tbuckley/cabot-search huggingface dataset:
Natural killer cells, miscarriage, and infertility
Authors: Ashley Moffett, Lesley Regan, Peter Braude
Journal: BMJ (2004)

perspective and doesn't fulfil requirements for equity at national or international levels.Introducing user charges is likely to be inequitable as well as adversely affecting adherence. 18 19Many families will already be living in poverty as a result of a reduction in income or paying for AIDS care.Providing free access to antiretroviral drugs based on rights and not ability to pay, 19 as occurs in the Senegal national programme, will be most equitable, will resolve dilemmas over the treatment of migrants, and will also reduce migration to obtain antiretroviral drugs. ConclusionsThe 3 by 5 initiative faces important challenges in meeting the desperate need for antiretroviral drugs in many developing countries,.Constructive dialogue between stakeholders with different agendas, including healthcare workers, public health managers, community and faith based organisations, and people with AIDS, will be crucial if the initiative is to succeed.The prevailing social strategies must be considered carefully when setting up programmes and working relationships, in order to capitalise on and not undermine the existing social order.In an interview in Bangkok, the executive director of UNAIDS noted that "antiretroviral therapy is still a rare commodity, and it will be for some time.The result of that is always higher price, and also higher price in terms of power.Who has access to it, and who comes first: it's a terrible issue."w20 Without addressing this and the other issues we have raised, the 3 by 5 initiative may fall short of its goals.ASF, IJH, and DSM have received support from Health and Development Networks (www.hdnet.org) to report on international AIDS events which have helped inform this article.The views expressed do not necessarily represent the views of organisations for which the authors work.We thank the external reviewers for their helpful comments.
3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Inhibitor, Fluvastatin, as a Novel Agent for Prophylaxis of Renal Cancer Metastasis
Authors: Akio Horiguchi, Makoto Sumitomo, Junichi Asakuma, Takako Asano, Tomohiko Asano, Masamichi Hayakawa
Journal: Clinical Cancer Research (2004)

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, also called statins, are currently used widely as a safe, effective therapeutic in the treatment of hypercholesterolemia. Recently, statins have been recognized for their activity against cancer. In the present study, we examined the effect of a synthetic statin, fluvastatin, on the development of renal cancer.The effects of fluvastatin on cell viability, cell cycle, in vitro angiogenesis, and invasive properties were examined in murine renal cancer cell Renca. The changes in cell cycle-associated proteins, p21(Waf1/Cip1) and p53, and rac1 phosphorylation were analyzed by Western blotting. The prophylactic efficacy of fluvastatin to murine pulmonary metastasis of Renca was examined.Fluvastatin inhibited in vitro growth of Renca cells in a time- and dose-dependent manner, with up to 70% inhibition at a concentration of 10 mumol/L. This inhibitory effect was due to cell cycle arrest at the G(1) phase and induction of apoptosis accompanied by up-regulation of p21(Waf1/Cip1) and p53. The invasive properties of Renca cells through Matrigel were inhibited by fluvastatin, with decreased phosphorylation of rac1. In vitro angiogenesis was also inhibited by fluvastatin. Furthermore, oral administration at doses of 1 to 10 mg/kg/d, for 12 days after inoculation of Renca cells via the tail vein, significantly decreased the amount of pulmonary metastasis.Because our results suggest that fluvastatin may effectively inhibit in vitro tumor growth, invasion, angiogenesis, and metastasis of Renca cells, oral administration of fluvastatin could be a novel, safe, and effective agent for preventing metastasis of renal cancer.
Reviews, Notes, and Listings: Gastroenterology: Double Contrast Gastrointestinal Radiology
Authors: Dina F. Caroline
Journal: Annals of Internal Medicine (1993)

Literature of Medicine1 February 1993Reviews, Notes, and Listings: Gastroenterology: Double Contrast Gastrointestinal RadiologyDina F. Caroline, MDDina F. Caroline, MDTemple University Hospital, Philadelphia, PA 19140.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-3-199302010-00046 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Double Contrast Gastrointestinal RadiologySecond edition. Igor Laufer and Marc S. Levine; eds. 701 pages. Philadelphia: W.B. Saunders Co.; 1992. $125.00.As the long-awaited second edition to the classic text on double-contrast technique, this volume lives up to all expectations. Dr. Laufer, one of the acknowledged leaders in gastrointestinal radiology, is an articulate proponent and teacher of double-contrast technique. He is joined in editing this edition by his protege and colleague Marc Levine, who has an established reputation as an expert in his own right.The format retains the original organization. Introductory chapters are devoted to principles and techniques. Each organ of the ... Author, Article, and Disclosure InformationAffiliations: Temple University Hospital, Philadelphia, PA 19140. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1993Volume 118, Issue 3Page: 238KeywordsColorectal cancerDiagnostic radiologyEsophagusGastroenterology and hepatologyInflammatory bowel diseaseMotivationPharynxRadiologistsRectumStomach ePublished: 15 August 2000 Issue Published: 1 February 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Treating preinfected wounds
Authors: J. A. Raeburn
Journal: BMJ (1969)

MBICA OHNAL coronary care.The patient with an apparently mild myocardial infarction is at as great a risk of developing fatal ventricular dysrhythmia as the patient with a clinically severe infarct.4In Newcastle the interval between the receipt of the call from the practitioner and the arrival of the coronary care team with the patient (mean 21 minutes) contrasts with the Belfast time (median 10 minutes).The inordinate delay may contribute to the lack of interest of the Newcastle practitioners in the scheme.Dr. Dewar and his colleagues indicate that only 420% of the Newcastle practitioners use the mobile unit and that the number is not increasing.A questionary conducted by one of us (Dr.Zaidi) in March 1969 indicated that 89% of the Belfast practitioners use the mobile scheme.Another important difference between the two schemes is that in Belfast only personnel who have gained experience in the hospital coronary care unit are allowed to go on the mobile team.We agree with Dr. Dewar and his colleagues that it is most important to have adequate inpatient coronary care facilities for reception of patients managed by a mobile unit.It should be stressed, however, that all the available data indicate that at least two-thirds of the deaths from myo- cardial infarction occur outside hospital and that therefore when problems of staffing exist priority should be given to staffing of the mobile unit.-Weare, etc.,
Abstract 5205: Iron metabolism informs glioblastoma stem cell maintenance
Authors: David L. Schonberg, Jeremy N. Rich
Journal: Cancer Research (2012)

Abstract Glioblastoma is a highly lethal cancer that is characterized by florid angiogenesis, invasion into normal brain, and therapeutic resistance. Glioblastomas display cellular hierarchies with a self-renewing, tumorigenic glioblastoma stem cell (GSC) at the apex. The significance of GSCs in tumor biology has been supported by work from our group and others showing that GSCs are relatively resistant to conventional therapies, promote tumor angiogenesis, and are highly invasive. By comparing GSCs to matched differentiated tumor bulk, we have identified a number of molecular targets that function in maintenance of the cellular hierarchy and tumor growth. We have now identified increased iron metabolism as a characteristic of GSCs. Normal glial progenitors accumulate iron to increase migration and proliferation. Brain tumors accumulate iron and iron regulators are associated with poor survival. As hypoxia induces iron regulators and maintains the cellular hierarchy, we are investigating iron regulation in GSCs. Ectopic delivery of iron to GSCs increases tumorsphere growth while disrupting iron metabolism in GSCs using shRNA reduces cell growth and decreases the expression of angiogenic growth factors. Collectively, these results suggest that iron metabolism is important for GSC maintenance and tumorigenic potential. 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 5205. doi:1538-7445.AM2012-5205
Mannose corrects altered N-glycosylation in carbohydrate-deficient glycoprotein syndrome fibroblasts.
Authors: K Panneerselvam, H H Freeze
Journal: Journal of Clinical Investigation (1996)

Type I carbohydrate-deficient glycoprotein syndrome (CDGS) patients fail to add entire N-linked oligosaccharide chains to some serum glycoproteins. Here we show that four CDGS fibroblast cell lines have two related glycosylation abnormalities. First, they incorporate 3-10-fold less [3H] mannose into proteins, and, second, the size of the lipid-linked oligosaccharide precursor (LLO) is much smaller than in controls. Addition of exogenous mannose, but not glucose, to these CDGS cells corrects both the lowered [3H] mannose incorporation and the size of LLO. These corrections are not permanent, and the defects immediately reappear when mannose is removed. To explore further the basis of mannose correction, we analyzed the amount of 3H-labeled LLO intermediates. Except for dolichol-P-mannose, other precursors, including mannose, mannose-6-phosphate, mannose-1-phosphate, and GDP-mannose, all showed a 3-10-fold decrease in CDGS cells. Thus, there are no obvious lesions in the intracellular conversion of mannose into LLO, and, once inside the cell, [3H]mannose appeared to be metabolized normally. Initial velocities of [3H]mannose uptake were two- to threefold less in CDGS cells compared with controls, and this slower transport may partially explain the reduced [3H]mannose incorporation in CDGS cells. Since we previously showed that the enzymes converting glucose to mannose-6-phosphate appear to be normal, our results suggest that cells may acquire or generate mannose in other ways. Although we have not identified the primary defect in CDGS, these studies show that intracellular mannose is limited and that some patients might benefit from including mannose in their regular diets.
Book: Bodies Politic: Disease, Death and Doctors in Britain, 1650–1900
Authors: Eoin O'Brien
Journal: BMJ (2001)

Bodies Politic: Disease, Death and Doctors in Britain, 1650-1900 by Roy Porter. Reaktion Books, £25, pp 328. ISBN 1 86189 094 X. Rating: ★★


This book comes well announced: “. . . splendid book . . . a tonic to those dismayed by the current writing-down of English history” (Sunday Telegraph); “. . . exhilarating” (Sunday Times); “simply superb” (New Statesman). This should be enough not only to whet the reviewer's appetite but also to bias opinion. And yet my reaction at the end of an enjoyable read is one of disappointment, disappointment that a magnificent opportunity to do justice to an immense and unique labour of historiography has been squandered. Let me explain. 




Roy Porter's purpose in Bodies Politic is to rescue imagery from obscurity and academic denigration, and to integrate it with the traditional way of portraying history in writing. He rightly sees the microcosm of medicine as “a costume drama or a travelling circus, embodied in performance, rhetoric, and ritual history,” which is therefore ideally suited to the application of an added dimension, namely the pictorial medium.

On one front he succeeds, but his publisher fails him, and fails him badly. In a book that espouses imagery, presentation, design, and reproduction of the chosen imagery are paramount, and this book fails in all of these and does the author a grave disservice. Bodies Politic, by the author's own admission, purports to be a “coffee table” book, yet it lacks all the merits of that often deprecated species. It is too small to allow for illustrative display, the design is awful, the pictures are badly reproduced (especially the black and white illustrations), the colour illustrations are grouped in sections so that the reader is forced to flick forward or back to find them, and when they are located the print size of the captions is so small as to be painful to read.

Leaving aside these criticisms, the text is indeed a rollicking jaunt through a quarter century of English medical history. The extent of Porter's research is truly vast, and yet he manages to assemble his material in an erudite and readable style full of surprises and not infrequent gems. For example, when John Radcliffe, who often assumed an anti-intellectual pose, even going so far as to claim he had never read Hippocrates, bequeathed his library to Oxford, Samuel Garth quipped that “it was a bit like a eunuch founding a seraglio.” The social attitudes of the times are joyously put in perspective (and not so joyously illustrated) from Swift's denigration of the aging trollop, to James Graham's exhortation that “the genitals are the true pulse, and infallible barometer of health,” and onwards to the Victorian era and the likes of Lancet founder Thomas Wakley, whose contribution to progress, in Porter's view, was his recognition that the sorry state of medicine was attributable to it being “a house divided against itself.”

Bodies Politic is both a failure and a success. One hopes that the book can be published again doing justice to the illustrative material.
Diagnostic Decision
Authors: KENNETH M. MOSER
Journal: Annals of Internal Medicine (1983)

Use of the balloon-tipped (Swan-Ganz) pulmonary artery catheter has increased in recent years. The device has three fundamental applications: pressure measurement, flow measurement, and blood sampling. Like any invasive procedure, this catheter should be used only after careful assessment of factors that affect its risk/benefit ratio. There must be a well-defined indication for the procedure. Physicians must be aware of the factors that can influence the validity of the measurements. Familiarity with the technical details of the procedure and with potential complications and how to avoid or manage them is essential to minimize risks and increase the likelihood of obtaining useful information.
P123The rescue of Ca2+ cycling abnormalities conferred by HCM-causing mutations with analogues of the green tea polyphenol epigallocatechin-3-gallate
Authors: P Robinson, X Liu, Y-H Zhang, A Khandelwal, B Blagg, B Casadei, H Watkins, C Redwood
Journal: Cardiovascular Research (2014)

Mutations in thin filament regulatory proteins that cause hypertrophic cardiomyopathy (HCM) confer distinct primary alterations of cardiac contractility. We have shown that altered Ca2+-buffering by mutant thin filaments leads to altered Ca2+ handling and results in stimulation of Ca2+-dependent signalling pathways. To do this we have used adenoviral mediated expression of cTnT R92Q, cTnI R145G and α-TM D175N in adult guinea pig cardiomyocytes at a ratio of 1:1 with the endogenous protein. Simultaneous measurement of unloaded sarcomere-shortening and Ca2+ transients using fura-2 loading, showed the HCM mutations caused a significant decrease in the basal sarcomere length coupled with an increase in the diastolic Ca2+ concentration. The mechanism of alterations to EC-coupling was also investigated using tetracaine and caffeine challenging combined with simultaneous whole cell patch clamping. HCM mutant cells displayed reduced SR load (~1.4fold), slowed NCX calcium extrusion (~2.5fold), unchanged SERCA2 activity, increased ryanodine receptor leak (~5fold) and increased calcium buffering (~3fold). This was coupled to an increase in Ca2+ dependent NFAT nuclear localisation. Further studies using the green tea catechin, epigallocatechin gallate (EGCg) and sister compound epicatechin-3-gallate (ECG), have shown that the compounds can partiality reverse the increase in diastolic Ca2+ observed in cardiomyocytes containing HCM causing mutations. The mechanism is thought to be via an interaction with cTnC (measured using intrinsic cTnC tyrosine fluorescence) which in turn causes a reduction of in vitro thin filament Ca2+ affinity (measured using cTnC labelled with IAANS fluorophore at Cys 35). Data acquired so far suggests that catechins and their derivative compounds may provide a possible therapeutic approach for correcting Ca2+ regulation and Ca2+ dependent remodelling in HCM. We have recently obtained library of 37 EGCg analogues which we have screened for cTnC affinity and thin filament Ca2+ affinity. We have now identified several catechins with potentially greater efficacy than the parent compound, and plan to test their ability to rescue the cellular HCM phenotype characterised above.
Policy Analysis, Politics and the Problems of Health Care
Authors: William B. Schwartz
Journal: New England Journal of Medicine (1972)

At the very moment that the nation embarks on a major restructuring of the health-care system, it has become increasingly evident that we face enormous unsolved problems in planning and in implementation of change. A glimpse of the difficulties that can be anticipated is perhaps most dramatically evident from experience with the Medicare-Medicaid program. A fundamental error in the design of this program, and one that promises to be repeated in each of the proposed bills designed to insure comprehensive care, lies in the almost exclusive concern with payment and the virtually complete indifference to the problem of increasing the . . .
Location of the lower oesophageal sphincter and the squamous columnar mucosal junction in 109 healthy controls and 778 patients with different degrees of endoscopic oesophagitis.
Authors: A Csendes, F Maluenda, I Braghetto, P Csendes, A Henriquez, M S Quesada
Journal: Gut (1993)

In this study the location of the lower oesophageal sphincter measured by manometry and the location of the squamous columnar junction measured by endoscopy were determined in 109 healthy controls and 778 patients with different degrees of endoscopic oesophagitis. No significant differences in the prevalence and severity of the heartburn and regurgitation were observed when different degrees of oesophagitis were compared but dysphagia was more common and severe in patients with complicated Barrett9s oesophagus (p &lt; 0.001). This group also showed a male predominance and older age compared with other groups. The total length of the oesophagus, measured by the location of the distal end of the lower oesophageal sphincter was similar in all patients; however, the location of the squamous columnar junction extended more proximally and was related to the increasing severity of endoscopic oesophagitis. The manometric defects at the cardia were more frequent in severe oesophagitis (p &lt; 0.001). These results suggest that, during the course of oesophagitis, the squamous columnar junction is displaced proximally. This displacement is limited to the mucosa, however, and does not involve the muscular layer, because the lower oesophageal sphincter undergoes no dislocation.
Traumatic Rupture of the Aorta
Authors: Gus J. Vlahakes, Ralph L. Warren
Journal: New England Journal of Medicine (1995)

The report in this issue of the Journal by Smith et al.1 on the use of transesophageal echocardiography in the diagnosis of traumatic disruption of the thoracic aorta represents an important step forward in the evaluation of patients with major chest trauma. Rupture of the aorta is a frequent cause of death after trauma. Most patients who sustain such injuries die at the trauma scene from sudden, massive exsanguination. For those who survive to reach a trauma center, a high index of suspicion for the injury on the part of clinicians, sensitive diagnostic tests to confirm or exclude the diagnosis, . . .
Abstract 5104: Identification of cancer-specific COPI inhibitors and their associated apoptotic cell death pathways
Authors: David J. Oliver, Anusha Chaparala, Emeka Okafor, Carlos J. Camacho, Alexander S. Doemling, Felix T. Wieland, Igor B. Roninson, Michael Shtutman
Journal: Cancer Research (2014)

Abstract The COPI complex is a heptameric complex involved in multiple aspects of intravesicular transport. Recently, Shtutman et al. identified the ζ1 subunit of the COPI complex as a potential target for cancer therapy1. The ζ subunit of COPI is coded for by two genes, COPZ1 and COPZ2. In normal tissue, both COPZ genes are expressed and the protein products are functional isoforms within the COPI complex. In numerous different cancers, COPZ2 is silenced and the cells must depend on the ζ1 isoform for COPI function. When ζ1 is inhibited by siRNAs, cancer cells undergo apoptotic cell death while normal cells, which retain the ζ2 isoform, survive. Thus, the ζ1 subunit of the COPI complex is a potential target for cancer therapy. Here we present our work to develop and test small molecule inhibitors of ζ1-containing COPI complexes, as well as the identification of the apoptotic cell death pathways activated upon ζ1 depletion with siRNAs. We have identified a small molecule which disrupts the formation of COPI vesicles in biochemical and immunofluorescence studies, and also kills cells in a ζ1-specific manner. In addition we have shown that the unfolded protein response (UPR) is activated by ζ1 depletion but that it is not the primary activator of apoptotic cell death in cancer cells. The identification of small molecules which can inhibit ζ1-containing COPI will be a valuable tool for cancer therapy as well as the study of COPI biology. In addition, elucidation of the mechanism of activation and execution of apoptosis upon COPI depletion will provide insight into methods for combination therapy. Citation Format: David J. Oliver, Anusha Chaparala, Emeka Okafor, Carlos J. Camacho, Alexander S. Doemling, Felix T. Wieland, Igor B. Roninson, Michael Shtutman. Identification of cancer-specific COPI inhibitors and their associated apoptotic cell death pathways. [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 5104. doi:10.1158/1538-7445.AM2014-5104