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 female sex develops autoimmune disease far more often than the male. This is claimed to be due to differences in peripheral sex steroid levels. We have examined in the bursa of Fabricius of Obese strain (OS) chickens, which spontaneously develop autoimmune thyroiditis, as well as in their healthy counterparts androgen(AR)-, estrogen(ER)-, progestin(PR)- and glucocorticoid(GR)-receptors in an attempt to elucidate possible further pathomechanisms, namely at the target site of steroid hormones. The characterization (affinity, specificity, association- and dissociation-rate, sedimentation behaviour) of all four types of receptors revealed no difference between sex or strain. Furthermore, the ontogeny study of the receptor capacity and affinity from the 7th embryonic day (i.e. before lymphocyte settlement) until bursa involution, again showed no difference between OS and healthy chickens of either sex. Thus, it can be concluded that the principal sex dependency of the susceptibility to autoimmune disease results predominantly from differences in sex steroid levels per se, although alterations in mechanisms beyond the cytosolic receptor level can presently not be excluded.
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PMID:Sex steroid and glucocorticoid receptors in the bursa of Fabricius of obese strain chickens spontaneously developing autoimmune thyroiditis. 375 1

Lymphocytes were isolated from the infiltrated thyroid glands of 2- to 5-wk-old Obese strain (OS) chickens with spontaneous autoimmune thyroiditis (SAT). Immunofluorescence analysis performed by using a panel of monoclonal and polyclonal antibodies revealed that 60% of thyroid infiltrating leukocytes (TIL) were mature T cells, a large portion of which seemed to be in an activated state bearing Ia-like antigens (10%) as well as a surface determinant associated with T cell activation (16%), i.e., possibly the receptor for interleukin 2 (IL 2). Furthermore, a relatively high plasma cell content (5%) was observed. TIL exhibited high proliferative responses to T cell mitogens (concanavalin A, phytohemagglutinin) and IL 2, but only weak responses to the B cell mitogen LPS from Salmonella typhimurium. When injected into newly hatched, MHC-identical, irradiated normal chickens, TIL induced both the production of autoantibodies and thyroid infiltration. Peripheral lymphocytes from spleen and blood and thymocytes from the same OS donors had no effect. Analysis of chemically (cyclophosphamide) bursectomized OS chickens suggested that an intact B cell system was not obligatory for the induction of SAT. TIL from these chickens consisted of 77% T cells and less than 1% B lymphocytes, yet were capable of inducing severe thyroid infiltration upon transfer into normal recipients. These findings emphasize the importance of the T cell system in the initiation of SAT.
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PMID:Analysis of lymphocytes infiltrating the thyroid gland of Obese strain chickens. 389 75

This report reveals a surprisingly high incidence of thyroid hormone (T3 and T4) autoantibodies (THA) and thyroglobulin autoantibodies in a closed flock of untreated Cornell strain (CS) White Leghorn chickens. This flock is closely related to the Obese strain chicken, which develops a severe spontaneous autoimmune thyroiditis. A sensitive electrophoretic autoradiographic assay for THA was developed. This assay was applied to the study of autoantibodies to T3 and T4 in the sera of adult female CS chickens. Of 109 females, 29.4% had antibodies to T3 and 18.4% had antibodies to T4. The incidence of thyroglobulin antibodies, determined by passive hemagglutination, was 15.6%. The presence of THA affected RIA measurements because serum T3 and T4 hormone concentrations appeared elevated in those birds with moderate to high antibody levels. There was major variance in the electrophoretic heterogeneity of the THA from individual chickens; i.e., some of the sera contained antibodies to T3 or T4 that appeared to be monoclonal, whereas other sera exhibited polyclonal multi-banded patterns. To determine if antibodies reactive with T3 and T4 (which are haptens) were generated by antibody responses to the T3/T4 sites on the thyroglobulin molecule, competitive binding assays were performed to determine the relative binding affinities of the antibodies for the haptens (T3/T4) and the "hapten-conjugate" (thyroglobulin). In these assays, thyroglobulin competed with the haptens, thus supporting the above hypothesis.
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PMID:Analysis of triiodothyronine and thyroxine-binding autoantibodies in chickens susceptible to autoimmune thyroiditis. 398 98

This essay uses the form of an imaginary debate between an immunologist and a non-immunologist to discuss the problem of immunological self-recognition and the clinical relevance of this phenomenon to the development of autoimmune disease. The first part deals with the communication between different cell types involved in normal and abnormal immune reactions. Then the problems of "physiological" autoimmunity and regulation of the normal immune response are discussed. The development of autoimmune diseases is reviewed on the basis of data obtained in the so-called Obese strain (OS) of chickens, which show a spontaneous hereditary autoimmune thyroiditis analogous to human Hashimoto thyroiditis. The role played by the thymus for the homeostasis of a normal immunological reactivity is emphasized. Finally, parallels are drawn between those mechanisms underlying the development of autoimmune disease and changes in the normal immune system with increasing age. The contribution finishes with some thoughts on the potential applications of our present knowledge of the process of auto-immunity to new therapeutic approaches to this large group of human diseases.
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PMID:[The self and its enemy]. 399 46

Obese strain chickens develop severe spontaneous autoimmune thyroiditis several weeks after hatching, characterized by mononuclear cell infiltration and antibodies to thyroglobulin (Tg). The presence of antibodies to Tg suggests that Tg is an important antigen in this disease, but it does not provide definitive evidence. To clarify this point, Obese strain chicks were tolerized at hatching with Tg and then examined up to 6 wk later for antibodies to Tg, thyroid pathology, and function. Various tolerance regimens were tested. The optimal conditions were i.v. injection of Tg within 24 hr of hatching, and injection of at least 1 mg. Tg isolated from normal thyroid glands was satisfactory, and it did not have to be deaggregated. Tolerance induced by the above procedure significantly retarded all parameters of autoimmunity, although by 6 wk of age some of the tolerized chicks had severe thyroiditis. Multiple weekly injections of Tg were no more effective than a single injection at hatching. Interestingly, a single injection at hatching was very effective, yet it was cleared from the circulation within 24 hr. In summary, tolerance induced with Tg had a profound effect on the disease and thus provides good evidence for the role of Tg in this disease.
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PMID:The induction of tolerance to thyroglobulin significantly reduces the severity of thyroiditis in obese strain chickens. 399 65

The effect of testosterone on organ-specific spontaneous autoimmune thyroiditis (SAT) was examined in two strains of chicken: the Obese (OS) strain, which develops SAT at several weeks of age and the control Special C (Sp. C) strain. Both were originally selected from the C strain and are homozygous for the B13 major histocompatibility haplotype. Testes development and testosterone levels in the OS strain were considerably less than those found in comparably aged birds of the Sp. C strain. Testosterone supplementation of the OS strain significantly decreased thyroid infiltration by lymphocytes while castration of the Sp. C strain significantly enhanced infiltration. These results suggest that testosterone reduces SAT and that the hormonal constitution in both strains of chicken affect the frequency of occurrence and severity of this disorder.
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PMID:Effects of testosterone on the development of autoimmune thyroiditis in two strains of chicken. 403 96

The effects of dietary thyroxine (T4) supplementation for specific periods on the early development of the primary lymphoid organs and spontaneous autoimmune thyroiditis (SAT) was examined in the Obese (OS) strain of chicken. Effects of the treatments on concentrations of serum growth hormone (GH) and testosterone were also determined. All treatment groups were examined at 6 weeks. T4 supplementation did not affect serum testosterone or GH concentrations. However T4 given for the first three weeks resulted in significantly increased bursa weights, no change in thymic weights, significantly decreased lymphoid infiltration of the thyroid and reduced thyroglobulin autoantibody levels (TgAAb). T4 supplementation for the full six weeks resulted in no change in bursal weight, significantly increased thymic weight, significantly decreased lymphoid infiltration of the thyroid, and reduced TgAAb. These results suggest that the effects of T4 supplementation on SAT and immune development are dependent on the interval during which it is administered and that testosterone and GH probably do not mediate these effects.
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PMID:Differential effects of thyroxine on immune development and autoimmune thyroiditis in the obese strain chicken. 404 83

In this study we investigated the genetic background of primary abnormalities found in the thyroid gland of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis (SAT), i.e., susceptibility to passively transferred antibodies to thyroglobulin (TgAb) and incomplete suppression of iodine uptake by thyroxine (T4). Several crosses between the B15/B15 subline of OS chickens and the inbred CB line (B12/B12) were done and the progeny was analyzed for thyroiditis after injection of OS serum containing high titers of TgAb. It was found that passive transfer of TgAb increased the lymphoid infiltration in the thyroids of OS chickens, but had no effect on CB birds. A genetic analysis of backcrosses revealed that this trait is, in the case of simple Mendelian inheritance, encoded by at least three recessive genes. The thyroidal 131I uptake of these crosses under T4 was also determined and we found that this trait is most probably encoded by only one recessive gene.
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PMID:Spontaneous autoimmune thyroiditis in obese strain chickens: a genetic analysis of target organ abnormalities. 405 27

A thymocyte-specific alloantigen, designated AT (avian thymus)-1.1, has been detected in Cornell C strain (CS) and Obese strain (OS) chickens, the latter being a strain derived from CS which develops a spontaneous form of autoimmune thyroiditis (SAT). Antisera specific for this antigen were developed first in a turkey immunized with thymocytes from an OS chicken and, later, in AT-1.1-negative CS chickens immunized with AT-1.1-positive thymocytes. AT-1.1 was detected in 50-70% of cells in a thymus cell suspension, but was not seen on peripheral blood lymphocytes, erythrocytes, or cells from bursa, spleen, kidney, liver, or brain. It was present on thymocytes of chickens at all ages tested, from 1 day to 6 months of age. AT-1.1 was not detected in six chicken lymphoid tumor cell lines tested, and birds expressing it were found to be negative for the presence of Marek's disease viral antigens. Pedigree studies on 287 (OS X CS)F2 chickens demonstrated that AT-1.1 is expressed in a dominant or codominant manner, and the gene coding for this antigen was not linked to the beta (major histocompatibility) complex. The genetics and tissue distributions of AT-1.1 indicate that it differs from thymus cell surface antigens, avian or mammalian, previously described.
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PMID:AT-1.1: a thymus-specific alloantigen of chickens. 614 92

This study demonstrates immune complexes in thyroid glands of Obese strain (OS) chickens, that consist of thyroglobulin (Tg) and antibodies to Tg. In IIF tests it was shown that these complexes fix complement with an age-dependent increase from 12% in 19-day-old embryos up to 100% in 6-week-old animals. This finding and the observation that the deposition of complement-binding immune complexes precede cellular infiltration of the thyroid gland and correlate with the serum titer of Tg-Ab (as one parameter of the disease) points towards a role as one initial effector mechanism for the development of spontaneous autoimmune thyroiditis (SAT).
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PMID:Immunofluorescence studies on the codistribution immune deposits and complement in the thyroid glands of Obese strain (OS) chickens. 622 80


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