tbuckley/cabot-search huggingface dataset:
Corticosteroid effect on factor VIII
Authors: Şinasi Özsoylu
Journal: American Journal of Hematology (1994)

CLAUDINE ROUANETvon Willebrand factor antigenic dosage: 10%).DDAVP therapy was ineffective.Post viral hepatitis mild liver cirrhosis developed.The first recurrent bleeding complications occurred in 1984; these remained unexplained.From September 1991, severe bleeding episodes (hematemesis and melena) developed, requiring repeated red blood cell transfusions and von Willebrand factor concentrate injections.At this time, several esogastroscopies and colonoscopies showed the presence of multiple digestive angiodysplastic lesions.Some of them were treated by laser, but bleeding episodes recurred, with life threatening intensity (9 episodes over a 9-month period, requiring the transfusion of 18 packed red cells units, 10 of them during one episode).On the endoscopic control performed in May 1992, diffuse angiodysplastic lesions were noted on the colonic wall and the terminal ileum.A hormonal therapy was then started (norethisterone 1 mg; ethinylestradiol 0.05 mgiday).Bleeding episodes disappeared immediately, and in an 18-month period only one moderate bleeding episode was noted.The last endoscopic examination revealed only small duodenal lesions: colonic examination was normal.No humoral hepatic disturbance has been noted to date, a-fetoprotein level remaining within a strictly normal range.Hepatic echography remains normal.The sole side effects noted were significant gynecomastia and impotence.von Willebrand factor level was not notified by hormonal therapy.This case inspired us with some comments:
FACTORS IN SELECTION OF PSYCHIATRIC TREATMENT FOR INSTITUTIONALIZED AGED PERSONS
Authors: ROBERT L. KAHN, ALVIN I. GOLDFARB, MAX POLLACK, ARTHUR PECK
Journal: American Journal of Psychiatry (1961)

The selection of aged patients for psychotherapy appears to follow the same sociopsychological trends as in younger persons. This manner of selection may tend to weed out the most helpless, anxious and most psychotherapeutically malleable candidates for psychiatric care.
Editorial: Update on Stem Cell Research
Authors: R. Paul Robertson, Linda C. Giudice
Journal: Endocrine Reviews (2009)

It is hard to imagine a more engaging contemporary issue than stem cell research.It fires the imagination of scientists bent on preventing and curing disease.At the same time, caution about being overly enthusiastic is in order.How long will it take to translate this opportunity into clinical measures that will increase human wellness?Stem cell research stimulates rich debate about the ethics and morals of the procurement and use of human tissues suitable for research.Many of these arguments seem not likely to be resolved, yet they all deserve close attention by proponents and opponents alike.Stem cell research has been a hot topic of governmental regulation for the past 8 years.Recently, scientists have been encouraged about governmental relaxation of regulation in the United States that has opened the doors to more freedom for intellectual inquiry.In this issue of Endocrine Reviews, designated as a special focus issue that we call the Recent Progress in Hormone Research issue, several areas of stem cell research are highlighted.Unlike the usual issues of Endocrine Reviews, we have invited authors especially to emphasize work in their own spheres.At the same time, the manuscripts have been peerreviewed to ensure appropriate citations of work by others, consistent with the usual rigor characteristic of manuscripts published in Endocrine Reviews.Contained within you will find a review and critique on ethical issues in stem cell research by Bernard Lo.He points out that "…human stem cell research also raises sharp ethical and political controversies.The derivation of pluripotent stem cell lines from oocytes and embryos is fraught with disputes about the onset of human personhood."He emphasizes the need to discuss ethical and policy issues freely to ensure that stem cell research is carried out in an ethically
Randomized comparison between chemotherapy plus best supportive care with best supportive care in advanced gastric cancer
Authors: B. Glimelius, K. Ekström, K. Hoffman, W. Graf, P.-O. Sjödén, U. Haglund, C. Svensson, L.-K. Enander, T. Linné, H. Sellsröm, R. Heuman
Journal: Annals of Oncology (1997)
Viral Gene Transfer of the Antiapoptotic Factor Bcl-2 Protects Against Chronic Postischemic Heart Failure
Authors: Subhasis Chatterjee, Allan S. Stewart, Lawrence T. Bish, Vasant Jayasankar, Elizabeth M. Kim, Timothy Pirolli, Jeffrey Burdick, Y. Joseph Woo, Timothy J. Gardner, H. Lee Sweeney
Journal: Circulation (2002)

Apoptosis secondary to acute ischemia and chronic remodeling is implicated as a mediator of heart failure. This study was designed to assess the effect of in vivo viral gene transfer of the anti-apoptotic factor Bcl-2 to block apoptosis and preserve ventricular geometry and function.In a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adeno-Bcl-2 was compared with a control group receiving empty vector adeno-null. Function was assessed by echocardiography, and sonomicrometry of the border zone was compared with the normal left ventricle (LV). Animals were killed at 6 weeks, and an additional group was killed after 3 days to see whether virus administration conferred an immediate effect. Animals that were administered Bcl-2 maintained higher ejection fractions at 2, 4, and 6 weeks compared with controls. Sonomicrocrystals demonstrated greater protection of border zone fractional shortening at 6 weeks. The Bcl-2 group had superior preservation of LV geometry with less ventricular dilatation and wall thinning. There was also reduced apoptosis compared with the controls. Finally, in the animals killed at 3 days, no functional difference was observed between the Bcl-2 and control groups.Gene transfer of Bcl-2 preserves LV function after ischemia despite the absence of an observed acute protective effect. The benefit at 6 weeks is postulated to result from a Bcl-2-mediated reduction in apoptosis and ventricular remodeling. Adeno-Bcl-2 administration offers a potential strategy to protect the heart from late postischemic heart failure.
Accounting for cellular heterogeneity is critical in epigenome-wide association studies
Authors: Andrew E Jaffe, Rafael A Irizarry
Journal: Genome biology (2014)

Abstract Background Epigenome-wide association studies of human disease and other quantitative traits are becoming increasingly common. A series of papers reporting age-related changes in DNA methylation profiles in peripheral blood have already been published. However, blood is a heterogeneous collection of different cell types, each with a very different DNA methylation profile. Results Using a statistical method that permits estimating the relative proportion of cell types from DNA methylation profiles, we examine data from five previously published studies, and find strong evidence of cell composition change across age in blood. We also demonstrate that, in these studies, cellular composition explains much of the observed variability in DNA methylation. Furthermore, we find high levels of confounding between age-related variability and cellular composition at the CpG level. Conclusions Our findings underscore the importance of considering cell composition variability in epigenetic studies based on whole blood and other heterogeneous tissue sources. We also provide software for estimating and exploring this composition confounding for the Illumina 450k microarray.
Nuclear and mitochondrial signalling Akts in cardiomyocytes
Authors: S. Miyamoto, M. Rubio, M. A. Sussman
Journal: Cardiovascular Research (2008)

Biological actions resulting from phosphoinositide synthesis trigger multiple downstream signalling cascades by recruiting proteins with pleckstrin homology domains, including phosphoinositide-dependent kinase-1 and protein kinase B (also known as Akt). Retrospectively, more attention has been focused on the plasma membrane-associated interactions of these molecules and resulting cytoplasmic target activation. The complex biological activities exerted by Akt activation suggest, however, that more subtle and complex subcellular control mechanisms are involved. This review examines the regulation of Akt activity from the perspective of subcellular compartmentalization and focuses specifically upon the actions of Akt activation downstream from phosphoinositide synthesis that influence cell biology by altering nuclear signalling leading to Pim-1 kinase induction as well as hexokinase phosphorylation that, together with Akt, serves to preserve mitochondrial integrity.
Why are patients prescribed proton pump inhibitors? Retrospective analysis of link between morbidity and prescribing in the General Practice Research Database
Authors: J. N R Bashford, J. Norwood, S. R Chapman
Journal: BMJ (1998)

To establish the relation between new prescriptions for proton pump inhibitors and recorded upper gastrointestinal morbidity within a large computerised general practitioner database.Retrospective survey of morbidity and prescribing data linked to new prescriptions for proton pump inhibitors and comparison with licensed indications between 1991 and 1995.General Practice Research Database and prescribing analysis and cost (PACT) data for the former West Midlands region.Information for 612 700 patients in the General Practice Research Database. Anonymous PACT data for all general practitioners in West Midlands region.Diagnostic codes linked to the first prescriptions issued for proton pump inhibitors; relation between new prescriptions and licensed indications; yearly change in ratio of new to repeat prescriptions and prescribing volumes measured as defined daily doses.Oesophagitis was the commonest recorded indication in 1991, accounting for 31% of new prescriptions, but was third in 1995 (14%). During the study new prescriptions increased substantially, especially for duodenal disease (780%) and non-ulcer dyspepsia (690%). In 1995 non-specific morbidity accounted for 46% of new prescriptions. The total volume of prescribing rose 10-fold between 1991 and 1995, when repeat prescribing accounted for 77% of the total.Changes in recorded morbidity associated with new prescriptions of proton pump inhibitors did not necessarily reflect changes in licensed indications. Although general practitioners seemed to respond to changes in licensing, particularly for duodenal and gastric disease, prescribing for unlicensed indications non-ulcer dyspepsia and non-specific abdominal pain increased.
Analysis of piRNA-Mediated Silencing of Active TEs in Drosophila melanogaster Suggests Limits on the Evolution of Host Genome Defense
Authors: Erin S. Kelleher, Daniel A. Barbash
Journal: Molecular Biology and Evolution (2013)

The Piwi-interacting RNA (piRNA) pathway defends animal genomes against the harmful consequences of transposable element (TE) infection by imposing small-RNA-mediated silencing. Because silencing is targeted by TE-derived piRNAs, piRNA production is posited to be central to the evolution of genome defense. We harnessed genomic data sets from Drosophila melanogaster, including genome-wide measures of piRNA, mRNA, and genomic abundance, along with estimates of age structure and risk of ectopic recombination, to address fundamental questions about the functional and evolutionary relationships between TE families and their regulatory piRNAs. We demonstrate that mRNA transcript abundance, robustness of "ping-pong" amplification, and representation in piRNA clusters together explain the majority of variation in piRNA abundance between TE families, providing the first robust statistical support for the prevailing model of piRNA biogenesis. Intriguingly, we also discover that the most transpositionally active TE families, with the greatest capacity to induce harmful mutations or disrupt gametogenesis, are not necessarily the most abundant among piRNAs. Rather, the level of piRNA targeting is largely independent of recent transposition rate for active TE families, but is rapidly lost for inactive TEs. These observations are consistent with population genetic theory that suggests a limited selective advantage for host repression of transposition. Additionally, we find no evidence that piRNA targeting responds to selection against a second major cost of TE infection: ectopic recombination between TE insertions. Our observations confirm the pivotal role of piRNA-mediated silencing in defending the genome against selfish transposition, yet also suggest limits to the optimization of host genome defense.
Spread of Excitation in the Atrioventricular Node of Isolated Rabbit Hearts Studied by Multiple Microelectrode Recording
Authors: Frans J. L. van Capelle, Michiel J. Janse, P. Jacob Varghese, Gerrit E. Freud, Carla Mater, Dirk Durrer
Journal: Circulation Research (1972)

The pattern of atrioventricular (AV) nodal activation in isolated rabbit hearts was studied by recording transmembrane action potentials in about 200 AV nodal fibers per heart. A brush electrode consisting of ten microelectrodes was used. Both antegrade and retrograde spread of excitation were mapped: retrograde conduction was not an exact mirror image of antegrade conduction. The major input during antegrade conduction was from the crista terminalis, but the major output during retrograde conduction was through the interatrial septum. Some parts of the AV node were excited without directly participating in either antegrade or retrograde transmission of the impulse. Simultaneous pacing of the atrium and the His bundle generated antegrade and retrograde wave fronts which collided at different levels of the AV node. In this way, cells which transmitted the impulse in both directions were distinguished from those which did not (dead-end pathways). Two types of dead-end pathways were found: type A probably consisted of superficial atrial fibers terminating in the base of the tricuspid valve and type B branched off from cells in the middle node. The shape of the action potential of AV nodal cells strongly depended on the direction of propagation. In some parts of the AV node, the amplitude of the action potential was larger during antegrade activation than it was during retrograde activation; in other parts, the amplitude was smaller during antegrade conduction. The largest amplitudes occurred when wave fronts collided.
Results of the Northern Manhattan Diabetes Community Outreach Project: A Randomized Trial Studying a Community Health Worker Intervention to Improve Diabetes Care in Hispanic Adults
Authors: Walter Palmas, Sally E. Findley, Miriam Mejia, Milagros Batista, Jeanne Teresi, Jian Kong, Stephanie Silver, Elaine M. Fleck, Jose A. Luchsinger, Olveen Carrasquillo
Journal: Diabetes Care (2014)

OBJECTIVE The Northern Manhattan Diabetes Community Outreach Project evaluated whether a community health worker (CHW) intervention improved clinically relevant markers of diabetes care in adult Hispanics. RESEARCH DESIGN AND METHODS Participants were adult Hispanics, ages 35-70 years, with recent hemoglobin A1c (A1C) ≥8% (≥64 mmol/mol), from a university-affiliated network of primary care practices in northern Manhattan (New York City, NY). They were randomized to a 12-month CHW intervention (n = 181), or enhanced usual care (educational materials mailed at 4-month intervals, preceded by phone calls, n = 179). The primary outcome was A1C at 12 months; the secondary outcomes were systolic blood pressure (SBP), diastolic blood pressure, and LDL-cholesterol levels. RESULTS There was a nonsignificant trend toward improvement in A1C levels in the intervention group (from unadjusted mean A1C of 8.77 to 8.40%), as compared with usual care (from 8.58 to 8.53%) (P = 0.131). There was also a nonsignificant trend toward an increase in SBP and LDL cholesterol in the intervention arm. Intervention fidelity, measured as the number of contacts in the intervention arm (visits, phone contacts, group support, and nutritional education), showed a borderline association with greater A1C reduction (P = 0.054). When assessed separately, phone contacts were associated with greater A1C reduction (P = 0.04). CONCLUSIONS The trend toward A1C reduction with the CHW intervention failed to achieve statistical significance. Greater intervention fidelity may achieve better glycemic control, and more accessible treatment models, such as phone-based interventions, may be more efficacious in socioeconomically disadvantaged populations.
The genetic contribution to severe post-traumatic osteoarthritis
Authors: Ana M Valdes, Sally A Doherty, Kenneth R Muir, Margaret Wheeler, Rose A Maciewicz, Weiya Zhang, Michael Doherty
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> to compare the combined role of genetic variants loci associated with risk of knee or hip osteoarthritis (OA) in post-traumatic (PT) and non-traumatic (NT) cases of clinically severe OA leading to total joint replacement. <h3>Methods</h3> A total of 1590 controls, 2168 total knee replacement (TKR) cases (33.2% PT) and 1567 total hip replacement (THR) cases (8.7% PT) from 2 UK cohorts were genotyped for 12 variants previously reported to be reproducibly associated with risk of knee or hip OA. A genetic risk score was generated and the association with PT and NT TKR and THR was assessed adjusting for covariates. <h3>Results</h3> For THR, each additional genetic risk variant conferred lower risk among PT cases (OR=1.07, 95% CI 0.96 to 1.19; p=0.24) than NT cases (OR 1.11, 95% CI 1.06 to 1.17; p=1.55×10<sup>−5</sup>). In contrast, for TKR, each risk variant conferred slightly higher risk among PT cases (OR 1.12, 95% CI 1.07 to 1.19; p=1.82×10<sup>−5</sup>) than among NT cases (OR 1.08, 95% CI 1.03 to 1.1; p=0.00063). <h3>Conclusions</h3> Based on the variants reported to date PT TKR cases have at least as high a genetic contribution as NT cases.
Spatial Distribution of Fibrosis Governs Fibrillation Wave Dynamics in the Posterior Left Atrium During Heart Failure
Authors: Kazuhiko Tanaka, Sharon Zlochiver, Karen. L. Vikstrom, Masatoshi Yamazaki, Javier Moreno, Matthew Klos, Alexey. V. Zaitsev, Ravi Vaidyanathan, David S. Auerbach, Steve Landas, Gérard Guiraudon, José Jalife, Omer Berenfeld, Jérôme Kalifa
Journal: Circulation Research (2007)

Heart failure (HF) commonly results in atrial fibrillation (AF) and fibrosis, but how the distribution of fibrosis impacts AF dynamics has not been studied. HF was induced in sheep by ventricular tachypacing (220 bpm, 6 to 7 weeks). Optical mapping (Di-4-ANEPPS, 300 frames/sec) of the posterior left atrial (PLA) endocardium was performed during sustained AF (burst pacing) in Langendorff-perfused HF (n=7, 4 μmol/L acetylcholine; n=3, no acetylcholine) and control (n=6) hearts. PLA breakthroughs were the most frequent activation pattern in both groups (72.0±4.6 and 90.2±2.7%, HF and control, respectively). However, unlike control, HF breakthroughs preferentially occurred at the PLAs periphery near the pulmonary vein ostia, and their beat-to-beat variability was greater than control (1.93±0.14 versus 1.47±0.07 changes/[beats/sec], respectively, P &lt;0.05). On histological analysis (picrosirius red), the area of diffuse fibrosis was larger in HF (23.4±0.4%) than control (14.1±0.6%; P &lt;0.001, n=4). Also the number and size of fibrous patches were significantly larger and their location was more peripheral in HF than control. Computer simulations using 2-dimensional human atrial models with structural and ionic remodeling as in HF demonstrated that changes in AF activation frequency and dynamics were controlled by the interaction of electrical waves with clusters of fibrotic patches of various sizes and individual pulmonary vein ostia. During AF in failing hearts, heterogeneous spatial distribution of fibrosis at the PLA governs AF dynamics and fractionation.
The pleasurability of scratching an itch: a psychophysical and topographical assessment
Authors: G.A. bin Saif, A.D.P. Papoiu, L. Banari, F. McGlone, S.G. Kwatra, Y‐H. Chan, G. Yosipovitch
Journal: British Journal of Dermatology (2012)

Background Scratching an itch is perceived as being pleasurable. However, an analysis of topographical variations in itch intensity, the effectiveness of scratching to provide itch relief and the associated pleasurability has not been performed at different body sites. Objectives To examine the role of scratching pleasurability in providing itch relief by investigating whether itch intensity is perceived differently at three different sites and to assess a potential correlation between the pleasurability and itch attenuation induced by scratching. Methods Itch was induced on the forearm, ankle and back using cowhage spicules in 18 healthy subjects. These sites were subsequently scratched by an investigator with a cytology brush immediately following itch induction. The intensity of itch with and without scratching at these sites and the pleasurability of scratching were recorded by taking visual analogue scale ratings at 30‐s intervals. Results Mean itch intensity and scratching pleasurability ratings at the ankle and back were significantly higher than on the forearm. For the forearm and ankle, the greater the itch while scratching, the higher was the pleasurability. A higher baseline itch was linked to a higher itch reduction secondary to scratching in all tested areas. Pleasurability paralleled the curve of itch reduction for the back and forearm; however, scratching pleasurability at the ankle remained elevated and only slightly decreased while itch was diminishing. Conclusions There are topographical differences in itch intensity, the effectiveness of scratching in relieving itch and the associated pleasurability. Experimental itch induced by cowhage was more intensely perceived at the ankle, while scratching attenuated itch most effectively on the back.
Cilengitide induces autophagy-mediated cell death in glioma cells
Authors: S. L. Lomonaco, S. Finniss, C. Xiang, H. K. Lee, W. Jiang, N. Lemke, S. A. Rempel, T. Mikkelsen, C. Brodie
Journal: Neuro-Oncology (2011)

We studied the effect of the integrin inhibitor cilengitide in glioma cells. Cilengitide induced cell detachment and decreased cell viability, and induction of autophagy followed by cell apoptosis. In addition, cilengitide decreased the cell renewal of glioma stem-like cells (GSCs). Inhibition of autophagy decreased the cytotoxic effect of cilengitide. Pretreatment of glioma cells and GSCs with cilengitide prior to γ-irradiation resulted in a larger increase in autophagy and a more significant decrease in cell survival. We found that cilengitide induced autophagy collectively in glioma cells, xenografts, and GSCs, which contributed to its cytotoxic effects and sensitized these cells to γ-radiation.
The level of TACI gene expression in myeloma cells is associated with a signature of microenvironment dependence versus a plasmablastic signature
Authors: Jérôme Moreaux, Friedrich W. Cremer, Thierry Reme, Marc Raab, Karene Mahtouk, Philine Kaukel, Veronique Pantesco, John De Vos, Eric Jourdan, Anna Jauch, Eric Legouffe, Marion Moos, Genevieve Fiol, Hartmut Goldschmidt, Jean François Rossi, Dirk Hose, Bernard Klein
Journal: Blood (2005)