tbuckley/cabot-search huggingface dataset:
Overexpression of GATA-3 Protects against the Development of Hypersensitivity Pneumonitis
Authors: Yosuke Matsuno, Yukio Ishii, Keigyou Yoh, Yuko Morishima, Norihiro Haraguchi, Norihiro Kikuchi, Takashi Iizuka, Takumi Kiwamoto, Shinsuke Homma, Akihiro Nomura, Tohru Sakamoto, Morio Ohtsuka, Nobuyuki Hizawa, Satoru Takahashi
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Hypersensitivity pneumonitis (HP) is mediated by a Th1 immune response. Transcription factor GATA binding protein-3 (GATA-3) is believed to be a key regulator of Th2 differentiation and thus might play regulatory roles in the pathogenesis of hypersensitivity pneumonitis (HP).Objectives: We examined the effect of GATA-3 overexpression on the development of HP in mice.Methods: Wild-type C57BL/6 mice and GATA-3–overexpressing mice of the same background were used in this study. HP was induced by repeated exposure to Saccharopolyspora rectivirgula, the causative antigen of farmer's lung.Measurements and Main Results: Antigen exposure resulted in a marked inflammatory response with enhanced pulmonary expression of T-bet and the Th1 cytokine interferon (IFN)-γ in wild-type mice. The degree of pulmonary inflammation was much less severe in GATA-3–overexpressing mice. The induction of T-bet and IFN-γ genes was suppressed, but a significant induction of Th2 cytokines, including IL-5 and IL-13, was observed in the lungs of GATA-3–overexpressing mice after antigen exposure. Supplementation with recombinant IFN-γ enhanced lung inflammatory responses in GATA-3–overexpressing mice to the level of wild-type mice. Because antigen-induced IFN-γ production predominantly occurred in CD4+ T cells, nude mice were transferred with CD4+ T cells from either wild-type or GATA-3–overexpressing mice and subsequently exposed to antigen. Lung inflammatory responses were significantly lower in nude mice transferred with CD4+ T cells from GATA-3–overexpressing mice than in those with wild-type CD4+ T cells, with a reduction of lung IFN-γ level.Conclusions: These results indicate that overexpression of GATA-3 attenuates the development of HP by correcting the Th1-polarizing condition.
Analyses of 7,635 Patients with Colorectal Cancer Using Independent Training and Validation Cohorts Show That rs9929218 in <i>CDH1</i> Is a Prognostic Marker of Survival
Authors: Christopher G. Smith, David Fisher, Rebecca Harris, Timothy S. Maughan, Amanda I. Phipps, Susan Richman, Matthew Seymour, Ian Tomlinson, Dan Rosmarin, David Kerr, Andrew T. Chan, Ulrike Peters, Polly A. Newcomb, Shelley Idziaszczyk, Hannah West, Angela Meade, Richard Kaplan, Jeremy P. Cheadle
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Genome-wide association studies have identified numerous loci associated with colorectal cancer risk. Several of these have also been associated with patient survival, although none have been validated. Here, we used large independent training and validation cohorts to identify robust prognostic biomarkers for colorectal cancer. Experimental Design: In our training phase, we analyzed 20 colorectal cancer-risk SNPs from 14 genome-wide associated loci, for their effects on survival in 2,083 patients with advanced colorectal cancer. A Cox survival model was used, stratified for treatment, adjusted for known prognostic factors, and corrected for multiple testing. Three SNPs were subsequently analyzed in an independent validation cohort of 5,552 colorectal cancer patients. A validated SNP was analyzed by disease stage and response to treatment. Results: Three variants associated with survival in the training phase; however, only rs9929218 at 16q22 (intron 2 of CDH1, encoding E-cadherin) was significant in the validation phase. Patients homozygous for the minor allele (AA genotype) had worse survival (training phase HR, 1.43; 95% confidence intervals; CI, 1.20–1.71, P = 5.8 × 10−5; validation phase HR, 1.18; 95% CI, 1.01–1.37, P = 3.2 × 10−2; combined HR, 1.28; 95% CI, 1.14–1.43, P = 2.2 × 10−5). This effect was independent of known prognostic factors, and was significant amongst patients with stage IV disease (P = 2.7 × 10−5). rs9929218 was also associated with poor response to chemotherapy (P = 3.9 × 10−4). Conclusions: We demonstrate the potential of common inherited genetic variants to inform patient outcome and show that rs9929218 identifies approximately 8% of colorectal cancer patients with poor prognosis. rs9929218 may affect CDH1 expression and E-cadherin plays a role in epithelial-to-mesenchymal transition providing a mechanism underlying its prognostic potential. Clin Cancer Res; 21(15); 3453–61. ©2015 AACR.
Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies: an Italian multicentre prospective survey
Authors: E.M. Trecarichi, L. Pagano, A. Candoni, D. Pastore, C. Cattaneo, R. Fanci, A. Nosari, M. Caira, A. Spadea, A. Busca, N. Vianelli, M. Tumbarello
Journal: Clinical Microbiology and Infection (2014)
Abstract 1103: Expression profile and role of thromboxane synthase in NSCLC: Correlation with tumor angiogenesis and patient survival
Authors: Mary-Clare Cathcart, Kathy Gately, Elaine Kay, John V. Reynolds, Kenneth J. O’ Byrne, Graham P. Pidgeon
Journal: Cancer Research (2011)

Abstract Introduction: Thromboxane synthase metabolizes PGH2 into thromboxanes, which are biologically active on cancer cells. TXS over-expression is frequently reported in cancers, and has previously been associated with VEGF and a poor prognosis. TXS blockade inhibits angiogenesis and induces tumor cell death, providing a rationale for intervention. This study aimed to determine the expression profile of TXS, its link to tumor angiogenesis, and if it is prognostic and/or a survival factor in NSCLC. Methods: TXS expression was examined in human NSCLC samples (protein and tissue) and matched controls by western analysis and IHC. TXS metabolite levels were measured in human NSCLC plasma samples and age-matched controls by EIA. TXS metabolite levels were correlated with VEGF. A 200-patient NSCLC TMA was stained for TXS, VEGF, and CD-31. Staining was correlated with clinical parameters, including 5-year patient survival. TXS expression pattern was correlated with angiogenic markers, VEGF and CD-31 (microvessel density). Stable TXS over-expressing clones were generated and their effect on tumor growth was examined both in-vitro (BrdU) and in-vivo (xenograft mouse model). Results: TXS was over-expressed in human NSCLC samples, relative to matched controls. Increased TXS and TXB2 levels were observed in protein and plasma samples respectively. TXB2 levels were significantly (p&amp;lt;0.05) correlated with VEGF, while both TXB2 and VEGF levels were higher in adenocarcinoma. Both TXS and VEGF tissue expression were also significantly higher in adenocarcinoma (p&amp;lt;0.001) and female patients (p&amp;lt;0.05). TXS tissue expression was also significantly correlated with that of VEGF (p&amp;lt;0.0001) and CD-31. However, no correlation of TXS with patient survival was observed. Stable TXS over-expression significantly increased tumor cell growth in-vitro and also increased tumor growth in-vivo. Conclusion: TXS is over-expressed in NSCLC, particularly in the adenocarcinoma subtype and female patients. While TXS was not found to be prognostic, over-expression of this enzyme significantly increased tumor growth both in-vivo and in-vitro, suggesting that TXS promotes tumor survival in NSCLC. Our study also demonstrated a significant correlation of TXS with both VEGF and tumor vessel count, suggesting that the pro-tumor effects of TXS expression are at least partly mediated via tumor angiogenesis. Further studies using in-vivo models will confirm this observation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1103. doi:10.1158/1538-7445.AM2011-1103
Mutually Exclusive Inactivation of DMP1 and ARF/p53 in Lung Cancer
Authors: Ali Mallakin, Takayuki Sugiyama, Pankaj Taneja, Lauren A. Matise, Donna P. Frazier, Mayur Choudhary, Gregory A. Hawkins, Ralph B. D'Agostino, Mark C. Willingham, Kazushi Inoue
Journal: Cancer Cell (2007)
Service Quality in Health Care
Authors: John W. Kenagy
Journal: JAMA (1999)

Although US health care is described as "the world's largest service industry," the quality of service—that is, the characteristics that shape the experience of care beyond technical competence—is rarely discussed in the medical literature. This article illustrates service quality principles by analyzing a routine encounter in health care from a service quality point of view. This illustration and a review of related literature from both inside and outside health care has led to the following 2 premises: First, if high-quality service had a greater presence in our practices and institutions, it would improve clinical outcomes and patient and physician satisfaction while reducing cost, and it would create competitive advantage for those who are expert in its application. Second, many other industries in the service sector have taken service quality to a high level, their techniques are readily transferable to health care, and physicians caring for patients can learn from them.
Identification of three accessory cell populations in human bone marrow with erythroid burst-promoting properties.
Authors: D C Linch, J M Lipton, D G Nathan
Journal: Journal of Clinical Investigation (1985)

Several laboratories have demonstrated a requirement for burst-promoting activity (BPA), a product of T cells, or T cell/monocyte collaboration in the induction of differentiation of peripheral blood erythroid burst-forming units (BFU-E) in vitro. The physiologic significance of this finding is brought into question by patients with severe mature T cell deficiency who have normal in vivo erythropoiesis. The studies described here were designed to determine whether the burst-promoting effects of marrow T cells and adherent cells are similar to those of peripheral blood, to define whether a third population of marrow cells is capable of production of BPA, and to describe the BPA requirements of immature and mature marrow erythroid progenitors. To that end we prepared adherence- and E-depleted low-density peripheral blood mononuclear cells as a source of BFU-E and demonstrated that their optimal erythropoietin-induced differentiation requires BPA. We then determined that both bone marrow and peripheral blood T cells and monocytes could provide the necessary BPA to induce their erythropoietin dependent differentiation. BPA production by T cells was sensitive to irradiation, but that of the whole bone marrow low-density population was considerably less sensitive. This in itself demonstrated that BPA production in marrow is not T cell dependent. We further demonstrated a potent, albeit infrequent, third population of BPA-producing marrow cells. These proved to be nonadherent, E receptor-negative, granulocyte antigen-negative, and gamma-Fc receptor-positive. Finally, we separated all of these BPA-producing cells from marrow erythroid progenitors and concentrated the latter into a population in which they comprised 6% of the cells. With this population we demonstrated that both immature (BFU-E) and mature (colony-forming units [CFU-E]) erythroid progenitors require BPA in addition to erythropoietin to induce them to form erythroid colonies in vitro. These results may explain the normal erythropoiesis found in patients with mature T cell deficiency. Though the differentiation of both BFU-E and CFU-E requires BPA, this need can be met by a special class of nonadherent, radioresistant, E receptor-negative, granulocyte antigen-negative, and gamma-Fc-positive cells.
Increasing NHS productivity: working 9 to 5.20
Authors: Des Spence
Journal: BMJ (2010)

The NHS is trying to save money. There have been many suggestions, like cutting numbers of pin-striped management consultants and petty, jobsworth bureaucrats—nice easy scapegoats that make us all feel better. But time is money. We doctors are all busy, running at 110% and clamouring for ever more resources. The NHS needs to look at time management. Could a time and motion study, with clip boarded observers, be the answer? This would be pointless, because we would run around like headless chickens during the study period, claiming to be always busy. In truth …
Tickle Responses in Eczema Patients and Normal Controls
Authors: D.G. Brown
Journal: Psychotherapy and Psychosomatics (1974)

Kepecs' Tickle Test was applied in a modified form to 69 eczema patients and 20 normal controls. Whilst Kepecs' ideas were supported, the presence or duration of an After-Sensation was found to distinguish between eczema patients with and without overt emotional disturbance more than the response during application of a 2-min tickle stimulus; but tickle responses on the eczema itself, rather than unaffected forehead and palm, did powerfully discriminate. Hand eczema cases suggest the possibility that the cathexis or counter-cathexis of the hands, as executants of conflictful sexual or aggressive impulses, explains the different 'gradients' of ticklishness in the two types of eczema patient. The responses seem to interact meaningfully with several personality variables. Further work is needed.
Alcoholic Cardiomyopathy Managed with Prolonged Bed Rest
Authors: C. D. MCDONALD
Journal: Annals of Internal Medicine (1971)

The influence of complete prolonged bed rest on the clinical course of 48 patients with alcoholic cardiomyopathy was studied. Heart size returned to normal with bed rest in 21 (57%) of the 37 patients who cooperated fully, decreased considerably in 11 (30%), and did not change in 5 (13%). Of the 21 patients whose heart size returned to normal, 13 (62%) are presently living, 9 (43%) with normal heart size. Of the other 27 patients only 10 (37%) are known to be presently alive, none with normal heart size. Response to bed rest therapy and long-term prognosis apparently are affected by duration and severity of the heart disease at the time bed rest is instituted. Unfortunately, the ultimate prognosis in many patients is poor because of delay in diagnosis, unwillingness to accept prolonged bed rest therapy, inability to refrain from alcohol consumption, inadequate nutrition, and excessive physical activity.
PTH-104 The Routine Measurement of Thiopurine Metabolite Levels Results in Dose Optimisation in One Third of IBD Patients; Results from a District General Hospital
Authors: H M Dewhurst, H E Johnson, J Begley, S A Weaver, S D McLaughlin
Journal: Gut (2013)

<h3>Introduction</h3> Measuring azathioprine or mercaptopurine (AZA) metabolite levels 6-TGN and 6-MMPN allows identification of patients who are: 1. Non compliant with their medication, 2. On a sub-optimal doe, 3. On a supra-therapeutic dose, 4. Are preferentially metabolising azathioprine to methylated metabolites (6-MMPN:6-TGN ratio &gt; 11). Our own and others published data demonstrate that measuring metabolite levels in patients failing azathioprine therapy followed by appropriate changes in dosing and/or the addition of allopurinol (with 75% dose reduction in AZA) can result in clinical remission in the majority of patients 1. We report the outcome of the routine measurement of metabolite levels in patients treated with AZA who were in a clinical remission without side effects or abnormal liver function tests (LFTs). <h3>Methods</h3> All patients underwent TPMT testing, azathioprine and mercaptopurine were initiated at doses of 2mg/kg and 1mg/kg respectively in those with wild-type TPMT with a 50% reduction in dose in TPMT heterozygotes. We searched the prospective database maintained by our biochemistry department for all patients who underwent metabolite level testing from September 2011 to November 2012, hospital case notes for these patients were reviewed. The indications, results of testing, changes in clinical management and patient outcomes were recorded. <h3>Results</h3> 108 patients underwent metabolite testing, median length of follow-up since testing was 287.6 days (range 21–441), all were stable on AZA for &gt; 4 weeks with normal LFTs and in a clinical remission. 38 (35.2%) had UC, 66 (61.1%) CD, 52 (48.1%) were male. 17 (15.7%) patients had a sub-theraputic 6-TGN, 10 (9.3%) supra-theraputic 6-TGN level (&gt; 800) all of whom had dose optimisation. 6 (5.6%) patients were hypermethylators these were switched to allopurinol co-therapy with an appropriate reduction in AZA dose. <h3>Conclusion</h3> In the present study the routine measurement of AZA metabolites resulted in a change in clinical management in 30.6% of patients. Whilst unproven in prospective longitudinal studies logic suggests that the routine measurement of AZA metabolites in all patients commenced on thiopurines followed by appropriate dose optimisation (with or without allopurinol co-prescription) should reduce or prevent the development of drug side effects, abnormal LFTs and bone marrow suppression and reduce the risk of disease relapse. We recommend that AZA metabolite testing is performed in all patients 4–6 weeks after commencing AZA. <h3>Disclosure of Interest</h3> None Declared.
Animal research will not provide new therapies for cardiovascular disease
Authors: V. Coleman
Journal: Cardiovascular Research (1994)

Journal Article Animal research will not provide new therapies for cardiovascular disease Get access Vernon Coleman Vernon Coleman European Medical Journal, Lynmouth, Devon EX35 6EE, United Kingdom: Dr V Coleman (Editor). Letters relating to this or its companion article should be addressed to The Editor, Cardiovascular Research, Box 2, St Thomas' Hospital, London SE1 7EH. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 7, July 1994, Page 1103, https://doi.org/10.1093/cvr/28.7.1103 Published: 01 July 1994
Abstract 2776: Prostate cancer and dietary calcium: Effect modification by the vitamin D receptor Cdx-2 polymorphism in the California Collaborative Prostate Cancer Study
Authors: Glovioell W. Rowland, Sue A. Ingles
Journal: Cancer Research (2011)

Abstract Background: Calcium is classified as a probable cause of prostate cancer by the World Cancer Research Fund. We previously showed that the relationship between dietary calcium intake and prostate cancer risk was modified by a the vitamin D receptor, Cdx-2 polymorphism among African Americans. The high absorption A allele increases calcium absorption and is common among African Americans. The A alleles is less common among Caucasians, who have a lower incidence of prostate cancer compared to African Americans. Methods: We examined Caucasian and African American prostate cancer cases and controls from the California Collaborative Prostate Cancer Study. Of 1854 cases, 1140 were advanced stage at diagnosis and 714 were localized; 500 were African American and 1354 were Caucasian. Dietary calcium was assessed from a 74-item modified Block food frequency questionnaire. The VDR Cdx-2 genotype was measured by TaqMan assay. Main effects of genotype and of dietary calcium, and diet-gene interactions were estimated using conditional logistic regression, adjusting for study site (Northern/Southern California), Hispanic ancestry, socio-economic status, age, and family history of prostate cancer. Results: Analysis of race-specific quartiles of calcium intake showed that intake of more than 680 mg/day (above the median for African Americans or above the first quartile for whites) was associated with increased prostate cancer risk (odds ratio 1.48, 95% confidence interval 1.25 – 1.77). The effect of calcium intake on risk of advanced (but not localized) prostate cancer was modified by the VDR Cdx-2 genotype for both African Americans and whites. High calcium intake (&amp;gt;680 mg/day) was significantly associated with increased risk only among those with the VDR Cdx-2 GG low calcium absorption genotype (OR=1.90, 95% CI 1.40 – 2.57). High absorption genotypes (GA and AA) were associated with increased risk only among those consuming less than 680 mg/day of calcium. Odds ratios were 1.24 (95% CI: 0.82 – 1.87) for genotype GA and 1.69 (95% CI: 1.05 – 2.74) for genotype AA compared to genotype GG. Conclusions: Our findings suggest that genetically-determined high calcium absorption among African Americans could contribute to racial ethnic disparities in prostate cancer incidence. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2776. doi:10.1158/1538-7445.AM2011-2776
Long-Term Prognostic Value of Neopterin
Authors: Kausik K. Ray, David A. Morrow, Marc S. Sabatine, Amy Shui, Nader Rifai, Christopher P. Cannon, Eugene Braunwald
Journal: Circulation (2007)

Background— Monocyte activation is believed to play an important role in the pathogenesis of acute coronary syndromes (ACS). Neopterin is a soluble marker of monocyte activation, and elevated levels are of prognostic value in patients with stable coronary artery disease. Methods and Results— Neopterin levels were measured on average at 7 days (in 3946 patients) and at 4 months (in 3369 patients) after ACS in the PRavastatin Or atorVastatin Evaluation Infection Therapy–Thrombolysis In Myocardial Infarction (PROVE IT–TIMI 22) trial. We assessed the relationship between plasma neopterin levels and the risk of death and death or acute coronary events (nonfatal myocardial infarction or unstable angina) over 2 years. Seven days after an ACS event, neopterin levels ≥12.11 nmol/L (upper quartile, derived from a post hoc analysis) were associated with an increased risk of death and an increased risk of death or acute coronary events after adjustment for age, gender, history of diabetes mellitus, history of hypertension, history of smoking, type of ACS presentation, use of percutaneous coronary intervention for the index event, statin regimen, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (hazard ratio, 1.86 [95% CI, 1.24 to 2.77], P =0.003; and hazard ratio, 1.33 [95% CI, 1.09 to 1.63] P =0.006, respectively). Neopterin levels ≥12.11 nmol/L at 4 months remained a predictor of death alone and of death or acute coronary events after multivariable adjustment that included adjustment for month 4 low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and statin regimen (hazard ratio, 2.39 [95% CI, 1.43 to 3.99], P =0.001; and hazard ratio, 1.60 [95% CI, 1.21 to 2.11], P =0.001). High-dose atorvastatin significantly attenuated the risk among subjects with neopterin levels ≥12.11 nmol/L at baseline (interaction P for death or acute coronary event, 0.018). Conclusions— Increased monocyte activation detected by an elevated plasma neopterin level identifies patients at long-term risk of death or recurrent acute coronary events after ACS. Intensive statin therapy significantly attenuates the risk of recurrent events among patients with an elevated neopterin level.