tbuckley/cabot-search huggingface dataset:
Abstract 3550: Role of TNFα in the cytotoxicity of docetaxel and in docetaxel resistance in MCF-7 cells
Authors: Jason A. Sprowl, Amadeo Parissenti
Journal: Cancer Research (2010)

Abstract Taxanes such as paclitaxel and docetaxel are widely used in cancer chemotherapy regimens due to their ability to stabilize microtubules and to arrest cell division in mitosis (Chazard, 1994). While the events leading to mitotic arrest are well understood, the mechanism by which the drug induces cytotoxicity is unclear. Paclitaxel has previously been shown to promote secretion of TNFα in macrophages; however this has not been observed in other cell lines (Bogdan, 1992). TNFα induces cell death in many cell lines through interaction with its receptor TNFR1 (Hsu, 1996). TNFα also binds to a second receptor, TNFR2, which does not possess a death domain. TNFR2 does however retain the ability to induce expression of NFκB-dependent survival genes. Our laboratory group recently selected MCF-7 cells for survival in increasing concentrations (doses) of paclitaxel or docetaxel (MCF-7TAX and MCF-7TXT, respectively). Resistance was only achieved at or above selection dose 9 (3.33nM docetaxel) (Hembruff et al., 2008). MCF-7 cells were also “selected” in the absence of these drugs to control for changes simply associated with extended cell propagation. The ABC transporter inhibitor cyclosporin A either had no effect on docetaxel sensitivity at selection dose 9, or partially restored sensitivity at selection dose 12 (Hembruff, 2008). These observations suggest there are likely additional mechanisms of docetaxel resistance at selection doses 9 through 12. Interestingly, we observed that docetaxel concentrations between 1.11nM and 3.33nM induced a &amp;gt;100-fold increase in TNFα secretion from MCF-7 cells, which likely contributes to cytotoxicity. Consistent with this view, a neutralizing TNFR1 antibody decreased cytotoxicity of docetaxel in MCF-7 cells. We also discovered that MCF-7TXT and MCF-7TAX cells at or above selection dose 9 were resistant to TNFα-induced cell death. Moreover, MCF-7TXT cells displayed downregulation of TNFR1 upon the acquisition of resistance to taxanes. Increased levels of TNFα were observed within the media of MCF-7TXT cells selected to dose levels 9 and 10, but not dose levels 11 or 12. We further provide evidence that the increased levels of TNFα in the medium of MCF-7TXT cells contributes to increased cell survivability through a TNFR2-dependent activation of NFκB and its resulting increase in the expression of cell survival genes. 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 3550.
Emergency Sedation and Pain Management
Authors: Devi E. Nampiaparampil
Journal: JAMA (2008)

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
Determinants of Vancomycin Resistance and Mortality Rates in Enterococcal Bacteremia: A Prospective Multicenter Study
Authors: Emanuel N. Vergis, Mary K. Hayden, Joseph W. Chow, David R. Snydman, Marcus J. Zervos, Peter K. Linden, Marilyn M. Wagener, Barbara Schmitt, Robert R. Muder
Journal: Annals of Internal Medicine (2001)

Background: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. Objective: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. Design: Prospective observational study. Setting: Four academic medical centers and a community hospital. Patients: All patients with enterococcal bacteremia. Measurements: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. Results: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin–dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to 0.80]; P = 0.02). Conclusions: Vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival.
THE APPLIED PHYSIOLOGY OF THE EXTRAHEPATIC BILIARY TRACT
Authors: A. C. IVY
Journal: JAMA (1934)

Since an epoch in the advance of knowledge of the physiology and functional pathology of the biliary tract has been witnessed during the past decade, it is appropriate to outline the present state of information concerning it.  The gallbladder manifests, like the intestine, three types of activity: absorption, secretion and motor activity.1  ABSORPTION OR CONCENTRATION  In the process of absorption, the gallbladder concentrates the hepatic bile that enters it from four to ten times. Chiefly water and certain inorganic constituents are absorbed. In the process of absorption the bile, which is alkaline as it leaves the liver, is slightly acidified. The bile acids render the fats and cholesterol soluble at the acid reaction of gallbladder bile.  The concentrating function of the gallbladder renders it a reservoir of small volume but large capacity. In the fasting human being or dog it may store the entire twelve or twenty-four hour output
Probing the Exome in Alzheimer Disease and Other Neurodegenerative Disorders
Authors: Lars Bertram, Christine Klein
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
Targeting Fibroblast Growth Factor Pathways in Prostate Cancer
Authors: Paul G. Corn, Fen Wang, Wallace L. McKeehan, Nora Navone
Journal: Clinical Cancer Research (2013)

Advanced prostate cancer carries a poor prognosis and novel therapies are needed. Research has focused on identifying mechanisms that promote angiogenesis and cellular proliferation during prostate cancer progression from the primary tumor to bone-the principal site of prostate cancer metastases. One candidate pathway is the fibroblast growth factor (FGF) axis. Aberrant expression of FGF ligands and FGF receptors leads to constitutive activation of multiple downstream pathways involved in prostate cancer progression including mitogen-activated protein kinase, phosphoinositide 3-kinase, and phospholipase Cγ. The involvement of FGF pathways in multiple mechanisms relevant to prostate tumorigenesis provides a rationale for the therapeutic blockade of this pathway, and two small-molecule tyrosine kinase inhibitors-dovitinib and nintedanib-are currently in phase II clinical development for advanced prostate cancer. Preliminary results from these trials suggest that FGF pathway inhibition represents a promising new strategy to treat castrate-resistant disease.
L-selectin–mediated Leukocyte Adhesion In Vivo: Microvillous Distribution Determines Tethering Efficiency, But Not Rolling Velocity
Authors: Jens V. Stein, Guiying Cheng, Britt M. Stockton, Brian P. Fors, Eugene C. Butcher, Ulrich H. von Andrian
Journal: The Journal of Experimental Medicine (1999)

Adhesion receptors that are known to initiate contact (tethering) between blood-borne leukocytes and their endothelial counterreceptors are frequently concentrated on the microvilli of leukocytes. Other adhesion molecules are displayed either randomly or preferentially on the planar cell body. To determine whether ultrastructural distribution plays a role during tethering in vivo, we used pre-B cell transfectants expressing L- or E-selectin ectodomains linked to transmembrane/intracellular domains that mediated different surface distribution patterns. We analyzed the frequency and velocity of transfectant rolling in high endothelial venules of peripheral lymph nodes using an intravital microscopy model. Ectodomains on microvilli conferred a higher efficiency at initiating rolling than random distribution which, in turn, was more efficient than preferential expression on the cell body. The role of microvillous presentation was less accentuated in venules below 20 μm in diameter than in larger venules. In the narrow venules, tethering of cells with cell body expression may have been aided by forced margination through collision with erythrocytes. L-selectin transfected cells rolled 10-fold faster than E-selectin transfectants. Interestingly, rolling velocity histograms of cell lines expressing equivalent copy numbers of the same ectodomain were always similar, irrespective of the topographic distribution. Our data indicate that the distribution of adhesion receptors has a dramatic impact on contact initiation between leukocytes and endothelial cells, but does not play a role once rolling has been established.
When Doctors Say No: The Battleground of Medical Futility
Authors: Lois Snyder
Journal: Annals of Internal Medicine (1999)

Medical Writings: Book Notes4 May 1999When Doctors Say No: The Battleground of Medical FutilityLois Snyder, JDLois Snyder, JDCenter for Ethics and Professionalism, American College of Physicians-American Society of Internal Medicine, Philadelphia, Pennsylvania. (Snyder)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-9-199905040-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Rubin SB. 191 pages. Bloomington, IN: Indiana Univ Pr; 1998. $24.95. ISBN 0253334632. Order phone 800-842-6796.Field of medicine: Medical ethics.Format: Hardcover book.Audience: Bioethicists, physicians, and policymakers.Purpose: To critique arguments in the current debate over futility and explore alternatives to unilateral decision making by physicians in cases where medical treatment is deemed “futile.”Content: The book provides context for, definitions in, and analysis of the concept of medical futility. Specific chapters discuss evaluative futility judgments (“a treatment is inappropriate because it would just not be worth it”) and physiologic futility judgments (“a treatment is ineffective because it ... Author, Article, and Disclosure InformationAffiliations: Center for Ethics and Professionalism, American College of Physicians-American Society of Internal Medicine, Philadelphia, Pennsylvania. (Snyder) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 May 1999Volume 130, Issue 9Page: 787KeywordsComputer softwareDecision makingMedical ethicsPatients ePublished: 15 August 2000 Issue Published: 4 May 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
IMPACT OF TYPE 2 DIABETES ON CORONARY ATHEROSCLEROSIS RELATED TO VULNERABLE PLAQUE IN ASYMPTOMATIC PATIENTS WITHOUT CORONARY ARTERY CALCIFICATION USING MULTISLICE COMPUTED TOMOGRAPHY
Authors: Kenji Harada, Akihiro Saito, Takanobu Okumura, Norihito Kageyama, Takashi Yamamoto, Hiroyuki Fujinaga
Journal: Journal of the American College of Cardiology (2010)
Role of Gastrin in Hypersecretory Disorders in Man
Authors: J E McGuigan
Journal: Annual Review of Medicine (1974)

Secretion of hydrochloric acid by the stomach has captured the attention and research efforts of some of the most distinguished investigators in the history of gastrointestinal physiology. Enormous interest in hydrochloric acid secretion by the stomach has been retained both because of the extraordinary sequence of physiologi­ cal events that permits the stomach to concentrate hydrogen ions by more than one millionfold in gastric juice and also because of the direct clinical implications of abnormalities in rates of gastric acid secretion. A variety of common, unusual, and rare clinical syndromes and diseases are associated with disturbances in rates of acid secretion by the stomach. In several of these diseases disordered gastric acid secre­ tion appears to be of crucial importance in the initiation and/or perpetuation of the pathological process. The precise mechanism(s) by which acid secretion participates in the pathogenesis of some of these diseases, e.g. peptic ulcer, remains to be clarified in completeness. It is in relation to the control of gastric acid secretion that we direct our attention to a substance about which an enormous amount of information has been recently accumulated and which appears to play a most important role in stimulating gastric acid secretion-the polypeptide hormone gastrin.
The alpha 4 integrin chain is a ligand for alpha 4 beta 7 and alpha 4 beta 1.
Authors: P Altevogt, M Hubbe, M Ruppert, J Lohr, P von Hoegen, M Sammar, D P Andrew, L McEvoy, M J Humphries, E C Butcher
Journal: The Journal of Experimental Medicine (1995)

The heterodimeric alpha 4 integrins alpha 4 beta 7 lymphocyte Peyer's patch adhesion molecule ([LPAM]-1) and alpha 4 beta 1 (very late antigen-4) are cell surface adhesion molecules involved in lymphocyte trafficking and lymphocyte-cell and matrix interactions. Known cellular ligands include vascular cell adhesion molecule (VCAM)-1, which binds to alpha 4 beta 1 and alpha 4 beta 7, and the mucosal addressin cell adhesion molecule (MAdCAM)-1, which binds to alpha 4 beta 7. Here we show that the alpha 4 chain of these integrins can itself serve as a ligand. The alpha 4 chain, immunoaffinity purified and immobilized on glass slides, binds thymocytes and T lymphocytes. Binding exhibits divalent cation requirements and temperature sensitivity which are characteristic of integrin-mediated interactions, and is specifically inhibited by anti-alpha 4 integrin antibodies, which exert their effect at the cell surface. Cells expressing exclusively alpha 4 beta 7 (TK-1) or alpha 4 beta 1 (L1-2) both bound avidly, whereas alpha 4-negative cells did not. A soluble 34-kD alpha 4 chain fragment retained binding activity, and it inhibited lymphocyte adhesion to alpha 4 ligands. It has been shown that alpha 4 integrin binding to fibronectin involves an leucine-aspartic acid-valine (LDV) motif in the HepII/IIICS region of fibronectin (CS-1 peptide), and homologous sequences are important in binding to VCAM-1 and MAdCAM-1. Three conserved LDV motifs occur in the extracellular sequence of alpha 4. A synthetic LDV-containing alpha 4-derived oligopeptide supports alpha 4-integrin-dependent lymphocyte adhesion and blocks binding to the 34-kD alpha 4 chain fragment. Our results suggest that alpha 4 beta 7 and alpha 4 beta 1 integrins may be able to bind to the alpha 4 subunit on adjacent cells, providing a novel mechanism for alpha 4 integrin-mediated and activation-regulated lymphocyte interactions during immune responses.
Coronary-Artery Spasm Immediately after Myocardial Revascularization
Authors: Alfred E. Buxton, Sheldon Goldberg, Alden Harken, John Hirshfeld, John A. Kastor
Journal: New England Journal of Medicine (1981)

We investigated coronary-artery spasm in six patents who had had unexpected hemodynamic collapse within two hours after cardiopulmonary bypass for myocardial revascularization. All six had profound hypotension and recurrent ST-segment elevation in electrocardiographic Leads II, III, and aVF. All had either normal or noncritical luminal irregularities of dominant right coronary arteries and more than 75 per cent occlusions in the left coronary circulation. Right-coronary-artery spasm, which was reversed after intracoronary nitroglycerin, was demonstrated angiographically in one patient; a patent right coronary artery was found at autopsy in another patient. Three patients died despite large intravenous doses of nitroglycerin. Two patients who had been unresponsive to intravenous nitroglycerin recovered after direct infusion of nitroglycerin into the right coronary artery. Coronary-artery spasm immediately after myocardial revascularization may cause circulatory collapse and death; although the spasm may be refractory to usual therapy, it may respond to intracoronary nitroglycerin.
Rifaximin Is Safe and Well Tolerated for Long-term Maintenance of Remission From Overt Hepatic Encephalopathy
Authors: Kevin D. Mullen, Arun J. Sanyal, Nathan M. Bass, Fred F. Poordad, Muhammad Y. Sheikh, R. Todd Frederick, Enoch Bortey, William P. Forbes
Journal: Clinical Gastroenterology and Hepatology (2013)

Background & AimsRifaximin is a gut-selective, oral antimicrobial agent shown to reduce the recurrence of overt hepatic encephalopathy (HE) and HE-related hospitalizations in a 6-month, randomized, controlled trial (RCT). We performed a phase 3, open-label maintenance study to assess the safety and rate of hospitalization with long-term rifaximin use.MethodsWe conducted a 24-month, open-label maintenance study of rifaximin (550 mg, twice daily) in patients with HE who participated in the previous RCT of rifaximin or new patients enrolled from March 2007 to December 2010. Safety was assessed (adverse events, clinical laboratory parameters) for the integrated population of all patients, who were given rifaximin 550 mg twice daily (all-rifaximin population, N = 392). Safety and hospitalization data were compared between the group given placebo in the original RCT (n = 159) and those given rifaximin (n = 140).ResultsIn the all-rifaximin population, the median exposure to rifaximin was 427.0 days (range, 2–1427 d), with 510.5 person-years of exposure. The profile and rate of adverse events with long-term rifaximin treatment were similar to those of the original RCT. There was no increase in the rate of infections, including with Clostridium difficile, or development of bacterial antibiotic resistance. Rates of hospitalizations with long-term rifaximin administration remained low: the HE-related hospitalization rate, normalized for exposure (0.21; all-rifaximin population), was similar to that of the rifaximin group in the original RCT (0.30), and lower than that for the placebo group (0.72).ConclusionsLong-term treatment (≥24 mo) with rifaximin (550 mg, twice daily) appears to provide a continued reduction in the rate of HE-related and all-cause hospitalization, without an increased rate of adverse events. ClinicalTrials.gov number: NCT00686920.
Depression and Risk for Onset of Type II Diabetes: A prospective population-based study
Authors: William W Eaton, Haroutune Armenian, Joseph Gallo, Laurie Pratt, Daniel E Ford
Journal: Diabetes Care (1996)

OBJECTIVE To determine whether depression is associated with an increased risk for onset of diabetes. RESEARCH DESIGN AND METHODS In 1981, a total of 3,481 household-residing adults participated in the Epidemiologic Catchment Area (ECA) Program survey at the East Baltimore site. A follow-up of that cohort after 13 years completed 1,897 interviews, amounting to &amp;gt;72% of survivors. In 1981, depression was assessed with the National Institutes of Mental Health (NIMH) Diagnostic Interview Schedule and diabetes, by self-report. This prospective analysis focused on subjects at risk for onset of diabetes by removing from the analysis individuals with diabetes in 1981. RESULTS There were 89 new cases of diabetes among 1,715 individuals at risk, yielding a 13-year cumulative incidence of diabetes of 5.2%. In logistic models, major depressive disorder, but not milder forms of depression or other forms of psychiatric disorder, predicted the onset of diabetes (estimated relative risk, 2.23; 95% CI 0.90–5.55). Controlling for age, race, sex, socioeconomic status, education, use of health services, other psychiatric disorders, and body weight did not weaken the relationship. CONCLUSIONS Major depressive disorder signals increased risk for onset of type II diabetes. Limitations of the findings arise from the difficulty in determining temporal order with two chronic conditions, even when the temporal order of measurement is clear. In addition, even though control variables were introduced for the use of health services, it is possible that the treatment for depression led to an earlier diagnosis of diabetes in this sample.
Frequent demonstration of human herpesvirus 8 (HHV-8) in bone marrow biopsy samples from Turkish patients with multiple myeloma (MM)
Authors: M Beksac, M Ma, C Akyerli, M DerDanielian, L Zhang, J Liu, M Arat, N Konuk, H Koc, T Ozcelik, R Vescio, JR Berenson
Journal: Leukemia (2001)