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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The BB rat spontaneously develops autoimmune abnormalities such as insulin-dependent diabetes mellitus and thyroiditis. The autoimmunity of the BB rat is controlled in part by genes of the major histocompatibility complex (MHC), known as the RT1 complex in the rat, and accumulating evidence suggests the involvement of MHC class II molecules. The RT1 complex specifies two types of class II molecules, which are encoded by the loci RT1.B and RT1.D. We have determined the relative steady-state mRNA levels of the class II genes RT1.B beta, RT1.D alpha, and RT1.D beta in splenic lymphocytes from individual autoimmune BB rats of various ages and from age-matched histocompatible normal Wistar-Furth (WF) rats. The relative steady-state mRNA levels of the RT1.D alpha and RT1.D beta genes, but not of the RT1.B beta gene, were elevated approximately 2.5-fold in lymphocytes of prediabetic BB rats 45-75 days old in comparison with age-matched normal WF rats and older BB rats greater than 75 days old. In the diabetic and nondiabetic BB rats greater than 75 days old, the RT1.D alpha and RT1.D beta transcripts were found at lower normal levels, similar to that of WF rats. In contrast, the RT1.B beta transcripts were found at comparable levels in lymphocytes of the BB and WF rats at all ages examined. The increased steady-state mRNA levels of the RT1.D alpha and RT1.D beta genes in the prediabetic BB rats may reflect differences in the proportion of lymphocytes expressing these genes and thus differences in splenic lymphocyte populations.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1988 Dec
PMID:Elevated mRNA levels of major histocompatibility complex class II genes in lymphocytes of autoimmune BB rats. 314

The effect of T4 on the incidence of lymphocytic thyroiditis and on titers of antibodies to thyroglobulin and thyroid microsomal antigen was studied in BB/W rats that are prone to develop spontaneously autoimmune thyroiditis and diabetes. Thirty-three animals were separated in two groups. Rats in one group had 1 mg T4 per liter of drinking water, and the other group was given no T4. After 3-4 months of therapy the T4-treated group had a reduced production of antibody to thyroglobulin (p less than 0.05) and to microsomal antigen (p less than 0.005) and a significantly lower frequency of lymphocytic thyroiditis (p less than 0.05). Our data are consistent with previous findings in experimentally induced thyroiditis in rats and suggest that T4 has an immunosuppressive effect.
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PMID:The effect of thyroxine on spontaneous thyroiditis in BB/W rats. 320 67

Chronic L-thyroxine administration (6 micrograms/100g BW, ip, daily) for 2 or 3 months suppressed serum TSH concentrations and decreased both the incidence of spontaneous lymphocytic thyroiditis (LT) and the serum levels of anti-thyroglobulin (anti-Tg) antibodies in the diabetes prone BB/Wor rat. This suggests that TSH may play a role in the occurrence of LT in this rat model. In contrast to these observations, L-thyroxine administration did not affect the markedly increased incidence of LT or the elevated serum anti-Tg antibodies in iodine supplemented BB/Wor rats, suggesting that TSH stimulation is not necessary for the development of iodine induced LT in this rat model. Other factors, such as the increased antigenicity of highly iodinated Tg, may be more important.
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PMID:Effect of L-thyroxine administration on the incidence of iodine induced and spontaneous lymphocytic thyroiditis in the BB/Wor rat. 334 51

We typed patient groups with type I diabetes (n = 78), Graves' disease (n = 81), goitrous autoimmune (n = 52), "silent" (n = 18) and postpartum thyroiditis (n = 15) for human leucocyte antigens (HLA) A, B, C, DR and DQ. The results were compared to those obtained from 256 healthy controls typed for HLA-A, -B, -C and 140 typed for -DR. All these 140 controls were genotyped. Previously described associations of DR3 (OR (odds ratio) = 2.68, p less than 0.005) and DR4 (OR = 3.26, p less than 0.0001) in type I diabetes is confirmed. In this series, however, HLA-DR3/DR4 heterozygotes were apparently at no greater risk for type I diabetes than DR3 or DR4 homozygotes. The relative risk conferred by DR3/DR4 heterozygotes (6.48) was less than that for DR3 homozygosity (2.8), suggesting a recessive major histocompatibility complex-related susceptibility to type I diabetes. Graves' disease was associated with DR3 (OR = 3.02, p less than 0.0005); the increased frequency of DR3 homozygotes in this series is consistent with recessive HLA-linked susceptibility to Graves' disease proposed on the basis of family data. Hashimoto's thyroiditis, on the other hand, was associated with HLA-DR4 (OR = 3.08, p less than 0.0001), the latter finding confirming our earlier report on 21 patients. The increase of HLA-DR4 in both post-partum and silent thyroiditis suggests that these conditions are immunogenetically related, and may well represent variants of chronic autoimmune thyroiditis.
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PMID:HLA and autoimmune endocrine disease 1985. 348 59

Although target tissues or glands differ, several common threads have begun to emerge that link the diseases of the autoimmune endocrine syndromes. In the polyglandular syndrome type II, a defect resides in one of the genes of the major histocompatibility locus which, in concert with other gene(s), results in susceptibility. Genetic susceptibility is necessary but not sufficient to produce the disorder. This is illustrated by the lack of 100% concordance of disease in identical twins. This lack of concordance has led to the search for environmental influences or "triggers" of the autoimmune process. These "triggers" have not been well defined, but may include amiodarone or other iodine-containing medications for thyroid autoimmunity and congenital rubella for some patients with diabetes and thyroiditis. The autoimmune destruction of most target glands appears to be a slow process with a long preclinical prodrome that may last for years. During this period, autoantibodies, lymphocyte abnormalities, and subclinical endocrine defects are usually present. As knowledge of target antigens has progressed, it appears that despite polyendocrine disease, within each gland specific antigens are the targets of the autoimmune process. When the genetic defect(s) and environmental influences of organ specific autoimmunity are better understood, it may be possible to devise specific "replacement" or corrective therapies. In the absence of this knowledge, therapies directed at partial immunosuppression are currently being studied in Type I diabetes and Graves' ophthalmopathy. Given the similar features of many of the organ-specific autoimmune disorders, it is likely that if immunotherapeutic modalities are successful in one disease, they may be of benefit in related disorders.
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PMID:Polyglandular autoimmunity. 351 21

Spontaneous insulin-dependent diabetes mellitus (IDDM) and other autoimmune manifestations, such as lymphocytic thyroiditis and atrophic gastritis, develop in diabetes-prone (high-risk) lines of Wistar-derived BioBreeding (BB) rats. To examine whether Cyclosporin A (CsA) would abrogate multiple autoimmune manifestations in BB rats, we treated them prophylactically with CsA from 5-6 weeks to 23-25 weeks of age. IDDM developed in 0/58 CsA-treated rats; 47% (29 out of 62) of sex- and age-matched controls treated with vehicle developed IDDM (p less than 0.001). CsA-treated rats had no or minimal lymphocytic infiltration and parenchymal changes in the pancreas, stomach and thyroid at the time of cessation of treatment. IDDM, glycosuria and hyperglycemia developed in 0/22 rats followed up to 370 days of age (up to 210 days following the cessation of CsA therapy); histologic examination of their islets was normal. We conclude that CsA completely abrogates the development of clinical IDDM in the BB rat, and that it inhibits or abolishes lymphocyte infiltration in several organs against which there is autoimmunity. The data also suggest that the protective effect of CsA persists well past the duration of therapy, and that cell-mediated autoimmunity (with or without humoral immunity) may be an important pathogenetic mechanism in the destruction of beta cells in the BB rat.
Diabetes Res 1986 Jan
PMID:Cyclosporin prophylaxis induces long-term prevention of diabetes, and inhibits lymphocytic infiltration in multiple target tissues in the high-risk BB rat. 351 66

Diabetes-prone BioBreeding/Worcester (BB/Wor) rats received thrice weekly injections of mAb against antigens expressed on the surface of all T cells (OX19), cytotoxic/suppressor, and NK cells (OX8), helper/inducer cells (W3/25, OX35, OX38), and Ia+ cells (OX6, 3JP, OX17). Treatment with OX8 or OX19 achieved stable reductions of splenic and peripheral blood NK cells and helper/inducer T lymphocytes, respectively, and protected against diabetes. OX19 injections also prevented lymphocytic insulitis, thyroiditis, and the synthesis of autoantibodies to thyroid colloid and smooth muscle antigens. OX8 injections reduced splenic NK-mediated YAC-1 cell lysis, but did not prevent insulitis, thyroiditis, or autoantibody synthesis. Injections of mAb specific for antigens on the surface of helper/inducer cells, and for cells expressing IaE antigens provided marginal protection against diabetes without reductions of phenotypic subsets. These findings suggest that pancreatic beta cell destruction in the spontaneously diabetic BB/Wor rat is mediated by the combined action of NK and helper/inducer cells.
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PMID:Prevention of diabetes in BioBreeding/Worcester rats with monoclonal antibodies that recognize T lymphocytes or natural killer cells. 353 81

Cyclosporine is an 11 aminoacid cyclic peptide of fungal origin endowed with potent immunosuppressive activity. Unlike the conventional immunosuppressants, cyclosporine does not interfere with DNA metabolism, but it selectively and reversibly inhibits lymphocyte T-helper activation by inhibiting the production of interleukin-2 which plays a role in immune response development. Cyclosporine has little effect on lymphocytes B and does not modify the production of antibodies when it is in progress. The drug is effective in preventing spontaneous or autoantigen-induced auto-immune diseases in animals. The best studied models are experimental allergic encephalomyelitis, uveitis in the rat and spontaneous diabetes of BB rats. However, cyclosporine has no effect on diseases exclusively due to the pathogenic action of antibodies, such as spontaneous thyroiditis of the obese chicken. It is also possible to obtain a curative effect, this type of model being nearer to therapeutic conditions in humans than the previous models.
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PMID:[Cyclosporin and autoimmune diseases. 1: Experimental bases]. 355 Sep 87

We investigated the serial changes in the plasma levels of anti-thyroglobulin antibody (ATA) by solid-phase enzyme immunoassay, thyroid hormones and blood glucose, since spontaneous occurring lymphocytic thyroiditis (LT) has been found in spontaneously diabetic Bio Breeding/Worcester (BB/W) rat. We also observed the correlation between these levels and histological findings in the thyroid gland. The incidence of diabetes was 0% in 5 week old rats (group A), 70% in 11 week old rats (group B), and 86% in 20 week old rats (group C), while LT was observed in 0% in group A, 20% in group B and 48% in group C. Although the incidence of both increased with age, there was no link between LT and diabetes. Plasma ATA levels were 91.4 +/- 28.5 (OD492 X 1,000, mean +/- SEM) in the control (14 week old Wistar Furth) rats. 49.5 +/- 15.4 in group A, 197.8 +/- 41.5 in group B, and 376.7 +/- 48.7 in group C, again showing a clear increase with age. In group C, the plasma levels of ATA in rats with LT were significantly higher than those without LT. In addition, 6 out of 11 rats without LT had abnormaly high ATA levels. In group C, the plasma levels of free 3,5,3'-triiodothyronine (FT3) and total thyroxine (TT4), and also the FT3/TT4 ratio were significantly lower and the plasma levels of blood glucose were higher than in the other groups. There was no difference between the plasma thyroid hormone levels in rats with LT and those without LT. These studies suggest that LT may occur independently of insulitis, namely diabetes, ATA levels and the incidence of LT increase with age, the site of ATA production may not be confined to the thyroid gland, and the derangement of glucose metabolism may be one of the factors in the decrease in plasma thyroid hormone. The BB/W rat is not only a useful animal model to use in exploring the pathogenesis of human insulin-dependent diabetes mellitus, but also spontaneous autoimmune thyroiditis.
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PMID:Spontaneous autoimmune thyroiditis in Bio Breeding/Worcester (BB/W) rat. 355 49

We have recently reported that iodine administration (0.05% iodine in drinking water) to weanling, diabetes mellitus- and lymphocytic thyroiditis (LT)-prone Biobreeding Worcester (BB/W) rats strikingly increases the incidence of LT without occurrence of iodine-induced hypothyroidism, which frequently results when excess iodine is administered to euthyroid patients with Hashimoto's thyroiditis. Since hypothyroidism did not occur in the iodine-treated BB/W rats, hemithyroidectomy was carried out in 30-day-old BB/W rats to increase thyroid mass and functional reserve. Iodine administration for 60 days markedly increased antithyroglobulin antibodies (0.40 +/- 0.08 vs. 0.15 +/- 0.06 OD; P less than 0.02), the incidence of LT (68% vs. 13%; P less than 0.001), and thyroid weight of the residual lobe (10.5 +/- 0.7 vs. 6.3 +/- 0.3 mg/100 g BW; P less than 0.001) and induced hypothyroidism (T4, 2.5 +/- 0.2 vs. 3.0 micrograms/dL; P less than 0.05; T3, 25.1 +/- 1.9 vs. 37.5 ng/dL; P less than 0.001; TSH, 252 +/- 49 vs. 61 +/- 14 microU/mL; P less than 0.02). Hypothyroidism in the iodine-treated rats occurred primarily in those with LT. Similar studies were carried out in the non-diabetes mellitus-, non-LT-prone, genetically equivalent BB/W rats (W-line), the parent strain Wistar-Furth rats, and Sprague-Dawley rats. Iodine administration did not induce LT or antithyroglobulin antibodies in these three strains and did not affect thyroid function in Wistar-Furth and Sprague-Dawley rats. However, in the W-line rats, iodine excess did induce thyroid enlargement in the residual lobe (8.4 +/- 0.2 vs. 6.4 +/- 0.2 mg/100 g BW; P less than 0.001), a decrease in serum T3 (71.5 +/- 2.9 vs. 86.0 +/- 2.5 ng/dL; P less than 0.001), and an increase in serum TSH (344 +/- 65 vs. 69 +/- 6.0 microU/mL; P less than 0.001). It is evident, therefore, that hemithyroidectomy in BB/W rats sufficiently reduces functioning thyroid tissue, resulting in iodine-induced LT and hypothyroidism, similar to iodine-induced hypothyroidism in euthyroid patients with Hashimoto's thyroiditis. It is unclear, however, why iodine administration also induced hypothyroidism in hemithyroidectomized, genetically similar, W-line rats in the absence of LT. This observation suggests that iodine-induced hypothyroidism in rats may be genetically determined.
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PMID:Iodine-induced thyroiditis and hypothyroidism in the hemithyroidectomized BB/W rat. 359 27


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