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Biomedical subjects

N R Farid

Publications and source records attributed to N R Farid.

At least 19 recordsLinked to original sources
PubMed1979

The association of HLA--B8 with atrophic thyroiditis.

One-hundred-and-forty-seven patients with autoimmune thyroiditis were studied with respect to HLA antigens as they related to various clinical features. HLA--B8 was found to be significantly increased among 59 patients with atrophic thyroiditis (57% vs. 26% for controls) but was identical to controls in 88 patients with goitrous thyroiditis (26%). No relation was found in either group between B8 and thyroid autoantibody titer or, in the case of goitrous thyroiditis, the rate of progression of the disease. Thus a link seems to be established between Graves' disease and atrophic thyroiditis in that both are significantly associated with HLA-B8. This study stresses the need to take clinical features into consideration when examining for HLA/disease associations.

Atrophy↗
PubMed1979

Polymorphic variants of the third component of complement in Graves' disease.

We have examined electrophoretic variants of the third complement component (C3) in 294 controls and in 44 patients suffering from Graves' disease, drawn from the Avalon Peninsula of Newfoundland. Two common C3 variants, S and F, account for 99% of the gene frequencies. The S homozygote phenotype was observed in 170 controls and in 27 patients; 18 controls were found to be homozygous for the F allele (3 patients), and the FS phenotype was observed in 103 controls and 14 patients. The phenotypic frequencies did not differ significantly between controls and patients. It is concluded that C3 variants do not distinguish individuals who have Graves' disease.

Adolescent↗
PubMed1979

A study of human leukocyte D locus related antigens in Graves' disease.

An association between Graves' disease and the human leukocyte antigen (HLA) system has previously been reported. The disease was more strongly associated with the HLA D locus antigen Dw3 than with HLA B8. Products of the HLA D locus are determined by the interaction of test cells with standard typing lymphocytes, a technically difficult procedure. Recently, it has been possible to type serologically for D locus related (DRw) specificities on peripheral bone marrow-derived (B) lymphocytes. Blood B lymphocytes from 50 unrelated controls and 41 patients with Graves' disease were typed for seven HLA DRw specificities. 28 patients with Graves' disease (68%) were positive for DRw3, in contrast to 14 controls (28%); whereas only 21 patients (50%) were HLA B8 positive, compared with 13 (26%) controls. Thus, positivity for DRw3 afforded a relative risk for Graves' disease of 5.5, whereas that for HLA B8 amounted to 3.0. Additionally, a family with multiple cases of Graves' disease in which the disease was previously shown to be inherited with the haplotype, was linked to DRw2, which suggests that the susceptibility to the disease was inherited in association with that antigen. Two HLA B/glyoxalase recombination events were observed in this family; in both instances HLA DRw followed HLA B. This study thus demonstrates that the disease susceptibility gene for Graves' disease is in strong linkage disequilibrium with DRw3; however, it may be associated with other DRw specificities and inherited within family units in association with them.

Alleles↗
PubMed1979

HLA-D--related (DRw) antigens in juvenile diabetes mellitus.

We studied the distribution of HLA-D--related (DRw) antigens in 40 patients with juvenile diabetes mellitus (JDM) and 79 matched controls. We found that DRw2 was significantly decreased in the JDM group, suggesting a protective effect of the antigen and that the decrease observed in B7 was secondary. HLA-DRw3 and HLA-DRw4 were increased in the diabetic group, and, as with B8/B15, these two antigen predisposed to the disease additively. The susceptibility for JDM was found to be more strongly related to HLA-DRw3 that to B8. On the other hand, B15 rather than DRw4 showed the stronger association with JDM. Moreover, we found that this second diabetogenic gene is associated primarily with B15 and only secondarily with Cw3, which is in linkage disequilibrium with B15. This study further emphasizes the immunogenetic heterogeneity of JDM.

Diabetes Mellitus, Type 1↗
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

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

Serum lipids in hypothyroidism--a re-evaluation.

One hundred and forty-two persons referred for assessment of thyroid function were studied in relation to their thyroid function and fasting serum lipids. Forty-five individuals, who had no family history of thyroid disease, were euthyroid, and were negative for thyroid antibodies formed the control group. The remaining 97 patients were fitted into six groups as follows--euthyroid Hashimoto's thyroiditis, thyroiditis with exagggerated TSH response to TRH, and four groups of increasing grades of thyroid failure based on the level of serum TSH. Only in the two most severely hypothyroid groups was cholesterol significantly elevated as compared with control levels. A graded increase in mean serum triglyceride, was observed as thyroid failure increased; however, values were not different (P greater than 0.05) from the control group. However, partial correlation analysis indicated that serum cholesterol was related to increasing levels of serum TSH and that this dependency was not influenced by age or weight. Although serum cholesterol was related to thyroid function in the study population, it was an insensitive indicator of the metabolic effects of thyroid hormone.

Cholesterol↗
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

Gm phenotypes in autoimmune thyroid disease.

The Gm phenotype Gm f,b or Gm f,n,b was found in all forty patients with Graves' disease studied, contrasted with thirty-five out of forty controls and twenty out of thirty-one patients with thyroiditis. The difference between the two groups with autoimmune thyroid disease was significant. These results suggest that thyroid stimulating antibodies may be allotypically restricted.

Alleles↗
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↗
PubMed1977

Assessment of a method for measuring serum thyroxine by radioimmunoassay, with use of polyethylene glycol precipitation.

We assessed the efficacy of a new thyroxine radioimmunoassay kit (Abott) in which polyethylene glycol is used to separate bound from free hormone. Mean serum thyroxine was 88 +/- 15 (+/-SD) microgram/liter for 96 normal persons. Results for hypothyroid and hyperthyroid persons were clearly separated from those for normal individuals. Women taking oral contraceptive preparations showed variable increases in their serum thyroxine values. The coefficient of variation ranged from 1 to 3% within assay and from 5.4 to 11% among different assays. Excellent parallelism was demonstrated between thyroxine values estimated by this method and those obtained either by competitive protein binding or by a separate radioimmunoassay for the hormone.

Adolescent↗
PubMed1976

Blood coagulation and fibrinolysis in thyroid disease.

Fibrinolytic activity and factor VIII concentration were studied in 30 patients with moderate to minimal hypothyroidism and in 7 patients with hyperthyroidism. In the hypothyroid group, the results were related to serum thyroxine levels, HL-A phenotypes and thyroid autoantibody titres. As serum thyroxine decreased so did factor VIII concentration, however, euglobulin lysis time was correspondingly prolonged. Factor VIII appears to be the most sensitive among coagulation factors to the deterioration of thyroid function tests. There was a significant correlation between the reciprocal of thyroid antibody titres and fibrinolysis; however, there was no relationship between factor VIII concentration or fibrinolysis and a specific HL-A phenotype although the incidence of HL-A8 was increased in the group as a whole. Euglobulin lysis time was prolonged in 6 out of 7 patients with Graves' hyperthyroidism. Factor VIII was elevated in only 3 of these patients.

Autoantibodies↗
PubMed1976

A population of human lymphocytes staining for esterases.

A population of lymphocytes is found to stain positively for esterases. The positively staining lymphocytes are more predominant among T than B lymphocytes and are significantly increased on stimulation with PHA. Treatment with cholinestrase inhibitors reduces their number significantly.

B-Lymphocytes↗