tbuckley/cabot-search huggingface dataset:
Abstract 12638: Hsp20-Reprogrammed Exosomes Derived From Cardiomyocytes Provide Protection Against Diabetic Cardiomyopathy in Mice
Authors: Xiaohong Wang, Haitao Gu, Wei Huang, Yigang Wang, Guo-Chang Fan
Journal: Circulation (2014)

Background:  It has been shown that exosomes, a group of nanovesicles naturally released from living cells, have either beneficial or deleterious effects on cell behavior, depending on the contents encased. We recently showed that Hsp20, as a chaperon protein, could be included in cardiomyocyte exosomes which promoted angiogenesis. Whether such exosomes derived from Hsp20-overexpressing myocytes play any protective role in diabetic animals remains unknown.   Methods and Results:  Cultured myocytes were infected with Ad-Hsp20 to overexpress Hsp20. Ad-GFP was used as controls. Then supernatants were collected for purification of exosomes by differential centrifugation. While exosomes derived from Hsp20-myocytes (Hsp20-Exo) displayed similar size and molecular markers (CD63 and CD81) to those originated from the control GFP-myocytes (GFP-Exo), the protein contents encased were different. Western-blotting or ELISA assays revealed that Hsp20-Exo contained higher levels of Hsp20, VEGFR2, Survivin, p-Akt, and SOD1 than GFP-Exo. We next tested the effects of such exosomes in vivo using a diabetic mouse model, which was induced by daily peritoneal injection of streptozotocin (STZ, 50μg/g) for 5 days. Three days after the last injection of STZ, blood glucose levels were measured. Mice were considered diabetic (≥15 mmol/L) and used for the study. We then treated such diabetic mice with exosomes via the tail vein injection (5μg/g body weight). One month later, cardiac function was measured by echocardiography, and showed that left ventricular ejection fraction (EF) and fractional shortening (FS) were increased by 33% and 28%, respectively, in Hsp20-Exo-treated mice, compared with GFP-Exo-controls. We also found that Hsp20-Exo led to an increased density of cardiac blood vessels and reduction of myocardial fibrosis to a greater degree than GFP-Exo-samples. Mechanistically, we identified that PKH67-labled exosomes could be detected in mouse hearts at 2 hours after the tail vein injection and confirmed that exosomal Hsp20 was transferred to the in vivo hearts.   Conclusions:  This study indicates that the exosome contents can be modified by Hsp20 in cardiomyocytes. Injection of Hsp20-reprogrammed exosomes protects diabetic animals against cardiomyopathy.
Medical Students Reach Out to Rural Communities in "WWAMI Land"
Authors: Rebecca Voelker
Journal: JAMA (2003)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
The EDAR370A allele attenuates the severity of hypohidrotic ectodermal dysplasia caused by EDA gene mutation
Authors: C. Cluzeau, S. Hadj-Rabia, E. Bal, F. Clauss, A. Munnich, C. Bodemer, D. Headon, A. Smahi
Journal: British Journal of Dermatology (2011)

Journal Article The EDAR370A allele attenuates the severity of hypohidrotic ectodermal dysplasia caused by EDA gene mutation Get access C. Cluzeau, C. Cluzeau Université Paris Descartes and INSERM U781, Hôpital Necker‐Enfants Malades, Paris 75015, France Search for other works by this author on: Oxford Academic Google Scholar S. Hadj‐Rabia, S. Hadj‐Rabia Université Paris Descartes and INSERM U781, Hôpital Necker‐Enfants Malades, Paris 75015, FranceCentre de Référence National des Maladies Génétiques à Expression Cutanée, Service de Dermatologie, Hôpital Necker‐Enfants Malades, Paris 75015, France Smail Hadj‐Rabia. E‐mail: smail.hadj@inserm.fr Search for other works by this author on: Oxford Academic Google Scholar E. Bal, E. Bal Université Paris Descartes and INSERM U781, Hôpital Necker‐Enfants Malades, Paris 75015, France Search for other works by this author on: Oxford Academic Google Scholar F. Clauss, F. Clauss Département Odontologie Pédiatrique, Centre de Référence National pour les Maladies Génétiques à Expression Odontologique, Hôpitaux Universitaires, Strasbourg 67091, FranceNSERM UMR977, Faculté Dentaire, Université de Strasbourg, Strasbourg 67091, France Search for other works by this author on: Oxford Academic Google Scholar A. Munnich, A. Munnich Université Paris Descartes and INSERM U781, Hôpital Necker‐Enfants Malades, Paris 75015, France Search for other works by this author on: Oxford Academic Google Scholar C. Bodemer, C. Bodemer Université Paris Descartes and INSERM U781, Hôpital Necker‐Enfants Malades, Paris 75015, FranceCentre de Référence National des Maladies Génétiques à Expression Cutanée, Service de Dermatologie, Hôpital Necker‐Enfants Malades, Paris 75015, France Search for other works by this author on: Oxford Academic Google Scholar D. Headon, D. Headon The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh EH25 9PS, U.K Search for other works by this author on: Oxford Academic Google Scholar A. Smahi A. Smahi Université Paris Descartes and INSERM U781, Hôpital Necker‐Enfants Malades, Paris 75015, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 166, Issue 3, 1 March 2012, Pages 678–681, https://doi.org/10.1111/j.1365-2133.2011.10620.x Published: 01 March 2012
Abstract 12189: Molecular Mechanisms Underlying Fasting Modulated Liver Insulin Sensitivity and Metabolism in Male Lipodystrophic Bscl2/Seipin-Deficient Mice
Authors: Weiqin Chen, Hongyi Zhou, Pradip Saha, Luge Li, Lawrence Chan
Journal: Circulation (2014)

Bscl2–/– mice recapitulate many of the major metabolic manifestations in Berardinelli-Seip Congenital Lipodystrophy type 2 (BSCL2) individuals, including lipodystrophy, hepatomegly, hepatic steatosis and insulin resistance. The mechanisms that underlie hepatic steatosis and insulin resistance in Bscl2–/– mice are poorly understood. To address this issue, we performed hyperinsulinemic-euglycemic clamp on Bscl2–/– and wild-type mice after an overnight (16-h) fast, and found that Bscl2–/– actually displayed increased hepatic insulin sensitivity. Interestingly, liver in Bscl2–/– mice after a short term (4-h) fast had impaired acute insulin signaling, a defect that disappeared after a 16-h fast. Notably, fasting dependent hepatic insulin signaling in Bscl2–/– mice was not associated with liver diacylglyceride and ceramide contents, but could be attributable in part to the expression of hepatic insulin signaling receptor and substrates. Meanwhile, increased de novo lipogenesis and decreased β-oxidation led to severe hepatic steatosis in fed or short fasted Bscl2–/– mice while liver lipid accumulation and metabolism in Bscl2–/– mice was markedly impacted by prolonged fasting. Furthermore, mice with liver-specific inactivation of Bscl2 manifested no hepatic steatosis even under high fat diet, suggesting Bscl2 does not play a cell autonomous role in regulating liver lipid homeostasis. Overall, our results offered new insights into the metabolic adaptations of liver in response to fasting and uncovered a novel fasting-dependent regulation of hepatic insulin signaling in a mouse model of human BSCL2.
Piperacillin To Prevent Cholangitis after Endoscopic Retrograde Cholangiopancreatography
Authors: Sven J. van den Hazel
Journal: Annals of Internal Medicine (1996)

Background: Cholangitis does not often occur after endoscopic retrograde cholangiopancreatography (ERCP), but it can be a serious complication of this procedure. Antibiotic prophylaxis is therefore frequently used in patients having ERCP, but existing data are insufficient to allow evaluation of the effectiveness of this practice. Objective: To determine the efficacy of single-dose antibiotic prophylaxis with piperacillin for ERCP-induced cholangitis. Design: Randomized, double-blind, placebo-controlled clinical trial. Setting: Tertiary referral center for ERCP. Patients: Patients who had ERCP for suspected biliary tract stones or distal common bile duct stricture were eligible. Major exclusion criteria were previous ERCP within 7 days, biliary endoprosthesis in situ, and use of antimicrobial agents or presence of fever within 7 days before the procedure. Intervention: Piperacillin, 4 g, or placebo was given intravenously approximately 30 minutes before ERCP. Measurements: Duration of follow-up was 1 week. Acute cholangitis was diagnosed if a patient had a body temperature greater than 38 °C, a clinically apparent need for antibiotic treatment, and no symptoms indicating infection outside of the biliary tree. Results: 551 consecutive patients were enrolled. During ERCP, stones were found in 147 patients, malignant distal strictures were found in 203 patients, other pathologic findings were seen in 88 patients, and normal biliary tracts were seen in 113 patients. Seventeen of the 281 patients who received placebo (6.0%) and 12 of the 270 patients who received piperacillin (4.4%) developed acute cholangitis (relative risk, 0.73 [95% CI, 0.36 to 1.51]). The absolute risk reduction was 1.6% (CI, −5.3% to 2.1%). All cases of cholangitis (with the exception of one case seen in a patient in the piperacillin group) were mild or moderate in severity. Conclusion: Single-dose prophylaxis with piperacillin is not associated with a clinically significant reduction in the incidence of acute cholangitis after ERCP in patients suspected of having biliary tract stones or distal common bile duct stricture.
Silent mysteries: epigenetic paradigms could hold the key to conquering the epidemic of allergy and immune disease
Authors: D. J. Martino, S. L. Prescott
Journal: Allergy (2009)

Abstract Epigenetic mechanisms provide new insights into how environmental changes may mediate the increasing propensity for complex immune diseases such as allergic disease. There is now strong evidence that early environmental exposures play a key role in activating or silencing genes by altering DNA and histone methylation, histone acetylation and chromatin structure. These modifications determine the degree of DNA compaction and accessibility for gene transcription, altering gene expression, phenotype and disease susceptibility. While there is already evidence that a number of early environmental exposures are associated with an increased risk of allergic disease, several new studies indicate in utero microbial and dietary exposures can modify gene expression and allergic disease propensity through epigenetic modification. This review explores the evidence that immune development is under clear epigenetic regulation, including the pattern of T helper (Th)1 and Th2 cell differentiation, regulatory T cell differentiation, and more recently, Th17 development. It also considers the mechanisms of epigenetic regulation and early immune defects in allergy prone neonates. The inherent plasticity conferred by epigenetic mechanisms clearly also provides opportunities for environmental strategies that can re‐programme gene expression for disease prevention. Identifying genes that are differentially silenced or activated in relation to subsequent disease will not only assist in identifying causal pathways, but may also help identify the contributing environmental factors.
Abstract MP21: Achieving Cardiovascular Health in Young Adulthood - Do Adolescent Factors Matter?
Authors: Holly C Gooding, Carly Milliren, Christina M Shay, Tracy K Richmond, Alison E Field, Matthew W Gillman
Journal: Circulation (2015)

Introduction: Adults who reach middle age with optimal levels of three physiologic factors – blood pressure, cholesterol, and blood glucose – have lower rates of CVD mortality compared to those with one or more of these risk factors in the non-optimal range. The American Heart Association has identified four healthy lifestyle components – BMI, smoking, diet, and physical activity – important for preserving optimal cardiovascular health as people age. However, which lifestyle components in adolescence are most strongly associated with physiologic markers of cardiovascular health in adulthood is unclear. The purpose of this study was to quantify associations between lifestyle components measured in adolescence and optimal physiologic cardiovascular health in young adulthood. Methods: Analyses included 9,697 young adults, age 24-32 years in 2007-2008, who participated in Wave IV of the National Longitudinal Study of Adolescent Health. We defined optimal physiologic cardiovascular heath as untreated blood pressure &lt;120/80 mmHg, untreated fasting blood glucose &lt;100 mg/dL and hemoglobin A1C &lt; 5.7%, untreated total cholesterol in the bottom 7 (women) or 6 (men) deciles for the study population, and absence of diabetes or CVD as measured at Wave IV. We used logistic regression models to estimate the odds of having optimal physiologic cardiovascular health in young adulthood according to BMI category, smoking status, and physical activity patterns measured during Waves I and II when participants were ages 11-20 years. Dietary data were not available. Models were adjusted for age, sex, race, educational attainment, and income in young adulthood. Results: Few young adults (16%, 1,592 of 9,697) had optimal physiologic cardiovascular health. Young adults who had been normal-weighted in adolescence were more likely to have optimal physiologic cardiovascular health (18.4%, 1,382 of 7,206) compared to those who had been overweight (9.4%, 142 of 1,429) or obese (6.9%, 68 of 1,062). In models adjusted for young adult sociodemographic factors, participants who had been overweight or obese as adolescents were less than half as likely as those who had been normal-weighted to have optimal physiologic cardiovascular health in young adulthood (overweight odds ratio (OR) 0.43, 95% confidence interval (CI) 0.35-0.61; obese OR 0.40, 95% CI 0.28-0.57). Adolescent tobacco smoking and physical activity were not associated with young adult cardiovascular health. Conclusions: Maintaining a healthy weight in adolescence may be the most important lifestyle factor for reaching young adulthood with optimal physiologic cardiovascular health. Overweight and obese adolescents should be encouraged to achieve a healthy weight through adherence to diet and physical activity goals.
Homocystinuria
Authors: Brian Fowler, Jan Kraus, Seymour Packman, Leon E. Rosenberg
Journal: Journal of Clinical Investigation (1978)

We have compared in vivo pyridoxine responsiveness with in vitro cystathionine beta-synthase activity in extracts of confluent fibroblasts from 14 synthase-deficient patients. Enzyme activity was measured with and without addition of its cofactor, pyridoxal-5'-phosphate, using a radioisotopic assay which detects as little as 0.25% of control activity. Six of seven lines from responsive patients had measurable activity without the added cofactor (0.6-15% of mean control). Two of these lines showed a five- and sevenfold stimulation of cystathionine beta-synthase activity with added pyridoxal-5'-phosphate; in the other four, the cofactor addition increased activity only modestly, as in controls. Two of seven lines from nonresponsive patients had measurable activity (each 3% of mean control) which increased two- and fivefold with the added cofactor. Cystathionine beta-synthase activity was undetectable in one line from a responsive patient and in five lines from nonresponsive ones. To characterize control and mutant synthase further, dissociation constants for pyridoxal-5'-phosphate were estimated and thermostability (54 degrees C) was studied in two control and five mutant lines. In one mutant, both parameters were normal; in the others, the affinity for the cofactor was reduced 3-to 11-fold and thermostability was much impaired. We conclude that at least three general classes of cystathionine beta-synthase mutants exist: those with no residual activity; those with reduced activity and normal affinity for pyridoxal-5' phosphate; and those with reduced activity and a reduced affinity for the cofactor. Pyridoxine responsiveness in vivo cannot be correlated simply with the presence or absence of residual synthase activity in vitro or with stimulation of in vitro enzyme activity by cofactor.
Screening for familial hypercholesterolaemia
Authors: J J P Kastelein
Journal: BMJ (2000)

Papers p 1497 

Familial hypercholesterolaemia is a common disorder of lipid metabolism associated with a high risk of early mortality from coronary artery disease.1 It is so common that general practitioners often have one or two families with the disorder in their practices, although they are frequently unaware of this.2 People with familial hypercholesterolaemia often die from atherosclerotic heart disease before the age of 40; this is particularly true for men. These sudden deaths are tragic because they can easily be prevented once the condition has been recognised and treated properly.3 It has been well established that the clinical sequelae of familial hypercholesterolaemia are the consequence of the extremely high concentrations of low density lipoprotein cholesterol that these patients have been exposed to since early childhood.1

The most effective and most widely prescribed class of cholesterol lowering drugs, the statins, was shown to be particularly effective in patients with this condition.4 While it would seem logical to assume that treatment with statins …
Reducing exacerbations in COPD with OM-85: A multicentre, double-blind, placebo-controlled trial
Authors: Dario Olivieri
Journal: European Respiratory Journal (2011)

Background:  Acute exacerbations in COPD (AE-COPD) are a key driver of morbidity and mortality. They are mainly triggered by respiratory infections. OM-85 is a bacterial lysate with immunostimulating properties already known to reduce AE-COPD.   Aims and objectives:  Confirm and further investigate the efficacy and safety of OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®) with a specific dosage regimen in reducing the rate of acute exacerbations in moderate to severe COPD patients.   Methods:  This randomised, placebo-controlled, double-blind, multicentre trial was performed with 340 patients from 5 countries, past or active smoker, over 40 years old, with COPD stage II or III, with a history of at least 2 documented AE-COPD in the previous year, and a FEV1 between 30% and 80%. The specific dosage regimen was 1 capsule daily during month 1, and 1 capsule daily for 10 days in months 3 to 5.   Results:  Preliminary results show that OM-85 significantly reduced the rate of AE-COPD by 35.4% after the 5 months treatment period (p=0.0155). The mean duration of AE-COPD was significantly decreased by 1.4 days in the OM-85 group (2.79 days), as compared to placebo (4.15 days) (p=0.0498).The rate of treatment-emergent adverse events (TEAEs) was similar in both treatment groups (OM-85: 44.1%, placebo: 43.3%).   Conclusion:  OM-85 significantly reduced the rate and duration of AE-COPD in moderate to severe COPD patients. Safety and tolerance were excellent.
A possible novel Francisellagenomic species isolated from blood and urine of a patient with severe illness
Authors: R. Escudero, M. Elía, J.A. Sáez-Nieto, V. Menéndez, A. Toledo, G. Royo, M. Rodríguez-Vargas, M.J. Whipp, H. Gil, I. Jado, P. Anda
Journal: Clinical Microbiology and Infection (2009)
Antibiotic Chemoprophylaxis and HIV Infection in Kenyan Sex Workers
Authors: Richard Steen, Gina Dallabetta, Graham Neilsen
Journal: JAMA (2004)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Adrenergic Receptors in Man
Authors: Harvey J. Motulsky, Paul A. Insel
Journal: New England Journal of Medicine (1982)

THE catecholamines norepinephrine and epinephrine are key regulators of many physiologic events in human beings; norepinephrine acts primarily as a neurotransmitter released from sympathetic-nerve terminals, and epinephrine functions as a circulating hormone released from the adrenal medulla. These catecholamines initiate target-cell responses by binding to specific recognition sites, the adrenergic receptors. That receptors are the initial decoders of extracellular messages is a concept that has guided research on hormone and neurotransmitter action for many years. Studies of adrenergic receptors focused first on physiologic responses that are promoted by adrenergic stimulation and demonstrated the existence of two primary types of adrenergic . . .
Starry Night With Astronauts
Authors: M. Therese Southgate
Journal: JAMA (2003)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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