PubMed Health⌕ Search

Biomedical subjects

T J Cobain

Publications and source records attributed to T J Cobain.

9 recordsLinked to original sources
PubMed1990

Differences in gene copy number carried by different MHC ancestral haplotypes. Quantitation after physical separation of haplotypes by pulsed field gel electrophoresis.

We have examined the hypothesis that MHC ancestral haplotypes have a specific content of genes regulating the extent of autoimmune reactions. Gene copy number was quantitated by objective densitometry after PFGE was used to separate heterozygous AHs of different lengths. Initially we analyzed examples of known gene copy number at the C4 and 21 hydroxylase loci and showed that the approach provides predictable results. We then studied heterozygotes containing one characterized and one uncharacterized AH with particular attention to the gene copy number at the C4, Cyp21, and DRB loci. Each AH studied has a characteristic gene copy number at each locus studied. The same may be true of TNF, but other possibilities must be considered. AHs are markers for extensive chromosomal segments including particular numbers of several functional genes. Since AHs mark susceptibility to autoimmune disease, differences in gene copy number may be implicated.

Blotting, Southern↗
PubMed1988

Influence of C4 null genes on infection with human immunodeficiency virus.

The hypothesis that complement is important in the host response to human immunodeficiency virus (HIV) was tested. Complement C4 and Bf allotypes were determined in 26 patients who fulfilled the diagnostic criteria for persistent generalised lymphadenopathy due to HIV, 72 homosexuals who were negative for antibody to HIV, and 185 control subjects drawn from the local population. HLA-A, B, and DR were also typed and the phenotypes examined for the presence of supratypes and C4BQ0. Eleven patients (42%) had C4B null alleles compared with only 13 (18%) homosexuals who were negative for antibody and 28 (15%) controls. From estimates of gene frequencies the difference between the patients with lymphadenopathy and the controls was significant after conservative correction. In the patients only a minority (six) of the C4B null alleles were contained within ancestral haplotypes. Together with the fact that C4 null alleles result in partial deficiency of C4, this finding suggests that products of complement genes are important in infection with HIV or its consequences, or both. A role is proposed for complement and Fc receptors.

Acquired Immunodeficiency Syndrome↗
PubMed1988

C4 allotyping on plasma or serum: application to routine laboratories.

Allotypes of the fourth component of complement (C4) can be detected by electrophoresis and immunofixation after treatment of EDTA plasma with neuraminidase (NAse). We have assessed the value of additional treatment with carboxypeptidase B (CPseB). Following treatment with CPseB + NAse, each allele is resolved into a single band, permitting clear definition of overlapping bands seen following treatment with NAse alone. More importantly, C4 allotypes can be determined using stored heparinized plasma or serum. Most C4 null alleles can be assigned without requiring family studies. The approach described is suitable for routine use by tissue typing laboratories.

Alleles↗
PubMed1988

Comparison and standardization of measurement of anti-acetylcholine receptor antibody between laboratories.

The presence of autoantibodies to the acetylcholine receptor (anti-AChR) is useful in the diagnosis of myasthenia gravis, and their titre correlates with severity of the disease. Standardization of their measurement is therefore clinically important. Six laboratories world-wide were asked to determine anti-AChR under local conditions in coded samples and to repeat the measurement on the same samples recorded. There was a high degree of consensus over rank order of the samples but a wide systematic variation in the titres obtained. Standardization of units is an important next step in improving the comparability of anti-AChR data between laboratories.

Autoantibodies↗
PubMed1986

The immunological detection of a 21-OH deficiency mutation HLA supratype.

Previous studies have shown that the late-onset and cryptic forms of 21-hydroxylase deficiency are highly associated with the HLA supratype HLA-B14,C4A2,C4B1/2,DR1. Since cells from a number of unrelated normal individuals from different ethnic backgrounds expressing the DR1 associated with this supratype failed to stimulate two different DR1-restricted T-cell clones that proliferated in the presence of most other DR1 cells, we decided to test the hypothesis that cells with this supratype express "abnormal" DR1 molecules that have been affected in some way by the chromosomal mutation responsible for B14,DR1-associated 21-hydroxylase deficiency (21-OH-defL). The results showed an association between "abnormal" DR1 and 21-OH-defL (elevated rates of 17 alpha-hydroxyprogesterone [17-OHP] increase and elevated peak 17-OHP values following ACTH stimulation). The presence of the B14,DR1 supratype can be used to predict the presence of "abnormal" DR1 and the clinical status of individuals not previously known to be 21-OH-defL carriers.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Family studies of IgA deficiency.

Seventeen immunoglobulin A (IgA)-deficient subjects and other members from 13 families were examined at HLA-A, B and DR, C4A, C4B, and Bf loci. Of the 29 independent haplotypes in the IgA-deficient subjects, 22 included deletions, duplications, or defects at the C4 or 21-hydroxylase loci. It is suggested that there may be a gene regulating serum IgA concentrations in this same region of chromosome 6. Three main supratypes explain most of the previously reported HLA associations with IgA deficiency. These are A1, Cw7, B8, C4AQ0, C4B1, BfS, DR3, Bw65(14), C4A2, C4B1/2, BfS, and Bw57(17), C4A6, C4B1, BfS. All three are proposed to carry a gene for IgA deficiency, while other supratypes carrying the same B allele generally do not. Other supratypes possibly associated with IgA deficiency were also identified. A survey of about 150 individuals with at least 1 of the 3 main supratypes revealed only 2 IgA-deficient subjects, and these were among the 20 that had 2 of these supratypes. This suggests the possibility of a recessive mode of inheritance, with penetrance determined by another factor which is not major histocompatibility complex-linked. All the supratypes found in this group of IgA-deficient subjects would then carry the putative recessive allele for IgA deficiency.

Alleles↗