tbuckley/cabot-search huggingface dataset:
Abstract 1656: Vegf Induces vWF Release via A VEGFR2/Tyr1175-PLC- gamma1 Pathway
Authors: Yan Xiong, Yingqing Huo, Chao Chen, Xiaofan Lu, Jincai Luo
Journal: Circulation (2008)

Many endothelial inflammatory and prothrombotic mediators are stored in and rapidly released from Weibel-Palade bodies (WPBs), endothelium-specific storage organelles upon stimulation. The von Willebrand factor (vWF), a major component inside WPBs, mediates the initial contact of platelets with the injured vessel wall and thus plays an important role in haemostasis and thrombosis. It has previously been shown that vascular endothelial growth factor (VEGF) triggers a rapid release of vWF. However, specific VEGF receptors and their potential downstream pathways involved in this process have not been carefully determined. To dissect the role of VEGF receptors in vWF release activation, we utilized two approaches: one is to use receptor-specific ligands and the other is to use a chimeric receptor approach. The ligands for VEGF receptor 2 (VEGFR2), but not VEGF receptor 1 (VEGFR1), stimulated vWF release. The predominant role of VEGFR2 in vWF release regulation was further confirmed by using a chimeric receptor approach in which the extracellular domain of the epidermal growth factor receptor was substituted for that of VEGFR1 or VEGFR2, and was then expressed in early-passage HUVECs. Further, the knockdown of phospholipase C-γ1 (PLCγ1) suppressed VEGF-triggered intracellular calcium increase and blocked VEGF-induced vWF release. In addition, the two products of PLCγ1 hydrolysis, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), are both required for VEGF-induced vWF release. Finally, combined with point mutagenesis, the responsible binding sites for PLCγ1 and their importance in VEGFR2-activated vWF release have been determined. Point mutation of a single tyrosine residue Tyr1175, a putative binding site for PLCγ1 on the C-terminus, abolished VEGFR2-activated vWF release. This study presents the first evidence that the PLCγ1 is essential for VEGF-triggered vWF release mediated through a VEGFR2/Tyr1175 pathway.
Abstract 9856: Intrinsic Cardiac Nerve Activities and Atrial Arrhythmias in Patients Recovering From Open Heart Surgery
Authors: Mark J Shen, Arthur C Coffey, Daniel S Ice, Steven J Miller, Jason B Garlie, Susan P Straka, David E Adams, David B Wagner, Changyu Shen, Lan S Chen, Shien-Fong Lin, Peng-Sheng Chen
Journal: Circulation (2011)

Introduction- Intrinsic cardiac nerve activities (ICNA) are invariable triggers of paroxysmal atrial tachyarrhythmias in ambulatory dogs. We sought to record ICNA in human patients to determine if ICNA are associated with atrial arrhythmias. Hypothesis- ICNA are associated with the development of post-operative atrial arrhythmias. Methods- The study protocol was approved by the IRB. Five patients (56±10 years old; 4 male and 1 female) undergoing open heart surgery consented for this study. Two temporary pacing electrodes were placed on the epicardial fat pad at the left superior pulmonary vein-left atrium (LSPV-LA) junction during surgery. ICNA were continuously recorded for up to 3 days after surgery. Nerve activities were considered present if there was a 3-fold increase in the amplitude over baseline noise. Results- We processed 5440 minutes of recordings (1088±1065 minutes per patient). ICNA were recorded in 10.2% of the time. We identified a total 3914 episodes of high amplitude spike discharge activity (HASDA, Figure A) and 51 episodes of low-amplitude burst discharge activity (LABDA, Figure B). A total of 872 episodes of premature atrial contractions (PACs) were noted. Of those, 308 episodes (35.8%) were preceded by ICNA (Figures A and B). In comparison, among 872 control time segments (3 min prior to the PACs), only 28 episodes (3.2%) were preceded by ICNA ( P &lt;0.001). The absence of ICNA had high specificity (96.8%) for predicting subsequent occurrence of PACs. Conclusions- ICNA can be recorded from human patients in the post-operative period. Both HASDA and LABDA are observed. There is a significant association between ICNA and subsequent PACs.
The design and synthesis of a novel series of androgen receptor antagonists leading to the discovery of the clinical candidate BMS-641988
Authors: Aaron Balog, Mark Salvati, Richard Rampulla, Soren Giese, Steven Spergel, Andrew Nation, Raj Misra, Kenneth Leavitt, Soong-Hoon Kim, Hai-Yun Xiao, Weifang Shan, Gregory Vite, Ricardo Attar, Janet Dell-John, Maria Jure-Kunkel, Jieping Geng, Cheryl Rizzo, Thomas Spires, Marco Gottardis, Stanley Krystek, Mary Obermeier, Carrie Xu, Arvind Mathur, Robert Jeyaseelan, Dan Kukral, William Foster, Stephanie Powlin, Xue-Qing Chen, Gregory Martin, David Fairfax
Journal: Cancer Research (2008)

1314   Carcinoma of the prostate (CaP) is the 2 nd  leading cause of cancer-related death in men in the United States. Androgen ablation via surgical or chemical castration or by treatment with an antiandrogen is currently the treatment of choice for advanced CaP. Although this therapy initially shows an 80-90% response rate, approximately 50% of patients progress to fatal androgen independent CaP (AI-CaP) after about 18 months of treatment. Recent advances in the field have shown that reactivation of the androgen receptor (AR) signaling pathway is the root cause for the development of AI-CaP. The identification of the role of the AR in AI-CaP suggests that new agents that act at the level of the AR may be effective in the treatment of this disease. Here will be presented structure-based design efforts to identify novel chemotypes that show potent binding to, and antagonism of, the AR. In particular, a series of [2.2.1]-oxobicyclic imide-based AR antagonists showed great promise and the structure activity relationships (SAR) of this novel series will be presented in detail. All new analogs were screened via whole cell competitive binding and transactivation assays in MB-MDA-453 cells to generate  in vitro  SAR around the wild-type AR. Promising leads from these  in vitro  assays were then screened through an immature rat prostate weight PK/PD model (IRPW, PO, QD x 4 days). Analogs showing optimal PK and PD effects in the IRPW were then tested in the human cancer xenograft model CWR22, implanted in nude mice. These approaches resulted in the identification of BMS-641988 as a development candidate for the treatment of advanced CaP.
Suicide among subjects with personality disorders
Authors: E T Isometsä, M M Henriksson, M E Heikkinen, H M Aro, M J Marttunen, K I Kuoppasalmi, J K Lönnqvist
Journal: American Journal of Psychiatry (1996)

There have been few psychological autopsy studies of suicide among individuals with personality disorders. The possible specificity of characteristics of suicide among such individuals has been little investigated.A random sample of 229 subjects who committed suicide, representing all suicide victims in Finland within a 12-month period, were comprehensively examined by using the psychological autopsy method and were diagnosed according to DSM-III-R criteria. Within this random sample the authors investigated all subjects with axis II personality disorders (N = 67) and divided them into clusters B (N = 43), C (N = 23), and A (N = 1). Individuals with clusters B and C personality disorders were separately compared with sex- and age-matched suicide victims without personality disorder, in terms of sociodemographic characteristics, comorbid axis I and III syndromes, treatment histories, previous suicide attempts, communication of suicide intent, and suicide methods.All suicide victims with a personality disorder received at least one axis I diagnosis. In 95% this included a depressive syndrome, a psychoactive substance use disorder, or both. Individuals with cluster B personality disorders were more likely than comparison subjects to have psychoactive substance use disorders (79% versus 40%) and previous nonfatal suicide attempts (70% versus 37%) and were less likely to have axis III physical disorders (29% versus 50%). Subjects with cluster C personality disorders were not found to differ from the control subjects in any of the variables examined.Suicide victims with personality disorders were almost always found to have had current depressive syndromes, psychoactive substance use disorders, or both. Suicide victims with cluster B personality disorders differed from other suicide victims in several characteristics, while those with cluster C personality disorders did not.
Constipation
Authors: Brijen J. Shah, Nisha Rughwani, Suzanne Rose
Journal: Annals of Internal Medicine (2015)

This issue provides a clinical overview of constipation, focusing on prevention, diagnosis, treatment, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.
Itraconazole Combined with Daunorubicin Synergistically Inhibit Proliferation and Enhance Apoptosis on KG-1a Cell Line through the Suppression of Hedgehog Pathway
Authors: Ruiqing Zhou, Xiaojun Xu, Jing Wang, Huiqing He, Ziwen Guo, Weichao Li, Guinian Huang, Zhijuan Ren, Qifa Liu
Journal: Blood (2014)
Abstract B50: Abrogating cholesterol esterification suppresses pancreatic cancer growth and metastasis mediated by caveolin-1
Authors: Junjie Li, Seung-Young Lee, Dongsheng Gu, Bing Song, Shaoxiong Chen, Stephen Konieczny, Timothy Ratliff, Xiaoqi Liu, Jingwu Xie, Ji-Xin Cheng
Journal: Cancer Research (2015)

Abstract Pancreatic cancer is one of the most lethal human cancers due to the lack of early diagnosis and its high propensity for metastases. Recent advances in cancer metabolism research have manifested new promises for therapy. However, cholesterol metabolism in pancreatic cancer remains poorly understood. Here, by employing label-free Raman spectromicroscopy, we found an aberrant accumulation of cholesteryl ester (CE) in human pancreatic cancer tissues and cell lines, but not in normal ones. Our biochemical study revealed that accumulation of CE is a consequence of activated PI3K/Akt/mTOR pathway. Pharmaceutical blocking and genetic knockdown of the cholesterol esterification enzyme, acyl-CoA cholesterol acyltransferase-1 (ACAT-1), reduced pancreatic cancer cell proliferation, migration and invasion rate. In an orthotopic mouse model of pancreatic cancer, ACAT-1 inhibition significantly suppressed tumor growth and metastasis. Furthermore, we showed that ACAT-1 inhibition suppressed pancreatic cancer growth and metastasis by induction of intracellular free cholesterol toxicity and down-regulation of Akt and MAPK pathway mediated by caveolin-1. Collectively, our study opens a new opportunity for treating pancreatic cancer by targeting the altered cholesterol metabolism. Citation Format: Junjie Li, Seung-Young Lee, Dongsheng Gu, Bing Song, Shaoxiong Chen, Stephen Konieczny, Timothy Ratliff, Xiaoqi Liu, Jingwu Xie, Ji-Xin Cheng. Abrogating cholesterol esterification suppresses pancreatic cancer growth and metastasis mediated by caveolin-1. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B50.
An unusual suspect: an uncommon human-specific synonymous coding variant within the UGT1A6 gene explains a GWAS signal and protects against bladder cancer
Authors: Wei Tang, Yi-Ping Fu, Jonine D Figueroa, Núria Malats, Montserrat Garcia-Closas, Nilanjan Chatterjee, Manolis Kogevinas, Dalsu Baris, Michael Thun, Jennifer L Hall, Immaculata De Vivo, Demetrius Albanes, Patricia Porter-Gill, Mark P Purdue, Laurie Burdett, Luyang Liu, Amy Hutchinson, Timothy Myers, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina Garcia-Closas, Josep Lloreta, Alison Johnson, Molly Schwenn, Margaret R Karagas, Alan Schned, Amanda Black, Eric J Jacobs, W Ryan Diver, Susan M Gapstur, Jarmo Virtamo, David J Hunter, Joseph F Fraumeni, Stephen J Chanock, Debra T Silverman, Nathaniel Rothman, Ludmila Prokunina-Olsson
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
Abstract 11087: Autoantibody Titer Directed Against β1-Adrenergic Receptors is a Predictor of Reverse Remodeling During Carvedilol Therapy for Chronic Heart Failure: Japanese Chronic Heart Failure (J-CHF) Study
Authors: Yuji Nagatomo, Tsutomu Yoshikawa, Hiroshi Okamoto, Akira Kitabatake, Masatsugu Hori
Journal: Circulation (2014)

Introduction: Autoimmune disorder is one of the features characterizing congestive heart failure (CHF) not only due to idiopathic dilated cardiomyopathy, but due to other etiologies. Autoantibody directed against β1-adrenergic receptors (β1-AAb) exerts agonist-like action inducing receptor uncoupling, and elicits persistent myocardial damage. We, therefore, attempted to determine the significance of β1-AAb in patients with CHF who received β-blocker carvedilol in the substudy of J-CHF study. Methods: In this prospective, randomized, multicenter trial, 117 patients (left ventricular ejection fraction [LVEF] ≤ 40%) with mild to moderate CHF were assigned to 2.5mg/5mg/20mg (n=38/36/43) carvedilol groups according to the target dose. Sera were collected at baseline and β1-AAb titer was determined using ELISA. Results: ELISA showed 66 patients as negative and 36/7/7/1 patients as 20-fold (x20) / x40 / x80 / x160 positive, respectively. When the study population was divided into β1-AAb high titer (≥ x40, H) and low titer (≤ x20, L) groups, there were no significant differences in vital signs or cardiac function at baseline between 2 groups. The % change of LVEF during 56 weeks after carvedilol introduction (ΔLVEF) was significantly larger in H than L (H, +85±78% vs. L, +43±65%, p=0.04). LV end-diastolic volume (LVEDV) and end-systolic volume (LVESV) decreased to a greater extent in H than L during 56 weeks (LVEDV, 182±50 to 119±43 ml vs. 202±52 to 167±58 ml, p&lt;0.005 by ANOVA; LVESV, 136±47 to 62±36 ml vs. 141±47 to 97±53 ml, p=0.048 by ANOVA). β1-AAb titer was significantly correlated with ΔLVEF and the % change of LV volume (LVEF, r=0.24, p=0.02; LVEDV, r=-0.26, p=0.02; LVESV r=-0.27, p=0.01). Multiple regression analysis demonstrated that β1-AAb titer was an independent predictor of ΔLVEF and the % changes of LV volume after adjusting for age, gender, allocated dose of carvedilol, heart rate at baseline, plasma BNP at baseline, etiology of CHF and the presence of atrial fibrillation (ΔLVEF β=0.286, p=0.01; ΔLVEDV β=-0.227, p=0.04; ΔLVESV, β=-0.250, p=0.02). Conclusions: The findings in the present study suggested that β1-AAb has a crucial role as one of the determinants of reverse remodeling during carvedilol therapy for patients with CHF.
Anaesthetists are tested under examination conditions
Authors: G. Findlay, J. Warwick
Journal: BMJ (1995)

of the genital tract significantly increases the rate of transmission of HIV.4 Genitourinary medicine services have a pivotal role in preventing HIV infection by education, counselling, and the management of other sexually transmissible infections.It is thus of particular concern that many prisons in Scotland have no specific genitourinary medicine services, and the few existing services may be under threat.Policies to reduce harm need to address all aspects of potential transmission of HIV and not to concentrate on injecting drug use to the exclusion of others.Furthermore, the provision of entirely confidential, high quality open access genitourinary medicine services to this group of people should be an important component of such policies.
Review of<i>Women With Epilepsy: A Practical Management Handbook</i>
Authors: Kan Ding
Journal: JAMA Neurology (2015)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Neurology journal
Abstract 5672: Novel SCN5A Mutations and SNP in Patients with Brugada Syndrome
Authors: Kazufumi Nakamura, Daiji Miura, Kaoru Kobayashi, Mamoru Ouchida, Kenji Shimizu, Iori Ohmori, Nobuhiro Nishii, Satoshi Nagase, Hiroshi Morita, Yoshiki Hata, Takefumi Oka, Kengo Kusano, Tohru Ohe
Journal: Circulation (2008)

Background: Sodium channel alpha 5 subunit (SCN5A) mutations are important genetic abnormalities of Brugada syndrome (BS). Here we report novel SCN5A mutations in patients with BS. Methods and Results: Genomic mutations in the SCN5A gene were analyzed by PCR and direct sequencing in 121 patients with BS (119 men and 2 women). Thirteen (11%) of the patients had SCN5A mutation and five (4%) of the patients had single nucleotide polymorphisms (SNP) associated with BS. Eleven patients had single point mutations, one patient had a deletion (1380 del N) and one patient had a mutation within the splicing junction (IVS21+1 g&gt;a). The whole-cell patch clamp technique revealed that four novel mutations (F532C, R814Q, G833R, R878C) showed loss of function, and peak INa of a novel SNP (L1988R) transiently expressed in HEK 293 cells was significantly reduced (P&lt;0.05). RT-PCR analysis revealed that the intronic mutation (IVS21+1 g&gt;a) resulted in exon 21 deletion of SCN5A in cardiac biopsy specimens from the patient (Figure ). Conclusions: We detected five novel SCN5A mutations (1380 del N, F532C, R814Q, G833R, R878C) and a novel disease-associated SNP (L1988R) in patients with BS. We showed a novel analysis of splicing mutation (IVS21+1 g&gt;a) that resulted in exon skipping in the heart.
Metformin Lowers The Mitochondrial Potential Of Lymphoma Cells and Its Use During Front-Line Rituximab-Based Chemo-Immunotherapy Improves The Clinical Outcome Of Diffuse Large B-Cell Lymphoma
Authors: Anil Singh, Juan Gu, Vivek Yanamadala, Myron S. Czuczman, Francisco J. Hernandez-Ilizaliturri
Journal: Blood (2013)
hnRNPH1, A differentially expressed African American prostate cancer gene induces mitogenic response via a ligand-independent activation of androgen receptor
Authors: Dingwu Jia, Rodney Davis, Krishnarao Moparty, Salima Haque, Sudesh K. Srivastav, Asim B. Abdel-Mageed
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4173 

Introduction and Objective: The causes of high incidence and mortality of prostate cancer (CaP) in African Americans (AA) as opposed to Caucasians (CS) and other ethnic groups are not well understood. We hypothesized that certain gene(s) are crucial for such ethnic disparity of CaP. Using laser capture-microdissected (LCM), suppressive subtractive hybridization (SSH) and custom array chips in tandem(SSH) on age-matched (55–60 years) and tumor grade-matched (Gleason score 6) flash-frozen specimens, we identified for the first time differential expression of heterogeneous nuclear ribnucleoprotein H1 (hnRNPH1) in 90% of tumor specimens of AA in comparison to CS patients. This study characterizes the functional significance of hnRNPH-1 in progression of CaP using AA-derived (MDA-PCa-2b), and CS-derived (PC-3) CaP cells. Methods: We employed quantitative RT-PCR (QtPCR) and immunocytochemical analysis (ICA) to measure the constitutive expression level and identify localization of hnRNPH1 in PC-3 and MDA-PCa-2b cells. The growth stimulatory effect of hnRNPH1 in both cell lines was assessed using siRNA silencing and overexpression strategies AA and CS patients. The ability of hnRNPH1 to activate androgen receptor (AR) was examined in presence or absence of the androgen (R1881) using luciferase reporter assays. Results: As opposed to CS-derived PC-3 cells, QtPCR analysis revealed a 7-fold increase in the basal level of hnRNPH1 in the AA-derived MDA-PCa-2b cells hnRNPH1 protein in MDA-PCa-2b cells was primarily localized in the nucleus as determined by ICA. Furthermore, siRNA silencing of hnRNPH1 resulted growth arrest of MDA-PCa-2b cells, but not PC-3 cells. In contrast, overexpression of hnRNPH1 stimulated a mitogenic response in CaP cells. Based on luciferase reporter assays, hnRNPH-1 overexpression caused significant transactivation of the AR in a ligand-independent manner. Conclusions: We here report for the first time the differential expression of hnRNPH1 gene in AA prostate cancer. We further demonstrate that hnRNPH1 is localized to the nucleus and is critical for stimulation of growth of AA-derived, but not CS-derived, CaP cells. Our study implicates a role for hnRNPH1 in AA prostate cancer progression and provides a new frontier for identifying relevant preventive and/or therapeutic targets for CaP in AA patients.
Abstract 16349: Mammalian Target of Rapamycin Regulates Cardiac Iron Homeostasis in vitro and in vivo through Modulation of Tristetraprolin Expression
Authors: Marina Bayeva, Arineh Khechaduri, Hossein Ardehali
Journal: Circulation (2011)

Background: Iron deficiency affects over 2 billion people worldwide and can lead to anemia, cardiomyopathy and shortened lifespan, yet the mechanisms behind it remain elusive. Here we report that m...
Impact of Metabolic Syndrome on Progression of Aortic Stenosis
Authors: Romain Capoulade, Marie-Annick Clavel, Jean G. Dumesnil, Kwan L. Chan, Koon K. Teo, James W. Tam, Nancy Côté, Patrick Mathieu, Jean-Pierre Després, Philippe Pibarot
Journal: Journal of the American College of Cardiology (2012)