tbuckley/cabot-search huggingface dataset:
COP9 Signalosome Regulates Autophagosome Maturation
Authors: Huabo Su, Faqian Li, Mark J. Ranek, Ning Wei, Xuejun Wang
Journal: Circulation (2011)

Background— Autophagy is essential to intracellular homeostasis and is involved in the pathophysiology of a variety of diseases. Mechanisms regulating selective autophagy remain poorly understood. The COP9 signalosome (CSN) is a conserved protein complex consisting of 8 subunits (CSN1 through CSN8), and is known to regulate the ubiquitin-proteasome system. However, it is unknown whether CSN plays a role in autophagy. Methods and Results— Marked increases in the LC3-II and p62 proteins were observed on Csn8 depletion in the cardiomyocytes of mouse hearts with cardiomyocyte-restricted knockout of the gene encoding CSN subunit 8 (CR-Csn8KO). The increases in autophagosomes were confirmed by probing with green fluorescent protein–LC3 and electron microscopy. Autophagic flux assessments revealed that defective autophagosome removal was the cause of autophagosome accumulation and occurred before a global ubiquitin-proteasome system impairment in Csn8-deficient hearts. Analyzing the prevalence of different stages of autophagic vacuoles revealed defective autophagosome maturation. Downregulation of Rab7 was found to colocalize strikingly with the autophagosome accumulation at the individual cardiomyocyte level. A significantly higher percent of cardiomyocytes with autophagosome accumulation underwent necrosis in CR-Csn8KO hearts. Long-term lysosomal inhibition with chloroquine induced cardiomyocyte necrosis in mice. Rab7 knockdown impaired autophagosome maturation of nonselective and selective autophagy and exacerbated cell death induced by proteasome inhibition in cultured cardiomyocytes. Conclusions— Csn8/CSN is a central regulator in not only the proteasomal proteolytic pathway, but also selective autophagy. Likely through regulating the expression of Rab7, Csn8/CSN plays a critical role in autophagosome maturation. Impaired autophagosome maturation causes cardiomyocytes to undergo necrosis.
Diagnosis of Infectious Mononucleosis
Authors: Allen Silverstein
Journal: JAMA (1973)

<h3>To the Editor.—</h3> In a recent letter (226:78, 1973), Dr. John Dirckx called attention to the need for observance of strict criteria for the diagnosis of infectious mononucleosis. While I have no arguments with this general concept, I would like to answer certain criticisms raised by Dr. Dirckx about our reporting 15 patients who had neurological manifestations as the heralding or major manifestation of the disease.<sup>1</sup> After quoting three sentences from the materials and methods section of this article—a quotation that left out a reference to Hoagland's diagnostic criteria<sup>2</sup>(cited in our original article)—Dr. Dirckx stated he failed to understand the exclusion of the usual clinical criteria for the diagnosis of infectious mononucleosis. This was done because the article dealt with patients who came to the neurologist with essentially neurological illnesses. It was not a report of infectious mononucleosis alone; nor was it of the neurological manifestations, which
Roentgenographic Exercise Test
Authors: Gary M. Boelling
Journal: JAMA (1967)

In the roentgenographic exercise test, the systolic heart size (transverse diameter) is recorded before and immediately after a 100-yard walk. All normal subjects in this study responded with a 1- to 10-mm reduction in diameter. The diameter became larger or did not change in 83% of patients with angina pectoris. Myocardial infarction provoked abnormal response during convalescence. Persistent abnormality was noted only in those patients who continued to have chest pain. Normal response was unaffected by valvular disease, noncardiac chest pain, pulmonary embolism, or nonspecific electrocardiographic abnormalities in the absence of myocardial disease. Roentgenographic exercise tests accurately indicated the presence of coronary disease when the patient was resting and when the electrocardiograms from the Master 2-step test were normal. When performed, coronary angiography confirmed the results of roentgenographic exercise tests in each instance. The test appears to be a useful means of determining the state of the myocardium.
Abstract 5312: Quantitative proteomic analysis of cell-surface membrane proteins: Biomarker discovery in esophageal squamous cancer
Authors: Emi Harada, Satoshi Serada, Tsuyoshi Takahashi, Minoru Fujimoto, Tetsuji Naka
Journal: Cancer Research (2014)

Abstract Background. Esophageal squamous cell cancer (ESCC) is associated with a poor prognosis and high recurrence rate. Identification of proteins that are useful for prognostic assessment and therapeutic targets in ESCC is required. Quantitative proteomic analysis provides a powerful approach in screening for alterations in protein levels. An analysis of the differential expression of cell-surface membrane proteins would be useful for identification of proteins associated with cell proliferation, cell migration, drug resistance and therapeutic target for antibody-based therapy. Purpose of study. To identify cell-surface membrane proteins overexpressed in ESCC compared with normal esophageal epithelial cells, which may represent novel biomarkers of disease and therapeutic targets. Procedures. We performed a biotinylation-based approach for cell-surface membrane enrichment combined with iTRAQ (isobaric tags for relative and absolute quantitation) technology using nano-LC-MS/MS analysis, to identify cell surface proteins overexpressed in ESCC cell lines compared with control normal esophageal epithelial cell line. Results. By combining biotinylation of cell-surface membrane proteins and iTRAQ analysis, 1635 proteins were identified, which contained 402 cell surface membrane proteins. We identified overexpression of 12 membrane proteins, whose expression increased more than twofold in at least four of six ESCC cell lines compared with a normal esophageal epithelial cell line (HEEpic). By this proteomic approach, we identified several tumor antigens which included antigens previously associated with ESCC and antigens not previously reported in this disease. Furthermore, we also successfully identified novel antigen associated with proliferation of ESCC. Cell surface expression of this antigen on ESCC was confirmed by FACS analysis and immunohistochemistry. By transfection of siRNA specific for this novel antigen, significant growth suppression was shown by WST8 assay and induction of apoptosis was detected by caspase-3 assay. Conclusions. By using a high throughput cell-surface membrane proteomic analysis combining biotinylation of cell-surface membrane protein and iTRAQ technology, several ESCC candidate antigens were identified. Further studies on the physiological role of novel tumor antigens overexpressed in ESCC and their application as biomarkers/therapeutic targets are underway. . Note: This abstract was not presented at the meeting. Citation Format: Emi Harada, Satoshi Serada, Tsuyoshi Takahashi, Minoru Fujimoto, Tetsuji Naka. Quantitative proteomic analysis of cell-surface membrane proteins: Biomarker discovery in esophageal squamous cancer. [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 5312. doi:10.1158/1538-7445.AM2014-5312
Drug Interactions: A Source Book of Adverse Interactions, Their Mechanisms, Clinical Importance and Management
Authors: Donald R. Miller
Journal: Annals of Internal Medicine (2000)

Medical Writings: Book Notes7 November 2000Drug Interactions: A Source Book of Adverse Interactions, Their Mechanisms, Clinical Importance and ManagementDonald R. Miller, PharmDDonald R. Miller, PharmDCollege of Pharmacy, North Dakota State University, Fargo, North Dakota. (Miller)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-9-200011070-00041 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Fifth edition. Stockley IH. 948 pages. London: Pharmaceutical Pr; 1999. $120.00. ISBN 0853694249. Order phone 44-1-491-829-272.Field of medicine: Pharmacology.Format: Hardcover book.Audience: Physicians and pharmacists.Purpose: To provide busy health professionals with a concise source of useful information on drug interactions.Content: An introductory chapter presents general considerations and mechanisms of drug interactions. The rest of the book comprises 24 chapters, each of which covers a major drug class. In each chapter, individual monographs on drug interactions are organized by clinical evidence, mechanism, and importance and management. The index, which is arranged by generic drug names, makes it ... Author, Article, and Disclosure InformationAffiliations: College of Pharmacy, North Dakota State University, Fargo, North Dakota. (Miller) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 7 November 2000Volume 133, Issue 9Page: 760KeywordsComputer softwareDrug informationDrug interactionsDrugsHealth information technologyPharmacistsPharmacologySoftware tools ePublished: 7 November 2000 Issue Published: 7 November 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Leslie Le Quesne
Authors: P. Davies
Journal: BMJ (2011)

Outcomes focused surgeon who worked on deep vein thromboses



Leslie Le Quesne, who has died aged 91, was a bold and innovative surgeon, renowned research scientist, and revered teacher. As professor of surgery at the Middlesex Hospital, London, he helped to revolutionise care for patients after operation. His work on deep vein thrombosis (DVT) had a big impact and led to elastic stockings being supplied to long haul air travellers. Under his direction, the British Journal of Surgery vastly expanded its readership and influence. And he was the first surgery professor to become deputy vice chancellor of London University.

As a young surgeon in the 1950s Le Quesne was one of a new breed who cared about outcomes as much as technique and was dissatisfied when patients died after operations judged to have been successful. He investigated factors such as nutritional fitness for surgery and the body’s response after an operation. His groundbreaking 1954 monograph, Fluid Balance in Surgical Practice , was based on his own observations at the Middlesex. A slim volume …
Mid Staffs is evidence of all that is wrong with NHS management
Authors: Heather Wood
Journal: BMJ (2013)

The balance of power must shift back to the clinicians

The horrors at Stafford Hospital were failures of clinical care—but these were the symptoms, albeit deeply distressing, of a serious underlying illness. And that deep rooted pathology is the stranglehold that managers, many apparently devoid of an ethical code and certainly without a regulatory body, have on the NHS. Some of what follows has been expressed much more eloquently by Brian Jarman, director of the Dr Foster unit at Imperial College London,1 in his recent editorial, “When managers rule.”2

The line promulgated by the chief executive of the NHS in his evidence to the Francis inquiry that Mid Staffordshire was a one off is simply not sustainable. The media, the Patients Association, Age UK, and others reinforce the picture of poor care of older people.

In all the investigations involving acute hospitals that I led on behalf of the Healthcare Commission we found clear evidence of poor care on general wards, even when the focus was specifically on, for example, outbreaks of Clostridium difficile . Where some poor care may, arguably, stem from a fault line in the training of nurses, we found evidence that the poor care and failure to control infection were related to the determination of managers to drive through financial restraint and achievement of targets.

All the failings at Mid Staffs derived from the handing of control of decisions on priorities from the clinical professions to managers who were ultimately expected to follow the orders of senior managers. Those giving the orders often ignore or …
Materials and Orthopaedic Surgery
Authors: Leonard F. Peltier
Journal: JAMA (1980)

This book is a timely review of the current state of our knowledge of materials, particularly metals, and their uses in orthopedic surgery. It is divided into two parts. The first deals with the structure and properties of the materials themselves and the biologic response of tissues to their implantation. The chapter on the design, use, and care of implants is particularly valuable for surgeons and operating room personnel responsible for handling the implants before and during the operation. The second portion of the book deals with the applications to orthopedic surgery of the wide variety of materials. The use of materials in the treatment of fractures and reconstructive operations is considered in detail. Some might say that this portion of the book is redundant. However, the basic principles are well laid out, and their application to surgical practice is well illustrated by technical descriptions of the operative procedures. The
End-Stage Renal Disease Attributable to Diabetes Mellitus
Authors: Thomas V. Perneger, Frederick L. Brancati, Paul K. Whelton, Michael J. Klag
Journal: Annals of Internal Medicine (1994)

Objective: To determine the proportion of end-stage renal disease associated with diabetes mellitus in a biracial population, using population-attributable risk estimates. Design: Case-control study. Setting: Population-based study in Maryland, Virginia, West Virginia, and Washington, D.C. Participants: 716 newly treated patients with kidney failure aged 20 to 64 years and 361 age-matched controls. Measurements: Self-reported history of diabetes mellitus, including type, duration, treatment, and complications. Results: Persons with insulin-dependent diabetes (odds ratio, 33.7) and non–insulin-dependent diabetes (odds ratio, 7.0) were at greater risk for end-stage renal disease than were persons without diabetes. The odds ratio was only slightly increased for diabetes lasting less than 15 years, but the ratio increased more than 20-fold for diabetes lasting 15 years or more. The population-attributable risk for kidney failure was 21% for insulin-dependent diabetes and 21% for non–insulin-dependent diabetes (42% overall). A similar proportion of end-stage renal disease was attributed to diabetes in whites (44%) and in blacks (41%). Insulin-dependent diabetes had a relatively greater effect on the incidence of kidney failure in whites; in contrast, non–insulin-dependent diabetes had a relatively greater effect on kidney failure in blacks. Conclusions: Diabetes mellitus has a major effect on the incidence of end-stage renal disease in nonelderly adults. In black persons, diabetes may be responsible for a larger proportion of end-stage renal disease than is suggested by the use of clinical diagnoses of underlying renal disease made by patients' nephrologists. Prevention of end-stage renal disease associated with diabetes mellitus (both insulin-dependent and non–insulin-dependent diabetes) requires increased attention from laboratory and clinical researchers.
General-practitioner Hospitals
Authors: A. M. W. Porter
Journal: BMJ (1966)

MEBRITCISH 1425 therefore more expensive, than one would require if housing oneself privately.Now that the Review Body have said that the Health Department and the representa- tives of the profession should negotiate a system of charges based on the abolition of the lodging charge for compulsory resident medical staff (paragraph 138 (a) ), what hap- pens to the married houseman or registrar who is a compulsory resident in hospital married accommodation ?Will his rent fall by the appropriate amount or will he con- tinue to pay the lodging charge, not only for himself but also for his dependants ?Will our representatives negotiate a system where- by we have a right of appeal against rent increases ?Will our representatives ensure that resident married housemen receive a fair and just deal in view of the Review Body's report about the abolition of lodging charges ?-I am, etc.,
TOMOGRAPHIC ASSESSMENT OF LEFT VENTRICULAR MASS IN NORMAL AND INFARCTED CANINE HEARTS USING A NEW AUTOMATED EDGE-DETECTION PROGRAM
Authors: Craig J. Thompson, Israel Mena, Jean C. Maublant, Kenneth A. Narahara
Journal: Clinical Nuclear Medicine (1984)

We evaluated a new automated edge detection program to determine the feasability of determining left ventricular (LV) mass from single photon emission tomography (SPECT) of thallium-201 (T1) images in 7 dogs. Two of the seven dogs underwent repeat SPECT imaging 4 hours after coronary artery occlusion, with a closed-chest technique. All studies were obtained with the animal sedated and without gating. True LV mass was determined at sacrifice within one hour of the last Tl study. LV mass determined by SPECT correlated well with measured LV mass (r = .81; p < .05) over a range of 90 to 156 grams. The mean intra-observer error with the new automated technique was 3.8 gm. In the two dogs who had a control and post infarct study, total LV mass by SPECT varied by less than 4 grams (+3%). We conclude that SPECT tomography can define LV mass accurately and reproducibly in this model. The ability of the SPECT LV mass program to detect both normal and infarcted tissue suggests the possibility of (1) documenting interventions designed to alter LV mass and (2) of sizing acute infarcts and assessing interventions that may alter acute infarct size.
Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function.
Authors: K S Hathcock, G Laszlo, C Pucillo, P Linsley, R J Hodes
Journal: The Journal of Experimental Medicine (1994)

Antigen-specific T cell activation requires the engagement of the T cell receptor (TCR) with antigen as well as the engagement of appropriate costimulatory molecules. The most extensively characterized pathway of costimulation has been that involving the interaction of CD28 and CTLA4 on the T cell with B7 (now termed B7-1) on antigen presenting cells. Recently, B7-2 a second costimulatory ligand for CTLA4, was described, demonstrating the potential complexity of costimulatory interactions. This report examines and compares the expression and function of B7-1 and B7-2. Overall these results indicate that (a) B7-1 and B7-2 can be expressed by multiple cell types, including B cells, T cells, macrophages, and dendritic cells, all of which are therefore candidate populations for delivering costimulatory signals mediated by these molecules; (b) stimulating B cells with either LPS or anti-IgD-dextran induced expression of both B7-1 and B7-2, and peak expression of both costimulatory molecules occurred after 18-42 h of culture. Expression of B7-2 on these B cell populations was significantly higher than expression of B7-1 at all times assayed after stimulation; (c) blocking of B7-2 costimulatory activity inhibited TCR-dependent T cell proliferation and cytokine production, without affecting early consequences of TCR signaling such as induction of CD69 or interleukin 2 receptor alpha (IL-2R alpha); and (d) expression of B7-1 and of B7-2 can be regulated by a variety of stimuli. Moreover, expression of B7-1 and B7-2 can be independently regulated by the same stimulus, providing an additional complexity in the mechanisms available for regulating costimulation and hence immune response.
Carcinogenicity of Tobacco and Tobacco Smoke
Authors: F. J. C. Roe, A. Levene
Journal: BMJ (1967)

RNA 615 -probability that the dangerous part of the cigarette is the part which is raised to a high temperature by the match flame.The carcinogenic factor(s) seem therefore to be contained in the smoke inhaled from the super-heated area.I should like to see an nquiry made into the habits of smokers in *or"er to distinguish those who inhale the first puff of a cigarette from those who reject it before inhaling the subsequent ones.-Iam, etc.,
Fats, Oil, Health
Authors: Daniel Ullmann
Journal: JAMA (1990)

<h3>To the Editor.—</h3> Trevisan and colleagues<sup>1</sup>report a cross-sectional study in Italy that correlated the consumption of various fats with risk factors for coronary heart disease. An increased consumption of olive oil was associated with significantly lower levels of systolic blood pressure, blood glucose, and blood cholesterol in Italian men and women. Several points about this study should be emphasized. First, the study estimated olive oil consumption only approximately by "low, medium, and high" amounts consumed. This was not a quantitative study, a fact that weakens the conclusions greatly. The difference in serum cholesterol levels between high and low consumers of olive oil was only 0.15 mmol/L, an amount that should not stimulate olive oil consumption. Second, the implication that a fat such as olive oil has a positive effect on health is misleading. Olive oil is low in saturated fat relative to butter and other saturated fats. Yet,
Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction
Authors: Yuichiro Maekawa, Toshihisa Anzai, Tsutomu Yoshikawa, Yasuo Sugano, Keitaro Mahara, Takashi Kohno, Toshiyuki Takahashi, Satoshi Ogawa
Journal: Journal of the American College of Cardiology (2004)
Ode to an Everyman
Authors: Richard Bronson
Journal: Annals of Internal Medicine (2011)

Ad Libitum15 November 2011Ode to an EverymanRichard Bronson, MDRichard Bronson, MDStony Brook University Medical Center, Stony Brook, NY 11794-8091Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-10-201111150-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I hold you in my hands,an embryono bigger than a dust motewithin a droplet—one of manynurtured in the darkof an incubator this day.Conjured from a sperm and egg,each a life to be fulfilled—ascendance, then decay.What might you becomeonce I place you there—a cutpurse or a Liszt,or die a little deathwithin the womb? Author, Article, and Disclosure InformationAffiliations: Stony Brook University Medical Center, Stony Brook, NY 11794-8091Current Author Address: Richard Bronson, MD, Department of Obstetrics & Gynecology, Stony Brook University Medical Center, HSC T9-080, Stony Brook, NY 11794-8091. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 November 2011Volume 155, Issue 10Page: 713KeywordsDustEmbryosSpermUterus ePublished: 15 November 2011 Issue Published: 15 November 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Renal Pelvic Anatomy Is Associated with Incidence, Grade, and Need for Intervention for Urine Leak Following Partial Nephrectomy
Authors: Jeffrey J Tomaszewski, Bic Cung, Marc C Smaldone, Reza Mehrazin, Alexander Kutikov, Rosalia Viterbo, David Y T Chen, Richard E Greenberg, Robert G Uzzo
Journal: European Urology (2013)