tbuckley/cabot-search huggingface dataset:
Abstract 4196: MSH3 mediates sensitization of colorectal cancer cells to cisplatin, oxaliplatin and a poly(ADP-ribose) polymerase inhibitor
Authors: Masanobu Takahashi, Minoru Koi, Francesc Balaguer, C. Richard Boland, Ajay Goel
Journal: Cancer Research (2011)

Abstract Introduction:The MSH3 gene is one of the DNA mismatch repair (MMR) genes that has undergone somatic mutation frequently in MMR-deficient cancers. MSH3, together with MSH2 forms the MutSβ heteroduplex, which interacts with interstrand crosslinks (ICLs) induced by drugs such as cisplatin and psoralen. However, the precise role of MSH3 in mediating the cytotoxic effects of ICL-inducing agents remains poorly understood. MethodsIn this study, we first examined the effects of MSH3 deficiency on cytotoxicity caused by cisplatin and oxaliplatin, another ICL-inducing platinum drug. Results: Using isogenic HCT116-derived clones in which MSH3 expression is controlled by shRNA expression in a tet-off system, we discovered that MSH3 deficiency sensitized cells to both cisplatin and oxaliplatin at clinically relevant doses. Interestingly, siRNA-induced down-regulation of the MLH1 protein did not affect MSH3-dependent toxicity of these drugs, indicating that this process does not require participation of the canonical MMR pathway. Furthermore, MSH3-deficient cells maintained higher levels of pH2AX after oxaliplatin treatment in comparison to MSH3-proficient cells, suggesting that MSH3 plays an important role in repairing DNA double strand breaks (DSB). This role of MSH3 was further supported by our findings that MSH3-deficient cells were sensitive to olaparib, a Poly(ADP-ribose) polymerase inhibitor. Moreover, the combination of oxaliplatin and olaparib exhibited more than 10-fold increase in toxicity compared to either treatment individually. Conclusion:Collectively, our results provide novel evidence that MSH3 deficiency contributes to the cytotoxicity of platinum drugs through deficient DSB repair. These data lay foundation for the development of effective prediction and treatments for cancers with MSH3 deficiency. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4196. doi:10.1158/1538-7445.AM2011-4196
Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus
Authors: Sergey V Kozyrev, Anna-Karin Abelson, Jerome Wojcik, Ammar Zaghlool, M V Prasad Linga Reddy, Elena Sanchez, Iva Gunnarsson, Elisabet Svenungsson, Gunnar Sturfelt, Andreas Jönsen, Lennart Truedsson, Bernardo A Pons-Estel, Torsten Witte, Sandra D'Alfonso, Nadia Barizzone, Maria Giovanna Danieli, Carmen Gutierrez, Ana Suarez, Peter Junker, Helle Laustrup, Maria Francisca González-Escribano, Javier Martin, Hadi Abderrahim, Marta E Alarcón-Riquelme
Journal: Nature Genetics (2008)
Induced pluripotent stem cells: A new era for hepatology
Authors: Samira Asgari, Behshad Pournasr, Ghasem Hosseini Salekdeh, Arefeh Ghodsizadeh, Michael Ott, Hossein Baharvand
Journal: Journal of Hepatology (2010)

Stem cell transplantation has been proposed as an attractive alternative approach to restore liver mass and function. Recent progress has been reported on the generation of induced pluripotent stem (iPS) cells from somatic cells. Human-iPS cells can be differentiated towards the hepatic lineage which presents possibilities for improving research on diseases, drug development, tissue engineering, the development of bio-artificial livers, and a foundation for producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. This focused review will discuss how human iPS cell advances are likely to have an impact on hepatology.
HIV Prevention: Community Planning Groups-Reply
Authors: Jeff Stryker
Journal: JAMA (1995)

<h3>In Reply.</h3> —Dr Holtgrave is correct. There is no recent development in the field of HIV prevention at once both so radical and logical as the CDC community planning efforts. This development was not addressed in our recent overview of HIV prevention science and policy because of space constraints, rather than lack of interest or support. The CDC's belated support for localized community planning is an acknowledgment of one of the stark realities of the HIV epidemic—although the acquired immunodeficiency synrome is a national challenge that must concern us all, HIV disease has not blanketed the country uniformly. The HIV epidemic is best characterized as a series of localized epidemics differing from one locale to another—in some places, from one neighborhood to another.<sup>1</sup> In our federal system, it is not always a simple task to target resources to local areas most in need. Yet targeting of HIV prevention resources
A variant allele of Growth Factor Independence 1 (GFI1) is associated with acute myeloid leukemia
Authors: Cyrus Khandanpour, Christian Thiede, Peter J. M. Valk, Ehssan Sharif-Askari, Holger Nückel, Dietmar Lohmann, Bernhard Horsthemke, Winfried Siffert, Andreas Neubauer, Karl-Heinz Grzeschik, Clara D. Bloomfield, Guido Marcucci, Kati Maharry, Marilyn L. Slovak, Bert A. van der Reijden, Joop H. Jansen, Hans K. Schackert, Khashayar Afshar, Susanne Schnittger, Justine K. Peeters, Frank Kroschinsky, Gerhard Ehninger, Bob Lowenberg, Ulrich Dührsen, Tarik Möröy
Journal: Blood (2010)
Selective loss of nucleoside carrier expression in rat hepatocarcinomas
Authors: Yvonne Dragan, Raquel Valdés, Mireia Gomez-Angelats, Antonio Felipe, Javier F. Casado, Henry Pitot, Marçal Pastor-Anglada
Journal: Hepatology (2000)

Evidence that hepatoma cell lines show differential expression of concentrative nucleoside transporters (CNT1 and CNT2) prompted us to study the transporter proteins in 2 models of hepatocarcinogenesis, the chemically induced Solt and Farber model and the albumin-SV40 large T antigen (Alb-SV40) transgenic rat. CNT1 expression was lower in tumor biopsy specimens from Alb-SV40 rat livers than in normal tissue. Immunocytochemistry revealed that the CNT1 protein was indeed absent in the tumor lesions. CNT1 was also absent in a cell line, L25, derived from the Alb-SV40 transgenic rat liver tumors, whereas another cell line, L37, derived from the normal-appearing parenchyma, retained the expression of both carrier isoforms. The protein expression correlated with the nucleoside transport properties of these cell lines. Moreover, although CNT2 expression was highly dependent on the growth characteristics of the 2 cell lines, as was CNT1 (albeit to a lower extent) in L37 cells, it was not expressed in L25 cells at any stage of cell growth. In contrast to the transgenic model of hepatocarcinogenesis, in the chemically induced tumors the expression of CNT2 was lower, although still detectable. In summary, these data indicate that hepatocarcinogenesis leads to a selective loss or diminished expression of nucleoside carrier isoforms, a feature that may be relevant to our understanding of the molecular basis of the bioavailability of those drugs that are nucleoside derivatives and may be substrates of these carriers. The transport properties and isoform-expression profile of the L25 and L37 cell lines make them suitable hepatocyte culture models with which to study nucleoside transport processes and drug sensitivity.
General practice "out of step," claim managers
Authors: J. Warden
Journal: BMJ (1986)

Wherever you turn at Westminster these days one or other aspect of the health service is under scrutiny.Wednesday of last week was not out of the ordinary.For six hours medical topics were under non- stop discussion somewhere in the Palace of Westminster.Let us observe that one day in the life of parliament.It starts in an upstairs committee room, where the social services select committee is hearing evidence on primary care in parallel with the government's own AgendaforDiscussion.The witnesses are from the Institute of Health Services Management.Their rather bland advance paper could hardly have prepared the committee for the more robust testimony that came out in cross examination.The health service managers have quite definite ideas about how to organise primary care on a neighbourhood scale.It is soon clear that family doctors do not fit in as tidily as the institute would like.The trouble is that the general practitioner's list does not necessarily align with the geography of the neighbourhood support services.Yes, the witnesses thought, the answer might be the zoning of general practice and some restriction of patient choice, though by way of evolution not compulsion.While acknowledging the value of the list and the freedom of choice it affords, Mr Michael Schofield, district general manager of Rochdale Health Authority, who is soon to take up an academic post at Manchester University, added: "We must recognise that in many ways it is general practice that is out of step with the way other services are developing."Dr Maureen Dixon, the institute's director, went on to explain how this apparent isolation of family practitioners might be remedied.The trick would be to create a single authority to plan and manage the hospitals, the community services, and the family practitioner service."Sadly, we have seen family practitioner services move away from the rest of the health service and we would
LEFT ATRIAL APPENDAGE OUTFLOW VELOCITY PREDICTS SINUS RHYTHM STABILITY IN PATIENTS WITH PERSISTENT ATRIAL FIBRILLATION UNDERGOING TEE-GUIDED RHYTHM CONTROL INTERVENTION
Authors: Lothar Faber, Christian Prinz, Johanna Socada, Georg Koenig, Detlef Hering, Olaf Oldenburg, Klaus P. Mellwig, Dieter Horstkotte
Journal: Journal of the American College of Cardiology (2011)
The Task of Medicine: Dialogue at Wickenburg
Authors: Nicholas E. Davies
Journal: JAMA (1989)

This book is a summary by Dr Kerr L. White of a 4-day conference sponsored by the Kaiser Foundation at which the future of medicine and medical education was discussed in depth. The conference's "point of departure," actually its focus, was a monograph by Charles E. Odegaard, former president of the University of Washington, entitled<i>Dear</i><i>Doctor</i>.<sup>1</sup>Additionally, the conference members were given "a series of commissioned papers and published reprints," many (all?) of which are included in the appendix to this book. There were 39 physicians and 6 nonphysicians in attendance. The large majority of physicians were academicians. After reading this book and its appendixes carefully, it became obvious that to understand it fully, one needs first to read<i>Dear Doctor</i>. This I did, and it was worth the effort. From all of this reading I have arrived at a summary statement, to wit: the conference at Wickenburg
Effects of Intensive Glucose Lowering in the Management of Patients With Type 2 Diabetes Mellitus in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial
Authors: Matthew C. Riddle
Journal: Circulation (2010)

Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was designed to test whether treatment targeting nearly normal glycemic control reduces the risk of cardiovascular events in type 2 diabetes mellitus.This aim was based on consistent epidemiological evidence that higher glucose and hemoglobin A 1c (HbA 1c ) levels are associated with greater cardiovascular risk, together with inconclusive results from smaller and shorter interventional studies. 1 All 10 251 participants in ACCORD were randomized to either a standard treatment strategy that targeted HbA 1c levels between 7% and 7.9% or an intensive strategy that sought to attain an HbA 1c Ͻ6.0%.With each strategy, investigators could prescribe any antihyperglycemic agent approved by regulatory authorities.The median HbA 1c with the standard strategy was 7.5%; the intensive strategy achieved a median HbA 1c of 6.4%. 2 However, the intensive strategy was stopped after a median follow-up of 3.4 years, Ϸ60% of that planned, because of 22% higher all-cause mortality. 2Participants previously using the intensive strategy were switched to the standard strategy and continued in the trial.The cardiovascular and microvascular effects after the full 5 years of follow-up will soon be reported.Meanwhile, debate continues as to why there was higher mortality with intensive treatment and the clinical implications.Several analyses of the data obtained during randomized treatment have shed light on these issues.
Iodine Supplementation During Pregnancy and Lactation
Authors: Alex Stagnaro-Green, Scott Sullivan, Elizabeth N. Pearce
Journal: JAMA (2012)

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
Spontaneous bacterial peritonitis and reagent strips
Authors: Jose Castellote
Journal: Hepatology (2007)

I read with interest the article by Nousbaum et al.1 about the diagnostic accuracy of the Multistix 8 SG reagent strip (Bayer HealthCare) for the diagnosis of spontaneous bacterial peritonitis (SBP). A test sensitivity of 45.3% is disappointing for an infectious complication with a still high mortality. The test was read by an investigator and a nurse; when there was discordance between the 2 readers, the highest value was registered. If we need to increase the sensitivity, it may be better to register the lowest value because the majority of the patients were free of SBP. Because concordance was good but not perfect, to recalculate statistics in this other way may substantially change the sensitivity and specificity. It would be interesting to know the sensitivity and specificity found in the study if a different cutoff were considered. In our study using Aution sticks (Menarini Diagnostics),2 the sensitivity increased to 89%-96% when the cutoff passed from ≥3 to ≥2 on a scale of 0-4, with only a slight decrease in specificity. Contrary to what the authors state in their discussion, only patients with cirrhosis were included in our study, and in only 1 of 228 cases did the patient have peritoneal carcinomatosis, but it was correctly classified by the reagent strip as a true negative. In 2 of 3 studies comparing Multistix with other reagent strips,1 the sensitivity was clearly lower with Multistix. We can conclude that Multistix is not enough sensitive and may be not used to diagnose SBP. Results with other strips are encouraging, although every dipstick should be tested and compared with others before its use is recommended. I agree with the authors that reagent strips should not systematically replace standard fluid analyses. However, they can be very useful when analyses are not quickly available or are unavailable. A clearly positive test is highly indicative of SBP and is an indication of antibiotic therapy; a clearly negative test excludes SBP with confidence because the negative predictive value has ranged from 96%-100% in all the studies reported until now. In those cases with intermediate results, a conventional polymorphonuclear leukocyte count is mandatory if it is available, and if it is not, empirical antibiotic therapy should be initiated. Finally, Nousbaum et al.1 reported a low prevalence of SBP in asymptomatic outpatients (0.57%). To the best of our knowledge, 5 studies have prospectively studied SBP prevalence in outpatients with asymptomatic cirrhosis undergoing large-volume paracentesis.3-7 Only 1 of 834 cases was diagnosed with SBP. In view of this figure, I think that ascitic fluid analysis may be not necessary in this clinical context. Jose Castellote*, * Servicio de Aparato Digestivo, IDIBELL—Hospital Universitario de Bellvitge, Barcelona, Spain.
Randomized, Double-Blind, Dose-Ranging Study of Otamixaban, a Novel, Parenteral, Short-Acting Direct Factor Xa Inhibitor, in Percutaneous Coronary Intervention
Authors: Marc Cohen, Deepak L. Bhatt, John H. Alexander, Gilles Montalescot, Christoph Bode, Timothy Henry, Jean-Francois Tamby, Jan Saaiman, Stanislas Simek, Johannes De Swart
Journal: Circulation (2007)

The optimal anticoagulant regimen for percutaneous coronary intervention (PCI) remains to be determined. Otamixaban, a selective and direct inhibitor of factor Xa, was investigated in patients undergoing nonurgent percutaneous coronary intervention.In this double-blind, double-dummy, parallel-group, dose-ranging trial, 947 patients were randomly assigned to either 1 of 5 weight-adjusted otamixaban regimens or weight-adjusted unfractionated heparin (UFH) before percutaneous coronary intervention. The primary end points were change in prothrombin fragments 1+2 (F1+2), and anti-factor Xa activity. The main secondary end points were Thrombolysis In Myocardial Infarction (TIMI) bleeding at day 3 or hospital discharge (whichever came first) and 30-day ischemic events. The median change in F1+2 from baseline to the end of infusion was greater with the highest otamixaban dose compared with UFH (-0.3 versus -0.2 ng/mL, P=0.008). Anti-factor Xa levels were 65, 155, 393, 571, and 691 ng/mL with otamixaban doses 1 to 5, respectively. Significant TIMI bleeding (major or minor) occurred in 2.0%, 1.9%, 3.8%, 3.9%, and 2.6% of patients receiving otamixaban doses 1 to 5, respectively, and in 3.8% of patients receiving UFH. Four TIMI major bleeds were observed. Ischemic events occurred in 5.8%, 7.1%, 3.8%, 2.5%, and 5.1% of patients receiving otamixaban doses 1 to 5, respectively, and in 5.6% of patients receiving UFH.Otamixaban reduced F1+2 significantly more than UFH at the highest dose regimen, whereas no significant difference in the incidence of TIMI bleeding was observed between the otamixaban and UFH groups. These results set the stage for adequately powered clinical outcome trials of selective direct factor Xa inhibition in patients with acute coronary syndromes.
Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival
Authors: Steffen Walter, Toni Weinschenk, Arnulf Stenzl, Romuald Zdrojowy, Anna Pluzanska, Cezary Szczylik, Michael Staehler, Wolfram Brugger, Pierre-Yves Dietrich, Regina Mendrzyk, Norbert Hilf, Oliver Schoor, Jens Fritsche, Andrea Mahr, Dominik Maurer, Verona Vass, Claudia Trautwein, Peter Lewandrowski, Christian Flohr, Heike Pohla, Janusz J Stanczak, Vincenzo Bronte, Susanna Mandruzzato, Tilo Biedermann, Graham Pawelec, Evelyna Derhovanessian, Hisakazu Yamagishi, Tsuneharu Miki, Fumiya Hongo, Natsuki Takaha, Kosei Hirakawa, Hiroaki Tanaka, Stefan Stevanovic, Jürgen Frisch, Andrea Mayer-Mokler, Alexandra Kirner, Hans-Georg Rammensee, Carsten Reinhardt, Harpreet Singh-Jasuja
Journal: Nature Medicine (2012)
TRANSIENT ELASTOGRAPHY OF THE LIVER FOR NON-INVASIVE ASSESSMENT OF CENTRAL VENOUS PRESSURES AND HEPATIC FIBROSIS IN PATIENTS WITH FONTAN CIRCULATION
Authors: Fred Wu, Roshan Raza, Sarah Harney, Chinweike Ukomadu, Michael Landzberg, Anne Marie Valente, Roger Breitbart, Michael Singh, Alexander Opotowsky, Kimberlee Gauvreau, Maureen M. Jonas
Journal: Journal of the American College of Cardiology (2013)
Road Traffic and Childhood Leukemia: The ESCALE Study (SFCE)
Authors: Alicia Amigou, Claire Sermage-Faure, Laurent Orsi, Guy Leverger, André Baruchel, Yves Bertrand, Brigitte Nelken, Alain Robert, Gérard Michel, Geneviève Margueritte, Yves Perel, Françoise Mechinaud, Pierre Bordigoni, Denis Hémon, Jacqueline Clavel
Journal: Environmental Health Perspectives (2010)

Traffic is a source of environmental exposures, including benzene, which may be related to childhood leukemia.A national registry-based case-control study [ESCALE (Etude Sur les Cancers et les Leucémies de l'Enfant, Study on Environmental and Genetic Risk Factors of Childhood Cancers and Leukemia)] carried out in France was used to assess the effect of exposure to road traffic exhaust fumes on the risk of childhood leukemia.Over the study period, 2003-2004, 763 cases and 1,681 controls < 15 years old were included, and the controls were frequency matched with the cases on age and sex. The ESCALE data were collected by a standardized telephone interview of the mothers. Various indicators of exposure to traffic and pollution were determined using the geocoded addresses at the time of diagnosis for the cases and of interview for the controls. Indicators of the distance from, and density of, main roads and traffic nitrogen dioxide (NO(2)) concentrations derived from traffic emission data were used. Odds ratios (ORs) were estimated using unconditional regression models adjusted for potential confounders.Acute leukemia (AL) was significantly associated with estimates of traffic NO(2) concentration at the place of residence > 27.7 µg/m(3) compared with NO(2) concentration < 21.9 µg/m(3) [OR=1.2; confidence interval (CI), 1.0-1.5] and with the presence of a heavy-traffic road within 500 m compared with the absence of a heavy-traffic road in the same area (OR=2.0; 95% CI, 1.0-3.6). There was a significant association between AL and a high density of heavy-traffic roads within 500 m compared with the reference category with no heavy-traffic road within 500 m (OR=2.2; 95% CI, 1.1-4.2), with a significant positive linear trend of the association of AL with the total length of heavy-traffic road within 500 m.This study supports the hypothesis that living close to heavy-traffic roads may increase the risk of childhood leukemia.