tbuckley/cabot-search huggingface dataset:
The OECD program to validate the rat uterotrophic bioassay to screen compounds for in vivo estrogenic responses: phase 1.
Authors: J Kanno, L Onyon, J Haseman, P Fenner-Crisp, J Ashby, W Owens
Journal: Environmental Health Perspectives (2001)

The Organisation for Economic Co-operation and Development has completed the first phase of an international validation program for the rodent uterotrophic bioassay. This uterotrophic bioassay is intended to identify the in vivo activity of compounds that are suspected agonists or antagonists of estrogen. This information could, for example, be used to help prioritize positive compounds for further testing. Using draft protocols, we tested and compared two model systems, the immature female rat and the adult ovariectomized rat. Data from 19 participating laboratories using a high-potency reference agonist, ethinyl estradiol (EE), and an antagonist, ZM 189,154, indicate no substantive performance differences between models. All laboratories and all protocols successfully detected increases in uterine weights using EE in phase 1. These significant uterine weight increases were achieved under a variety of experimental conditions (e.g., strain, diet, housing protocol, bedding, vehicle). For each protocol, there was generally good agreement among laboratories with regard to the actual EE doses both in producing the first significant increase in uterine weights and achieving the maximum uterine response. Furthermore, the Hill equation appears to model the dose response satisfactorily and indicates general agreement based on calculated effective dose (ED)(10) and ED(50) within and among laboratories. The feasibility of an antagonist assay was also successfully demonstrated. Therefore, both models appear robust, reproducible, and transferable across laboratories for high-potency estrogen agonists such as EE. For the next phase of the OECD validation program, both models will be tested against a battery of weak, partial estrogen agonists.
Effects of diosgenin, A plant-derived steroid, on bile secretion and hepatocellular cholestasis induced by estrogens in the rat
Authors: Luigi Accatino, Margarita Pizarro, Nancy Solís, Cecilia S. Koenig
Journal: Hepatology (1998)

Increased biliary secretion of cholesterol and lipid vesicles (unilamellae and multilamellae) induced by diosgenin (D), a plant-derived steroid, has cytoprotective effects in the rat liver subjected to obstructive cholestasis. In this study, our aims were to investigate the following: 1) the effects of D on the bile secretory process and on the cholestasis induced by estradiol-17β -(β - d -glucuronide) (E17G) or 17 α-ethynylestradiol (E) administration; 2) whether the potentially protective effects of D are related to D-induced increase of biliary cholesterol and lipid lamellae; and 3) whether D has other effects capable of modifying specific bile secretory processes or preventing the cholestatic effects of estrogens. Rats were fed a standard ground chow (control group) or chow containing D for 6 days. E17G was administered i.v. to control and D-fed rats and bile flow, bile salt output, and alkaline phosphatase excretion were examined. 17α-E was administered from days 4 to 6 to rats fed standard chow or chow plus D for 6 days and different functional parameters of the bile secretory process as well as the ultrastructure of hepatocytes and histochemistry of alkaline phosphatase and Mg 2+ -adenosine triphosphatase (ATPase) were examined. D-treatment markedly increased cholesterol and lamellar structures in bile and attenuated the acute cholestatic effects of E17G. D-feeding prevented the decrease of taurocholate maximum secretory rate and the increase of biliary alkaline phosphatase and Ca 2+ ,Mg 2+ -EctoATPase (EctoATPase) excretion, as well as the increase of cholesterol/phospholipids ratio, alkaline phosphatase activity, and EctoATPase content in canalicular plasma membranes induced by E. D-feeding did not prevent E-induced decrease of basal bile flow, bile salt, cholesterol, and phospholipid secretory rates nor the decrease of Na + ,K + -ATPase activity and Na + -taurocholate cotransporting polypeptide (Ntcp) content in isolated sinusoidal membranes. Cholestatic alterations of canalicular domain were apparent in E-treated rats. D administration was also associated with changes of ultraestructure and histochemistry of hepatocytes. E-induced alterations in ultrastructure and acinar distribution and intensity of histochemical reaction of both enzymes were partially prevented by D-feeding. We conclude that D administration, in addition to inducing a marked increase of biliary cholesterol and lipid lamellar structures output, was associated to changes in hepatocyte morphology and plasma membrane composition, enzymes activity, and histochemistry. D-feeding attenuated the acute cholestatic effects of E17G. D-induced increase of bile cholesterol and lipid lamellae content was not apparent when D-fed rats received E. Despite this fact, D administration prevented some cholestatic effects of E, probably through different metabolic effects and/or direct membrane effects, not related to increased lipid lamellae excretion.
Role of leukotrienes in leukocyte adhesion following systemic administration of oxidatively modified human low density lipoprotein in hamsters.
Authors: H A Lehr, C Hübner, B Finckh, S Angermüller, D Nolte, U Beisiegel, A Kohlschütter, K Messmer
Journal: Journal of Clinical Investigation (1991)

In vitro studies indicate that oxidatively modified low density lipoprotein (oxLDL) promotes leukocyte adhesion to the vascular endothelium, a constant feature of early atherogenesis. Using intravital fluorescence microscopy in the dorsal skinfold chamber model in awake Syrian golden hamsters, we studied whether (a) oxLDL elicits leukocyte/endothelium interaction in vivo, and whether (b) leukotrienes play a mediator role in this event. Leukocyte/endothelium interaction was assessed in the time course after intravenous injection of native human LDL (4 mg/kg body wt) and of oxLDL (7.5 microM Cu++, 6 h, 37 degrees C) into control hamsters and into hamsters, pretreated with the selective leukotriene biosynthesis inhibitor MK-886 (20 mumol/kg, i.v.). While no effect was seen after injection of native LDL, oxLDL elicited an immediate induction of leukocyte adhesion to the endothelium of arterioles and postcapillary venules. Total and differential leukocyte counts suggest that all leukocyte subsets were likewise affected by oxLDL with no specific preference for monocytes. Stimulation of leukocyte adhesion was entirely prevented in inhibitor-treated animals, suggesting the important mediator role of leukotrienes in oxLDL-induced leukocyte/endothelium interaction.
Nonspecific and specific bronchial responsiveness in occupational asthma caused by platinum salts after allergen avoidance.
Authors: R Merget, M Reineke, A Rueckmann, E M Bergmann, G Schultze-Werninghaus
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Most data about the course of occupational asthma after removal from exposure are based upon the longitudinal assessment of employees exposed to substances inducing late asthmatic reactions in bronchial provocation tests. It was the aim of this study to describe the course of immediate-type occupational asthma after allergen avoidance. Twenty-four platinum refinery workers were examined on two occasions. All subjects reported work-related asthma while they worked in the refinery department. The diagnosis of platinum salt asthma was established by a positive bronchial challenge test with hexachloroplatinic acid in each case. Eleven of the 24 subjects were still exposed to platinum salts at the time of the first investigation, but all had been removed from exposure for 19 mo (1 to 77) on the second investigation. Asthma was still reported by 17 subjects, and all but two showed bronchial hyperresponsiveness (PC50SGaw < 8 mg/ml) on the second investigation. Bronchial responsiveness to methacholine, skin reactivity, and bronchial responsiveness to platinum salt, as well as FEV1, did not change between assessments. Total serum IgE decreased from 126 to 103 U/ml (p < 0.005). Analysis of variance showed no association of the individual differences in PC50 (methacholine) between both investigations with smoking, time from the onset of symptoms to removal, time from removal to the first or second investigation, skin sensitization to environmental allergens, or total IgE. We conclude that both nonspecific and specific bronchial responsiveness do not decrease after removal from exposure in immediate-type asthma caused by platinum salts.
1144 A phase 2 clinical study evaluating safety and efficacy of Hepex-B, a mixture of two human monoclonal antibodies to HBsAg in combination with lamivudine in chronic HBV patients
Authors: E GALUN, R SAFADI, A MILCHEM, Z AKERMAN, Y ASHUR, I MATHOT, Z YOUNOSSI, G MINUK, O NUSSBAUM, D TERKIELTAUB
Journal: Hepatology (2003)
Dronedarone in Atrial Fibrillation — Jekyll and Hyde?
Authors: Stanley Nattel
Journal: New England Journal of Medicine (2011)

Atrial fibrillation, the most common type of sustained cardiac arrhythmia, is associated with increased morbidity and mortality and is often therapeutically challenging.1 Dronedarone is a recently introduced antiarrhythmic drug that was developed by modifying the structure of amiodarone in an effort to reduce toxicity and improve pharmacokinetic properties.1 Dronedarone has properties of all of the major classes of antiarrhythmic drugs.1 In the ATHENA trial (A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death from Any Cause in Patients with Atrial Fibrillation/Atrial Flutter; ClinicalTrials.gov number, NCT00174785),2 dronedarone . . .
Abstract 4056: Elevated Troponins in Heart Failure Patients: Is there an Association with Kidney Function?
Authors: Claudine Jurkovitz, William S Weintraub, Edward Ewen
Journal: Circulation (2006)

Background. Cardiac troponin Ts (cTnT) are often increased in asymptomatic patients with end-stage renal disease and are predictors of higher mortality. This increase in cTnT is likely related to l...
Reversibility of defective adipocyte insulin receptor kinase activity in non-insulin-dependent diabetes mellitus. Effect of weight loss.
Authors: G R Freidenberg, D Reichart, J M Olefsky, R R Henry
Journal: Journal of Clinical Investigation (1988)

Insulin-stimulated kinase activity of adipocyte-derived insulin receptors is reduced in subjects with non-insulin-dependent diabetes mellitus (NIDDM) but normal in obese nondiabetics. To assess the reversibility of the kinase defect in NIDDM, insulin receptor kinase activity was measured before and after weight loss in 10 NIDDM and 5 obese nondiabetic subjects. Peripheral insulin action was also assessed in vivo by glucose disposal rates (GDR) measured during a hyperinsulinemic (300 mU/M2 per min) euglycemic clamp. In the NIDDMs, insulin receptor kinase activity was reduced by 50-80% and rose to approximately 65-90% (P less than 0.01) of normal after 13.2 +/- 2.0 kg (P less than 0.01) weight loss; comparable weight loss (18.2 +/- 1.5 kg, P less than 0.01) in the nondiabetics resulted in no significant change in insulin receptor kinase activity. Relative to GDR measured in lean nondiabetics, GDR in the NIDDMs was 35% of normal initially and 67% (P less than 0.01) of normal after diet therapy; weight loss in the nondiabetics resulted in an increase in GDR from 53 to 76% of normal (P less than 0.05). These results indicate that the insulin receptor kinase defect that is present in NIDDM is largely reversible after weight reduction. In contrast, the improvement in GDR, in the absence of any change in insulin receptor kinase activity in the nondiabetics, suggests that the main cause of insulin resistance in obesity lies distal to the kinase.
THE RELATIONSHIP OF RISK FACTOR BURDEN AND THE PREVALENCE, MORPHOLOGY AND SEVERITY OF CORONARY ARTERY DISEASE IN YOUNG PATIENTS REFERRED FOR CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY
Authors: Seth Uretsky, Alan Rozanski, Azhar Supariwala, Subu Nair, Randy Cohen, Srinivasa Gurram, Sri Lakshmi Kala Bonda, Prema Bezwada, Naganath Thota, Seema Manchireddy, M. Robert Peters, Steven Wolff
Journal: Journal of the American College of Cardiology (2013)
Influence of Phase Duration of Biphasic Waveforms on Defibrillation Energy Requirements With a 70-μF Capacitance
Authors: Patrick Schauerte, Friedrich A. Schöndube, Marius Grossmann, Hilmar Dörge, Frank Stein, Bernd Dohmen, Abdel Moumen, Konstantin Erena, Bruno J. Messmer, Peter Hanrath, Christoph Stellbrink
Journal: Circulation (1998)

Background —Phase duration of biphasic shocks may be an important determinant of defibrillation success. The purpose of this study was to investigate the effect of changing phase duration of biphasic pulses delivered by 70-μF capacitors on defibrillation energy requirements. This may be clinically relevant for the optimization of implantable cardioverter-defibrillator design and programming. Methods and Results —Defibrillation thresholds (DFTs) were determined for 13 waveforms in 13 pigs by application of a 70-μF capacitance and a transvenous/submuscular lead system. In part I, phase-1 duration varied, preserving a phase-1/phase-2 duration ratio of 60%/40%. The phase-1 durations were 1, 2, 3, 4, 5, and 6 ms. The DFT was lowest (22.9±7 J) for phase 1=3 ms compared with phase 1=1 ms (36.4±7.5 J), 2 ms (25±6.5 J), 4 ms (25±7.6 J), 5 ms (30.7±7.3 J), or 6 ms (32.9±8.1 J) ( P &lt;.001). In part II, phase-1 duration was 3 ms but phase-2 duration varied: 0.7, 1.3, 2, 2.7, 3.3, 4, and 6 ms. Significant DFT minima were found at phase 2=2 ms (22.5±4.2 J) and phase 2=4 ms (22.5±4.2 J) compared with phase 2=0.7 ms (31.7±9.3 J), phase 2=3.3 ms (26.7±6.1 J), or phase 2=6 ms (28.3±6.8 J) ( P &lt;.05). Conclusions —The strength-duration curve of biphasic defibrillation shocks demonstrates a single optimum for phase-1 duration. In contrast, two optima with minimal energy requirements were found for phase-2 duration. Optimization of both phases of low-capacitance biphasic shocks may reduce energy requirements for defibrillation.
Incidence of syphilis in UK rises as HIV diagnoses hold steady
Authors: Claire Frauenfelder
Journal: BMJ (2006)

The number of new diagnoses of HIV in the United Kingdom last year was close to the 2004 figure, says a report from the Health Protection Agency, but the number of new cases of syphilis rose by 23% (from 2282 to 2816). The number of new cases of HIV was 7450 in 2005 and 7492 in 2004. 

In 2005 an estimated 63 500 adults in the UK were …
Functionally Abnormal Na+-K+ Pump in Erythrocytes of a Morbidly Obese Patient
Authors: Mario Deluise, Jeffrey S. Flier
Journal: Journal of Clinical Investigation (1982)

The Na+-K+ pump in the erythrocytes of a mordibly obese patient shows a unique constellation of functional abnormalities. The number of pump units, measured by [3H]ouabain binding to intact cells, as well as the enzymatic activity of the (Na+-K+)-dependent ATPase in erythrocyte membranes were found to be markedly increased compared with control cells (18-fold and 14-fold, respectively). There was a concomitant fivefold increase in the rate of pump-mediated uptake of 86Rubidium (a K analogue); this was balanced by an increased rate of 86Rb efflux. In striking contrast to normal cells, however, a major portion of this efflux (80%) was inhibited by ouabain, and thus appeared to be mediated by the Na+-K+ pump.
Alopeciamental retardation syndrome: clinical and molecular characterization of four patients
Authors: A. Tzschach, B. Bozorgmehr, V. Hadavi, K. Kahrizi, M. Garshasbi, M.M. Motazacker, H.-H. Ropers, A.W. Kuss, H. Najmabadi
Journal: British Journal of Dermatology (2008)
Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials
Authors: W.J. Cunliffe, R. Caputo, B. Dreno, L. Förström, M. Heenen, C.E. Orfanos, Y. Privat, A.Robledo Aguilar, J. Meynadier, Mohsen Alirezai, S. Jablonska, A. Shalita, J.S. Weiss, D.K. Chalker, C.N. Ellis, A. Greenspan, H.I. Katz, I. Kantor, L.E. Millikan, J.M. Swinehart, L. Swinyer, C. Whitmore, J. Czernielewski, M. Verschoore
Journal: Journal of the American Academy of Dermatology (1997)
Fetal Exposure to Parental Smoking and the Risk of Type 2 Diabetes in Adult Women
Authors: Vincent W.V. Jaddoe, Layla L. de Jonge, Rob M. van Dam, Walter C. Willett, Holly Harris, Meir J. Stampfer, Frank B. Hu, Karin B. Michels
Journal: Diabetes Care (2014)

OBJECTIVE We evaluated the associations of both maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters and explored whether any association was explained by weight at birth or BMI throughout life. RESEARCH DESIGN AND METHODS We used data from 34,453 participants of the Nurses’ Health Study II. We used Cox proportional hazards models to examine the associations of maternal and paternal smoking during pregnancy with incidence of type 2 diabetes in daughters between 1989 and 2009. RESULTS Maternal smoking during the first trimester only was associated with the risk of type 2 diabetes in the offspring, independent of confounders, birth weight, and later-life BMI (fully adjusted hazard ratio 1.34 [95% CI 1.01, 1.76]). In the age-adjusted models, both continued maternal smoking during pregnancy and paternal smoking tended to be associated with an increased risk of type 2 diabetes in daughters. Perinatal and adult life variables did not explain these associations, but additional adjustment for current BMI fully attenuated the effect estimates. CONCLUSIONS The associations of maternal and paternal smoking during pregnancy with the risk of type 2 diabetes in daughters were largely explained by BMI throughout the life course. Further studies are needed to explore the role of first-trimester-only maternal smoking on insulin resistance in the offspring. Also, similar effect estimates for maternal and paternal smoking suggest that the associations reflect shared family-based or lifestyle-related factors.
Have microbes, will travel
Authors: Kelley Lee
Journal: The Lancet (2007)

For most of us, our experience of crossing borders will be a queue at an airport or seaport, passport in hand, awaiting scrutiny by an immigration official. If our documents are in order, we then proceed through customs where officials cast their eyes over goods entering or leaving the country. From this occasional experience, we could be forgiven for thinking that the crossborder flow of people and goods occurs without difficulty.
Mechanisms of IFN-γ–induced apoptosis of human skin keratinocytes in patients with atopic dermatitis
Authors: Ana Rebane, Maya Zimmermann, Alar Aab, Hansjörg Baurecht, Andrea Koreck, Maire Karelson, Kristi Abram, Tauno Metsalu, Maire Pihlap, Norbert Meyer, Regina Fölster-Holst, Nikoletta Nagy, Lajos Kemeny, Külli Kingo, Jaak Vilo, Thomas Illig, Mübeccel Akdis, Andre Franke, Natalija Novak, Stephan Weidinger, Cezmi A. Akdis
Journal: Journal of Allergy and Clinical Immunology (2012)
Higher-intensity continuous renal-replacement therapy did not reduce mortality in critically ill patients with kidney injury
Authors: Chirag R. Parikh
Journal: Annals of Internal Medicine (2010)

ACP Journal Club16 February 2010Higher-intensity continuous renal-replacement therapy did not reduce mortality in critically ill patients with kidney injuryChirag R. Parikh, MD, PhD, Justin Belcher, MDChirag R. Parikh, MD, PhDYale University, New Haven, Connecticut, USA (C.R.P., J.B.)Search for more papers by this author, Justin Belcher, MDYale University, New Haven, Connecticut, USA (C.R.P., J.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-152-4-201002160-02005 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationThe RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361:1627-38. https://pubmed.ncbi.nlm.nih.gov/19846848Clinical Impact RatingsHospitalists: Critical Care: Nephrology: References1 Uchino S, Kellum JA, Bellomo R, et al; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813-8. [PMID: 16106006] Google Scholar2 Palevsky PM. Intensity of continuous renal replacement therapy in acute kidney injury. Semin Dial. 2009;22:151-4. [PMID: 19426419] Google Scholar3 VA/NIH Acute Renal Failure Trial Network, Palevsky PM, Zhang JH, et al. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008;359:7-20. [PMID: 18492867] Google Scholar Author, Article, and Disclosure InformationAffiliations: Yale University, New Haven, Connecticut, USA (C.R.P., J.B.)This article was published at Annals.org on 2 February 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byNephrologie auf der Intensivstation 16 February 2010Volume 152, Issue 4Page: JC2-5KeywordsAcute renal failureClinical trialsEffluentIntensive care unitsMedical dialysisRenal failureResuscitationUrea ePublished: 16 February 2010 Issue Published: 16 February 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Localization of the apoptosis-inducing activity of lupus anticoagulant in an annexin V-binding antibody subset.
Authors: N Nakamura, T Ban, K Yamaji, Y Yoneda, Y Wada
Journal: Journal of Clinical Investigation (1998)

Lupus anticoagulant (LAC) is associated with arterial and venous thrombosis, thrombocytopenia, and recurrent fetal loss. We have reported previously that plasma with LAC activity induces apoptosis in endothelial cells and binds annexin V (Nakamura, N., Y. Shidara, N. Kawaguchi, C. Azuma, N. Mitsuda, S. Onishi, K. Yamaji, and Y. Wada. 1994. Biochem. Biophys. Res. Commun. 205:1488-1493). In this study, we separated two IgG antibody fractions, one with and one without affinity for annexin V, from 10 patients with LAC. LAC and apoptotic activities were localized in the annexin V-binding fraction in all 10 patients. DNA fragmentation was dose-dependent, paralleling the amount of IgG added to the human umbilical vein endothelial cell culture medium, and was inhibited by preincubation with annexin V. Removal of the antiphospholipid antibodies from patient IgG with phospholipid liposomes did not abolish the apoptosis-inducing activities or binding to annexin V. These results imply that patients with LAC often have antibodies that do not bind phospholipids and are responsible for the induction of apoptosis in endothelial cells.
Partial Exchange Transfusion in Sickle Cell Anemia Complicated by Heart Disease
Authors: Annemarie Sommer
Journal: JAMA (1971)

An 11-year-old boy with sickle cell anemia and heart disease was treated with "partial exchange transfusion" to decrease the number of thrombotic crises by reducing hemoglobin S concentration and to improve cardiovascular status. The procedure involves the use of renal dialysis equipment. Several measurements of blood viscosity with the Wells Brookfield microviscometer were useful in the treatment of the patient.