tbuckley/cabot-search huggingface dataset:
A novel nuclear variant of Bmp4
Authors: Trina Sudweeks, Laura Bridgewater
Journal: Cancer Research (2007)

3790  The transforming growth factor beta (TGFβ) superfamily is responsible for several growth pathways that promote differentiation and proliferation. There are over 100 members in the TGFβ family. One such protein is bone morphogenetic protein 4 (Bmp4), a growth factor that regulates gene expression. Bmp4 is synthesized as a preproprotein, which is cleaved while in the secretory pathway and dimerizes to form a mature growth factor that functions via the SMAD signaling pathway. Bmp4 induces ectopic bone formation and is also involved in forebrain development, inner ear development, and mesoderm formation. Bmp4 has also been identified as an important factor in several cancers, including melanoma, ovarian cancer, and colon cancer. Interestingly, Juan Madoz-Gurpide et al. (Molecular & Cellular Proteomics, 2006) observed Bmp4 in the nuclei of a minor percentage of cells in colon cancer tissues. In addition, we have recently discovered a nuclear variant of Bmp2 (nBmp2), the TGFβ family member most closely related to Bmp4. These observations led us to hypothesize that a nuclear variant of Bmp4 also exists. To test this hypothesis, we produced a Bmp4/GFP fusion protein expression plasmid and transfected it into rat chondrosarcoma (RCS) cells. The fusion protein was, indeed, detectable in the nucleus. Immunohistochemistry was also performed, which verified the presence of endogenous Bmp4 in the nuclei of RCS cells. Computer analysis of the Bmp4 proprotein sequence predicted several nuclear localization signals (NLS). To test the functionality of the predicted NLS sequences, we fused each one to GFP and transfected the fusion constructs into RCS cells. One predicted signal, a bipartite NLS that overlaps the site of proteolytic cleavage, was found to direct GFP to the nucleus. This result suggests that the nuclear variant of Bmp4 is an uncleaved proprotein, as protein processing would cleave and thus inactivate the bipartite NLS. Preliminary results indicate that the nuclear variant of Bmp4 is translated from an alternative start codon downstream from the signal peptide. Without the N-terminal signal peptide, the protein is translated in the cytoplasm rather than the endoplasmic reticulum and thus avoids protein processing and secretion. Instead, the bipartite NLS directs translocation to the nucleus. Nuclear Bmp4 has so far been observed in rat chondrosarcoma cells and colon cancer tissues, suggesting that this novel nuclear variant may play a role in carcinogenesis.
Negative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol-controlled clinical trial with olanzapine
Authors: G D Tollefson, T M Sanger
Journal: American Journal of Psychiatry (1997)

The authors investigated whether primary negative symptoms of schizophrenia are enduring or treatment-responsive.Previously, a double-blind, random-assignment trial of the novel antipsychotic olanzapine (in low, medium, and high dose ranges), placebo, or haloperidol (10-20 mg/day) for 335 schizophrenic inpatients was conducted for up to 52 weeks. Changes in the treatment groups from baseline to endpoint in summary scores on the Scale for the Assessment of Negative Symptoms (SANS) and several secondary measures were compared. This article describes a path analysis to determine to what extent the total treatment effect on negative symptoms was direct or indirect (i.e., mediated by differential effects on positive symptoms, extrapyramidal symptoms, or mood).Significantly greater improvement was achieved with high-dose olanzapine than with placebo or haloperidol. Olanzapine had a significantly greater direct effect than placebo on all SANS dimensions except anhedonia-asociality. Olanzapine also demonstrated a significantly greater direct effect than haloperidol on negative symptoms, especially on the dimensions of affective flattening and avolition-apathy. Olanzapine's superior effects were replicated in a subgroup with SANS-defined prominent negative symptoms (N = 116) and a subgroup with a BPRS-defined cross-sectional proxy for the deficit state (N = 117).These results suggest that the negative symptoms of schizophrenia are directly responsive to treatment. The significantly greater direct and indirect effects of olanzapine than of haloperidol on negative symptoms are likely related to olanzapine's pleotrophic pharmacology, which includes dopaminergic, serotonergic, muscarinic, and adrenergic activities. The results contribute to the hypothesis that negative symptoms may be under the influence of several neurotransmitters within one or more neuroanatomic circuits.
Investigation of the mechanism(s) of oxygen-induced ciliated epithelial loss in bovine bronchus tissue
Authors: Hanady Al-Sahib, Robert Sneyd, Roy Moate, Peter Macnaughton, John Moody
Journal: European Respiratory Journal (2014)

Although elevated oxygen fractions are used in intensive care units around the world, pathophisiological changes in the pulmonary tissue have been shown to occur, with prolonged exposure to hyperoxia. The present study aimed at evaluating and analysing the effect of hyperoxia on epithelial layer in bovine bronchus  in vitro . Lactate dehydrogenase (LDH), Thiobarbituric acid reactive substances (TBARS), comet assay, total glutathione assay and OxyBlot kit were performed to determine the relative extent of cells injury in hyperoxic condition. Cultured samples were exposed to normoxia, 21%O 2 as a control and hyperoxia, 95%O 2  with an interface surface model. The data clearly show that hyperoxia treatment has time-dependent increase in LDH released to medium ( P  -1  wet weight tissue in 95%O 2 , 188.62 ± 14.62 µmol/ g -1  wet weight tissue in 21%O 2 ), associated with about 59% increase in the tail DNA damage (18.70 ± 2.22 in 95% O 2 , 11.08 ± 1.5 in 21% O 2 ), and increased lipid peroxidation (351.92 ± 16.26 µmol g -1  wet weight tissue in hyperoxic group, 247.35 ± 10.84 µmol g -1  wet weight tissue in normoxic group). Furthermore, oxidative proteins increased significantly  P
Book: The Government's Annual Report 98/99
Authors: R. Klein
Journal: BMJ (1999)

The prime minister Stationery Office Books, £2.99, pp 88 ISBN 0 10 144012 X Rating: ![Graphic][1]</img> One of the occupational diseases of all parliamentary ministers, whatever their party, is a chronic sense of being misunderstood and unappreciated. If only they could speak directly to the public, if only they could break through the distorting screen of the media, then their real achievements would be understood and applauded. With their policies and actions constantly being misinterpreted, as they see it, they search out every opportunity to put the record straight From this flows the concern with managing and massaging the media From this springs the eagerness of ministers to rush to the radio and television studios, whatever the hour. From this, too, comes one of the innovations of the Blair era: the government's annual report to the people. The aim of this, as the prime minister explains in his introduction to … [1]: /embed/inline-graphic-1.gif
Image of various providers of sexual health care varies
Authors: A. Pallecaros, A. Robinson, J Greenaway, D Holland
Journal: BMJ (1996)

An opportunistic survey of 1000 university students determined that the students assign considerable differences to British National Health Service providers based on whether they are termed genitourinary medicine clinic sexual health clinic family planning (FP) clinic or general practitioner.  When students were asked to choose which of these providers they would go to first for help in various scenarios FP clinics were chosen for preventive needs general practitioners and genitourinary clinics for symptomatic needs and sexual health clinics for both.  Students were more likely to feel that they knew what went on in a FP clinic or a general practitioners office than in a sexual health clinic or genitourinary medicine clinic.  A coordinated strategy for providing services to young people can be attained through liaison and training across these four types of service provision.
Mechanism and functional role of XIAP and Mcl-1 down-regulation in flavopiridol/vorinostat antileukemic interactions.
Authors: Roberto Rosato, Jorge Almenara, Sarah Kolla, Sonia Maggio, Stefanie Coe, Maria Gimenez, Paul Dent, Steven Grant
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3213 

The mechanism and functional significance of XIAP and Mcl-1 down-regulation in human leukemia cells exposed to the HDAC inhibitor vorinostat and the CDK inhibitor flavopiridol was investigated. Combined exposure of U937 leukemia cells to marginally toxic concentrations of vorinostat and flavopiridol resulted in a marked increase in mitochondrial damage and apoptosis accompanied by pronounced reductions in XIAP and Mcl-1 mRNA and protein. Down-regulation of Mcl-1 and XIAP expression by vorinostat/flavopiridol was associated with enhanced inhibition of phosphorylation of RNA PolII and was amplified by caspase-mediated protein degradation. Chromatin immunoprecipitation (ChIP) analysis revealed that XIAP and Mcl-1 down-regulation were also accompanied by both decreased association of NF-κB (XIAP) and increased E2F1 association (Mcl-1) with their promoter regions, respectively. Ectopic expression of Mcl-1 but not XIAP partially protected cells from flavopiridol/vorinostat-mediated mitochondrial injury at 48 hr, but neither significantly restored clonogenic potential. Flavopiridol/vorinostat-mediated transcriptional repression of XIAP and Mcl-1, enhanced apoptosis, and loss of clonogenic potential also occurred in primary AML blasts. Together, these findings indicate that transcriptional repression of XIAP and Mcl-1 by flavopiridol/vorinostat contributes functionally to apoptosis induction at early exposure intervals, and raise the possibility that expression levels may be a useful surrogate marker for activity in current trials.
Abstract 3551: Waist Circumference, Body Mass Index, and Their Association with Cardiometabolic and Global Risk Among Whites and Racial/Ethnic Minorities
Authors: Allison H Christian, Lori Mosca
Journal: Circulation (2007)

Purpose : To determine if waist circumference (WC) or body mass index (BMI) is more strongly associated with cardiometabolic risk factors among family members of patients hospitalized for cardiac disease, overall and by race/ethnicity. Methods : Participants in the NHLBI F amily I ntervention T rial for Heart Health ( F.I.T. Heart ) were included in this analysis (n=472; mean age 48±14 years, 67% female, 36% non-white). Height, weight, WC, BMI, blood pressure, high density lipoprotein (HDL)-cholesterol, triglycerides, fasting glucose, and c-reactive protein (hs-CRP) were systematically measured in all participants. Global risk was calculated using the Framingham function. Results : The prevalence of cardiometabolic risk factors and their association with WC and BMI is shown in Table 1 . The most common correlate of increased WC and BMI was elevated hs-CRP. Overall, increased WC was the strongest correlate of glucose≥100 and hs-CRP≥3.0. BMI≥25 was the strongest predictor of blood pressure≥140/90, low HDL, triglycerides≥150, and global risk≥10%. Among non-whites, increased WC did not identify those with blood pressure≥140/90, glucose≥100 or global risk≥10% and BMI≥25 did not identify those with low HDL or glucose≥100. There was a significant interaction between race/ethnicity and increased BMI in predicting low HDL (p&lt;0.01), with a stronger correlation in whites than non-whites. Conclusions : The prevalence of cardiometabolic risk factors and their correlation with WC and BMI varies by race/ethnicity. Our data support inclusion of both WC and BMI in screening guidelines for diverse populations to identify individuals at increased cardiometabolic and global risk. Table 1. Prevalence of and Association between Indices of Obesity and Cardiometabolic Risk
Abstract 52: Associations of Nonalcoholic Fatty Liver Disease with Subclinical Myocardial Dysfunction: The CARDIA Study
Authors: Lisa B VanWagner, Jane E Wilcox, Laura A Colangelo, Donald M Lloyd-Jones, J J Carr, Joao A Lima, Cora E Lewis, Sanjiv J Shah
Journal: Circulation (2014)

Background: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition with high cardiovascular morbidity. NAFLD patients often have echocardiographic features of left ventricular (LV) diastolic dysfunction. In a large population-based cross-sectional sample of black and white adults free from prevalent liver or heart disease, we tested the hypothesis that NAFLD is associated with subclinical myocardial dysfunction independent of BMI or visceral adipose tissue (VAT). Methods: Participants from the Coronary Artery Risk Development in Young Adults study (Y25 exam; age 43-55 years) with concurrent CT quantification of liver fat and tissue Doppler echocardiography with myocardial strain measured by speckle tracking were included (n=2,572). NAFLD was defined as liver attenuation ≤ 40 Hounsfield units after exclusion of other causes of liver fat (medication/alcohol use). Linear regression models were used to test associations. Results: NAFLD prevalence was 9.9%. NAFLD participants were more likely to be male (57.1% vs. 41.5%), white (57.5% vs. 50.6%), and had higher BMI (36.3 vs. 29.8 kg/m2) and VAT (222.4 vs. 120.5 cm3) than non-NAFLD. Those with NAFLD also had lower e’ tissue velocity (10.8 vs. 11.9 cm/s), lower E/A ratio (1.2 vs. 1.3), and higher E/e’ ratio (8.4 vs. 7.7). Increased LV mass, left atrial area, LV relative wall thickness, and cardiac output (CO) were present in NAFLD. Global longitudinal strain was also worse in NAFLD (-14.2% vs. -15.2%, all p&lt;0.05). In multivariable analyses adjusted for demographics, health behaviors and BMI, the associations of NAFLD with markers of subclinical myocardial dysfunction were attenuated but remained significant (Table 1). Only e’ velocity, LV mass and CO remained significant after adjustment for VAT. Effect modification by race and sex was not statistically significant. Conclusion: NAFLD is associated with subclinical myocardial dysfunction independent of BMI. Attenuation of the relationship by VAT supports the hypothesis that VAT may be a marker of NAFLD.
Abstract 923: Nitric oxide signaling pathway as a pathogenic driver in pancreatic cancer
Authors: Jian Wang, Peijun He, Matthias M. Gaida, Shouhui Yang, Aaron Schetter, Jochen Gaedcke, Michael Ghadimi, Thomas Ried, Harris G. Yfantis, Dong H. Lee, Jonathan M. Weiss, Nadar Hanna, H. Richard Alexander, S. Perwez Hussain
Journal: Cancer Research (2015)

Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is among the most malignant cancers, with 5-year survival of 6%. Chronic inflammation is associated with increased risk of PDAC. Nitric oxide (NO) is an important mediator of inflammatory responses and plays a role in tumorigenesis. The principal source of an increased and sustained level of NO is inducible nitric oxide synthase (NOS2). In this study, we’ve tested the hypothesis that NO enhances tumor progression in pancreatic cancer. We found that higher NOS2 expression in tumors was associated with poor survival in resected PDAC patients (p = 0.011). We then investigated the role of NO by deleting NOS2 gene in a genetically engineered mouse model of pancreatic cancer (KPC mice) with pancreas-specific activation of mutant KRAS and P53, which faithfully recapitulates the development and progression of human pancreatic cancer. NOS2-deficient KPC mice showed longer survival compared to the KPC littermates with wildtype NOS2 (p&amp;lt;0.01). Compared to tumors from KPC mice, KPC/NOS2−/− tumors were less vascularized (p&amp;lt;0.001) and with less macrophage recruitment (p&amp;lt;0.005), indicated by decreased expression of CD31 and F4/80 respectively. NOS2 deficiency led to attenuated proliferation and invasion, and enhanced apoptosis indicated by high level of cleaved caspase-3 (p = 0.02). Consistent with the less malignant phenotype, NOS2 deficiency reduced nuclear pERK accumulation (P = 0.034) and the subsequent phosphorylation of FOXO3 (p = 0.026). Further investigation showed a positive correlation between NOS2 expression and pFOXO level in human PDAC specimen (p = 0.005). In addition, NOS2 deficiency reduced the expression of a well known oncogenic microRNA, miR21 (p = 0.001). In summary, NOS2 gene expression in tumors is a candidate prognostic marker in resected pancreatic cancer patients, and NOS2/NO signaling may contribute to the pancreatic tumor progression by inactivating FOXO3 in KPC mice. In this ongoing study, we are further investigating the mechanistic role of NO in disease progression. Citation Format: Jian Wang, Peijun He, Matthias M. Gaida, Shouhui Yang, Aaron Schetter, Jochen Gaedcke, Michael Ghadimi, Thomas Ried, Harris G. Yfantis, Dong H. Lee, Jonathan M. Weiss, Nadar Hanna, H. Richard Alexander, S. Perwez Hussain. Nitric oxide signaling pathway as a pathogenic driver in pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 923. doi:10.1158/1538-7445.AM2015-923
Abstract P023: Burden of Hypertension, Prehypertension and Associated Lifestyle Risk Factors Among Tribals in Tribal and Urban Areas in the Northern State of Sub-Himalayan Region of India
Authors: Dhiraj Kapoor
Journal: Circulation (2015)

Introduction: Rapid urbanization has been associated with high prevalence of hypertension in indigenous populations . Hypothesis: The study is based on the hypothesis of the effect of lifestyle changes on hypertension in nomadic tribes settled in urban areas . Objectives: To determine the prevalence of hypertension and evaluate associated risk factors in traditional tribal individuals residing in tribal areas and migrated tribals in urban areas . Methodology: It was a population based cross sectional study .The population studied were the tribals , representing the traditional people settled in mountainous terrain centuries ago leading a nomadic life and migrating from upper reaches of Himalayas to Himalayan foothills during winters .Some of them settled in urban areas . Men and women above 20 years were considered as eligible subjects . A probabilistic proportionate sampling method was used.The final sample of 8000 individuals consisting of 4000 subjects each of tribal and urban tribals were evaluated wh...
Medical Education in the United States 1972-1973
Authors: J T Shepherd
Journal: JAMA (1973)

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
Abstract 16736: Medical vs. Surgical Management of Perivalvular Abscess in Infective Endocarditis: A Propensity Analysis From the International Collaboration on Endocarditis Prospective Cohort Study (ICE-PCS)
Authors: Stuart A Dickerman, Bruno Barsic, Vivian H Chu, V G Fowler, Paul A Pappas, Arnold Bayer
Journal: Circulation (2011)

Introduction Myocardial abscess is generally regarded as an indication for surgical intervention in infective endocarditis (IE). There is little information, however, comparing outcomes with medical vs. surgical management of such periannular complications of IE. This study used the database of the ICE-PCS to perform a propensity analysis, comparing one year mortality in patients with IE and abscess subjected to either medical or surgical treatment. Methods ICE-PCS enrolled 4794 patients between 2000 and 2006, from 64 centers in 28 countries. There were 699 cases of IE with abscess. A statistical model was built to predict surgery in this cohort.158 patients who underwent surgery for abscess were matched to 158 patients who did not. These 316 patients formed the basis of the analysis. Results In the unadjusted group of 699 patients, the one-year survival with medical treatment was 45%, vs. 67% with surgical management (p&lt;.0001). Differences favoring surgery were similar whether or not the patients had poor prognostic indicators (S. aureus infection; prosthetic valve involvement; CHF). Patients with strep viridans infection, however, had similar survival with medical or surgical management (70%, 14/20 vs.77%, 65/84). In the propensity analysis, the one-year survival with medical management was 44%, compared to 58% in the surgical group (p=.0021). (See graph). Conclusion One-year survival of IE patients with abscess was superior with surgical compared to medical management. These findings support current recommendations that surgical management of perivalvular extension of infection is generally the preferred approach. Patients with strep viridans infection, however, seem to fare equally well with medical or surgical treatment.
Measurement of mood and affect in schizophrenic inpatients
Authors: Thomas J. Craig, Mary Ann Richardson, Raymond Pass, Zachary Bregman
Journal: American Journal of Psychiatry (1985)

Ratings of mood and affect using the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression, the Center for Epidemiologic Studies Depression Scale (CES-D), and an affective flattening scale in 32 male schizophrenic inpatients revealed high total scale reliability but lower intra-item reliability, especially for specific depression items. Interscale correlations suggested several dimensions of mood and affect: anxiety-depression (psychological dysphoria, motor activation, and somatic symptoms), retardation-affective blunting, thought disturbance, and hostility-suspiciousness. Correlation with a rating of extrapyramidal symptoms suggested an association with the presence of depressive symptoms. These results suggest that although adequate total scale reliability was obtained, these indexes of depression may measure different dimensions in schizophrenic patients than they do in patients with affective disorders.
Abstract 15272: Genetic Deficiency of CD40L Attenuates Diet-Induced Adipose Tissue Inflammation - but Does Not Protect From Insulin Resistance and Hepatic Steatosis in Mice
Authors: Dennis Wolf, Felix Jehle, Ingo Hilgendorf, Peter Stachon, Christoph J Binder, Christoph Bode, Andreas Zirlik, Karlheinz Peter
Journal: Circulation (2011)

Background: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L - an established marker and mediator of cardiovascular disease - induces inflammatory cytokine ...