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

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

The majority of patients with diabetes mellitus can be classified as suffering from either Type 1 or Type 2 diabetes. The pathogenetic pathways for these two categories of diabetes appear to be distinct and separate. Both forms of diabetes have a genetic as well as environmental component in their pathogenesis. Type 1 diabetes has a weaker genetic link; its association with HLA antigens is well established. Type 2 diabetes has a stronger genetic association but the exact gene or genes responsible is unknown. The environmental trigger in Type 1 diabetes may be a viral infection while urbanisation, obesity, physical inactivity and stress may trigger the development of Type 2 diabetes. Type 1 diabetes is a chronic autoimmune disease where beta cell destruction may occur over a number of years before clinical diabetes is diagnosed. Type 2 diabetes is the result of an interplay of relative insulin deficiency or a defect in insulin release together with insulin resistance. Hyperglycaemia perpetuates the problem of beta cell defect and insulin resistance. The understanding of pathogenesis of diabetes is the key to prevention and treatment of diabetes mellitus.
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PMID:Pathogenesis of type 1 and type 2 diabetes mellitus. 222 10

The steroid prehormone, dehydroepiandrosterone (DHEA) has potent antihyperglycemic effects when fed in the diet of genetically diabetic C57BL/KsJ-db/db mice. The purpose of this investigation was to analyze changes in sex steroid levels in serum of mice fed DHEA, and to compare the antihyperglycemic potencies of the various metabolites in order to clarify the mechanism of DHEA action. Steroid radioimmunoassays showed that dietary DHEA entered the blood in high concentrations and was actively metabolized to both androgens (testosterone, T; dihydrotestosterone, DHT) and estrogens (estrone, E1; 17 beta-estradiol, E2). This metabolism did not require intact adrenal glands or gonads. In C57BL/KsJ normal (+/+) males, conversion of DHEA to androgens was the prominent feature; in db/db males, DHEA feeding not only increased serum T and DHT, but also serum E1 and E2 levels. The db/db mice had increased amounts of adipose tissue that sequestered more intravenously injected 3H-E2; this additional body fat could account for increased aromatization of DHEA-derived estrogen precursors. Comparisons of the relative antihyperglycemic potencies of androgenic and estrogenic steroid metabolites of DHEA in db/db mice showed that the estrogens and metabolites with estrogenic properties (androstenediol) or those convertible to estrogens (DHEA sulfate) were the most potent. Although 17 beta-E2 was effective by injection or per os, DHEA was effective only when administered per os, implicating alimentary tract conversion of DHEA to more biologically active reactants. Based on the pivotal position of DHEA as a prehormone for androgens, estrogens, and etiocholanolones, an explanation of the seemingly paradoxical effects exerted by this compound in blocking autoimmune disease, hyperglycemia, obesity, and neoplasia was proposed.
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PMID:Androgenic and estrogenic metabolites in serum of mice fed dehydroepiandrosterone: relationship to antihyperglycemic effects. 295 67

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

Two-thirds of all deaths in developed countries are caused by the major noncommunicable diseases, e.g., cardiovascular disease, cancer, and non-insulin-dependent diabetes mellitus (NIDDM). There is increasing evidence that these diseases are a consequence of life-style change, and they have a number of risk factors in common. Primary prevention of both insulin-dependent diabetes mellitus (IDDM) and NIDDM has become increasingly important because of their significant morbidity and mortality and the human and economic costs associated with diabetes and its complications. Prevention of the two major forms of diabetes, IDDM and NIDDM, are quite separate issues. The former appears to be an autoimmune disorder, whereas the latter should be considered along with other life-style-related noncommunicable diseases. The primary prevention of NIDDM appears to offer the greatest promise of success. The uncertainty that still exists as to the role of obesity and other risk factors in the development of NIDDM gives support to a multiple-risk-factor intervention approach (through a healthy life-style strategy) for NIDDM prevention.
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PMID:Primary prevention of diabetes mellitus. 341 80

The enhanced T cell reactivity (ConA hyperresponsiveness and IL 2 hypersecretion) of spleen lymphocytes of Obese strain (OS) chickens with spontaneous autoimmune thyroiditis has recently been shown to be due to a defect in macrophage-derived non-specific suppressor factors that regulate IL 2 secretion and IL 2-promoted T lymphoblast proliferation in normal healthy animals. In the present study, we present several lines of evidence that the increased T cell response of peripheral blood lymphocytes (PBL) of OS chickens is due to mechanisms entirely different from the described dysregulation of splenic T cells: 1) In contrast to the splenic macrophages, peripheral blood monocytes of OS animals are not deficient in the production of IL 2 antagonistic activity (IAA); 2) therefore, cocultivation of PBL from OS and Normal White Leghorn (NWL) chickens in communicating culture chambers did not abrogate the difference in Con A response as previously observed with spleen lymphocytes. 3) Immunofluorescence with a monoclonal antibody (INN CH 16) against the chicken IL 2 receptor revealed enhanced numbers of mitogen activatable T cells in OS PBL but not OS spleen lymphocytes. 4) After prolonged Con A stimulation of PBL, OS and NWL lymphoblasts did not differ from each other in functional aspects. In contrast to this, Con A lymphoblasts from OS spleens exhibited enhanced staining with INN CH 16 in parallel with an increased proliferative response to IL 2. Thus, the primary T cell dysfunction involved in the development of autoimmune disease in OS chickens is the result of at least two separate regulatory defects.
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PMID:T cell hyperreactivity in obese strain (OS) chickens. Different mechanisms operative in spleen and peripheral blood lymphocyte activation. 350 Jan 18

In Obese strain (OS) chickens the role of maternal antibodies, passively transferred through the egg to the developing chick, was evaluated as a causative factor in the early development of spontaneous autoimmune thyroiditis (SAT). In the egg, passive antibody titers were highest in the yolk and lower in the allantoic fluid and sera of developing embryos. This passage of antibodies was documented by use of radiolabeled antibodies. In dams with high antibody titers, antibodies could be found in the sera of chicks at the time of hatch. Thyroglobulin was absent in the yolk of OS eggs during embryonal life, as compared with its detection in normal eggs. Immune complexes (thyroglobulin-autoantibody) detected in the thyroids of OS, but not CS, chicks at the time of hatch, or earlier, appear to reflect the presence of the maternally transferred antibodies. A pair of crosses between OS chickens, with thyroiditis, and the C strain (CS), without thyroiditis, was made to evaluate the role of transferred antibodies in the pathogenesis of autoimmune disease. When an OS chicken was the dam, maternal antibodies could be passively transferred; when a CS chicken was the dam, no maternal antibodies were present to be transferred. Nevertheless, both hybrids developed full-blown thyroiditis, demonstrating that binding of transferred maternal antibody to thyroglobulin is not a prerequisite for the induction of SAT. However, presence of maternal antibodies precipitated the onset of disease. Immune complexes formed in the embryonic thyroid are likely to participate in early autoimmune disease, although the development of full-blown thyroiditis may await the competency of the chick's immune system to provide the characteristic cellular infiltrate.
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PMID:Materno-embryonally transferred antibodies precipitate autoimmune thyroiditis in obese strain (OS) chickens. 372 17

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

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 cases are described of 3 female adolescents evaluated at the Cincinnati Adolescent Clinic for delayed or incomplete secondary sexual development due to primary ovarian failure. All 3 patients had normal blood leukocyte and ovarian tissue karyotypes. The clinical, laboratory, and pathological findings are discussed with emphasis on distinguishing chromosome incompetent ovarian failure (CIOF-Turner's syndrome) from chromosome competent ovarian failure (CCOF). The patients included a 15 1/2 year old black female who sought evaluation of obesity and lethargy, a 17 1/2 year old white female with secondary amenorrhea in whom oral provera failed to induce menstrual flow, and a 17 1/2 year old black female with scanty, infrequent menses who achieved a normal amount and duration of menstrual flow with Norinyl 1 + 80. Hypoestrogenization should be suspected in cases of incomplete breast development for age, thin vaginal mucosa with a prepubertal pattern of the vaginal cytology, scant cervical mucus without ferning, and lack of withdrawal bleeding after progesterone administration. If any decrease in ovarian steroid production is clinically suspected in an adolescent with primary or secondary amenorrhea associated with delayed or incomplete puberty, serum gonadotropin levels should be measured. A single elevated follicle stimulating hormone (FSH) level in the menopausal range is diagnostic of primary ovarian failure in an adolescent. If the FSH is low or normal, hypothalamic or pituitary disease would be suspected. A blood leukocyte karyotype is the next diagnostic procedure for patients with primary ovarian failure to distinguish between CCOF and CIOF. If the blood karyotype is XO or a variant without a Y cell line, no further cytogenic workup or visualization of the gonads is needed, but girls with blood karyotype of XX or a mosaic pattern with 1 cell line with a Y chromosome should undergo laparoscopy and gonadal biopsy. A unilateral testis should be removed to avoid malignant changes in later years. Patients with CCOF may have other endocrine dysfunction, particularly autoimmune disease. Other possible diagnoses include resistant ovary syndrome, pure gonadal dysgenesis, premature menopause, or infectious, chemical, or other causes of ovarian failure. The incidence of CIOF is greater than that of CCOF among patients with primary ovarian failure. Optimal treatment requires medical and psychosocial intervention.
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PMID:Chromosomally competent ovarian failure at adolescence. 631 54


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