tbuckley/cabot-search huggingface dataset:
PWE-083 Buccal cells as a potential surrogate for DNA methylation biomarker to identify those at increased colorectal cancer risk
Authors: H Staley, D M Bradburn, J C Mathers
Journal: Gut (2012)

<h3>Introduction</h3> Colorectal cancer (CRC) screening programmes are an opportunity to alter the survival of patients with early CRC. Cells from the alimentary tract can be obtained from both the mouth and large bowel. If biomarkers of CRC risk could be identified in buccal cells, such assays could be more convenient and acceptable than those requiring rectal biopsies. One potential CRC risk biomarker is methylation of the WNT-related gene encoding the Secreted Frizzled Related Protein 4 (<i>SFRP 4</i>). <h3>Methods</h3> DNA was extracted from macroscopically normal rectal biopsies and matched buccal cell swabs from volunteers at a relatively lower (healthy volunteers) and higher (patients with adenomatous polyps) CRC risk in the BORICC Study. Methylation of <i>SFRP4</i> was quantified by Pyrosequencing. <h3>Results</h3> <i>SFRP4</i> promotor methylation was quantified in rectal biopsies and matched buccal cells in 233 lower and 89 higher CRC risk participants. For rectal biopsies, <i>SFRP4</i> promotor methylation was significantly (p=0.001) higher in those with polyps than in healthy controls. However, for buccal cells, the reverse was observed with significantly (p&lt;0.001) higher <i>SFRP4</i> promotor methylation in the healthy controls. At CpG sites 1 and 4 only, <i>SFRP4</i> methylation was correlated significantly (p=0.001 and p=0.041 respectively) between the two patient groups. <h3>Conclusion</h3> <i>SFRP4</i> promotor methylation in rectal biopsies is not the same as that in matched buccal cells. However, <i>SFRP4</i> methylation was significantly different between patient groups at each site, providing encouragement for further studies of the utility of buccal cells as a surrogate tissue for identification of those at increased CRC risk. <h3>Competing interests</h3> None declared.
1276 WAIST CIRCUMFERENCE GREATER THAN 90CM IS A RISK FACTOR FOR HEPATIC STEATOSIS IN OTHERWISE HEALTHY ADULTS - A 3 TESLA MAGNETIC RESONANCE SPECTROSCOPY STUDY
Authors: R. Banerjee, B.F. Rial, J. Suttie, A. Lewandowski, M.D. Robson, J. Schneider, L. Hodson, B. Fielding, J.D. Collier, E. Barnes, S. Neubauer
Journal: Journal of Hepatology (2012)
Micronutrient Supplementation and Pregnancy Outcomes
Authors: Jian-meng Liu, Zuguo Mei, Rongwei Ye, Mary K Serdula, Aiguo Ren, Mary E Cogswell
Journal: JAMA Internal Medicine (2013)

Beyond perinatal folic acid supplementation, the need for additional prenatal prophylaxis of iron with or without other micronutrients remains unclear. We aim to investigate the maternal and infant health effects of iron plus folic acid and multiple micronutrient supplements vs folic acid alone when provided to pregnant women with no or mild anemia.In this randomized double-blind controlled trial, 18,775 nulliparous pregnant women with mild or no anemia were enrolled from 5 counties of northern China from May 2006 through April 2009. Women were randomly assigned to daily folic acid (400 μg) (control), folic acid-iron (30 mg), or folic acid, iron, and 13 additional vitamins and minerals provided before 20 weeks gestation to delivery. Primary outcome was perinatal mortality. Secondary outcomes included neonatal and infant mortality, preterm delivery, birth weight, birth length, gestational duration, and maternal hemoglobin concentration and anemia.A total of 92.7% of women consumed 80% to 100% of supplements as instructed. On average, women consumed 177 supplements. Compared with daily prenatal folic acid, supplementation with iron-folic acid with or without other micronutrients did not affect the rate of perinatal mortality (8.8, 8.7, and 8.3, respectively) per 1000 births, and relative risks (RRs) were 1.00 (95% CI, 0.68-1.46; P = .99) and 0.94 (95% CI, 0.64-1.39; P = .76), respectively. Risk of other adverse maternal and infant outcomes also did not differ, except that RRs for third-trimester maternal anemia were 0.72 (95% CI, 0.63-0.83; P < .001) and 0.71 (95% CI, 0.62-0.82; P < .001), respectively.Prenatal iron-folic acid and other micronutrient supplements provided to Chinese women with no or mild anemia prevented later pregnancy anemia beyond any benefit conferred by folic acid alone but did not affect perinatal mortality or other infant outcomes.clinicaltrials.gov Identifier: NCT00133744.
Preexisting helminth infection induces inhibition of innate pulmonary anti-tuberculosis defense by engaging the IL-4 receptor pathway
Authors: Julius A. Potian, Wasiulla Rafi, Kamlesh Bhatt, Amanda McBride, William C. Gause, Padmini Salgame
Journal: The Journal of Experimental Medicine (2011)

Tuberculosis and helminthic infections coexist in many parts of the world, yet the impact of helminth-elicited Th2 responses on the ability of the host to control Mycobacterium tuberculosis (Mtb) infection has not been fully explored. We show that mice infected with the intestinal helminth Nippostrongylus brasiliensis (Nb) exhibit a transitory impairment of resistance to airborne Mtb infection. Furthermore, a second dose of Nb infection substantially increases the bacterial burden in the lungs of co-infected mice. Interestingly, the Th2 response in the co-infected animals did not impair the onset and development of the protective Mtb-specific Th1 cellular immune responses. However, the helminth-induced Th2 environment resulted in the accumulation of alternatively activated macrophages (AAMs) in the lung. Co-infected mice lacking interleukin (IL) 4Rα exhibited improved ability to control Mtb infection, which was accompanied by significantly reduced accumulation of AAMs. Moreover, IL-4Rα−/− mice adoptively transferred with wild-type macrophages had a significantly higher Mtb load in their lungs compared with those that received IL-4Rα−/− macrophages, suggesting a direct contribution for the IL-4R pathway to the heightened susceptibility of co-infected animals. The Th2 response can thus enhance the intracellular persistence of Mtb, in part by mediating the alternative activation of macrophages via the IL-4Rα signaling pathway.
Interleukin 10 is a growth factor for a population of regulatory T cells
Authors: C ASSEMAN, F POWRIE
Journal: Gut (1998)

Induction and maintenance of peripheral tolerance are important mechanisms to maintain the balance of the immune system. In addition to the deletion of T cells and their failure to respond in certain circumstances, active suppression mediated by T cells or T-cell factors has been proposed as a mechanism for maintaining peripheral tolerance. However, the inability to isolate and clone regulatory T cells involved in antigen-specific inhibition of immune responses has made it difficult to understand the mechanisms underlying such suppression. Here, we show that chronic activation of both human and murine CD4+ T cells in the presence of interleukin (IL)-10 gives rise to CD4+ T-cell clones with low proliferative capacity, producing high levels of IL-10, low levels of IL-2 and no IL-4. These antigen-specific T-cell clones suppress the proliferation of CD4+ T cells in response to antigen, and prevent colitis induced in SCID mice by pathogenic CD4+CD45RBhigh splenic T cells. Thus IL-10 drives the generation of a CD4+ T-cell subset, designated T regulatory cells 1 (Tr1), which suppresses antigen-specific immune responses and actively downregulates a pathological immune response in vivo.
Two-Dimensional Computer Color Graphics of Gastric Mucosal Blood Distribution in Normal Subjects and Ulcer Patients
Authors: S Kawano, N Sato, S Tsuji, N Hayashi, M Tsujii, E Masuda, Y Takei, K Nagano, H Fusamoto, T Ogihara
Journal: Endoscopy (1991)

The mucosal blood volume in 20 to 24 different regions of stomach was estimated by reflectance spectrophotometry during endoscopy, and an image showing mucosal blood distribution was made by two-dimensional computer color graphics with the aid of a personal computer. In 55 normal controls, the estimated mucosal blood volume (EMBV) was greater in the corpus mucosa than in the antral mucosa, and less in the lesser curvature than in the greater curvature. The volume in the anterior and posterior walls was almost the same. In 15 patients with active gastric ulcers in the angular region, the EMBV was decreased in all regions in the stomach. In 37 patients with healing ulcers, the EMBV increased, resuming the same levels as in normal controls. However, the EMBV around the ulcer increased remarkably at this stage. In 35 patients with ulcers in the scarring stage, the distribution of the EMBV was similar to that in the normal controls. These hemodynamic changes were shown clearly in a color display with the aid of a personal computer. This method could offer new possibilities in endoscopic research.
Prediction of sites of progression of native coronary disease in-vivo based on identification of sites of low endothelial shear stress
Authors: Peter H. Stone, Ahmet U. Coskun, Scott Kinlay, Maureen E. Clark, Milan Sonka, Andreas Wahle, Olusegun J. Ilegbusi, Jeffrey J. Popma, Richard E. Kuntz, Charles L. Feldman
Journal: Journal of the American College of Cardiology (2002)
Scientific rationale for inhaled combination therapy with long-acting β<sub>2</sub>-agonists and corticosteroids
Authors: P.J. Barnes
Journal: European Respiratory Journal (2002)

The addition of an inhaled long-acting beta2-agonist (LABA) to an inhaled corticosteroid (ICS) gives optimal control of asthma in most patients and two fixed combination inhalers (salmeterol/fluticasone and formoterol/budesonide) are increasingly used as a convenient controller in patients with persistent asthma. There is a strong scientific rationale for the combination of these two drug classes. ICS suppress the chronic inflammation of asthma and reduce airway hyperresponsiveness and this is achieved at low doses in most patients. LABA act on different aspects of the pathophysiology of asthma. In addition to their bronchodilator action, LABA also inhibit mast cell mediator release, plasma exudation and may reduce sensory nerve activation. Thus these two classes of drug address complementary aspects of the pathophysiology of asthma that neither drug class is able to achieve alone. There are several positive interactions between LABA and ICS. Corticosteroids increase the expression of beta2-receptors by increasing gene transcription. Experimentally this protects against the loss of beta2-receptors in response to long-term exposure to beta2-agonists. While this is unlikely to be important in bronchodilator responses to beta2-agonists, in view of the large beta-receptor reserve, it is probably important in preventing loss of beta-agonist effects on the nonbronchodilator actions of LABA discussed earlier. beta2-Agonists may potentiate the molecular mechanism of corticosteroid actions, with increased nuclear localization of glucocorticoid receptors and additive or sometimes synergistic suppression of inflammatory mediator release. Thus LABA and ICS may optimize each others beneficial actions in the airways, but the low systemic effects of these drugs do not result in any increase in adverse effects. Long-acting beta2-agonists corticosteroid inhaler therapy is therefore a logical advance and results in effective control of asthma in the majority of patients without significant adverse effects. This simplified approach to long-term asthma therapy has a strong scientific rationale.
Lymphocyte subpopulations, serum immunoglobulins and complement factors in patients with atopic dermatitis
Authors: L. R. BRAATHEN, O. FORRE, J. B. NATVIG, G. RAJKA
Journal: British Journal of Dermatology (1978)

The percentages of lymphocytes carrying different classes of membrane-bound Ig, and lymphocytes forming rosettes with sheep erythrocytes (E-RFC), as well as lymphocytes with receptor for the Fc-part of IgG (EA-RFC) were determined in 19 patients with atopic dermatitis. Lymphocyte suspensions were also stained with a specific rabbit anti-human T-lymphocyte antiserum. Furthermore, the serum concentration of IgG, IgA, IgM and IgE and the complement factors C3 and C4 were measured. A small but significant increase in lymphocytes with membrane-bound IgE and an increase in the serum concentration of IgE and complement factor C4 were observed. A decrease in the percentages of lymphocytes with receptors for sheep erythrocytes (E-RFC) was also found. The percentages of lymphocytes that stained with the anti-T antiserum correlated well with the percentages of lymphocytes forming rosettes with sheep erythrocytes. In one patient we found increased IgE positive lymphocytes, increased IgE serum concentration and a decreased T-cell number.
No increased mortality in incident cases of rheumatoid arthritis during the new millennium
Authors: K Puolakka, H Kautiainen, T Pohjolainen, L Virta
Journal: Annals of the Rheumatic Diseases (2010)

Ample evidence shows that rheumatoid arthritis (RA) is associated with a shortened life expectancy, with indicators of severe disease and rheumatoid factor (RF) as risk factors.1,–,3 Early and aggressive treatment strategies over the past decade have resulted in more favourable functional and radiological outcomes, probably also having an impact on mortality. Methotrexate treatment has been associated with decreased preterm deaths.4 Some studies have found no difference in mortality between patients and the general population.5 6

To examine the present status in Finland, we used the national registry of the Social Insurance Institution, covering all residents, to identify all incident cases of RA with an index day between 1 January 2000 and 31 December 2007. The case definition was eligibility—for the first time during the lifetime—for special …
Interferon‐inducible cholesterol‐25‐hydroxylase restricts hepatitis C virus replication through blockage of membranous web formation
Authors: None Anggakusuma, Inés Romero‐Brey, Carola Berger, Che C. Colpitts, Tujana Boldanova, Michael Engelmann, Daniel Todt, Paula Monteiro Perin, Patrick Behrendt, Florian W.R. Vondran, Shuting Xu, Christine Goffinet, Luis M. Schang, Markus H. Heim, Ralf Bartenschlager, Thomas Pietschmann, Eike Steinmann
Journal: Hepatology (2015)

Hepatitis C virus (HCV) is a positive-strand RNA virus that primarily infects human hepatocytes. Infections with HCV constitute a global health problem, with 180 million people currently chronically infected. Recent studies have reported that cholesterol 25-hydroxylase (CH25H) is expressed as an interferon-stimulated gene and mediates antiviral activities against different enveloped viruses through the production of 25-hydroxycholesterol (25HC). However, the intrinsic regulation of human CH25H (hCH25H) expression within the liver as well as its mechanistic effects on HCV infectivity remain elusive. In this study, we characterized the expression of hCH25H using liver biopsies and primary human hepatocytes. In addition, the antiviral properties of this protein and its enzymatic product, 25HC, were further characterized against HCV in tissue culture. Levels of hCH25H messenger RNA were significantly up-regulated both in HCV-positive liver biopsies and in HCV-infected primary human hepatocytes. The expression of hCH25H in primary human hepatocytes was primarily and transiently induced by type I interferon. Transient expression of hCH25H in human hepatoma cells restricted HCV infection in a genotype-independent manner. This inhibition required the enzymatic activity of CH25H. We observed an inhibition of viral membrane fusion during the entry process by 25HC, which was not due to a virucidal effect. Yet the primary effect by 25HC on HCV was at the level of RNA replication, which was observed using subgenomic replicons of two different genotypes. Further analysis using electron microscopy revealed that 25HC inhibited formation of the membranous web, the HCV replication factory, independent of RNA replication.Infection with HCV causes up-regulation of interferon-inducible CH25H in vivo, and its product, 25HC, restricts HCV primarily at the level of RNA replication by preventing formation of the viral replication factory.
Selection of cytotoxic T-cell precursors specific for minor histocompatibility determinants. I. Negative selection across H-2 barriers induced with disrupted cells but not with glutaraldehyde-treated cells: evidence for antigen processing.
Authors: R Korngold, J Sprent
Journal: The Journal of Experimental Medicine (1980)

Intravenous injection of CBA mice with H-2-compatible irradiated B10.BR spleen cells led to a sequence of negative and positive selection of the host T-cell response against the multiple foreign minor histocompatibility antigens (HA) on the injected cells. By 1 d posttransfer, thoracic duct lymphocytes (TDL) of the host had lost the capacity to differentiate in vitro into cytotoxic cells specific for the injected minor HA; spleen and lymph node cells, by contrast, gave normal or enriched responses at this time. By 5 d posttransfer, TDL were hyperresponsive to the injected antigens. Selection with disrupted (sonicated) cells gave similar findings. With injection of either irradiated of disrupted spleen cells, the H-2 haplotype of the minor HA-bearing cells had no apparent effect on the magnitude of selection. By contrast, treatment of spleen cells with glutaraldehyde before injection led to H-2 restriction of selection, i.e., negative selection of the CBA response to B10.BR was marked with injection of glutaraldehyde-treated H-2-compatible B10.BR cells but was minimal with H-2-different B10 or B10.D2 cells. These data are taken to imply that, at least in H-2-incompatible situations, the minor HA-bearing cells must be processed by host cells, i.e., to allow the antigens to become associated with self H-2 determinants. Circumstantial evidence from studies on the specificity of selection induced with glutaraldehyde-treated cells from mice of the B10 recombinant strains suggested that I region-restricted T cells may control the induction of H2K, D-restricted cytotoxic precursor cells.
ANTIBODY PRODUCTION AFTER PARTIAL ADRENALECTOMY IN GUINEA PIGS
Authors: Frederick L. Gates
Journal: The Journal of Experimental Medicine (1918)

By careful aseptic operation it was found possible to remove approximately three-quarters to seven-eighths of the adrenal tissue of guinea pigs without causing symptoms of adrenal insufficiency. Guinea pigs were immunized to Bacillus typhosus or to hen corpuscles at varying intervals before or after the operation, and the curves of antibody formation traced for 2 to 3 months after immunization. Comparisons with the antibody curves of control animals similarly immunized fail to show that the adrenalectomy had any influence upon the rise or persistence of antibodies in the blood. For the purposes of the study it was not deemed necessary to produce an acute adrenal insufficiency. If the adrenal glands were the site of antibody formation or played an essential part in immunity processes, it does not seem probable that the small remainder of adrenal tissue left in situ to sustain life would affect quantitatively the antibody response to a given antigen injection as do the entire normal glands. We therefore interpret the experiments to indicate that not only are the adrenal glands not one of the important sources of typhoid agglutinins, or of hemagglutinins or hemolysins, but they play no essential part in the mechanism by which these antibodies are produced and maintained in the body.
Rapid diagnosis of pulmonary tuberculosis by an enzyme-linked immunospot assay using induced sputum cells
Authors: Doosoo Jeon, Seung Eun Lee, Woo Hyun Cho, Yun Seong Kim, Eun-Soon Son, Min-Sun Hong, Seok-Yong Eum
Journal: European Respiratory Journal (2013)

Background   The purpose of this study was to evaluate the diagnostic utility and predictors for determinate results of an enzyme-linked immunospot assay using induced sputum cells (IS ELISPOT) for a rapid diagnosis of pulmonary tuberculosis (TB).   Methods   Subjects suspected of pulmonary TB who had either sputum acid fast bacilli smear-negative or not producing sputum spontaneously were prospectively enrolled in the study. ELISPOT assay was performed using cells from induced sputum.   Results   A total of 43 subjects, including 25 with TB (TB group) and 18 with non-TB disease (non-TB group) were enrolled in the study. Results of IS ELISPOT were determinate in only 17/43 (39%) subjects, but all of determinate results were consistent with the final diagnosis. Of the 43 sputum samples, 11 (26%) were inadequate to perform IS ELISPOT. Of 32 adequate sputum samples, the proportion of determinate results was significantly higher in the TB group (75%, 15/20) than in the non-TB group (17%, 2/12) (p = 0.002). Smear positivity and extent of chest radiograph were not predictors for determinate results in the TB group. Sensitivity of IS ELISPOT (75%, 9/12) was higher than that of TB-PCR (25%, 3/12) in smear-negative TB.   Conclusion   IS ELISPOT, in its current format, is not clinically useful because of the high proportion of inconclusive results. However, in the TB group, IS ELISPOT showed relatively high diagnostic value and accuracy regardless of smear positivity. IS ELISPOT may provide additional diagnostic yield for microbiological tools in the rapid diagnosis of smear-negative TB.
Outdoor air pollution and respiratory health in patients with COPD
Authors: J. L. Peacock, H. R. Anderson, S. A. Bremner, L. Marston, T. A. Seemungal, D. P. Strachan, J. A. Wedzicha
Journal: Thorax (2011)

<h3>Objectives</h3> Time series studies have shown adverse effects of outdoor air pollution on mortality and hospital admissions in patients with chronic obstructive pulmonary disease (COPD) but panel studies have been inconsistent. This study investigates short-term effects of outdoor nitrogen dioxide, ozone, sulfur dioxide, particulate matter (PM<sub>10</sub>) and black smoke on exacerbations, respiratory symptoms and lung function in 94 patients with COPD in east London. <h3>Methods</h3> Patients were recruited from an outpatient clinic and were asked to complete daily diary cards (median follow-up 518 days) recording exacerbations, symptoms and lung function, and the amount of time spent outdoors. Outdoor air pollution exposure (lag 1 day) was obtained from local background monitoring stations. <h3>Results</h3> Symptoms but not lung function showed associations with raised pollution levels. Dyspnoea was significantly associated with PM<sub>10</sub> (increase in odds for an IQR change in pollutant: 13% (95% CI 4% to 23%)) and this association remained after adjustment for other the pollutants measured. An IQR increase in nitrogen dioxide was associated with a 6% (0–13%) increase in the odds of a symptomatic fall in peak flow rate. The corresponding effect sizes for PM<sub>10</sub> and black smoke were 12% (2–25%) and 7% (1–13%), respectively. <h3>Conclusion</h3> It is concluded that outdoor air pollution is associated with important adverse effects on symptoms in patients with COPD living in London.