tbuckley/cabot-search huggingface dataset:
Reaction to iron sorbitol injection.
Authors: M. Soots, G. D. Hart
Journal: BMJ (1970)

MEBRITJSHgo home, having no obvious sequelae.His liver function tests, electrolytes, and urea were repeated on the day of his discharge and all were normal.Glibenclamide and its metabolites are more than 970' bonded by serum proteins.About 25 °, of radioactive glibenclamide is excreted in the faeces and the rest in the urine.In contrast to chlorpropamide, the hypoglycaemic reaction to glibencamide is not protracted and is easily controlled by a reduction of the dosage.It is interesting to note phenformin has no hypoglycaemic action in normal people, but this is obviously not so in glibenclamide.This patient's recovery appeared to be fairly rapid and without any immediate damage to kidneys or liver as judged by crude tests of liver function, electrolytes, and urea.
Abstract 2372: Detecting driver genes based on tumor whole-exome sequencing studies
Authors: Xing Hua, Teresa Maria Landi, Jianxin Shi
Journal: Cancer Research (2014)

Abstract Driver somatic mutations confer a selective growth advantage to tumors while passenger mutations do not. Genes carrying driver mutations are detected in whole-exome sequencing (WES) studies if their non-synonymous mutations are significantly more frequent than their silent mutations, adjusting for the heterogeneous mutation rates across genomic locations, subjects and mutation types. Typical tumor WES studies (∼100-300 tumor samples) lack statistical power, and thus can identify only small numbers of candidate driver genes and possibly miss the well-established ones. The best algorithm to detect driver genes to date is MutSigCV. For each target gene, MutSigCV identifies its “bagel”, a set of genes predicted to have similar background mutation rates to the target gene and use the “bagels” to estimate the background mutation rate. Based on the identified “bagels”, we developed a novel statistical method implementing a series of algorithms to improve the statistical power while maintaining the type-I error rate. First, we developed a statistical framework for testing the selective growth advantage of each mutation type and appropriately integrating evidence of growth advantage across mutation types to achieve robust power. We then extended the algorithm to consider spatial clustering information. This substantially improves the statistical power when non-silent mutations are clustered into a few short regions or nucleotides. We applied this novel method to TCGA melanoma WES including 271 tumor samples. Without modeling spatial clustering information, over 30 candidate driver genes, including BRAF, NRAS, PTEN, TP53, PPP6C and CDKN2A were detected controlling FDR=0.01. Modeling spatial information of somatic mutations detected additional rarely mutated genes, including DISP1 (P=1.3×10-20, involved in cellular proliferation and differentiation that leads to normal development of embryonic structures), IDH1 (P=1.0×10-8, previously identified in relation to gliobalstoma and acute myeloid leukemia), MAP2K1 (P=5×10-18, a member of the mitogen-activated protein kinases that also include BRAF, MEK and other important players in melanoma), INTS8 (P=7.7×10-15, an integrator of small nuclear RNA processing), and STK19 (P=1.2×10-10, encoding a serine/threonine kinase, previously identified in melanoma). Finally, we developed methods to simultaneously analyze multiple cancers to improve the power for genes mutated in more than one cancer type, which will be illustrated by analyzing 12 major cancers in TCGA. Our method will provide an important tool for improving driver gene mutation detection in cancer. Citation Format: Xing Hua, Teresa Maria Landi, Jianxin Shi. Detecting driver genes based on tumor whole-exome sequencing studies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2372. doi:10.1158/1538-7445.AM2014-2372
Independent prescribing advice affects doctors' behaviour
Authors: David Spurgeon
Journal: BMJ (2004)

A series of printed letters from a credible and trusted source had a clinically significant impact on doctors' prescribing of drugs to newly treated patients, a new study has found ( CMAJ 2004;171:1057-61).

Researchers from Canada and the United States found that the probability of prescribing a drug recommended in Therapeutics Letter (www.ti.ubc.ca), rather than another drug in the same class, increased by 30% in the three months after the mailing of the letter, relative to the preceding three months, adjusted for any before-after changes in the control group (relative risk 1.30; 95% confidence interval 1.13 to 1.52). No single letter achieved statistical …
Inclusion group systems and cis-trans effects in responses controlled by the two complementing Ir-GLphi genes.
Authors: M E Dorf, P H Maurer, F Merryman, B Benacerraf
Journal: The Journal of Experimental Medicine (1976)

The immune responses to the random linear terpolymers of L-amino acids, poly-(glu57, lys38, tyr5), poly-(glu51, lys34, tyr15,), and poly-(glu53, lys36, phe11) are each controlled by two dominant H-linked Ir genes. The immune responses to these three related terpolymers demonstrate different H-2 distributions, however, the H-2 patterns are part of a single inclusion group system. The alpha- and beta-genes are dominant; however, most effective gene interactions occur when the two genes are in the cis configuration. The potential significance of this cis-trans effect is discussed.
Dual Specificity Phosphatase 1/CL100 Is a Direct Transcriptional Target of E2F-1 in the Apoptotic Response to Oxidative Stress
Authors: Jianli Wang, David P. Yin, Yu-Xin Liu, Richard Baer, Yuxin Yin
Journal: Cancer Research (2007)

Abstract E2F-1 mediates apoptosis through transcriptional regulation of its targets. We report here that E2F-1 acts as a direct transcriptional regulator of dual specificity phosphatase 1 (DUSP1; CL100), a threonine and tyrosine phosphatase that inhibits mitogen-activated protein (MAP) kinases. We found that DUSP1 is transcriptionally induced by ectopic E2F-1 expression and that extracellular signal–regulated kinase 1/2 are dephosphorylated in the presence of E2F-1 and DUSP1. E2F-1 mediates apoptosis in the cellular response to oxidative stress. DUSP1 levels are significantly increased in an E2F-1–dependent manner following oxidative stress but not other stresses examined. DUSP1 mediates the cellular response to oxidative stress. We found that E2F-1 binds to chromatin encompassing the DUSP1 promoter and greatly stimulates the promoter activity of the DUSP1 gene. In particular, E2F-1 physically binds to an E2F-1 consensus sequence and a palindromic motif in the DUSP1 promoter. Interestingly, E2F-1 is acetylated following oxidative stress. Our findings show that E2F-1 is a transcriptional activator of DUSP1 and that DUSP1 is a link between E2F-1 and MAP kinases. [Cancer Res 2007;67(14):6737–44]
Studies on human platelet granules and membranes.
Authors: A J Marcus, D Zucker-Franklin, L B Safier, H L Ullman
Journal: Journal of Clinical Investigation (1966)

Some of the numerous biochemical substances that have been identified in blood platelets are as- sociated with known platelet functions (1), but the role of many others is not clear (2).Since most previous investigations had been carried out on whole platelets, we initiated a study of enzymes and coagulation properties of isolated subcellular platelet components.Preliminary investigations, employing differ- ential centrifugation, provided useful information, but were not entirely satisfactory due to unavoid- able mixing of membrane and granule fractions (3).However, by means of isopycnic gradient ultracentrifugation, platelet homogenates were satisfactorily fractionated and studied (4).This report describes the preparation of platelet ho- mogenates, their separation by ultracentrifugation in a continuous sucrose gradient, identification of the fractions by electron microscopy, and some bio- chemical and physiological properties of the resulting components. MethodsThe starting material was 425 ml of whole blood ob- tained from a fasting donor with a normal platelet count.Collection was carried out in plastic bags with either acid-citrate-dextrose solution or EDTA as anticoagulant.1The bag was centrifuged at 400 X g for 15 minutes (40 C) and the platelet-rich plasma transferred to 45-or 50-ml conical polypropylene tubes.2The platelet-rich plasma was centrifuged for 30 minutes (40) at 2,000 X g.
Merck used ghostwriters and selective data in Vioxx publications, <i>JAMA</i> says
Authors: Janice Hopkins Tanne
Journal: BMJ (2008)

Researchers and editors claim in two papers and an editorial this week that Merck, the makers of the arthritis drug rofecoxib (Vioxx), misrepresented study results and used ghostwriters to prepare manuscripts for journal publication.

The authors of the articles have drawn their evidence from thousands of documents released during lawsuits against Merck over adverse events related to the drug ( JAMA 2008;299:1800-12, 1813-7, and 1833-5). 

Rofecoxib was withdrawn worldwide in September 2004 after a study showed that it doubled the risk of heart attack or stroke if it was taken for more than 18 months ( BMJ 2004;329:816; doi: 10.1136/bmj.329.7470.816-a).

Merck said in a statement that it “believes that many of the comments in a Journal of the American Medical Association ( JAMA ) news release and in the 16 April 2008 issue of JAMA related to Vioxx are false, misleading, or lack context.” 

The statement said, “The articles, based on analyses of documents conducted by consultants hired by trial lawyers as part of their work in the Vioxx product liability litigation, make allegations similar to …
Abstract LB-12: Estrogen-induced redox signaling via NRF-1 is involved in the development of breast cancer
Authors: Victor Okoh, Quentin H. Felty, Deodutta Roy
Journal: Cancer Research (2011)

Abstract The purpose of this study was to determine the role of estrogen-induced reactive oxygen species (ROS) signaling pathways in the development of breast cancer. Here we tested the postulate that activation of a redox sensitive transcription factor, nuclear respiratory factor-1 (NRF-1) signaling is essential for 4-hydroxyestradiol (4-OH-E2)-induced tumorigenesis. We observed that (i) 4-OH-E2 treatment of MCF-10A or MCF-7 cells increased the formation of ROS, (ii) Estrogen-induced ROS activated redox sensitive transcription factor NRF-1, (iii) 4-OH-E2 through activating a redox sensitive serine-threonine kinase AKT phosphorylated NRF-1, (iv) Overexpression of catalase and MnSOD, as well as silencing of NRF-1 prevented 4-OH-E2-induced anchorage-independent growth of MCF-10A and MCF-7 cells and xenograft tumor formation, and (v) 4-OH-E2-induced ROS through stimulating AKT kinase and histone acetyltransferase of CREB binding protein-associated factor (P/CAF), respectively, controlled phosphorylation and acetylation of NRF-1. The results also showed that 4-OH-E2-induced post-translational changes lead to NRF-1 activation, and silencing of NRF-1 and overexpression of MnSOD or catalase prevented 4-OH-E2-induced tumor formation. Taken together, these findings suggest a new paradigm for estrogen-induced breast carcinogenesis that deregulation of phosphorylation and aceytylation of NRF-1 may represent a major mechanism of 4-OH-E2-induced neoplastic transformation and tumorigenesis. 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 LB-12. doi:10.1158/1538-7445.AM2011-LB-12
The Clinical Nursing Conference
Authors: Nobel Guthrie, John W. Runyan, Glenn Clark, Oscar Marvin
Journal: New England Journal of Medicine (1964)

ONE of the most perplexing problems in modern medicine is that of offering care to the thousands of people with chronic diseases. In the Mid-South the prevalence of some of these diseases are as follows (unpublished census statistics): heart conditions, 30 per 1000 population; high blood pressure, 36 per 1000 population; diabetes, 9.4 per 1000 population; peptic ulcer, 14.3 per 1000 population; arthritis, 69.8 per 1000 population; and chronic respiratory disease, 53.4 per 1000 population.In the days before the development of effective treatment of most chronic diseases it made little difference whether patients were seen regularly. However, modern drug . . .
Targeting Fanconi Anemia/BRCA2 Pathway Defects in Cancer: The Significance of Preclinical Pharmacogenomic Models
Authors: Eike Gallmeier, Scott E. Kern
Journal: Clinical Cancer Research (2007)

Abstract Defects in the Fanconi anemia (FA) pathway occur in subsets of diverse human cancers. The hypersensitivity of FA pathway-deficient cells to DNA interstrand cross-linking and possibly other agents renders these genes attractive targets for a genotype-based, individualized anticancer therapy. A prerequisite before clinical trials is the validation and quantification of this hypersensitivity in suitable preclinical pharmacogenomic models. In addition, the effects of combinational therapy need to be evaluated and novel agents sought. We discuss here the pitfalls and limitations in the interpretation of common FA models when applied to the validation of FA gene defects as therapeutic targets. In general, all preclinical models are prone to certain artifacts and, thus, promising results in a single or few models rarely translate into clinical success. Nevertheless, the extraordinary robustness of FA pathway-deficient cells to interstrand cross-linking agents, which are observable in virtually any model independent of species, cell type, or technique used to engineer the gene defect, in various in vitro and in vivo settings, renders these gene defects particularly attractive for targeted therapy. Clinical trials are now under way.
Abnormal γIFN and αTNF secretion in purified CD2+ cells from autoimmune thrombocytopenic purpura (ATP) patients: Their implication in the clinical course of the disease
Authors: J. Garcia‐Suarez, A. Prieto, E. Reyes, L. Manzano, K. Arribalzaga, M. Alvarez‐Mon
Journal: American Journal of Hematology (1995)

Abstract Gamma inferferon (γIFN), alpha tumor necrosis factor (αTNF), and interleukin 6 (IL‐60) are cytomines produced by a wide variety of cells, incuding T lymphocys and NK cells. These cytokines affect B‐cell proliferation and differentiation into immunoglobulin seceting cells. In addition, γIFN and αTNF also enhance the function of macrophagesm, upregulating the expresson of their igG receptors. Abonormalities in the production of these cytokines may be involved in the clinical course of autoimmune thrombocytopenic purpura (ATP). This paper describes the production of these cytokines in PHA‐stimulated peripheral blood CCD2+ cells from ATP patients. Both γIFN and αTNF were significantly increased in PHA‐stimulated CD2+ cells from therapy‐dependent ATP patients (platelet counts &lt;50,000/μl), as compared to ATP patients with stable disease (sustained platelet counts &gt;50,000/μl without need treatment) ( P &lt; 0.05). No significant differences were found in γlFN production by PHA‐stimulated CD2+ cells between therapy‐dependent ATP patients and healthy controls ( P &lt; 0.05). However, the production of αTNF by PHA‐stimulated CD2+ cells from therapy‐dependent ATP patients was significantly higher compared to that found in healthy controls ( P &lt; 0.05). There were no significant differences in IL‐6 production by PHA‐stimulated CD2+ cells from ATP patients and healthy controls ( P &lt; 0.05). These findings demonstrate abnormal γlFN and αTNF secretion in purified CD2 cells from ATP patients. The clinical severity of the disease is associated with the altered secretion of these lymphokines by CD2 cells. © 1995 Wiley‐Liss, Inc.
Rare Diseases and Lesions: Their Contributions to Clinical Medicine
Authors: Norman B. Roberg
Journal: JAMA (1968)

This book offers an intimate account of Dr. Bean's interest in patients with unusual diseases. It is a vivid and interesting survey of rare diseases, some no longer rare, and others unusual only because they cut across conventional classifications and ontological concepts. Students, residents, and practitioners will find brief and illuminating descriptions and wise advice, which will enlarge their knowledge and lead them to observe patients better and with greater interest. The sections on bleeding from the gut, angiomatosis, the lung, and miscellaneous diseases are especially good. The preface comments upon, but does not explain, Hippocratic, Platonic and ontological thought. The epilogue is a potpourri: "A pigeon breast may contain a cooing dove murmur, though the two are not usually related" and "The body as a volume container may be disgraced by obscene obesity or violated as an empty shrine of neglect in anorexia nervosa." The reader encounters a distinct
Systems Approach to Understanding Electromechanical Activity in the Human Heart
Authors: Yoram Rudy, Michael J. Ackerman, Donald M. Bers, Colleen E. Clancy, Steven R. Houser, Barry London, Andrew D. McCulloch, Dennis A. Przywara, Randall L. Rasmusson, R. John Solaro, Natalia A. Trayanova, David R. Van Wagoner, András Varró, James N. Weiss, David A. Lathrop
Journal: Circulation (2008)

The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of cardiologists, cardiac electrophysiologists, cell biophysicists, and computational modelers on August 20 and 21, 2007, in Washington, DC, to advise the NHLBI on new research directions needed to develop integrative approaches to elucidate human cardiac function. The workshop strove to identify limitations in the use of data from nonhuman animal species for elucidation of human electromechanical function/activity and to identify what specific information on ion channel kinetics, calcium handling, and dynamic changes in the intracellular/extracellular milieu is needed from human cardiac tissues to develop more robust computational models of human cardiac electromechanical activity. This article summarizes the workshop discussions and recommendations on the following topics: (1) limitations of animal models and differences from human electrophysiology, (2) modeling ion channel structure/function in the context of whole-cell electrophysiology, (3) excitation–contraction coupling and regulatory pathways, (4) whole-heart simulations of human electromechanical activity, and (5) what human data are currently needed and how to obtain them. The recommendations can be found on the NHLBI Web site at http://www.nhlbi.nih.gov/meetings/workshops/electro.htm.
TCT-44 LEADERS: 5-Year Follow-Up from a Prospective, Randomized Trial of Biolimus A9-Eluting Stents with a Biodegradable Polymer vs. Sirolimus-Eluting Stents with a Durable Polymer- Final report of the LEADERS study
Authors: Patrick Serruys, Paweł Buszman, Axel Linke, Thomas Ischinger, Diethmar Antoni, Volker Klauss, Hae-Young Sohn, Franz Eberli, Roberto Corti, William Wijns, Marie-Claude Morice, Carlo Di Mario, Peter Juni, Stephan Windecker
Journal: Journal of the American College of Cardiology (2012)
Use of DNA Fingerprinting To Assess Tuberculosis Infection Control
Authors: Audrey L. French
Journal: Annals of Internal Medicine (1998)

Background: DNA fingerprinting establishes the genetic relatedness of Mycobacterium tuberculosis isolates and has become a powerful tool in tuberculosis epidemiology. Objective: To use DNA fingerprinting to assess the efficacy of current tuberculosis infection-control practices. Design: Retrospective molecular and descriptive epidemiologic study. Setting: A 700-bed urban public hospital that follows the Centers for Disease Control and Prevention (CDC) guidelines for tuberculosis infection control. Patients: 183 patients who had positive cultures for M. tuberculosis from 1 April 1995 to 31 March 1996. Results: 173 of 183 M. tuberculosis isolates from the study period underwent DNA fingerprinting. Fingerprinting revealed that five isolates represented false-positive cultures and that 91 (54%) of the remaining 168 isolates were in 15 DNA fingerprinting clusters, which ranged in size from 2 to 29 isolates. Risk factors for clustering were birth in the United States, African-American ethnicity, homelessness, substance abuse, and male sex. Retrospective epidemiologic analysis of inpatient and outpatient visits by the 91 patients who had clustered isolates revealed only one possible instance of patient-to-patient transmission. Conclusions: The DNA fingerprinting of all M. tuberculosis isolates from a 1-year period revealed one possible instance of nosocomial transmission and five false-positive M. tuberculosis cultures. However, these results did not lead to changes in infection-control practices or in clinical care. The study findings do not support the use of DNA fingerprinting for nosocomial tuberculosis surveillance, but they suggest that compliance with the CDC tuberculosis infection-control guidelines may control patient-to-patient transmission in high-risk urban hospitals.
Patients taking stable doses of morphine may drive
Authors: A M Smith
Journal: BMJ (1996)

The preparations were cultured for lactobacilli on MRS agar (Unipath, Basingstoke, Hampshire), for enterococci on m-enterococcus agar (Difco, East Molesey, Surrey), and for anaerobes on Columbia agar (Unipath) plus 5% whole horse blood.Either one whole tablet was crushed in a sterile mortar or the content of a capsule (opened under aseptic conditions) or a weighed amount of powder (approximately 500 mg) was suspended in 10 ml of MRS broth, blended with a Vortex mixer for 1 minute, and allowed to stand for 30 minutes; viable counts were made from the supernatant fractions.Plates were incubated for 48 hours at
Chronic Liver Disease and Hepatitis-B Antigen: A Prospective Study
Authors: L. Van Waes, J. Segers, J. Van Egmond, L. Van Nimmen, F. Barbier, R. Wieme, L. Demeulenaere
Journal: BMJ (1974)

A long-term follow-up of 45 patients with chronic hepatitis and 41 with cirrhosis is reported. Hepatitis-B antigen (HBAg) was present in 19 (42%) of the chronic hepatitis patients and in 20 (49%) of those with cirrhosis. The clinical course and biochemical and histological findings in the HBAg-positive and the HBAg-negative cases were similar, suggesting that HBAg-positive chronic liver disease is not a distinct clinical entity. The presence of antigen and autoantibodies was not found to be mutually exclusive. In HBAg-positive cases antigen tended to persist for months and years. When no irreversible lesions exist disappearance of the antigen may be a sign that the liver disease will resolve.
Detection of aneuploidy in human sperm.
Authors: R W Kapp
Journal: Environmental Health Perspectives (1979)

Adequate methods for monitoring any type of gametic mutation directly in man are virtually nonexistent. A method is presented by which one can monitor Y chromosomal nondisjunction directly in the male gamete by quantifying the number of spermatozoa with two fluorescent bodies (YFF) in 1000 sperm counted. Dried semen slides are stained with quinacrine dihydrochloride and examined under a fluorescent microscope with dark field illumination. This method eliminates the biopsy required for other meiotic studies and further eliminates bias in gametogenic selection by evaluating ejaculated mature spermatozoa. Since chromosomal numerical errors are found in 0.4% of term births and 35% of miscarriages, it is evident that chromosomal aneuploidy constitutes the major mutagenic load in man. In view of the increases observed in the incidence of YFF sperm in patients receiving antineoplastic therapy and in the DBCP-exposed workers, it may be prudent for men who have a history of exposure to mutagens and who are contemplating reproduction to be evaluated by this method prior to attempting conception. Further, this procedure could also be applied to the clinical phase of new drug testing to evaluate the effects of that agent with respect to aneuploidy since the increases in Y chromosomal nondisjunction may well act as a barometer for increases in overall autosomal nondisjunction.