tbuckley/cabot-search huggingface dataset:
High IgE levels to α‐lactalbumin, β‐lactoglobulin and casein predict less successful cow's milk oral immunotherapy
Authors: M. Kuitunen, H. Englund, S. Remes, R. Movérare, A. Pelkonen, M. P. Borres, M. J. Mäkelä
Journal: Allergy (2015)

Abstract Background A new treatment option for persistent cow's milk allergy ( CMA ) is oral immunotherapy ( OIT ). Not all patients develop tolerance during therapy, and markers to identify those who will benefit from it are needed. The objective was to study the IgE and IgG 4 antibody profiles to milk and milk proteins before and after OIT in relation to clinical outcome. Methods Seventy‐six children (5–17 years) with challenge‐verified CMA were subjected to a 6‐month OIT protocol. The treatment aimed at reaching a maintenance dose of 200 ml CM (high dose = HD ). Those who did not reach target were analysed as a low‐dose ( LD ) group. Sera were characterized before and after OIT regarding serum levels of IgE and IgG 4 to milk and five milk allergen components evaluated together with clinical CMA symptoms and outcome of OIT . Results Fifty‐five (72%) patients reached the maintenance dose ( HD ) during therapy. High specific IgE levels towards the milk allergens α‐lactalbumin ( P = 0.048), β‐lactoglobulin ( P = 0.006) and casein ( P = 0.015) before OIT start were associated with lower maintenance dose reached. Patients who developed desensitization had a larger increase in IgG 4 levels to α‐lactalbumin ( P = 0.034), β‐lactoglobulin ( P = 0.010), casein ( P = 0.047) and lactoferrin ( P = 0.030) during treatment than those who failed. Conclusions Component‐resolved diagnostics before OIT can help to identify children with lower probability of a successful OIT outcome, as high IgE levels to α‐lactalbumin, β‐lactoglobulin and casein are associated with lower maintenance dose reached. An increase in the IgG 4 concentration to milk components during treatment indicated effective desensitization.
Synergism between ipratropium and theophylline in asthma.
Authors: H Kreisman, H Frank, N Wolkove, M Gent
Journal: Thorax (1981)

Ipratropium bromide is a bronchodilator whose effect has been compared with beta agonists but not with theophylline. Twelve asthmatics were given four two-week courses of the different combinations of ipratropium (40 micrograms in two puffs), theophylline capsules, and their corresponding placebos in a random, double-blind fashion. There was a significant increase in FEV1 and MMFR 60 minutes after theophylline was administered (p less than 0.05) when measured after one and two weeks of therapy. FEV1 and MMFR were significantly increased (p less than 0.05) 30 and 60 minutes after ipratropium inhalation and this increase was significantly greater when the patient had also been taking theophylline compared with placebo capsules (p less than 0.05). There was no toxicity associated with this combination. The synergism demonstrated may be related to the time sequence of drug administration, mechanical or cellular factors.
Behaviour of the rectal juvenile polyp in vitro
Authors: H. Romer, C. Cotte, E. Essenfeld-Yahr
Journal: Gut (1971)

The behaviour of the juvenile polyp in vitro and its cellular development from explants have been studied using cellular dispersion by the trypsinization technique. Only the fibroblastic cells have been found to grow. The significance of this finding suggests that the juvenile polyp is a hamartoma.
Helicobacter pylori DNA decreases pro-inflammatory cytokine production by dendritic cells and attenuates dextran sodium sulphate-induced colitis
Authors: J. Luther, S. Y. Owyang, T. Takeuchi, T. S. Cole, M. Zhang, M. Liu, J. Erb-Downward, J. H. Rubenstein, C.-C. Chen, A. V. Pierzchala, J. A. Paul, J. Y. Kao
Journal: Gut (2011)

<h3>Background and aims</h3> Epidemiological data have recently emerged to suggest <i>Helicobacter pylori</i> may protect against certain chronic inflammatory diseases such as inflammatory bowel disease (IBD). However, the mechanism for the observed inverse association between <i>H pylori</i> and IBD has not been described. <h3>Methods</h3> The frequency of immunoregulatory (IRS) to immunostimulatory (ISS) sequences within the genome of various bacteria was calculated using MacVector software. The induction of type I IFN and IL-12 responses by DNA-pulsed murine bone marrow-derived dendritic cells (BMDC) and human plasmacytoid dendritic cells (DC) was analysed by cytokine production. The effect of <i>H pylori</i> DNA on <i>Escherichia coli</i> DNA production of type I IFN and IL-12 was assessed. The in-vivo significance of <i>H pylori</i> DNA suppression was assessed in a dextran sodium sulphate (DSS) model of colitis. The systemic levels of type I IFN were assessed in <i>H pylori</i>-colonised and non-colonised patients. <h3>Results</h3> <i>H pylori</i> DNA has a significantly elevated IRS:ISS ratio. In-vitro experiments revealed the inability of <i>H pylori</i> DNA to stimulate type I IFN or IL-12 production from mouse BMDC or human plasmacytoid DC. <i>H pylori</i> DNA was also able to suppress <i>E coli</i> DNA production of type I IFN and IL-12. The administration of <i>H pylori</i> DNA before the induction of DSS colitis significantly ameliorated the severity of colitis compared with <i>E coli</i> DNA or vehicle control in both an acute and chronic model. Finally, the systemic levels of type I IFN were found to be lower in <i>H pylori</i>-colonised patients than non-colonised controls. <h3>Conclusions</h3> This study indicates that <i>H pylori</i> DNA has the ability to downregulate pro-inflammatory responses from DC and this may partly explain the inverse association between <i>H pylori</i> and IBD.
Serotype prevalence in adults hospitalised with pneumococcal non-invasive community-acquired pneumonia
Authors: Thomas Bewick, Carmen Sheppard, Sonia Greenwood, Mary Slack, Caroline Trotter, Robert George, Wei Shen Lim
Journal: Thorax (2012)

<h3>Background</h3> The distribution of pneumococcal serotypes implicated in non-invasive community-acquired pneumonia (CAP) in adults is currently unknown. <h3>Methods</h3> A prospective observational cohort study was conducted over 2 years in a large UK teaching hospital trust. Urine samples, in addition to routine blood and sputum samples, were obtained from consecutive adults admitted to the hospital with CAP. Pneumococcal serotype was determined from urine samples using a validated multiplex immunoassay which detects 14 serotypes. <h3>Results</h3> Of 920 patients with CAP, 366 had pneumococcal CAP; 242 had a serotype determined. Thirty-day mortality was 10% for all-cause CAP and 9.6% for pneumococcal CAP. Annual incidence of pneumococcal CAP was 36.5 per 100 000, increasing from 12.1 to 274.1 per 100 000 for ages 16–44 years and ≥85 years, respectively. The most prevalent serotypes were 14, 1, 8, 3 and 19A. Less invasive serotypes were significantly associated with increasing age (OR per increasing age group: 1.5, 95% CI 1.2 to 1.9, p&lt;0.001) and co-morbidity (OR per increasing Charlson index group: 1.4, 95% CI 1.0 to 2.0, p=0.036), and with higher 30-day mortality (OR adjusted for age and co-morbidity: 5.5, 95% CI 1.2 to 25.3, p=0.028) compared with highly invasive serotypes. The proportion of patients in whom serotypes contained within the seven-valent childhood pneumococcal conjugate vaccine was identified increased with age (15.6% for patients aged 16–44 years, 41.0% for patients aged ≥85 years; p&lt;0.05). <h3>Conclusions</h3> In adult invasive and non-invasive pneumococcal CAP, the most common serotypes implicated were 14, 1, 8, 3 and 19A. Age and co-morbidity were associated with the distribution of serotypes identified.
Decreased inward rectifier current in adult rabbit ventricular myocytes maintained in primary culture: a single-channel study
Authors: M Veldkamp
Journal: Cardiovascular Research (1999)

Objective: Regulation of ion channel function in heart has been shown to be affected by changes in the cellular environment. Recently it was shown that rabbit ventricular myocytes kept in primary culture, show a strong reduction in inward rectifier current (IK1). The aim of the present study was to elucidate the mechanism underlying this decrease in IK1, using single-channel measurements. In addition, we studied the effects of primary culture on the ATP-regulated K+ (K.ATP) channel, also a member of the inwardly rectifying K+ channel family. Methods: Adult rabbit ventricular myocytes were cultured for up to 3 days in Ham's F-10 medium complemented with 1% rabbit serum and 5% glutamine. IK1 and K.ATP channel activity was studied in the inside-out patch configuration of the patch–clamp technique with equimolar K+ concentrations (140 mM K+) on the intra- and extracellular side. Single channel characteristics were determined at various times during culture and compared to those present in freshly isolated myocytes. Results: IK1 channels in freshly isolated myocytes (day 0) had a single-channel conductance of 56.1±2.5 pS (mean±SEM) and an open probability of 0.64±0.05 (mean±SEM). Neither the single-channel conductance nor the open probability (Po) underwent significant changes during culture. The mean number of channels per patch, however, was drastically reduced from 1.2±0.3 (mean±SEM) at day 0 to 0.17±0.06 at day three. K.ATP channel density and open probability, on the other hand, were both increased with an optimum at day two. Po increased from 0.27±0.06 at day 0 to 0.63±0.06 at day three. The mean number of channels per patch was 2.29±0.57 and 3.25±0.48 at days 0 and 3 respectively. The unitary current amplitude at −50 mV remained unchanged, suggesting no change in the K.ATP single-channel conductance. Conclusions: The decrease in IK1 in rabbit ventricular myocytes as has been observed during primary culture is the result of a reduction in the number of active channels and not of altered kinetic or conductive channel properties. The increase in K.ATP channel activity under the same conditions suggests that gene expression of both channel types is differently regulated.
n-3 Polyunsaturated Fatty Acids in the Prevention of Atrial Fibrillation Recurrences After Electrical Cardioversion
Authors: Savina Nodari, Marco Triggiani, Umberto Campia, Alessandra Manerba, Giuseppe Milesi, Bruno M. Cesana, Mihai Gheorghiade, Livio Dei Cas
Journal: Circulation (2011)

Background— n-3 polyunsaturated fatty acids (n-3 PUFAs) exert antiarrhythmic effects and reduce sudden cardiac death. However, their role in the prevention of atrial fibrillation remains controversial. We aimed to determine the effect of n-3 PUFAs in addition to amiodarone and a renin-angiotensin-aldosterone system inhibitor on the maintenance of sinus rhythm after direct current cardioversion in patients with persistent atrial fibrillation. Methods and Results— We conducted a randomized, double-blind, placebo-controlled, parallel-arm trial in patients with persistent atrial fibrillation, with at least 1 relapse after cardioversion, and treated with amiodarone and a renin-angiotensin-aldosterone system inhibitor. Participants were assigned to placebo or n-3 PUFAs 2 g/d and then underwent direct current cardioversion 4 weeks later. The primary end point was the probability of maintenance of sinus rhythm at 1 year after cardioversion. Of 254 screened patients, 199 were found to be eligible and randomized. At the 1-year follow up, the probability of maintenance of sinus rhythm was significantly higher in the n-3 PUFAs–treated patients compared with the placebo group (hazard ratio, 0.62 [95% confidence interval, 0.52 to 0.72] and 0.36 [95% confidence interval, 0.26 to 0.46], respectively; P =0.0001). Conclusions— In patients with persistent atrial fibrillation on amiodarone and a renin-angiotensin-aldosterone system inhibitor, the addition of n-3 PUFAs 2 g/d improves the probability of the maintenance of sinus rhythm after direct current cardioversion. Our data suggest that n-3 PUFAs may exert beneficial effects in the prevention of atrial fibrillation recurrence. Further studies are needed to confirm and expand our findings. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01198275.
The IOC consensus statement: beyond the Female Athlete Triad—Relative Energy Deficiency in Sport (RED-S)
Authors: Margo Mountjoy, Jorunn Sundgot-Borgen, Louise Burke, Susan Carter, Naama Constantini, Constance Lebrun, Nanna Meyer, Roberta Sherman, Kathrin Steffen, Richard Budgett, Arne Ljungqvist
Journal: British Journal of Sports Medicine (2014)

Protecting the health of the athlete is a goal of the International Olympic Committee (IOC). The IOC convened an expert panel to update the 2005 IOC Consensus Statement on the Female Athlete Triad. This Consensus Statement replaces the previous and provides guidelines to guide risk assessment, treatment and return-to-play decisions. The IOC expert working group introduces a broader, more comprehensive term for the condition previously known as ‘Female Athlete Triad’. The term ‘Relative Energy Deficiency in Sport’ (RED-S), points to the complexity involved and the fact that male athletes are also affected. The syndrome of RED-S refers to impaired physiological function including, but not limited to, metabolic rate, menstrual function, bone health, immunity, protein synthesis, cardiovascular health caused by relative energy deficiency. The cause of this syndrome is energy deficiency relative to the balance between dietary energy intake and energy expenditure required for health and activities of daily living, growth and sporting activities. Psychological consequences can either precede RED-S or be the result of RED-S. The clinical phenomenon is not a ‘triad’ of the three entities of energy availability, menstrual function and bone health, but rather a syndrome that affects many aspects of physiological function, health and athletic performance. This Consensus Statement also recommends practical clinical models for the management of affected athletes. The ‘Sport Risk Assessment and Return to Play Model’ categorises the syndrome into three groups and translates these classifications into clinical recommendations.
ALDH isozymes downregulation affects cell growth, cell motility and gene expression in lung cancer cells
Authors: Jan S Moreb, Henry V Baker, Lung-Ji Chang, Maria Amaya, M Cecilia Lopez, Blanca Ostmark, Wayne Chou
Journal: Molecular Cancer (2008)

Aldehyde dehydrogenase isozymes ALDH1A1 and ALDH3A1 are highly expressed in non small cell lung cancer. Neither the mechanisms nor the biologic significance for such over expression have been studied. We have employed oligonucleotide microarrays to analyze changes in gene profiles in A549 lung cancer cell line in which ALDH activity was reduced by up to 95% using lentiviral mediated expression of siRNA against both isozymes (Lenti 1+3). Stringent analysis methods were used to identify gene expression patterns that are specific to the knock down of ALDH activity and significantly different in comparison to wild type A549 cells (WT) or cells similarly transduced with green fluorescent protein (GFP) siRNA. We confirmed significant and specific down regulation of ALDH1A1 and ALDH3A1 in Lenti 1+3 cells and in comparison to 12 other ALDH genes detected. The results of the microarray analysis were validated by real time RT-PCR on RNA obtained from Lenti 1+3 or WT cells treated with ALDH activity inhibitors. Detailed functional analysis was performed on 101 genes that were significantly different (P < 0.001) and their expression changed by ≥ 2 folds in the Lenti 1+3 group versus the control groups. There were 75 down regulated and 26 up regulated genes. Protein binding, organ development, signal transduction, transcription, lipid metabolism, and cell migration and adhesion were among the most affected pathways. These molecular effects of the ALDH knock-down are associated with in vitro functional changes in the proliferation and motility of these cells and demonstrate the significance of ALDH enzymes in cell homeostasis with a potentially significant impact on the treatment of lung cancer.
Kinematic and kinetic parameters associated with running in different shoes.
Authors: P J McNair, R N Marshall
Journal: British Journal of Sports Medicine (1994)

The characteristics of the midsole were examined in four pairs of running shoes by a materials test. The variables of interest were the peak acceleration, time to peak acceleration and the kinetic energy absorbed. Ten subjects then ran at a recreational jogging pace (3.5 ms-1) barefoot and in the shoes. An accelerometer secured to the lower tibia was used to measure the peak acceleration and time to peak acceleration associated with footstrike. Subjects were also videoed and a kinematic analysis was undertaken at the knee and ankle joints. The results from the materials test showed that the shoes differed in their midsole characteristics, however, no significant differences (P &gt; 0.05) were observed in the peak acceleration and time to peak acceleration during running in shoes. These variables were significantly greater in the barefoot running condition (P &lt; 0.05), as compared with running in shoes. Small and subtle kinematic differences were observed between the barefoot and shoe conditions. It appears that the differences observed between the shoes in the materials test were not sufficient to elicit the kinematic changes observed between the barefoot and shoe conditions. It is suggested that runners operate within a 'kinetic bandwidth' when responding to impact stresses.
Increased adhesion of Escherichia coli to mucosal cells from infants with protracted diarrhoea: a possible factor in the pathogenesis of bacterial overgrowth and diarrhoea.
Authors: D C Candy, T S Leung, W C Marshall, J T Harries
Journal: Gut (1983)

Mucosal adhesion of bacteria has been studied in eight infants with protracted diarrhoea and malnutrition, using a buccal epithelial cell technique. A known non-adhesive strain of Escherichia coli (O1:K1:H7) adhered to a significantly greater (p less than 0.001) proportion of buccal epithelial cells from patients with protracted diarrhoea, compared with children with acute diarrhoea, healthy infants, and healthy adults. Also, Enterobacteria isolated from the jejunum or stools of patients with protracted diarrhoea adhered to far greater numbers of their own buccal epithelial cells compared with healthy adults. These results suggest that bacterial adhesion may play an important role in the pathogenesis of protracted diarrhoea.
Exon 19 Deletion Mutations of Epidermal Growth Factor Receptor Are Associated with Prolonged Survival in Non–Small Cell Lung Cancer Patients Treated with Gefitinib or Erlotinib
Authors: David M. Jackman, Beow Y. Yeap, Lecia V. Sequist, Neal Lindeman, Alison J. Holmes, Victoria A. Joshi, Daphne W. Bell, Mark S. Huberman, Balazs Halmos, Michael S. Rabin, Daniel A. Haber, Thomas J. Lynch, Matthew Meyerson, Bruce E. Johnson, Pasi A. Jänne
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Somatic mutations in the epidermal growth factor receptor (EGFR) have been detected in patients with non–small cell lung cancer (NSCLC) and are associated with sensitivity to treatment with gefitinib or erlotinib. Our study explored the relationship between the two most common types of somatic EGFR mutations, exon 19 deletions and the L858R point mutation, and outcomes of patients following treatment with gefitinib or erlotinib. Experimental Design: Tumor specimens obtained before treatment with gefitinib or erlotinib were analyzed for EGFR mutations. Patients with exon 19 deletion or L858R mutations were identified. The response rate, time to progression, and overall survival were determined for the two groups. Results: We identified 36 patients with NSCLC and an EGFR mutation who were treated with gefitinib or erlotinib. Patients with an exon 19 deletion had a significantly longer overall survival compared with patients with an L858R mutation (38 versus 17 months; P = 0.04). There were also trends toward higher response rate (73% versus 50%) and improved time to progression (24 versus 10 months) for the patients with an exon 19 deletion, although these were not independently significant in a multivariate analysis. A difference in response rate for patients treated with gefitinib compared with erlotinib was also noted [18 of 23 (78%) versus 3 of 9 (33%); P = 0.04]. No obvious difference in time to progression or overall survival was noted between gefitinib- and erlotinib-treated patients. Conclusions: Patients with NSCLC and EGFR exon 19 deletions have a longer survival following treatment with gefitinib or erlotinib compared with those with the L858R mutation. Pooling of greater numbers of patients and completion of prospective trials are needed to further define the predictive and prognostic roles of different EGFR mutations with respect to treatment with gefitinib, erlotinib, and other EGFR inhibitors.
Women with rheumatoid arthritis negative for anti-cyclic citrullinated peptide and rheumatoid factor are more likely to improve during pregnancy, whereas in autoantibody-positive women autoantibody levels are not influenced by pregnancy
Authors: Y A de Man, L E Bakker-Jonges, C M Dufour-van den Goorbergh, S P R Tillemans, H Hooijkaas, J M W Hazes, R J E M Dolhain
Journal: Annals of the Rheumatic Diseases (2009)

Objectives: To determine whether changes in levels of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) are associated with the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and with the subsequent flare post partum. Methods: Disease activity scores from the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study of 118 patients were available for analysis. Before conception (if applicable), at each trimester and at 6, 12 and 26 weeks post partum, levels of the autoantibodies anti-CCP, IgM-RF, IgG-RF and IgA-RF were determined. Responses in disease activity were classified according to European League Against Rheumatism (EULAR) response criteria during pregnancy and post partum, and associated with the presence or absence of autoantibodies. Results: The median levels of anti-CCP and all subclasses of RF during pregnancy were stable, whereas post partum the levels of anti-CCP, IgM-RF and IgA-RF declined. A significantly higher percentage of women without autoantibodies (negative for anti-CCP and RF) improved compared with women positive for either or both autoantibodies (75% vs 39%, p = 0.01). The occurrence of a flare post partum was comparable between these groups. Conclusions: Improvement of disease activity of RA during pregnancy was not associated with changes in levels of autoantibodies during pregnancy, however, improvement may occur more frequently in the absence of anti-CCP and RF.
Validity Studies of the Radioactive Microsphere Method for the Study of the Distribution of Cardiac Output, Organ Blood Flow, and Resistance in the Conscious Rhesus Monkey
Authors: B. I. Hoffbrand, R. P. Forsyth
Journal: Cardiovascular Research (1969)

Investigations have been carried out to determine the reliability and validity of a method for making repeated measurements of the distribution of cardiac output, organ blood flow, and resistance in the unanaesthetized restrained rhesus monkey free from the influences of recent surgery. The data presented indicate that this "labelled microsphere" method, despite some problems, is a sensitive and reliable way to study regional haemodynamic changes in the monkey.