211 research outputs found

    Association of the Major Histocompatibility Complex with Autism

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    The pathogenesis of autism has proven difficult to characterize. However, in many recent studies, it is suggested that the onset of this disorder is the result of multiple etiological factors, which include genetic, immunologic, and viral elements. Possible immunological influences found in subpopulations of patients with autism include decreased lymphocyte responsiveness, reduced natural killer cell activity, abnormal response to rubella vaccine, abnormal immune response to brain tissue, and decreased plasma levels of the fourth component of complement(C4). These aberrations and others imply a possible autoimmune mechanism in some cases for the development of autism. C4 deficiencies have been found in subjects with established autoimmune disorders, such as systemic lupus erythematosus and chronic active hepatitis, in recent investigations. There is also evidence that the major histocompatibility genes play an intimate role in autoimmune processes. Therefore, in knowing that the C4 genes are closely linked to the major histocompatibility genes, this study determined and analyzed the human leukocyte antigen profile of autistic patients, their siblings, and parents. In this study, it was found that the C4B complement null allele occurred in autistic patients at nearly twice the frequency compared to normals. However, the C4A complement null allele frequency was not found to be significantly altered. Several extended haplotypes were represented within the patients studied. However, the extended haplotype B44- SC30-DR4 was the only one found at a significantly increased frequency. Further investigations are needed to better understand the significance of these findings

    Candidiasis During Pregnancy May Result From Isogenic Commensal Strains

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    Objective: Our laboratory previously demonstrated that asymptomatic vaginal colonization during pregnancy is a factor predisposing patients to subsequent symptomatic vulvovaginal candidiasis. It is unknown whether symptoms result from strain replacement or a change in host relationship to the original colonizing strain. This study was undertaken to determine whether Candida albicans isolates from asymptomatic women could be responsible for subsequent symptomatic vaginitis. Methods: We retained isolates of C. albicans from women followed longitudinally through pregnancy, and identified six pairs of cultures from women who were colonized without symptoms and who later became symptomatic (average time 14 weeks). We used a random amplification of polymorphic DNA (RAPD) analysis to determine whether isolates from our study patients were genetically similar or dissimilar. Results: Analysis of these pairs of yeast strains by RAPD revealed that five of the six women had symptoms apparently due to the same yeast strain that was found initially as a commensal strain. To increase the power of these observations, we also performed RAPD analysis on six randomly selected yeast strains from other women in this study who had not become symptomatic to determine whether any of these unrelated strains matched strains from those women who became symptomatic. Conclusion: Symptomatic yeast vaginitis is usually due to strains of C. albicans already carried in the lower genital tract, underscoring the need to understand regulation of growth and virulence of the organism in vivo

    Murine Cytomegalovirus Is Regulated by a Discrete Subset of Natural Killer Cells Reactive with Monoclonal Antibody to Ly49h

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    Antiviral roles of natural killer (NK) cell subsets were examined in C57BL/6 mice infected with murine cytomegalovirus (MCMV) and other viruses, including lymphocytic choriomeningitis virus (LCMV), vaccinia virus (VV), and mouse hepatitis virus (MHV). Each virus vigorously induced an NK cell infiltrate into the peritoneal cavity and liver, causing some redistributions of NK cell subsets defined by monoclonal antibody (mAb) directed against Ly49A, C/I, D, and G2. Striking results were seen with a mAb (1F8) reactive with the positively signaling molecule Ly49H, present in MCMV-resistant C57BL/6 mice. mAb 1F8 also stains Ly49 C and I, but exclusion of those reactivities with mAb 5E6, which recognizes Ly49 C and I, indicated that Ly49H+ cells infiltrated the peritoneal cavity and liver and were particularly effective at synthesizing interferon Ī³. Depletion of 1F8+ but not 5E6+ cells in vivo by mAb injections enhanced MCMV titers by 20-1,000-fold in the spleen and approximately fivefold in the liver. Titers of LCMV or VV were not enhanced. These anti-MCMV effects were attributed to prototypical NK1.1+CD3āˆ’ NK cells and not to NK1.1+CD3+ ā€œNK/Tā€ cells. This is the first evidence that control of a virus infection in vivo is mediated by a distinct NK cell subset

    FAA Capstone Program: Phase II Baseline Report (Southeast Alaska)

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    This report provides the Federal Aviation Administration (FAA) with information on air safety and aviation infrastructure in southeast Alaska as of December 31, 2002. The data will establish a baseline to enable the University of Alaska Anchorage (UAA) to conduct an independent evaluation of how the Capstone program affects aviation safety in the region. The FAA contracted with UAAā€™s Institute of Social and Economic Research and Aviation Technology Division to do a variety of training and evaluation tasks related to the Capstone program. The program is a joint effort of industry and the FAA to improve aviation safety and efficiency in select regions of Alaska, through government-furnished avionics equipment and improvements in ground infrastructure.Federal Aviation Administration (Alaskan Region

    2018 Atmospheric Motion Vector (AMV): intercomparison study

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    Atmospheric Motion Vectors (AMVs) calculated by six different institutions (Brazil Center for Weather Prediction and Climate Studies/CPTEC/INPE, European Organization for the Exploitation of Meteorological Satellites/EUMETSAT, Japan Meteorological Agency/JMA, Korea Meteorological Administration/KMA, Unites States National Oceanic and Atmospheric Administration/NOAA, and the Satellite Application Facility on Support to Nowcasting and Very short range forecasting/NWCSAF) with JMAā€™s Himawari-8 satellite data and other common input data are here compared. The comparison is based on two different AMV input datasets, calculated with two different image triplets for 21 July 2016, and the use of a prescribed and a specific configuration. The main results of the study are summarized as follows: (1) the differences in the AMV datasets depend very much on the ā€˜AMV height assignmentā€™ used and much less on the use of a prescribed or specific configuration; (2) the use of the ā€˜Common Quality Indicator (CQI)ā€™ has a quantified skill in filtering collocated AMVs for an improved statistical agreement between centers; (3) Among the six AMV operational algorithms verified by this AMV Intercomparison, JMA AMV algorithm has the best overall performance considering all validation metrics, mainly due to its new height assignment method: ā€˜Optimal estimation method considering the observed infrared radiances, the vertical profile of the Numerical Weather Prediction wind, and the estimated brightness temperature using a radiative transfer modelā€™.The ā€œSpace Science and Engineering Centerā€ (SSEC) of the ā€œUniversity ofWisconsin-Madisonā€ (UW) was funded to do this research by the ā€œEuropean Organization for the Exploitation of Meteorological Satellites (EUMETSAT)ā€, through the ā€œSatellite Application Facility on Support to Nowcasting and Very short range forecasting (NWCSAF)ā€ ā€œVisiting Scientist Activity (VSA)ā€ program

    Natriuretic peptides and integrated risk assessment for cardiovascular disease. an individual-participant-data meta-analysis

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    BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7Ā·5%, and ā‰„7Ā·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95ā€ˆ617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1Ā·76 (95% CI 1Ā·56-1Ā·98) for the combination of coronary heart disease and stroke and 2Ā·00 (1Ā·77-2Ā·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0Ā·012 (0Ā·010-0Ā·014) and a net reclassification improvement of 0Ā·027 (0Ā·019-0Ā·036) for the combination of coronary heart disease and stroke and a C-index increase of 0Ā·019 (0Ā·016-0Ā·022) and a net reclassification improvement of 0Ā·028 (0Ā·019-0Ā·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention

    Evidence for high bi-allelic expression of activating Ly49 receptors

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    Stochastic expression is a hallmark of the Ly49 family that encode the main MHC class-I-recognizing receptors of mouse natural killer (NK) cells. This highly polygenic and polymorphic family includes both activating and inhibitory receptor genes and is one of genome's fastest evolving loci. The inhibitory Ly49 genes are expressed in a stochastic mono-allelic manner, possibly under the control of an upstream bi-directional early promoter and show mono-allelic DNA methylation patterns. To date, no studies have directly addressed the transcriptional regulation of the activating Ly49 receptors. Our study shows differences in DNA methylation pattern between activating and inhibitory genes in C57BL/6 and F1 hybrid mouse strains. We also show a bias towards bi-allelic expression of the activating receptors based on allele-specific single-cell RTā€“PCR in F1 hybrid NK cells for Ly49d and Ly49H expression in Ly49h+/āˆ’ mice. Furthermore, we have identified a region of high sequence identity with possible transcriptional regulatory capacity for the activating Ly49 genes. Our results also point to a likely difference between NK and T-cells in their ability to transcribe the activating Ly49 genes. These studies highlight the complex regulation of this rapidly evolving gene family of central importance in mouse NK cell function

    Measurement of tibial nerve excursion during ankle joint dorsiflexion in a weight-bearing position with ultrasound imaging

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    The ability of peripheral nerves to stretch and slide is thought to be of paramount importance to maintain ideal neural function. Excursion in peripheral nerves such as the tibial can be measured by analysis of ultrasound images. The aim of this study was to assess the degree of longitudinal tibial nerve excursion as the ankle moved from plantar flexion to dorsiflexion in a standardised weight-bearing position. The reliability of ultrasound imaging to measure tibial nerve excursion was also quantified
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