Passive immunity in calf rotavirus infections: maternal vaccination increases and prolongs immunoglobulin G1 antibody secretion in milk.

Ten heifers were inoculated on two occasions with an inactivated preparation of tissue culture-grown calf rotavirus, and a further ten heifers received a placebo vaccine. Serum anti-rotavirus antibody titers were significantly increased throughout pregnancy in the vaccinated group. After calving, the mean neutralizing antibody titer of colostral whey in control cows was 100, associated with immunoglobulins A and G1. No antibody was detected in the milk of these cows after the 4th day postpartum. The colostral whey from the vaccinated cows had a mean antibody titer of 20,452; 28 days after calving, the mean milk antibody titer was 320, associated mainly with immunoglobulin G1. Calves were challenged with a large oral inoculum of calf rotavirus at the 7th day of age. There was significant lengthening of the incubation and prepatent periods in calves born to vaccinated dams, but rotavirus-associated diarrhea of equal severity occurred in both groups. Evidence is presented which suggests that rotavirus antibody in milk can protect against a smaller challenge dose. Maternal immunization against rotavirus may be a practical proposition.     

A NOS1 variant implicated in cognitive performance influences evoked neural responses during a high density EEG study of early visual perception

Background: The nitric oxide synthasase‐1 gene (NOS1) has been implicated in mental disorders including schizophrenia and variation in cognition. The NOS1 variant rs6490121 identified in a genome wide association study of schizophrenia has recently been associated with variation in general intelligence and working memory in both patients and healthy participants. Whether this variant is also associated with variation in early sensory processing remains unclear. Methods: We investigated differences in the P1 visual evoked potential in a high density EEG study of 54 healthy participants. Given both NOS1's association with cognition and recent evidence that cognitive performance and P1 response are correlated, we investigated whether NOS1's effect on P1 response was independent of its effects on cognition using CANTAB's spatial working memory (SWM) task. Results: We found that carriers of the previously identified risk “G” allele showed significantly lower P1 responses than non‐carriers. We also found that while P1 response and SWM performance were correlated, NOS1 continued to explain a significant proportion of variation in P1 response even when its effects on cognition were accounted for. Conclusion: The schizophrenia implicated NOS1 variants rs6490121 influences visual sensory processing as measured by the P1 response, either as part of the gene's pleiotropic effects on multiple aspects of brain function, or because of a primary influence on sensory processing that mediates the effects already seen in higher cognitive processes. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.     

Stability of plasma levels of cytokines and soluble activation markers in patients with human immunodeficiency virus infection

Cytokine and immune activation marker levels in plasma are valuable measurements of immune status and treatment effects in human immunodeficiency virus (HIV) infection and AIDS. Five populations representing various stages of disease were studied: controls, 2 AIDS groups with <50/mm3 CD4 cells, and 2 groups of HIV-positive subjects-1 with stable CD4 T cells (median, 545/mm3) and 1 with >100/mm3 CD4 cell decline in 1 year. Relatively stable levels of tumor necrosis factor (TNF)-alpha, soluble TNF receptor (R)II, soluble interleukin-2R, neopterin, and beta2-microglobulin (beta2M) were documented over 5-8 weeks in patients with AIDS and for 1-4 years in the other groups. beta2M was generally the most stable marker. Interferon-gamma levels, however, fluctuated substantially. Individuals, whether normal or HIV-positive, maintain characteristic plasma levels of cytokines and immune activation markers. Thus, documented changes, in excess of the variability observed in this study, are likely to be significant indicators of change in disease status or effects of therapy.     

Analytical performance of a highly sensitive C-reactive protein-based immunoassay and the effects of laboratory variables on levels of protein in blood

C-reactive protein (CRP) is an acute-phase reactant whose levels increase in response to a variety of inflammatory stimuli. Elevated levels in serum are observed after trauma, tissue necrosis, infection, surgery, and myocardial infarction and are associated with an increased risk of cardiovascular disease. CRP levels are also elevated in noninflammatory states, such as obesity, sleep disturbances, depression, chronic fatigue, aging, and physical inactivity. In this study, the performance of a highly sensitive CRP enzyme immunoassay was evaluated, along with common laboratory variables (specimen type, processing time, and storage conditions) that may influence measured blood concentrations of CRP. The measurement range of the assay was from 0.4 to 50 microg/liter. Total imprecision (coefficient of variation) ranged from 8.1 to 11.4%. CRP levels obtained with the enzyme immunoassay were highly correlated with those obtained with an automated immunonephelometric assay. Comparable results were obtained for plasma (heparin and EDTA treated) and serum samples, and levels were unaffected by delays in sample processing and storage temperature. CRP levels were also unaffected by up to seven freeze-thaw cycles. The median CRP concentration in healthy adults was determined to be 0.94 mg/liter, with a 95% working reference interval of 0 to 6.9 mg/liter. In view of these data, we recommend that serial serum or plasma samples for CRP should be stored at 4 degrees C for short periods of time or at -70 degrees C for longer periods and tested within the same run to minimize interassay variability.     

Antibodies with Differing Molecular Sizes in Mice

The antibody responses of C₃H mice to haemocyanin, pneumococcal polysaccharide (SSS III) and sheep erythrocytes were studied after a single intravenous administration. Serum antibody against each antigen was present on the fifth, but not on the third day.

Antibodies against haemocyanin and against SSS III migrated electrophoretically as γ globulins and had the ultracentrifugal sedimentation properties of 6.5S globulins. Sheep erythrocyte haemolysins were largely γ macroglobulins which sedimented in the ultracentrifuge in the manner of 18S globulins. A small proportion of haemolysin activity was found among the 6.5S γ globulins.

     

Copy number variants in patients with short stature

Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes.