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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The presence of antithyroid plasma membrane antibodies (ATMA) has been detected in 97% of patients with untreated hyperthyroid Graves' disease, 85% of methimazole treated hyperthyroid Graves' disease, 25% of Hashimoto's thyroiditis and 6.9% of patients with toxic nodular goitre. The ATMA index was negative in all healthy blood donors, in patients with non-toxic nodular goitre, with the thyrocardiac syndrome and with simple obesity. Studies of patients with non-thyroid autoimmune diseases revealed that ATMA is positive in 11% of patients with scleroderma, 17.6% of systemic lupus erythematosus and 16% of rheumatoid arthritis. The amount of immunoglobulin bound to thyroid plasma membranes after pre-incubation with serum from patients with Graves' disease varied from 4.2 to 25.2 pmoles per mg of membrane protein; these values are several times higher than the maximal binding capacity for thyrotrophin which is 1.28 pmole/mg protein. In the majority of the cases studied TSH did not significantly inhibit IgG bound from thyroid plasma membranes. Significant amounts of IgG were displaced by an excess of TSH only in three cases with untreated hyperthyroid Graves' disease.
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PMID:The presence of autoantibodies directed to thyroid plasma membrane antigens in sera of patients with thyroid disorders, estimated by the reaction with labelled protein A. 632 47

Organ-specific autoantibodies (AAb) to thyroid and non-thyroid antigens of various endocrine and exocrine glands (glandular stomach, pancreas, adrenal, parathyroid, and striated muscle) were determined by different serological procedures in sera from Obese strain (OS), Cornell C strain (CS), normal inbred strains (CC and CB), and outbred normal White Leghorn (NWL) chickens. Thyroglobulin autoantibodies (Tg-AAbs), evaluated by immunodiffusion, passive hemagglutination, enzyme-linked immunosorbent assay, and indirect immunofluorescence, as well as other organ-specific AAbs determined by indirect immunofluorescence, predominated in OS chickens. Tg-AAbs were found in the highest frequency, thyroid microsomal AAbs in intermediate frequency, and the other organ-specific AAbs in low frequency in OS chickens. Thyroid and non-thyroid organ-specific AAbs were found only occasionally in control chickens and then only in low titers. Thus, spontaneous autoimmune thyroiditis of OS chickens correlates closely with human Hashimoto thyroiditis not only in respect to AAbs to thyroid antigens but also to nonthyroid organ-specific antigens. Non-organ-specific AAbs, such as antinuclear antibodies, antibodies to chicken red blood cell nuclei, mitochondrial AAbs, smooth muscle antibodies, and reticulin AAbs occur in high frequency in all strains of chickens tested. Even a slight prevalence in NWL chickens was seen, indicating that the abnormal immune response in OS chickens is restricted to organ-specific antigens of the thyroid gland and in some cases also to other exocrine or endocrine glands.
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PMID:Nonthyroid autoantibodies in obese strain (OS) chickens. 642 87

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

Autoimmune diseases have a multifactorial pathogenesis including essential genetic and nonessential modulatory factors. Among the essential factors, not only should genes coding for an abnormal reactivity of the immune system be considered, but we have, in addition, provided experimental evidence for the existence of genes responsible for a susceptibility of the target organ/structure for the autoimmune attack. Only when both sets of essential genes are present does an autoimmune disease develop at all. The modulatory factors then determine the final outcome in each case. The present contribution discusses the immunomodulating role of glucocorticoid and sex steroids focussing on the Obese Strain (OS) of chickens, a model for Hashimoto thyroiditis.
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PMID:Altered immunoendocrine dialogue in autoimmune disease. 846 66

Skin grafts were performed to prove the level of genetic diversity in chicken populations of the Obese strain (OS), which develops a spontaneous Hashimoto's-like thyroiditis, and University of California at Davis (UCD) Line-200 chickens, which are hereditarily afflicted with progressive systemic sclerosis (scleroderma). As controls, Cornell C-strain (CS) and inbred, normal White Leghorn CB chickens were included in the genetic monitoring program. At the commencement of this study in 1988, median allograft rejections were observed after 9 to 12 d (range 8 to 14 d) in OS and CS chickens that derived from large flocks at Cornell University, whereas OS sublines of the smaller, more closely-bred colonies at the University of Innsbruck, Austria, showed median allograft rejection after 19 d (range 12 to 35 d). From 1988 to 1993, allograft survival was only slightly prolonged in the OS sublines. However, the results of the skin allotransplantations in inbred UCD-200 chickens revealed two subpopulations in this line. In one subgroup the median of allograft rejection was calculated with 13 d (range 6 to 37 d) in 1989, 30 d (10 to 37 d) in 1990, 21 d (8 to 90 d) in 1991, and 16 d (7 to 26 d) in 1993. In the other subgroup allografts were accepted at rates similar to autografts. In addition, the inbreeding coefficient was calculated for eight male and eight female OSB5B5Cornell (C) and OSB5B5Innsbruck (INN) chickens, respectively, hatched in 1993. On the basis of mating records, the minimal estimate of the inbreeding coefficient was calculated to be 0.0679 in the OSB5B5C and 0.1035 in the OSB5B5INN population. The results demonstrated a higher degree of consanguinity in the smaller population of OSB5B5INN chickens compared to OSB5B5C birds. The later are maintained in larger numbers, therefore, the frequency of matings between related individuals should be lower.
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PMID:Skin allograft survival in chicken strains with spontaneous autoimmune diseases. 877 18

According to our concept, the development of autoimmune disease depends on the presence of two sets of essential genes, one coding for an abnormal autoreactivity of the immune system, the other for a primary susceptibility of the target organ/structure for the immune attack. The final outcome of the disease in a given individual is then fine tuned by modulatory factors, such as diet or hormones. With regard to the latter, the immuno-endocrine interaction via the hypothalamo-pituitary-adrenal (HPA) axis has proven to be of special importance. Investigating the so-called Obese strain (OS) of chickens, an animal model with a spontaneously occurring Hashimoto-like autoimmune thyroiditis, we have first shown an impaired surge of glucocorticoid hormones after stimulation of the HPA axis by antigens or certain cytokines (glucocorticoid-increasing factors--GIFs). More recently, we have found a similar behavior in models with systemic autoimmune diseases, that is, murine lupus erythematosus and avian scleroderma. More detailed studies have, however, proven that the mechanisms underlying this altered immuno-endocrine communication via the HPA axis differs in different models. Finally, recent data point to the possibility that the classical pathways of glucocorticoid-T-cell interactions also take place in the thymus itself, which has been shown to be a site of steroid hormone production.
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PMID:Neuroendocrine-immune disturbances in animal models with spontaneous autoimmune diseases. 962 86

Chickens of the Obese strain (OS) are hereditarily affected with spontaneous autoimmune thyroiditis that resembles Hashimoto's thyroiditis of humans in clinical, histopathological, serological, and endocrinological aspects. In this review, the natural history of the OS, reflecting the development and maintenance of the stock and its improvement of productivity over many years at Cornell University, is summarized. To underline the value and usefulness of this animal model, the concept of the multifactorial pathogenesis of autoimmune diseases, which was mainly established at the University of Innsbruck, Austria, is briefly outlined. This detailed analysis on the natural history of the OS was only made feasible by the availability of four decades of records on this chicken line at Cornell University. The report starts with the initial occurrence of a few pullets within the Cornell C-strain (CS) flock that showed obesity, long and silky feathers, and small body size, which, therefore, caused these birds to look notably different than the other CS birds. Experimental findings indicated an autoimmune basis for these characteristics, and the objectives of matings were initially focused on increasing the number of obese individuals for studies on the etiopathology and the mode of inheritance. In subsequent years, matings were directed toward increasing the penetrance and severity of the obese trait in the population. In recent years, the reproductive capability of the obese stock was improved by mating only the best breeders of the population in terms of body weight, egg weight, egg production, fertility, hatchability, and the expression of the obese phenotype. Housing conditions for OS chickens at Cornell and the qualification standards and selection procedures for breeders are described in detail, and results of blood typings are shown. A specific recent finding in OS hens is the high incidence of residues of the right Mullerian duct with cyst formation.
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PMID:The natural history of the obese strain of chickens--an animal model for spontaneous autoimmune thyroiditis. 1053 82

Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible anymore. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models--albeit rare--reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present chapter describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and -206) with a scleroderma-like disease, and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome.
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PMID:Avian models with spontaneous autoimmune diseases. 1714 2


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