Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The spontaneous autoimmune thyroiditis (SAT) which develops in the Obese strain (OS) of chickens depends on an intact B-dependent portion of immune system. T helper cells have been shown to be required for the production of thyroglobulin autoantibodies (Tg-AAb), but a possible contribution of cytotoxic T cells in the initial phases of SAT still remains to be elucidated. Cyclosporin A (CsA), an immunosuppressive drug with selective activity on T blast formation was used as a probe to clarify this issue: (a) the immunosuppressive potential of CsA was first verified for an avian species by demonstrating prolongation of skin allograft survival; (b) posthatching treatment of OS chickens with CsA until they were killed at 3 weeks of age did not alter the frequency and severity of SAT and the incidence and titer of Tg-AAb; (c) treatment of OS embryos on days 15, 17 and 19 of incubation entailed the development of significantly more severe disease and higher titers of Tg-AAb as compared to controls. A possible effect of CsA on precursors of suppressor T cells in the chicken is postulated. Cytotoxic T cells seem to play a minor role in the beginning of thyroid infiltration. It is concluded that CsA may not be the drug of choice for treatment of at least some autoimmune diseases.
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PMID:Effect of cyclosporin A on spontaneous autoimmune thyroiditis of Obese strain (OS) chickens. 675 38

Two lines of Obese strain (OS) chickens of identical MHC (B) genotype, B5B5, bred over 10 years with different selection parameters, differ in their severity of spontaneous autoimmune thyroiditis. To determine whether alterations in immune responsiveness underly this discrepancy, the two lines were compared for their thyroiditis effector mechanisms. The OS B5B5 chickens, selected for high levels of serum thyroglobulin autoantibody, had correspondingly higher levels of thyroid-specific cytotoxic cells and also antibody dependent cellular cytotoxicity (ADCC) than the equivalent B5B5 line selected solely for the phenotypic trait of hypothyroidism. These results thus emphasize the importance of the non-MHC locus controlling immune responsiveness, in the 3 locus-model for this autoimmune disorder.
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PMID:Genetically-controlled severity of autoimmune thyroiditis in Obese strains (OS) chickens is expressed at both the humoral and cellular effector mechanism levels. 688 5

A combination of neonatal thymectomy and intensive treatment with a highly specific turkey anti-chicken T cell serum effectively abrogates the spontaneous development of thyroiditis and thyroglobulin autoantibodies in the Obese strain chicken. Thus, in addition to a restraining influence of suppressor T cells on the disease process indicated by earlier studies, it would appear that T cells also make a positive contribution to pathogenesis.
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PMID:Requirement of T cells for the development of spontaneous autoimmune thyroiditis in obese strain (OS) chickens. 696 60

Different forms of cellular cytotoxicity that may constitute potential effector mechanisms in the spontaneous autoimmune thyroiditis (SAT) arising in Obese strain (OS) chickens have been investigated. A microcytotoxicity assay (MCA) employing 51Cr-labelled-, thyroglobulin (Tg) coated-chicken red blood cells (Tg-CRBC) was used to detect cells mediating Tg-specific direct cellular cytotoxicity (DCC). Tg-CRBC presensitized with anti-Tg autoantibody (Tg-AAB) obtained from high titer OS sera served as targets for antibody-dependent cell-mediated cytotoxicity (ADCC). Tannic acid-only treated CRBC (TA-CRBC) were used simultaneously as specificity controls for DCC and also as targets for cells eliciting spontaneous cellular cytotoxicity (SCC) to surface-modified normal cells. The results demonstrated that Tg-specific cytotoxic cells exist in the OS and thus represent an effector mechanism in SAT, in addition to the previously well-documented role of antibody. This DCC appears to be unrelated to the presence and titer of circulating Tg-AAb. It is present in highest levels in the peripheral blood of OS chickens, but in only 55% of the animals tested, indicating either a secondary importance to humoral immunity in the disease process or the possibility of different effector mechanisms prevailing in different birds. There were no overall differences in ADCC between OS and normal chickens when the two strains were considered as a whole. Chronological analysis, however, revealed very low ADCC in the peripheral blood of young OS birds, followed by a later elevation above that in the normal control chickens. Destruction of the gland by ADCC may be initiated via maternally-derived of in situ-produced anti-Tg antibody. No overall significant differences in SCC were observed between OS and normal chickens.
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PMID:Effector mechanisms in the spontaneous autoimmune thyroiditis of obese strain (OS) chickens: analysis of cytotoxic cells. 698 71

Neonatal thyroidectomy of Obese strain (OS) chickens showed that the spontaneous development of thyroid autoimmunity in these animals was fully dependent upon the presence of autoantigen, and could not be ascribed essentially to antigen-independent mechanisms such as polyclonal lymphocyte activation or innate distortions within the idiotype network. Similarly, removal of the gland in animals with established thyroiditis demonstrated the need for antigen to maintain the autoimmune response. Thyroglobulin from normal chickens induced autoantibodies in neonatally thyroidectomized OS birds, suggesting that an abnormality in the structure of this protein is not a prerequisite for the development of autoimmunity. This contention is supported by the finding that OS and normal thyroglobulin were immunochemically indistinguishable, whether compared using OS autoantibodies or rabbit anti-chicken thyroglobulin sera.
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PMID:The role of self-antigen in the development of autoimmunity in Obese strain chickens with spontaneous autoallergic thyroiditis. 706 70

Primary diseases of the thyroid gland, especially lymphocytic thyroiditis and idiopathic follicular atrophy, were the most common lesions associated with clinical hypothyroidism in pet dogs. Lymphocytic thyroiditis resembled naturally occurring lymphocytic thyroiditis in the Obese-strain of White Leghorn chickens and Hashimoto's thyroiditis in man. The morphology of the thyroid lesion and frequent occurrence of circulating thyroglobulin autoantibodies suggested that lymphocytic thyroiditis was immune-mediated in pet dogs. Thyroid lesions similar to naturally occurring autoimmune thyroiditis in experimental dogs were induced by a local thyroidal graft-versus-host reaction. The lesions observed in the thyroid lobe which was not injected with immunocompetent cells appeared to develop from the formation of thyroid antibodies in the gland by migrating host lymphocytes. Autoimmune lymphocytic thyroiditis occurred secondary to an unrelated immune response occurring in target tissue.
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PMID:Autoimmune lymphocytic thyroiditis in dogs. 710 21

Obese strain (OS) chickens develop spontaneous autoimmune thyroiditis (SAT) comparable in many aspects to human Hashimoto's thyroiditis. In a chronologic study on chickens of the Obese strain with B1B1 and B4B4 genotypes, immune and electron dense deposits suggesting immune complexes (IC) were found in the basal lamina of thyroid follicles (BLTF) as early as the time of hatching. The incidence of IC deposition in BLTF increased with age. In some of the chickens studied, thyroglobulin could also be demonstrated in the immune deposits. In addition, IC were also detected in the glomerular basement membrane of kidneys and in basement membranes of cecal tonsils. The early occurrence of IC in tissues of OS chickens suggests a possible primary role of these immune reactants in the pathogenesis of SAT.
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PMID:Immune complexes in tissues of obese strain (OS) chickens. 722 75

A 51chromium (51Cr)release microcytotoxicity assay has been established for studying cell-mediated immunity in chickens to a potentially wide variety of antigens. The system investigated in detail uses thyroglobulin-coated chicken red blood cells (Tg-CRBC) to analyse effector cell mechanisms operative in spontaneous autoimmune thyroiditis in Obese strain (OS) chickens. A variety of technical parameters were investigated in order to optimise reliable, reproducible target cell preparation and to minimise spontaneous 51Cr-release. The final method adopted used tannic acid for coupling antigen to carefully selected donor erythrocytes of uniform MHC genotype. For the study of antibody dependent, cell-mediated cytotoxicity, Tg-CRBC were pre-sensitised with OS serum containing high titre Tg-autoantibody. Tannic acid-treated CRBC (TA-CRBC) served simultaneously as controls for the Tg specificity of direct cellular cytotoxicity (DCC) to Tg-CRBC, and also as target cells for natural, or spontaneous cellular cytotoxicity (SCC). With such an assay, cells capable of mediating Tg-specific DCC were demonstrated in the OS, but not in normal chickens. No differences in ADCC or SCC were observed when the two strains were considered as a whole, i.e. regardless of age, sex, MHC genotype or extent of disease.
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PMID:Killer cells in the chicken: a microcytotoxicity assay using antigen-coated erythrocytes as targets. 740 May 85

Circulating antibody titers (1:20 to 1:2560) against thyroglobulin were demonstrated in 48% of pet dogs with hypothyroidism by the chromic chloride passive hemagglutination test. Four of six dogs with acanthosis nigricans (1:20) and one of six male dogs with hyperestrogenism (1:40) had low titers of antibody against thyroglobulin whereas clinically normal pet dogs and dogs with other selected endocrinopathies (hypoadrenocorticism, cortisol-excess, diabetes mellitus) or obesity were consistently negative. Circulating immune complexes evaluated by the mastocytoma cell-assay were present in the sera of 20% of pet dogs with hypothyroidism but were absent in clinically normal dogs. Although variations in dose significantly altered the quantitative response of the thyroid gland to thyrotropin the qualitative pattern of response was similar for T3 but not T4 in clinically normal laboratory beagles. The peak increases for serum triiodothyronine and thyroxine were observed either at eight (0.1 and 0.2 I.U bTSH/5 lbs) or 12 (1.0 I.U. bTYSH/5 lbs) hours postthyrotropin. Dogs with naturally occurring hypothyroidism had a decreased serum T3 and T4 at baseline and eight hours postthyrotropin (1.0 I.U. bTSH/5 lbs) compared to clinically normal pet dogs, laboratory beagles and dogs with other clinical endocrinopathies. The consistent lack of a significant increase of serum T3 and T4 in response to thyrotropin was necessary for the separation of certain hypothyroid from euthyroid pet dogs in which the baseline level of thyroid hormones were equivocal.
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PMID:Biochemical and immunological investigations on hypothyroidism in dogs. 740 88

The present study examines the role of thyroid cell injury in the initiation of autoimmune thyroiditis by iodine in Obese strain (OS) chickens, a strain genetically susceptible to spontaneous autoimmune thyroiditis. OS and normal strain chickens were placed on an iodine depletion regimen started in ovo. This regimen is known to prevent thyroiditis in OS chickens. The chickens were injected with NaI every 24 h for up to 7 days starting at 3 weeks of age. Both strains showed evidence of mild thyrocyte injury 12 h after NaI. However, significant and sustained infiltration, beginning 24 h after NaI, was seen only in the OS. The infiltrating cells were primarily mononuclear. Polymorphonuclear cells were not observed. Immunohistological analysis showed the infiltrate to be composed of CD8 T cells, CD4 T cells, B cells, and macrophages in the ratio 40:20:22:17. The infiltration was sustained and progressive for at least 7 days. Thyroid infiltration after NaI repletion was significantly reduced in OS chickens tolerized to thyroglobulin at hatching. Prior treatment with the antioxidant drug ethoxyquin completely prevented both the thyrocyte injury and the infiltration induced by iodine. Treatment with antioxidant drugs had no effect on the uptake and incorporation of iodine by the thyroid. In summary, 1) iodine caused thyrocyte injury in both OS and normal chickens. 2) The injury was followed by cellular infiltration in the OS but not in normal chickens. 3) The infiltration appeared to be immune mediated in being primarily lymphocytic and at least partially thyroglobulin sensitive. 4) Prevention of thyroid injury by antioxidant drug treatment also prevented infiltration. We conclude that thyroid cell injury may be an initial event in the induction of autoimmune thyroiditis by iodine.
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PMID:Thyroid cell injury is an initial event in the induction of autoimmune thyroiditis by iodine in obese strain chickens. 758 41


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