tbuckley/cabot-search huggingface dataset:
Long-Term Prognosis of Patients Diagnosed With Brugada Syndrome
Authors: V. Probst, C. Veltmann, L. Eckardt, P.G. Meregalli, F. Gaita, H.L. Tan, D. Babuty, F. Sacher, C. Giustetto, E. Schulze-Bahr, M. Borggrefe, M. Haissaguerre, P. Mabo, H. Le Marec, C. Wolpert, A.A.M. Wilde
Journal: Circulation (2010)

Background— Brugada syndrome is characterized by ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD). Fundamental questions remain on the best strategy for assessing the real disease-associated arrhythmic risk, especially in asymptomatic patients. The aim of the present study was to evaluate the prognosis and risk factors of SCD in Brugada syndrome patients in the FINGER (France, Italy, Netherlands, Germany) Brugada syndrome registry. Methods and Results— Patients were recruited in 11 tertiary centers in 4 European countries. Inclusion criteria consisted of a type 1 ECG present either at baseline or after drug challenge, after exclusion of diseases that mimic Brugada syndrome. The registry included 1029 consecutive individuals (745 men; 72%) with a median age of 45 (35 to 55) years. Diagnosis was based on (1) aborted SCD (6%); (2) syncope, otherwise unexplained (30%); and (3) asymptomatic patients (64%). During a median follow-up of 31.9 (14 to 54.4) months, 51 cardiac events (5%) occurred (44 patients experienced appropriate implantable cardioverter-defibrillator shocks, and 7 died suddenly). The cardiac event rate per year was 7.7% in patients with aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients. Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events, whereas gender, familial history of SCD, inducibility of ventricular tachyarrhythmias during electrophysiological study, and the presence of an SCN5A mutation were not predictive of arrhythmic events. Conclusions— In the largest series of Brugada syndrome patients thus far, event rates in asymptomatic patients were low. Inducibility of ventricular tachyarrhythmia and family history of SCD were not predictors of cardiac events.
GOLD classifications and mortality in chronic obstructive pulmonary disease: the HUNT Study, Norway
Authors: Linda Leivseth, Ben Michael Brumpton, Tom Ivar Lund Nilsen, Xiao-Mei Mai, Roar Johnsen, Arnulf Langhammer
Journal: Thorax (2013)

How different Global Initiative for Chronic Obstructive Lung Disease (GOLD) classifications of chronic obstructive pulmonary disease (COPD) predict mortality is unclear.To examine the association of spirometric GOLD grades and the new ABCD groups with mortality, and to compare their informativeness in relation to mortality.We studied 1540 people with post-bronchodilator COPD who participated in the Norwegian Nord-Trøndelag Health Study 1995-1997 and were followed up on all-cause mortality until May 2012. The associations of spirometric GOLD grades and ABCD groups with mortality were estimated by sex specific adjusted HRs from Cox regression and standardised mortality ratios. To assess the informativeness of spirometric GOLD grades and ABCD groups at predicting mortality we used the difference in twice the log-likelihood of a Cox regression model with and without each COPD classification.The distribution of participants was 28% in GOLD 1, 57% in GOLD 2, 13% in GOLD 3 and 2% in GOLD 4, in contrast to 61% in group A, 18% in group B, 12% in group C and 10% in group D. During a median of 14.6 years of follow-up, 837 people (54%) died. Mortality increased gradually from GOLD 1 to 4, while it was generally similar in groups A and B, and in groups C and D. Spirometric GOLD grades were substantially more informative than ABCD groups at predicting mortality.Spirometric GOLD grades predicted mortality better than the new ABCD groups among people with COPD from a Norwegian general population.
Role of medullary hemodynamics in the natriuresis of drug-induced renal vasodilation in the rat.
Authors: N Lameire, R Vanholder, S Ringoir, I Leusen
Journal: Circulation Research (1980)

In contrast to most renal vasodilators, such as acetylcholine (ACh), secretin increases renal blood flow in the dog without a marked effect on sodium excretion (UNaV). To investigate this observation, we studied the relationship between renal vasodilation, UNaV, and papillary plasma flow (PPF) in rats, infused either with ACh or secretin into the aorta at the level of both renal arteries. ACh significantly increased GFR, PAH clearance, and UNaV (delta + 0.35 ml/min, + 2.11 ml/min and + 1.77 muEq/min, respectively; P < 0.05). PPF rose from 50 +/- 2.6 ml/min 100 g (mean +/- SE) in control rats to 91 +/- 4.7 ml/min 100 g after ACh (p < 0.001). Despite a similar increase in PAH clearance after secretin (+ 2.21 ml/min; P < 0.01), UNaV remained unchanged and PPF was only slightly, although significantly, increased (from 50 +/- 2.6 ml/min 100 g to 65 +/- 2.75 ml/min 100 g; P < 0.05). Both total kidney and papillary vasodilation, and the increase in UNaV after ACh were blocked by previous administration of meclofenamate (M), a prostaglandin inhibitor. No effect of M in secretin-infused rats was observed. In conclusion, the relationship between a total renal vasodilation and natriuresis was dissociated with secretin, but not with ACh. However, a relationship between the natriuresis and influence on papillary hemodynamics was observed with both vasodilators. Finally, the renal hemodynamic and natriuretic effects of ACh are probably mediated by prostaglandin release.
Selective Bispecific T Cell Recruiting Antibody and Antitumor Activity of Adoptive T Cell Transfer
Authors: Sebastian Kobold, Julius Steffen, Michael Chaloupka, Simon Grassmann, Jonas Henkel, Raffaella Castoldi, Yi Zeng, Markus Chmielewski, Jan C. Schmollinger, Max Schnurr, Simon Rothenfußer, Dolores J. Schendel, Hinrich Abken, Claudio Sustmann, Gerhard Niederfellner, Christian Klein, Carole Bourquin, Stefan Endres
Journal: JNCI Journal of the National Cancer Institute (2014)

Background:One bottleneck for adoptive T cell therapy (ACT) is recruitment of T cells into tumors. We hypothesized that combining tumor-specific T cells, modified with a marker antigen and a bispecific antibody (BiAb) that selectively recognizes transduced T cells and tumor cells would improve T cell recruitment to tumors and enhance therapeutic efficacy.
Acute Myocardial Infarction and Congestive Heart Failure Outcomes at Specialty Cardiac Hospitals
Authors: Brahmajee K. Nallamothu, Yongfei Wang, Peter Cram, John D. Birkmeyer, Joseph S. Ross, Sharon-Lise T. Normand, Harlan M. Krumholz
Journal: Circulation (2007)

Outcomes of patients with acute myocardial infarction (AMI) and congestive heart failure (CHF) at specialty cardiac hospitals are uncertain.From 2003 Medicare data, we used hierarchical regression to calculate 30-day standardized mortality ratios and risk-standardized mortality rates for AMI and CHF at 16 cardiac and 121 peer general hospitals in 15 healthcare markets. We then compared cardiac and general hospitals by determining (1) the proportion of facilities with statistically higher, no different, or lower than expected mortality based on 95% interval estimates of standardized mortality ratios and (2) differences in risk-standardized mortality rates between the types of facilities after stratification within healthcare markets. We identified 1912 patients with AMI and 1275 patients with CHF at cardiac hospitals and 13,158 patients with AMI and 18,295 patients with CHF at general hospitals. Patients at cardiac hospitals were younger, were more likely to be male, and had a much lower prevalence of noncardiovascular diseases. After adjustment for patient differences, standardized mortality ratios were significantly better than expected for 4 (25%) and 5 (31%) cardiac hospitals for AMI and CHF, respectively, compared with 5 (4%) and 6 (5%) general hospitals. Risk-standardized mortality rates were modestly lower at cardiac hospitals (15.0% versus 16.2% for AMI, P<0.001, and 10.7% versus 11.3% for CHF, P<0.01).Patients with AMI and CHF at cardiac hospitals differ considerably from those at peer general hospitals. Although outcomes were modestly better at cardiac hospitals, substantial variation was noted across individual facilities.
Protein synthesis and degradation during starvation-induced cardiac atrophy in rabbits.
Authors: A M Samarel, M S Parmacek, N M Magid, R S Decker, M Lesch
Journal: Circulation Research (1987)

To determine the relative importance of protein degradation in the development of starvation-induced cardiac atrophy, in vivo fractional synthetic rates of total cardiac protein, myosin heavy chain, actin, light chain 1, and light chain 2 were measured in fed and fasted rabbits by continuous infusion of [3H] leucine. In addition, the rate of left ventricular protein accumulation and loss were assessed in weight-matched control and fasted rabbits. Rates of total cardiac protein degradation were then estimated as the difference between rates of synthesis and growth. Fasting produced left ventricular atrophy by decreasing the rate of left ventricular protein synthesis (34.8 +/- 1.4, 27.3 +/- 3.0, and 19.3 +/- 1.2 mg/day of left ventricular protein synthesized for 0-, 3-, and 7-day fasted rabbits, respectively). Inhibition of contractile protein synthesis was evident by significant reductions in the fractional synthetic rates of all myofibrillar protein subunits. Although fractional rates of protein degradation increased significantly within 7 days of fasting, actual amounts of left ventricular protein degraded per day were unaffected. Thus, prolonged fasting profoundly inhibits the synthesis of new cardiac protein, including the major protein constituents of the myofibril. Both this inhibition in new protein synthesis as well as a smaller but significant reduction in the average half-lives of cardiac proteins are responsible for atrophy of the heart in response to fasting.
Which smokers will acquire COPD
Authors: M Johnson
Journal: Thorax (2004)

▴ Celedon JC, Lange C, Raby BA, et al . The transforming growth factor-β1 (TGFB1) gene is associated with chronic obstructive pulmonary disease (COPD). Hum Mol Genet2004;13:1649–56

[OpenUrl][1][Abstract/FREE Full Text][2]



This study uses two sequential approaches to identify genetic determinants of COPD in the absence of α1-antitrypsin deficiency. Firstly, using subjects from the Boston Early-Onset COPD Study (FEV1 ⩽40% predicted, age <53 years, not α1-antitrypsin deficient), linkage analysis …

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Epidemiologic Evidence Showing That Human Papillomavirus Infection Causes Most Cervical Intraepithelial Neoplasia
Authors: M. H. Schiffman, H. M. Bauer, R. N. Hoover, A. G. Glass, D. M. Cadell, B. B. Rush, D. R. Scott, M. E. Sherman, R. J. Kurman, S. Wacholder, C. K. Stanton, M. M. Manos
Journal: JNCI Journal of the National Cancer Institute (1993)

Experimental studies have provided strong evidence that human papillomavirus (HPV) is the long-sought venereal cause of cervical neoplasia, but the epidemiologic evidence has been inconsistent.Given improvements in HPV testing that have revealed a strong link between sexual activity history and cervical HPV infection, we conducted a large case-control study of HPV and cervical intraepithelial neoplasia (CIN) to evaluate whether sexual behavior and the other established risk factors for CIN influence risk primarily via HPV infection.We studied 500 women with CIN and 500 control subjects receiving cytologic screening at Kaiser Permanente, a large prepaid health plan, in Portland, Ore. The established epidemiologic risk factors for CIN were assessed by telephone interview. We performed HPV testing of cervicovaginal lavage specimens by gene amplification using polymerase chain reaction with a consensus primer to target the L1 gene region of HPV. Unconditional logistic regression analysis was used to estimate relative risk of CIN and to adjust the epidemiologic associations for HPV test results to demonstrate whether the associations were mediated by HPV.The case subjects demonstrated the typical epidemiologic profile of CIN: They had more sex partners, more cigarette smoking, earlier ages at first sexual intercourse, and lower socioeconomic status. Statistical adjustment for HPV infection substantially reduced the size of each of these case-control differences. Seventy-six percent of cases could be attributed to HPV infection; the results of cytologic review suggested that the true percentage was even higher. Once HPV infection was taken into account, an association of parity with risk of CIN was observed in both HPV-negative and HPV-positive women.The data show that the great majority of all grades of CIN can be attributed to HPV infection, particularly with the cancer-associated types of HPV.In light of this conclusion, the investigation of the natural history of HPV has preventive as well as etiologic importance.
Chronic myeloid leukemia and interferon-α: a study of complete cytogenetic responders
Authors: Francesca Bonifazi, Antonio de Vivo, Gianantonio Rosti, François Guilhot, Joëlle Guilhot, Elena Trabacchi, Rüdiger Hehlmann, Andreas Hochhaus, Patricia C. A. Shepherd, Juan Luis Steegmann, Hanneke C. Kluin-Nelemans, Josef Thaler, Bengt Simonsson, Andries Louwagie, Josy Reiffers, François Xavier Mahon, Enrico Montefusco, Giuliana Alimena, Joerg Hasford, Sue Richards, Giuseppe Saglio, Nicoletta Testoni, Giovanni Martinelli, Sante Tura, Michele Baccarani
Journal: Blood (2001)
Expression of molecular markers in mediastinal nodes from resected stage I non-small-cell lung cancer (NSCLC): prognostic impact and potential role as markers of occult micrometastases
Authors: S. Benlloch, J.M. Galbis-Caravajal, C. Alenda, F.M. Peiró, M. Sanchez-Ronco, J.M. Rodríguez-Paniagua, B. Baschwitz, E. Rojas, B. Massutí
Journal: Annals of Oncology (2008)
Evidence that Localized Variation in Primate Sequence Divergence Arises from an Influence of Nucleosome Placement on DNA Repair
Authors: H. Ying, J. Epps, R. Williams, G. Huttley
Journal: Molecular Biology and Evolution (2009)

Understanding the origins of localized substitution rate heterogeneity has important implications for identifying functional genomic sequences. Outside of gene regions, the origins of rate heterogeneity remain unclear. Experimental studies establish that chromatin compaction affects rates of both DNA lesion formation and repair. A functional association between chromatin status and 5-methyl-cytosine also exists. These suggest that both the total rate and the type of substitution will be affected by chromatin status. Regular positioning of nucleosomes, the building block of chromatin, further predicts that substitution rate and type should vary spatially in an oscillating manner. We addressed chromatin's influence on substitution rate and type in primates. Matched numbers of sites were sampled from Dnase I hypersensitive (DHS) and closed chromatin control flank (Flank). Likelihood ratio tests revealed significant excesses of total and of transition substitutions in Flank compared with matched DHS for both intergenic and intronic samples. An additional excess of CpG transitions was evident for the intergenic, but not intronic, regions. Fluctuation in substitution rate along ∼1,800 primate promoters was measured using phylogenetic footprinting. Significant positive correlations were evident between the substitution rate and a nucleosome score from resting human T-cells, with up to ∼50% of the variance in substitution rate accounted for. Using signal processing techniques, a dominant oscillation at ∼200 bp was evident in both the substitution rate and the nucleosome score. Our results support a role for differential DNA repair rates between open and closed chromatin in the spatial distribution of rate heterogeneity.
Gap Junctions in Vascular Tissues
Authors: George J. Christ, David C. Spray, Marwan El-Sabban, Lisa K. Moore, Peter R. Brink
Journal: Circulation Research (1996)

Integration and coordination of responses among vascular wall cells are critical to the local modulation of vasomotor tone and to the maintenance of circulatory homeostasis. This article reviews the vast literature concerning the principles that govern the initiation and propagation of vasoactive stimuli among vascular smooth muscle cells, which are nominally the final effectors of vasomotor tone. In light of the abundance of new information concerning the distribution and function of gap junctions between vascular wall cells throughout the vascular tree, particular attention is paid to this integral aspect of vascular physiology. Evidence is provided for the important contribution of intercellular communication to vascular function at all levels of the circulation, from the largest elastic artery to the terminal arterioles. The thesis of this review is that the presence of gap junctions, in concert with the autonomic nervous system, pacemaker cells, myogenic mechanisms, and/or electrotonic current spread (both hyperpolarizing and depolarizing waves through gap junctions), confers a plasticity, adaptability, and flexibility to vasculature that may well account for the observed diversity in regulation and function of vascular tissues throughout the vascular tree. It is hoped that the summary information provided here will serve as a launching pad for a new discourse on the mechanistic basis of the integrative regulation and function of vasculature, which painstakingly accounts for the undoubtedly complex and manifold role of gap junctions in vascular physiology/dysfunction.
Fibrinogen A Thr312Ala polymorphism is associated with chronic thromboembolic pulmonary hypertension
Authors: J. Suntharalingam, K. Goldsmith, V. van Marion, L. Long, C. M. Treacy, F. Dudbridge, M. R. Toshner, J. Pepke-Zaba, J. C. J. Eikenboom, N. W. Morrell
Journal: European Respiratory Journal (2007)

Although chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by the persistence of organised thrombus, few pro-thrombotic risk factors have been identified in subjects with the disease. The aim of the present study was to compare the prevalence of eight functionally relevant haemostatic polymorphisms between CTEPH subjects and healthy controls. Genomic DNA was isolated from 214 CTEPH subjects and 200 healthy controls, and analysed for Factor V Leiden, prothrombin guanine (G) to adenine (A) substitution at nucleotide 20210 (20210G&gt;A), plasminogen activator inhibitor-1 4G/5G, tissue plasminogen activator 7351 cytosine (C)&gt;thymidine (T), Factor XIII 100G&gt;T, fibrinogen Aα substitution of threonine with alanine at position 312 (Thr312Ala), fibrinogen Bβ substitution of arginine with lysine at position 448 (Arg448Lys) and fibrinogen Bβ 455G&gt;A polymorphisms. A significant difference was demonstrated in fibrinogen Aα Thr312Ala genotype and allele frequencies between CTEPH subjects and controls. The presence of the alanine allele significantly increased the risk of CTEPH. The fibrinogen Aα alanine 312 allele alters fibrinogen α–α chain cross-linkage and has previously been associated with both increased risk of embolisation and increased resistance to thrombolysis. An association between this polymorphism and chronic thromboembolic pulmonary hypertension, therefore, supports an embolic aetiology for this disease, and may provide a mechanism by which thrombus persists following an acute event.
Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization
Authors: Klaus Bønnelykke, Melanie C Matheson, Tune H Pers, Raquel Granell, David P Strachan, Alexessander Couto Alves, Allan Linneberg, John A Curtin, Nicole M Warrington, Marie Standl, Marjan Kerkhof, Ingileif Jonsdottir, Blazenka K Bukvic, Marika Kaakinen, Patrick Sleimann, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Katharina Schramm, Svetlana Baltic, Eskil Kreiner-Møller, Angela Simpson, Beate St Pourcain, Lachlan Coin, Jennie Hui, Eugene H Walters, Carla M T Tiesler, David L Duffy, Graham Jones, Susan M Ring, Wendy L McArdle, Loren Price, Colin F Robertson, Juha Pekkanen, Clara S Tang, Elisabeth Thiering, Grant W Montgomery, Anna-Liisa Hartikainen, Shyamali C Dharmage, Lise L Husemoen, Christian Herder, John P Kemp, Paul Elliot, Alan James, Melanie Waldenberger, Michael J Abramson, Benjamin P Fairfax, Julian C Knight, Ramneek Gupta, Philip J Thompson, Patrick Holt, Peter Sly, Joel N Hirschhorn, Mario Blekic, Stephan Weidinger, Hakon Hakonarsson, Kari Stefansson, Joachim Heinrich, Dirkje S Postma, Adnan Custovic, Craig E Pennell, Marjo-Riitta Jarvelin, Gerard H Koppelman, Nicholas Timpson, Manuel A Ferreira, Hans Bisgaard
Journal: Nature Genetics (2013)
CELLULAR HETEROGENEITY IN THE PRODUCTION OF AN ANTI-HAPTEN ANTIBODY
Authors: O. Mäkelä
Journal: The Journal of Experimental Medicine (1967)

Single lymph node cells from rats immunized with a conjugate of 3-iodo-4-hydroxy-5-nitrophenyl acetic acid chloride (NIP) and chicken globulin were tested against either NIP or NNP conjugated with bacteriophage. NNP is related to NIP but has a nitro group instead of iodine. The conjugated phages were still infective but easily inactivated by anti-hapten sera at a serum concentration of 10(-7). Phages carrying a related hapten were less sensitive to antibody than phages conjugated with the immunogenic hapten. When NIP-T2 and NNP-T4 conjugates were incubated in microdrops containing a single lymph node cell from an anti-NIP animal, strong inactivation of either or both phages occurred in some cases. For the reasons given in the text this inactivation was considered to be due to anti-NIP antibody produced by the cell in the microdrop. Inactivation of the two kinds of phages by the anti-NIP cells was highly nonrandom; some cells inactivated almost all of the 1700 or so NIP-T2 phages in the drop but left almost all NNP-T4 phages viable. Others had a very strong cross-reaction and inactivated equal proportions (up to 75%) of both phages. The remaining active cells exhibited an intermediate degree of cross-reaction. Control experiments indicated that there was a true cellular heterogeneity in the specificity of the anti-NIP produced by different cells. They suggested that the observed heterogeneity of specificities was limited to the structure of the hapten and was not influenced by the structure of the carrier. As all the cells studied were induced by a single hapten, the observed cellular heterogeneity was probably not caused by a heterogeneous antigen. It seems more likely that latent heterogeneity was present in the cells before they were stimulated by the NIP hapten.