tbuckley/cabot-search huggingface dataset:
Sarcoplasmic reticulum Ca2+ ATPase promoter activity during endothelin-1 induced hypertrophy of cultured rat cardiomyocytes
Authors: H van Heugten
Journal: Cardiovascular Research (1998)

Objectives: Characterization of an in vitro model of endothelin-1 induced hypertrophy of cultured neonatal rat ventricular myocytes and subsequent analysis of transcription regulation of the rat promoter of the sarcoplasmic reticulum Ca2+ ATPase gene. Methods: Neonatal rat ventricular myocytes were cultured in serum free medium and hypertrophy was induced by addition of endothelin-1 to 10−8 M up to 48 h. Hypertrophy was characterized biochemically, and gene expression regulation was evaluated by Northern blotting. A sarcoplasmic reticulum Ca2+ ATPase promoter fragment, isolated from a rat library was cloned in a reporter vector. Promoter activity during hypertrophy was assessed after transfection of the reporter plasmid to cultured cardiomyocytes. Results: Stimulation with endothelin-1 resulted in increased cell size, as indicated by protein/DNA ratio as well as by augmented protein synthesis. When compared to angiotensin II or α1-adrenergic agonist, endothelin-1 was the strongest inducer of hypertrophy (protein/DNA ratio) after 48 h of stimulation. Endothelin-1 induced hypertrophy was accompanied by a twofold increase in total RNA content per cell as well as to increased glyceraldehydephosphate dehydrogenase mRNA levels. The level of atrial natriuretic factor mRNA was increased more than twofold, relative to glyceraldehydephosphate dehydrogenase, while the expression of the sarcoplasmic reticulum Ca2+ pump and phospholamban genes was decreased (by 26 and 49%, respectively) after induction of hypertrophy by stimulation with endothelin-1. In the same model, a 1.9 kb sarcoplasmic reticulum Ca2+ pump gene promoter fragment (including 0.4 kb of the 5′ UTR of the mRNA) directed down-regulation of the expression of the reporter gene to the same magnitude as endogenous Ca2+ pump mRNA relative to glyceraldehydephosphate dehydrogenase mRNA. However, absolute mRNA level per cell did not change for either the reporter gene or the endogenous Ca2+ pump. Conclusions: Endothelin-1 can induce phenotypic changes in cultured rat ventricular myocytes that are reminiscent of hypertrophy in vivo. In this model, a 1.9 kb sarcoplasmic reticulum Ca2+ pump promoter fragment directed gene expression of a reporter gene identical to the endogenous regulation of the Ca2+ pump. Furthermore, expression of the Ca2+ pump during hypertrophy was only downregulated when compared to (increased levels of) glyceraldehydephosphate dehydrogenase mRNA, but absolute Ca2+ ATPase mRNA amounts remained unchanged. This suggests that the Ca2+ pump promoter is not responding to the increase in transcriptional activity that accompanies hypertrophy.
The Influence of Partner’s Behavior on Health Behavior Change
Authors: Sarah E. Jackson, Andrew Steptoe, Jane Wardle
Journal: JAMA Internal Medicine (2015)

Couples are highly concordant for unhealthy behaviors, and a change in one partner's health behavior is often associated with a change in the other partner's behavior. However, no studies have explicitly compared the influence of having a partner who takes up healthy behavior (eg, quits smoking) with one whose behavior is consistently healthy (eg, never smokes).To examine the influence of partner's behavior on making positive health behavior changes.We used prospective data from married and cohabiting couples (n, 3722) participating in the English Longitudinal Study of Ageing, a large population-based cohort of older adults (≥50 years). Studying men and women who had unhealthy behaviors in 3 domains at baseline (ie, smoking, physically inactive, or overweight/obese), we used logistic regression analysis to examine the influence of the partner's behavior in the same domain on the odds of positive health behavior change over time.Smoking cessation, increased physical activity, and 5% weight loss or greater.Across all domains, we found that when one partner changed to a healthier behavior (newly healthy), the other partner was more likely to make a positive health behavior change than if their partner remained unhealthy (smoking: men 48% vs 8%, adjusted odds ratio [OR], 11.82 [95% CI, 4.84-28.90]; women 50% vs 8%, OR, 11.23 [4.58-27.52]) (physical activity: men 67% vs 26%, OR, 5.28 [3.70-7.54]; women 66% vs 24%, OR, 5.36 [3.74-7.68]) (weight loss: men 26% vs 10%, OR, 3.05 [1.96-4.74]; women 36% vs 15%, OR, 3.08 [1.98-4.80]). For smoking and physical activity, having a consistently healthy partner also predicted positive change, but for each domain, the odds were significantly higher in individuals with a newly healthy partner than those with a consistently healthy partner (smoking: men OR, 3.08 [1.43-6.62]; women OR, 5.45 [2.44-12.16]) (physical activity: men OR, 1.92 [1.37-2.70]; women OR, 1.84 [1.33-2.53]) (weight loss: men OR, 2.28 [1.36-3.84]; women OR, 2.86 [1.55-5.26]).Men and women are more likely to make a positive health behavior change if their partner does too, and with a stronger effect than if the partner had been consistently healthy in that domain. Involving partners in behavior change interventions may therefore help improve outcomes.
Capillary Observations in Patients with Hemorrhagic Fever and Other Infectious Illnesses1
Authors: Sheldon E. Greisman
Journal: Journal of Clinical Investigation (1957)

This report describes the changes detected during serial observations of the nail-fold capillary bed of such patients with hemorrhagic fever. The capillary alterations observed in patients with other infectious diseases who were studied in a similar manner are also described. The findings indicate that significant alterations of the capillary vessels may be observed directly during hemorrhagic fever and during certain other infectious illnesses, and that these capillary alterations can be correlated with the clinical course and pathological findings.
NATURAL LANGUAGE PROCESSING IMPROVES PHENOTYPIC ACCURACY IN AN ELECTRONIC MEDICAL RECORD COHORT OF TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE
Authors: Vishesh Kumar, Katherine Liao, Su-Chun Cheng, Sheng Yu, Uri Kartoun, Ari Brettman, Vivian Gainer, Andrew Cagan, Shawn Murphy, Guergana Savova, Pei Chen, Peter Szolovits, Zongqi Xia, Elizabeth Karlson, Robert Plenge, Ashwin Ananthakrishnan, Susanne Churchill, Tianxi Cai, Isaac Kohane, Stanley Shaw
Journal: Journal of the American College of Cardiology (2014)
439 Improving antiviral therapy in chronic hepatitis B: Maximal viral suppression at week 24 correlates with better clinical efficacy at one year
Authors: T. Poynard, C.L. Lai, N.W.Y. Leung, E.K. Teo, M. Tong, F. Wong, H.W. Hann, S. Han, M. Myers, G. Chao, D. Lloyd, N.A. Brown
Journal: Journal of Hepatology (2004)
Psychiatrist who made "one-off" error of judgment should not be disciplined
Authors: C. Dyer
Journal: BMJ (2009)

A forensic psychiatrist whose patient killed a man after absconding from hospital grounds has won a long running battle at the High Court in London to stop her employers suspending her and taking disciplinary proceedings against her.

Gill Mezey authorised John Barrett, who has paranoid schizophrenia and a history of violence, to take one hour’s unsupervised “ground leave” in the grounds of Springfield Hospital without seeing him in September 2004. Mr Barrett had been readmitted to the hospital in South London for assessment because of concerns about a possible deterioration in his condition. 

Dr Mezey was away from the hospital on other duties and was unable to assess him immediately. She authorised the unsupervised leave on the basis of what she was told by colleagues. Mr Barrett left the grounds and a day later killed the banker Denis Finnegan, a stranger …
Ethical issues in prenatal diagnosis
Authors: A. Davis
Journal: BMJ (1984)

Mrs Tew equates intranatal care by midwives and general practitioners with non-intervention.There was some intervention at home such as forceps and breech deliveries, though less than in hospital.Mrs Tew deplores the policy of admitting everybody to hospital for delivery because this policy eliminates evidence which could have helped her prove that delivery at home and in general practitioner units was safer than in hospital.Is this really an adequate reason for encouraging delivery at home ?Mrs Tew turns a blind eye to the fact that in 1946 when the first survey was conducted both maternal and perinatal mortality were extremely high in spite of 42% of all babies being born in the "safe" environment of home.In 1958, when
Diverse regulation of NF-?B and peroxisome proliferator-activated receptors in murine nonalcoholic fatty liver
Authors: Laszlo Romics, Karen Kodys, Angela Dolganiuc, Lucia Graham, Arumugam Velayudham, Pranoti Mandrekar, Gyongyi Szabo
Journal: Hepatology (2004)

Fatty liver is highly sensitive to inflammatory activation. Peroxisome proliferator-activated receptors (PPAR) have anti-inflammatory effects and regulate lipid metabolism in the fatty liver. We hypothesized that fatty liver leads to endotoxin sensitivity through an imbalance between pro- and anti-inflammatory signals. Leptin-deficient, ob/ob mice and their lean littermates were challenged with single or double insults and pro- and anti-inflammatory pathways were tested on cytokine production and activation of nuclear regulatory factors NF-κB and peroxisome proliferator receptor element (PPRE). Ob/ob mice produced significantly higher serum tumor necrosis factor α (TNF-α) and interleukin (IL) 6 and showed increased hepatic NF-κB activation compared to lean littermates after stimulation with a single dose of lipopolysaccharide (LPS) or alcohol. In ob/ob mice, double insults with alcohol and LPS augmented proinflammatory responses mediated by increased degradation of inhibitory κB (IκB)-α and IκB-β and preferential induction of the p65/p50 NF-κB heterodimer. In lean mice, in contrast, acute alcohol attenuated LPS-induced TNF-α, IL-6 production, and NF-κB activation through reduced IκB-α degradation and induction of p50/p50 homodimers. PPRE binding was increased in fatty but not in lean livers after alcohol or LPS stimulation. However, cotreatment with alcohol and LPS reduced both PPRE binding and nuclear levels of PPAR-α in fatty livers but increased those in lean livers. In conclusion , our results show opposite PPRE and NF-κB activation in fatty and lean livers. PPAR activation may represent an anti-inflammatory mechanism that fails in the fatty liver on increased proinflammatory pressure. Thus, an imbalance between PPAR-mediated anti-inflammatory and NF-κB-mediated proinflammatory signals may contribute to increased inflammation in the fatty liver. (Hepatology 2004;40:376-385.)
Birds, Fish, and Subspecialists
Authors: Richard A. Davidson
Journal: JAMA (1983)

Many elegant surveys have characterized the future American internist during the past few years. About 75% of residents plan on subspecialty training, and certain characteristics (religion, economic status, and training in or out of their home states) seem to be associated with this decision.<sup>1</sup>In addition, we know that two thirds of residents in traditional training programs who were planning general internal medicine careers change their plans in the course of their training,<sup>2</sup>despite the generally noted conclusion that there are no longer glaring deficiencies of medical subspecialists in this country. What are the reasons for this distribution? Neither future subspecialists nor future generalists selected their fields on the basis of financial rewards.<sup>1</sup>One great predictor is the desire for control over working conditions.<sup>1</sup>However, there are certainly more reasons than can be explored by surveys. Most internal medicine training programs would state their goal as
Abstract 3042: Investigating microRNA expression profiles in colon cancer cells in response to cyclooxygenase 2 signaling
Authors: Kelsey L. Harpster, Ronald R. Bean, Rolf Jakobi, Yu-Wen E. Chang
Journal: Cancer Research (2010)

Abstract MicroRNAs (miRNAs) are emerging as central players in cancer progression. Aberrant expression of miRNAs leads to malignant transformation and correlates with staging, progression and prognosis of cancers. Unfortunately, signaling pathways leading to altered expression of miRNAs are largely unknown. During early development of colon cancer, the expression of cyclooxygenase 2 (COX-2) is constitutively induced. We and others have shown that constitutive expression of COX-2 promotes colon carcinogenesis. However, the underlying mechanisms are not completely understood. To determine if COX-2 signaling alters expression of miRNAs, we used the Human Cancer RT2-miRNA PCR arrays to profile miRNA expression in HCA-7 human colon cancer cells treated with or without the COX-2 selective inhibitor NS-398. HCA-7 cells constitutively express endogenous COX-2. We found that expression levels of 39 miRNAs are different in HCA-7 cells as compared to HCA-7 cells treated with NS-398; 8 miRNAs were up-regulated and 31 miRNAs were down-regulated. To confirm the data from the PCR array, we used quantitative RT-PCR to quantify expression of 8 miRNAs in HCA-7 cells with or without NS-398 treatment. These 8 miRNAs were selected due to their relevance to cancer invasion and metastasis. We also compared the expression of these miRNAs in HCT-15 human colon cancer cells that were engineered to stably express COX-2 (HCT-15-COX-2) to the parental HCT-15 cells. Expression levels of 6 of the 8 examined miRNAs (miR-23b, 124, 146b-5p, 155, 183, 184) were significantly lower in HCT-15-COX-2 or HCA-7 cells than in parental HCT-15 or HCA-7 cells that were treated with NS-398. Therefore, we identified 6 miRNAs that are modulated by COX-2 and may play a role in mediating COX-2 signaling to promote colon carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3042.
Pyruvate:NADP Oxidoreductase from the Mitochondrion of Euglena gracilis and from the Apicomplexan Cryptosporidium parvum: A Biochemical Relic Linking Pyruvate Metabolism in Mitochondriate and Amitochondriate Protists
Authors: Carmen Rotte, Frantisek Stejskal, Guan Zhu, Janet S. Keithly, William Martin
Journal: Molecular Biology and Evolution (2001)

Most eukaryotes perform the oxidative decarboxylation of pyruvate in mitochondria using pyruvate dehydrogenase (PDH). Eukaryotes that lack mitochondria also lack PDH, using instead the O(2)-sensitive enzyme pyruvate : ferredoxin oxidoreductase (PFO), which is localized either in the cytosol or in hydrogenosomes. The facultatively anaerobic mitochondria of the photosynthetic protist Euglena gracilis constitute a hitherto unique exception in that these mitochondria oxidize pyruvate with the O(2)-sensitive enzyme pyruvate : NADP oxidoreductase (PNO). Cloning and analysis of Euglena PNO revealed that the cDNA encodes a mitochondrial transit peptide followed by an N-terminal PFO domain that is fused to a C-terminal NADPH-cytochrome P450 reductase (CPR) domain. Two independent 5.8-kb full-size cDNAs for Euglena mitochondrial PNO were isolated; the gene was expressed in cultures supplied with 2% CO(2) in air and with 2% CO(2) in N(2). The apicomplexan Cryptosporidium parvum was also shown to encode and express the same PFO-CPR fusion, except that, unlike E. gracilis, no mitochondrial transit peptide for C. parvum PNO was found. Recombination-derived remnants of PNO are conserved in the genomes of Saccharomyces cerevisiae and Schizosaccharomyces pombe as proteins involved in sulfite reduction. Notably, Trypanosoma brucei was found to encode homologs of both PFO and all four PDH subunits. Gene organization and phylogeny revealed that eukaryotic nuclear genes for mitochondrial, hydrogenosomal, and cytosolic PFO trace to a single eubacterial acquisition. These findings suggest a common ancestry of PFO in amitochondriate protists with Euglena mitochondrial PNO and Cryptosporidium PNO. They are also consistent with the view that eukaryotic PFO domains are biochemical relics inherited from a facultatively anaerobic, eubacterial ancestor of mitochondria and hydrogenosomes.
Number of NHS organisations in the red doubled last year, finds Audit Commission
Authors: H. Mooney
Journal: BMJ (2012)

The number of NHS organisations ending the year in the red has risen sharply, according to figures from the Audit Commission.

Thirty one NHS and foundation trusts ended the 2011-12 financial year in debt compared with only 13 in 2010-11.1

The figures show that 10 NHS trusts and 21 foundation trusts failed to break even, with 39 NHS trusts reporting a worse financial position last year than the year before. Eighteen NHS trusts and foundation trusts received financial support from the Department of Health.

The report also shows stark differences in the finances of NHS organisations around the country, with most of the trusts in …
Dose-response of chronic beta-blocker treatment in heart failure from either idiopathic dilated or ischemic cardiomyopathy. Bucindolol Investigators.
Authors: M R Bristow, J B O'Connell, E M Gilbert, W J French, G Leatherman, N E Kantrowitz, J Orie, M L Smucker, G Marshall, P Kelly
Journal: Circulation (1994)

Small-scale clinical investigations have demonstrated that single doses of beta-blocking agents can improve left ventricular function in heart failure from idiopathic dilated cardiomyopathy (IDC). The purpose of this multicenter clinical trial was to determine the dose-effect characteristics of beta-blockade in a heart failure population that includes ischemic dilated cardiomyopathy (ISCD).Bucindolol is a nonselective beta-blocking agent with mild vasodilatory properties. One hundred forty-one subjects with class II or III heart failure, left ventricular ejection fraction (LVEF) < or = 0.40, and background therapy of angiotensin-converting enzyme inhibitors, digoxin, and diuretics were given an initial challenge dose of bucindolol 12.5 mg. One hundred thirty-nine subjects (99 with IDC, 40 with ISCDC) tolerated challenge and were randomized to treatment with placebo or bucindolol 12.5 mg/d (low dose), 50 mg/d (medium dose), or 200 mg/d (high dose). At the end of 12 weeks, left ventricular function and other parameters were measured and compared with baseline values. There was a dose-related improvement in left ventricular function in bucindolol-treated subjects. In the high-dose bucindolol group, radionuclide-measured LVEF improved by 7.8 EF units (%) compared with 1.8 units in the placebo group (P < .05), and compared with the placebo group, a greater percentage of subjects had an increase in LVEF by > or = 5 units. In contrast, all three bucindolol doses prevented deterioration of myocardial function as defined by an LVEF decline of > or = 5 units.In heart failure from systolic dysfunction, beta-blockade with bucindolol produces a dose-related improvement in and prevents deterioration of left ventricular function.
967. Transgenic Genomic Reporter Assays for Functional Studies and Stem Cell Therapy
Authors: Joseph P. Sarsero, Samuel McLenachan, Timothy P. Holloway, Lingli Li, Kerry J. Fowler, Ivan Bertoncello, Lucille Voullaire, Sophie Gazeas, Panos A. Ioannou
Journal: Molecular Therapy (2005)

The development of Genomic Reporters Assays (GRAs), in which a reporter fusion is made to a gene in the context of its entire genomic locus on a Bacterial Artificial Chromosome (BAC) clone, preserves the normal location and spacing of many cis-acting regulatory elements that may be positioned over large distances in the surrounding chromosomal region, and facilitate the recapitulation of normal gene expression patterns. The generation of transgenic mice containing human genomic reporters readily facilitates the evaluation of developmental and tissue specific aspects of human gene expression in a whole animal model.
Functional Lecithin: Cholesterol Acyltransferase Is Not Required for Efficient Atheroprotection in Humans
Authors: L. Calabresi, D. Baldassarre, S. Castelnuovo, P. Conca, L. Bocchi, C. Candini, B. Frigerio, M. Amato, C. R. Sirtori, P. Alessandrini, M. Arca, G. Boscutti, L. Cattin, L. Gesualdo, T. Sampietro, G. Vaudo, F. Veglia, S. Calandra, G. Franceschini
Journal: Circulation (2009)

Mutations in the LCAT gene cause lecithin:cholesterol acyltransferase (LCAT) deficiency, a very rare metabolic disorder with 2 hypoalphalipoproteinemia syndromes: classic familial LCAT deficiency (Online Mendelian Inheritance in Man No. 245900), characterized by complete lack of enzyme activity, and fish-eye disease (Online Mendelian Inheritance in Man No. 136120), with a partially defective enzyme. Theoretically, hypoalphalipoproteinemia cases with LCAT deficiency should be at increased cardiovascular risk because of high-density lipoprotein deficiency and defective reverse cholesterol transport.The extent of preclinical atherosclerosis was assessed in 40 carriers of LCAT gene mutations from 13 Italian families and 80 healthy controls by measuring carotid intima-media thickness (IMT). The average and maximum IMT values in the carriers were 0.07 and 0.21 mm smaller than in controls (P=0.0003 and P=0.0027), respectively. Moreover, the inheritance of a mutated LCAT genotype had a remarkable gene-dose-dependent effect in reducing carotid IMT (P=0.0003 for average IMT; P=0.001 for maximum IMT). Finally, no significant difference in carotid IMT was found between carriers of LCAT gene mutations that cause total or partial LCAT deficiency (ie, familial LCAT deficiency or fish-eye disease).Genetically determined low LCAT activity in Italian families is not associated with enhanced preclinical atherosclerosis despite low high-density lipoprotein cholesterol levels. This finding challenges the notion that LCAT is required for effective atheroprotection and suggests that elevating LCAT expression or activity is not a promising therapeutic strategy to reduce cardiovascular risk.
Long-term ethanol administration alters the degradation of acetaldehyde adducts by liver endothelial cells
Authors: G M Thiele, J A Miller, L W Klassen, D J Tuma
Journal: Hepatology (1996)

Previous reports have shown that long-term ethanol administration alters receptor-mediated endocytosis (RME) of a variety of macromolecules by liver endothelial cells (LEC). Acetaldehyde is the major metabolic product of ethanol metabolism and has been shown to bind to proteins to form adducts. In this study, the level of protein modification by acetaldehyde necessary for the uptake and degradation of acetaldehyde-modified proteins by LEC was investigated. Bovine serum albumin (BSA) acetaldehyde adducts were prepared by incubation of albumin with acetaldehyde at 100 mmol/L for 1 hour at 37 degrees C, and 1 mmol/L or 0.2 mmol/L for 5 days at 37 degrees C. In situ liver perfusion in the presence of these adducts resulted in the degradation of 107 +/- 10.02 microg, 69.82 +/- 5 microg, and 2.5 +/- 0.42 microg of acetaldehyde-adducted albumin, respectively, during a 4-hour period. These values were decreased by 53%, 67%, and nearly 100%, respectively, in livers from ethanol-fed rats. Additionally, modification of protein with 1 mmol/L of acetaldehyde for different periods of time and/or pH altered the amount of 14C-acetaldehyde binding, but no significant changes in degradation were observed. Finally, an excess of formaldehyde-modified albumin totally inhibited the degradation of acetaldehyde adducts, suggesting that they use the same receptor. These data show that acetaldehyde-modified proteins may be taken up and degraded by the scavenger receptor on LEC. This uptake and degradation are dependent on the extent modification of the protein by acetaldehyde, and long-term ethanol consumption decreases the degradation of acetaldehyde-protein adducts.