tbuckley/cabot-search huggingface dataset:
Pressure Overload–Induced Alterations in Fibrillar Collagen Content and Myocardial Diastolic Function
Authors: Amy D. Bradshaw, Catalin F. Baicu, Tyler J. Rentz, An O. Van Laer, Janet Boggs, John M. Lacy, Michael R. Zile
Journal: Circulation (2009)

Chronic pressure overload causes myocardial hypertrophy, increased fibrillar collagen content, and abnormal diastolic function. We hypothesized that one determinant of these pressure overload-induced changes is the extracellular processing of newly synthesized procollagen into mature collagen fibrils. We further hypothesized that secreted protein acidic and rich in cysteine (SPARC) plays a key role in post-synthetic procollagen processing in normal and pressure-overloaded myocardium.To determine whether pressure overload-induced changes in collagen content and diastolic function are affected by the absence of SPARC, age-matched wild-type (WT) and SPARC-null mice underwent either transverse aortic constriction (TAC) for 4 weeks or served as nonoperated controls. Left ventricular (LV) collagen content was measured histologically by collagen volume fraction, collagen composition was measured by hydroxyproline assay as soluble collagen (1 mol/L NaCl extractable) versus insoluble collagen (mature cross-linked collagen), and collagen morphological structure was examined by scanning electron microscopy. SPARC expression was measured by immunoblot. LV, myocardial, and cardiomyocyte structure and function were assessed by echocardiographic, papillary muscle, and isolated cardiomyocyte studies. In WT mice, TAC increased LV mass, SPARC expression, myocardial diastolic stiffness, fibrillar collagen content, and soluble and insoluble collagen. In SPARC-null mice, TAC increased LV mass to an extent similar to WT mice. In addition, in SPARC-null mice, TAC increased fibrillar collagen content, albeit significantly less than that seen in WT TAC mice. Furthermore, the proportion of LV collagen that was insoluble was less in the SPARC-null TAC mice (86+/-2%) than in WT TAC mice (99+/-2%, P<0.05), and the proportion of collagen that was soluble was greater in the SPARC-null TAC mice (14+/-2%) than in WT TAC mice (1+/-2%, P<0.05) As a result, myocardial diastolic stiffness was lower in SPARC-null TAC mice (0.075+/-0.005) than in WT TAC mice (0.045+/-0.005, P<0.05).The absence of SPARC reduced pressure overload-induced alterations in extracellular matrix fibrillar collagen and diastolic function. These data support the hypothesis that SPARC plays a key role in post-synthetic procollagen processing and the development of mature cross-linked collagen fibrils in normal and pressure-overloaded myocardium.
Late lethal hepatitis B virus reactivation after rituximab treatment of low-grade cutaneous B-cell lymphoma
Authors: G. Perceau, N. Diris, O. Estines, C. Derancourt, S. Lévy, P. Bernard
Journal: British Journal of Dermatology (2006)

Journal Article Late lethal hepatitis B virus reactivation after rituximab treatment of low‐grade cutaneous B‐cell lymphoma Get access G. Perceau, G. Perceau CHU de Reims, Hôpital Robert‐Debré, Service de Dermatologie et *Service de Gastroentérologie, avenue du Général Koenig, 51092 Reims Cedex, France Search for other works by this author on: Oxford Academic Google Scholar N. Diris, N. Diris CHU de Reims, Hôpital Robert‐Debré, Service de Dermatologie et *Service de Gastroentérologie, avenue du Général Koenig, 51092 Reims Cedex, France Search for other works by this author on: Oxford Academic Google Scholar O. Estines, O. Estines CHU de Reims, Hôpital Robert‐Debré, Service de Dermatologie et *Service de Gastroentérologie, avenue du Général Koenig, 51092 Reims Cedex, France Search for other works by this author on: Oxford Academic Google Scholar C. Derancourt, C. Derancourt CHU de Reims, Hôpital Robert‐Debré, Service de Dermatologie et *Service de Gastroentérologie, avenue du Général Koenig, 51092 Reims Cedex, France Search for other works by this author on: Oxford Academic Google Scholar S. Lévy, S. Lévy CHU de Reims, Hôpital Robert‐Debré, Service de Dermatologie et *Service de Gastroentérologie, avenue du Général Koenig, 51092 Reims Cedex, France Search for other works by this author on: Oxford Academic Google Scholar P. Bernard P. Bernard CHU de Reims, Hôpital Robert‐Debré, Service de Dermatologie et *Service de Gastroentérologie, avenue du Général Koenig, 51092 Reims Cedex, France Pr P. Bernard. E‐mail: pbernard@chu‐reims.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 5, 1 November 2006, Pages 1053–1056, https://doi.org/10.1111/j.1365-2133.2006.07451.x Published: 01 November 2006 Article history Accepted: 03 May 2006 Published: 01 November 2006
Idiopathic Hypertrophic Subaortic Stenosis
Authors: STUART FRANK, EUGENE BRAUNWALD
Journal: Circulation (1968)

While considerable information concerning the hemodynamic and angiographic features of idiopathic hypertrophic subaortic stenosis (IHSS) is available, data concerning the natural history of the disease are limited. The clinical courses of 126 patients with hemodynamically documented IHSS, examined repeatedly for up to 12 years, were analyzed. The older patients tended to be more severely symptomatic. Although the course was extremely variable, the patients who were asymptomatic initially tended to remain so, while those who were more disabled generally deteriorated, died, or improved spontaneously. Bacterial endocarditis occurred in three patients. Ten patients died as a consequence of the natural history of IHSS; six of these deaths were unexpected. Sudden deaths occurred usually in patients with no or mild obstruction, and in patients with both the familial and sporadic forms of the disease. Atrial fibrillation was observed in 8% of the patients, and abnormalities of atrioventricular conduction, in 30%. Absence of voltage criteria for left ventricular hypertrophy occurred more frequently in asymptomatic patients, those with mild obstruction, and those with familial IHSS. Pulmonary hypertension occurred in one third of the patients, and was associated with considerable clinical disability. Obstruction to right ventricular outflow occurred in eight patients (15%), two of whom had no associated obstruction to left ventricular outflow.
Outcomes after cessation of mepolizumab therapy in severe eosinophilic asthma: A 12-month follow-up analysis
Authors: Pranabashis Haldar, Christopher E. Brightling, Amisha Singapuri, Beverley Hargadon, Sumit Gupta, William Monteiro, Peter Bradding, Ruth H. Green, Andrew J. Wardlaw, Hector Ortega, Ian D. Pavord
Journal: Journal of Allergy and Clinical Immunology (2014)
Farm workers’occupational allergy to <i>Tetranychus urticae</i>: clinical and immunologic aspects
Authors: C. Astarita, A. Franzese, G. Scala, S. Sproviero, G. Raucci
Journal: Allergy (1994)

A group of 46 farm workers (32 men), affected by a recurrent "occupational disease of undetermined origin", underwent an immunologic investigation with a Tetranychus urticae (TU) whole-body extract (TU-WBE) prepared in our laboratory. The patients suffered from seasonal attacks of rhinitis, during the summer and autumn periods, when working in open fields (30 subjects) or in greenhouse flower cultivation (16 subjects). In most patients, rhinitis was associated with bronchial asthma (16 subjects), urticaria (14 subjects), or both (three subjects). Allergic alveolitis or other common allergic diseases had been excluded, and a diagnosis of "occupational disease of undetermined origin" had been made before by other medical centers. Ten healthy farm workers and 10 atopic townsmen were chosen as control groups. An in vivo and in vitro diagnostic trial by skin prick testing (SPT) and serum specific IgE dosage with TU-WBE were done in all subjects. Thirty-six patients (78%) were found to be positive to both SPT and the IgE enzyme allergosorbent test (EAST), with a good correlation between IgE serum levels and cutaneous wheal size. Control groups did not show any reaction. The IgE-EAST homologous inhibition test was positive. The IgE-EAST cross-inhibition test excluded cross-reactivity between TU and Dermatophagoides pteronyssinus. The TU-exposure test was positive for the 36 patients with TU-WBE-specific IgE. Three patients who were negative for TU-WBE-specific IgE reacted to the TU-exposure test; in these patients, the scratch-chamber test (Finn chamber) with eggs and droppings from TU was positive.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 2806: BRAF and MEK inhibitor profiling across 240 tumor cell lines to correlate with sensitivity and resistant biomarkers
Authors: Karen Bernards, Yulia Ovechkina, Jushun Cheng, John Kushleika, Alison Angione, James Hnilo, Christine O'Day
Journal: Cancer Research (2012)

Abstract Activated kinases that induce cell proliferation have been attractive targets for targeted cancer therapy development. Cancer cells could become dependent on tumor-specific activated kinases and this tendency has been coined oncogene addiction. Here, we investigated three activated kinase inhibitors: BRAF inhibitor, PLX-4032 analog, and the MEK inhibitors, CI1040 and PD0325901. We established a high throughput cellular approach to profile 240 human tumor cell lines identifying genotype-correlated sensitivity or resistance. Proliferative, apoptotic and cell cycle arrest responses were measured using multiplexed high content screening with automated fluorescence microscopy and image analysis based technology. Growth index was measured using nuclear dye. Activated caspase 3 antibodies were used for the apoptosis induction detection. Phospho-histone H3 antibodies were used to measure the cell cycle block. We generated cell line profiles to reveal drug sensitivity and resistance patterns that may correlate with the clinical genotype responses. Cell lines with BRAFV600E mutations showed overlapping sensitivity to all three MEK and BRAF inhibitors. RAS mutations confer resistance to the BRAF inhibitor and confer sensitivity to both MEK inhibitors. In addition, we used Alphascreen technology to measure phosphoERK across the 240 non-treated tumor cell line panel. We found that the majority of PLX-4032 sensitive cell lines expressed high levels of phosphoERK. In addition, we investigated BRAF, MEK and EGFR inhibitor combinations to evaluate potential synergies. This preclinical approach can be used to predict mechanisms of susceptibility or resistance to these agents which in turn could be used for the optimization of targeted cancer therapeutics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2806. doi:1538-7445.AM2012-2806
Plagues, Products and Politics: Emergent Public Health Hazards and National Policymaking
Authors: Myron E. Wegman
Journal: JAMA (1996)

Disease outbreaks are part and parcel of any public health officer's life, but the challenge can be daunting when an episode continues. Christopher Foreman, a senior fellow at the Brookings Institution, looks beyond the "health detective" approach of Berton Roueché's delightful "Eleven Blue Men" to examine policy implications and government's capacity to respond to "unpleasant surprises." His many examples include infectious diseases, like AIDS and Legionnaires' disease, and product-related dangers, like the Dalkon Shield and criminal insertion of poisons in over-the-counter remedies. "Hazard" comprises far more than the acute contagion or dread virus that usually captures the public eye. Chapter titles are, successively, "Visible Victims," "Institutions," "Detection," "Interventions," "Education," "Regulation," "Research," and "Prospects." Although this sequence is unusual for the agent/host/environment— oriented health care worker and leads to unavoidable retracing of steps, it helps clarify the dilemmas policymakers often face when time to collect data is scarce and immediate action
Alterations of Coagulation and Fibrinolytic and Kallikrein-Kinin Systems in the Acute and Postacute Phases in Patients With Unstable Angina Pectoris
Authors: Hans Martin Hoffmeister, Michael Jur, Hans Peter Wendel, Wolfgang Heller, Ludger Seipel
Journal: Circulation (1995)

Unstable angina pectoris is frequently associated with intracoronary thrombus formation. In a prospective study, we investigated in 35 patients with unstable angina pectoris markers of coagulation and the kallikrein-kinin and fibrinolytic systems in the acute and postacute phases.We determined serially in the patients up to 10 days after admission factor XII and the beta-factor XIIa inhibition, kallikrein-like activity, prekallikrein, C1-esterase inhibitor, kallikrein inhibition, high molecular weight kininogen as indicators of the contact phase and bradykinin generation, thrombin-antithrombin III (TAT) complex as marker of the activated coagulation cascade, fibrinogen, plasminogen, plasminogen activator inhibitor-1 (PAI-1), tissue-type plasminogen activator (TPA), and D-dimers as indicators of the fibrinolytic system. Data were compared with those from control subjects (n = 25) and from patients with stable angina pectoris (n = 25). In patients with unstable angina pectoris, initially the contact phase and the kallikrein-kinin system were markedly elevated (factor XII, 96 +/- 5% versus 117 +/- 5%; kallikrein-like activity, 35.7 +/- 2.9 versus 27.4 +/- 1.3 U/L; high molecular weight kininogen, 52.7 +/- 5.2% versus 87.7 +/- 3.9%; P < .01 versus control subjects). Contact-phase activation persisted for the following 10 days, whereas the initially enhanced bradykinin generation normalized after 2 days. Furthermore, we had evidence of a hypercoagulative state (TAT, 10.9 +/- 3.1 versus 4.5 +/- 0.7 micrograms/L, P < .05; D-dimer, 474 +/- 81 versus 272 +/- 71 ng/mL) persisting longer than the clinically symptomatic period in association with disturbed fibrinolysis (TPA, 15.9 +/- 1.9 versus 5.1 +/- 0.4 ng/mL; P < .01; PAI-1, 9.9 +/- 2.6 versus 4.6 +/- 1.6 AU/mL; P = NS) in the presence of elevated fibrinogen levels.Our data indicate that in patients with unstable angina pectoris, intracoronary thrombus formation is associated with a hypercoagulative state, including activation of the contact phase and of the kallikrein system and increased bradykinin generation. The persistence of this hypercoagulative state, together with a disturbed fibrinolysis, might indicate an increased risk for further coronary events.
Avascular necrosis of bone after renal transplantation: role of parathyroid hormone and vitamin D.
Authors: C M Page, B Hulme, S E Papapoulos, J L O'Riordan
Journal: BMJ (1978)

Renal damage during treatment with antirheumatic drugs Beta-N-acetyl glucosaminidase (NAG) is a lyosomal enzyme found in high concentrations in the epithelial cells of renal tubules.It is excreted in the urine of normal people, but much larger quantities are excreted by patients with renal disease,' those taking nephrotoxic drugs,' and those starting treatment with aspirin.3Measuring NAG excretion may be a convenient way of assessing early damage to renal tubules: the output rises sharply within a few days of the onset of the insult.The present study used NAG excretion to explore the possibility that non-steroidal anti-inflammatory drugs other than aspirin might also damage renal tubules.Enzyme excretion was also monitored in patients with rheumatoid arthritis receiving long-term treatment with D-penicillamine or levamisole. Methods and resultsNormal subjects, or patients with osteoarthritis but no renal disease or hypertension, were included in the first study.Aliquots of urine were obtained before giving the drugs, and again at intervals during the course of treatment.The drugs studied were aspirin, diflunisal, indomethacin, ibuprofen, naproxen, and azopropazone in their usual therapeutic doses.Aspirin and diflunisal were tested in both highand low-dose regimens.In a second study, patients with rheumatoid arthritis starting treatment with D-penicillamine or levamisole were observed for intervals up to six months.Measurements of disease activity were observed over the same period.Specimens were stored at 4°C before analysis by the fluorimetric method of Tucker et al.4The results are shown in the table.No significant increase in NAG excretion was seen with the lower dose of aspirin or diflunisal, but concen- trations were appreciably increased with higher dosage, this effect being sustained at six weeks.In tests on patients taking the other non-steroidal anti-inflammatory drugs, no increase in urinary excretion of NAG was observed.When patients with rheumatoid arthritis were treated with either D-penicillamine or levamisole a significant fall in NAG excretion was observed by the 12th week, and maintained at 26 weeks.This decrease seemed to correlate with improvement in clinical estimates of disease activity.No increase in NAG excretion was observed in eight other patients receiving D-penicillamine who developed proteinuria.
KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes
Authors: Audrey Putoux, Sophie Thomas, Karlien L M Coene, Erica E Davis, Yasemin Alanay, Gönül Ogur, Elif Uz, Daniela Buzas, Céline Gomes, Sophie Patrier, Christopher L Bennett, Nadia Elkhartoufi, Marie-Hélène Saint Frison, Luc Rigonnot, Nicole Joyé, Solenn Pruvost, Gulen Eda Utine, Koray Boduroglu, Patrick Nitschke, Laura Fertitta, Christel Thauvin-Robinet, Arnold Munnich, Valérie Cormier-Daire, Raoul Hennekam, Estelle Colin, Nurten Ayse Akarsu, Christine Bole-Feysot, Nicolas Cagnard, Alain Schmitt, Nicolas Goudin, Stanislas Lyonnet, Férechté Encha-Razavi, Jean-Pierre Siffroi, Mark Winey, Nicholas Katsanis, Marie Gonzales, Michel Vekemans, Philip L Beales, Tania Attié-Bitach
Journal: Nature Genetics (2011)
France is set to radically overhaul its drug regulatory system
Authors: S. Arie
Journal: BMJ (2011)

<h3>Abstract</h3> <h3>Summary</h3> Currently, gene information available for <i>Oryza sativa</i> species is located in various online heterogeneous data sources. Moreover, methods of access are also diverse, mostly web-based and sometimes query APIs, which might not always be straightforward for domain experts. The challenge is to collect information quickly from these applications and combine it logically, to facilitate scientific research. We developed a Python package named PyRice, a unified programming API to access all supported databases at the same time with consistent output. PyRice design is modular and implements a smart query system which fits the computing resources to optimize the query speed. As a result, PyRice is easy to use and produces intuitive results. <h3>Availability and implementation</h3> https://github.com/SouthGreenPlatform/PyRice <h3>Documentation</h3> https://pyrice.readthedocs.io <h3>Contact</h3> pierre.larmande@ird.fr <h3>Licence information</h3> MIT <h3>Supplementary information</h3> Supplementary data are available at <i>Bioinformatics</i> online.
Unreported cholesterol drug data released by company
Authors: Jeanne Lenzer
Journal: BMJ (2008)

The makers of a popular cholesterol lowering drug have posted results of a study showing it was ineffective—but only after a Congressional inquiry was set up to look into why they had not published their results two years after the study was completed.

Merck and Schering-Plough Pharmaceuticals, manufacturers of ezetimibe (Zetia), posted results on their websites earlier this month showing that 356 people treated with ezetimibe (10 mg) plus simvastatin (80 mg) fared no better than 360 who had received simvastatin alone (www.sch-plough.com/schering_plough/news/release.jsp?releaseID=1095943).

The study, known as the ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin vs Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia) trial, measured the thickness of carotid artery intima media as its primary end point. Although ezetimibe did cause an additional lowering of cholesterol, plaque progression was worse in the ezetimibe arm.

Ezetimibe, sold singly as Zetia or in combination with simvastatin as Vytorin, has become a blockbuster drug since it was approved in 2002, with an estimated $5bn (£2.6bn; €3.4bn) in sales in 2006. The Congressional investigation into the delayed publication of the ENHANCE trial results, which is ongoing, is now being followed by another Congressional investigation that will scrutinise claims …
Transfusion-related Acute Lung Injury in the Critically Ill
Authors: Ognjen Gajic, Rimki Rana, Jeffrey L. Winters, Murat Yilmaz, Jose L. Mendez, Otis B. Rickman, Megan M. O'Byrne, Laura K. Evenson, Michael Malinchoc, Steven R. DeGoey, Bekele Afessa, Rolf D. Hubmayr, S. Breanndan Moore
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Acute lung injury (ALI) that develops 6 hours after transfusion (TRALI) is the leading cause of transfusion-related mortality. Several transfusion characteristics have been postulated as risk factors for TRALI, but the evidence is limited to retrospective studies.
Comparison of the reliability and validity of outcome instruments for cutaneous dermatomyositis
Authors: R.Q. Klein, C.A. Bangert, M. Costner, M.K. Connolly, A. Tanikawa, J. Okawa, M. Rose, S.S. Fakharzadeh, D. Fiorentino, L.A. Lee, R.D. Sontheimer, L. Taylor, A.B. Troxel, V.P. Werth
Journal: British Journal of Dermatology (2008)

Reliable and validated measures of skin disease severity are needed for cutaneous dermatomyositis (DM). Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Dermatomyositis Skin Severity Index (DSSI) and Cutaneous Assessment Tool (CAT) skin indices have been developed as outcome instruments.We sought to demonstrate reliability and validity of the CDASI, and to compare the CDASI with other potential tools for use in measuring disease severity in cutaneous dermatomyositis.CDASI has four activity and two damage measures, with scores from 0 to 148. DSSI assesses activity based on body surface area and severity on a scale of 0-72. CAT uses 21 activity and damage items, for a range of 0-175 for activity and 0-33 for damage. Ten dermatologists used the instruments to score the same 12-16 patients in one session. Global validation measures were administered to physicians and patients.Global validation measures correlated with the three outcome instruments (P < 0.0001). CAT displayed lower inter- and intrarater reliability relative to the CDASI. All scales correlate better with physician than patient global skin measures.It appears that the CDASI may be a useful outcome measure for studies of cutaneous DM. Further testing to compare responsiveness of all three measures is necessary.
Management and Outcome of Permanent Pacemaker and Implantable Cardioverter-Defibrillator Infections
Authors: Muhammad R. Sohail, Daniel Z. Uslan, Akbar H. Khan, Paul A. Friedman, David L. Hayes, Walter R. Wilson, James M. Steckelberg, Sarah Stoner, Larry M. Baddour
Journal: Journal of the American College of Cardiology (2007)
Severe disseminated mycobacterial infection in a boy with a novel mutation leading to IFN-γR2 deficiency
Authors: Sara Sebnem Kilic, Annelies van Wengen, Roelof A. de Paus, Solmaz Celebi, Bouchra Meziane, Demet Hafizoglu, Jaap T. van Dissel, Esther van de Vosse
Journal: Journal of Infection (2012)