tbuckley/cabot-search huggingface dataset:
Endoplasmic Reticulum Stress in the Proapoptotic Action of Edelfosine in Solid Tumor Cells
Authors: Teresa Nieto-Miguel, Rosalba I. Fonteriz, Laura Vay, Consuelo Gajate, Silvia López-Hernández, Faustino Mollinedo
Journal: Cancer Research (2007)

Abstract The endoplasmic reticulum (ER) has been posited as a potential anticancer target. The synthetic antitumor alkyl-lysophospholipid analogue edelfosine accumulates in the ER of solid tumor cells. This ER accumulation of the drug leads to the inhibition of phosphatidylcholine and protein synthesis, G2-M arrest, depletion of ER-stored Ca2+, Bax up-regulation and activation, transcriptional factor growth arrest and DNA damage–inducible gene 153 up-regulation, caspase-4 and caspase-8 activation, and eventually to apoptosis. Edelfosine prompted ER stress apoptotic signaling, but not the survival unfolded protein response. Edelfosine also induced persistent c-Jun NH2-terminal kinase (JNK) activation. Gene transfer–mediated overexpression of apoptosis signal–regulating kinase 1, which plays a crucial role in ER stress, enhanced edelfosine-induced JNK activation and apoptosis. Inhibition of JNK, caspase-4, or caspase-8 activation diminished edelfosine-induced apoptosis. Edelfosine treatment led to the generation of the p20 caspase-8 cleavage fragment of BAP31, directing proapoptotic signals between the ER and the mitochondria. bax−/−bak−/− double-knockout cells fail to undergo edelfosine-induced ER-stored Ca2+ release and apoptosis. Wild-type and bax−/−bak−/− cells showed similar patterns of phosphatidylcholine and protein synthesis inhibition, despite their differences in drug sensitivity. Thus, edelfosine-induced apoptosis is dependent on Bax/Bak-mediated ER-stored Ca2+ release, but phosphatidylcholine and protein synthesis inhibition is not critical. Transfection-enforced expression of Bcl-XL, which localizes specifically in mitochondria, prevented apoptosis without inhibiting ER-stored Ca2+ release. These data reveal that edelfosine induces an ER stress response in solid tumor cells, providing novel insights into the edelfosine-mediated antitumor activity. Our data also indicate that mitochondria are indispensable for this edelfosine-induced cell death initiated by ER stress. [Cancer Res 2007;67(21):10368–78]
Liver biopsy under ultrasound control: implications for training in the Calman era
Authors: S SHAH, J F MAYBERRY, A C B WICKS, Y REES, R J PLAYFORD
Journal: Gut (1999)

Liver biopsy is the standard procedure for the investigation of a wide range of liver pathologies. It is generally a safe procedure but mortality rates range from 1:1000 to 1:10 000.1 2Although a biopsy sample is traditionally taken “blind”, many centres now carry out biopsies under ultrasound control, and this change in technique has impacted directly on the training of general physicians and gastroenterologists. In this article, we review the evidence for the safety of a real time ultrasound guided approach against the traditional blind biopsy, and examine the implications of this change for trainee clinicians who rotate through centres who now use an ultrasound guided technique.

The basic technique for liver biopsy was first described by Sherlock in 19453; the earliest approaches used Tru-Cut and Menghini needles to remove tissue and required inpatient care for 24 hours after the procedure. More recently, liver biopsy patients have been day cases, with no evidence of increased risk.4 Histological diagnosis provides useful guidance for the future management of many liver conditions, and is particularly useful in the recommendation of interferon treatment for patients with hepatitis C. The wide availability of ultrasonography has increased the use of direct visualisation in liver biopsy which has, consequently, improved the diagnostic …
Prevalence of naturally occurring surface gene variants of hepatitis B virus in nonimmunized surface antigen–negative Chinese carriers
Authors: Jinlin Hou, Zhanghui Wang, Jinjun Cheng, Yulong Lin, George K. K. Lau, Jian Sun, Fuyuan Zhou, Jenny Waters, Peter Karayiannis, Kangxian Luo
Journal: Hepatology (2001)

Previous studies have suggested that hepatitis B virus (HBV) variants may account for the presence of HBV DNA in hepatitis B surface antigen (HBsAg)-negative patients (occult HBV infection). However, it is not known how widespread these variants are and how they influence the course of liver disease. To determine the prevalence of variants within the major hydrophilic region (MHR) of HBsAg, we investigated 2,565 subjects, including subjects with chronic hepatitis, cryptogenic cirrhosis, hemodialysis patients, and blood donors. Fifty-one of them had occult HBV infection. The entire S gene from 46 of these patients was sequenced from amplified serum HBV DNA. Forty-three percent (20 of 46) had mutations in the MHR of HBsAg. Thirty-two amino acid substitutions between positions 100-160 of the MHR of HBsAg were detected in 18 patients, and these ranged from 1 to 4 per patient. These changes involved 11 positions inside and 5 outside of the historical first and second loops of the “a” determinant, and included the following: Q101K, T115A, K122N, T123A, T126N, Q129N, G130R, T131I, M133T, F134L, C138Y, K141E, P142S, G145R, N146S, and C147F/R. Combinations of mutations were detected in 9 patients, and 7 of these have not been described before. Two further patients had insertion mutations immediately before the “a” determinant. Monoclonal antibody binding tests with the Royal Free hepatitis B surface (RFHBs) panel of antibodies revealed decreased immunoreactivity in 6 novel variants of HBsAg. The existence of patients with occult HBV infection caused by HBsAg variants, therefore, has implications for their possible transmission through sexual contact and by blood transfusion.
Causation and Disease: A Chronological Journey
Authors: Myron E. Wegman
Journal: JAMA (1994)

Establishing causation of disease has been one of Alfred Evans' major concerns throughout his distinguished career. In this personalized and interesting monograph he brings historical perspective to his thoughts on determining whether a particular agent or factor causes a particular disease or condition. A distinctive part of  presentation is attention to  personalities of  players, a technique that makes  story more lively. Many illustrations, both drawings and photographs, help bring a human touch. the justification for seeking control of cigarette smoke in attacking lung cancer without necessarily knowing  precise etiologic chain  Evans starts with  Bible and leprosy, moves quickly to Fracastoro and syphilis, and then describes four pre-bacteriology epidemics, scurvy and lead colic in  18th century and cholera and puerperal sepsis in  19th, as examples of how astute observers deduced causation. Evans uses  reasoning process of  four heroes—James Lind, George Baker,
No convincing evidence for a biological preparedness explanation of phobias
Authors: Peter J. de Jong, Harald Merckelbach
Journal: Behavioral and Brain Sciences (1997)

The nonrandom distribution of fears is not as clearly related to phylogenetically survival relevance as preparedness theory seems to imply. Although delayed extinction reflects some of the best human evidence for preparedness, even this phenomenon is not as robust as it once seemed to be. Apart from the evidence reviewed by Davey, recent studies from our laboratory provide further evidence for an expectancy bias model of selective associations.
Influence of Prolonged Hypothermia and Hyperthermia On Myocardial Sodium, Potassium and Chloride
Authors: G. B. SPURR, GEORGE BARLOW
Journal: Circulation Research (1959)

In dogs cooled to 25 C. and in animals maintained at this rectal temperature for 2 and 4 hours there was a progressive increase in K and decrease in Na content of the left ventricular muscle, with no change in total Cl and H 2 O. Animals heated to a rectal temperature of 41.5 C. for 1 hour exhibited an elevated total K and no change in total Na, Cl and H 2 O contents of the myocardium.
Heart Failure and Arteriovenous Fistula
Authors: SOHAN L. DUA
Journal: Annals of Internal Medicine (1974)

Letters1 May 1974Heart Failure and Arteriovenous FistulaSOHAN L. DUA, M.D.SOHAN L. DUA, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-5-671 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The Cimino-Brescia (1) fistula has been claimed to be one of the great advances in the technique of hemodialysis. A modification (2) with saphenous vein graft has been devised. Although it is generally accepted that the increased cardiac output produced by the fistula is not clinically significant (1, 3), a few cases of congestive heart failure have been reported (4, 5). A similar case of a patient who went into acute heart failure after the construction of such a saphenous vein graft arteriovenous fistula is reported here.In 1963, a 63-year-old Chinese man was treated with diuretic...References1. BRESCIACIMINOAPPEL MJK: Chronic hemodialysis using venipuncture and a surgically created arteriovenous fistula. N Engl J Med 275:1089-1092, 1966 CrossrefMedlineGoogle Scholar2. GIRARDETHACKETTGOODWIN RRN: Thirteen months experience with the saphenous vein graft arteriovenous fistula for maintenance hemodialysis. Trans Am Soc Artif Intern Organs 16:285-291, 1970 MedlineGoogle Scholar3. WALSH A: The Cimino-Brescia fistula, in Dialysis and Renal Transplantation, vol. 5. Amsterdam, Excerpta Medica Foundation, 1969, pp. 391-404 Google Scholar4. AHEARNMAHER DJ: Heart failure as a complication of hemodialysis arteriovenous fistula. Ann Intern Med 77:201-204, 1972 LinkGoogle Scholar5. DRAUR R: Heart failure and dialysis fistula (letter). Ann Intern Med 79:765, 1973 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: SOHAN L. DUA, M.D.Affiliations: Kaiser-Permanente Medical Center Sacramento, California 95825 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1974Volume 80, Issue 5Page: 671-671KeywordsCardiac outputDiureticsFistulasHeart failureVeins ePublished: 1 December 2008 Issue Published: 1 May 1974 PDF downloadLoading ...
Impact of Stent Overlap on Angiographic and Long-Term Clinical Outcome in Patients Undergoing Drug-Eluting Stent Implantation
Authors: Lorenz Räber, Peter Jüni, Lukas Löffel, Simon Wandel, Stéphane Cook, Peter Wenaweser, Mario Togni, Rolf Vogel, Christian Seiler, Franz Eberli, Thomas Lüscher, Bernhard Meier, Stephan Windecker
Journal: Journal of the American College of Cardiology (2010)
Fine Particulate Matter Components and Emergency Department Visits for Cardiovascular and Respiratory Diseases in the St. Louis, Missouri–Illinois, Metropolitan Area
Authors: Stefanie Ebelt Sarnat, Andrea Winquist, James J. Schauer, Jay R. Turner, Jeremy A. Sarnat
Journal: Environmental Health Perspectives (2015)

Background:Given that fine particulate matter (≤ 2.5 μm; PM2.5) is a mixture of multiple components, it has been of high interest to identify its specific health-relevant physical and/or chemical features.Objectives:We conducted a time-series study of PM2.5 and cardiorespiratory emergency department (ED) visits in the St. Louis, Missouri–Illinois metropolitan area, using 2 years of daily PM2.5 and PM2.5 component measurements (including ions, carbon, particle-phase organic compounds, and elements) made at the St. Louis-Midwest Supersite, a monitoring site of the U.S. Environmental Protection Agency Supersites ambient air monitoring research program.Methods:Using Poisson generalized linear models, we assessed short-term associations between daily cardiorespiratory ED visit counts and daily levels of 24 selected pollutants. Associations were estimated for interquartile range changes in each pollutant. To allow comparison of relationships among multiple pollutants and outcomes with potentially different lag structures, we used 3-day unconstrained distributed lag models controlling for time trends and meteorology.Results:Considering results of our primary models, as well as sensitivity analyses and models assessing co-pollutant confounding, we observed robust associations of cardiovascular disease visits with 17α(H),21β(H)-hopane and congestive heart failure visits with elemental carbon. We also observed a robust association of respiratory disease visits with ozone. For asthma/wheeze, associations were strongest with ozone and nitrogen dioxide; observed associations of asthma/wheeze with PM2.5 and its components were attenuated in two-pollutant models with these gases. Differential measurement error due to differential patterns of spatiotemporal variability may have influenced patterns of observed associations across pollutants.Conclusions:Our findings add to the growing field examining the health effects of PM2.5 components. Combustion-related components of the pollutant mix showed particularly strong associations with cardiorespiratory ED visit outcomes.Citation:Sarnat SE, Winquist A, Schauer JJ, Turner JR, Sarnat JA. 2015. Fine particulate matter components and emergency department visits for cardiovascular and respiratory diseases in the St. Louis, Missouri–Illinois, metropolitan area. Environ Health Perspect 123:437–444; http://dx.doi.org/10.1289/ehp.1307776
Complications of Therapy and a Diagnostic Dilemma Case
Authors: P. Cackett, J. Stebbing, B. Dhillon
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.02.068 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 14673055 Complications of Therapy and a Diagnostic Dilemma Case CASE 1. RADIATION MACULOPATHY FOLLOWING TREATMENT OF NASOPHARYNGEAL CARCINOMA P. CackettxP. CackettSearch for articles by this author , J. StebbingxJ. StebbingSearch for articles by this author , B. DhillonxB. DhillonSearch for articles by this author Show More Princess Alexandra Eye Pavillion, Edinburgh, Scotland, UK https://doi.org/10.1200/JCO.2003.02.068 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Traumatic arteriovenous fistula of the superficial temporal vessels: a case for protective headgear when playing squash?
Authors: S R Stubington, K M Rigg
Journal: British Journal of Sports Medicine (1995)

A 35 year old semiprofessional squash player developed the symptoms and signs of an arteriovenous fistula of the left superficial temporal vessels after a squash ball injury. This was sufficiently symptomatic to halt his intensive training programme and required exploration, ligation and excision. Although a rare injury from any cause this would have been prevented by protective headgear.
Novel Lipogenic Enzyme ELOVL7 Is Involved in Prostate Cancer Growth through Saturated Long-Chain Fatty Acid Metabolism
Authors: Kenji Tamura, Asami Makino, Françoise Hullin-Matsuda, Toshihide Kobayashi, Mutsuo Furihata, Suyoun Chung, Shingo Ashida, Tsuneharu Miki, Tomoaki Fujioka, Taro Shuin, Yusuke Nakamura, Hidewaki Nakagawa
Journal: Cancer Research (2009)

Abstract A number of epidemiologic studies have indicated a strong association between dietary fat intake and prostate cancer development, suggesting that lipid metabolism plays some important roles in prostate carcinogenesis and its progression. In this study, through our genome-wide gene expression analysis of clinical prostate cancer cells, we identified a novel lipogenic gene, ELOVL7, coding a possible long-chain fatty acid elongase, as overexpressed in prostate cancer cells. ELOVL7 expression is regulated by the androgen pathway through SREBP1, as well as other lipogenic enzymes. Knockdown of ELOVL7 resulted in drastic attenuation of prostate cancer cell growth, and it is notable that high-fat diet promoted the growth of in vivo tumors of ELOVL7-expressed prostate cancer. In vitro fatty acid elongation assay and fatty acid composition analysis indicated that ELOVL7 was preferentially involved in fatty acid elongation of saturated very-long-chain fatty acids (SVLFA, C20:0∼). Lipid profiles showed that knockdown of ELOVL7 in prostate cancer cells affected SVLFAs in the phospholipids and the neutral lipids, such as cholesterol ester. Focusing on cholesterol ester as a source of de novo steroid synthesis, we show that ELOVL7 affected de novo androgen synthesis in prostate cancer cells. These findings suggest that EVOLV7 could be involved in prostate cancer growth and survival through the metabolism of SVLFAs and their derivatives, could be a key molecule to elucidate the association between fat dietary intake and prostate carcinogenesis, and could also be a promising molecular target for development of new therapeutic or preventive strategies for prostate cancers. [Cancer Res 2009;69(20):8133–40]
Switching statins: How to do it without tears and to benefit the NHS
Authors: Thomas Lau
Journal: BMJ (2006)

Contraction and convergence: myth and realityEditor-The review of climate change issues in the BMJ of 10 June was comprehensive.On grounds of morality, the principle of contraction and convergence is unassailable. 1 In the real world, it is a pipe dream.It would work only by being enforcible, which implies an international policing authority with real teeth.Can we seriously believe that the United States, China, or Russia would submit to such an authority?Sadly there is no mileage in morality when affluent lifestyles are threatened.It is right to plead for changes in individual behaviour, but only the de-carbonising of energy at source will make a predictable and sustained impact on carbon dioxide emissions.The only long term route to this goal will be through the adoption of renewable energy technologies on two levels.Firstly, small scale to micro-generation systems are rapidly approaching market viability.Within five to 10 years, millions of homes could become cost effective mini-power stations linked to a local mini-grid under the umbrella of distributed generation.The Energy Saving Trust estimates that this sector could meet 40% of UK electricity demand. 2 Secondly, base load electricity could be provided by gigawatt scale technologies mostly drawing energy from wind, rivers, and seas.Tidal stream, tidal estuary, tidal impoundment, wave power, and offshore wind could more than match the output of today's nuclear power. 3 In the short term, "balancing power" to compensate for intermittency would be provided by combined cycle gas power plants.In the longer term, surplus electricity, which is an intrinsic problem with renewables, will be directed to producing hydrogen for grid connected gigawatt scale fuel cells in a symbiotic coupling with high energy density renewables installations.All this will, of course, depend on massive government investment, but so would nuclear energy.On the demand side, buildings are the biggest carbon culprits.The only effective answer, embracing both new and existing buildings, is the concept of the carbon budget, enforcible by law.This could also be adapted for transport.These have complex implications, perhaps for another time.
Calpastatin Counteracts Pathological Angiogenesis by Inhibiting Suppressor of Cytokine Signaling 3 Degradation in Vascular Endothelial Cells
Authors: Takuro Miyazaki, Yoshitaka Taketomi, Yuta Saito, Tomohiko Hosono, Xiao-Feng Lei, Joo-ri Kim-Kaneyama, Satoru Arata, Haruo Takahashi, Makoto Murakami, Akira Miyazaki
Journal: Circulation Research (2015)

Janus kinase/signal transducer and activator of transcription (JAK/STAT) signals and their endogenous inhibitor, suppressor of cytokine signaling 3 (SOCS3), in vascular endothelial cells (ECs) reportedly dominate the pathological angiogenesis. However, how these inflammatory signals are potentiated during pathological angiogenesis has not been fully elucidated. We suspected that an intracellular protease calpain, which composes the multifunctional proteolytic systems together with its endogenous inhibitor calpastatin (CAST), contributes to the JAK/STAT regulations.To specify the effect of EC calpain/CAST systems on JAK/STAT signals and their relationship with pathological angiogenesis.The loss of CAST, which is ensured by several growth factor classes, was detectable in neovessels in murine allograft tumors, some human malignant tissues, and oxygen-induced retinopathy lesions in mice. EC-specific transgenic introduction of CAST caused downregulation of JAK/STAT signals, upregulation of SOCS3 expression, and depletion of vascular endothelial growth factor (VEGF)-C, thereby counteracting unstable pathological neovessels and disease progression in tumors and oxygen-induced retinopathy lesions in mice. Neutralizing antibody against VEGF-C ameliorated pathological angiogenesis in oxygen-induced retinopathy lesions. Small interfering RNA-based silencing of endogenous CAST in cultured ECs facilitated μ-calpain-induced proteolytic degradation of SOCS3, leading to VEGF-C production through amplified interleukin-6-driven STAT3 signals. Interleukin-6-induced angiogenic tube formation in cultured ECs was accelerated by CAST silencing, which is suppressible by pharmacological inhibition of JAK/STAT signals, antibody-based blockage of VEGF-C, and transfection of calpain-resistant SOCS3, whereas transfection of wild-type SOCS3 exhibited modest angiostatic effects.Loss of CAST in angiogenic ECs facilitates μ-calpain-induced SOCS3 degradation, which amplifies pathological angiogenesis through interleukin-6/STAT3/VEGF-C axis.
Fatty acid amide hydrolase shapes NKT cell responses by influencing the serum transport of lipid antigen in mice
Authors: Stefan Freigang, Victoria Zadorozhny, Michele K McKinney, Philippe Krebs, Rana Herro, Joanna Pawlak, Lisa Kain, Nicolas Schrantz, Kim Masuda, Yang Liu, Paul B Savage, Albert Bendelac, Benjamin F Cravatt, Luc Teyton
Journal: Journal of Clinical Investigation (2010)

The potent regulatory properties of NKT cells render this subset of lipid-specific T cells a promising target for immunotherapeutic interventions. The marine sponge glycolipid α-galactosylceramide (αGalCer) is the proto­typic NKT cell agonist, which elicits this function when bound to CD1d. However, our understanding of the in vivo properties of NKT cell agonists and the host factors that control their bioactivity remains very limited. In this report, we isolated the enzyme fatty acid amide hydrolase (FAAH) from mouse serum as an αGalCer-binding protein that modulates the induction of key effector functions of NKT cells in vivo. FAAH bound αGalCer in vivo and in vitro and was required for the efficient targeting of lipid antigens for CD1d presentation. Immunization of Faah-deficient mice with αGalCer resulted in a reduced systemic cytokine production, but enhanced expansion of splenic NKT cells. This distinct NKT response conferred a drastically increased adjuvant effect and strongly promoted protective CTL responses. Thus, our findings identify not only the presence of FAAH in normal mouse serum, but also its critical role in the tuning of immune responses to lipid antigens by orchestrating their transport and targeting for NKT cell activation. Our results suggest that the serum transport of lipid antigens directly shapes the quality of NKT cell responses, which could potentially be modulated in support of novel vaccination strategies.