The influence of the HLA-DRB1*13 allele on measles vaccine response

BACKGROUND: Measles remains a public health threat in the United States with over 50,000 cases being reported from 1989 through 1991 with continued smaller outbreaks. Measles vaccine failure is in part to blame for these large-scale outbreaks. The human leukocyte antigen (HLA) genes are important determinants of immune response to measles virus and vaccine. To examine the influence that HLA polymorphisms may have on measles vaccine antibody response, we compared the distribution of HLA-DRB1 alleles between measles vaccine nonresponders and hyper-responders. METHODS: We determined the seroprevalence of measles antibody in 881 school children immunized with measles-mumps-rubella-II at age 15 months using a whole virus IgG EIA. We performed class II HLA-DR typing by PCR with sequence specific primers (PCR-SSP) on 81 nonresponders (IgG seronegative) and 65 hyper-responders (from the upper 10th percentile of IgG levels of all subjects). We then compared the distribution of alleles between nonresponders and hyper-responders. RESULTS: The distribution of HLA-DRB1 alleles among nonresponders compared to hyper-responders was significantly different (p = 0.014). Nonresponders were significantly less likely to carry the HLA-DRB1*13 alleles than were hyper-responders (7.4% vs 16.2%;p = 0.02). Nonresponders also had an excess of HLA-DRB1*07 alleles (15.4% vs 6.2%; p = 0.015). CONCLUSIONS: The absence of HLA-DRB1*13 alleles is associated with measles vaccine nonresponse. The absence of this allele has also been associated with susceptibility to other infectious diseases. The role of this gene in the immunogenetic response to infectious diseases requires further study.     

Prion protein immunohistochemical staining in the brains of monkeys with transmissible spongiform encephalopathy

BACKGROUND: Spirituality is receiving greater attention in the medical literature, especially in the family practice journals. A widely applicable instrument to assess spirituality has been lacking, however, and this has hampered research on the relationship between spirituality and health in the clinical setting. METHODS: A new instrument, called the Spiritual Involvement and Beliefs Scale, was designed to be widely applicable across religious traditions, to assess actions as well as beliefs to address key components not assessed in other available measures, and to be easily administered and scored. The instrument is a questionnaire containing 26 items in a modified Likert-type format. Following careful pretesting, the instrument was administered to 50 family practice patients and 33 family practice educators. The validity and reliability of the instrument were then evaluated. RESULTS: By several measures, instrument reliability and validity are very good, with high internal consistency (Cronbach's alpha = .92); strong test-retest reliability (r = .92); a clear four-factor structure; and a high correlation (r = .80) with another established measure of spirituality, the Spiritual Well-Being Scale. CONCLUSIONS: The Spiritual Involvement and Beliefs Scale (SIBS) appears to have good reliability and validity. Compared with other instruments that assess spirituality, the SIBS has several theoretical advantages, including broader scope, use of terms that avoid cultural-religious bias, and assessment of both beliefs and actions. More testing is underway to further assess its usefulness.     

Lung volume reduction surgery for severe emphysema

In hairless mice, a moderate vitamin-A deficiency, without any clinical signs or weight changes, reduces the activity of soluble cytoplasmic hepatic transglutaminase without affecting the membrane form of the enzyme. This attack of soluble transglutaminase appears to be a biological marker of early deficiency. The relations between this disturbance and the hepatocyte sensitivity to aggressors at this stage are discussed.     

Functional expression of the cystic fibrosis transmembrane conductance regulator in yeast

Recombinant human cystic fibrosis transmembrane conductance regulator (CFTR) has been produced in a Saccharomyces cerevisiae expression system used previously to produce transport ATPases with high yields. The arrangement of the bases in the region immediately upstream from the ATG start codon of the CFTR is extremely important for high expression levels. The maximal CFTR expression level is about 5-10% of that in Sf9 insect cells as judged by comparison of immunoblots. Upon sucrose gradient centrifugation, the majority of the CFTR is found in a light vesicle fraction separated from the yeast plasma membrane in a heavier fraction. It thus appears that most of expressed CFTR is not directed to the plasma membrane in this system. CFTR expressed in yeast has the same mobility (ca. 140 kDa) as recombinant CFTR produced in Sf9 cells in a high resolution SDS-PAGE gel before and after N-glycosidase F treatment, suggesting that it is not glycosylated. The channel function of the expressed CFTR was measured by an isotope flux assay in isolated yeast membrane vesicles and single channel recording following reconstitution into planar lipid bilayers. In the isotope flux assay, protein kinase A (PKA) increased the rate of 125I- uptake by about 30% in membrane vesicles containing the CFTR, but not in control membranes. The single channel recordings showed that a PKA-activated small conductance anion channel (8 pS) with a linear I-V relationship was present in the CFTR membranes, but not in control membranes. These results show that the human CFTR has been expressed in functional form in yeast. With the reasonably high yield and the ability to grow massive quantities of yeast at low cost, this CFTR expression system may provide a valuable new source of starting material for purification of large quantities of the CFTR for biochemical studies.