tbuckley/cabot-search huggingface dataset:
The Roles of Thymidylate Synthase and p53 in Regulating Fas-Mediated Apoptosis in Response to Antimetabolites
Authors: Daniel Broderick Longley, Wendy Louise Allen, Ultan McDermott, Timothy Richard Wilson, Tariq Latif, John Boyer, Maria Lynch, Patrick Gerard Johnston
Journal: Clinical Cancer Research (2004)

Abstract Fas (CD95/Apo-1) is a member of the tumor necrosis factor receptor family. Receptor binding results in activation of caspase 8, leading to activation of proapoptotic downstream molecules. We found that expression of Fas was up-regulated &amp;gt;10-fold in MCF-7 breast and HCT116 and RKO colon cancer cell lines after treatment with IC60 doses of 5-fluorouracil (5-FU) and raltitrexed (RTX). Combined treatment with the agonistic Fas antibody CH-11 and either 5-FU or RTX resulted in a highly synergistic induction of apoptosis in these cell lines. Similar results were obtained for another antifolate, Alimta. Induction of thymidylate synthase expression inhibited Fas induction in response to RTX and Alimta, but not in response to 5-FU. Furthermore, thymidylate synthase induction abrogated the synergy between CH-11 and both antifolates but had no effect on the synergistic interaction between 5-FU and CH-11. Inactivation of p53 in MCF-7 and HCT116 cell lines blocked 5-FU- and antifolate-mediated up-regulation of Fas. Furthermore, Fas was not up-regulated in response to 5-FU or antifolates in the p53-mutant H630 colon cancer cell line. Lack of Fas up-regulation in the p53-null and -mutant lines abolished the synergistic interaction between 5-FU and CH-11. Interestingly, synergy was still observed between the antifolates and CH-11 in the p53-null HCT116 and p53-mutant H630 cell lines, although this was significantly reduced compared with the p53 wild-type cell lines. Our results indicate that Fas is an important mediator of apoptosis in response to both 5-FU and antifolates.
A Case of Unexpected Gastric Mass
Authors: Corrado Pedrazzani, Marco Vitali, Alfredo Guglielmi
Journal: JAMA Surgery (2015)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal
TIM-2 tones down Th2
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Debating DAP12Mice that lack the adaptor protein DAP12 defy deadly bacterial infections, according to Turnbull and colleagues on page 363.DAP12-deficient mice developed a muted inflammatory response, allowing the immune system to clear the bacteria without triggering septic shock.DAP12 is a transmembrane adaptor protein that is associated with an array of DAP12-deficient mice (dotted line) are resistant to a lethal endotoxin challenge.
Response to Hjelmesæth et al.
Authors: Victor M. Montori, Ananda Basu, Patricia J. Erwin, Sherine E. Gabriel, Yogish C. Kudva
Journal: Diabetes Care (2002)

We appreciate the comments of Hjelmesaeth et al. (1) in this issue of Diabetes Care , who have made important contributions to the field of post-transplantation diabetes (PTD) and thank them for their interest in our work. We echo their remarks about the uncertainty surrounding the true incidence of PTD and agree that prospective studies conducted using sound methods are the best source of reliable estimates of the incidence of PTD. Their work on the impact of glucocorticoids on PTD concurs with the results of …
Correlations between magnetic resonance spectroscopy alterations and cerebral ammonia and glucose metabolism in cirrhotic patients with and without hepatic encephalopathy
Authors: K. Weissenborn, B. Ahl, D. Fischer-Wasels, J. van den Hoff, H. Hecker, W. Burchert, H. Kostler
Journal: Gut (2007)

Hepatic encephalopathy is considered to be mainly caused by increased ammonia metabolism of the brain. If this hypothesis is true, cerebral glucose utilisation, which is considered to represent brain function, should be closely related to cerebral ammonia metabolism. The aim of the present study was to analyse whether cerebral ammonia and glucose metabolism in cirrhotic patients with early grades of hepatic encephalopathy are as closely related as could be expected from current hypotheses on hepatic encephalopathy.(13)N-ammonia and (18)F-fluorodesoxyglucose positron emission tomography, magnetic resonance imaging and magnetic resonance spectroscopy (MRS) were performed in 21 cirrhotic patients with grade 0-1 hepatic encephalopathy. Quantitative values of cerebral ammonia uptake and retention rate and glucose utilisation were derived for several regions of interest and were correlated with the MRS data of the basal ganglia, white matter and frontal cortex.A significant correlation between plasma ammonia levels and cerebral ammonia metabolism, respectively, and MRS alterations could be shown only for white matter. In contrast, MRS alterations in all three regions studied were significantly correlated with the glucose utilisation of several brain regions. Cerebral ammonia and glucose metabolism were not correlated.Increase of cerebral ammonia metabolism is an important but not exclusive causal factor for the development of hepatic encephalopathy.
Roles of KLF6 and KLF6-SV1 in Ovarian Cancer Progression and Intraperitoneal Dissemination
Authors: Analisa DiFeo, Goutham Narla, Jennifer Hirshfeld, Olga Camacho-Vanegas, Jyothsna Narla, Stephen L. Rose, Tamara Kalir, Shen Yao, Alice Levine, Michael J. Birrer, Tomas Bonome, Scott L. Friedman, Richard E. Buller, John A. Martignetti
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We investigated the role of the KLF6 tumor suppressor gene and its alternatively spliced isoform KLF6-SV1 in epithelial ovarian cancer (EOC). Experimental Design: We first analyzed tumors from 68 females with EOC for KLF6 gene inactivation using fluorescent loss of heterozygosity (LOH) analysis and direct DNA sequencing and then defined changes in KLF6 and KLF6-SV1 expression levels by quantitative real-time PCR. We then directly tested the effect of KLF6 and KLF6-SV1 inhibition in SKOV-3 stable cell lines on cellular invasion and proliferation in culture and tumor growth, i.p. dissemination, ascites production, and angiogenesis in vivo using BALB/c nu/nu mice. All statistical tests were two sided. Results: LOH was present in 59% of samples in a cell type–specific manner, highest in serous (72%) and endometrioid (75%) subtypes, but absent in clear cell tumors. LOH was significantly correlated with tumor stage and grade. In addition, KLF6 expression was decreased in tumors when compared with ovarian surface epithelial cells. In contrast, KLF6-SV1 expression was increased ∼5-fold and was associated with increased tumor grade regardless of LOH status. Consistent with these findings, KLF6 silencing increased cellular and tumor growth, angiogenesis, and vascular endothelial growth factor expression, i.p. dissemination, and ascites production. Conversely, KLF6-SV1 down-regulation decreased cell proliferation and invasion and completely suppressed in vivo tumor formation. Conclusion: Our results show that KLF6 and KLF6-SV1 are associated with key clinical features of EOC and suggest that their therapeutic targeting may alter ovarian cancer growth, progression, and dissemination.
Does This Woman Have an Ectopic Pregnancy?
Authors: John R. Crochet, Lori A. Bastian, Monique V. Chireau
Journal: JAMA (2013)

The rapid identification and accurate diagnosis of women who may have an ectopic pregnancy is critically important for reducing the maternal morbidity and mortality associated with this condition.To systematically review the accuracy and precision of the patient history, clinical examination, readily available laboratory values, and sonography in the diagnosis of ectopic pregnancy in women with abdominal pain or vaginal bleeding during early pregnancy.We conducted MEDLINE and EMBASE searches for English-language articles from 1965 to December 2012 reporting on the diagnosis of ectopic pregnancy.The analysis included prospective studies of 100 or more pregnant women with abdominal pain or vaginal bleeding that evaluated patient history, physical examination, laboratory values, and sonography compared with a reference standard of either (1) direct surgical visualization of ectopic pregnancy or (2) clinical follow-up for all pregnancies to prove that ectopic pregnancy was not missed. Of 10,890 articles identified by the search, 14 studies with 12,101 patients met the inclusion criteria.Two authors (J.R.C. and M.V.C.) independently extracted data and assessed the quality of each study. A third author (L.A.B.) resolved any discrepancies.All components of the patient history had a positive likelihood ratio (LR+) less than 1.5. The presence of an adnexal mass in the absence of an intrauterine pregnancy on transvaginal sonography (LR+ 111; 95% CI, 12-1028; n = 6885), and the physical examination findings of cervical motion tenderness (LR+ 4.9; 95% CI, 1.7-14; n = 1435), an adnexal mass (LR+ 2.4; 95% CI, 1.6-3.7; n = 1378), and adnexal tenderness (LR+ 1.9; 95% CI, 1.0-3.5; n = 1435) all increase the likelihood of ectopic pregnancy. A lack of adnexal abnormalities on transvaginal sonography (negative LR [LR-] 0.12; 95% CI, 0.03-0.55; n = 6885) decreases the likelihood of ectopic pregnancy. Existing studies do not establish a single serum human chorionic gonadotropin (hCG) level that is diagnostic of ectopic pregnancy.Transvaginal sonography is the single best diagnostic modality for evaluating women with suspected ectopic pregnancy. The presence of abdominal pain or vaginal bleeding during early pregnancy should prompt a transvaginal sonogram and quantitative serum hCG testing.
Emergency treatment of malignant extradural spinal cord compression: an evidence-based guideline.
Authors: D A Loblaw, N J Laperriere
Journal: Journal of Clinical Oncology (1998)

PURPOSE To review the literature for malignant extradural spinal cord compression (MSCC), produce evidence-based recommendations based on the criteria used by the Canadian Task Force on the Periodic Health Examination, and make suggestions regarding future research directives. METHODS A systematic review of the literature with explicit study selection and evaluation criteria was performed. Primary outcome measure was posttreatment ambulation rate. RESULTS There is good evidence to support the use of high-dose dexamethasone (96 mg/d), but inconclusive evidence for the use of moderate-dose steroids (16 mg/d) in conjunction with radiotherapy (RT) for the treatment of MSCC. Fair evidence exists for not using steroids in patients who are nonparetic and ambulatory pretreatment, and to give radiation to patients with subclinical spinal cord compression (SCC). The remainder of the recommendations are based on inconclusive evidence: RT alone should be the first-line treatment for ambulatory patients except when there is spinal instability, bony compression, or paraplegia on presentation, in which case surgery should be performed. Either modality can be used for paraparetic patients who are nonambulatory. Postoperative RT should be considered for tumor in residua. Ambulatory, undiagnosed patients should have needle biopsy attempted first. Patients should be aggressively screened and educated about SCC. CONCLUSION In general, there were very few papers of high methodologic quality found in the literature. More studies are needed to satisfy the validity of many of the clinical decisions that are made today with regard to the management of MSCC.
Germinal Centers without T Cells
Authors: Carola García de Vinuesa, Matthew C. Cook, Jennifer Ball, Marion Drew, Yvonne Sunners, Marilia Cascalho, Matthias Wabl, Gerry G.B. Klaus, Ian C.M. MacLennan
Journal: The Journal of Experimental Medicine (2000)

Germinal centers are critical for affinity maturation of antibody (Ab) responses. This process allows the production of high-efficiency neutralizing Ab that protects against virus infection and bacterial exotoxins. In germinal centers, responding B cells selectively mutate the genes that encode their receptors for antigen. This process can change Ab affinity and specificity. The mutated cells that produce high-affinity Ab are selected to become Ab-forming or memory B cells, whereas cells that have lost affinity or acquired autoreactivity are eliminated. Normally, T cells are critical for germinal center formation and subsequent B cell selection. Both processes involve engagement of CD40 on B cells by T cells. This report describes how high-affinity B cells can be induced to form large germinal centers in response to (4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll in the absence of T cells or signaling through CD40 or CD28. This requires extensive cross-linking of the B cell receptors, and a frequency of antigen-specific B cells of at least 1 in 1,000. These germinal centers abort dramatically at the time when mutated high-affinity B cells are normally selected by T cells. Thus, there is a fail-safe mechanism against autoreactivity, even in the event of thymus-independent germinal center formation.
Distribution and metabolism in healthy volunteers of disodium azodisalicylate, a potential therapeutic agent for ulcerative colitis.
Authors: C P Willoughby, J K Aronson, H Agback, N O Bodin, S C Truelove
Journal: Gut (1982)

A series of experiments has been performed in healthy male volunteers to investigate the disposition of orally administered disodium azodisalicylate, a potentially useful drug for the treatment of ulcerative colitis. The drug was given by mouth in doses of up to 2 g a day for six weeks and there were no adverse effects. Serum concentrations of the intact compound were low and the serum half-time was 4-12.8 days, probably because of a combination of a low clearance rate and a high apparent volume of distribution. Less than 5% of the ingested dose was excreted unchanged in the urine. Circulating concentrations of 5-ASA and N-acetyl-5-ASA were low and 30% of the equivalent daily dose was excreted in the urine, predominantly as N-acetyl-5-ASA. In most subjects more than 30% of the equivalent daily dose of 5-ASA was recovered from the faeces, either as 5-ASA itself or as the acetylated derivative. As 5-ASA has been shown to be the active therapeutic moiety of sulphasalazine, disodium azodisalicylate appears to be suitable for therapeutic trial in ulcerative colitis.
Heterozygote detection in Fabry's disease using mailed hair roots
Authors: A.J.M. Vermorken, C.A. van Bennekom, C.H.M.M. de Bruyn, T.L. Oei, J. Frohlich
Journal: British Journal of Dermatology (1980)

Journal Article Heterozygote detection in Fabry's disease using mailed hair roots Get access A.J.M. Vermorken, A.J.M. Vermorken Department of Pharmacology, Human Genetics and Biochemistry, University of Nijmegen, The Netherlands Dr A.J.M. Vermorken, Department of Pharmacology, University of Nijmegen, Geert Grooteplein Noord 21, Nijmegen, The Netherlands. Search for other works by this author on: Oxford Academic Google Scholar C.A. van Bennekom, C.A. van Bennekom Department of Human Genetics, Faculty of Medicine, University of Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar C.H.M.M. de Bruyn, C.H.M.M. de Bruyn Department of Human Genetics, Faculty of Medicine, University of Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar T.L. Oei, T.L. Oei Department of Human Genetics, Faculty of Medicine, University of Nijmegen, The Netherlands Search for other works by this author on: Oxford Academic Google Scholar J. Frohlich J. Frohlich Vancouver General Hospital, Division of Clinical Chemistry and Department of Pathology, University of British Columbia, Vancouver, B.C., Canada Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 103, Issue 1, 1 July 1980, Pages 101–103, https://doi.org/10.1111/j.1365-2133.1980.tb15845.x Published: 01 July 1980
Immunomonitoring Tumor-Specific T Cells in Delayed-Type Hypersensitivity Skin Biopsies After Dendritic Cell Vaccination Correlates With Clinical Outcome
Authors: I. Jolanda M. de Vries, Monique R. Bernsen, W. Joost Lesterhuis, Nicole M. Scharenborg, Simon P. Strijk, Marie-Jeanne P. Gerritsen, Dirk J. Ruiter, Carl G. Figdor, Cornelis J.A. Punt, Gosse J. Adema
Journal: Journal of Clinical Oncology (2005)

Tumor-specific immunomonitoring is essential to evaluate the efficacy of vaccination against cancer. In this study, we investigated the predictive value of the presence or absence of antigen-specific T cells in biopsies from delayed-type hypersensitivity (DTH) sites.In our ongoing clinical trials, HLA-A2.1+ melanoma patients were vaccinated with mature dendritic cells (DC) pulsed with melanoma-associated peptides (gp100 and tyrosinase) and keyhole limpet hemocyanin.After intradermal administration of a DTH challenge with gp100- and tyrosinase peptide-loaded DC, essentially all patients showed a positive induration. In clinically responding patients, T cells specific for the antigen preferentially accumulated in the DTH site, as visualized by in situ tetramer staining. Furthermore, significant numbers of functional gp100 and tyrosinase tetramer-positive T cells could be isolated from these DTH biopsies, in accordance with the applied antigen in the DTH challenge. We observed a direct correlation between the presence of DC vaccine-related T cells in the DTH biopsies of stage IV melanoma patients and a positive clinical outcome (P = .0012).These findings demonstrate the potency of this novel approach in the monitoring of vaccination studies in cancer patients.
CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia
Authors: Megan E. McNerney, Christopher D. Brown, Xiaoyue Wang, Elizabeth T. Bartom, Subhradip Karmakar, Chaitanya Bandlamudi, Shan Yu, Jinkyung Ko, Barry P. Sandall, Thomas Stricker, John Anastasi, Robert L. Grossman, John M. Cunningham, Michelle M. Le Beau, Kevin P. White
Journal: Blood (2012)
Comparison of Atenolol, Amlodipine, Enalapril, Hydrochlorothiazide, and Losartan for Antihypertensive Treatment in Patients with Obstructive Sleep Apnea
Authors: HOLGER KRAICZI, JAN HEDNER, YÜKSEL PEKER, LUDGER GROTE
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We compared the effects of atenolol (50 mg), amlodipine (5 mg), enalapril (20 mg), hydrochlorothiazide (25 mg), and losartan (50 mg) given in once-daily oral doses on office and ambulatory blood pressures (BPs) in patients with hypertension and obstructive sleep apnea (OSA). Each of 40 randomized patients was treated in sequence with two of the five agents (balanced incomplete block design). Treatment periods lasted 6 wk and were separated by a 3-wk washout period. Changes in BP from baseline with the study substances were compared through analysis of variance. Office diastolic BP, our primary outcome variable, was most effectively lowered by atenolol, with all four post hoc differences between atenolol and the remaining substances being statistically significant. Reductions in office systolic and daytime ambulatory BP were not significantly different among the five compounds. However, atenolol reduced mean nighttime ambulatory diastolic and systolic BP more effectively than did amlodipine, enalapril, or losartan (but not hydrochlorothiazide). Severity of sleep-disordered breathing and well-being during the day were not significantly influenced by any of the study compounds. Our findings are in accordance with the hypothesis that an overactivity of the sympathetic nervous system is an important mechanism behind the development or maintenance of hypertension in patients with OSA.
Epoxycyclopentenone-Containing Oxidized Phospholipids Restore Endothelial Barrier Function via Cdc42 and Rac
Authors: Konstantin G. Birukov, Valery N. Bochkov, Anna A. Birukova, Kamon Kawkitinarong, Alexander Rios, Alexander Leitner, Alexander D. Verin, Gary M. Bokoch, Norbert Leitinger, Joe. G.N. Garcia
Journal: Circulation Research (2004)

After an acute phase of inflammation or injury, restoration of the endothelial barrier is important to regain vascular integrity and to prevent edema formation. However, little is known about mediators that control restoration of endothelial barrier function. We show here that oxidized phospholipids that accumulate at sites of inflammation and tissue damage are potent regulators of endothelial barrier function. Oxygenated epoxyisoprostane-containing phospholipids, but not fragmented oxidized phospholipids, exhibited barrier-protective effects mediated by small GTPases Cdc42 and Rac and their cytoskeletal, focal adhesion, and adherens junction effector proteins. Oxidized phospholipid-induced cytoskeletal rearrangements resulted in a unique peripheral actin rim formation, which was mimicked by coexpression of constitutively active Cdc42 and Rac, and abolished by coexpression of dominant-negative Rac and Cdc42. Thus, oxidative modification of phospholipids during inflammation leads to the formation of novel regulators that may be critically involved in restoration of vascular barrier function.
Peroxynitrite Is a Major Contributor to Cytokine-Induced Myocardial Contractile Failure
Authors: Péter Ferdinandy, Hajira Danial, Ildikó Ambrus, Richard A. Rothery, Richard Schulz
Journal: Circulation Research (2000)

Abstract —Proinflammatory cytokines depress myocardial contractile function by enhancing the expression of inducible NO synthase (iNOS), yet the mechanism of iNOS-mediated myocardial injury is not clear. As the reaction of NO with superoxide to form peroxynitrite markedly enhances the toxicity of NO, we hypothesized that peroxynitrite itself is responsible for cytokine-induced cardiac depression. Isolated working rat hearts were perfused for 120 minutes with buffer containing interleukin-1β, interferon-γ, and tumor necrosis factor-α. Cardiac mechanical function and myocardial iNOS, xanthine oxidoreductase (XOR), and NAD(P)H oxidase activities (sources of superoxide) were measured during the perfusion. Cytokines induced a marked decline in myocardial contractile function accompanied by enhanced activity of myocardial XOR, NADH oxidase, and iNOS. Cardiac NO content, myocardial superoxide production, and perfusate nitrotyrosine and dityrosine levels, markers of peroxynitrite, were increased in cytokine-treated hearts. The peroxynitrite decomposition catalyst FeTPPS (5,10,15,20-tetrakis-[4-sulfonatophenyl]-porphyrinato-iron[III]), the NO synthase inhibitor N G -nitro- l -arginine, and the superoxide scavenger tiron each inhibited the decline in myocardial function and decreased perfusate nitrotyrosine levels. Proinflammatory cytokines stimulate the concerted enhancement in superoxide and NO-generating activities in the heart, thereby enhancing peroxynitrite generation, which causes myocardial contractile failure.
Role of trehalose in resistance to macrophage killing: study with a tps1/tps1 trehalose-deficient mutant of Candida albicans
Authors: M. Martínez-Esparza, A. Aguinaga, P. González-Párraga, P. García-Peñarrubia, T. Jouault, J.C. Argüelles
Journal: Clinical Microbiology and Infection (2007)