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 thyroid glands of four patients with Graves' disease and five patients with Hashimoto's thyroiditis were investigated to demonstrate in vivo immune complex deposition. By electron microscopy, electron-dense deposits were observed in the follicular basal lamina--basement membrane--(FBL) often associated with lymphocytic and plasma cell infiltration. A positive correlation was obtained with all cases by immunofluorescent studies using anti-IgG, IgA, IgM, C3 and antithyroglobulin conjugated serums. The staining was of a granular pattern and coincided to the FBL region. No discrepancies were noted in electron microscopic and immunofluorescent observations between patients with Graves' disease and Hashimoto's thyroiditis, and the occasional observation of immune complexes in areas devoid of infiltrate in some patients with Graves' disease. Morphologically, the deposits were found to be similar to those described in the Obese Strain chickens with spontaneous autoimmune thyroiditis.
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PMID:Immune complex deposits in Graves' disease and Hashimoto's thyroiditis. 33 99

The Obese strain (OS) of White Leghorn chickens develops a spontaneous autoimmune thyroiditis with circulating thyroglobulin-autoantibodies (Tg-AAb) similar to human Hashimoto thyroiditis. The paper describes attempts to localize the site of Tg-AAb production in various organs of these animals using the immunofluorescence method. Tg-AAb producing plasma cells and germinal centers could be detected in the infiltrated thyroid glands but not in spleen, bone marrow, coecal tonsils, thymus, bursa of Fabricius and Harderian glands.
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PMID:Immunofluorescent localization of thyroglobulin--autoantibody producing cells in various organs of obese strain (OS) chickens. 56 3

Interleukin 2 (IL-2) is a lymphokine that may disrupt immunological self-tolerance. While being incapable of interfering with intrathymic or peripheral clonal deletion, IL-2 may overcome functional antigen unresponsiveness in anergic T lymphocytes. Anergy of T helper cells of the inflammatory phenotype implies selective silencing of the transcription of the IL-2 gene and thus precludes autocrine IL-2/IL-2 receptor (IL-2R) mediated growth, as well as delivery of help to other T cells or B lymphocytes. Thus, IL-2 serves as a servomodulator regulating post-deletional self-tolerance. IL-2-producing and IL-2-receptive cells are present in a variety of autoimmune lesions, including spontaneous autoimmune thyroiditis developing in the Obese strain (OS) of chickens, in Hashimoto's struma lymphomatosa, and in Graves' disease. Whereas the OS is characterized by a hyperinducibility of the IL-2/IL-2R system that predisposes to the development of severe thyroid infiltration, the state of the IL-2/IL-R system in circulating lymphocytes of patients developing thyroid autoimmunity, or at risk of doing so, remains to be defined. The most frequent autoimmune side-effect of IL-2 treatment concerns the thyroid gland. IL-2 induces a lymphoid thyroiditis leading to primary hypothyroidism, especially in those patients that have pre-treatment antithyroid autoantibodies. The hypothesis is extrapolated that IL-2 induces autoimmune disease in those patients that bear undeleted thyroid-specific T cells, and in which the lack of manifest thyroiditis relies upon peripheral, post-deletional tolerance.
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PMID:The role of interleukin 2 in the development of autoimmune thyroiditis. 148 52

In both mammals and chickens, immunization with exogenous antigens results in a surge of serum glucocorticoid hormone levels concomitant with the antibody response. This effect is mediated by glucocorticoid-increasing factors (GIF) produced by cells of the immune system. In the avian system, GIF appear to act via the hypothalamo-pituitary axis and not directly on the adrenal gland. Interleukin 1 is the main active substance responsible for GIF activity, as shown by molecular sieve and immunoaffinity chromatography studies. In contrast to data from mammals, we found no evidence that interleukin 2 elevates chicken corticosterone. Obese strain chickens with spontaneous Hashimoto-like autoimmune thyroiditis are deficient in their in vivo GIF response. Because no differences were found between autoimmune and healthy chickens in the corticosterone response of the adrenal gland after ACTH administration, and since autoimmune animals are able to react normally to immobilization stress, it is assumed that this deficiency is due to a specific defect rather than a general disturbance in the endocrine system.
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PMID:Analysis of the immune-encodrine feedback loop in the avian system and its alteration in chickens with spontaneous autoimmune thyroiditis. 224 53

A management programme is described for a small colony of Obese strain (OS) chickens afflicted with spontaneous hereditary thyroiditis. Animals of this White Leghorn line are used as an animal model for Hashimoto's thyroiditis of man to study possible mechanisms of autoimmunity in general and organ-specific autoimmune diseases in particular. Due to the severe mononuclear cell infiltration of the thyroid glands, OS chickens show symptoms of hypothyroidism, including small body size, subcutaneous and abdominal fat deposits, long silky feathers, small combs and wattles, cold sensitivity, low fertility and poor hatchability. Successful breeding of this line, especially in a small population, can therefore be done only if rigid precautions are taken in aspects of animal care. The selection of breeding stock, the principal requirements for adequate housing and food, the artificial insemination procedure, and recommendations for collecting and incubating chicken eggs are reported in detail. Precautions necessary during the incubation of fertilized eggs, and fertility and hatchability are reported. During the hatching period several specific features must be considered. The important role of staff involved in a small chicken breeding unit is emphasized.
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PMID:Housing, breeding and selecting chickens of the Obese strain (OS) with spontaneous autoimmune thyroiditis. 281 Dec 74

Chickens of the Obese strain (OS) develop a hereditary spontaneous autoimmune thyroiditis (SAT) which closely resembles human Hashimoto's disease. Analysis of the endogenous viruses harboured by these animals revealed a new endogenous virus (ev22) detected as a 5.5 kb Sac I fragment. Crossbreeding experiments showed that ev22 is vertically transmitted as an autosomal trait not associated with major histocompatibility (MHC) alleles. Preliminary experiments indicate that ev22 does not necessarily cause SAT, however, it may have a modulatory role in the development of the disease.
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PMID:ev 22, a new endogenous avian leukosis virus locus found in chickens with spontaneous autoimmune thyroiditis. 284 Aug 75

The Obese strain (OS) of chickens, which is afflicted with Hashimoto-like spontaneous autoimmune thyroiditis (SAT), displays elevated T cell proliferation, interleukin (IL)2 production and IL2 receptor expression upon mitogen stimulation, and defects in the neuroendocrine control of the immune system including elevated corticosteroid-binding globulin (CBG) and a deficient increase of serum corticosterone (CN) upon cytokine injection. Recently this strain has further been shown to harbor retrovirus-related sequences (endogenous virus no. 22, ev22) absent in healthy control strains. To determine the number of genes responsible for SAT-associated immunodysregulation and to unravel possible ev22 associations, we analyzed the above immune and endocrine parameters in F1 hybrids and backcrosses of the autoimmune OS B15B15 with healthy inbred CB B12B12 chickens. OS-like T cell hyperproliferation and IL2 hypersecretion in response to both concanavalin A and phytohemagglutinin were transmitted as autosomal dominant traits and co-segregated in backcross animals. In vivo hyporesponse of the OS to the corticosterone-inducing effect of cytokine preparations was inherited dominantly and the elevated CBG serum levels recessively. None of these traits appeared to be major histocompatibility complex (MHC) linked. However, while T cell abnormalities and elevated CBG serum levels were not associated with the autosomal ev22 locus, in vivo hyporesponsiveness to glucocortocoid-inducing cytokines co-segregated with this OS-specific provirus. These results add to the concept of SAT as a polyetiological and plurigenetic disease and do not support our previous hypothesis that T cell hyperreactivity and immunoendocrine dysfunction might be functionally related.
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PMID:Genetic analysis of extrathyroidal features of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis. 305 29

Development of organ-specific autoimmune diseases depends on both an abnormal immune regulation and a genetically determined primary susceptibility of the target organ to the autoimmune attack. In addition to the essential genetically determined prerequisites there are also facultative, modulating factors that influence the outcome of an autoimmune disease. This concept is exemplified in the Obese strain (OS) chicken model which develops a spontaneous autoimmune thyroiditis closely resembling human Hashimoto disease. Three modulating factors are specifically addressed, viz. (a) the lower threshold of OS thyroid epithelial cells for the gamma-interferon-induced MHC class II antigen expression as compared to normal controls, (b) the decreased glucocorticoid tonus of the OS and (c) the presence of a new endogenous virus (ev 22) locus in the OS that has so far not been found in any normal strain and which seems to influence the glucocorticoid-mediated immunoregulatory process.
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PMID:The multi-factorial pathogenesis of autoimmune disease. 312 34

Various degrees of persistent or paroxysmal paresis involving only the hindlimbs or all four limbs were observed in 3 dogs with hypothyroidism and lymphocytic thyroiditis. Clinical features included lethargy, obesity, alopecia, insidious and progressive paresis, hypotonia, and slow segmental reflexes in 2 dogs. Obesity, alopecia, paroxysmal paresis, and behavior change were observed in the third dog. Laboratory tests indicated that thyroid function was less than normal in all 3 dogs. Abnormal electromyographic potentials and slow motor nerve conduction velocities were found in each dog. Muscle biopsy specimen abnormalities included selective type-II myofiber atrophy in all dogs, whereas one dog had angular atrophy of type-I and type-II myofibers indicative of denervation. A substance that stained with para-aminosalicylic acid was observed within vacuoles of type-I myofibers in one dog. Lymphocytic thyroiditis characterized by lymphocytic infiltration of excised thyroid glands was observed in all dogs.
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PMID:Neuromuscular abnormalities associated with hypothyroidism and lymphocytic thyroiditis in three dogs. 355 92

Antigenic challenge as well as injection of lymphokine-containing media lead to a transient increase of serum glucocorticoids, a phenomenon that has been implicated in the regulation of the specificity of immune responses. In the present study we examined the dialogue between the immune and the neuroendocrine systems in Obese strain (OS) chickens, an animal model for human Hashimoto thyroiditis. The following results were obtained: A) OS and normal White Leghorn (NWL) chickens, 5-mo-old, were immunized with sheep red blood cells followed by daily monitoring of corticosterone (CN) serum levels. Whereas in NWL animals CN serum levels markedly increase 3 to 4 days after immunization, OS animals did not respond with CN elevation. B) A single i.v. injection of conditioned medium (CM) from concanavalin A-stimulated spleen cells also led to a transient, dose-dependent peak in plasma CN (maximum after 30 min). This CN response to a given CM preparation was significantly lower in OS than in NWL animals. C) CM, whether obtained from OS or NWL splenocytes, were equally effective to stimulate CN production. D) A single i.v. injection of CM leads--concomitantly to the CN peak--to a decrease of the concanavalin A-mediated proliferative response of peripheral blood lymphocytes in both OS and NWL chickens. This suppression, however, was significantly more pronounced in NWL chickens. In summary, these data suggest a disturbance of the immune-neuroendocrine communication in OS chickens with spontaneous thyroid autoimmunity. The possible implications for the generation of "forbidden" autoimmune responses are discussed.
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PMID:Disturbed immune-endocrine communication in autoimmune disease. Lack of corticosterone response to immune signals in obese strain chickens with spontaneous autoimmune thyroiditis. 362 71


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