16 research outputs found
Immunogenicity ofEscherichia coli O antigen in upper urinary tract infection
Immunogenicity ofEscherichia coli O antigen in upper urinary tract infection. The role of immunogenicity of the infecting organism (Escherichia coli) in the antibody response to O antigen in upper urinary tract infection was investigated Heat-killed vaccines were prepared from âimmunogenicâ organisms which had produced upper urinary tract infection associated with high titers of hemag-glutinating antibody to O antigen and ânonimmunogenicâ organisms which had produced upper urinary tract infection without a rise in antibody titer. âImmunogenicâ 06 vaccine produced high titers of antibody in patients regarded as possibly âpoor producersâ of antibody, but ânonimmunogenicâ 011 vaccine was not associated with a rise in titer in patients previously regarded as âgood producersâ. These vaccines were significantly different in immunogenicity (P < 0.05). Five vaccines were tested in 50 rats. The difference in hemagglutinating titers to O antigen between 06 and 011 was highly significant (P < 0.001). Immunogenicity of the infecting organism appears to be a significant factor in determining antibody response to O antigen in upper urinary tract infection.ImmunogĂ©nicitĂ© de l'antigĂšne O d'Escherichia coli dans les infections du haut appareil urinaire. Le rĂŽle de l'immunogĂ©nicitĂ© de l'organisme infectant (Escherichia coli) dans la rĂ©ponse immune Ă l'antigĂšne O au cours des infections du haut appareil urinaire a Ă©tĂ© Ă©tudiĂ©. Des vaccins tuĂ©s par la chaleur ont Ă©tĂ© prĂ©parĂ©s Ă partir d'organismes âimmunogĂ©niquesâ qui ont Ă©tĂ© responsables d'infection du haut appareil urinaire associĂ©es Ă des titres Ă©levĂ©s d'anticorps hĂ©magglutinants contre l'antigĂšne O et d'organismes ânon immunogĂ©niquesâ qui ont produit une infection du haut appareil sans augmentation du titre d'anticorps. Le vaccin âimmunogĂ©niqueâ 06 produit des titres Ă©levĂ©s d'anticorps chez des malades considĂ©rĂ©s comme de faibles producteurs d'anticorps et le vaccin ânon immunogĂ©niqueâ 011 ne dĂ©termine pas d'augmentation du titre chez des malades antĂ©rieurement considĂ©rĂ©s comme de âbons producteursâ. Ces vaccins diffĂšrent significativement en âimmunogĂ©nicitĂ©â (P < 0, 05). Cinq vaccins ont Ă©tĂ© essayĂ©s chez 50 rats. La diffĂ©rence dans les titres d'hĂ©mmaglutination vis Ă vis de l'antigĂšne O est trĂšs significative entre 06 et 011 (P < 0, 001). L'immunogĂ©nicitĂ© de l'organisme infectant parait ĂȘtre un facteur important dans la dĂ©termination de la rĂ©ponse immune Ă l'antigĂšne O au cours des infections du haut appareil urinaire
Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study
Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008â11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003â13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 Ă 10â10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 Ă 10â8 DHFR p=8·37 Ă 10â7 MTRNR2L2 p=2·15 Ă 10â9) and to a lesser extent in REGISTRY (MSH3 p=9·36 Ă 10â4 DHFR p=8·45 Ă 10â4 MTRNR2L2 p=1·20 Ă 10â3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 Ă 10â8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16â0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06â0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation
The Moderators and Mediators of Door-in-the-Face Requests: Is it a Negotiation or a Helping Experience?
Coagulation factor levels in neurosurgical patients with mild prolongation of prothrombin time: effect on plasma transfusion therapy
Functional characterization of T-cells from palatine tonsils in patients with chronic tonsillitis
Microbiota Dynamics in Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection
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Databases for Congenital Heart Defect Public Health Studies Across the Lifespan
Initial invasive or conservative strategy for stable coronary disease
BACKGROUND Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, 121.8 percentage points; 95% CI, 124.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used