tbuckley/cabot-search huggingface dataset:
COX-2 induction by unconjugated bile acids involves reactive oxygen species-mediated signalling pathways in Barrett's oesophagus and oesophageal adenocarcinoma
Authors: S. Song, S. Guha, K. Liu, N. S Buttar, R. S Bresalier
Journal: Gut (2007)

<h3>Objectives:</h3> Bile reflux contributes to oesophageal injury and neoplasia. COX-2 is involved in both inflammation and carcinogenesis; however, the precise mechanisms by which bile acids promote COX-2 expression in the oesophagus are largely unknown. We analysed the molecular mechanisms that govern bile acid-mediated expression of COX-2 in Barrett's oesophagus and oesophageal adenocarcinoma (OA). <h3>Design:</h3> The effects of bile acids on COX-2 expression were analysed in immortalised Barrett's oesophagus and OA cells using immunoblotting and transient transfections. Pharmacological inhibitors, phospho-specific antibodies, dominant-negative mutants and siRNA techniques were used to identify relevant signalling pathways. Flow cytometry and reactive oxygen species (ROS) scavengers were used to examine ROS involvement. Immunohistochemistry was performed on oesophageal mucosa obtained from an established rat model of bile reflux. <h3>Results:</h3> Unconjugated bile acids potently stimulated COX-2 expression and induced AKT and ERK1/2 phosphorylation in concert with COX-2 induction. These findings were mimicked in the <i>in vivo</i> rat model. Dominant-negative (DN) AKT and LY294002 (PI3K inhibitor) or U0126 (MEK-1/2 inhibitor) blocked chenodeoxycholic acid (CD) and deoxycholic acid (DC) mediated COX-2 induction. CD and DC also induced CREB phosphorylation and AP-1 activity. CREB-specific siRNA and DN AP-1 blocked CD and DC-induced COX-2 induction. Finally, CD and DC increased intracellular ROS, while ROS scavengers blocked COX-2 induction and the signalling pathways involved. <h3>Conclusions:</h3> Unconjugated bile acids induce CREB and AP-1-dependent COX-2 expression in Barrett's oesophagus and OA through ROS-mediated activation of PI3K/AKT and ERK1/2. This study enhances our understanding of the molecular mechanisms by which bile acids promote the development of oesophageal adenocarcinoma.
Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence
Authors: Wahid Boukouaci, Laura Lauden, Johan Siewiera, Noemie Dam, Hocine-Rachid Hocine, Zena Khaznadar, Ryad Tamouza, Luis R. Borlado, Dominique Charron, Nabila Jabrane-Ferrat, Reem Al-Daccak
Journal: Cardiovascular Research (2014)

Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are promising candidates for cardiac repair. They interact with T cells, major effectors of the adaptive immune response, inducing 'paracrine' anti-inflammatory effects that could sustain tissue repair/regeneration. Natural killer (NK) cells are major effectors of the innate immune system that might influence the persistence of therapeutic stem/progenitor cells. Therefore, to get through successful clinical translation and anticipate allogeneic hCPC persistence, we defined their crosstalk with NK cells under steady state and inflammatory conditions. By using an experimental model of allogeneic hCPC/NK cell interaction, we demonstrate that hCPC moderately trigger cytokine-activated, but not resting, NK cell killing that occurs through formation of lytic immunological synapse and NK cell natural cytotoxicity. Yet, inflammatory context substantially decreases their capacity to set cytokine-activated NK cell functions towards NK cell-cytotoxicity and protects hCPC from NK cell killing. Allogeneic hCPC also restrain NK cell-cytotoxicity against conventional targets and inflammatory cytokine secretion biasing the latter towards anti-inflammatory cytokines. Thus, hCPC are unprivileged targets for allogeneic NK cells and can restrain NK cell functions in allogeneic setting. Collectively, our data suggest that allogeneic hCPC/innate NK cells crosstalk within injured inflamed myocardium would permit their retention and might contribute to attenuating inflammation and to preventing adverse cardiac remodelling.
A Controlled Evaluation of Staging Dietary Patterns to Reduce the Risk of Diabetes in African-American Women
Authors: Wendy Auslander, Debra Haire-Joshu, Cheryl Houston, Chaie-Won Rhee, James Herbert Williams
Journal: Diabetes Care (2002)

OBJECTIVE—This study evaluated the 3-month follow-up data of the Eat Well, Live Well Nutrition Program, a culturally specific, peer-led dietary change program designed to reduce the risk of type 2 diabetes in low-income African-American women. This peer-led program was delivered in the community and was tailored to the participants’ stage of change for individual dietary patterns. We report the results of the 3-month intervention and the extent to which dietary changes and other key outcomes were maintained at a 3-month follow-up assessment. RESEARCH DESIGN AND METHODS—Using an experimental control group design, 294 overweight African-American women (ages 25–55 years), recruited in collaboration with a neighborhood organization, completed pre- and posttest and 3-month follow-up interviews of dietary behaviors, knowledge, attitudes, fat intake, and weight. RESULTS—Significant reductions were found in fat intake among women in the treatment condition when compared with women in the control group; these reductions were maintained at 3-month follow-up assessment. Likewise, significant changes in dietary patterns were reported after the study and were maintained, except for one dietary pattern (replacement). CONCLUSIONS—This model of health promotion, which individually tailors dietary patterns through staging and use of peer educators, has the potential for decreasing fat intake and increasing and maintaining specific low-fat dietary patterns among overweight African-American women at risk for diabetes.
Influence of Chemotherapy on <i>EGFR</i> Mutation Status Among Patients With Non–Small-Cell Lung Cancer
Authors: Hua Bai, Zhijie Wang, Keneng Chen, Jun Zhao, J. Jack Lee, Shuhang Wang, Qinghua Zhou, Minglei Zhuo, Li Mao, Tongtong An, Jianchun Duan, Lu Yang, Meina Wu, Zhen Liang, Yuyan Wang, Xiaozheng Kang, Jie Wang
Journal: Journal of Clinical Oncology (2012)

EGFR mutation is a predictor of epidermal growth factor receptor-tyrosine kinase inhibitor treatment response in patients with non-small-cell lung cancer (NSCLC). However, it remains unclear whether chemotherapy affects EGFR mutation status in NSCLC. We investigated the influence of chemotherapy on EGFR mutations in plasma and tumor tissues from patients with NSCLC.Samples were derived from three cohorts: one, 264 patients with advanced NSCLC who received first-line chemotherapy with matched pre- and postchemotherapy blood samples; two, 63 patients with stages IIb to IIIb disease with pre- and post-neoadjuvant chemotherapy tumor tissues; and three, 79 patients with advanced NSCLC who underwent palliative surgery. EGFR mutation status was determined and analyzed to reveal potential impact of chemotherapy.In the first cohort, EGFR mutations were detected in 34.5% of the prechemotherapy plasma samples (91 of 264) but in only 23.1% of the postchemotherapy plasma samples (61 of 264). The decrease in EGFR mutation rate was statistically significant (P < .001). Patients whose EGFR mutations switched from positive to negative after chemotherapy had a better partial response (PR) than patients with a reverse change (P = .037). A similar decrease in EGFR mutation rate was observed in tissues after neoadjuvant chemotherapy in the second cohort (34.9% [22 of 63] v 19.0% [12 of 63]; P = .013). In the third cohort, 38.0% of the tumors (30 of 79) showed an intratumor heterogeneity of EGFR mutation, whereas 62.0% (49 of 79) were homogeneous, either with EGFR mutation or no mutation.Our results suggest that chemotherapy may reduce EGFR mutation frequency in patients with NSCLC, likely the result of a preferential response of subclones with EGFR mutations in tumors with heterogeneous tumor cell populations.
Protection by beta-blocking agents against free radical-mediated sarcolemmal lipid peroxidation.
Authors: I T Mak, W B Weglicki
Journal: Circulation Research (1988)

The effects of beta-blocking and class I antiarrhythmic agents on free radical-mediated sarcolemmal lipid peroxidation were examined. Highly purified canine myocytic sarcolemmal membranes were pretreated with 10-800 microM of selected beta-blocking (propranolol, pindolol, metoprolol, atenolol, or sotalol) and class I (quinidine, lidocaine, procainamide, or diphenylhydantoin) antiarrhythmic agents at 37 degrees C for 10 minutes. Subsequently, a superoxide radical (derived from dihydroxyfumarate) driven, Fe3+-ADP catalyzed free radical generating system was added and incubated for up to 45 minutes. Lipid peroxidation of sarcolemma was determined by malondialdehyde formation. Pretreatment of the membranes with the five beta-blockers resulted in various degrees (20-95%) of inhibition of sarcolemmal peroxidation in a concentration- and time-dependent manner. All the class I agents were less effective (less than 20% inhibition). The order of potency of the beta-blockers was propranolol greater than pindolol greater than metoprolol greater than atenolol greater than sotalol and appeared to relate to their degree of lipophilicity. Propranolol, the most potent agent, achieved half-maximal inhibition of peroxidation at about 100 microM and achieved significance (p less than 0.01) at 20 microM. At pH 6.0, the efficacy of pindolol, metoprolol, atenolol, and sotalol diminished by 30-50% compared to pH 7.2, but the potency of propranolol remained unchanged. Since increased free radical production may occur during myocardial ischemia/reperfusion injury, the above findings suggest that the lipophilic beta-blockers may provide additional antiperoxidative protection of ischemic tissue.
Bleeding Increases the Risk of Ischemic Events in Patients With Peripheral Arterial Disease
Authors: Eline S. van Hattum, Ale Algra, James A. Lawson, Bert C. Eikelboom, Frans L. Moll, Marco J.D. Tangelder
Journal: Circulation (2009)

Background— Patients with peripheral arterial disease are at high risk of ischemic events and therefore are treated with antithrombotics. In patients with coronary artery disease or cerebrovascular disease, bleeding is related to the subsequent occurrence of ischemic events. Our objective was to assess whether this is also the case in patients with peripheral arterial disease. Methods and Results— All patients from the Dutch Bypass and Oral Anticoagulants or Aspirin (BOA) Study, a multicenter randomized trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery, were included. The primary outcome event was the composite of nonfatal myocardial infarction, nonfatal ischemic stroke, major amputation, and cardiovascular death. To identify major bleeding as an independent predictor for ischemic events, crude and adjusted hazard ratios with 95% confidence intervals were calculated with multivariable Cox regression models. From 1995 until 1998, 2650 patients were included with 101 nonfatal major bleedings. During a mean follow-up of 14 months, the primary outcome event occurred in 218 patients; 22 events were preceded by a major bleeding. The mean time between major bleeding and the primary outcome event was 4 months. Major bleeding was associated with a 3-fold increased risk of subsequent ischemic events (crude hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.6; adjusted hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.7). Conclusions— In patients with peripheral arterial disease, as in patients with coronary artery disease or cerebrovascular disease, major bleeding was independently associated with major ischemic complications. Without compromising the benefits of antithrombotics, these findings call for caution relative to the risks of major bleeding.
The Transcriptional Promoter Regulates Hypermutation of the Antibody Heavy Chain Locus
Authors: Kathleen Tumas-Brundage, Tim Manser
Journal: The Journal of Experimental Medicine (1997)

A somatic process introduces mutations into antibody variable (V) region genes at a high rate in many vertebrates, and is a major source of antibody diversity. The mechanism of this hypermutation process remains enigmatic, although retrospective studies and transgenic experiments have recently suggested a role for transcriptional regulatory elements. Here, we demonstrate that mouse heavy (H) chain loci in which the natural VH promoter has been replaced by a heterologous promoter undergo hypermutation. However, while the distribution of mutation in such loci appears normal, the frequency of mutation does not. Conversely, moving the VH promoter 750 bp upstream of its normal location results in a commensurate change in the site specificity of hypermutation in H chain loci, and the foreign DNA inserted into the VH leader intron to produce this promoter displacement is hypermutated in a manner indistinguishable from natural Ig DNA. These data establish a direct mechanistic link between the IgH transcription and hypermutation processes.
Trends in the Evidence Level for the American Diabetes Association's “Standards of Medical Care in Diabetes” From 2005 to 2014
Authors: Richard W. Grant, M. Sue Kirkman
Journal: Diabetes Care (2014)

In the January Supplement of Diabetes Care , the American Diabetes Association (ADA) has published the newest version of the “Standards of Medical Care in Diabetes” (1). These Standards provide guidelines to help clinicians in the management of their patients with diabetes or at risk for diabetes. Published in one form or another since 1989, the Standards cover multiple aspects of clinical care, such as screening and diagnosis, glycemic management, and cardiovascular risk reduction. Over the past decade, the ADA has made a concerted effort to be transparent and evidence-based in its guideline development as recommended by the Institute of Medicine for guideline-setting organizations (2). We reviewed the ADA recommendations from the past decade to assess trends in the quality of evidence cited to support these recommendations.

Each year, the recommendations in the Standards are reviewed and revised in light of emerging and changing evidence. We examined the total number and evidence level for all bulleted recommendations made by the Standards of Care each year from 2005 to 2014. Recommendations are assigned ratings of A, B, C, or E depending on the quality of evidence (Table 1). For our analyses of trends over the past decade, we combined A- and B-level recommendations into a “higher-level evidence” category and combined C- and E-level recommendations into a “lower-level evidence” category. We then calculated the proportion of overall recommendations that were based on higher-level evidence each year. We also examined trends in the recommendations within …
Galectin-7 in Lymphoma: Elevated Expression in Human Lymphoid Malignancies and Decreased Lymphoma Dissemination by Antisense Strategies in Experimental Model
Authors: Mélanie Demers, Katherine Biron-Pain, Josée Hébert, Alain Lamarre, Thierry Magnaldo, Yves St-Pierre
Journal: Cancer Research (2007)

Abstract Galectin-7 is found mainly in stratified squamous epithelia as well as in various other types of cancer cells. As with other members of the galectin family, the expression of galectin-7 has been shown to negatively regulate the development of some tumors while correlating with the progression of other tumor types. For example, up-regulation of galectin-7 is associated with rat mammary carcinomas and with progression to T-cell malignancy. Here, we provide evidence indicating that galectin-7 functions as an important molecule in the dissemination of lymphoma cells in vivo. We found that stable transfection of lymphoma cells with a plasmid encoding antisense galectin-7 cDNA significantly inhibited the dissemination and invasion of lymphoma cells to peripheral organs, thereby increasing the survival of mice. We also found that inhibition of galectin-7 in aggressive lymphoma cells correlated with a decreased invasion of tumor cells in target organs and a reduced expression of matrix metalloproteinase-9, a gene associated with a poor prognosis in non–Hodgkin's lymphoma. We finally examined the expression of galectin-7 in 50 specimens of different mature B-cell neoplasms and found high galectin-7 expression levels in a significant proportion of mature B-cell neoplasms but not in normal B cells. Taken together, these findings suggest that galectin-7 is a potential therapeutic target in the treatment of lymphoid malignancies. [Cancer Res 2007;67(6):2824–9]
TRANSPLANTATION OF A SEGMENT OF SMALL INTESTINE TO REPAIR THE RESECTED SIGMOID FLEXURE
Authors: W. S. Fenwick
Journal: BMJ (1911)

A COLOTOMY, to say the least, is anl unpleasant thing.I tlhink olie m:ay, state without cxaggeration that there are fewv patients who, learning for tlhe,first time that an arti- ficial anus has to be miade, regard the prospect with any- thinig slhort of absoluLte horror.Apart fronm the actual inlconvemience from the soilinig of the skin of the abdomen alid tlhe w'earing of a colotomy belt, the seuse of decency is affrolnted.Social intercourse to all tllose doomed to a pormiaiient colotonmy mullst necessavily be a constant source of anxiety.It is true that some patients whose bowels naturally act with regtularity maniage a colotomy with suirprising success, bIut even they have to be most careful in matter-s of diet anid exorcise.When, lowever, thle bowvels are nornlally loose, great difficulty is experience( in controlling the evacuations, anid life becomes utterly IIiiserable.This was the case.with the patient upon whom I per- formede the operation described below, and which I devised after witnessillg hiis distress when told bllat the artificial anus could not be dispensed witlh.For tlhree weeks lie lhad cstrulggled witlh his colotomy.A belt lhad been fitted, bbut -was constantly -soiled, hiisclothlinga was ruined, anc, as lie said, it was imiipossible for hlimi to associate witlr-bis fellow-men.The patient (C.T. B.), a maan aged 51, was first seen by mue in constltationi withl Dr. Roiald A. Taylor, of Adelaide R{oad, Hampstead, on January 18th, 1911.I founid lhillm obviouisly suiffering fromn chronic intestinal -obstruction, andl frolmi the hiistory that lie gave I lhad little dloubt that a stricture of cancerous nature exzisted in the siagnoid flexure of the -colon.Owing to tlle kindlness of Sir Frederick C. Wallis I was able to admit lhim to Cliaring Cross Hospital, and on tllh 21st I opened the abdomiien between the umbilicus andl pubes.and fou-nd a small, hard, freely movable growtll situated in the coloil just at the brini of tlhe pelvis.
Prediction of the effectiveness of long-term β-blocker therapy for dilated cardiomyopathy by signal-averaged electrocardiography: a prospective study
Authors: T. Yamada, M. Fukunami, T. Shimonagata, K. Kumagai, S. Sanada, H. Ogita, Y. Asano, N. Hoki
Journal: Journal of the American College of Cardiology (1998)
Plants and Fungi as Etiologic Agents of Cirrhosis
Authors: Charles S. Davidson
Journal: New England Journal of Medicine (1963)

THE causes of cirrhosis are by no means entirely known. In alcoholic patients malnutrition, probably alcohol and possibly virus hepatitis need to be considered.1 Among patients without alcoholism hepatitis virus and malnutrition have been invoked as possible causes, and yet neither alone nor in combination do these seem to be sufficient to account for the worldwide presence but varied incidence of this disease. Other possible factors need to be searched for and studied, among which is a number of plants and fungi known to produce liver lesions when ingested by animals and, in some cases, by man.2 The great emphasis . . .
Economic Evaluation of Breast Cancer Treatment: Considering the Value of Patient Choice
Authors: Daniel Polsky, Jeanne S. Mandelblatt, Jane C. Weeks, Laura Venditti, Yi-Ting Hwang, Henry A. Glick, Jack Hadley, Kevin A. Schulman
Journal: Journal of Clinical Oncology (2003)

To use 5 years of primary data to compare the incremental cost-effectiveness of breast conservation and radiation versus mastectomy with the restriction of choice to a single therapy versus providing a choice of either therapy.We evaluated a random retrospective cohort of 2,517 Medicare beneficiaries treated for newly diagnosed stage I or II breast cancer from 1992 through 1994. The outcome measures were quality-adjusted life-years (QALYs) and 5-year medical costs. Risk and propensity score adjustments were used in the analysis.A breast conservation and radiation regimen has significantly higher costs than mastectomy in the first year after surgery; the adjusted 5-year costs are $14,054 (95% confidence interval, $9,791 to $18,312) greater than those of mastectomy. The adjusted incremental cost-effectiveness ratio comparing breast conservation and radiation to mastectomy was $219,594 per QALY for the comparison of the two strategies. If the possibility of patient choice from maintaining the availability of multiple treatments versus restricting choice to mastectomy alone provides a quality-of-life gain of 0.031 QALYs, then the cost-effectiveness ratio of this choice option is $80,440 per QALY.The current system of providing a choice between mastectomy and breast conservation surgery is economically attractive when the economic analysis includes the benefit of patient choice of treatment.
FAK Deficiency in Cells Contributing to the Basal Lamina Results in Cortical Abnormalities Resembling Congenital Muscular Dystrophies
Authors: Hilary E. Beggs, Dorreyah Schahin-Reed, Keling Zang, Sandra Goebbels, Klaus-Armin Nave, Jessica Gorski, Kevin R. Jones, David Sretavan, Louis F. Reichardt
Journal: Neuron (2003)
QuantiFERON-TB Gold and the TST are both useful for latent tuberculosis infection screening in autoimmune diseases
Authors: F. Bartalesi, S. Vicidomini, D. Goletti, C. Fiorelli, G. Fiori, D. Melchiorre, E. Tortoli, A. Mantella, M. Benucci, E. Girardi, M. M. Cerinic, A. Bartoloni
Journal: European Respiratory Journal (2008)

Screening for active tuberculosis (TB) and latent TB infection (LTBI) is mandatory prior to the initiation of tumour necrosis factor-alpha inhibitor therapy. However, no agreement exists on the best strategy for detecting LTBI in this population. The aim of the present study was to analyse the performance of the tuberculin skin test (TST) and QuantiFERON-TB Gold in-tube (QFT-GIT) on LTBI detection in subjects with immunomediated inflammatory diseases (IMID). The TST and QFT-GIT were prospectively performed in 398 consecutive IMID subjects, 310 (78%) on immunosuppressive therapy and only 16 (4%) had been bacillus Calmette-Guérin (BCG) vaccinated. Indeterminate results to QFT-GIT were found in five (1.2%) subjects. Overall, 74 (19%) out of 393 subjects were TST-positive and 52 (13%) were QFT-GIT-positive. Concordance between TST and QFT-GIT results was good (87.7%): 13 were QFT-GIT-positive/TST-negative and 35 QFT-GIT-negative/TST-positive. By multivariate analysis both tests were significantly associated with older age. Only the TST was associated with BCG vaccination and radiological lesions of past TB. Use of immunosuppressive drugs differently modulated QFT-GIT or TST scoring. Use of the QuantiFERON-TB Gold in-tube, as a screening tool for latent tuberculosis among immunomediated inflammatory disease subjects, is feasible. Until further data will elucidate discordant tuberculin skin test/QuantiFERON-TB Gold in-tube results, a strategy of simultaneous tuberculin skin and QuantiFERON-TB Gold in-tube testing in a low prevalence bacillus Calmette-Guérin vaccinated population, should maximise potentials of latent tuberculosis diagnosis.