Search PubMed⌕ Search

Biomedical subjects

J M Barnard

Publications and source records attributed to J M Barnard.

34 records · Page 2Linked to original sources
PubMed1978

The HLA B w4/w6 diallelic system in Graves' disease.

We studied the diallelic system HLA--Bw4/w6 in patients with Graves' disease and control subjects. Twenty-one out of the 22 patients with Graves' disease were found to be HLA--Bw6 positive and 16 of these were homozygous, contrasted with 28 and 9 out of 34 controls, respectively. HLA--Bw6 positivity results in a relative risk for Graves' disease of 3.27; homozygosity for that allele further increases the risk to 7.4. It is possible that the increased risk attached to HLA--Bw6 is secondary to the increase in HLA--B8 previously described in Graves' disease.

Alleles↗
PubMed1978

Tuberculosis associated with HLA--B8, BfS in a Newfoundland community study.

In three adjacent Newfoundland communities comprising some 1500 people, 589 people have been HLA typed. Forty-six of the typed people gave a history of previous clinical tuberculosis which required treatment. Fifty-six percent of the TB patients carried HLA B8 compared with 20% of the remainder of the population. This is a highly significant difference (P less than 0.01). In each community the frequency of B8 as an epidemiological marker correlated with the incidence of tuberculosis. B8 is associated with TB in ths study with a relative risk of 5.2 which compares with combined relative risks in the literature for coeliac disease and Addison's disease of 9.5 and 6.4, respectively, and which is greater than the risks for all the other B8-related diseases. The factor B allele, Bf S, was found on all the B8 haplotypes, but the overall Bf gene frequencies in tuberculosis patients did not deviate from expected values.

Cytotoxicity Tests, Immunologic↗
PubMed1978

The operation of immunological networks in Graves' disease.

Association between Graves' disease and HLA--B8 has been previously documented, as have been associations between 1 gG heavy chain allotype markers (Gm). We found a significant increase in the phenotype fnb/fb (ie. positivity for fb) in patients with Graves' disease compared to controls, raising the possibility of allotypic restriction of thyroid stimulating antibodies thought to be causally related to the disease. The influence of fb on the susceptibility to Graves' disease was found to be independent of HLA--B8 status suggesting that the immunological network operated by the Histocompatibility-linked genes is independent of that centered around IgG allotypes. It is postulated that, whereas the former genes determine the level of helper T lymphocyte function in the production of thyroid stimulating antibodies in Graves' disease, a person who also happens to carry the Gm marker fb would be assured of the production of IgG antibodies with thyroid stimulatory activity.

Adult↗
PubMed1978

The association of HLA with juvenile diabetes mellitus in Newfoundland.

In view of the reported variation in the association between HLA antigens and Juvenile Diabetes Mellitus (J.D.M.) among different Caucasian populations, we have undertaken a study of these antigens among 44 Caucasian Newfoundlanders and 135 matched controls. We have also studied the allotypic markers for Immunoglobulin G (Gm) and variants of C3 among 36 of these patients. We found that both HLA--B8 and B15 were increased among the patient group, resulting in a relative risk of 3.9 and 4.4 respectively. While these values are the highest to be described for J.D.M. among Caucasians, and fell outside the 95% confidence intervals for the combined relative risk calculated from published series, it is still possible that they can be accounted for by sampling. The combination of the two antigens increased the relative risk for J.D.M. in an additive fashion. Additionally, we also found that the combination of HLA B8 and B18, but not B15 and B18, also appear to act in an additive manner. The incidence of Gm allotypes and variants of C3 were not different in the J.D.M. group from those observed among controls.

Adolescent↗
PubMed1978

HLA/Bf haplotypes in a Newfoundland family.

HLA/Bf haplotypes were examined in a large three-generation Newfoundland family with a high incidence of Graves' disease. In that family Graves' disease was inherited in association with the haplotype HLA Aw24, Bw39 in some instances and with HLA B8-containing haplotypes in other instances. As all seven members of the family who suffered from Graves' disease were homozygous for the Bf S allele, the study for Bf was uninformative. However, the examination of other HLA/Bf haplotypes disclosed some interesting associations. One-hundred-and-five out of 168 HLA-A, -B, -Bf haplotypes were Bf S. Although numerically deviant, no unusual HLA B/Bf associations were observed. Bf F entered the family only once. A new finding is the association between HLA B27 and Bf S1; the haplotype entered the family once and was passed on to eight family members over three generations. Bf S1 was previously reported in association with HLA B12 or W21. None of these family members had ankylosing spondylitis. The Bf allele F1 entered the family three times, always in association with HLA B18.

Alleles↗
PubMed1977

HLA in familial Hodgkin's disease. Results and a new hypothesis;.

A familial aggregate of seven cases of Hodgkin's disease (HD) has been investigated by HLA typing. Over 600 people in the immediate population (i.e. about half) have been HLA typed and haplotypes have been obtained for 95% of them. It was expected that the cases would share a particular HLA haplotype or at least that they would have one or two HLA antigens of the same series in common. However, this was not the case so no simple idea of association of HLA with HD cases was upheld. When antigen frequencies were examined in the whole population, it was found that HLA B18 increased progressively in incidence from 0.08 to 0.4 in successive groups of individuals each one more closely related to the HD cases. Similarly the community with the highest incidence of HD also had the highest incidence of B18. Thus B18, which in the world figures carries the highest relative risk, emerged as important in this study. Of four proposed interpretations of the data, we are most interested in the idea that the important HLA association is at a population level rather than at the level of the individual patient. A hypothesis, based on the concept of a "healthy carrier" for the HD agent, explains how such an association might operate. It is possible that B18-linked complement deficiency could be the basis for such a carrier state.

Antigens, Neoplasm↗
PubMed1977

Bf types of HLA haplotyped individuals in an isolated Newfoundland population.

Five hundred and fourteen individuals from an isolated NewFoundland population have been typed and haplotyped for HLA and Factor B (Bf locus). The Bf gene frequencies were: S0.704, F0.226, F1 0.052 and S1 0.018. Tracing the haplotypes backwards on the various pedigrees it was shown that 202 HLA/Bf haplotypes had been introduced into the study population. Some HLA alleles always appeared in association with particular Bf alleles and vice versa. Bf S1 had entered the population four times, always with HLA--A9, B12. Bf F1 had entered three times, always with HLA--B18. There were 17 entries of HLA--Al, B8 that had given rise to the 78 such haplotypes that were now present in the population; all were Bf S. There were 68 family units informative for Bf. They accounted for 240 children and 304 informative meioses. There were three recombinants in the HLA region but none could be shown to have occurred between the HLA-B and Bf loci.

Adult↗
PubMed1977

Thyroid autoimmune disease in a large Newfoundland family: the influence of HLA.

Ninety-eight members of a large Newfoundland family, seven of whose members over three generations suffered from Graves' disease, were studied with respect to the mode of transmission of the disease and its association with HLA. Compared to Newfoundland communities of similar size and geographical location, very little consanguinity was documented in this family. The susceptibility to Graves' disease appeared to be inherited as a dominant with a variable degree of expressivity; the degree of expressivity being determined by the female sex. In part of the pedigree, the susceptibility to Graves' disease entered the family with a wife. Three of her offspring who subsequently developed Graves' disease shared with her the haplotype A9, Bw16. Of the three remaining affected family members, two shared the haplotype A1, B8, whereas the third carried the haplotypes Aw32,b8; a9,bw16. Graves' disease could be associated with either of these two haplotypes in the last individual. This study shows that the susceptibility to Graves' disease is inherited associated with HLA and that whereas the disease susceptibility gene for Graves' disease is in linkage disequilibrium with HLA-B8 in Caucasians, it can be randomly associated with other HLA-B antigens.

Female↗
PubMed1976

The association of HLA with autoimmune thyroid disease in Newfoundland. The influence of HLA homozygosity in Graves' disease.

Forty-seven patients with Graves' disease, 73 with thyroiditis and 128 controls drawn from the same geographical area of Newfoundland were HLA typed. The frequency of HLA-B8 was significantly increased in the Graves' disease patients when compared to the control group giving a relative risk of 3.9. There were no significant HLA differences between the thyroiditis and control groups. Homozygosity for the HLA haplotype, which is common in this island population, was more common in Graves' disease patients (12.8%) than in controls (5.5%) but did not reach statistical significance in this sample. Homozygosity was due in five of the six cases to either an A1;B8 haplotype or an A2;B8 haplotype. This contrasted with an apparently random assortment of haplotypes in the control and thyroiditis groups. Calculations suggest that homozygosity for a B8 haplotype confers an additional risk over heterozygosity for B8 of about 3.5 fold; however, homozygosity had no observable influence on the severity of the disease. These results strengthen the idea that B8, or an allele in linkage disequilibrium with it, determines in part the susceptibility of an individual to developing Graves' disease.

Gene Frequency↗
PubMed1976

HLA haplotypes in a genetic isolate in Newfoundland. A population showing 8% homozygosity and a familial aggregate of lymphoma and immunodeficiency cases.

HLA typing was performed on 384 individuals of an isolated population of 1,500 people with a familial aggregate of lymphoma and immunodeficiency cases. Eighty-five % of the total population were descendants of the founding couple. First cousin marriages were common. There was a three-fold or higher increase of the following haplotypes as compared to the frequencies in Sheffield: HLA-A28,Bw35, HLA-A28, B18, HLA-A10, B18, HLA-A2, B18,HLA-A11, Bw40 and HLA-A11, B7. The frequency of HLA-A1, B8 was low (5.4%). The most common genotype was HLA-A2, B12/A2, B12 followed by HLA-A2, B12/A28, Bw35. We found 20 HLA homozygous individuals, of these 15 were HLA-A2, b12/a2, b12. There were two possible HLA cross-overs which may be confirmed and three postulated cross-overs which can never be confirmed as one or both parents of the individuals in question are deceased. Some of the haplotypes could be traced back to the first, second and third generations, i.e. to the first half of the nineteenth century. No single haplotype or antigen was shared by the patients.

Consanguinity↗
PubMedDate not supplied

Use of Markush structure analysis techniques for descriptor generation and clustering of large combinatorial libraries.

This article outlines a system in which a Markush structure representation is used for analysis of a combinatorial library, giving savings in terms of storage and processing requirements when compared with an enumerated library. The Markush representation used is described, along with the way in which it can be built from a reaction- and precursor-based description of a library. The process used to generate SMILES, and structure fingerprint and calculated property descriptors for each specific molecule in the library is discussed. Comparative performance figures are given for the Markush approach and various standard fingerprint generation programs based on the enumerated members of the library; the former shows time savings of a couple of orders of magnitude. The use of these rapidly generated fingerprints for clustering of large combinatorial libraries is described.

Cluster Analysis↗