tbuckley/cabot-search huggingface dataset:
GW28-e1208 SCN5A Mutants Associated with Familial Cardiac Sodium Overlap Syndrome Characterized as Sick Sinus Syndrome, Atrial Fibrillation, Brugada Syndrome, and Progressive Conduction Disease
Authors: Yubi Lin, Chunyu Deng, XianZhang Zhan, Zhe Xu, Jiening Zhu, Jia Chen, Fang Rao, Hui Yang, ZhiAn Zhong, Yang Liu, Feng Wang, Xin Li, Siqi He, Ruiling Feng, Zili Liao, Hai Deng, Hongtao Liao, Yueheng Wu, Yumei Xue, Bin Zhang, Guirong Li, Jianding Cheng, Zhixin Shan, Shulin Wu
Journal: Journal of the American College of Cardiology (2017)
Abstract LB-027: Evaluation of EGFR induced on-target and target-mediated adverse effects in a 3D human lung tumour/skin microphysiological co-culture system
Authors: Juliane Huebner, Marian Raschke, Katharina Schimek, Isabel Ruetschle, Sarah Graessle, Susanne Schnurre, Roland Lauster, Ilka Maschmeyer, Thomas Steger-Hartmann, Uwe Marx
Journal: Cancer Research (2019)

Abstract Organs-on-a-chip or microphysiological systems (MPS) are increasingly contributing to the preclinical characterization of mode of action and adverse events of drug candidates. The recent advent of robust human multi-organ-chip systems enables the establishment of co-cultures of human drug target tissues with healthy organ equivalents prone to off-target effects of the respective drug. The prediction of side effects, such as those occurring in the skin during cancer therapies with antibodies against the epithelial growth factor receptor (EGFR), is currently not possible in conventional in vitro systems and limited in existing animal models due to phylogenetic differences between species. Here we present a chip-based 5-day co-culture of human lung tumour spheroids (mucoepidermoid carcinoma H292) and human skin equivalents. We investigated the impact of repeated cetuximab exposure, an antibody against the EGF receptor to the co-culture and compared it with the effects on individual tissue cultures. Cetuximab showed an increased pro-apoptotic related gene expression in the tumor microtissues, and, simultaneously, proliferative keratinocytes in the basal layer of the skin microtissues were eliminated. Additionally, we compared the tumor-target related antibody effects with response data for afatinib - a small molecule EGFR inhibitor. Cetuximab showed an increased pro-apoptotic related gene expression in the tumor microtissues, and, simultaneously, proliferative keratinocytes in the basal layer of the skin microtissues were eliminated. The described MPS has the potential to provide a single platform for in vitro evaluation of the therapeutic window of drug candidates. Citation Format: Juliane Huebner, Marian Raschke, Katharina Schimek, Isabel Ruetschle, Sarah Graessle, Susanne Schnurre, Roland Lauster, Ilka Maschmeyer, Thomas Steger-Hartmann, Uwe Marx. Evaluation of EGFR induced on-target and target-mediated adverse effects in a 3D human lung tumour/skin microphysiological co-culture system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-027.
Multiple changes of immunologic parameters in prisoners of war. Assessments after release from a camp in Manjaca, Bosnia
Authors: D. Dekaris
Journal: JAMA (1993)

<h3>Objective.</h3> —To assess immune reactivity in men just released from a war prisoner camp. <h3>Participants.</h3> —Random sample of 29 men from a group of 764 liberated detainees in war prisoner camp in Bosnia, 15 matched healthy control subjects, and prewar historical control subjects. <h3>Main Outcome Measures.</h3> —Report on immune reactivity parameters, such as lymphocyte immunophenotypes, natural killer cell and phagocyte function, serum cytokines, and hormones. <h3>Results.</h3> —Compared with control subjects, detainees had significantly lowered red blood cell count, hemoglobin mass concentration, hematocrit, total serum proteins, and albumin level, while the percentage and count of monocytes and nonsegmented neutrophils were increased. Flow cytometry revealed a significant increase in percentage of activated lymphocytes, activated T lymphocytes, Tc/s lymphocytes, B lymphocytes, and total HLA-DR lymphocytes. The absolute counts of activated lymphocytes and activated T lymphocytes were also significantly increased. The percentages of naive Th/i lymphocytes and the ratio of CD4:CD8 lymphocytes were decreased. The in vitro natural killer cell cytotoxic activity and phagocytic functions of ingestion and digestion were significantly depressed. Serum interferon, serum cortisol, and prolactin were also significantly lowered. Serum tumor necrosis factor was increased. <h3>Conclusions.</h3> —Alterations in the main parameters of the immune system and depression of important immune effector functions may have resulted from the psychological stress, physical deprivation, and malnutrition experienced by these war camp prisoners during their detainment. (<i>JAMA</i>. 1993;270:595-599)
A Novel Bile Acid-Activated Vitamin D Receptor Signaling in Human Hepatocytes
Authors: Shuxin Han, Tiangang Li, Ewa Ellis, Steven Strom, John Y. L. Chiang
Journal: Endocrine Reviews (2010)

ABSTRACT Vitamin D receptor (VDR) is activated by natural ligands, 1α, 25-dihydroxy-vitamin D3 (1α, 25(OH)2-D3) and lithocholic acid (LCA). Our previous study shows that VDR is expressed in human hepatocytes, and VDR ligands inhibit bile acid synthesis and transcription of the gene encoding cholesterol 7α-hydroxylase (CYP7A1). Primary human hepatocytes were used to study LCA and 1α, 25(OH)2-D3 activation of VDR signaling. Confocal immunofluorescent microscopy imaging and immunoblot analysis showed that LCA and 1α, 25(OH)2-D3 induced intracellular translocation of VDR from the cytosol to the nucleus, and also plasma membrane where VDR co-localized with caveolin-1. VDR ligands induced tyrosine phosphorylation of c-Src and VDR, and their interaction. Inhibition of c-Src abrogated VDR ligand-dependent inhibition of CYP7A1 mRNA expression. Kinase assays showed that VDR ligands specifically activated the c-Raf/MEK1/2/ERK1/2 pathway, which stimulates serine phosphorylation of VDR and HNF4α, and their interaction. Mammalian two-hybrid assays showed a VDR ligand dependent interaction of nuclear receptor corepressor-1 (NCoR-1) and silencing mediator of retinoid and thyroid (SMRT) with VDR/RXRα. Chromatin immunoprecipitation assays revealed that an ERK1/2 inhibitor reversed VDR ligand-induced recruitment of VDR, RXRα and corepressors to human CYP7A1 promoter. In conclusion, VDR ligands activate membrane VDR signaling to activate the MEK1/2/ERK1/2 pathway, which stimulates nuclear VDR/RXRα recruitment of co-repressors to inhibit CYP7A1 gene transcription in human hepatocytes. This membrane VDR signaling pathway may be activated by bile acids to inhibit bile acid synthesis as a rapid response to protect hepatocytes from cholestatic liver injury.
Correction
Journal: Annals of the Rheumatic Diseases (2013)

A statistical error occurred in the above manuscript.On routine review of the analysis, the authors have uncovered a statistical error in their original baseline analysis that has resulted in an error in the attribution of metabolic syndrome (MetS) status to individuals in the cohort, such that a number of individuals have been misclassified by the algorithm reported.The error relates to how the authors used the coding commands in Stata for handling missing data.The authors' intention was to count the total number of MetS variables present in each individual and to allow patients with missing data to be included if they had sufficient data points to make a determination of their status.Instead, the command the authors originally used ('total') resulted in patients with any missing data being erroneously assigned a zero total for MetS components present (instead of the true number (if ≥3) or a missing status (if ≤2).This resulted in both an underestimation of the true prevalence and individuals being erroneously included in the experimental group when they should have been excluded, and thus a larger denominator group.The authors' initial manual checks of the data failed to identify this error.Correction of this error (using the command 'rowtotal') has resulted in a reduced cohort size and an overall increase in the number of patients classified as having MetS in the cohort (now 38.2% as opposed to 16% as originally reported).The prevalence estimates in all racial/ethnic subsets are therefore higher and the estimate for patients of African ancestry is particularly affected, such that the authors now report a high prevalence in this population (55.7%).Although the point estimates in the multivariate analysis of factors associated with MetS have changed, the actual factors remain very similar to the published multivariate model (see table A) and the authors' discussion of the impact of disease activity and exposure to steroids remains unchanged.In summary, the estimated prevalence of MetS in this cohort is now higher than that originally reported.The multivariate model has as a result of this changed, but remains similar to the authors' original report.Overall the key message of this paper remains the same in that "the observed ethnic variation in MetS susceptibility should help inform risk stratification in management of early disease.MetS is associated with a more severe disease phenotype and higher doses of corticosteroids, therefore balancing disease control while minimising corticosteroid exposure should be at the forefront of personalised treatment decisions in these patients".Updated tables and supplementary tables, as well as a revised abstract that summarises the corrected results accurately, are available online as a data supplement.The authors profoundly apologise for this error and feel it is important to communicate this to the research community in the interests of accuracy and scientific validity.
Correction: Guidelines for Using Antiretroviral Agents among HIV-Infected Adults and Adolescents
Journal: Annals of Internal Medicine (2002)

Corrections5 November 2002Correction: Guidelines for Using Antiretroviral Agents among HIV-Infected Adults and AdolescentsFREESearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-9-200211050-00032 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In a recent supplement article on guidelines for using antiretroviral agents among HIV-infected adults and adolescents (1), an error appeared in Table 6. In the fourth row, second column, the CD4+ T-cell count indicating initiation of antiretroviral therapy should be greater than 350/mm3 rather than less than 350/mm3.References1. . Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Ann Intern Med. 2002;137 2 5 381-433. MedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoGuidelines for Using Antiretroviral Agents among HIV-Infected Adults and Adolescents: The Panel on Clinical Practices for Treatment of HIV* Mark Dybul , Anthony S. Fauci , John G. Bartlett , Jonathan E. Kaplan , and Alice K. Pau Metrics 5 November 2002Volume 137, Issue 9Page: 778KeywordsAdolescentsAntiretroviral therapyAntiretrovirals ePublished: 5 November 2002 Issue Published: 5 November 2002 Copyright & PermissionsCopyright © 2002 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Needs for Public Health Intervention and Needs for New Research on Vinyl Halides and Their Polymers: A Public Policy Perspective
Authors: Dale Hattis
Journal: Environmental Health Perspectives (1981)

Consideration of needs for public health interventions and new research requires comparative assessments of the health benefits that are likely to result from alternative uses of limited regulatory and technical resources. This paper briefly examines regulatory and research priorities in the light of recent information on the carcinogenic hazards of vinyl chloride and alkyl and vinyl halides related to vinyl chloride, the respiratory-system hazards of poly (vinyl chloride), and the reproductive hazards of vinyl chloride. Specific suggestions are made for relatively promising types of efforts in these areas.
Aspirin's role in prevention now official
Authors: C. Marwick
Journal: JAMA (1997)

ASPIRIN is about to get broader official recognition as a useful agent in the prevention of heart attack and stroke. But it will be no news to those physicians who have been prescribing aspirin for their patients at risk of cardiovascular disease. Meeting jointly, 2 Food and Drug Administration (FDA) advisory committees, Cardio-Renal Drugs and Nonprescription Drugs, have recommended to the FDA commissioner that he approve the use of aspirin as a preventive measure in patients who are at high risk for cardiovascular disease but do not have a history of a myocardial infarction (MI) or have stable angina. Aspirin is currently recommended to reduce the risk of death or a nonfatal MI only in patients with a previous history of MI or in those with unstable angina. "When it's approved, it will be a major addition to the claims structure for aspirin. There are a lot of people with
Selective enhancement of lipid peroxidation in plasma membrane in two experimental models of liver regeneration: Partial hepatectomy and acute CCl4 administration
Authors: I Aguilar-Delfin
Journal: Hepatology (1996)

It has been proposed that lipid peroxidation (LP) might be a modulator of cell division, influencing initiation and cessation of mitosis in regenerating liver. However, the understanding of the participating role of this event in the onset of liver proliferation has been hampered by the fact that both higher or lower LP have been reported after two-thirds partial hepatectomy (PH). Therefore, the present study deals with the extent of LP in the main subcellular fractions from rat liver at early stages of regeneration, induced by either PH of 70% or acute CCl4 administration. Our results, using several methods to monitor LP, indicate a differential effect in the peroxidative pattern of specific subcellular fractions from regenerating liver after 24 hours of PH: a decrease in microsomes and an increase confined to plasma membrane and cytosolic fractions, peaking after 24 hours of PH. In CCl4-treated rats, higher LP was also noted in plasma membrane and cytosol, being maximal at the replicative stage in this experimental model (48 hours). In addition, increased LP was found in microsomal and nuclear fractions, declining before the 48 hours. In hepatectomized rats, changes in LP seem to be an organ-specific event and related to only PHs capable of triggering a synchronized proliferative response, namely above 40%. These results show that LP, promoted by PH and CCl4 administration, is qualitatively distinct among subcellular fractions and may indeed be a normal cell event of physiological importance in the regenerating liver.
In Brief
Journal: JAMA (1988)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Leads from the MMWR. Surveillance of hemophilia-associated acquired immunodeficiency syndrome
Journal: JAMA (1986)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Premature mortality from coronary heart disease. The Framingham study
Authors: T. Gordon
Journal: JAMA (1971)

Since 1948, a cohort of 5,209 residents of Framingham, Mass, have been examined biennially. In the first 14 years, 120 died of coronary heart disease (CHD) before reaching 65 years of age. Two thirds of these deaths occurred outside the hospital—the majority suddenly— within one hour of onset of the terminal event. Nearly one half of the deaths from the initial coronary attack were sudden and unexpected. One half of all persons with sudden deaths had no prior clinical heart disease. While nonsudden coronary deaths were ordinarily preceded by clinical CHD, the disease was frequently first manifest close to the final episode. Only a small percentage of persons were seriously disabled six months before their death. Even among persons with known CHD, nearly one half of the deaths occurred outside the hospital. It is concluded that the only road to a substantial reduction in premature CHD mortality is prevention of CHD.
MEMBERSHIP OF EDUCATIONAL COMMITTEES (AS OF OCT 1, 1981)
Journal: JAMA (1981)

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
BAL27862: A unique microtubule-targeted agent that severs microtubules and overcomes multifactorial drug resistance.
Authors: M. Estève, S. Honoré, N. McKay, F. Bachmann, H. Lane, D. Braguer
Journal: Journal of Clinical Oncology (2010)

e13589 Background: Microtubule-targeted agents (MTAs) are widely used to treat human malignancies. A major limitation of their efficacy is the development of resistance modulated by P-gp overexpression or tubulin and/or apoptotic pathway protein modifications. BAL27862 is a novel MTA that triggers apoptosis in cancer cells. In vitro, BAL27862 destabilizes microtubules to produce a microtubule phenotype distinct from that observed with other MTAs, and retains its antiproliferative activity against P-gp overexpressing tumor cells. BAL27862, when administered intravenously or orally, induces significant antitumor responses in a range of animal models of human cancer, including tumors refractory to conventional treatments. Methods: First, we compare the in vitro activity of BAL27862 with conventional MTAs paclitaxel (PTX) and vinblastine (VLB). The antiproliferative potency of BAL27862 was determined in a PTX- and VLB-resistant ovarian cancer cell line. Resistance was mediated by P-gp over-expression, Bcl-2 down-regulation and tubulin modifications. We then analyzed the effects of BAL27862 on microtubule dynamics (MDs) in SKBr3 breast cancer cells compared with PTX. Results: BAL27862 remained fully active against PTX- and VLB-resistant cells when compared with the chemosensitive parental line. The resistance factors observed (defined as EC50 ratio of resistant vs. parental cells) were 1.14 (NS), 147 (p<0.01) and 57 (p<0.01) for BAL27862, PTX and VLB respectively. These results confirm that BAL27862 overcomes P-gp overexpression-mediated resistance, and demonstrate that Bcl-2 status and tubulin modifications do not necessarily affect its antitumor activity. Analysis of MDs shows that BAL27862 elicited effects consistent with its destabilizing activity; suppression of MDs was 2-fold lower than observed with PTX. Strikingly, BAL27862 displayed a unique microtubule severing activity. Conclusions: Besides its microtubule-targeting activity, BAL27862 displays unique features in its mechanism of action that make it a promising compound for clinical investigation. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Basilea Pharmaceutica Basilea Pharmaceutica
Impact of hepatitis B virus-related immune reconstitution inflammatory syndrome on HBsAg loss in patients co-infected with human immunodeficiency virus
Authors: Sachiyo Yoshio, Shiori Yoshikawa, Taizo Mori, Hironari Kawai, Yuichi Yoshida, Yuriko Tsutsui, Taiji Yamazoe, Yosuke Osawa, Hiroyuki Gatanaga, Tatsuya Kanto
Journal: Journal of Hepatology (2020)
Semaine des Hôpitaux de Paris
Journal: JAMA (1964)

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