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Enhanced cytotoxic function of natural killer and natural killer T-like cells associated with decreased CD94 (Kp43) in the chronic obstructive pulmonary disease airway

Mon, 31 Dec 2012 13:30:00 GMT

Title: Enhanced cytotoxic function of natural killer and natural killer T-like cells associated with decreased CD94 (Kp43) in the chronic obstructive pulmonary disease airway Author: Hodge, Gregory Lionel; Mukaro, Violet Rudo Samantha; Holmes, Mark; Reynolds, Paul Nigel; Hodge, Sandra Joy Abstract: BACKGROUND AND OBJECTIVE: Natural killer (NK) and natural killer T (NKT)-like cells represent a small but important proportion of effector lymphocytes that we have previously shown to be major sources of pro-inflammatory cytokines and granzymes. We hypothesized that these cells would be increased in the airway in chronic obstructive pulmonary disease (COPD), accompanied by reduced expression of the inhibitory receptor CD94 (Kp43) and increased expression of cytotoxic mediators granzyme B and perforin. METHODS: We measured NK and NKT-like cells and their expression of CD94 in the blood of COPD patients (n = 71; 30 current and 41 ex-smokers), smokers (16) and healthy controls (25), and bronchoalveolar lavage fluid (BALF) from a cohort of subjects (19 controls, 12 smokers, 33 COPD). Activation was assessed by measuring CD69 in blood and the cytotoxic potential of NK cells by measuring granzymes A and B, and using a cytotoxicity assay in blood and BALF. RESULTS: In blood in COPD, there were no significant changes in the proportion of NK or NKT-like cells or expression of granzyme A or NK cytotoxic potential versus controls. There was, however, increased expression of granzyme B and decreased expression of CD94 by both cell types versus controls. The proportion of NK and NKT-like cells were increased in BALF in COPD, associated with increased NK cytotoxicity, increased expression of granzyme B and decreased expression of the inhibitory receptor CD94 by both cell types. CONCLUSIONS: Treatment strategies that target NK and NKT-like cells, their cytotoxicity and production of inflammatory mediators in the airway may improve COPD morbidity.

Common variants at 6p21.1 are associated with large artery atherosclerotic stroke

Sat, 31 Dec 2011 13:30:00 GMT

Title: Common variants at 6p21.1 are associated with large artery atherosclerotic stroke Author: Holliday, Elizabeth G.; Koblar, Simon Andrea; Jannes, Jim; Lewis, Martin David Abstract: Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR) = 1.62, P = 3.9 × 10−8) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR = 1.15, P = 3.9 × 10−4; discovery and replication combined OR = 1.21, P = 4.7 × 10−8). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke.

Effect of educational components and strategies associated with insulun pump therapy: a systematic review

Fri, 31 Dec 2010 13:30:00 GMT

Title: Effect of educational components and strategies associated with insulun pump therapy: a systematic review Author: Jayasekara Gangoda Arachchilag, Rasika Sirilal Jayasekara; Munn, Zachary Read; Lockwood, Craig Stuart Abstract: Objectives: The objectives of this review were to establish the effectiveness of approaches to the provision of education for adults with type 1 diabetes using or initiating insulin pump therapy (IPT), and identify the best available evidence on the association between intervals and duration of follow up and the stated outcome criteria. Inclusion criteria: This review considered all studies and papers that involved adults (aged 16 years or over) with type 1 diabetes using IPT as their primary form of therapy who participated in education or training, with no restrictions placed on gender or comorbidities. All forms of education, including resources utilised during education were included in the review. Search strategy: The search strategy sought to find both published and unpublished studies and papers written in the English language. An initial limited search of MEDLINE and CINAHL databases was undertaken to identify optimal search terms. A second search using all identified key words and index terms was then undertaken based on key words specific to each database across all included databases from 1998 to February 2008. Thirdly, the reference lists of all identified reports and articles were searched for additional studies. Methodological quality: Two independent reviewers assessed the methodological quality of retrieved papers using the corresponding checklist from the System for the Unified Management, Assessment and Review of Information (SUMARI) package. Results: A total of 142 studies were identified as potentially relevant to the review question in the first and second steps of the literature search. Based on the title and abstract, 24 papers that were relevant to the review topic were retrieved for evaluation of methodological quality. Following this stage, 20 papers were excluded. Whilst searching the reference lists of the selected studies (n = 4), one paper met the inclusion criteria. Therefore, a total of five descriptive studies were included in the review. The included papers reported a variety of educational methods and different outcome measures. Conclusion: In general, it is difficult to draw a strong conclusion regarding the effectiveness of components and strategies associated with IPT because of a lack of high-quality comparative studies, small sample sizes and a variability of reported methods in the included studies. However, included descriptive studies explored a range of issues related to the effectiveness of IPT therapy, and the educative requirements of patients. It is clear that type 1 diabetes patients initiating and utilising IPT need a comprehensive range of advice, education and training. The mixture of group and individual teaching, multidisciplinary teams as educators, educational materials, long-term training with multiple sessions and a variety of educational contents may all be effective for delivering IPT education and training.

Electrophoretic sperm isolation: Optimization of electrophoresis conditions and impact on oxidative stress

Fri, 31 Dec 2010 13:30:00 GMT

Title: Electrophoretic sperm isolation: Optimization of electrophoresis conditions and impact on oxidative stress Author: Aitken, R. John; Hanson, Adrienne Ruth; Kuczera, George Abstract: BACKGROUND The purpose of this study was to optimize the electrophoretic conditions that should be used for the effective isolation of functional human spermatozoa and to determine whether this method of isolating cells was associated with oxidative stress and DNA damage. METHODS Human spermatozoa were prepared by repeated centrifugation, discontinuous density gradient centrifugation and electrophoresis followed by assessments of sperm quality. RESULTS Systematic analysis of optimal electrophoresis conditions demonstrated that field strength was positively correlated with sperm recovery rates but negatively correlated with sperm movement, irrespective of whether the current or the voltage was held constant. This loss of functionality observed at high power settings was not associated with a major increase in superoxide generation or the induction of oxidative DNA damage. In contrast, discontinuous Percoll gradient centrifugation was shown to produce a significant rise in oxidative DNA base adduct expression in live cells (P < 0.05). As a result of these analyses, optimized electrophoretic conditions were defined that permitted sperm recovery rates of around 20%. These electrophoretically isolated cells were not only free of oxidative stress but exhibited significantly enhanced motility (P < 0.01) and vitality (P < 0.001) compared with the original samples. CONCLUSIONS We conclude that while field strength is positively correlated with sperm recovery rates; it is negatively associated with sperm motility. Optimized conditions are described that represent a balance between these opposing forces and permit the isolation of highly motile, vital sperm populations, free from the oxidative DNA damage associated with conventional density gradient centrifugation technologies.