tbuckley/cabot-search huggingface dataset:
Abstract 5128: Different effect of irinotecan induced apoptosis in k-Ras wild and mutant type colon cancer cell lines
Authors: Myoung Hee Kang, Jung Lim Kim, Bo Ram Kim, Yoo Jin Jang, Sun I. Lee, Jun Suk Kim, Sang cheul Oh
Journal: Cancer Research (2014)

Abstract Irinotecan(IRI) prevents DNA from unwinding by inhibition of topoisomerase I. Its main use is in colon cancer, in particular, in combination with other chemotherapy agents. Recent studies, those with Irinotecan treatment has a synergistic effect appears. However, there is no study on the effect of the Irinotecan mono-treatment. In addition their roles and the underlying mechanism in anti-tumorigenic function of solid tumor, especially kras wild and mutant type colon cancer, are not yet known. Bax protein is a key mediator of apoptosis and might be related to chemosensitivity. In this work, we evaluated the anti-tumorigenic action of these Irinotecan anti-cancer agent with especially k-ras wild and mutant type colon cancer cell lines, and investigated their apoptosis-inducing effects as the potential mechanism in this process. The results show that the growth inhibitory effects of 5-fuorouracil (5-FU), Oxaliplatin(OX) produced a dose- and time dependent fashion in k-ras wild(HT29, Colo205) and mutant type(HCT116, DLD-1) colon cancer cell lines. Otherwise, Irinotecan(IRI) produced a cell growth of k-ras wild type cell lines were resistant versus that shown in the sensitive k-ras mutant type cell lines. Cell cycle analysis by FACS indicated that IRI-treated cell lines showed an increase in the proportion of cells in sub-G1 phase, compared to untreated cells. Exposure of colon cancer cells to IRI also resulted in the increase in the percentage of annexin V- positive and PI-negative cells. The results by multiple in vitro experimental model, showed that IRI induce these k-ras mutant type colon cancer cells to undergo apoptosis with increased the Bax protein and a release of cytochrome C from mitochondria, the activation of caspase9, the cleavage of PARP. But Bax protein was inactivation in k-ras wild type colon cancer cell lines. Importantly, inhibition of ERK kinase activity demonstrated that IRI-induced apoptotic pathway was regulated by the ERK signaling cascade. These data indicate that Anti-cancer agent, Irinotecan, promotes Bax-mediate apoptosis of colon cancer cell lines by sequential activation of the ERK signaling pathway followed by the up-regulation of intrinsic pathway of caspase 9. Citation Format: Myoung Hee Kang, Jung Lim Kim, Bo Ram Kim, Yoo Jin Jang, Sun Il Lee, Jun Suk Kim, Sang cheul Oh. Different effect of irinotecan induced apoptosis in k-Ras wild and mutant type colon cancer cell lines. [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 5128. doi:10.1158/1538-7445.AM2014-5128
Aurora A Inhibitor (MLN8237) plus Vincristine plus Rituximab Is Synthetic Lethal and a Potential Curative Therapy in Aggressive B-cell Non-Hodgkin Lymphoma
Authors: Daruka Mahadevan, Amy Stejskal, Laurence S. Cooke, Ann Manziello, Carla Morales, Daniel O. Persky, Richard I. Fisher, Thomas P. Miller, Wenqing Qi
Journal: Clinical Cancer Research (2012)

Aurora A and B are oncogenic serine/threonine kinases that regulate mitosis. Overexpression of Auroras promotes resistance to microtubule-targeted agents. We investigated mechanistic synergy by inhibiting the mitotic spindle apparatus in the presence of MLN8237 [M], an Aurora A inhibitor with either vincristine [MV] or docetaxel [MD] in aggressive B-cell non-Hodgkin lymphoma (B-NHL). The addition of rituximab [R] to MV or MD was evaluated for synthetic lethality.Aggressive B-NHL cell subtypes were evaluated in vitro and in vivo for target modulation and anti-NHL activity with single agents, doublets, and triplets by analyzing cell proliferation, apoptosis, tumor growth, survival, and mechanisms of response/relapse by gene expression profiling with protein validation.MV is synergistic whereas MD is additive for cell proliferation inhibition in B-NHL cell culture models. Addition of rituximab to MV is superior to MD, but both significantly induce apoptosis compared with doublet therapy. Mouse xenograft models of mantle cell lymphoma showed modest single-agent activity for MLN8237, rituximab, docetaxel, and vincristine with tumor growth inhibition (TGI) of approximately 10% to 15%. Of the doublets, MV caused tumor regression, whereas TGI was observed with MD (approximately 55%-60%) and MR (approximately 25%-50%), respectively. Although MV caused tumor regression, mice relapsed 20 days after stopping therapy. In contrast, MVR was curative, whereas MDR led to TGI of approximately 85%. Proliferation cell nuclear antigen, Aurora B, cyclin B1, cyclin D1, and Bcl-2 proteins of harvested tumors confirmed response and resistance to therapy.Addition of rituximab to MV is a novel therapeutic strategy for aggressive B-NHL and warrants clinical trial evaluation.
A new deal on disease definition
Authors: R. Moynihan
Journal: BMJ (2011)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following A new deal on disease definition Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Modern Hernia Repair: The Embryological and Anatomical Basis of Surgery
Authors: Martin S. Litwin
Journal: JAMA (1997)

A highly competent and qualified group of surgeon-teachers have assembled to prepare a masterful text on hernias. Hernias of the ventral abdominal wall are well described and illustrated.  The Stoppa repair, in particular, is most interesting, because it is not well known or widely practiced in the United States. The sections on repair of peritoneal floor hernias, uterine prolapse, and enterocele are especially good. The descriptions of internal hernias and methods for their repair also are well illustrated. Laparoscopic procedures are difficult to describe and illustrate. The brief section on laparoscopic Nissen fundoplication comes as close as this reviewer has seen to adequately accomplishing this task.  Each chapter has a complete list of references. Unlike many such books, the table of contents is just as useful as the detailed index. However, the textual descriptions of most procedures are exceedingly brief, some to the point of losing their utility.  Modern Hernia
The role of immunoglobulin therapy in allergic diseases
Authors: N Rabinovitch, Ew Gelfand, Dym Leung
Journal: Allergy (1999)

Intravenous immunoglobulin (IVIG) has been used for many years to treat patients with primary immunodeficiencies. More recently, IVIG has been shown to have anti-inflammatory activity when used at substantially higher concentrations. A number of studies have examined the efficacy of IVIG in allergic diseases. For patients with severe refractory asthma, sinusitis, atopic dermatitis, and urticaria, IVIG offers an alternative therapy with relatively few side-effects. Although the mechanism by which IVIG may attenuate the allergic response is still undetermined, clinical studies have shown that immunoglobulin therapy can decrease serum IgE levels and increase glucocorticoid binding affinity, while in vitro studies have shown that IVIG can decrease T-cell secretion of TH2 cytokines. Further studies are needed to confirm the initial encouraging results seen in allergic patients with severe, resistant disease.
Carcinoma of the Biliary Tract
Authors: Henri Bismuth, Ronald A. Malt
Journal: New England Journal of Medicine (1979)

BILIARY cancer often gets short shrift in the differential diagnosis of obstructive jaundice because it is considered both rare and irremediable. Actually, cancer of the gallbladder and extrahepatic bile ducts is responsible for about 80 deaths in the United States weekly,1 and, if seldom curable, it can often be palliated, sometimes for nearly a decade.2*EpidemiologyThe preponderance of women in statistics on biliary cancer reflects their 67 per cent representation among patients with the relatively common gallbladder cancer, whereas 60 per cent of patients with the less frequent bile-duct cancers are men.3 Because gallstones are the major known . . .
Risk Factors for Infective Endocarditis
Authors: R. Paul Adams
Journal: Annals of Internal Medicine (1999)

Letters20 July 1999Risk Factors for Infective EndocarditisMichael Jacobson, MD, MPHMichael Jacobson, MD, MPHLenox Hill Hospital; New York, NY 10021 (Jacobson)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-2-199907200-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In a case–control study of patients with endocarditis (1), Strom and colleagues found no increase in dental procedures within 3 months before the onset of endocarditis compared with controls. They conclude that dental procedures are not a significant risk factor for infective endocarditis.The case-patients were drawn from a community-based population subject to conventional antibiotic prophylaxis before dental work. Although the authors state that “few patients received antibiotic prophylaxis,” in fact 27 of 35 case-patients and controls with known cardiac valvular abnormalities did receive such prophylaxis before dental work.If dental prophylaxis is indeed effective, one would ...Reference1. Strom BL, Abrutyn E, Berlin JA, Kinman JL, Feldman RS, Stolley PD, et al . Dental and cardiac risk factors for infective endocarditis. A population-based, case–control study. Ann Intern Med. 1998;129:761-9. LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Michael Jacobson, MD, MPHAffiliations: Lenox Hill Hospital; New York, NY 10021 (Jacobson) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDental and Cardiac Risk Factors for Infective Endocarditis: A Population-Based, Case-Control Study Brian L. Strom , Elias Abrutyn , Jesse A. Berlin , Judith L. Kinman , Roy S. Feldman , Paul D. Stolley , Matthew E. Levison , Oksana M. Korzeniowski , and Donald Kaye Risk Factors for Infective Endocarditis R. Paul Adams Risk Factors for Infective Endocarditis Peter Collignon Risk Factors for Infective Endocarditis Brian L. Strom , Judith L. Kinman , and Elias Abrutyn Metrics 20 July 1999Volume 131, Issue 2Page: 154KeywordsAntibiotic prophylaxisEndocarditisMedical risk factorsProphylaxis ePublished: 15 August 2000 Issue Published: 20 July 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Exsanguinating Hemorrhage from Diverticulosis of the Ascending Colon
Authors: Stephen J. Healey, Robert I. Pfeffer
Journal: New England Journal of Medicine (1965)

EXSANGUINATING hemorrhage requiring emergency operation is an infrequent complication of diverticular disease of the colon. In the past fifteen years at the Peter Bent Brigham Hospital massive hemorrhage has been the indication for operation in only 8 (5 per cent) of 160 patients surgically treated for diverticular disease.1 , 2 This is a report of the only case of exsanguinating hemorrhage in which the bleeding site could be demonstrated in a diverticulum of the ascending colon.Case ReportC.M., a 44-year-old mother of 1 child, entered the emergency room of the Peter Bent Brigham Hospital at 2 p.m. on February 25, 1965. . . .
The management of skin malignancy: to what extent should we rely on clinical diagnosis?
Authors: S.J. Brown, C.M. Lawrence
Journal: British Journal of Dermatology (2006)

Cutaneous malignancy forms a major part of the dermatologist's workload. Clinical diagnosis is an important factor in facilitating the urgent excision of squamous cell carcinomas (SCC) and malignant melanomas.To identify the numbers and types of malignant skin tumours managed in an NHS teaching hospital and to assess the diagnostic accuracy.Data were collected on every histologically proven malignant skin lesion over a 6-month period.One thousand one hundred and ninety-five malignant skin tumours were identified: 78% were basal cell carcinomas, 14% were SCC, 6% were malignant melanomas and the remaining 2% included Merkel cell tumours, malignant adnexal tumours and lentigo maligna. Eighty-one per cent of the tumours were managed by dermatologists. The correct clinical diagnosis had been made by the secondary care clinician in 84% of cases but an incorrect clinical diagnosis was given in 32% of SCC. Of the 1195 tumours, 916 (77%) had a primary excision and 92% (843 of 916) of these were completely excised.The majority of skin malignancies (968 of 1195, 81%) were managed by dermatologists. Where primary excision was attempted, this was complete in 91% (767 of 916) of cases. The correct clinical diagnosis was made in 84% of all tumours, but 32% of SCC were not correctly diagnosed prior to surgery.
Hepatitis E virus (HEV)-specific T-cell responses are associated with control of HEV infection
Authors: Pothakamuri Venkata Suneetha, Sven Pischke, Verena Schlaphoff, Jan Grabowski, Paraskevi Fytili, Anna Gronert, Birgit Bremer, Antoaneta Markova, Jerzy Jaroszewicz, Christoph Bara, Michael P. Manns, Markus Cornberg, Heiner Wedemeyer
Journal: Hepatology (2011)

Hepatitis E virus (HEV) infection is usually self-limited but may lead to acute hepatitis and rarely to fulminant hepatic failure. Persistent HEV infections have recently been described in organ transplant recipients receiving immunosuppressive medications, suggesting that HEV is controlled by adaptive immune responses. However, only few studies have investigated HEV-specific T-cell responses and immune correlates for the failure to clear HEV infection have not been established so far. We investigated T-cell responses against HEV in 38 subjects including anti-HEV-positive (exposed, n = 9) and anti-HEV-negative (n = 10) healthy controls, 12 anti-HEV-positive but HEV RNA-negative organ transplant recipients, and seven transplant recipients with chronic hepatitis E. Proliferation as well as cytokine production of CD4+ and CD8+ T cells was studied after stimulation with overlapping peptides spanning all proteins encoded by HEV-open reading frame (ORF)2 and HEV-ORF3. We show that (1) strong and multispecific HEV-specific T-cell responses are present in exposed healthy controls, and to a lesser extent also in recovered patients after transplantation; (2) that these responses are absent in patients with chronic hepatitis E but become detectable after viral clearance; and (3) that HEV-specific T-cell responses can be restored in vitro by blocking the PD-1 or CTLA-4 pathways. However, a combination of PD-1 and CTLA-4 blockade had no synergistic effects. We conclude that chronic hepatitis E is associated with impaired HEV-specific T-cell responses and suggest that enhancing adaptive cellular immunity against HEV might prevent persistent HEV infections.
331 Naive human mast cells (MC) transcribe IL-3, IL-5 and GM-CSF mRNA and secrete IL-5 and GM-CSF protein following FcεRI ligation
Authors: R BRESSLER, J LESKO, M JONES, M WASSERMAN, R DICKASON, S COOK, M HUSTON, D HUSTON
Journal: Journal of Allergy and Clinical Immunology (1996)
Do drug cheats ever prosper?
Authors: P McCrory
Journal: British Journal of Sports Medicine (2002)

The systems designed to eradicate drug use and cheating in sport need to be improved

Recent observers of international sporting meetings may have been disheartened yet again by the ongoing battle against the use of banned drugs in sport. This is particularly so for sports medicine clinicians, who usually attend these athletic meetings voluntarily and may be inadvertently brought into these controversial matters.

Often a team doctor is asked to chaperone an athlete during a drug test or provide information to the …
The Abuse of Caesarean Section
Authors: H. Jellett
Journal: BMJ (1927)

Tim BaIjATIOS t 451 - such system was advocated some time ago when the Medico- 1,egal Society irn London decided to urge the formation of a medico-legal institute.It should be possible to establish such inistitutes, not only in London, but in other centres, so arranged that the iwhole of the medico-legal work of the countrv could be under expert super-vision.The speaker instanced the conditions in Egypt, where all medico-legal cases of any importance came automatically under tho notice of the Medico-Legal Department of the Ministry of Justice.rhis department, which consisted of whole-time medical officers, chemists, and other officials, was attached to the Parquet, an investigating authority.All cases of poisoniing, in whatever part of the country they occurred, all examinations of blood alnd other stainis, and, in fact, all techniical examinations, were carried out in the central laboratories at Cairo, while experts were available for advice and assistance in the different centtres.A similar
Diagnosis and Treatment of Chronic Abacterial Prostatitis
Authors: Mary McNaughton Collins
Journal: Annals of Internal Medicine (2000)

Purpose: The optimal management of chronic abacterial prostatitis is not known. A systematic review of the literature was done to answer the following questions: Are there accurate, reliable tests to diagnose chronic abacterial prostatitis? Are there effective therapies for it? Data Sources: Studies were identified by searching MEDLINE (1966 to 1999), the Cochrane Library, and bibliographies of identified articles and reviews and by contacting an expert. Study Selection: Diagnostic test articles were included if they reported on controlled studies; treatment articles were included if they reported on randomized or controlled trials. No language restrictions were applied. Data Extraction: For each selected article, two investigators independently extracted key data on study design, patient characteristics, diagnostic test or treatment characteristics, and outcomes. Data Synthesis: 19 diagnostic test articles and 14 treatment trials met the inclusion criteria. The disparity among studies in design, interventions, and other factors precluded quantitative analysis or pooling of the findings. Diagnostic test articles included 1384 men (mean age, 33 to 67 years) and evaluated infection; inflammation, immunology, and biochemistry; psychological factors; and ultrasonography. Treatment trials included 570 men (mean age, 38 to 45 years) and evaluated medications used to treat benign prostatic hyperplasia, anti-inflammatory drugs, antibiotics, thermotherapy, and miscellaneous medications. No trial was done in the United States. Conclusions: There is no gold-standard diagnostic test for chronic abacterial prostatitis, and the methodologic quality of available studies of diagnostic tests is low. The few treatment trials are methodologically weak and involved small samples. The routine use of antibiotics and α-blockers to treat chronic abacterial prostatitis is not supported by the existing evidence.
Unusual effect of fenfluramine.
Authors: N W Imlah
Journal: BMJ (1970)

endocrine hypothesis.For example, there must be in the population many men who have regularly donated blood every six months for many years.Obviously this is not equivalent to a monthly menstrual bleed.Nevertheless it would be interesting to see whether these men are in any way protected against coronary thrombosis as compared with a group of non-donors.(2) If true the concept would mean that protection against coronary thrombosis could be provided at very low cost.There would be no need for life-long drug taking or dietary changes.(3) If the bleeding hypothesis were true, the blood transfusion service would cease to have any problem in acquiring blood.I realize that my hypothesis is very un- likely to be valid.But when so little pro- gress is being made in other directions and when the potential rewards are so great, a survey of the effects of blood donation on coronary disease would appear to be worthwhile.-Iam, etc.,
DEVELOPMENT OF DOUBLE-LUMENED TUBE FOR INTESTINAL INTUBATION
Authors: T. GRIER MILLER
Journal: JAMA (1949)

In 1934 the late William Osler Abbott and I 1 introduced small intestinal intubation as a practical clinical procedure. It was not the first time that the human small bowel had been intubated or that the significance of such a procedure had been appreciated. It was merely the first time that a technic had been described that permitted the ready accomplishment of the desired objectives. This was rendered possible by the development of a double-lumened rubber tube and the attachment at its distal end of a collapsible balloon.  PREVIOUS HISTORY  Although we were not familiar with his work until shortly before our original publication, Scheltema, 2 a Netherlands pediatrician, in 1908, twenty-six years earlier, had accomplished in children what he termed permeation or automatic sounding of the alimentary tract. The idea that such intubation could be accomplished passively (without activity on the part of the operator) occurred to him as
PREDICTORS OF PEAK OXYGEN CONSUMPTION IN HYPERTROPHIC CARDIOMYOPATHY PATIENTS UNDERGOING CARDIOPULMONARY EXERCISE TESTING
Authors: Lee Moschler Pierson, Ahmad Masri, Nicholas Smedira, Bruce Lytle, Peyman Naji, Maran Thamilarasan, Harry Lever, Leslie Cho, Milind Desai
Journal: Journal of the American College of Cardiology (2013)