tbuckley/cabot-search huggingface dataset:
The <b> <i>ADPRT V762A</i> </b> Genetic Variant Contributes to Prostate Cancer Susceptibility and Deficient Enzyme Function
Authors: Kristin L. Lockett, M. Craig Hall, Jianfeng Xu, S. Lilly Zheng, Marianne Berwick, Shu-Chun Chuang, Peter E. Clark, Scott D. Cramer, Kurt Lohman, Jennifer J. Hu
Journal: Cancer Research (2004)

Abstract The ADP-ribosyltransferase (ADPRT) gene encodes a zinc-finger DNA-binding protein, poly(ADP-ribose) polymerase-1 (PARP-1), that modifies various nuclear proteins by poly(ADP-ribosyl)ation and functions as a key enzyme in the base excision repair pathway. We have conducted two studies to test whether an amino acid substitution variant, ADPRT V762A (T2444C), is associated with prostate cancer (CaP) risk and decreased enzyme function. The first study used genomic DNA samples from an ongoing, clinic-based case-control study (488 cases and 524 controls) to show that a higher percentage of the CaP cases carried the ADPRT 762 AA genotype than controls (4% versus 2%). In Caucasians, the AA genotype was significantly associated with increased CaP risk [odds ratio (OR), 2.65; 95% confidence interval (CI), 1.08–6.49], and the VA genotype was associated with a slight but not significantly increased CaP risk (OR, 1.18; 95% CI, 0.85–1.64) using VV as the referent group after adjustment for age, benign prostatic hyperplasia, and family history. Furthermore, this association was stronger in younger (&amp;lt;65) men (OR, 4.77; 95% CI, 1.01–22.44) than older (≥65) men (OR, 1.78; 95% CI, 0.55–5.82). The second study used freshly isolated peripheral lymphocytes from 354 cancer-free subjects to demonstrate that the ADPRT 762 A allele contributed to significantly lower adenosine diphosphate ribosyl transferase (ADPRT)/PARP-1 activities in response to H2O2 in a gene dosage-dependent manner (P &amp;lt; 0.0001, test for linear trend). The PARP-1 activities (mean ± SD dpm/106 cells) were 18,554 ± 9,070 (n = 257), 14,847 ± 7,082 (n = 86), and 12,155 ± 6,334 (n = 11) for VV, VA, and AA genotypes, respectively. This study is the first to provide evidence that the ADPRT V762A-genetic variant contributes to CaP susceptibility and altered ADPRT/PARP-1 enzyme function in response to oxidative damage.
Deaths in police custody are being analysed retrospectively
Authors: G. Norfolk, J. Cartwright
Journal: BMJ (1996)

EDITOR,—The Police Complaints Authority has expressed its concern about deaths in police custody to the Home Office,1 and the Association of Police Surgeons has identified a need for further research to be undertaken into the issues concerned in these deaths. The two organisations are currently conducting a retrospective analysis of those deaths in custody that have already been investigated by the Police Complaints Authority. It is hoped that this study will highlight key issues that can then be considered by a confidential inquiry.

Vinod …
Extreme Eosinophilia with Iodide Hypersensitivity
Authors: Harry S. Jacob, James J. Sidd, Burton H. Greenberg, James F. Lingley
Journal: New England Journal of Medicine (1964)

THE differentiation of leukemoid reactions from leukemia, although frequently difficult, can be especially so when involving eosinophilic granulocytes. In cases of extreme leukocytosis the presence of neutrophils with toxic granulation, Döhle bodies or vacuolation1 strongly suggests a non-neoplastic cause of the reaction. With eosinophilic granulocytes, however, these aids are lacking, therefore preventing morphologic differentiation of eosinophilic leukemia from a variety of hypersensitivity syndromes manifesting eosinophilia. In addition, neutrophilic leukemoid reactions associated with septic or necrotic processes are generally brief, permitting early retrospective diagnosis. In contrast, prolonged eosinophilia occurs with many chronic allergic syndromes, compounding further the difficulties in differential diagnosis. . . .
Influence of coronary artery bypass grafting on the outcome of aortic valve replacement in the presence of left ventricular dysfunction: the VERDI (Valve Replacement with Left Ventricular Dysfunction Italian) surgical study
Authors: Roberto Lorusso, Cesare Beghi, Luca Ballore, Piersilvio Gerometta, Claudio Russo, Vincenzo Cianci, Andrea Garatti, Elena Ribera, Tiziano Gherli, Vincenzo Arena, Ettore Vitali, Salvatore Casari, Gaetano Minzioni
Journal: Journal of the American College of Cardiology (2002)
Synthesis of atrial natriuretic polypeptide in human failing hearts. Evidence for altered processing of atrial natriuretic polypeptide precursor and augmented synthesis of beta-human ANP.
Authors: A Sugawara, K Nakao, N Morii, T Yamada, H Itoh, S Shiono, Y Saito, M Mukoyama, H Arai, K Nishimura
Journal: Journal of Clinical Investigation (1988)

To elucidate the synthesis of atrial natriuretic polypeptide (ANP) in the failing heart, 20 human right auricles obtained at cardiovascular surgery were studied. The concentration of alpha-human ANP-like immunoreactivity (alpha-hANP-LI) in human right auricles ranged from 13.8 to 593.5 micrograms/g, and the tissue alpha-hANP-LI concentration in severe congestive heart failure (CHF) (New York Heart Association [NYHA] functional class III and class IV) (235.4 +/- 57.2 micrograms/g) was much higher than that in mild CHF (NYHA class I and class II) (52.5 +/- 15.6 micrograms/g). Atrial alpha-hANP-LI levels were significantly correlated with plasma concentrations of alpha-hANP-LI in these patients (r = 0.84, P less than 0.01). High performance gel permeation chromatography and reverse phase high performance liquid chromatography coupled with radioimmunoassay for ANP revealed that the alpha-hANP-LI in the human auricle consisted of three major components of ANP, gamma-human ANP (gamma-hANP), beta-human ANP (beta-hANP) and alpha-human ANP (alpha-hANP). Comparing percentages of gamma-hANP, beta-hANP, and alpha-hANP in alpha-hANP-LI in severe CHF with those in mild CHF, the predominant component of alpha-hANP-LI was gamma-hANP in mild CHF, whereas beta-hANP and/or alpha-hANP were prevailing in severe CHF and, especially, beta-hANP was markedly increased in human failing hearts. These results demonstrate that the total ANP concentration in the atrium of the human heart is increased in severe CHF and that the increase of ANP in the human failing heart is mainly due to the increase of small molecular weight forms of ANP, beta-hANP, and alpha-hANP, especially beta-hANP, and indicate that the processing of ANP precursor, or gamma-hANP, in the human failing heart differs from that in the normal heart, suggesting that the failing heart augments synthesis and secretion of ANP as one of its own compensatory responses.
Management of Pregnancy Complicated by Hypertrophic Obstructive Cardiomyopathy
Authors: G. M. Turner, C. M. Oakley, H. G. Dixon
Journal: BMJ (1968)

We report our experiences with nine women suffering from hypertrophic obstructive cardiomyopathy who between them had 13 pregnancies, 10 of which were directly managed by us. Though at first we felt that the theoretical hazards of vaginal delivery indicated elective caesarean section, experience has convinced us that in the absence of an obstetrical contraindication these patients may be delivered vaginally provided a betaadrenergic blocking drug is administered during pregnancy and especially during labour, ergometrine is given at the end of the second stage, adequate supplies of cross-matched blood are available, and prophylaxis against infective endocarditis is administered. We have found no evidence of any adverse effects of either propranolol or pronethalol on the foetus.
Folate sufficient subjects do not accumulate additional folates during supplementation
Authors: C.R. Santhosh-Kumar, James S. Bisping, Steven D. Kick, John C. Deutsch, J. Fred Kolhouse
Journal: American Journal of Hematology (2000)

In a double-blinded placebo-controlled trial of folic acid supplementation in 82 alcoholic subjects, it was found that whole blood folate levels, determined by a mass spectrometric method, do not increase in subjects whose baseline folate levels are above the third quartile (folate sufficiency). Since a state of folate sufficiency can now be identified, a recommended daily allowance (RDA) for folate can be determined using objective means. Am. J. Hematol. 64:71–72, 2000. © 2000 Wiley-Liss, Inc.
Methicillin-Resistant Staphylococcus aureus
Authors: William Brumfitt, Jeremy Hamilton-Miller
Journal: New England Journal of Medicine (1989)

STAPHYLOCOCCUS AUREUS is one of the most versatile human pathogens. In the late 1930s, sulfonamides offered the first challenge to S. aureus, but they failed because of their poor clinical performance in the presence of pus and the acquisition of resistance by the bacteria.1 In the early 1940s the introduction of benzylpenicillin (penicillin G) temporarily solved the problem of staphylococcal infections, but the continued use of this agent caused the selection of resistant strains, which produced penicillinase (β-lactamase). By 1948 the prevalence of resistant strains had seriously reduced the value of benzylpenicillin.2 By the end of the 1950s, S. . . .
Epidemiology in Devon
Authors: R. M. S. McConaghey
Journal: BMJ (1957)

The study of epidemic disease is one of the most fasci nating branches of medicine which we in general prac tice encounter. To unravel an outbreak of infection, from whatever cause, requires the detective powers of a Sherlock Holmes, the patience of a dermatologist, and the deductive reasoning of a skilful lawyer. Devon has been blessed with more than its share of epidemiologists. It has also, perhaps, been cursed with more than its share of epidemics. Broadly, we may divide the epidemiology of the country into five ages, according to the impact which certain diseases had upon life in each period. Thus we cannot think of life in the early Middle Ages without associating it with leprosy. The age of plague extended from the Black Death in 1348 to the Great Plague of London in 1665, when it died out as suddenly as it had arrived, over 300 years before. Its place as Captain of the Men of Death was almost immediately taken by smallpox. The age of smallpox extended until the first quarter of the nineteenth century, when it began to fade away under the gathering attack of the disciples of lenner. No sooner was it under control than a fresh invader?Asiatic cholera?took its place. Filthy over crowded hovels and a complete lack of sanitation fos tered not only cholera but also the enteric fevers, which flourished until the work of Chadwick and Simon, Snow and Budd, began to clear up the slums in which they were endemic. So we come to our own times : we live too near to say what fell disease will be singled out as our chief destroyer.
The minimally appropriate electrophysiologic study for the initial assessment of patients with documented sustained monomorphic ventricular tachycardia
Authors: Albert L. Waldo, Masood Akhtar, Pedro Brugada, Richard W. Henthorn, Melvin M. Scheinman, David E. Ward, Hein J.J. Wellens
Journal: Journal of the American College of Cardiology (1985)
Experimental and Clinical Experience with Pancreatic Homotransplantation.
Authors: Yasuo Idezuki
Journal: Annals of Internal Medicine (1968)

s1 May 1968Experimental and Clinical Experience with Pancreatic Homotransplantation.Yasuo Idezuki, M.D., John A. Feemster, M.D., Ronald H. Dietzman, M.D., Robert Ersek, M.D., Frederick Goetz, M.D., Richard C. Lillehei, M.D.Yasuo Idezuki, M.D.Search for more papers by this author, John A. Feemster, M.D.Search for more papers by this author, Ronald H. Dietzman, M.D.Search for more papers by this author, Robert Ersek, M.D.Search for more papers by this author, Frederick Goetz, M.D.Search for more papers by this author, Richard C. Lillehei, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1148_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTwo patients with terminal renal failure and severe diabetes mellitus have received combined cadaver kidney and pancreatic duodenal transplants. One patient survived for 4½ months and did not require insulin to maintain the blood glucose in the normal range while the other lived only 3 weeks. This procedure is soundly based on experimental studies in the dog which show that [1] pancreatectomized dogs can survive for long periods on pancreatic duodenal homografts; [2] when venous drainage of the pancreatic homograft is into the venous system rather than the portal venous system, there is no adverse effect on the activity of... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Yasuo Idezuki, M.D.; John A. Feemster, M.D.; Ronald H. Dietzman, M.D.; Robert Ersek, M.D.; Frederick Goetz, M.D.; Richard C. Lillehei, M.D.Affiliations: Minneapolis, Minnesota PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1148-1148KeywordsBloodDiabetes mellitusGlucoseHomograftsHomotransplantationInsulinRenal failureRenal transplantation ePublished: 1 December 2008 Issue Published: 1 May 1968 PDF downloadLoading ...
Poor response to erythropoietin
Authors: J. Strachan, L. Fleming, J. Dick, I. Henderson, C. Fraser, M. Jones, E. McGregor
Journal: BMJ (1995)

multicentre studies, and clinical trials, appropriate referencing systems need to be developed.I propose that use of a study's name instead of named authors, with details of the writing committee and collaborators clearly stated in a footnote on the title page, is self explanatory and the most elegant solution.This would avoid confusion, facilitate the identification of papers from a particular group, and benefit the individual contributors.
Photostimulation of Phox2b Medullary Neurons Activates Cardiorespiratory Function in Conscious Rats
Authors: Roy Kanbar, Ruth L. Stornetta, Devin R. Cash, Stephen J. Lewis, Patrice G. Guyenet
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Hypoventilation is typically treated with positive pressure ventilation or, in extreme cases, by phrenic nerve stimulation. This preclinical study explores whether direct stimulation of central chemoreceptors could be used as an alternative method to stimulate breathing.To determine whether activation of the retrotrapezoid nucleus (RTN), which is located in the rostral ventrolateral medulla (RVLM), stimulates breathing with appropriate selectivity.A lentivirus was used to induce expression of the photoactivatable cationic channel channelrhodopsin-2 (ChR2) by RVLM Phox2b-containing neurons, a population that consists of central chemoreceptors (the ccRTN neurons) and blood pressure (BP)-regulating neurons (the C1 cells). The transfected neurons were activated with pulses of laser light. Respiratory effects were measured by plethysmography or diaphragmatic EMG recording and cardiovascular effects by monitoring BP, renal sympathetic nerve discharge, and the baroreflex.The RVLM contained 600 to 900 ChR2-transfected neurons (63% C1, 37% ccRTN). RVLM photostimulation significantly increased breathing rate (+42%), tidal volume (21%), minute volume (68%), and peak expiratory flow (48%). Photostimulation increased diaphragm EMG amplitude (19%) and frequency (21%). Photostimulation increased BP (4 mmHg) and renal sympathetic nerve discharge (43%) while decreasing heart rate (15 bpm).Photostimulation of ChR2-transfected RVLM Phox2b neurons produces a vigorous stimulation of breathing accompanied by a small sympathetically mediated increase in BP. These results demonstrate that breathing can be relatively selectively activated in resting unanesthetized mammals via optogenetic manipulation of RVLM neurons presumed to be central chemoreceptors. This methodology could perhaps be used in the future to enhance respiration in humans.
Being non-rational rather than irrational
Authors: Kevin Barraclough
Journal: BMJ (2006)

My realisation that people are not even remotely rational beings came rather late. I think I was at that confusing time towards the end of childhood when the mocking adolescent in you begins to realise that people are generally somewhat frailer and more complicated that you thought. You begin to treat your parents more kindly, and the certainties that seemed blindingly obvious in your first foray into reason become less so. I suspect, though, that …
Routine Endoscopy Using a Magnifying Endoscope for Gastric Cancer Diagnosis
Authors: H. Tajiri, T. Doi, H. Endo, T. Nishina, T. Terao, I. Hyodo, K. Matsuda, K. Yagi
Journal: Endoscopy (2002)

It has been reported that the fine mucosal patterns of the gastric pits can be observed with magnification and this may assist in preliminary evaluation prior to histological diagnosis. The aim of this prospective study was to clarify the relationship between the fine mucosal patterns of gastric lesions and histological findings, and also to evaluate the usefulness of magnifying endoscopy during routine endoscopy.A recently developed magnifying video endoscope, which enables magnification up to 80 times, was used for gastrointestinal endoscopy in 318 patients between January 2000 and January 2001, at the National Shikoku Cancer Center. In total, 232 lesions were detected. However, patients diagnosed by conventional endoscopy as having advanced gastric cancer, malignant lymphoma, or submucosal tumor were excluded from the study. The endoscopic findings for 211 lesions included in this study were compared with the histological findings.Coarse and irregular mucosal patterns were observed in elevated-type cancers by magnifying endoscopy, and in depressed-type cancers there was a finer pit pattern than in the surrounding mucosa, destruction or disappearance of the mucosal microstructure, and abnormal capillary vessels. The magnifying endoscopy results were closely related to the mucosal microstructure observed by dissecting microscopy and to the histological features. The rate of presumptive diagnosis of small gastric cancers was significantly higher when a magnifying endoscope was used compared with conventional endoscopy. In this study, the sensitivity and specificity of magnifying endoscopy as a diagnostic method were 96.0% and 95.5%, respectively.The fine mucosal patterns and the features of capillary vessels, which were identified with the magnifying endoscope, correlated well with the pathological diagnosis. Magnifying endoscopy will be very useful in predicting the histological diagnosis during routine endoscopic procedures.
India's rural medical practitioners are reluctant to refer in severe cases, study finds
Authors: S. Bagcchi
Journal: BMJ (2015)

India urgently needs an appropriate intervention to reduce the potential harm caused by rural medical practitioners (RMPs) and to improve the healthcare they provide, a study has found.

The study, carried out by Swadhin Mondal, an assistant professor at the Institute for Studies in Industrial Development in New Delhi, found that 67% of people in India who require medical care visit RMPs.1 These practitioners do not have any formal medical training but “serve as the first point of contact for healthcare services, especially for outpatient care,” he said. Although countries such as Bangladesh, Malawi, Senegal, South Africa, and Uganda have successfully implemented RMPs for the treatment …
Low dose aspirin and cognitive function in the women's health study cognitive cohort
Authors: Jae Hee Kang, Nancy Cook, JoAnn Manson, Julie E Buring, Francine Grodstein
Journal: BMJ (2007)

<b>Objective</b> To determine whether low dose aspirin protects women aged 65 or more against cognitive decline. <b>Design</b> Cohort study within both arms of the women9s health study, a randomised, double blind, placebo controlled trial of low dose aspirin for the primary prevention of cardiovascular disease and cancer, 1992-5. <b>Setting</b> Women9s health study, 1998-2004. <b>Participants</b> 6377 women aged 65 or more. <b>Interventions</b> Low dose aspirin (100 mg on alternate days) or placebo for a mean of 9.6 years. <b>Main outcome measures</b> Women had three cognitive assessments at two year intervals by telephone. The battery to assess cognition included five tests measuring general cognition, verbal memory, and category fluency. The primary prespecified outcome was a global score, averaging performance across all tests. The key secondary outcome was a verbal memory score, averaging performance on four measures of verbal memory. <b>Results</b> At the initial assessment (mean 5.6 years after randomisation) cognitive performance in the aspirin group was similar to that of the placebo group (mean difference in global score −0.01, 95% confidence interval −0.04 to 0.02). Mean decline in the global score from the first to the final cognitive assessment was also similar in the aspirin compared with placebo groups (mean difference 0.01, −0.02 to 0.04). The risk of substantial decline (in the worst 10th centile of decline) was also comparable between the groups (relative risk 0.92, 0.77 to 1.10). Findings were similar for verbal memory; however, a 20% lower risk was observed for decline in category fluency with aspirin (relative risk 0.80, 0.67 to 0.97). <b>Conclusion</b> Long term use of low dose aspirin does not provide overall benefits for cognition among generally healthy women aged 65 or more.
Abstract 3287: Sensitizing cancer cells to chemotherapy.
Authors: Kathryn E. Wolak, Russell Bainer, Andrew Skol, Kenan Onel
Journal: Cancer Research (2013)

Abstract A wide range of cancers are either initially resistant to chemotherapy or are sensitive, but subsequently relapse through acquired drug resistance. Alterations in the p53 pathway are associated with drug resistance, underscoring its central role in determining response to chemotherapy. Using pediatric B-cell acute lymphoblastic leukemia as a model, we identified a set of p53-regulated transcriptional targets that comprise an apoptotic gene signature significantly associated with response to therapy and independently prognostic for outcome in pediatric ALL. We hypothesize that cells can be primed for an enhanced apoptotic response to chemotherapy by modulating expression levels of the p53-regulated apoptotic signature genes with small molecules before administering chemotherapy. We conducted a high-throughput screen to identify novel compounds that prime ALL cells for apoptosis to convert a chemotherapy-resistant cell into one that is sensitive. This screen was performed using 83,745 compounds in both the wild-type p53 cell line TK6 and the mutant-p53 line, WTK1. Cells were treated with either compound alone or compound plus daunorubicin, a drug used to treat ALL. Compounds were normalized and scored by using both the B-score and the robust Z-score. “Hits” were defined as compounds that do not significantly alter viability of the cells alone, but significantly increase daunorubicin-induced cell death. We confirmed the effects of the compounds in other B-cell ALL cell lines. In an effort in investigate mechanism, we looked at synergism using other chemotherapies with different modes of action. One compound was very synergistic with cisplatin, and we then extended the experiment to other cell types. We found that the synergism with cisplatin holds in all cell types tested, including T-cell ALL, lymphoma, breast, ovarian and colon cancer. In paired cisplatin-sensitive and resistant ovarian cancer cell lines, we find that the non-toxic doses of the compound can sensitize the resistant line and convert it to respond to cisplatin at the same doses as the parental sensitive line. Looking at the pathways induced by these compounds, we find important components in the cellular response to chemotherapy that can be manipulated to convert a chemoresistant cell into one that is sensitive. Citation Format: Kathryn E. Wolak, Russell Bainer, Andrew Skol, Kenan Onel. Sensitizing cancer cells to chemotherapy. [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 3287. doi:10.1158/1538-7445.AM2013-3287