Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The A subunit of the TSH receptor was prepared by reduction of human thyroid membranes with dithiothreitol, and partially purified by gel filtration. The ability of Graves' sera to inhibit TSH binding to the TSH receptor and to stimulate cyclic AMP release from isolated thyroid cells was abolished by incubation with crude and partially purified preparations of the A subunit.
Mol Cell Endocrinol 1985 Jul
PMID:The interaction between the TSH receptor and Graves' sera with TSH agonist or antagonist properties. 299 Oct 45

In studies on immunogenetic factors in autoimmune thyroid disease, the association among Graves' disease, Hashimoto's disease, HLA and Gm haplotypes was investigated in 37 families in which two or more first degree relatives had Graves' disease. The results showed that two genes linked to HLA and Gm appeared to control susceptibility to Graves' and Hashimoto's disease, respectively, and that the individuals who did not have immunogenetic factors were very unlikely to develop Graves' or Hashimoto's disease. In the second study, the role of HLA-DR antigen expression on thyrocytes was investigated in 18 patients with Graves' disease. It was found that DR-positive thyrocytes increased. DR-positive T-cells (from thyroids and peripheral blood) increased in Graves' disease. Interferon gamma increased DR expression on thyrocytes. The results indicated that these changes may cause a vicious circle to produce and perpetuate autoimmune processes in Graves' disease. Finally, the correlation between thyroids and immunoglobulins was investigated in 11 untreated patients with Graves' disease. Thyroid tissues obtained from untreated patients were incubated in organ culture systems with autologous as well as allogeneic immunoglobulins to observe the release of hormones. The release of hormone was stimulated only by autologous immunoglobulins and it is, therefore, postulated that the role of self-recognition, such as anti-idiotype antibody or anti-MHC antibody is crucial in the pathogenesis of Graves' disease.
Mol Biol Med 1986 Feb
PMID:The interaction of MHC and Gm in liability to autoimmune thyroid disease. 300 22

In a previous study we were able to separate, using cluster analysis, 196 patients with Graves' disease evaluated for a large number of clinical and laboratory characteristics, including HLA-A and HLA-B typing into one subset with recurring disease and a high prevalence of ophthalmopathy and another subset with mild disease and little ophthalmopathy. Prevalence of HLA-B8 was much higher in the first as compared to the second group. The present study was undertaken in 117 new patients with Graves' disease, typed for HLA-A, HLA-B, HLA-C and DR antigens and IgG heavy chain markers, to determine whether these characteristics could be used to segregate patients into clinically relevant subsets. There was a greater proportion of Gm fb homozygotes among patients than among controls (chi2 = 4.71, p less than 0.05) as well as individuals with HLA-B8 and DR3, previously documented for this disease. Two patient clusters were identified. In one (C1), there is a high incidence of exophthalmos, recurrence of hyperthyroidism after drug treatment, high titres of anti-thyroglobulin antibody, and an association with other autoimmune (including thyroid) diseases, a tendency for the disease to be familial and the presence of larger goitres. The incidence of HLA-B8 was greater in C1, while HLA-B12 was more frequent in the mild cluster, C2. HLA-DR3 was found to be associated with patients in the severe cluster and HLA-DR2 with patients in the mild cluster.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Biol Med 1986 Feb
PMID:Heterogeneity by cluster analysis techniques of Graves' patients typed for HLA DR and IgG heavy chain markers. 308 92

Highly purified preparations of steroid-inducible cytochromes P-450 have been isolated from liver microsomes of adult male Sprague-Dawley rats treated with pregnenolone-16 alpha-carbonitrile (PCN), phenobarbital (PB), or triacetyloleandomycin (TAO). The interrelationships among these preparations as well as their relationship to the major forms of cytochrome P-450 of this gene family identified in other laboratories have been evaluated by amino-terminal sequence analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, chromatography on DEAE-Sephacel, and Ouchterlony double-immunodiffusion. The results indicate that a cytochrome P-450 previously isolated in this laboratory and referred to as PCNa (P.E. Graves, L.S. Kaminsky, and J. Halpert (1987) Biochemistry 26, 3887-3894) is the major cytochrome P-450 induced in rats by TAO, and corresponds to P-450p (K.A. Hostetler, S.A. Wrighton, P. Kremers, and P.S. Guzelian (1987) Biochem. J. 245, 27-33) and to P450PCN1 (F.J. Gonzalez, B.J. Song, and J.P. Hardwick (1986) Mol. Cell. Biol. 6, 2969-2976). A second previously isolated cytochrome P-450 termed PCNb in this laboratory appears to be identical to PB/PCN-E (F.P. Guengerich, G.A. Dannan, S.T. Wright, M.V. Martin, and L.S. Kaminsky (1982) Biochemistry 21, 6019-6030). PCNb as well as a third cytochrome P-450 termed PCNc isolated from PB-treated rats both correspond in amino-terminal sequence to the putative protein product of the pP450PCN2/cDNA clone of Gonzalez et al. These results document at the protein level the multiplicity of steroid-inducible rat liver cytochromes P-450.
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PMID:Multiplicity of steroid-inducible cytochromes P-450 in rat liver microsomes. 313 Aug 3

Five overlapping cDNA clones representing the entire mRNA for human thyroid peroxidase (TPO) have been isolated from a human Graves' thyroid cDNA library. The cDNA sequence has been determined. Human TPO cDNA contains 3060 bases from the start of transcription to the beginning of the poly (A) tail at the 3'-end. The derived amino acid sequence of human TPO consists of 933 amino acids with a mol wt of 102,937. The derived amino acid sequence contains five potential glycosylation sites (Asn-X-Ser/Thr), a probable transmembrane signal peptide sequence at the amino terminus, and a hydrophobic putative membrane-spanning region beginning 85 amino acid residues from the carboxyl terminal end. Comparison of the human TPO amino acid sequence to that of pig TPO shows strong homology extending from the amino terminus to within 44 amino acid residues of the carboxyl-terminus.
Mol Endocrinol 1987 Nov
PMID:Molecular cloning of the complementary deoxyribonucleic acid for human thyroid peroxidase. 315 66

By typing a large quantity of family-based material for HLA-B, HLA-DR, C4, C2 and factor B, we were able to derive four-gene complement haplotypes (C4A, C4B, C2, BF) and six-gene MHC haplotypes (HLA-B, complement, HLA-DR). Fourteen six-gene MHC haplotypes showed linkage disequilibrium but exact frequencies could not be determined because it was not always possible to assign null C4 alleles in families where null genes were not clearly seen to segregate. Comparison of unrelated type I diabetes, Graves' disease and Hashimoto's thyroiditis patients with healthy unrelated controls revealed the following MHC allele associations: C4B*3, HLA-DR3 and HLA-DR4 with type I diabetes; BF*F1 and HLA-DR3 with Graves' disease; HLA-DR4 with Hashimoto's thyroiditis. By typing families of type I diabetes and Graves' disease patients we were able to derive two high-risk DR3+ MHC haplotypes for both type I diabetes and Graves' disease. These are HLA-B8 C4A*Q0 C4B*1 BF*S HLA-DR3 and HLA-B18 C4A*3 C4B*Q0 BF*F1 HLA-DR3, and these haplotypes account for most of the associations between these diseases and HLA-DR3. The MHC haplotype HLA-B15 C4A*3 C4B*3 BF*S HLA-DR4 also carries high risk for type I diabetes in this group of patients. Our data suggest that other DR4+ haplotypes, probably containing C4A*3 C4B*1, carry increased risk for type I diabetes whereas haplotypes containing DR4 and C4 C4A*3 C4B*Q0 do not. Our phenotype data suggest that DR4 in Hashimoto's thyroiditis is frequently associated with HLA-B44, C4A*3, C4B*1 and BF*S.
Mol Biol Med 1986 Apr
PMID:Class III alleles and high-risk MHC haplotypes in type I diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. 346 Dec 34

Recent epidemiological studies in Japan and Sweden have disclosed a high prevalence of transient thyroid dysfunction in women following delivery. These changes seem to reflect an immunoregulatory "rebound" following pregnancy-induced immunosuppression. Thyroid microsomal antibody titers characteristically decrease during pregnancy and increase again after delivery to maximum levels around six months postpartum. At this time some microsomal antibody-positive women develop goitrous hypothyroidism. Subsequently, the microsomal antibody titers fall, reaching the early pregnancy values one year postpartum by which time hypothyroidism subsides. The severity of hypothyroidism is closely related to the titer of microsomal antibody, especially the immunoglobulin G1 subclass of microsomal antibody, and partly predictable from the titer in early pregnancy. The HLA-DR4 antigen was observed in 58% of microsomal antibody-positive Swedish women as compared to 33.7% in the general population (relative risk = 2.71). This association was even stronger in microsomal antibody-positive women who developed postpartum hypothyroidism (69%; relative risk = 4.36). Finally, postpartum thyrotoxicosis with a high radioiodine uptake may occur in women with latent Graves' disease. In these cases changes of TSH-receptor-stimulating antibodies analogous to microsomal antibodies seem to occur.
Mol Biol Med 1986 Apr
PMID:Postpartum thyroid disease. 346 Dec 36

Graves' disease is associated with HLA-DR3 in Caucasoids. We have now demonstrated, on the basis of disease-associated MHC haplotypes (A1, Cw3, B8, DR3 and fragments thereof) from 38 families in which more than one member had Graves' disease compared with MHC haplotypes from 56 healthy families, that the risk was highest with the DR locus (relative risk for A1, B8, DR3 = 2.3, for B8, DR3 = 5.3, and for DR3 = 6.8). We further used the sib-pair method to explore linkage of Graves' disease liability to the MHC in 67 affected sib-pairs. The data were consistent with an MHC-linked recessive gene with a frequency of 0.2 to 0.3 and a penetrance of 7.2%; the data, however, accommodated penetrance of up to 16.3%. A recessive model was also consistent with the HLA-B8 genotype distribution in 286 unrelated patients. As the effect of the marker alleles on the course of the disease had been debated several times, we applied a cluster analysis method using 49 clinical and laboratory characteristics, including the HLA-A and HLA-B antigens of 196 patients. Three groups were identified, corresponding to patients with mild disease, Hashitoxicosis and severe (relapsing) disease. The prevalence of HLA-B8 was 8.9%, 21% and 87%, respectively (compared to 18.8% in 380 controls). This suggests the existence of an underlying continuum of genetic liability, apparently related to that for Graves' disease severity, associated with the MHC and mediated through immunoregulatory disturbances.
Mol Biol Med 1986 Feb
PMID:The role of HLA antigens in the manifestation and course of Graves' disease. 348 58

We typed patient groups with type I diabetes (n = 78), Graves' disease (n = 81), goitrous autoimmune (n = 52), "silent" (n = 18) and postpartum thyroiditis (n = 15) for human leucocyte antigens (HLA) A, B, C, DR and DQ. The results were compared to those obtained from 256 healthy controls typed for HLA-A, -B, -C and 140 typed for -DR. All these 140 controls were genotyped. Previously described associations of DR3 (OR (odds ratio) = 2.68, p less than 0.005) and DR4 (OR = 3.26, p less than 0.0001) in type I diabetes is confirmed. In this series, however, HLA-DR3/DR4 heterozygotes were apparently at no greater risk for type I diabetes than DR3 or DR4 homozygotes. The relative risk conferred by DR3/DR4 heterozygotes (6.48) was less than that for DR3 homozygosity (2.8), suggesting a recessive major histocompatibility complex-related susceptibility to type I diabetes. Graves' disease was associated with DR3 (OR = 3.02, p less than 0.0005); the increased frequency of DR3 homozygotes in this series is consistent with recessive HLA-linked susceptibility to Graves' disease proposed on the basis of family data. Hashimoto's thyroiditis, on the other hand, was associated with HLA-DR4 (OR = 3.08, p less than 0.0001), the latter finding confirming our earlier report on 21 patients. The increase of HLA-DR4 in both post-partum and silent thyroiditis suggests that these conditions are immunogenetically related, and may well represent variants of chronic autoimmune thyroiditis.
Mol Biol Med 1986 Feb
PMID:HLA and autoimmune endocrine disease 1985. 348 59

Autoantibodies in sera from newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients recognize a 64,000 Mr human islet cell antigen. The incidence of these antibodies was 86% in 28 insulin-dependent diabetes mellitus patients, 100% in seven first-degree relatives with abnormal glucose tolerance, 6% in 34 healthy individuals, 17% in 29 patients with Hashimoto's or Graves' disease, and 0% in five systemic lupus erythematosis patients. It is suggested that the 64,000 Mr human islet cell protein is the major target antigen of islet cell autoantibodies in insulin-dependent diabetes mellitus.
Mol Biol Med 1986 Apr
PMID:Immunoreactivity to a 64,000 Mr human islet cell antigen in sera from insulin-dependent diabetes mellitus patients and individuals with abnormal glucose tolerance. 352 81


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