tbuckley/cabot-search huggingface dataset:
Failure of montelukast to reduce sputum eosinophilia in high-dose corticosteroid-dependent asthma
Authors: L. Jayaram
Journal: European Respiratory Journal (2005)

Sputum eosinophilia is a sensitive predictor of benefit from corticosteroid treatment. Montelukast is a cysteinyl leukotriene antagonist, which also reduces sputum and blood eosinophils. The present study examined the possibility that montelukast has an added eosinophil-lowering effect in subjects with asthma who are corticosteroid responsive but relatively corticosteroid resistant. A total of 14 clinically stable adults with asthma requiring minimum treatment with a high-dose inhaled steroid or prednisone, with baseline sputum eosinophilia (≥5%), were randomised to receive 4 weeks of 10 mg montelukast or placebo daily in a double-blind crossover trial. The primary outcome was the effect of treatment on the percentage of sputum eosinophils. Secondary outcomes were changes in the blood eosinophil count, symptoms, forced expiratory volume in one second, peak expiratory flow and the need for salbutamol. The median (interquartile range, <i>i.e.</i> 75th–25th centile) for sputum eosinophils at baseline was 15.7% (22). The effect of adding montelukast was not significantly different from that of placebo, sputum eosinophils being 9.3% (18.9) after montelukast and 11.3% (22.8) after placebo. No difference was detected on secondary outcomes. No crossover interactions were observed. In conclusion, the addition of montelukast to existing high-dose corticosteroid therapy in subjects with asthma with elevated sputum eosinophils does not provide additional attenuation of airway eosinophilia.
Bath psoralen plus ultraviolet A for hidradenitis suppurativa: a review of 13 patients
Authors: M. Shareef, R. Dawe
Journal: British Journal of Dermatology (2010)

Journal Article Bath psoralen plus ultraviolet A for hidradenitis suppurativa: a review of 13 patients Get access M. Shareef, M. Shareef Photobiology Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: m.shareef@nhs.net Search for other works by this author on: Oxford Academic Google Scholar R. Dawe R. Dawe Photobiology Unit, Department of Dermatology, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: m.shareef@nhs.net Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 4, 1 April 2011, Pages 895–896, https://doi.org/10.1111/j.1365-2133.2010.10193.x Published: 01 April 2011
Think local, act global: How do fragmented representations of space allow seamless navigation?
Authors: Paul A. Dudchenko, Emma R. Wood, Roderick M. Grieves
Journal: Behavioral and Brain Sciences (2013)

Abstract In this commentary, we highlight a difficulty for metric navigation arising from recent data with grid and place cells: the integration of piecemeal representations of space in environments with repeated boundaries. Put simply, it is unclear how place and grid cells might provide a global representation of distance when their fields appear to represent repeated boundaries within an environment. One implication of this is that the capacity for spatial inferences may be limited.
Effect of mouth leak on effectiveness of nasal bilevel ventilatory assistance and sleep architecture
Authors: H Teschler, J Stampa, R Ragette, N Konietzko, M Berthon-Jones
Journal: European Respiratory Journal (1999)

Mouth leak is common during nasal ventilatory assistance, but its effects on ventilatory support and on sleep architecture are unknown. The acute effect of sealing the mouth on sleep architecture and transcutaneous carbon dioxide tension (Ptc,CO2) was tested in 9 patients (7 hypercapnic) on longterm nasal bilevel ventilation with symptomatic mouth leak. Patients slept with nasal bilevel ventilation at their usual settings on two nights in random order. On one night, the mouth was taped closed. Leak was measured with a pneumotachograph. Median leak fell from 0.35+/-0.07 (mean +/- SEM) L x s(-1) untaped to 0.06+/-0.03 L x s(-1) taped. Ptc,CO2 fell in 8/9, including all hypercapnic patients. Across all patients, the mean Ptc,CO2 fell by 1.02+/-0.28 kPa (7.7+/-2.1 mm Hg) with taping (p = 0.007). Arousal index fell in every patient. Mean arousal index fell from 35.0+/-3.0 to 13.9+/-1.2 h(-1) (p&lt;0.0001), and rapid eye movement (REM) sleep increased from 12.9+/-1.5% to 21.1+/-1.8% sleep time (p = 0.0016). Slow wave sleep changed inconsistently, from a mean of 13.1+/-1.6% to 19.5+/-2.2% of sleep (p = 0.09). Sleep latency and efficiency were unchanged. In four healthy volunteers ventilator-induced awake hypopharyngeal pressure swing during timed bilevel ventilation fell by 35+/-5% L(-1) x s(-1) of voluntary mouth leak (p&lt;0.0001). Mouth leak reduces effective nasal bilevel ventilatory support, increases transcutaneous carbon dioxide tension, and disrupts sleep architecture.
Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans
Authors: Meng-Yun Chou, Linda Fogelstrand, Karsten Hartvigsen, Lotte F. Hansen, Douglas Woelkers, Peter X. Shaw, Jeomil Choi, Thomas Perkmann, Fredrik Bäckhed, Yury I. Miller, Sohvi Hörkkö, Maripat Corr, Joseph L. Witztum, Christoph J. Binder
Journal: Journal of Clinical Investigation (2009)

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis.
Peptide length and sequence specificity of the mouse TAP1/TAP2 translocator.
Authors: T N Schumacher, D V Kantesaria, M T Heemels, P G Ashton-Rickardt, J C Shepherd, K Fruh, Y Yang, P A Peterson, S Tonegawa, H L Ploegh
Journal: The Journal of Experimental Medicine (1994)

The transporter associated with antigen processing (TAP) delivers peptides to the lumen of the endoplasmic reticulum in an adenosine triphosphate (ATP) dependent fashion for presentation by major histocompatibility complex class I molecules. We show that the mouse TAP translocator (H-2b haplotype) selects peptides based on a minimal size of nine residues, and on the presence of a hydrophobic COOH-terminal amino acid. The preponderance of COOH-terminal hydrophobic amino acids in peptides capable of binding to mouse class I molecules thus fits remarkably well with the specificity of the TAP translocator. In addition to transport in the lumenal direction, efflux of peptide in the cytosolic direction is observed in an ATP- and temperature-dependent manner. By maintaining a low peptide concentration at the site of class I assembly, this efflux mechanism may ensure that class I molecules are loaded preferentially with high affinity peptides.
Traffic-related air pollution, genetics and asthma development in children
Authors: T. Sandstrom, F. J Kelly
Journal: Thorax (2009)

In recent years, air pollution has increasingly become recognised as a major contributor to adverse health effects. Numerous studies have shown that poor air quality can adversely affect those with respiratory conditions such as asthma and chronic obstructive pulmonary disease and, more recently, cardiovascular conditions such as myocardial infarctions and stroke.1 Wherever the location, air pollution has been shown to be associated with deterioration in patients with these conditions, as well as with increased mortality.

In patients with asthma, air pollution increases symptoms, medication use, bronchoconstriction, emergency room admissions and hospitalisations. These effects are linked to pollutants such as ozone, nitrogen dioxide and particulate matter (PM) and, increasingly, the role of traffic-related air pollution has been highlighted. Traffic pollution consists of a complex mixture of particles and gases from gasoline and diesel engines, together with dust from wear of road surfaces, tyres and brakes. The coarse particles from road dust have been clearly associated with worsening of asthma and respiratory symptoms.2 Motor engine particles from diesel engines have been linked with worsening of asthma and increased bronchial hyper-responsiveness, a hallmark of asthma.3 There is also literature suggesting that diesel particles enhance allergen sensitisation in animals and humans and that they differentially affect the …
The Activation of Natural Killer Cell Effector Functions by Cetuximab-Coated, Epidermal Growth Factor Receptor–Positive Tumor Cells is Enhanced By Cytokines
Authors: Julie M. Roda, Trupti Joshi, Jonathan P. Butchar, Jaclyn W. McAlees, Amy Lehman, Susheela Tridandapani, William E. Carson
Journal: Clinical Cancer Research (2007)

Natural killer (NK) cells express an activating Fc receptor (FcgammaRIIIa) that mediates antibody-dependent cellular cytotoxicity (ADCC) and production of immune modulatory cytokines in response to antibody-coated targets. Cetuximab is a therapeutic monoclonal antibody directed against the HER1 antigen. We hypothesized that the NK cell response to cetuximab-coated tumor cells could be enhanced by the administration of NK cell-stimulatory cytokines.Human NK cells stimulated with cetuximab-coated tumor cells and interleukin-2 (IL-2), IL-12, or IL-21 were assessed for ADCC and secretion of IFN-gamma and T cell-recruiting chemokines. IL-21 and cetuximab were given to nude mice bearing HER1-positive xenografts.Stimulation of human NK cells with cetuximab-coated tumor cells and IL-2, IL-12, or IL-21 resulted in 3-fold to 10-fold higher IFN-gamma production than was observed with either agent alone. NK cell-derived IFN-gamma significantly enhanced monocyte ADCC against cetuximab-coated tumor cells. Costimulated NK cells also secreted elevated levels of chemokines (IL-8, macrophage inflammatory protein-1alpha, and RANTES) that could direct the migration of naive and activated T cells. IL-2, IL-12, and IL-21 enhanced NK cell ADCC against tumor cells treated with cetuximab. The combination of cetuximab, trastuzumab (an anti-HER2 monoclonal antibody), and IL-21 mediated greater NK cell cytokine secretion and ADCC than any agent alone. Furthermore, administration of IL-21 enhanced the effects of cetuximab in a murine tumor model.These results show that cetuximab-mediated NK cell activity can be significantly enhanced in the presence of NK cell-stimulatory cytokines. These factors, therefore, may be effective adjuvants to administer, in combination with cetuximab, to patients with HER1-positive malignancies.
Double oral esomeprazole after a 3-day intravenous esomeprazole infusion reduces recurrent peptic ulcer bleeding in high-risk patients: a randomised controlled study
Authors: Hsiu-Chi Cheng, Chung-Tai Wu, Wei-Lun Chang, Wei-Chun Cheng, Wei-Ying Chen, Bor-Shyang Sheu
Journal: Gut (2014)

<h3>Background</h3> Patients with high Rockall scores have increased risk of ulcer rebleeding after 3-day esomeprazole infusions. <h3>Objective</h3> To investigate whether double oral esomeprazole given after a 3-day esomeprazole infusion decreases ulcer rebleeding for patients with high Rockall scores. <h3>Design</h3> We prospectively enrolled 293 patients with peptic ulcer bleeding who had achieved endoscopic haemostasis. After a 3-day esomeprazole infusion, patients with Rockall scores ≥6 were randomised into the oral double-dose group (n=93) or the oral standard-dose group (n=94) to receive 11 days of oral esomeprazole 40 mg twice daily or once daily, respectively. The patients with Rockall scores &lt;6 served as controls (n=89); they received 11 days of oral esomeprazole 40 mg once daily. Thereafter, all patients received oral esomeprazole 40 mg once daily for two more weeks until the end of the 28-day study period. The primary end point was peptic ulcer rebleeding. <h3>Results</h3> Among patients with Rockall scores ≥6, the oral double-dose group had a higher cumulative rebleeding-free proportion than the oral standard-dose group (p=0.02, log-rank test). The proportion of patients free from recurrent bleeding during the 4th–28th day in the oral double-dose group remained lower than that of the group with Rockall scores &lt;6 (p=0.03, log-rank test). Among patients with Rockall scores ≥6, the rebleeding rate was lower in the oral double-dose group than in the oral standard-dose group (4th–28th day: 10.8% vs 28.7%, p=0.002). <h3>Conclusions</h3> Double oral esomeprazole at 40 mg twice daily after esomeprazole infusion reduced recurrent peptic ulcer bleeding in high-risk patients with Rockall scores ≥6. <h3>Trial registration number</h3> NCT01591083.
Adult-Onset Atypical (Type 1) Diabetes
Authors: Eva Aguilera, Roser Casamitjana, Guadalupe Ercilla, Josep Oriola, Ramon Gomis, Ignacio Conget
Journal: Diabetes Care (2004)

OBJECTIVE—In 1997, the American Diabetes Association proposed two subcategories for type 1 diabetes: type 1A or immunomediated diabetes and type 1B or idiopathic diabetes characterized by negative β-cell autoimmunity markers, lack of association with HLA, and fluctuating insulinopenia. The aim of this study was to examine clinical characteristics, β-cell function, HLA typing, and mutations in maturity-onset diabetes of the young (MODY) genes in patients with atypical type 1 diabetes (type 1 diabetes diagnosed at onset, without pancreatic autoantibodies and fluctuating insulinopenia). RESEARCH DESIGN AND METHODS—Eight patients with atypical type 1 diabetes (all men, 30.7 ± 7.6 years) and 16 newly diagnosed age- and sex-matched patients with type 1A diabetes were studied retrospectively. Islet cell, GAD, tyrosine phosphatase and insulin antibodies, and basal and stimulated plasma C-peptide were measured at onset and after 1 year. HLA-DRB1-DQA1-DQB1 typing and screening for mutations in the HNF-1α and HNF-4α genes were performed from genomic DNA. RESULTS—Atypical patients displayed significantly higher BMI and better β-cell function at onset and after 12 months. Three patients carried protective or neutral type 1 diabetes haplotypes, five patients displayed heterozygosity for susceptible and protective haplotypes, and seven patients showed Aspβ57. We found a nondescribed variant Pro436Ser in exon 10 of the HNF-4α gene in one atypical patient without susceptible haplotypes. CONCLUSIONS—In our population, there are atypical forms of young adult-onset ketosis-prone diabetes initially diagnosed as type 1 diabetes, differing from type 1 diabetes in the absence of β-cell autoimmunity, persistent β-cell function capacity, fluctuating insulin requirements and ketosis-prone episodes, as well as clinical features of type 2 diabetes. Only one subgroup could be strictly classified as having type 1B diabetes. Additional information is still needed to improve our understanding of the mechanisms that finally lead to the disease.
Effect of fish oil on arrhythmias and mortality: systematic review
Authors: H. Leon, M. C Shibata, S. Sivakumaran, M. Dorgan, T. Chatterley, R. T Tsuyuki
Journal: BMJ (2008)

<b>Objective</b> To synthesise the literature on the effects of fish oil—docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)—on mortality and arrhythmias and to explore dose response and formulation effects. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Medline, Embase, the Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal, Allied and Complementary Medicine, Academic OneFile, ProQuest Dissertations and Theses, Evidence-Based Complementary Medicine, and LILACS. <b>Studies reviewed</b> Randomised controlled trials of fish oil as dietary supplements in humans. <b>Data extraction</b> The primary outcomes of interest were the arrhythmic end points of appropriate implantable cardiac defibrillator intervention and sudden cardiac death. The secondary outcomes were all cause mortality and death from cardiac causes. Subgroup analyses included the effect of formulations of EPA and DHA on death from cardiac causes and effects of fish oil in patients with coronary artery disease or myocardial infarction. <b>Data synthesis</b> 12 studies totalling 32 779 patients met the inclusion criteria. A neutral effect was reported in three studies (n=1148) for appropriate implantable cardiac defibrillator intervention (odds ratio 0.90, 95% confidence interval 0.55 to 1.46) and in six studies (n=31 111) for sudden cardiac death (0.81, 0.52 to 1.25). 11 studies (n=32 439 and n=32 519) provided data on the effects of fish oil on all cause mortality (0.92, 0.82 to 1.03) and a reduction in deaths from cardiac causes (0.80, 0.69 to 0.92). The dose-response relation for DHA and EPA on reduction in deaths from cardiac causes was not significant. <b>Conclusions</b> Fish oil supplementation was associated with a significant reduction in deaths from cardiac causes but had no effect on arrhythmias or all cause mortality. Evidence to recommend an optimal formulation of EPA or DHA to reduce these outcomes is insufficient. Fish oils are a heterogeneous product, and the optimal formulations for DHA and EPA remain unclear.
Promotion of Aberrant Crypt Foci and Cancer in Rat Colon by Thermolyzed Protein
Authors: X.-M. Zhang, D. Stamp, S. Minkin, A. Medline, D. E. Corpet, W. R. Bruce, M. C. Archer
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Promotion of Aberrant Crypt Foci and Cancer in Rat Colon by Thermolyzed Protein Get access X.-M. Zhang, X.-M. Zhang Department of Medical Biophysics, University of Toronto, The Ontario Cancer InstituteToronto, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Stamp, D. Stamp Department of Medical Biophysics, University of Toronto, The Ontario Cancer InstituteToronto, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Minkin, S. Minkin Department of Medical Biophysics, University of Toronto, The Ontario Cancer InstituteToronto, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Medline, A. Medline Department of Pathology, University of Toronto Search for other works by this author on: Oxford Academic PubMed Google Scholar D. E. Corpet, D. E. Corpet Institut National de la Recherche AgronomiqueToulouse, France Search for other works by this author on: Oxford Academic PubMed Google Scholar W. R. Bruce, W. R. Bruce * Department of Medical Biophysics, University of Toronto, The Ontario Cancer InstituteToronto, Canada * Correspondence to: W. R. Bruce, M.D., The Ontario Cancer Institute, 500 Sherbourne St., Toronto, ON M4X 1K9, Canada. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. C. Archer M. C. Archer Department of Medical Biophysics, University of Toronto, The Ontario Cancer InstituteToronto, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 13, 1 July 1992, Pages 1026–1030, https://doi.org/10.1093/jnci/84.13.1026 Published: 01 July 1992 Article history Received: 24 January 1992 Accepted: 31 March 1992 Published: 01 July 1992 Revision received: 26 March 1996
Smoking and pathogenesis of psoriasis: a review of oxidative, inflammatory and genetic mechanisms
Authors: A.W. Armstrong, E.J. Armstrong, E.N. Fuller, M.E. Sockolov, S.V. Voyles
Journal: British Journal of Dermatology (2011)

Recent studies suggest that cigarette smoking may trigger the development of psoriasis through oxidative, inflammatory and genetic mechanisms. Smoking initiates formation of free radicals that stimulate cell signalling pathways active in psoriasis including mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK-STAT). Smoking damages the skin by increasing formation of reactive oxygen species and decreasing the gene expression of antioxidants. Nicotine also stimulates innate immune cells integral to the pathogenesis of psoriasis including dendritic cells, macrophages and keratinocytes. These cells release cytokines that activate T lymphocytes and perpetuate a cycle of chronic inflammation. Smoking also enhances expression of genes known to confer an increased risk of psoriasis, including HLA-Cw6, HLA-DQA1*0201 and CYP1A1. Improved understanding of the possible link between smoking and psoriasis pathogenesis may provide further insight into mechanisms underlying smoking, psoriasis and risk of subsequent cardiovascular disease.
Effects of inhibition of fatty acid oxidation on myocardial kinetics of 11C-labeled palmitate.
Authors: W Wyns, M Schwaiger, S C Huang, D B Buxton, H Hansen, C Selin, R Keen, M E Phelps, H R Schelbert
Journal: Circulation Research (1989)

The effects of glucose and lactate infusion on palmitate oxidation were compared with the effect of 2-tetradecylglycidic acid (TDGA), an irreversible inhibitor of the carnitine acyltransferase I, in normoxic canine myocardium. The initial capillary transit retention fraction of [1-11C]palmitate and its fractional distribution between oxidation and esterification in myocardium were measured by the residue detection method after intracoronary tracer injection, as well as by effluent measurements of 11CO2, the end product of palmitate oxidation. TDGA reduced the initial capillary transit retention fraction (from 56 +/- 13% to 37 +/- 6%; p less than 0.001) and oxidation of palmitate (n = 19), as also evidenced by the decrease in the fraction of tracer released as 11CO2 from 28 +/- 5% to 6 +/- 3% (p less than 0.001). Infusion of carbohydrate (glucose or lactate; n = 6) reduced 11CO2 production from 30 +/- 7% to 7 +/- 4% (p less than 0.05) but did not alter the initial capillary transit retention fraction of tracer (59 +/- 5% vs. 56 +/- 10%; NS). The latter was due to increased esterification into neutral lipids (41 +/- 11% of injected palmitate after carbohydrate infusion versus 21 +/- 12% in control conditions), as measured from multiexponential curve fittings. When carbohydrates were given after inhibition of palmitate oxidation by TDGA (n = 7), the 11C tissue clearance kinetics were strikingly similar to those observed after carbohydrate infusion alone. Thus, enhanced metabolic trapping of [1-11C]palmitate in myocardium resulted in initial capillary transit retention fractions that were not different from control conditions (41 +/- 5% vs. 48 +/- 12%; NS) despite inhibition of oxidation. The results show that the intracellular metabolism of palmitate contributes to the control of its uptake by myocardium. The findings are consistent with inhibition of palmitate oxidation by carbohydrates occurring at the same site as TDGA.