tbuckley/cabot-search huggingface dataset:
c-Src and c-Abl kinases control hierarchic phosphorylation and function of the CagA effector protein in Western and East Asian Helicobacter pylori strains
Authors: Doreen Mueller, Nicole Tegtmeyer, Sabine Brandt, Yoshio Yamaoka, Eimear De Poire, Dionyssios Sgouras, Silja Wessler, Javier Torres, Adam Smolka, Steffen Backert
Journal: Journal of Clinical Investigation (2012)

Many bacterial pathogens inject into host cells effector proteins that are substrates for host tyrosine kinases such as Src and Abl family kinases. Phosphorylated effectors eventually subvert host cell signaling, aiding disease development. In the case of the gastric pathogen Helicobacter pylori, which is a major risk factor for the development of gastric cancer, the only known effector protein injected into host cells is the oncoprotein CagA. Here, we followed the hierarchic tyrosine phosphorylation of H. pylori CagA as a model system to study early effector phosphorylation processes. Translocated CagA is phosphorylated on Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs EPIYA-A, EPIYA-B, and EPIYA-C in Western strains of H. pylori and EPIYA-A, EPIYA-B, and EPIYA-D in East Asian strains. We found that c-Src only phosphorylated EPIYA-C and EPIYA-D, whereas c-Abl phosphorylated EPIYA-A, EPIYA-B, EPIYA-C, and EPIYA-D. Further analysis revealed that CagA molecules were phosphorylated on 1 or 2 EPIYA motifs, but never simultaneously on 3 motifs. Furthermore, none of the phosphorylated EPIYA motifs alone was sufficient for inducing AGS cell scattering and elongation. The preferred combination of phosphorylated EPIYA motifs in Western strains was EPIYA-A and EPIYA-C, either across 2 CagA molecules or simultaneously on 1. Our study thus identifies a tightly regulated hierarchic phosphorylation model for CagA starting at EPIYA-C/D, followed by phosphorylation of EPIYA-A or EPIYA-B. These results provide insight for clinical H. pylori typing and clarify the role of phosphorylated bacterial effector proteins in pathogenesis.
80 BASELINE AND SEQUENTIAL LIVER STIFFNESS MEASUREMENTS (FIBROSCAN®) ARE INDEPENDENT PREDICTORS OF DEATH, LIVER TRANSPLANTATION OR LIVER DECOMPENSATION IN PRIMARY BILIARY CIRRHOSIS
Authors: C. Corpechot, A. Poujol-Robert, F. Gaouar, O. Chazouilleres, R. Poupon
Journal: Journal of Hepatology (2012)
The Quality of Mercy
Authors: Ralph Crawshaw
Journal: JAMA (1991)

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
Tumor Cell and Endothelial Cell Therapy of Oral Cancer by Dual Tyrosine Kinase Receptor Blockade
Authors: Orhan G. Yigitbasi, Maher N. Younes, Dao Doan, Samar A. Jasser, Bradley A. Schiff, Corazon D. Bucana, Benjamin N. Bekele, Isaiah J. Fidler, Jeffrey N. Myers
Journal: Cancer Research (2004)

Abstract Expression of the epidermal growth factor (EGF) and activation of its receptor (EGFR), a tyrosine kinase, are associated with progressive growth of head and neck cancer. Expression of the vascular endothelial growth factor (VEGF) is associated with angiogenesis and progressive growth of tumor. The tyrosine kinase inhibitor NVP-AEE788 (AEE788) blocks the EGF and VEGF signaling pathways. We examined the effects of AEE788 administered alone, or with paclitaxel (Taxol), on the progression of human head and neck cancer implanted orthotopically into nude mice. Cells of two different human oral cancer lines, JMAR and MDA1986, were injected into the tongues of nude mice. Mice with established tumors were randomized to receive three times per week oral AEE788, once weekly injected paclitaxel, AEE788 plus paclitaxel, or placebo. Oral tumors were resected at necropsy. Kinase activity, cell proliferation, apoptosis, and mean vessel density were determined by immunohistochemical immunofluorescent staining. AEE788 inhibited cell growth, induced apoptosis, and reduced the phosphorylation of EGFR, VEGFR-2, AKT, and mitogen-activated protein kinase in both cell lines. Mice treated with AEE788 and AEE788 plus paclitaxel had decreased microvessel density, decreased proliferative index, and increased apoptosis. Hence, AEE788 inhibited tumor vascularization and growth and prolonged survival. Inhibition of EGFR and VEGFR phosphorylation by AEE788 effectively inhibits cellular proliferation of squamous cell carcinoma of the head and neck, induces apoptosis of tumor endothelial cells and tumor cells, and is well tolerated in mice. These data recommend the consideration of patients with head and neck cancer for inclusion in clinical trials of AEE788.
Progression of Coronary Artery Disease Predicts Clinical Coronary Events
Authors: Stanley P. Azen, Wendy J. Mack, Linda Cashin-Hemphill, Laurie LaBree, Anne M. Shircore, Robert H. Selzer, David H. Blankenhorn, Howard N. Hodis
Journal: Circulation (1996)

Background Progression of coronary artery disease is assumed to be a surrogate end point for clinical coronary events. Because no single method or measure for a coronary angiographic end point is uniformly accepted as optimal, the utility and validity of surrogate end points for predicting clinical coronary events remain unsettled. Methods and Results The Cholesterol Lowering Atherosclerosis Study randomized 162 nonsmoking, 40- to 59-year-old men with previous coronary artery bypass graft surgery to colestipol/niacin plus diet or placebo plus diet. Atherosclerosis change on 2-year coronary angiograms was evaluated by a consensus panel and by quantitative coronary angiography (average per-subject change in percent diameter stenosis [%S] and minimum lumen diameter [MLD]). With all three end points, the benefit of colestipol/niacin treatment on coronary artery atherosclerosis has been reported. Annual follow-up for an average of 7 years (range, 6.3 months to 10 years) has been carried out on all subjects who completed the 2-year angiogram. Clinical coronary events (need for revascularization, nonfatal acute myocardial infarction, and coronary death) have been documented. Risk of clinical coronary events was positively related to coronary lesion progression for all three surrogate end points ( P &lt;.05). New lesion formation in bypass grafts ( P =.02) and progression of mild/moderate lesions (&lt;50%S) were predictive of clinical coronary events ( P &lt;.01). Change in MLD contributed significantly to the prediction of clinical coronary events beyond a model with %S alone ( P &lt;.05). Conclusions In this population of nonsmoking men with previous bypass surgery, both the consensus panel– and quantitative coronary angiography–based end points of coronary artery disease progression predict clinical coronary events. Subjects who demonstrate greater coronary artery lesion progression have an increased risk of future clinical coronary events. Design of shorter, smaller trials of antiatherosclerotic agents is justified.
At Risk: Can the Doctor-Patient Relationship Survive in a High-Tech World?
Authors: Richard E. Peschel
Journal: JAMA (1993)

We recommend this readable and enjoyable book to the general public as an introduction to some of the most troubling aspects of modern medicine. We also think that premedical and medical students would profit from this volume, which offers an introduction to what lies ahead of them: a lifelong struggle to balance the interests of the doctor-patient relationship with other powerful forces that tend to deemphasize this bond. Based on more than 25 years of experience in general medical practice, Charman, associate professor of medicine and director of graduate education at the Dartmouth-Hitchcock Medical Center, states, "The system of reimbursement does not favor patient-physician contact in the office. It favors technology and surgical procedures." We recommend this book for three main reasons. First, it is concise and easy to read. Even though the topics covered are complex, most lay people can read the entire book in one or two nights.
Homicide: A Psychiatric Perspective
Authors: Wade C. Myers
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
Prevalence of Metabolic Syndrome Among an Urban Population in Kenya
Authors: Lydia U. Kaduka, Yeri Kombe, Eucharia Kenya, Elizabeth Kuria, John K. Bore, Zipporah N. Bukania, Moses Mwangi
Journal: Diabetes Care (2012)

Developing countries are undergoing an epidemiologic transition accompanied by increasing burden of cardiovascular disease (CVD) linked to urbanization and lifestyle modifications. Metabolic syndrome is a cluster of CVD risk factors whose extent in Kenya remains unknown. The aim of this study was to determine the prevalence of metabolic syndrome and factors associated with its occurrence among an urban population in Kenya.This was a household cross-sectional survey comprising 539 adults (aged ≥18 years) living in Nairobi, drawn from 30 clusters across five socioeconomic classes. Measurements included waist circumference, HDL cholesterol, triacylglycerides (TAGs), fasting glucose, and blood pressure.The prevalence of metabolic syndrome was 34.6% and was higher in women than in men (40.2 vs. 29%; P < 0.001). The most frequently observed features were raised blood pressure, a higher waist circumference, and low HDL cholesterol (men: 96.2, 80.8, and 80%; women: 89.8, 97.2, and 96.3%, respectively), whereas raised fasting glucose and TAGs were observed less frequently (men: 26.9 and 63.3%; women: 26.9 and 30.6%, respectively). The main factors associated with the presence of metabolic syndrome were increasing age, socioeconomic status, and education.Metabolic syndrome is prevalent in this urban population, especially among women, but the incidence of individual factors suggests that poor glycemic control is not the major contributor. Longitudinal studies are required to establish true causes of metabolic syndrome in Kenya. The Kenyan government needs to create awareness, develop prevention strategies, and strengthen the health care system to accommodate screening and management of CVDs.
Anti-tumor Immunotherapy via Antigen Delivery from a Live Attenuated Genetically Engineered Pseudomonas aeruginosa Type III Secretion System-Based Vector
Authors: Olivier Epaulard, Bertrand Toussaint, Lauriane Quenee, Madiha Derouazi, Nabil Bosco, Christian Villiers, Rozenn Le Berre, Benoit Guery, Didier Filopon, Laurence Crombez, Patrice N. Marche, Benoit Polack
Journal: Molecular Therapy (2006)

Immunotherapy requiring an efficient T lymphocyte response is initiated by antigen delivery to antigen-presenting cells. Several studies have assessed the efficiency of various antigen loading procedures, including microbial vectors. Here a live strain of Pseudomonas aeruginosa was engineered to translocate a recombinant antigenic protein into mammalian cells via the type III secretion system, a bacterial device translocating effector proteins into host cells. Optimization of the vector included virulence attenuation and determination of the N-terminal sequence allowing translocation of fused antigens into cells. In vitro delivery of an ovalbumin fragment by the bacterial vector into dendritic cells induced the activation of ovalbumin-specific CD8(+) T lymphocytes. Mice injected with the ovalbumin-delivering vector developed ovalbumin-specific CD8(+) T lymphocytes and were resistant to a subsequent challenge with an ovalbumin-expressing melanoma. Moreover, in a curative assay, injection of the vaccine vector 5 and 12 days after tumor implantation led to a complete cure in five of six animals. These results highlight the utility of type III secretion system-based vectors for anti-tumor immunotherapy.
Louis Pasteur and rabies
Authors: L. A Bates
Journal: BMJ (1985)

During postnatal development in the peripheral nerve, differentiating Schwann cells are susceptible to apoptotic death. Schwann cell apoptosis is regulated by axons and serves as one mechanism through which axon and Schwann cell numbers are correctly matched. This regulation is mediated in part by the provision of limiting axon-derived trophic molecules, although neuregulin-1 (NRG-1) is the only trophic factor shown to date to support Schwann cell survival. In this report, we identify insulin-like growth factor-I (IGF-I) as an additional trophin that can promote Schwann cell survival<i>in vitro</i>. We find that IGF-I, like NRG-1, can prevent the apoptotic death of postnatal rat Schwann cells cultured under conditions of serum withdrawal. Moreover, we show that differentiating Schwann cells in the rat sciatic nerve express both the IGF-I receptor (IGF-I R) and IGF-I throughout postnatal development. These results indicate that IGF-I is likely to control Schwann cell viability in the developing peripheral nerve and, together with other findings, raise the interesting possibility that such survival regulation may switch during postnatal development from an axon-dependent mechanism to an autocrine and/or paracrine one.
Oral Contraceptives and Nonfatal Myocardial Infarction
Authors: Hershel Jick
Journal: JAMA (1978)

We obtained information on 107 women younger than 46 years who were discharged from a hospital with a diagnosis of acute myocardial infarction. In the series 26 women were otherwise apparently healthy and potentially childbearing. Among these 26 women, 20 (77%) were taking oral contraceptives just prior to admission, and one was taking conjugated estrogens. Among 59 control women, 14 (24%) were taking oral contraceptives and one was taking conjugated estrogens. The relative risk estimate, comparing oral contraceptive users with nonusers, is 14 with 90% confidence limits of 5.5 and 37. All but two of the 26 women were cigarette smokers. While this illness is rare in most healthy young women, the risk in women older than about 37 years who both smoke and take oral contraceptives appears to be high. (<i>JAMA</i>239:1403-1406, 1978)
215 LIVER STIFFNESS VALUES MEASURED BY TRANSIENT ELASTOGRAPHY ARE INCREASED IN PATIENTS WITH ACUTELY DECOMPENSATED HEART FAILURE
Authors: P. Pozzoni, D. Prati, A. Berzuini, A. Gerosa, C. Canovi, E.E. Molteni, M. Barbarini, F. Bonino, A. Colli
Journal: Journal of Hepatology (2009)
Anatomy of an Illness (as Perceived by the Patient)
Authors: Norman Cousins
Journal: New England Journal of Medicine (1976)

Ever since the publication of Adam Smith's much-talked-about Powers of the Mind some months ago, people have written to ask whether his account of my recovery from a supposedly incurable illness1 was accurately reported. In particular, readers have been eager to verify Mr. Smith's statement that I "laughed" my way out of a crippling disease that doctors believed to be irreversible.I have not written until now about my illness, which occurred in 1964, largely because I was fearful of creating false hopes in other persons similarly afflicted. Moreover, I knew that a single case has small standing in the . . .
Cyclosporine, Sympathetic Activity, and Hypertension
Authors: Allyn L. Mark
Journal: New England Journal of Medicine (1990)

Cyclosporine has dramatically advanced immunosuppressive therapy following organ transplantation, but this advance has been accompanied by a high incidence of hypertension in patients receiving this drug, particularly heart-transplant recipients. In this issue of the Journal, Scherrer et al.1 report that cyclosporine-induced elevations in arterial pressure are accompanied by striking increases in sympathetic-nerve traffic (measured directly with intraneural electrodes) and vascular resistance. Previous studies have demonstrated that short-term intravenous administration of cyclosporine increases renal sympathetic-nerve activity in rats.2 , 3 Thus, the finding of Scherrer et al. of increased sympathetic-nerve activity in patients taking cyclosporine has an experimental counterpart. However, plasma and urinary . . .
ADVANTAGES OF BENZOYL PEROXIDE OVER ZINC PEROXIDE OR SULFONAMIDES IN TREATING WOUNDS OR BURNS
Authors: C. D. Leake
Journal: JAMA (1942)

<h3>To the Editors:—</h3> Editorial comment recently appeared (The Journal, March 21, p. 981) on zinc peroxide and sulfonamide derivatives in the treatment of gas gangrene. This called attention to the work of F. L. Meleney (<i>Ann. Surg.</i><b>101</b>:997 [April] 1935;<b>109</b>:881 [June] 1939;<i>U. S. Nav. M. Bull.</i><b>40</b>:53 [Jan.] 1942) in showing the effectiveness of a 40 per cent watery suspension of zinc peroxide in preventing gas gangrene when applied to wounds infected with gas producing organisms. This has been confirmed by G. B. Reed and J. H. Orr (<i>War Med.</i><b>2</b>:79 [Jan.] 1942) and has been extended by them to include the use of sulfathiazole. They state that sulfathiazole is superior to other sulfonamide derivatives for this purpose. The latter opinion is at variance with the experience of surgeons at Pearl Harbor, who feel that there is less foreign body reaction in the wound
Sports Participation, Age at Smoking Initiation, and the Risk of Smoking Among US High School Students
Authors: Luis G. Escobedo
Journal: JAMA (1993)

<h3>Objective.</h3> —To examine smoking patterns, smoking initiation, and the relationship of sports participation and age at smoking initiation to regular and heavy smoking among adolescents. <h3>Design.</h3> —Survey. <h3>Participants.</h3> —A nationally representative sample of US high school students. <h3>Outcome Measures.</h3> —Prevalences of smoking patterns, prevalence and incidence of smoking initiation, and prevalences and odds of regular and heavy smoking in relation to sports participation and age at smoking initiation. <h3>Results.</h3> —Seventy-two percent of students reported experimenting with, formerly, or ever smoking cigarettes, and 32% reported smoking in the past 30 days. Students who had participated in interscholastic sports were less likely to be regular and heavy smokers than were others who had not participated. Smoking initiation rates increased rapidly after age 10 years and peaked at age 13 to 14 years. Students who began smoking at age 12 years or younger were more likely to be regular and heavy smokers than were students who began smoking at older ages. <h3>Conclusions.</h3> —These data suggest that smoking initiation at a young age can increase the risk of nicotine addiction during adolescence and that sports participation may influence smoking behavior. Interventions to prevent smoking should be available before age 12 years to help combat the smoking epidemic among youth. (<i>JAMA</i>. 1993;269:1391-1395)
The Case for Conservative Management of Early HIV Disease
Authors: William J. Burman
Journal: JAMA (1998)

viral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997;277:112-116. 13. Angel JB, Kumar A, Parato K, et al. Improvement in cell-mediated immune function during potent anti-human immunodeficiency virus therapy with ritonavir plus saquinavir. J Infect Dis. 1998;177:898-904. 14. Currier JS, Williams PL, Grimes JM, Squires KS, Fischl MA, Hammer SM. Incidence rates and risk factors for opportunistic infections in a phase III trial comparing indinavir + ZDV to ZDV + 3TC. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 1-5, 1998; Chicago, Ill. 15. Harrer T, Harrer E, Kalams SA, et al. Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. AIDS Res Hum Retroviruses. 1996;12:585-592. 16. Harrer T, Harrer E, Kalams SA, et al. Cytotoxic T lymphocytes in asymptomatic long-term nonprogressing HIV-1 infection: breadth and specificity of the response and relation to in vivo viral quasispecies in a person with prolonged infection and low viral load. J Immunol. 1996;156:2616-2623. 17. Rosenberg ES, Billingsley JM, Caliendo AM, et al. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science. 1997;278: 1447-1450. 18. Spruance SL, Pavia AT, Mellors JW, et al, for the Bristol-Myers Squibb Stavudine/019 Study Group. Clinical efficacy of monotherapy with stavudine compared with zidovudine in HIV-infected, zidovudine-experienced patients: a randomized, double-blind, controlled trial. Ann Intern Med. 1997;126:355-363. 19. Miller KD, Jones E, Yanovski JA, Shankar R, Feuerstein I, Falloon J. Visceral abdominal-fat accumulation associated with use of indinavir. Lancet. 1998; 351:871-875. 20. Lo JC, Mulligan K, Tai VW, Algren H, Schambelan M. “Buffalo hump” in men with HIV-1 infection. Lancet. 1998;351:867-870. 21. Miller K, Daly P, Sentochnik D, et al. Pseudo-Cushing’s syndrome in human immunodeficiency virus-infected patients. Clin Infect Dis. In press.