = 58) and a tester tumor group (n = 50). Results: The reference tumor group contained 28 HNPCC with proven germ-line mutations or positive Amsterdam I criteria (median age, 37 years) and loss of MLH1 expression, 14 sporadic MSI-H CRC tumors with loss of MLH1 expression and BRAF V600E mutation (median age, 80.5 years), and 16 sporadic MSS CRC (median age, 76.5 years). No MLH1 promoter methylation could be found in any MSS tumors. HNPCC patients showed no or low level of MLH1 promoter methylation. A cutoff value of 18% methylation extent could be determined in this study to define MLH1 hypermethylation specific for sporadic MSI-H cases. Methylation could also be verified qualitatively by melting point analysis. BRAF V600E mutations were not detected in any HNPCC patients (n = 22 informative cases). Conclusion: According to the present data, quantitative MLH1 methylation analysis in MSI-H CRC is a valuable molecular tool to distinguish between HNPCC and sporadic MSI-H CRC. The detection of a BRAF V600E mutation further supports the exclusion of HNPCC.
Prevalence of arrhythmias during 24-hour electrocardiographic monitoring and exercise testing in patients with obstructive and nonobstructive hypertrophic cardiomyopathy.
Authors: D D Savage, S F Seides, B J Maron, D J Myers, S E Epstein
Journal: Circulation (1979)

Many patients with hypertrophic cardiomyopathy die suddenly and unexpectedly, a significant number perhaps due to arrhythmia. Of 100 patients initially evaluated for signs or symptoms suggestive of heart disease or a family history of hypertrophic cardiomyopathy, 51 were selected solely because they met the echocardiographic criteria for the disease, and 49 patients were selected primarily because they had: 1) normal sinus rhythm despite left atrial enlargement, 2) a history of syncope, 3) a family history of premature death, or 4) a history of paroxysmal atrial fibrillation. All 100 patients were studied by 24-hour ambulatory electrocardiographic monitoring and 74 of them also underwent treadmill exercise testing. More than 50% of patients in repetitive ventricular premature depolarizations, including 19% who had ventricular tachycardia. Monitoring was superior to exercise testing for exposing these arrhythmias. Two patients experienced cardiac arrest within 2 months of monitoring; in each, monitoring had revealed ventricular tachycardia. Two patients with paroxysms of supraventricular tachycardia during monitoring developed fixed atrial fibrillation within 1 year. These preliminary observations suggest that monitoring may help identify patients at increased risk for significant arrhythmic events.
The IASLC Lung Cancer Staging Project: Data Elements for the Prospective Project
Authors: Dorothy J. Giroux, Ramón Rami-Porta, Kari Chansky, John J. Crowley, Patti A. Groome, Pieter E. Postmus, Valerie Rusch, Jean-Paul Sculier, Frances A. Shepherd, Leslie Sobin, Peter Goldstraw
Journal: Journal of Thoracic Oncology (2009)
Genomics at work: the global gene response to enteric bacteria
Authors: D KELLY
Journal: Gut (2001)

Human beings contain complex societies of indigenous microbes, yet little is known about how resident bacteria shape our physiology.We colonized germ-free mice with Bacteroides thetaiotaomicron, a prominent component of the normal mouse and human intestinal microflora.Global intestinal transcriptional responses to colonization were observed with DNA microarrays, and the cellular origins of selected responses were established by laser-capture microdissection.The results reveal that this commensal bacterium modulates expression of genes involved in several important intestinal functions, including nutrient absorption, mucosal barrier fortification, xenobiotic metabolism, angiogenesis, and postnatal intestinal maturation.These findings provide perspectives about the essential nature of the interactions between resident microorganisms and their hosts.
Insulin Therapy during Peritoneal Dialysis
Authors: Eduard Quellhorst
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Major fluctuations of blood glucose, hyperinsulinemia, and the formation of insulin antibodies can be prevented by intraperitoneal insulin administration during peritoneal dialysis in patients with diabetic nephropathy. The reduction in insulin requirement is most pronounced compared with subcutaneous administration when insulin is instilled into the empty abdominal cavity. If insulin is instilled into the abdominal cavity along with the dialysis fluid, there are losses of activity due to delayed absorption consequential to dilution by the fluid and adsorption to the plastic surface of the dialysis solution delivery systems. These may be so pronounced as to make intraperitoneal administration uneconomical. The effectiveness of peritoneal dialysis is not affected by intraperitoneal insulin administration. The frequency of peritonitis during intraperitoneal insulin administration increases slightly only in continuous ambulatory peritoneal dialysis, but not in intermittent peritoneal dialysis.
THE USE OF MICE IN TESTS OF IMMUNITY AGAINST YELLOW FEVER
Authors: W. A. Sawyer, Wray Lloyd
Journal: The Journal of Experimental Medicine (1931)

1. A method of testing sera for protective power against yellow fever is described and designated as the intraperitoneal protection test in mice. 2. The test consists essentially of the inoculation of mice intra-peritoneally with yellow fever virus, fixed for mice, together with the serum to be tested, and the simultaneous injection of starch solution into the brain to localize the virus. If the serum lacks protective power the mice die of yellow fever encephalitis. 3. The test is highly sensitive. Consequently it is useful in epidemiological studies to determine whether individuals have ever had yellow fever and in tests to find whether vaccinated persons or animals have in reality been immunized. 4. When mice were given large intraperitoneal injections of yellow fever virus fixed for mice, the virus could be recovered from the blood for 4 days although encephalitis did not occur. If the brain was mildly injured at the time of the intraperitoneal injection, the symptoms of yellow fever encephalitis appeared 6 days later, but the virus was then absent from the blood. 5. Strains of white mice vary greatly in their susceptibility to yellow fever.
Reliable and Effective Diagnostics Are Keys to Accelerating Personalized Cancer Medicine and Transforming Cancer Care: A Policy Statement from the American Association for Cancer Research
Authors: Charles L. Sawyers, Laura J. van ‘t Veer
Journal: Clinical Cancer Research (2014)

Diagnostics are enabling physicians to make more informed treatment decisions by tailoring treatments based on each patient's unique molecular profile. Diagnostics are also an increasingly vital tool for translating the state-of-the-art advances made in basic research into improved clinical outcomes
Regulatory T-lymphocytes in asthma
Authors: A. J. M. van Oosterhout
Journal: European Respiratory Journal (2005)

T-helper cell type (Th)2 lymphocytes play an important role in the initiation, progression and persistence of allergic diseases, including asthma. However, little is known about immunoregulatory mechanisms that determine susceptibility to, severity of, or persistence of asthma. The concept of a disturbed Th1/Th2 balance, although having furthered the present understanding of immunoregulation in asthma, has recently been named a "procrustean paradigm", because of its failure to adequately explain many (pre)clinical observations. In recent years, the general knowledge regarding the regulation of infectious, autoimmune diseases, asthma and allergen immunotherapy by T-regulatory (Treg) cells, has rapidly increased. Many different Treg subsets have been described, including CD8+ Treg cells, natural killer (NK) cells and several different CD4+ Treg cell subsets. In this review, the authors will focus on two major and well-described CD4+ Treg cell subsets. These consist of naturally occurring CD25+ Treg cells and adaptive Treg cells that are postulated to prevent immune responses against self-antigens and adaptive immune responses, respectively. The adaptive T-regulatory cells are further subdivided into T-regulatory cells type 1 and T-helper cell type 3 that mediate suppression exclusively via the cytokines interleukin-10 and transforming growth factor-beta, respectively.
Bronchodilator reversibility testing in chronic obstructive pulmonary disease
Authors: P M A Calverley
Journal: Thorax (2003)

A limited or absent bronchodilator response is used to classify chronic obstructive pulmonary disease (COPD) and can determine the treatment offered. The reliability of the recommended response criteria and their relationship to disease progression has not been established.660 patients meeting European Respiratory Society (ERS) diagnostic criteria for irreversible COPD were studied. Spirometric parameters were measured on three occasions before and after salbutamol and ipratropium bromide sequentially or in combination over 2 months. Responses were classified using the American Thoracic Society/GOLD (ATS) and ERS criteria. Patients were followed for 3 years with post-bronchodilator FEV(1) and exacerbation history recorded 3 monthly and health status 6 monthly.FEV(1) increased significantly with each bronchodilator, a response that was normally distributed. Mean post-bronchodilator FEV(1) was reproducible between visits (intraclass correlation 0.93). The absolute change in FEV(1) was independent of the pre-bronchodilator value but the percentage change correlated with pre-bronchodilator FEV(1) (r=-0.44; p<0.0001). Using ATS criteria, 52.1% of patients changed responder status between visits compared with 38.2% using ERS criteria. Smoking status, atopy, and withdrawing inhaled corticosteroids were unrelated to bronchodilator response, as was the rate of decline in FEV(1), decline in health status, and exacerbation rate.In moderate to severe COPD bronchodilator responsiveness is a continuous variable. Classifying patients as "responders" and "non-responders" can be misleading and does not predict disease progression.
The mouse stargazer gene encodes a neuronal Ca2+-channel γ subunit
Authors: Verity A. Letts, Ricardo Felix, Gloria H. Biddlecome, Jyothi Arikkath, Connie L. Mahaffey, Alicia Valenzuela, Frederick S. Bartlett, Yasuo Mori, Kevin P. Campbell, Wayne N. Frankel
Journal: Nature Genetics (1998)
Evaluation of Several Methods for Computing Stroke Volume from Central Aortic Pressure
Authors: C. Frank STARMER, PHILIP A. MCHALE, FREDERICK R. COBB, JOSEPH C. GREENFIELD
Journal: Circulation Research (1973)

Six pulse-contour methods for estimating stroke volume from a single central aortic blood pressure were evaluated in 8 dogs and 17 patients. In the dogs, wide variations in stroke volume, measured with an electromagnetic flowmeter, were obtained by pacing the heart at various rates during a control period and during several pharmacologic interventions. Good correlations existed between measured stroke volume and most estimators when the data from each intervention were analyzed separately. However, regression analysis revealed considerable variation in the individual slopes and intercepts, and thus a poor correlation was obtained when all data for one dog were combined in a single analysis. Similar evaluations were carried out in two groups of patients in whom the pressure-gradient technique was used to measure stroke volume. In the group with minimal variations in hemodynamic status, the correlations between estimated and true stroke volume were reasonably good. In the patients having a wide range of hemodynamic conditions, considerable variation in both slopes and intercepts was observed, and the combined correlation coefficients were generally poor. Although pulse contour methods of estimating stroke volume may work reasonably well over a range of stroke volumes when the variation is induced by a single perturbing agent, none of these methods perform adequately when the variation is induced by multiple perturbing agents; thus their clinical usefulness is markedly limited.
Non-invasive management of fever and breathlessness in HIV positive patients
Authors: RM Leach, AC Davidson, MJ O'Doherty, M Nayagam, A Tang, NT Bateman
Journal: European Respiratory Journal (1991)

In a prospective study of 72 human immunodeficiency virus (HIV) positive patients presenting with fever and breathlessness, a non-invasive management protocol, incorporating a scanning technique using radioactively labelled diethylenetriamine penta acetate (DTPA) and sputum induction, was found to be highly sensitive and specific in the early detection of Pneumocystis carinii pneumonia (PCP). At presentation, the DTPA scan was abnormal in 34 of 36 cases of PCP, irrespective of smoking history, whilst the chest radiograph was diffusely abnormal in 21 cases. Sputum induction identified 7 of 14 patients with PCP in the first six months of its use and 7 of 10 patients over the last six months. The DTPA lung scan and induced sputum examination are non-invasive techniques which can be used to investigate out-patients. In combination they detected all cases of PCP at presentation, reduced the need for bronchoscopy, resulted in a low case fatality (5.4%) and reduced the need for admission.