tbuckley/cabot-search huggingface dataset:
S48 NGAL inhibits cytoskeletal re-organisation, MMP-2 production and invasion in alveolar epithelial cells in an in vitro model of acute lung injury
Authors: C. M. O'Kane, E. Moran, D. F. McAuley
Journal: Thorax (2010)

<h3>Introduction</h3> We have identified bronchoalveolar lavage NGAL (neutrophil gelatinase associated lipocalin, also known as lipocalin-2) as a potential biomarker in acute lung injury (ALI). Rising NGAL concentrations over the first 72 h of illness, and higher absolute NGAL levels at day 3 predicted ICU survival. The biological mechanism by which NGAL is associated with improved survival is not known. Lipocalin-2 modulates the process of epithelial to mesenchymal transition (EMT) in breast cancer. We have demonstrated the typical morphological and proteomic changes and the invasive phenotype of EMT in alveolar epithelial cells <i>in vitro</i> in response to either ARDS BAL fluid or TNFalpha + TGFbeta, cytokines present in the lavage fluid of patients with ALI. We hypothesised that NGAL could alter EMT <i>in vitro</i> in alveolar epithelium. <h3>Methods</h3> A549 cells were stimulated with TNFalpha + TGFbeta in the presence or absence of NGAL (0.1–10 ng/ml). Cells were lysed at 72 h and probed by western blot for E-cadherin, Zo-1, fibronectin and vimentin. Supernatants were analysed by gelatin zymography for MMP-2. The invasive capacity of the cells was assessed using BD Biocoat Matrigel Invasion Assay Chambers. <h3>Results</h3> As previously described TNFalpha + TGFbeta caused loss of E-cadherin, Zo-1 and gain of vimentin and fibronectin in A549 cells, with an accompanying morphological change to spindle shaped cells, that secreted MMP-2 and invaded matrigel. Treatment with NGAL did not affect E-cadherin, Zo-1, fibronectin nor vimentin. However, treatment with NGAL abrogated the change in morphology, maintaining an epithelial-like cobblestone appearance (Abstract S48 Figure 1a). Additionally, NGAL inhibited the production of MMP-2 by these cells (from 1.8±0.3 to 0.9±0.2 relative gelatinolytic units, p=0.04) and reduced the capacity of the cells to migrate through basement membrane-type matrix (Abstract S48 Figure 1b). <h3>Conclusion</h3> NGAL inhibited some but not all of typical changes of EMT in this <i>in vitro</i> model of ALI. The protective effect of NGAL in patients with ALI may be mediated by maintaining alveolar epithelial morphology, reducing their production of the basement membrane-destructive enzyme MMP-2, and reducing their capacity to migrate to the sub-epithelial interstitial space. Further work is required to assess this mechanism <i>in vivo</i> and to examine the effects of supplementary NGAL in ALI.
Medical Professionalism in a Commercialized Health Care Market
Authors: Arnold S. Relman
Journal: JAMA (2007)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Rationing Antiretroviral Therapy in Africa — Treating Too Few, Too Late
Authors: Nathan Ford, Edward Mills, Alexandra Calmy
Journal: New England Journal of Medicine (2009)

The standard approach to HIV treatment in Africa is to wait until people are visibly sick, treat them with effective but poorly tolerated drugs, and then wait until they are sick again before switching regimens. Nathan Ford, Edward Mills, and Dr. Alexandra Calmy write that there are several problems with this approach.
Diagnosis of a Posttraumatic Arteriovenous Fistula by Dynamic Scintigraphy
Authors: FREDERICK L. DATZ, MURRAY GORDON, SAMUEL E. LEWIS, ROBERT W. PARKEY
Journal: Clinical Nuclear Medicine (1979)

DATZ, FREDERICK L. M.D.; GORDON, MURRAY M.D.; LEWIS, SAMUEL E. M.D.; PARKEY, ROBERT W. M.D. Author Information
Is Microvascular Invasion on Radical Prostatectomy Specimens a Useful Predictor of PSA Recurrence for Prostate Cancer Patients?
Authors: Alexandre de la Taille, Mark A. Rubin, Ralph Buttyan, Carl A. Olsson, Emilia Bagiella, Martin Burchardt, Ofer M. Wellisch, Aaron E. Katz
Journal: European Urology (2000)
Early posttransplantation donor-derived invariant natural killer T-cell recovery predicts the occurrence of acute graft-versus-host disease and overall survival
Authors: Marie-Thérèse Rubio, Lucia Moreira-Teixeira, Emmanuel Bachy, Marie Bouillié, Pierre Milpied, Tereza Coman, Felipe Suarez, Ambroise Marcais, David Sibon, Agnès Buzyn, Sophie Caillat-Zucman, Marina Cavazzana-Calvo, Bruno Varet, Michel Dy, Olivier Hermine, Maria Leite-de-Moraes
Journal: Blood (2012)
Abstract 1773: The addition of Reolysin, an oncolytic reovirus, to irinotecan shows synergistic anticancer activity in colorectal cancer cell lines
Authors: Raviraja N. Seetharam, Matthew C. Coffey, Lidija Klampfer, John Mariadason, Sanjay Goel
Journal: Cancer Research (2010)

Abstract Recent clinical data suggests that the anti EGFR antibodies, cetuximab and panitumumab, are ineffective in patients with colorectal cancer whose tumors harbor a mutation in the kras oncogene. Currently, for these patients, the only option after failure of front line therapy is irinotecan, and there is no drug that can be combined with it to improve clinical outcomes. We studied in vitro, the combination of Reolysin and irinotecan to develop a novel therapeutic approach for these patients. Reolysin (reovirus Serotype 3) has been shown to replicate specifically in tumors bearing an activated ras pathway. This specificity coupled with its relatively nonpathogenic nature in humans makes it an attractive anti-cancer therapy candidate. We have performed in vitro studies of Reo (multiplicity of infection 1 to 10), iri (0.5-10 µM), as single agents and in combination in human colorectal cancer cells to study the role of kras mutation. Reolysin was obtained from Oncolytics Biotech Inc. and irinotecan was obtained commercially. A panel of 8 colorectal cancer cell lines were infected with Reolysin (multiplicity of infection 1 to 10), irinotecan (0.5-10 µM), as a single agent or in combination. The cells were exposed to Reolysin for 6-8 hours and to irinotecan for 72 hours. Viable cells were determined 72 hours post treatment using MTT assay. The effect of Reolysin and irinotecan combination on cell viability was assessed using CalcuSyn software (Biosoft, UK) that generates combined cytotoxic effect by calculating combination indices (CIs). A CI of &amp;lt;1 indicates synergy, 1 denotes additive effect, and &amp;gt;1 denotes antagonism. We found that Reolysin and irinotecan as single agents were cytotoxic to all colon cell lines studied. Further, when Reolysin was combined with irinotecan, there was evidence of synergistic cytotoxicity in all (HT29, HCT116, DLD, KM12, SKCO-1, SW620, LIM2405) except one (SW948) cell line. There appears to be no association between kras mutation status and synergism. To further explore these findings and understand the mechanistic basis of drug synergism we are studying the effect of Reolysin and irinotecan in isogenic HCT116 (kras mutant) and Hke3 (kras WT) cell lines. In summary, the combination of Reolysin and irinotecan is synergistic in colorectal cancer cell lines including those with kras mutation and is worthy of exploration in human patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1773.
Legislating Screening for Atherosclerosis
Authors: Erling Falk
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Demise of the "Philadelphia Medical Journal."
Authors: George M. Gould.
Journal: JAMA (1903)

Philadelphia, June 29, 1903. <i>To the Editor</i>:—Certain inaccuracies in the statement made by the late editor-in-chief of the<i>Philadelphia Medical Journal</i>, in your issue for June 20, seem to need correction in order that the profession may be better able to point the moral which adorns this tale. I refer particularly to the words: "Two and a half years ago the<i>Philadelphia Medical Journal</i>reached a crisis in its affairs which led to a change in editorial management. There were many prominent medical men in Philadelphia and elsewhere who were interested in keeping the journal alive; and in spite of the fact that its short career up to that time had been marked by threatening disaster (due largely to the opposing aims and temperaments of men who commanded its various departments), a determined effort was made to rehabilitate the journal and give it a new lease of life. At
Effects of Tumor Necrosis Factor Gene Polymorphisms on Patients With Congestive Heart Failure
Authors: Toru Kubota, Dennis M. McNamara, Jue J. Wang, Mary Trost, Charles F. McTiernan, Douglas L. Mann, Arthur M. Feldman
Journal: Circulation (1998)

Background —Tumor necrosis factor-α (TNF-α) is known to be elevated in patients with congestive heart failure (CHF). Two biallelic polymorphisms have been identified in the TNF gene locus: one in the promoter region of TNF-α (TNFA1/2), and the other in the first intron of TNF-β (TNFB1/2). Both TNFA2 and TNFB2 alleles are associated with high TNF-α production in vitro and susceptibility to inflammatory diseases. Given the importance of TNF-α in the pathogenesis of CHF, we studied the prevalence of TNF gene polymorphisms in CHF patients and the correlation of genotypes to in vivo TNF-α levels. Methods and Results —TNFA and TNFB genotypes were determined by the polymerase chain reaction–restriction fragment length polymorphism technique. There were no differences in the TNF allele frequencies between CHF (n=229; TNFA1/2=0.84/0.16, TNFB1/2=0.33/0.67) and control subjects (n=139; TNFA1/2=0.84/0.16, TNFB1/2=0.32/0.68). In 211 patients with CHF, circulating levels of TNF-α and the soluble receptors type I and type II were measured by ELISA: 6.18±3.59 pg/mL, 1768±761 pg/mL, and 4484±1750 pg/mL, respectively. There were no correlations between TNFA or TNFB genotypes and circulating levels of TNF-α or its soluble receptors in the CHF patients. Conclusions —Despite their association with other inflammatory diseases, neither TNFA nor TNFB polymorphisms are related to the presence of CHF or the elevation of circulating TNF-α. Thus, other factors may be more important in determining the circulating levels of TNF-α in CHF.
Regulation of CLC-Ka/barttin by the ubiquitin ligase Nedd4-2 and the serum- and glucocorticoid-dependent kinases
Authors: Hamdy M. Embark, Christoph Böhmer, Monica Palmada, Jeyaganesh Rajamanickam, Amanda W. Wyatt, Sabine Wallisch, Giovambattista Capasso, Petra Waldegger, Hannsjörg W. Seyberth, Siegfried Waldegger, Florian Lang
Journal: Kidney International (2004)
Reversible malabsorption caused by methyldopa.
Authors: J M Shneerson, B G Gazzard
Journal: BMJ (1977)

Reversible malabsorption caused by methyldopaWe report a case in which a reversible histological abnormality of the small bowel with features of malabsorption was found to be related to treatment with methyldopa. Case reportA man aged 58 years presented with a short history of diabetes mellitus, and after a right-sided hemiparesis he was found to be hypertensive.After 12 months' treatment with a thiazide diuretic, methyldopa 250 mg thrice daily was added to the regimen.Six months later he was admitted to hospital
Thiopronine-induced herpetiform pemphigus: report of a case studied by immunoelectron microscopy and immunoblot analysis
Authors: S. VERDIER-SEVRAIN, P. JOLY, E. THOMINE, PH. BELANYI, D. GILBERT, F. TRON, PH. LAURET
Journal: British Journal of Dermatology (1994)

Summary We report a case of herpetiform pemphigus induced by thiopronine. Direct immunoelectron microscopy performed on peribullous skin showed IgG deposits predominantly located in the extracellular portion of desmosomes. By immunoblot analysis using bovine tongue extracts as the antigen, the patient's serum recognized a 160-kDa polypeptide which comigrated with desmoglein I. This study underlines the contribution of immunoblot analysis to the diagnosis of atypical cases of pemphigus, and confirms that herpetiform pemphigus may be a clinical variant of pemphigus foliaceus.
Anal tuberculosis: Report of a case and review of literature
Authors: Soniya Mathew
Journal: International Journal of Surgery (2006)

A case of anal tuberculosis with a perianal growth and anal ulceration is presented. The clinical features and the diagnostic problems along with increasing incidence of new cases of tuberculosis are discussed.The diagnosis, management and outcome of an adult male patient, who presented with perianal lesions are described.On a four drug anti-tuberculous regimen, the symptoms improved and perianal lesions healed.Anal tuberculosis although extremely rare, can be manifested in various forms. A high index of suspicion of tuberculosis should be borne in mind in all cases of perianal lesions with vague etiology or with diagnostic problems, which should be confirmed by histological and bacteriological analysis and treated specifically.
Systemically delivered glucocorticoid liposomes suppress bone erosion and inhibit osteoclast activation in synovium and bone marrow during experimental murine arthritis
Authors: W Hofkens, L C Grevers, B Walgreen, T J de Vries, P J M Leenen, V Everts, G Storm, W B van den Berg, P L van Lent
Journal: Annals of the Rheumatic Diseases (2010)

129593pGlucocorticoids are potent anti-infl ammatory drugs that slow down the progression of bone erosion in patients with rheumatoid arthritis.By delivery of glucocorticoids encapsulated into long circulating liposomes, their anti-infl ammatory effect over free drug can be increased.The aim of this study was to investigate the effect of systemic delivery of liposomal prednisolone phosphate (PLP) on bone erosion and osteoclast activity during experimental antigen-induced arthritis.Mice with established antigen-induced arthritis (AIA) were treated with a single intravenous injection of 10 mg/kg on July 19, 2023 by guest.
High False-Negative Rate of <i>HER2</i> Quantitative Reverse Transcription Polymerase Chain Reaction of the Onco<i>type</i> DX Test: An Independent Quality Assurance Study
Authors: David J. Dabbs, Molly E. Klein, Syed K. Mohsin, Raymond R. Tubbs, Yongli Shuai, Rohit Bhargava
Journal: Journal of Clinical Oncology (2011)

HER2 (ERBB2) status is an important prognostic and predictive marker in breast carcinoma. In recent years, Genomic Health (GHI), purveyors of the Oncotype DX test, has been separately reporting HER2 by reverse transcription polymerase chain reaction (RT-PCR) to oncologists. Because of the lack of independent evaluation, this quality assurance study was undertaken to define the concordance rate between immunohistochemistry (IHC)/fluorescent in situ hybridization (FISH) and GHI RT-PCR HER2 assay.All patients at three participating laboratories (Magee-Womens Hospital [Pittsburgh, PA], Cleveland Clinic [Cleveland, OH], and Riverside Methodist Hospital [Columbus, OH]) with available HER2 RT-PCR results from GHI were included in this study. All IHC-positive and equivocal patient cases were further evaluated and classified by FISH at respective laboratories.Of the total 843 patient cases, 784 (93%) were classified as negative, 36 (4%) as positive, and 23 (3%) as equivocal at the three institutions using IHC/FISH. Of the 784 negative patient cases, 779 (99%) were also classified as negative by GHI RT-PCR assay. However, all 23 equivocal patient cases were reported as negative by GHI. Of the 36 positive cases, only 10 (28%; 95% CI, 14% to 45%) were reported as positive, 12 (33%) as equivocal, and 14 (39%) as negative.There was an unacceptable false-negative rate for HER2 status with GHI HER2 assay in this independent study. This could create confusion in the decision-making process for targeted treatment and potentially lead to mismanagement of patients with breast cancer if only GHI HER2 information is used.
Diagnosis and Treatment of Hepatocellular Carcinoma
Authors: P JOHNSON
Journal: Gut (1998)

Diagnosis and Treatment of Hepatocellular Carcinoma. Edited by Livraghi T, Makuuchi M, Buscarini L. (Pp 454; illustrated; price not given.) London: Greenwich Medical Media, 1997. ISBN 1-900151-308.

Very early in my career I told a senior colleague that I was interested in trying to treat patients with hepatocellular carcinoma (HCC). “Oh, that is easy,” he replied, “Give them a bottle of whiskey and send them home!” In those days HCC was seldom even diagnosed during life let alone treated. Gut readers, many of whom will have been brought up on single authored textbooks of gastroenterology, may be dismayed to find that treatment and diagnosis of HCC can now fill an entire book of more than 400 pages. That this task requires more than 60 authors will compound their dismay. Indeed, it is probably the size of the book that tells the main story. There is no consensus on how best to diagnose, screen for, or treat this tumour, with the result …
CALCULUS VESICAe: SEVERE HAeMORRHAGE ONE HOUR AFTER THE OPERATION
Authors: W. T. Bell
Journal: BMJ (1855)

WILLIAM WADDINGHAA, aged 5, a fair stout boy, came under my care in July 18.55, suffering from symptoms of stoe.His father says he has had some difBoulty in peisg }his water for the last three years: two year ago, he Swas taken to a hospital, and was sounded, but no stone detected.Within the last two years his symptoms have
Abstract 4325: CD99 suppresses osteosarcoma cell migration by favouring the oncosoppressor N-cadherin/beta-catenin signalling pathway in contrast to ezrin.
Authors: Maria Cristina Manara, Cinzia Zucchini, Simona Pinca, Paola de Sanctis, Clara Guerzoni, Katia Scotlandi
Journal: Cancer Research (2012)

Abstract CD99 is a 32-kDa highly glycosylated transmembrane protein encoded by MIC2 gene which shares no homology with any known family of proteins except Xga and mouse CD99L2 proteins. Located in the pseudoautosomal region of chromosomes X and Y, MIC2 encodes two distinct products by alternative splicing of gene transcripts: a long form (32-kDa), corresponding to the full-length protein (CD99wt) and a short form harbouring a deletion in the intracytoplasmic domain (CD99 sh). CD99 is involved in multiple cellular events including cell adhesion, apoptosis, differentiation of T- cells and thymocytes, transendothelial migration of leukocytes, maintenance of cellular morphology and regulation of intracellular membrane protein trafficking either in physiology and in pathological conditions. In osteosarcoma, CD99 is expressed at low levels and functions as a tumor suppressor. The two alternative spliced isoforms are associated to distinct functional outcomes: CD99sh expression increases, whereas wtCD99 significantly inhibits migration, invasiveness and metastasis of osteosarcoma cells (Manara MC, 2006; Scotlandi K 2007). In this study, we specifically analyzed modulation of cell-cell contacts, reorganization of the actin cytoskeleton, and modulation of signalling pathways by comparing osteosarcoma cells characterized by different metastasis capabilities and CD99 expression, to identify molecular mechanisms responsible for metastasis. Our data indicate that expression of CD99wt induces recruitment of beta-catenin to adherens injunctions through N-cadherin up-regulation. In addition, forced expression of CD99wt inhibits the expression of several molecules crucial to remodeling the actin cytoskeleton, such as ACTR2 (also named ARP2), ARPC1A and ROCK II as well as ezrin, an ezrin/radixin/moesin (ERM) family member that has been clearly associated with tumor progression and metastatic spread either in experimental models and clinical samples of osteosarcoma. Functional studies by siRNA and/or specific inhibitors point to ROCKII as a crucial intracellular mediator regulating osteosarcoma metastasis capabilities. 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 4325. doi:1538-7445.AM2012-4325