tbuckley/cabot-search huggingface dataset:
Self-Assessment for Education and Recertification
Authors: Edward C. Rosenow
Journal: JAMA (1975)

The American College of Physicians and the American Board of Internal Medicine are pleased that nearly 3,400 internists have become recertified in 1974. This was done with the College's Medical Knowledge Self-Assessment Program III (MKSAP) as the primary educational tool, to ensure the recertification of 95% of the internists who took the examination conducted by the American Board of Internal Medicine. Lawrence E. Young, MD, Chairman, American College of Physicians Self-Assessment Committee, and Calvin F. Kay, MD, Deputy Executive Vice-President, American College of Physicians, are well along with plans for MKSAP IV, which will be available in early 1977. This is the plan: In early December 1976, subscribers will receive a syllabus of what the experts think is important recent new knowledge (five years) for any internist in general or primary care. The syllabus will be supplemental, with additional reference material, but it is intended that the syllabus will
Coeliac disease: characterisation of monoclonal antibodies raised against a synthetic peptide corresponding to amino acid residues 206-217 of A-gliadin.
Authors: H J Ellis, A P Doyle, R P Sturgess, P J Ciclitira
Journal: Gut (1992)

A dodecapeptide of A-gliadin, which shares amino acid homologies with the E1b protein of adenovirus 12, was used to produce murine monoclonal antibodies. Five monoclonal antibodies were produced and were screened by enzyme linked immunosorbant assay, immunodot assay, and immunoblotting. The antibodies were tested against whole wheat gliadin and its alpha, beta, gamma, and omega subfractions, and the prolamins of rye, barley, oats, maize, millet, rice, and sorghum. Four of the five antibodies cross reacted with one or more of the coeliac non-toxic cereals--maize, millet, sorghum, and rice. The monoclonal antibody that did not cross react with these non-toxic cereals, did not recognize Frazer9s fraction III, a peptic-tryptic digest of wheat gluten which is known to be toxic. The results suggest that the A-gliadin dodecapeptide shares a region of homology with cereals that do not exacerbate coeliac disease. This study does not support the hypothesis that prior infection with adenovirus 12 is a precipitating factor in coeliac disease.
Abstract LB-343: Defining mechanisms of endocrine resistance in breast cancer using whole exome sequencing
Authors: Natasha Chandiramani, Kelly S. Levano, Esther A. Peterson, Paraic A. Kenny
Journal: Cancer Research (2012)

Abstract About 70% of breast cancers are estrogen receptor positive (ER+) and current treatments target either ER activity (Tamoxifen and Fulvestrant) or the production of estrogen (aromatase inhibitors). These treatments have led to significant increases in disease-free and overall survival, but after initial response to these agents, many ER+ cancers progress to endocrine resistance. There have been several attempts to understand the molecular mechanisms that lead to acquired resistance, but a clear understanding is still lacking. We hypothesize that endocrine resistant cells in the tumor arise by acquiring compensatory somatic mutations, and that some of these driver mutations responsible for resistance are in oncogenes or tumor suppressor genes. To test this we performed whole exome sequencing on three of MCF7 breast cancer cell sublines that are resistant to either tamoxifen, fulvestrant or exemestane - drugs commonly used in the clinic to treat ER+ breast cancers. An Illumina TruSEQ adaptor-based exonic library was prepared using genomic DNA from the resistant and control cell lines, and multiplexed on an Illumina HiSeq 2000 sequencer (100bp paired-end reads). Reads were aligned to human genome build 19 using BWA, variants were called using SAMTools, somatic mutations in endocrine cell lines were determined with VarScan, and amino acid changes were annotated using ANNOVAR. We have identified several non-synonymous mutations in cancer-relevant genes and are currently working to validate these targets. Studying these genes will increase our understanding of how tumors overcome the requirement for estrogen signaling and ultimately, we hope that comparing tumor profiles of patients with endocrine resistance disease will lead to therapeutics targeted to these secondary mutational lesions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-343. doi:1538-7445.AM2012-LB-343
Interactions between isolated hepatocytes and kupffer cells in iron metabolism: A possible role for ferritin as an iron carrier protein
Authors: Jean-Claude Sibille, Hitoshi Kondo, Philip Aisen
Journal: Hepatology (1988)

Like the rat peritoneal macrophage, the isolated Kupffer cell is capable of processing and releasing iron acquired by phagocytosis of immunosensitized homologous red blood cells. When erythrophagocytosis is restrained to levels which do not affect cell viability, about one red cell per macrophage, close to 50% of iron acquired from red cells is released within 24 hr in the form of ferritin. Immunoradiometric assay of the extracellular medium indicates that 160 ng ferritin are released by 10(6) Kupffer cells after 24-hr incubation at 37 degrees C. Iron release is temperature-dependent, the rate at 37 degrees C being nearly 5-fold greater than at 4 degrees C. As estimated by sucrose-gradient ultracentrifugation, ferritin released by the erythrophagocytosing Kupffer cell averages 2,400 iron atoms per molecule. When reincubated with isolated hepatocytes, this released ferritin is rapidly taken up by the cells. Via this process, hepatocytes may accumulate more than 160,000 iron atoms per cell per min. Such accumulation is not impeded by the presence of iron-loaded transferrin in the culture medium, but is markedly depressed by rat liver ferritin. In contrast to the conservation of transferrin during its interaction with hepatocytes, the protein shell of the ferritin molecule is rapidly degraded into trichloroacetic acid-soluble fragments. Ferritin-mediated transfer of iron from Kupffer cells to hepatocytes may help explain the resistance of the liver to iron deficiency as well as the liver's susceptibility to iron overload.
Abstract 3429: Coordination of cell cycle repression and reduced cytoskeletal tension by the small molecule natural product, Schweinfurthin A.
Authors: Thomas Turbyville, Alla Brafman, De Chen, Kathryn Romanchuck, John Beutler, Karlyne Reilly, Stephen Lockett
Journal: Cancer Research (2013)

Abstract Malignant Peripheral Nerve Sheath Tumors (MPNST) are a frequent cause of morbidity and mortality in Neurofibromatosis type 1 patients, and arise in part from loss of the tumor suppressor function of the NF1 gene product, neurofibromin. We have previously shown that MPNST tumor cell lines, as well as astrocytoma cell lines, derived from both patients and a Nf1-/+;Trp53-/+ (NPcis) mouse model are differentially sensitive to the natural product, Schweinfurthin A (SA). In addition to its anti-proliferative effects, SA caused dramatic reorganization of the actin cytoskeleton. When the NF1 Ras-regulatory domain was re-expressed in an Nf1-/- astrocytoma cell line derived from the NPcis model, these cells became resistant to the effects of SA. This led us to hypothesize that SA mediates its effects on the actin cytoskeleton and proliferation by phenocopying neurofibromin in its regulation of Rho and mitogenic signaling pathways. Our objective is to understand if and how this is the case. To further that end, the goal of this study was to begin to probe the coordination of proliferation and cytoskeletal tension, as has been previously reported in other studies. We cultured individual SA- and DMSO-treated MPNST cells derived from the NPcis model onto pre-defined micropatterns of fibronectin. By constraining cell shape, quantitative structural properties of cells were revealed that were otherwise masked when cells were grown on standard coverslips. We observed dose-dependent increases in the concave curvature of cell edge segments not attached to the underlying fibronectin. Such curvature is known to represent decreased cell tension exerted by the actin cytoskeleton. Across the same SA doses, we measured a decrease in cyclin D1 and cyclin D3 total protein levels and a decrease in retinoblastoma protein phosphorylation, which was consistent with flow cytometry data showing a G1 blockade. Thus, we conclude that proliferation and cytoskeletal tension are coordinated in cells sensitive to the candidate drug, SA. Funded by NCI Contract No. HHSN261200800001E. Citation Format: Thomas Turbyville, Alla Brafman, De Chen, Kathryn Romanchuck, John Beutler, Karlyne Reilly, Stephen Lockett. Coordination of cell cycle repression and reduced cytoskeletal tension by the small molecule natural product, Schweinfurthin A. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3429. doi:10.1158/1538-7445.AM2013-3429
Equations for the determination of major regional blood flow in the mammalian fetus with radioactive microspheres
Authors: J. P. ARCHIE
Journal: Cardiovascular Research (1974)

Equations are presented for simultaneous determination of right and left ventricular outputs and ductus arteriosus, foramen ovale, and upper and lower body flows in the mammalian fetus. The method is a modification of indicator dilution theory as applied to the radioactive microsphere method of blood flow measurement, and can be used repeatedly in any fetus.
Vaccine for Meningococcal Meningitis Tested
Authors: Charles Marwick
Journal: JAMA (1991)

RESEARCHERS at the National Institutes of Health (NIH), Bethesda, Md, have developed a vaccine that potentially could immunize infants against almost all meningococcal meningitis in the United States. So far, however, the vaccine has only been tested in mice. Although there are vaccines against a number of meningococcal serotypes, these are not effective in infants and there are none against group B meningococci. But a development that might change this picture has just been reported (<i>Proc Nati Acad Sci U S A</i>. 1991;88:7175-7179). At the NIH's National Institute of Child Health and Human Development, Sarvamangala Devi, PhD, Rachel Schneerson, MD, John Robbins, MD, and coworkers say they have synthesized a conjugate vaccine that induces antibody against the capsular polysaccharides of both group B and group C meningococci. The vaccine also induces antibody to<i>Escherichia coli</i>K1. About a decade ago, Schneerson and Robbins discovered that the immunologic properties of<i>Haemophilus</i>
Multiple Tumors in a Child with Germ-Line Mutations in<i>TP53</i>and<i>PTEN</i>
Authors: Sharon E. Plon, Michael L. Pirics, Jed Nuchtern, John Hicks, Heidi Russell, Shipra Agrawal, Kevin Zbuk, Charis Eng, Madhuri Hegde, Ephrem Lip Hon Chin
Journal: New England Journal of Medicine (2008)

To the Editor: TP53, a tumor-suppressor gene, is frequently inactivated by somatic mutations in cancer. Inheritance of a heterozygous TP53 mutation results in the Li–Fraumeni syndrome of a heredita...
Pressor Reflexes Produced by Stimulation of Afferent Fibers in the Cardiac Sympathetic Nerves of the Cat
Authors: D. FRED PETERSON, ARTHUR M. BROWN
Journal: Circulation Research (1971)

Afferent fibers in cardiac sympathetic nerves were stimulated electrically in an attempt to evoke circulatory reflexes. A pressor response was always elicited during stimulation of the central end of the cut left inferior cardiac or pericoronary nerve in vagotomized intact-brain or spinal cats. The maximum blood pressure rise was 21.5 mm Hg during inferior cardiac nerve stimulation and 14.1 mm Hg during pericoronary nerve stimulation. Heart rate and respiration were unaffected by stimulation. The alpha-receptor-blocking agent phenoxybenzamine hydrochloride abolished the pressor response. Sequential sectioning of cardiac nerves arising from either the stellate ganglion or the thoracic sympathetic trunk, or of white rami 1 through 4, indicated that each branch carried afferents contributing to the pressor response. Evoked potentials revealed that excitation of Aδ fibers in the inferior cardiac nerve elicited a weak pressor response, and excitation of C fibers provoked a much stronger response. C fiber continuity between the pericoronary nerve and the inferior cardiac nerve was demonstrated.
Cyclo-oxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study
Authors: Muhammad Mamdani, David N Juurlink, Douglas S Lee, Paula A Rochon, Alex Kopp, Gary Naglie, Peter C Austin, Andreas Laupacis, Therese A Stukel
Journal: The Lancet (2004)
Prognostic Significance of Epicardial Blood Flow Before and After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndromes
Authors: Gjin Ndrepepa, Julinda Mehilli, Stefanie Schulz, Raisuke Iijima, Dritan Keta, Robert A. Byrne, Jürgen Pache, Melchior Seyfarth, Albert Schömig, Adnan Kastrati
Journal: Journal of the American College of Cardiology (2008)
Labour acts to cut NHS costs
Authors: J. Warden
Journal: BMJ (1997)

The new British government made its first moves last week to change the NHS, although the BMA and others in the field regard the changes as more cosmetic than creative. They include deferring the next round of GP fundholders to save £120m ($192m) and an £80m cut in management costs, to release an extra £10m to treat breast cancer.

These changes will honour Labour's commitment in its manifesto to reduce management costs by £100m this year. But they are no longer coupled to a pledge to trim hospital waiting lists by 100 000 in the face of new figures showing that lists rose by that amount in the previous year, to a total of 1 164 400.

Also implicit …
Statistics at Square Two
Authors: A. Russell Localio
Journal: Annals of Internal Medicine (2001)

Medical Writings: Book Notes18 December 2001Statistics at Square TwoA. Russell LocalioA. Russell LocalioDepartment of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, School of Medicine, University of Pennsylvania, Philadelphia, PA.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-135-12-200112180-00032 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Campbell MJ. 133 pages. London: BMJ Books; 2001. £12.95. ISBN 0727913948. Order at www.bmj.com.Field of medicine: Biostatistics and epidemiology.Format: Softcover book.Audience: Clinical investigators who need a concise overview of multivariable methods of analysis, advanced students who are considering research careers, peer reviewers who need guidance on more advanced statistical methods, and critical readers of clinical research.Purpose: A handy, portable overview of multivariable statistical methods commonly seen in the biomedical literature.Content: The book focuses on multiple linear regression, logistic regression, and survival analyses. Two additional chapters cover the more advanced topics of random effects models, Poisson ... Author, Article, and Disclosure InformationAffiliations: Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, School of Medicine, University of Pennsylvania, Philadelphia, PA. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 18 December 2001Volume 135, Issue 12Page: 1097KeywordsBiostatisticsCareers in researchEpidemiologyLinear regression analysisResearch and reporting methodsSoftware toolsStatistical dataStatistical methodsStatistical modelsSurvival analysis ePublished: 18 December 2001 Issue Published: 18 December 2001 Copyright & PermissionsCopyright © 2001 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
IFN-γ–mediated inhibition of MAPK phosphatase expression results in prolonged MAPK activity in response to M-CSF and inhibition of proliferation
Authors: Annabel F. Valledor, Luís Arpa, Ester Sánchez-Tilló, Mònica Comalada, Cristina Casals, Jordi Xaus, Carme Caelles, Jorge Lloberas, Antonio Celada
Journal: Blood (2008)
Hydrochlorothiazide-Dependent Thrombocytopenia Due to IgM Antibody
Authors: Eric V. Eisner
Journal: JAMA (1971)

A case of immune thrombocytopenic purpura is found due to ingestion of hydrochlorothiazide. To our knowledge, this is the first case of drug-induced purpura in which the responsible circulating factor, presumably an antibody, has been identified as a macroglobulin.
Preconditioning against myocardial dysfunction after ischemia and reperfusion by an alpha 1-adrenergic mechanism.
Authors: A Banerjee, C Locke-Winter, K B Rogers, M B Mitchell, E C Brew, C B Cairns, D D Bensard, A H Harken
Journal: Circulation Research (1993)

Preconditioning may find ready applicability in humans facing scheduled global cardiac ischemia-reperfusion (IR) during bypass or transplantation, where such a maneuver is feasible before arrest. Our objective was to delineate and exploit the endogenous preconditioning mechanism triggered by transient ischemia (TI) and thereby attenuate myocardial postischemic mechanical dysfunction by clinically acceptable means. Preconditioning by 2 minutes of TI followed by 10 minutes of normal perfusion protected isolated rat left ventricle function assessed after 20 minutes of global, 37 degrees C ischemia and 40 minutes of reperfusion. Final recovery of developed pressure (DP) was improved (91.5 +/- 1.9% of equilibration DP versus unconditioned IR control, 57.4 +/- 2.4%, P &lt; .01) and was accompanied by increased contractility (+/- dP/dt). Norepinephrine release increased after TI, and reserpine pretreatment abolished TI preconditioning. This suggests that endogenous norepinephrine mediates functional preconditioning in rat. Brief pretreatment (2 minutes) with exogenous norepinephrine reproduced the protection (89.1 +/- 1.4%) of postischemic function. Functional protection persisted after the hemodynamic effects had resolved. Norepinephrine-induced preconditioning was simulated by phenylephrine and blocked by alpha 1-adrenergic receptor antagonist. TI preconditioning was similarly lost after selective alpha 1-adrenergic receptor blockade. We conclude that transient ischemic preconditioning is mediated by the sympathetic neurotransmitter release and alpha 1-adrenergic receptor stimulation. Although the postreceptor mechanism remains unclear, functional protection after IR does not seem related to the magnitude of ATP depletion and elevation of resting pressure during ischemia. Rather, the endogenous mechanisms facilitate both recovery of mechanical function and ATP repletion during reperfusion.
Head injuries, helmets, cycle lanes, and cyclists
Authors: A H R W Simpson, P S Unwin, I W Nelson
Journal: BMJ (1988)

The incidence of head injuries in accidents to cyclists studied by the accident service oxford were reported in this article. The effects that wearing helmets and the use of separate cycle lanes might have on such injuries were also discussed. The study was undertaken between 1 January 1983 and 31 may 1985. Injuries to the head or face or both occurred in 958 (52%) of accidents. The abbreviated injury scale was used to classify the injuries sustained. A comparison was also made between head injuries sustained in accidents by cyclists with those sustained by motorcyclists, who wear a helmet by law. To make speeds compatable only accidents in built up areas were compared. A significantly higher proportion of pedal cyclists compared with motorcyclists had head injuries, and these tended to be more severe. The study also indicated that cycle lanes were safer than ordinary roads, as the number of accidents per kilometre was less on such lanes.
Public education campaign could overwhelm sexual health services
Authors: Caroline White
Journal: BMJ (2005)

Government proposals to mount a public education campaign on sexual health later this year threaten to bring specialist services to breaking point, a leading expert has warned a parliamentary select committee.

Professor Kinghorn, senior consultant in genitourinary medicine at Sheffield Teaching Hospitals NHS Foundation Trust, told the House of Commons Health Committee that primary care trusts, which commission services, have been diverting government funds, earmarked for sexual health, into other areas.

Professor Kinghorn is one of several witnesses called to give evidence to the committee, which began its inquiry last week into new developments …
Immunoglobulin synthesis and tumour cell number and the natural history of multiple myeloma.
Authors: S E Salmon
Journal: BMJ (1971)

the major prolongation is in the Gi phase of the cell cycle.When nutritional limitations on growth are overcome evidence is obtained that crowding and contact inhibition as well as soluble metabolic factors may contribute to the limitations on proliferation.The lymphoid and plasma cells in culture provide an interest- ing, though not completely analagous, model for studies of cell proliferation in vivo.The stationary culture shift to prolonged Gl phase, like a comparable event in vivo, should make cells resistant to chemotherapeutic agents that act primarily on DNA synthesis (S phase events).Mechanisms for affecting Gl cells or bringing arrested cells out of Gl are beginning to be explored.
Elevated Admission Glucose and Mortality in Elderly Patients Hospitalized With Heart Failure
Authors: Mikhail Kosiborod, Silvio E. Inzucchi, John A. Spertus, Yongfei Wang, Frederick A. Masoudi, Edward P. Havranek, Harlan M. Krumholz
Journal: Circulation (2009)

Background— Although some professional societies recommend target-driven glucose control for all hospitalized patients, the association between elevated glucose and adverse outcomes has not been well established in patients hospitalized with heart failure. Methods and Results— We evaluated a nationally representative cohort of 50 532 elderly patients hospitalized with heart failure in the United States between April 1998 and June 2001. The association between admission glucose and all-cause mortality at 30 days and 1 year was analyzed with multivariable Cox regression models, both in the entire cohort and in patients with and without diabetes mellitus. After multivariable adjustment, no significant relationship was found between glucose and 30-day mortality (for glucose groups of &gt;110 to 140, &gt;140 to 170, &gt;170 to 200, and &gt;200 mg/dL; hazard ratios for 30-day mortality were 1.09 (95% confidence interval, 0.98 to 1.22), 1.27 (95% confidence interval, 1.11 to 1.45), 1.16 (95% confidence interval, 0.98 to 1.37), and 1.00 (95% confidence interval, 0.87 to 1.15), respectively, versus glucose ≤110 mg/dL; P for linear trend=0.53). Results were similar for 1-year mortality and did not differ between patients with and without known diabetes mellitus (for diabetes×glucose interaction, P =0.11 and 0.55 for 30-day and 1-year mortality, respectively). Conclusions— We found no significant association between admission glucose levels and mortality in a large cohort of patients hospitalized with heart failure. Our findings suggest that the relationship between hyperglycemia and adverse outcomes seen in acute myocardial infarction cannot be automatically extended to patients hospitalized with other cardiovascular conditions.