tbuckley/cabot-search huggingface dataset:
Abstract 18901: Calgranulins S100A8, S100A9 and S100A12 are Novel Genes Modified by n-3 PUFA Supplementation and Evoked Endotoxemia in Humans
Authors: Jane F Ferguson, Chenyi Xue, Mingyao Li, Rachana Shah, Muredach P Reilly
Journal: Circulation (2014)

Introduction: We have previously identified genes involved in the adipose transcriptomic response to evoked endotoxemia in humans. Long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may modulate chronic low-grade systemic and adipose inflammation, conferring protection in cardiometabolic disease. However, given subtle effects of n-3 PUFA in vivo, intervention studies often lack power to detect effects on resting biomarkers. We applied unbiased transcriptomics (RNASeq) to human adipose tissue in healthy individuals following supplementation with n-3 PUFA in combination with evoked endotoxemia (LPS) as a unique genomic discovery model in n-3 PUFA modulation of inflammation. Methods: Using RNASeq we analyzed transcriptomes of adipose tissue biopsies from healthy individuals at three timepoints: before and after n-3 PUFA supplementation (n=7; 3600mg/day EPA/DHA) for 6-8 weeks compared with placebo (n=6), as well as during a subsequent evoked inflammatory challenge (LPS 0.6 ng/kg I.V.). We further explored candidate gene expression in response to n-3 PUFA and LPS using human monocytes and adipocytes in vitro. Results: The transcriptomic response to LPS was altered by n-3 PUFA supplementation. We found increased up-regulation of calgranulin genes in n-3 PUFA (S100A8 16-fold, p=0.002; S100A9 8-fold, p=0.002; S100A12 32-fold, p=0.01) compared with placebo (S100A8 2-fold, p=0.003; S100A9 1.4-fold, p=0.4; S100A12 5-fold, p=0.04). These inflammasome-activating genes may be involved in atherogenesis and inflammatory diseases, and may play a role in the recruitment of inflammatory cells to adipose tissue. We found differing calgranulin gene expression in vitro in adipocytes and monocytes after n-3 PUFA (up in monocytes, down in adipocytes post DHA p&lt;0.001) and LPS treatment (n-3 PUFA dependent decrease in monocytes, increase in adipocytes) consistent with n-3 PUFA-dependent cell-type-specific responses to inflammatory activation. Conclusions: Unbiased transcriptomics and evoked inflammation permits enhanced genomic discovery in the context of nutritional intervention. A novel mechanism of n-3 PUFA protective effects in vivo may be through modulation of expression of calgranulin genes in response to innate immune activation.
Are All β-Blockers for Heart Failure the Same?
Authors: John G. F. Cleland
Journal: Circulation (2000)

Are All ␤-Blockers for Heart Failure the Same?To the Editor:Kukin et al 1 suggest that little difference may exist between the benefits of metoprolol, a ␤ 1 -selective blocker, and carvedilol, an ␣and nonselective ␤-blocker with antioxidant properties, on pathophysiological variables in patients with heart failure.The study was unblinded and randomized only 67 patients, with more older patients who had advanced symptoms and coronary disease allocated to receive carvedilol.Considerable evidence shows that patients with left ventricular systolic dysfunction due to coronary disease have a more heterogenous improvement in ejection fraction than do patients with dilated cardiomyopathy. 2Moreover, a study that randomized many more (nϭ120) patients showed that when compared with metoprolol, carvedilol had greater effects on ejection fraction and filling pressures. 3 No widely accepted surrogates exist for morbidity or mortality in heart failure; therefore, physicians should not assume that a similar hemodynamic benefit leads to equal clinical benefit.The Carvedilol or Metoprolol European Trial (COMET) is currently comparing metoprolol and carvedilol in Ͼ3000 patients with chronic heart failure to determine whether the effects of these drugs on mortality and/or morbidity differ.This is the first adequately powered study to compare outcomes between ␤-blockers in any clinical setting. 4 The authors are appropriately and commendably cautious in the interpretation of their data; some commentators are less so. 5 Currently, only carvedilol is approved for use in heart failure.Even if metoprolol is as effective as carvedilol, where is the clinician to get the doses required for initiating therapy?The manual preparation of small quantities of reconstituted low-dose metoprolol is likely to be expensive; the problems of quality control and erratic dosing also exist.It is also inappropriate to assume that substituting maintenance carvedilol with metoprolol is safe.Illicit, large-scale production of generic metoprolol in small doses may occur, but will this be endorsed without proper appraisal by regulatory authorities?Heart failure is a dangerous condition and its treatment with ␤-blockers requires caution.When treating a malignant disease, it seems wise to use treatments that have passed the "acid-test" of official regulatory approval and that are manufactured to an adequate standard.In both the short-and long-term, it may be cheaper and more cost-effective to use carvedilol, which is available in the right doses and with the appropriate pharmaceutical quality control, rather than preparations of ␤-blockers of uncertain strength and efficacy.If heart failure was cancerous rather than merely malignant, what do you think doctors and patients would choose?
Altered protein homeostasis in pulmonary fibrosis indicates a role for proteasomal activator 200
Authors: Nora Semren, Vanessa Welk, Martina Korfei, Isis Fernandez, Andreas Günther, Oliver Eickelberg, Silke Meiners
Journal: European Respiratory Journal (2014)

The proteasome, a multicatalytic protease complex, is essential for maintaining cellular function and protein homeostasis. Proteasome activator 200 (PA200) associates with the proteasome thereby activating its protease activities. Fibrotic lung disease involves alterations of protein homeostasis but regulation of proteasomal function is unknown. Here, we investigated the role of PA200 for proteasome function in pulmonary fibrosis.  We first analyzed expression of PA200 and its association to proteasome core complexes in TGF-β1 treated lung fibroblasts (CCL206) as well as in experimental lung fibrosis and human IPF tissue by various approaches. mRNA and protein levels of the activator remained unchanged in TGF-β1 treated CCL206 despite an increase in overall proteasome activity. However, we observed an enhanced association of PA200 with the 26S proteasome as determined by native gel analysis and following separation of the proteasome complexes by SDS-PAGE. This correlated with an increased activation of the proteasome complexes. Moreover, PA200 protein levels were increased in fibrotic lungs of bleomycin-treated mice and human IPF lungs. Immunohistochemistry staining of IPF lungs identified myofibroblasts and ciliated bronchial cells as the main cell types overexpressing PA200 in fibroblast foci of IPF lungs.  Concluding, these results suggest a participation of PA200 in induction of proteasome activity in the course of myofibroblast differentiation in pulmonary fibrosis and provide a new aspect on regulation of protein homeostasis in lung fibrosis.
Value of Molecular Monitoring for Minimal Residual Disease Preceding Autologous SCT Following Diagnosis of B Cell Acute Lymphoblastic Leukemia in Patients Treated with the MRC UKALL12 Protocol.
Authors: Letizia Foroni, Wayne Mitchell, Lena J. Rai, Anouska Casanova, Bella Patel, Sue Richards, Adele Fielding, Anthony H. Goldstone
Journal: Blood (2005)
Abstract 19963: Different Patterns of Mortality Associated with Treatment Options in Late Follow-up of Stable Multivessel Coronary Artery Disease Patients.
Authors: Ricardo D Vieira, Paulo Rezende, Cibele Garzillo, Eduardo Lima, Alexandre C Pereira, Paulo Soares, Desiderio Favarato, Luis A Dallan, Neuza Lopes, Whady Hueb, Jose A Ramires
Journal: Circulation (2010)

Introduction: The therapeutic options to patients with stable multivessel coronary artery disease (CAD) and normal ventricle function are coronary artery bypass graft (CABG), angioplasty (PCI) or m...
BACTERIOLOGY OF ENDOCARDITIS WITH REPORT OF TWO UNUSUAL CASES
Authors: MOSES SAMUEL SHILING, M.D., Med.Sc.D.
Journal: Annals of Internal Medicine (1939)

ExcerptSince 1900, every review1, 2, 3, 4, 5 of the exciting causes of bacterial endocarditis has always included the Streptococcus, hemolyticus and mitior, Diplococcus pneumoniae, the Hemophilus influenzae, the Staphylococcus aureus and the Neisseria gonorrheae. These organisms no longer arouse comment when found. However, it is still unusual to see cases due to other bacteria and this report concerns itself mainly with the rarer forms of bacterial endocarditis.A review of the literature reveals reports of many isolated cases of endocarditis due to organisms ordinarily considered non-pathogenic, some of cases due to organisms pathogenic for man but rarely involving the...
Book: Gout: The Patrician Malady
Authors: J Dequeker
Journal: BMJ (1999)

Roy Porter, G S Rousseau Yale University Press, $25, pp393 ISBN 0 300073860 Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Gout has been recognised since antiquity, and descriptions of the disease date back to the Babylonian empire. It was certainly well described by Hippocrates. Called the “king of diseases” and the “disease of kings,” gout is more the “disease of plenty.” In Gout Porter and Rousseau track medical thinking about the disease across the centuries, from Hippocrates and Galen to Paracelsus, Harvey, Archibald Garrod in the Victorian era, and beyond. They discuss the cultural, moral, religious, and personal qualities associated with the condition, examining social commentary, personal writings, cartoons … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Abstract 13397: Determining the Optimal Cutpoint Value for the Diagnosis of Hypertriglyceridemia in the Nonfasting Population
Authors: Khendi T White, M.V. Moorthy, Akintunde O Akinkuolie, Olga Demler, Paul M Ridker, Nancy R Cook, Samia Mora
Journal: Circulation (2014)

Background: Nonfasting triglycerides may be superior to fasting triglycerides at predicting CVD. However, guideline cutpoints are based on fasting triglycerides. We aimed to determine the optimal clinical cutpoint for nonfasting triglycerides. Methods: Among 26,509 apparently healthy women, nonfasting blood samples (&lt;8 hours since last meal) were obtained from 6,391 participants who were prospectively followed for up to 17 years for incident CVD (MI, ischemic stroke, CABG/PTCA, CVD death). The optimal diagnostic threshold for nonfasting triglycerides was determined by univariate logistic regression model using c-statistics for triglycerides between 100-300 mg/dL, with 10-fold cross-validation and bootstrapping in multivariable models. In addition, we tested the proposed nonfasting cutpoints of 175 mg/dL (European Atherosclerosis Society), 180 mg/dL (Athens Expert Panel), and 200 mg/dL (AHA). Results: The optimal threshold was identified as 175 mg/dL (Table). Performance of this optimal threshold was evaluated using 10-fold cross validation and bootstrapping in multivariable models that included age, smoking, blood pressure, hormone use, menopausal status, lipids, diabetes, BMI, and CRP. The adjusted hazard ratio (HR) for nonfasting triglycerides ≥ vs &lt;175 mg/dL predicting incident CVD events was 1.69 (95% CI, 1.34-2.13, p&lt;0.001). Adjusted HRs for triglycerides ≥ vs &lt;175 mg/dL measured 0-4 and 4-8 hours since last meal were 1.73 (1.27-2.36, p&lt;0.001) and 1.63 (1.15-2.32, p=0.006), respectively. Conclusion: This is the first study to identify a diagnostic threshold for nonfasting hypertriglyceridemia, finding an optimal cutpoint of 175 mg/dL. Of note, the currently recommended AHA cutpoint for nonfasting triglycerides of 200 mg/dL had substantially lower sensitivity and could under-diagnose hypertriglyceridemia among nonfasting individuals.
Association of Supply Type with Fecal Contamination of Source Water and Household Stored Drinking Water in Developing Countries: A Bivariate Meta-analysis
Authors: Katherine F. Shields, Robert E.S. Bain, Ryan Cronk, Jim A. Wright, Jamie Bartram
Journal: Environmental Health Perspectives (2015)

BackgroundAccess to safe drinking water is essential for health. Monitoring access to drinking water focuses on water supply type at the source, but there is limited evidence on whether quality differences at the source persist in water stored in the household.ObjectivesWe assessed the extent of fecal contamination at the source and in household stored water (HSW) and explored the relationship between contamination at each sampling point and water supply type.MethodsWe performed a bivariate random-effects meta-analysis of 45 studies, identified through a systematic review, that reported either the proportion of samples free of fecal indicator bacteria and/or individual sample bacteria counts for source and HSW, disaggregated by supply type.ResultsWater quality deteriorated substantially between source and stored water. The mean percentage of contaminated samples (noncompliance) at the source was 46% (95% CI: 33, 60%), whereas mean noncompliance in HSW was 75% (95% CI: 64, 84%). Water supply type was significantly associated with noncompliance at the source (p < 0.001) and in HSW (p = 0.03). Source water (OR = 0.2; 95% CI: 0.1, 0.5) and HSW (OR = 0.3; 95% CI: 0.2, 0.8) from piped supplies had significantly lower odds of contamination compared with non-piped water, potentially due to residual chlorine.ConclusionsPiped water is less likely to be contaminated compared with other water supply types at both the source and in HSW. A focus on upgrading water services to piped supplies may help improve safety, including for those drinking stored water.CitationShields KF, Bain RE, Cronk R, Wright JA, Bartram J. 2015. Association of supply type with fecal contamination of source water and household stored drinking water in developing countries: a bivariate meta-analysis. Environ Health Perspect 123:1222–1231; http://dx.doi.org/10.1289/ehp.1409002
Abstract 15867: Myogenic Target of Mir-290 Cluster Promotes Reprogramming of Skeletal Myoblast to Produce Induced Pluripotent Stem Cells
Authors: Lei Wang, Hideyuki Kondo, Ruilian Ma, Linlin Guo, Ha Won Kim, Yi-Gang Wang
Journal: Circulation (2014)

Background: Skeletal myoblasts (SkMs) are an ideal candidate for reprogramming due to inherent myogenic properties. MicroRNAs (miRNAs) play an important role in cell reprogramming by producing induced pluripotent stem (iPS) cells. Pax7 is a powerful myogenic inducer and plays a critical role in muscle development and regeneration. This study investigates the potential mechanisms of the miR-290s cluster for promoting reprogramming efficiency of SkMs. Methods and Results: The SkMs cells were isolated from the hind limb skeletal muscle of 2 to 4-week-old mice. RT-PCR and immunocytochemical analysis showed that SkMs endogenously expressed not only myogenic genes but also some of pluripotency genes Nanog, Oct4, Sox2, Klf4 and cMyc. SkMs were then infected to produce iPS cells, and embryonic stem (ES) cell-like colonies appeared at 15 days after transfection. SkM-derived iPS (SiPS) cells were profiled by microarray to determine miRNAs responsible for reprogramming of SkMs. Expression of each member of the miR-2...
The Old Musician
Authors: M. Therese Southgate
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
STAT1 expression and activation is increased in lesional psoriatic skin
Authors: A. Hald, R.M. Andrés, M.L. Salskov-Iversen, R.B. Kjellerup, L. Iversen, C. Johansen
Journal: British Journal of Dermatology (2012)

Background The JAK (Janus kinase)/STAT (signal transducer and activator of transcription) signalling pathway is known to play an important role in many cellular processes including inflammation. The activation of STAT1 is dependent on tyrosine 701 and serine 727 phosphorylation, which leads to the formation of the STAT dimer and modulation of STAT1 activity, respectively. Objective To determine STAT1 expression and activation in psoriatic skin. Methods Biopsies were collected from patients with psoriasis. mRNA expression was evaluated by quantitative polymerase chain reaction, whereas the protein and phosphorylation level of STAT1 were evaluated by Western blotting. STAT1 localization was determined by immunofluorescence analysis and STAT1‐induced transcriptional activity was analysed in cultured human keratinocytes using a reporter assay. Results The expression of STAT1 was demonstrated to be significantly increased at both mRNA and protein level in lesional psoriatic skin. In addition, the phosphorylation level of STAT1(Tyr701) and STAT1(Ser727) was significantly increased in lesional compared with nonlesional psoriatic skin. Luciferase assays showed a significant induction of the STAT1‐induced transcriptional activity when cultured human keratinocytes were stimulated with either interferon (IFN)‐α or IFN‐γ. STAT1(Ser727) phosphorylation induced by IFN‐α, IFN‐γ or ultraviolet B was mediated by a protein kinase C (PKC)‐δ‐ and p38 mitogen‐activated protein kinase‐dependent mechanism in human keratinocytes, whereas IFN‐α‐induced STAT1(Tyr701) phosphorylation was mediated by a PKC‐δ‐dependent mechanism. Conclusions This study demonstrates for the first time that the phosphorylation level of STAT1(Tyr701) and STAT1(Ser727) is increased in lesional psoriatic skin. In addition, specific signalling pathways leading to this phosphorylation have been identified. Together, our data indicate an important role of STAT1 in the pathogenesis of psoriasis.
Abstract 17106: Transition From Adipose to Fibrotic Tissue in the Atrial Subepicardium in Humans and in a Sheep Model of Atrial Fibrillation
Authors: Peter Haemers, Hadhami Hamdi, Piet Claus, Patrick Farahmand, Patrick Bruneval, Uwe Lendeckel, José Jalife, Pierre Jaïs, Rik Willems, Stéphane Hatem
Journal: Circulation (2014)

Epicardial adipose tissue (EAT) is recognized as potentially involved in the pathophysiology of atrial fibrillation (AF). In addition to EAT fatty infiltration commonly observed in myocardium might be also associated with the substrate for AF. We conducted a histological study in 93 human right atrial samples obtained during cardiac surgery and in a sheep model of long-term persistent AF (PAF) induced by atrial tachypacing (24±8 weeks) (15 PAF, 11 SR). Upon Sirius Red and Harris Haematoxylin staining, human atria showed various degree of fatty infiltration starting from the epicardium (rarely from vessels), which could be associated with various degree of subepicardial fibrosis realizing in some cases a true fibro-fatty infiltration. The extent of remodeled epicardium was assessed as % of infiltrating and fibrotic epicardium±adipose tissue to total epicardial length; 44±26 % of the epicardium was remodeled. A multiple regression model (including history of AF, % adipose tissue, age, BodyMassIndex, coronary artery bypass, ejection fraction) significantly predicted the percentage of epicardial remodeling (R=0.501, p=0.003). Only AF and the % adipose tissue were significant predictors (respectively β=0.27;p=0.016 and β=-0.267;p=0.016). To further analyze the relationship between fibro-fatty infiltration and AF, a histological study was performed in LA specimen of a sheep PAF model which revealed 4 grades of subepicardial infiltrates from pure fatty to dense fibro-fatty infiltration (fig A). EAT infiltrates (316) were graded, demonstrating a shift towards more severe grades in the AF group p&lt;0.0001) (fig B). Inflammatory cells were detected in 14 fatty infiltrations (grade 2 and 3) of 6 AF sheep (and only in 1 fatty infiltration of SR sheep). Conclusion: , AF is associated with the transformation of fat into fibro-fatty infiltrations suggesting that the subepicardial adipose tissue plays a role in the atrial fibrotic remodeling.
Doripenem Versus Meropenem For Empirical Antimicrobial Therapy In High Risk Febrile Neutropenic Patients With Hematological Malignancies: A Randomized, Controlled Trial
Authors: Yuka Fujisawa, Tatsuo Oyake, Takahiro Mine, Yusei Aoki, Yasuhiko Tsukushi, Takeshi Sugawara, Masato Seguchi, Ichiro Hanamura, Yasuaki Nakagawa, Kazunori Murai, Shigeki Ito, Yoji Ishida
Journal: Blood (2013)
Abstract 19641: Novel Microprinted Elisa Platform for High Throughput Screening of Protein Secretion Reveals a Comprehensive Strategy to Prevent Ischemia Reperfusion Induced Apoptosis
Authors: Kshitiz Kz, David E Ellison, Junaid Afzal, Maimon E Hubbi, Segun Bernard, Ruchi Goyal, Connie Chang, Roselle Abraham, Andre C Levchenko
Journal: Circulation (2014)

Introduction: A major challenge in using stem cells to treat myocardial infarction (MI) is the massive cell death post transplant. Many progenitor cell types limit disrepair post MI without significant cardiac differentiation, possibly by anti-apoptotic signals in their secretions. The signature of these secretions is however not well known. Methods: We created a novel high throughput microELISA platform by combining microprinting and microfluidics to precisely estimate secretions of a small population of cells over time. Screening the secretions in many stem cell types used previously to treat MI, i.e. BMSCs (Bone marrow derived stem cells), CDCs (Cardiosphere derived cells), and iPSC-CMs (induced pluripotent stem cell derived cardiomyocytes), we found a common preserved secretory signature of growth factors. Results: Using a high throughput screen of pro-apoptotic factors that prevent CDCs from peroxide induced cell death, we surprisingly found that these factors were identical to the preserved secretory signature. Using the constituents of the anti-apoptotic secretory signature in combination with ischemic and mechanical preconditioning in myocardium mimicking rigidity, we created a comprehensive cytoprotective cocktail to prevent CDCs from ischemia induced cell death. We tested the cocktail in a rat model of ischemia reperfusion, and found a stark reduction in CDC retention post injection. Figures: (A) MicroELISA schematic. Secretions from cells in left are detected by rows of microprinted capture antibodies; photograph in (C-D). Bioluminescence imaging of CDCs treated with comprehensive cocktail show significantly high cell retention vs untreated CDCs.