tbuckley/cabot-search huggingface dataset:
Determinants of BRAF Mutations in Primary Melanomas
Authors: J. L. Maldonado, J. Fridlyand, H. Patel, A. N. Jain, K. Busam, T. Kageshita, T. Ono, D. G. Albertson, D. Pinkel, B. C. Bastian
Journal: JNCI Journal of the National Cancer Institute (2003)

The RAS/mitogen-activated protein kinase pathway sends external growth-promoting signals to the nucleus. BRAF, a critical serine/threonine kinase in this pathway, is frequently activated by somatic mutation in melanoma. Using a cohort of 115 patients with primary invasive melanomas, we show that BRAF mutations are statistically significantly more common in melanomas occurring on skin subject to intermittent sun exposure than elsewhere (23 of 43 patients; P<.001, two-sided Fisher's exact test). By contrast, BRAF mutations in melanomas on chronically sun-damaged skin (1 of 12 patients) and melanomas on skin relatively or completely unexposed to sun, such as palms, soles, subungual sites (6 of 39 patients), and mucosal membranes (2 of 21 patients) are rare. We found no association of mutation status with clinical outcome or with the presence of an associated melanocytic nevus. The mutated BRAF allele was frequently found at an elevated copy number, implicating BRAF as one of the factors driving selection for the frequent copy number increases of chromosome 7q in melanoma. In summary, the uneven distribution of BRAF mutations strongly suggests distinct genetic pathways leading to melanoma. The high mutation frequency in melanomas arising on intermittently sun-exposed skin suggests a complex causative role of such exposure that mandates further evaluation.
Phase II trial of temozolomide and cisplatin followed by whole brain radiotherapy in non-small-cell lung cancer patients with brain metastases: a GLOT-GFPC study
Authors: A.B. Cortot, L. Gerinière, G. Robinet, J.-L. Breton, R. Corre, L. Falchero, H. Berard, C. Gimenez, J.-M. Chavaillon, M. Perol, P. Bombaron, C. Mercier, P.-J. Souquet
Journal: Annals of Oncology (2006)
Bronchial Kaposi's sarcoma after single lung transplantation
Authors: C Sleiman, H Mal, C Roue, O Groussard, P Baldeyrou, P Olivier, M Fournier, R Pariente
Journal: European Respiratory Journal (1997)

Kaposi's sarcoma (KS) has been reported in 6% of malignancies of solid organ transplant recipients. Most of the observations have been in recipients of renal allografts but, so far, KS has not been described in lung transplantation. We report a case of bronchial KS occurring in a black patient 6 months after single lung-transplantation. Skin lesions were absent and, interestingly, KS lesions were observed solely in the trachea and the native lung. Following reduction of the immunosuppressive regimen a complete remission was obtained 1 year later. Up to the present time, this clinical remission is very encouraging, but close surveillance remains necessary to detect rejection episodes or the reappearance of KS following manipulation of the immunosuppressive therapy.
Increased Frequency of <i>Chlamydia pneumoniae</i> Antibodies in Patients with Asthma
Authors: MESUT GENCAY, JOCHEN J. RÜDIGER, MICHAEL TAMM, MARKUS SOLÉR, ANDRÉ P. PERRUCHOUD, MICHAEL ROTH
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The worldwide increase in asthma incidences and the impact of the disease on public health care have led to new investigations of the cause of the disease. Besides well-defined environmental causes, accumulating evidence suggests that respiratory tract infections play an important role in the pathogenesis of asthma. Among these microorganisms Chlamydia pneumoniae is an intracellular pathogen causing persistent infection. Chlamydia pneumoniae infection has been discussed as possibly inducing the development of asthma. This study was designed to investigate the presence of C. pneumoniae-specific IgG, IgA, and IgM antibodies in serum samples of 33 adults with a clinical history of asthma, positive methacholine test, and reduced FEV(1). Patients with asthma were compared with age-, sex-, and locality-matched control subjects (n = 33). We observed no acute infection either in patients with asthma or in control subjects, but 63% of all investigated individuals had signs of past infection. Chlamydia pneumoniae-specific IgA was detected in 52% of the patients with asthma and in 15% of the healthy control subjects (p < 0.01). Serological evidence of chronic infection with C. pneumoniae (high IgG [> pr = 1:512] and high IgA [> or = 1:40]) was more frequent in patients with asthma (18.2%) compared with control subjects (3.0%) (p < 0.01). Our results provide further evidence that chronic infection with C. pneumoniae is linked to asthma.
Troponin T- and troponin I-like proteins in bovine vascular smooth muscle.
Authors: A M Zanellato, A C Borrione, L Saggin, L Giuriato, S Schiaffino, S Sartore
Journal: Circulation Research (1991)

We have tested the hypothesis whether proteins with biochemical and immunochemical properties similar to those of troponin T (TnT) and troponin I (TnI) are expressed in bovine vascular smooth muscle (SM). Three monoclonal anti-TnT antibodies (TT-1, TT-2, and RV-C2) specific for the two isoforms of TnT present in the bovine cardiac muscle and two monoclonal antibodies (TI-1 and TI-5) reacting with cardiac TnI were used in this study. Anti-TnT antibodies were found to be unreactive with 1) skeletal and nonmuscle isoforms of glyceraldehyde-3-phosphate dehydrogenase, a glycolytic enzyme that shares some structural homologies with skeletal TnT, and 2) calponin, a TnT-like calmodulin/tropomyosin binding protein with some antigenic properties in common with TnT. When tested on SM extracts from aorta or coronary arteries by Western blotting, the anti-TnT antibodies were able to react exclusively with one or two polypeptides whose electrophoretic mobility corresponds to the cardiac TnT subunits. Similarly, anti-TnI antibodies specifically recognized a component in the aortic or coronary SM extracts with electrophoretic properties identical to the cardiac TnI. Immunofluorescence analysis performed on the vascular SM cells of bovine aorta, coronary arteries, and intramural branches of coronary vessels confirmed the existence of cardiac troponin immunoreactivity in these tissues. In addition, differences in the distribution of cardiac TnT- and TnI-like proteins were evidenced in nonvascular and vascular SM cells. This study shows for the first time that polypeptides with some structural properties in common with cardiac TnT and TnI can be found in the vascular SM system.
Pretreatment with Prasugrel in Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Gilles Montalescot, Leonardo Bolognese, Dariusz Dudek, Patrick Goldstein, Christian Hamm, Jean-Francois Tanguay, Jurrien M ten Berg, Debra L Miller, Timothy M Costigan, Jochen Goedicke, Johanne Silvain, Paolo Angioli, Jacek Legutko, Margit Niethammer, Zuzana Motovska, Joseph A Jakubowski, Guillaume Cayla, Luigi Oltrona Visconti, Eric Vicaut, Petr Widimsky
Journal: New England Journal of Medicine (2013)

Although P2Y12 antagonists are effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes, the effect of the timing of administration--before or after coronary angiography--is not known. We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention (PCI) was indicated.We enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after randomization. Patients were randomly assigned to receive prasugrel (a 30-mg loading dose) before the angiography (pretreatment group) or placebo (control group). When PCI was indicated, an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group.The rate of the primary efficacy end point, a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy (glycoprotein IIb/IIIa bailout) through day 7, did not differ significantly between the two groups (hazard ratio with pretreatment, 1.02; 95% confidence interval [CI], 0.84 to 1.25; P=0.81). The rate of the key safety end point of all Thrombolysis in Myocardial Infarction (TIMI) major bleeding episodes, whether related or not related to coronary-artery bypass grafting (CABG), through day 7 was increased with pretreatment (hazard ratio, 1.90; 95% CI, 1.19 to 3.02; P=0.006). The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6, respectively. Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI (69% of the patients) but increased the rate of TIMI major bleeding at 7 days. All the results were confirmed at 30 days and in prespecified subgroups.Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).
COMPARATIVE LIPID BURDEN OF CULPRIT LESIONS ACCORDING TO THE CLINICAL PRESENTATION OF ACUTE CORONARY SYNDROME
Authors: Ryan Madder, Mustafa Husaini, Jan Harnek, Matthias Gotberg, Margaret Chi, Zaahir Turfe, Sarah Dionne, Andrew Schmale, Stacie Vanoosterhout, David Erlinge
Journal: Journal of the American College of Cardiology (2014)
A locus for bipolar affective disorder on chromosome 4p
Authors: Douglas H.R. Blackwood, Lin He, Stewart W. Morris, Alan McLean, Claire Whitton, Marian Thomson, Maura T. Walker, Kirstie Woodburn, Cliff M. Sharp, Allan F. Wright,, Yoshiro Shibasaki, David M. St. Clair, David J. Poreous, Walter J. Muir
Journal: Nature Genetics (1996)
Glucose-independent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition
Authors: Swenja Kröller-Schön, Maike Knorr, Michael Hausding, Matthias Oelze, Alexandra Schuff, Richard Schell, Stephan Sudowe, Alexander Scholz, Steffen Daub, Susanne Karbach, Sabine Kossmann, Tommaso Gori, Philip Wenzel, Eberhard Schulz, Stephan Grabbe, Thomas Klein, Thomas Münzel, Andreas Daiber
Journal: Cardiovascular Research (2012)

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a novel class of drugs for the treatment of hyperglycaemia. Preliminary evidence suggests that their antioxidant and anti-inflammatory effects may have beneficial effects on the cardiovascular complications of diabetes. In the present study, we investigate in an experimental sepsis model whether linagliptin exerts pleiotropic vascular effects independent of its glucose-lowering properties. Linagliptin (83 mg/kg chow for 7days) was administered in a rat model of lipopolysaccharide (LPS) (10 mg/kg, single i.p. dose/24 h)-induced sepsis. Vascular relaxation, reactive oxygen species (ROS) formation, expression of NADPH oxidase subunits and proinflammatory markers, and white blood cell infiltration in the vasculature were determined. Oxidative burst and adhesion of isolated human neutrophils to endothelial cells were measured in the presence of different DPP-4 inhibitors, and their direct vasodilatory effects (isometric tension in isolated aortic rings) were compared. In vivo linagliptin treatment ameliorated LPS-induced endothelial dysfunction and was associated with reduced formation of vascular, cardiac, and blood ROS, aortic expression of inflammatory genes and NADPH oxidase subunits in addition to reduced aortic infiltration with inflammatory cells. Linagliptin was the most potent inhibitor of oxidative burst in isolated activated human neutrophils and it suppressed their adhesion to activated endothelial cells. Of the inhibitors tested, linagliptin and alogliptin had the most pronounced direct vasodilatory potency. Linagliptin demonstrated pleiotropic vasodilatory, antioxidant, and anti-inflammatory properties independent of its glucose-lowering properties. These pleiotropic properties are generally not shared by other DPP-4 inhibitors and might translate into cardiovascular benefits in diabetic patients.
THE INDUCTION OF AUTOIMMUNITY IN RABBITS FOLLOWING INJECTION OF HETEROLOGOUS OR ALTERED HOMOLOGOUS THYROGLOBULIN
Authors: William O. Weigle
Journal: The Journal of Experimental Medicine (1965)

Experimental autoimmunity was produced in rabbits following injection of altered homologous thyroglobulin. The thyroglobulin was altered by coupling to chemically defined haptens and by heating. With some preparations antibody to native thyroglobulin as well as thyroid lesions were produced. Injections of thyroglobulin coupled to the diazonium derivatives of arsanilic acid and sulfanilic acid were effective when given in either soluble form or incorporated into incomplete Freund's adjuvant) while injections of the same preparations precipitated by alum had relatively little effect on production of antibody or induction of lesions. The injection of native thyroglobulin in soluble form, incorporated into incomplete adjuvant or precipitated by alum usually resulted in production of little or no antibody and only rarely in the formation of lesions. The injection of a heterologous thyroglobulin into rabbits resulted in the production of antibody reacting with both the heterologous and rabbit thyroglobulin, but no thyroid lesions were observed.
Synergistic Effect of Propranolol and Nicotinic Acid on the Inhibition of Plasma Free Fatty Acid Release in the Dog
Authors: MANUEL J. LIPSON, SHAPUR NAIMI, SAMUEL PROGER
Journal: Circulation Research (1971)

Fatty acid mobilization was effected in 24 anesthetized dogs by infusion of norepinephrine over a four-hour period. Infusions of propranolol and nicotinic acid at various doses, individually and in combination, were added and free fatty acid levels were serially determined. Synergistic action of the two agents was apparent in that minimally effective concentrations of the two agents when used in combination suppressed the release of free fatty acids to 29 percent of levels achieved with norepinephrine (1,186 µEq/L). and 70 percent of levels in saline control animals (501 µEq/L). Large individual doses were no more effective than low doses used in combination. The synergistic action of propranolol and nicotinic acid in the suppression of free fatty acid mobilization may be explained by the action of these two agents on the inhibition of the adenyl cyclase system of the adipose tissue cell. This synergistic action in reducing plasma free fatty acids and their effect on lipid synthesis would allow the use of smaller doses that could reduce the risk of side effects.
Epidemiology, pathophysiology, diagnosis, and management of intracranial artery dissection
Authors: Stéphanie Debette, Annette Compter, Marc-Antoine Labeyrie, Maarten Uyttenboogaart, Tina M Metso, Jennifer J Majersik, Barbara Goeggel-Simonetti, Stefan T Engelter, Alessandro Pezzini, Philippe Bijlenga, Andrew M Southerland, Olivier Naggara, Yannick Béjot, John W Cole, Anne Ducros, Giacomo Giacalone, Sabrina Schilling, Peggy Reiner, Hakan Sarikaya, Janna C Welleweerd, L Jaap Kappelle, Gert Jan de Borst, Leo H Bonati, Simon Jung, Vincent Thijs, Juan J Martin, Tobias Brandt, Caspar Grond-Ginsbach, Manja Kloss, Tohru Mizutani, Kazuo Minematsu, James F Meschia, Vitor M Pereira, Anna Bersano, Emmanuel Touzé, Philippe A Lyrer, Didier Leys, Hugues Chabriat, Hugh S Markus, Bradford B Worrall, Stéphane Chabrier, Ralph Baumgartner, Christian Stapf, Turgut Tatlisumak, Marcel Arnold, Marie-Germaine Bousser
Journal: The Lancet Neurology (2015)
Are adaptive randomised trials or non-randomised studies the best way to address the Ebola outbreak in west Africa?
Authors: Simone Lanini, Alimuddin Zumla, John P A Ioannidis, Antonino Di Caro, Sanjeev Krishna, Lawrence Gostin, Enrico Girardi, Michel Pletschette, Gino Strada, Aldo Baritussio, Gina Portella, Giovanni Apolone, Silvio Cavuto, Roberto Satolli, Peter Kremsner, Francesco Vairo, Giuseppe Ippolito
Journal: The Lancet Infectious Diseases (2015)
Treatment of attacks with plasma-derived C1-inhibitor concentrate in pediatric hereditary angioedema patients
Authors: Henriette Farkas, Dorottya Csuka, Zsuzsanna Zotter, Erika Szabó, Ibolya Czaller, Lilian Varga, János Fejes, George Füst, George Harmat
Journal: Journal of Allergy and Clinical Immunology (2012)
The Reconstruction of Transcriptional Networks Reveals Critical Genes with Implications for Clinical Outcome of Multiple Myeloma
Authors: Luca Agnelli, Mattia Forcato, Francesco Ferrari, Giacomo Tuana, Katia Todoerti, Brian A. Walker, Gareth J. Morgan, Luigia Lombardi, Silvio Bicciato, Antonino Neri
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The combined use of microarray technologies and bioinformatics analysis has improved our understanding of biological complexity of multiple myeloma (MM). In contrast, the application of the same technology in the attempt to predict clinical outcome has been less successful with the identification of heterogeneous molecular signatures. Herein, we have reconstructed gene regulatory networks in a panel of 1,883 samples from MM patients derived from publicly available gene expression sets, to allow the identification of robust and reproducible signatures associated with poor prognosis across independent data sets. Experimental Design: Gene regulatory networks were reconstructed by using Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) and microarray data from seven MM data sets. Critical analysis of network components was applied to identify genes playing an essential role in transcriptional networks, which are conserved between data sets. Results: Network critical analysis revealed that (i) CCND1 and CCND2 were the most critical genes; (ii) CCND2, AIF1, and BLNK had the largest number of connections shared among the data sets; (iii) robust gene signatures with prognostic power were derived from the most critical transcripts and from shared primary neighbors of the most connected nodes. Specifically, a critical-gene model, comprising FAM53B, KIF21B, WHSC1, and TMPO, and a neighbor-gene model, comprising BLNK shared neighbors CSGALNACT1 and SLC7A7, predicted survival in all data sets with follow-up information. Conclusions: The reconstruction of gene regulatory networks in a large panel of MM tumors defined robust and reproducible signatures with prognostic importance, and may lead to identify novel molecular mechanisms central to MM biology. Clin Cancer Res; 17(23); 7402–12. ©2011 AACR.
Recurrent Amplifications and Deletions of Satellite DNA Accompanied Chromosomal Diversification in South American Tuco-tucos (Genus Ctenomys, Rodentia: Octodontidae): A Phylogenetic Approach
Authors: Claudio H. Slamovits, Joseph A. Cook, Enrique P. Lessa, M. Susana Rossi
Journal: Molecular Biology and Evolution (2001)

We investigated the relationship between satellite copy number and chromosomal evolution in tuco-tucos (genus Ctenomys), a karyotypically diverse clade of rodents. To explore phylogenetic relationships among 23 species and 5 undescribed forms, we sequenced the complete mitochondrial cytochrome b genes of 27 specimens and incorporated 27 previously published sequences. We then used quantitative dot-blot techniques to assess changes in the copy number of the major Ctenomys satellite DNA (satDNA), named RPCS. Our analysis of the relationship between variation in copy number of RPCS and chromosomal changes employed a maximum-likelihood approach to infer the copy number of the satellite RPCS in the ancestors of each clade. We found that amplifications and deletions of RPCS were associated with extensive chromosomal rearrangements even among closely related species. In contrast, RPCS copy number stability was observed within clades characterized by chromosomal stability. This example reinforces the suspected role of amplification, deletion, and intragenomic movement of satDNA in promoting extensive chromosomal evolution.
Effect of Medicare’s Nonpayment for Hospital-Acquired Conditions
Authors: Teresa M. Waters, Michael J. Daniels, Gloria J. Bazzoli, Eli Perencevich, Nancy Dunton, Vincent S. Staggs, Catima Potter, Naleef Fareed, Minzhao Liu, Ronald I. Shorr
Journal: JAMA Internal Medicine (2015)

In 2008, Medicare implemented the Hospital-Acquired Conditions (HACs) Initiative, a policy denying incremental payment for 8 complications of hospital care, also known as never events. The regulation's effect on these events has not been well studied.To measure the association between Medicare's nonpayment policy and 4 outcomes addressed by the HACs Initiative: central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), hospital-acquired pressure ulcers (HAPUs), and injurious inpatient falls.Quasi-experimental study of adult nursing units from 1381 US hospitals participating in the National Database of Nursing Quality Indicators (NDNQI), a program of the American Nurses Association. The NDNQI data were combined with American Hospital Association, Medicare Cost Report, and local market data to examine adjusted outcomes. Multilevel models were used to evaluate the effect of Medicare's nonpayment policy on never events.United States hospitals providing treatment for Medicare patients were subject to the new payment policy beginning in October 2008.Changes in unit-level rates of HAPUs, injurious falls, CLABSIs, and CAUTIs after initiation of the policy.Medicare's nonpayment policy was associated with an 11% reduction in the rate of change in CLABSIs (incidence rate ratio [IRR], 0.89; 95% CI, 0.83-0.95) and a 10% reduction in the rate of change in CAUTIs (IRR, 0.90; 95% CI, 0.85-0.95), but was not associated with a significant change in injurious falls (IRR, 0.99; 95% CI, 0.99-1.00) or HAPUs (odds ratio, 0.98; 95% CI, 0.96-1.01). Consideration of unit-, hospital-, and market-level factors did not significantly alter our findings.The HACs Initiative was associated with improvements in CLABSI and CAUTI trends, conditions for which there is strong evidence that better hospital processes yield better outcomes. However, the HACs Initiative was not associated with improvements in HAPU or injurious fall trends, conditions for which there is less evidence that changing hospital processes leads to significantly better outcomes.
What makes large epidemiological studies comparable?
Authors: I. Cerveri, R. De Marco
Journal: European Respiratory Journal (2010)

Repeated cross-sectional surveys have been largely used to assess temporal trends in the prevalence of diseases. To be reliable, these should respect the following simple, but essential, rules: 1) the same source population should be randomly sampled and studied on different occasions, using the same sampling frame; 2) similar numbers of subjects should be selected; 3) the disease should be diagnosed by using the same criteria and identical protocols; and 4) the data should be analysed by specific statistical techniques with appropriate adjustments of the differences in response rates.

In the respiratory field, repeated cross-sectional studies have been successfully used to monitor the prevalence of asthma 1–4 and also risk factors, such as smoking 5. The epidemiological diagnosis of asthma, being mainly based on symptoms, requires only validated questionnaires, and the only stringent requirement is that neither questions nor instructions are modified 6, 7. For chronic obstructive pulmonary disease (COPD), owing to the greater complexity of diagnosis, even in a clinical setting, it is glaringly obvious that epidemiological studies meet more methodological difficulties than those for asthma. A crucial point in this respect is the use and interpretation of spirometry.

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