tbuckley/cabot-search huggingface dataset:
Autotaxin Promotes Cancer Invasion via the Lysophosphatidic Acid Receptor 4: Participation of the Cyclic AMP/EPAC/Rac1 Signaling Pathway in Invadopodia Formation
Authors: Kelly Harper, Dominique Arsenault, Stephanie Boulay-Jean, Annie Lauzier, Fabrice Lucien, Claire M. Dubois
Journal: Cancer Research (2010)

The ability of cancer cells to invade and metastasize is the major cause of death in cancer patients. Autotaxin (ATX) is a secreted lysophospholipase whose level of expression within tumors correlates strongly with their aggressiveness and invasiveness. ATX is the major enzyme involved in the production of lysophosphatidic acid (LPA), a phospholipid that is known to act mostly through its three first characterized receptors (LPA(1), LPA(2), and LPA(3)). Tumor cell invasion across tissue boundaries and metastasis are dependent on the capacity of invasive cancer cells to breach the basement membrane. This process can be initiated by the formation of the actin-rich cell protrusions, invadopodia. In this study, we show that ATX is implicated in the formation of invadopodia in various cancer cells types and this effect is dependent on the production of LPA. We further provide evidence that LPA(4) signaling in fibrosarcoma cells regulates invadopodia formation downstream of ATX, a process mediated through the activation of EPAC by cyclic AMP and subsequent Rac1 activation. Results using LPA(4) shRNA support the requirement of the LPA(4) receptor for cell invasion and in vivo metastasis formation. This work presents evidence that blocking the LPA receptor, LPA(4), in fibrosarcoma cells could provide an additional tool to improve the efficacy of treatment of metastasis in patients. Because LPA receptors and ATX are currently being targeted in preclinical trials, the current findings should stimulate future studies to evaluate the expression pattern and clinical outcome of LPA(4), together with other LPA receptors, in various cancer patients.
378 HUMAN SERUM METABOLIC PROFILING REVEALS NOVEL BIOMARKERS ASSOCIATED WITH NAFLD PROGRESSION
Authors: M. Vazquez-Chantada, J. Barr, C. Alonso, A. Galan, A. Tran, J. Tordjman, Y. Le Marchand-Brustel, P. Gual, M. Martinez-Chantar, S.C. Lu, A. Castro, J.M. Mato
Journal: Journal of Hepatology (2010)
Epidemiology and Prevention of Hepatitis A in Travelers
Authors: Robert Steffen
Journal: JAMA (1994)

To assess the risk of hepatitis A in international travelers and to recommend preventive measures.Index Medicus, 1974 through 1983; MEDLINE, 1984 through 1993; and unpublished data of the Centers for Disease Control and Prevention.Review of all retrospective and cohort studies on hepatitis A and other vaccine-preventable diseases in travelers, of seroepidemiologic surveys of hepatitis A virus (HAV) antibodies in travelers, of data on the various hepatitis A vaccines, of economic analyses, and of recommendations of recognized organizations.Independent analysis by multiple observers.The incidence rate for unprotected travelers, including those staying in luxury hotels, is estimated to be three per 1000 travelers per month of stay in a developing country. Persons eating and drinking under poor hygienic conditions have a rate of 20/1000 per month. This makes hepatitis A the most frequent infection in travelers that may be prevented by immunization. In many industrialized countries persons born after 1945 have an HAV antibody seroprevalence (immunity) of less than 20%. New inactivated HAV vaccines induce protective antibodies in more than 95% of recipients and offer protection estimated to last for 10 years or more, whereas protection by immune globulin lasts only 3 to 5 months.Hepatitis A vaccine, or immune globulin where HAV vaccine is not available, is recommended for all nonimmune travelers visiting developing countries. Prescreening for antibodies to HAV in travelers living in countries with low prevalence is usually not necessary in persons born after 1945.
Effects of rosiglitazone on the liver histology and mitochondrial function in ob/ob mice
Authors: Inmaculada García‐Ruiz, Cristina Rodríguez‐Juan, Teresa Díaz‐Sanjuán, Miguel Ángel Martínez, Teresa Muñoz‐Yagüe, José A. Solís‐Herruzo
Journal: Hepatology (2007)

Insulin resistance is present in almost all patients with nonalcoholic steatohepatitis (NAFLD), and mitochondrial dysfunction likely plays a critical role in the progression of fatty liver into nonalcoholic steatohepatitis. Rosiglitazone, a selective ligand of peroxisome proliferator-activated receptor gamma (PPARγ), is an insulin sensitizer drug that has been used in a number of insulin-resistant conditions, including NAFLD. The aim of this study was to analyze the effects of rosiglitazone on the liver histology and mitochondrial function in a model of NAFLD. All studies were carried out in wild-type and leptin-deficient (ob/ob) C57BL/6J mice. Ob/ob mice were treated with 1 mg/kg/day, and activity of mitochondrial respiratory chain (MRC), beta-oxidation, lipid peroxidation, glutathione content in mitochondria, and 3-tyrosine–nitrated proteins in mitochondria were measured. In addition, histological and ultrastructural changes induced by rosiglitazone were also noted. Rosiglitazone treatment increased liver steatosis, particularly microvesicular steatosis. In these animals, mitochondria were markedly swollen with cristae peripherally placed. In ob/ob mice, this drug increased PPARγ protein expression and lipid peroxide content in liver tissue and decreased glutathione concentration in mitochondria. Rosiglitazone suppressed the activity of complex I of the MRC in ob/ob mice, but did not affect beta-oxidation. 3-Tyrosine nitrated mitochondrial proteins, significantly increased in ob/ob mice, were not modified by rosiglitazone treatment. Conclusion: Treatment of ob/ob mice with rosiglitazone did not reverse histological lesions of NAFLD or improve MRC activity. On the contrary, rosiglitazone reduced activity of complex I and increased oxidative stress and liver steatosis. (HEPATOLOGY 2007.)
Abstract 346: Differentiation induced apoptosis in AML cells: The role of p73 in p53-independent versus p53-mediated apoptosis
Authors: Michael Roberts, Rizwan Saffie, Harold Salmons, Mansoor Ghoto, Juliana Schneider, Jeffrey Forrester
Journal: Cancer Research (2014)

Abstract Human acute myeloid cell lines can be induced to differentiate into macrophage-like cells by phorbol esters. Differentiation is accompanied by cessation of cell proliferation and initiation of apoptosis. Many of these cell lines, like HL-60, are p53 deficient and therefore execute a differentiation-induced, p53-independent program of cell death. Evaluating changes in gene expression during a time course of PMA-induced HL-60 cell differentiation by DNA microarray analyses and RT-qPCR reveals up-regulation of several pro-apoptotic genes (ex. TNF, MCL1, EGR2, BCL3) and down-regulation of several anti-apoptotic genes (ex. BCL2, ANXA3, TSC22D3). Interestingly, RNA levels of p73 are unchanged, suggesting p73 does not substitute for the missing p53 function via activation of p73 gene transcription, however, we report here that p73 protein levels increase dramatically during the differentiation time course. By reintroducing p53 into HL-60 cells, we compare the changing gene expression profile during p53-mediated apoptosis versus that which occurs during phorbol ester-induced p73 accumulation through protein stabilization. Common and unique gene expression changes define the putative p73-dependent apoptosis program compared to p53-dependent apoptosis. Citation Format: Michael Roberts, Rizwan Saffie, Harold Salmons, Mansoor Ghoto, Juliana Schneider, Jeffrey Forrester. Differentiation induced apoptosis in AML cells: The role of p73 in p53-independent versus p53-mediated apoptosis. [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 346. doi:10.1158/1538-7445.AM2014-346
Care of the Patient with Chronic Uremia.
Authors: Ivan J. Mader
Journal: Annals of Internal Medicine (1964)

s1 February 1964Care of the Patient with Chronic Uremia.Ivan J. Mader, M.D. (Associate), Yoshikazu Morita, M.D. (Associate)Ivan J. Mader, M.D. (Associate)Search for more papers by this author, Yoshikazu Morita, M.D. (Associate)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-60-2-338_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe management of uremia due to irreversible terminal chronic glomerulonephritis in three young adults is described. All are treated by weekly hemodialysis, and all have Scribner plastic arteriovenous shunts inserted into the forearm. The durations of treatment were 9 months, 6 months, and 3 months. The endogenous creatinine clearance is less than 2.5 ml/min in each patient. Typical values in plasma chemistry at the beginning and end of dialysis are: creatinine, 14 mg to 6 mg/100 ml; phosphorus, 11 mg to 6 mg/100 ml; uric acid, 9 mg to 4 mg/100 ml; urea nitrogen, 120 mg to 40 mg/100 ml.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Detroit, Michigan PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1964Volume 60, Issue 2_Part_1Page: 338-338KeywordsBlood plasmaCreatinineGlomerulonephritisMedical dialysisPatientsPhosphorusUreaUric acidYoung adults Issue Published: 1 February 1964 PDF DownloadLoading ...
Abstract P4-07-02: Expression of Cell Adhesion Molecules Predicts Prognosis in Early Breast Cancer Patients
Authors: EM de Kruijf, S Saadatman, A Sajet, W Boer, N van Velzen, H Putter, VTHBM Smit, GJ Liefers, CJH van de Velde, PJK. Kuppen
Journal: Cancer Research (2010)

Abstract Purpose: New prognostic and predictive factors are sought for improvement of tailored treatment in early breast cancer. We examined the clinical impact of cell adhesion molecules (CAM): E-cadherin, N-cadherin, Ep-CAM and CEA. Patients and Methods: Our study population (n=574) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. A tissue micro array (TMA) of formalin-fixed paraffin-embedded tumor tissue was immunohistochemically stained for expression of mentioned CAM. The percentage of membranous stained cells was microscopically analyzed. Based on the median score, all CAM were classified in two groups: low expression versus high expression. For CEA, high expression was further subdivided based on the intensity of staining: high expression and highest expression. Results: High expression was seen for E-cadherin, N-cadherin and Ep-CAM in 49%, 46%, 27% of patients respectively. Low expression, high expression and highest expression were found in respectively 48%, 45% and 8% of cases for CEA. Low expression of E-cadherin (p=0.015) and higher expression levels of N-cadherin, Ep-CAM, CEA (p=0.004; 0.046; 0.001 respectively) all resulted in a worse relapse free period (RFP) of patients. Multivariate analysis revealed only E-cadherin and CEA to be independent prognostic variables. A combination variable was created with expression of both markers: (1) E-cadherin high expression, (2) E-cadherin low or CEA low or high expression (3) CEA highest expression. This variable revealed to be an independent prognostic parameter with high discriminative power for RFP (P&amp;lt;0.001, E-cadherin low or CEA low or high expression versus E-cadherin high expression: Hazard Ratio (HR)= 1.9; CEA highest expression versus E-cadherin high expression: HR= 3.6). A statistically significant interaction was found between expression of both CAM (P&amp;lt;0.001), suggesting a biological connection in their functioning. Conclusion: We have demonstrated that E-cadherin, N-cadherin, Ep-CAM and CEA are of prognostic influence on outcome concerning RFP in breast cancer patients. A combined variable of E-cadherin and CEA expression revealed to have prognostic influence on RFP with high discriminative power and therefore is a candidate parameter for future outcome prediction of patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-07-02.
Closed-Chest Resuscitation in a Cardiac Catheterization Laboratory
Authors: BRIAN DAWSON, EMERSON A. MOFFITT, WILLIAM J. GLOVER, H. J. C. SWAN
Journal: Circulation (1962)

Closed-chest massage and defibrillation were used successfully in the management of six acute cardiac emergencies occurring in a cardiac catheterization laboratory. A modification of the Kouwenhoven method of closed-chest massage was used in infants and small children. It is concluded that open-chest resuscitation is usually unnecessary during cardiac catheterization.
Involvement of Anterior Horn of Spinal Cord in Infectious Mononucleosis
Authors: S. K. Mukherjee
Journal: BMJ (1965)

immediate reduction of the displaced acetabular fragments in cases of sciatic-nerve palsy.He stated that the nerve was usually stretched over the sharp margin of the tilted fragment and that recovery was jeopardized by delay.The decision to operate in this case was taken because the large posterior fragment could be fixed more securely with internal fixation than by conservative treatment.If an opera- tion had not been performed the patient might have developed a delayed sciatic palsy due to movements of the fragment or to involvement in the healing fracture.This emphasizes the need for open reduction in fracture-dislocations of the hip with large posterior fragments of the acetabulum even without clinical evidence of sciatic palsy.
12-o-Tetradecanoyl-phorbol-13-acetate-differentiated U937 cells express a macrophage-like profile of neutral proteinases. High levels of secreted collagenase and collagenase inhibitor accompany low levels of intracellular elastase and cathepsin G.
Authors: H G Welgus, N L Connolly, R M Senior
Journal: Journal of Clinical Investigation (1986)

Human monocytic tumor cells of the U937 cell line contain substantial quantities of two neutrophil neutral proteinases, elastase and cathepsin G, raising the question of whether their presence reflects an expression of transformation or whether normal monocytes undergo a developmental stage in which they produce certain neutrophil proteinases. To address this issue, we examined U937 cells for production of collagenase, since human alveolar macrophages release fibroblast-like collagenase, an enzyme that is distinct from neutrophil collagenase. Using an immunoassay that utilized antibody to skin fibroblast collagenase, we found that U937 cells secreted barely detectable quantities of enzyme, 10-12 ng/10(6) cells per 24 h, under basal conditions. Upon incubation with 10 nM 12-o-tetradecanoyl-phorbol-13-acetate (TPA), however, collagenase release increased 200-fold, comparable to the amount secreted by phorbol-stimulated human fibroblasts. Metabolic labeling and immunoprecipitation confirmed the enhanced synthesis of U937 cell collagenase upon TPA exposure. This enzyme activity further resembled fibroblast collagenase and differed from neutrophil collagenase by exhibiting preferential cleavage of monomeric type III collagen relative to type I. As previously observed with human alveolar macrophages, U937 cells also released a protein identical to the collagenase inhibitor produced by human skin fibroblasts, a molecule not associated with neutrophils. Release of this inhibitor increased 10-fold with TPA exposure. In contrast to collagenase and collagense inhibitor, TPA-treated U937 cells contained only 10-15% as much elastase and cathepsin G activities as control cells. Thus, TPA-induced differentiation modified the presence of these enzymes in the direction of their content in normal monocytes. Since the neutral proteinase profile of undifferentiated U937 cells resembles that of neutrophils and changes markedly after cellular differentiation to one that is characteristic of monocytes, these data suggest that neutrophilic proteinases may be produced by normal monocytes during the early stages of their differentiation.
Renal Angioplasty for Lowering Blood Pressure
Authors: Eberhard Ritz, Johannes F.E. Mann
Journal: New England Journal of Medicine (2000)

The great economist Joseph Schumpeter regarded creative destruction as an indispensable element of economic progress. In a similar vein, the report by van Jaarsveld et al.1 in this issue of the Journal furthers medical progress by doing away with past dogmas on atherosclerotic renal-artery stenosis. The authors report the results of the largest study performed so far to compare the effects of percutaneous transluminal renal angioplasty and (if necessary) antihypertensive-drug therapy with antihypertensive-drug therapy alone with respect to hypertension and renal function in patients with atherosclerotic renal-artery stenosis. The negative results confirm those of two similar but smaller randomized trials. . . .
PGE1 and vasospastic disease.
Authors: V Spence
Journal: BMJ (1980)

One explanation of these anomalies is that talc may be acting as a particulate adjuvant, promoting cell-mediated hypersensitivity reactions to polysaccharide antigens of starch in susceptible individuals.For these reasons we would support efforts to eliminate talc, which although not directly pathogenic in low con- centration, may facilitate cell-mediated re- action to other agents on the surface of surgical gloves.
Pressures are growing to publish clinical trials
Authors: Elizabeth Wager
Journal: BMJ (2004)

EDITOR—After the threat of a court case in New York, GlaxoSmithKline has announced that it will publish results of all its clinical trials on its website.1 2 Eli Lilly recently made a similar announcement, including a commitment to publish all findings in peer reviewed journals.3

This will be welcome news to people such as Abrams and me, who have been (independently) …
The low-frequency isoform of platelet glycoprotein VIb attenuates ligand-mediated signal transduction but not receptor expression or ligand binding
Authors: Elisabetta Trifiro, Shirley A. Williams, Yann Cheli, Kenichi Furihata, Fabio M. Pulcinelli, Diane J. Nugent, Thomas J. Kunicki
Journal: Blood (2009)
Reviews, Notes, and Listings: Living with HIV: Experiment in Courage
Authors: William O. Harrison
Journal: Annals of Internal Medicine (1993)

Literature of Medicine15 December 1993Reviews, Notes, and Listings: Living with HIV: Experiment in CourageWilliam O. Harrison, MDWilliam O. Harrison, MDCalifornia Department of Corrections, San Diego, CA 92122Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-12-199312150-00028 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Living with HIV: Experiment in CourageMary Elizabeth O'Brien. 222 pages. New York: Auburn House; 1992. $49.95.In the beginning was the epidemic of cases of the acquired immunodeficiency syndrome (AIDS), soon followed by the epidemic of AIDS conferences. Now we are seeing the epidemic of AIDS-related books. Only a few of these should be a part of most medical libraries; Living with HIV: An Experiment in Courage is not one of these. Although it is a well written and obviously compassionate book, its scope and tenor are too narrow to be of general appeal.The book is based on a study of ... Author, Article, and Disclosure InformationAffiliations: California Department of Corrections, San Diego, CA 92122 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 1993Volume 119, Issue 12Page: 1234KeywordsAIDSAllied health care professionalsChildrenHIVHIV infectionsHeterosexualsHomosexualsInjecting drug usersLibrariesPediatric infections ePublished: 15 August 2000 Issue Published: 15 December 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Slow-growing melanoma: a dermoscopy follow-up study
Authors: G. Argenziano, H. Kittler, G. Ferrara, P. Rubegni, J. Malvehy, S. Puig, L. Cowell, I. Stanganelli, V. De Giorgi, L. Thomas, P. Bahadoran, S.W. Menzies, D. Piccolo, A.A. Marghoob, I. Zalaudek
Journal: British Journal of Dermatology (2009)

Background Recent evidence suggests that melanoma is a family of different tumours with varying abilities to grow and metastasize. Trends in melanoma epidemiology show a strong increase in the incidence of thin melanoma, with no corresponding increase in mortality or incidence of thick melanoma. We initially evaluated five cases and found that none had baseline features suggestive of melanoma; excision was performed based on slight changes visible only in side‐by‐side comparisons of dermoscopic images. Objectives To assess the clinico‐dermoscopic features and the growth patterns of melanomas that were excised after a follow‐up of 1 year or more due to their inconspicuous features at the baseline consultation. Methods In a multicentre, retrospective study of histopathologically confirmed melanomas excised after follow‐up, we analysed dermoscopic images obtained at the initial consultation and compared them with images obtained at the last follow‐up consultation. Images were analysed and graded using standard algorithms and scored for changes in size, symmetrical or asymmetrical structural change, and development of new melanoma‐specific criteria. An overall score reflecting the amount of change was calculated for each lesion. Results Our series consisted of 103 melanomas. After a median follow‐up of 20 months, most lesions were still in situ or early invasive (median Breslow thickness of 0·48 mm), with only three lesions showing tumour thickness of 1 mm or more. The most frequent baseline characteristics were asymmetrical pigmentation (78·6% of lesions), reticular overall pattern (62·1%), and regression features (35·9%). Most melanomas (58·3%) showed minor to moderate changes over time, with < 2 mm size increase, with asymmetrical structural change, and without development of new melanoma‐specific criteria. Major changes were visible only after a mean follow‐up of 33 months. Conclusions This study provides evidence for the existence of a subgroup of slow‐growing melanomas, which may explain the increase in the incidence of thin melanoma, despite stable rates of thick melanoma and melanoma‐associated mortality.