Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The frequency of cell precursors producing Ig of different classes and Ag-binding activities were determined, using EBV-infection and limiting dilution assays, in healthy subjects and patients with autoimmune disease. A large proportion of circulating B cells from healthy subjects were committed to the production of IgM antibodies that were polyreactive and bound a variety of self- and exogenous Ag, i.e., IgG Fc fragment, ssDNA, thyroglobulin, thyroid microsomal Ag, insulin, and tetanus toxoid. Similar frequencies of these polyreactive antibody-producing cells were found in patients with Hashimoto's disease and SLE. In contrast, significantly higher frequencies of cell precursors producing monoreactive IgG autoantibodies to thyroid Ag (thyroglobulin and thyroid microsomal Ag) and ssDNA were found in Hashimoto's disease and SLE patients, respectively. Calculation of the Kd revealed that monoclonal polyreactive antibodies were in general low affinity (Kd, 10(-3) to 10(-7) mol/liter), whereas monoclonal monoreactive autoantibodies were high affinity (Kd, 10(-9) to 10(-11) mol/liter). The detected frequency and high affinity of the monoreactive autoantibodies in Hashimoto's disease and SLE patients were comparable to those of anti-tetanus toxoid and anti-insulin IgG mAb produced by B cell clones from vaccinated healthy subjects and insulin-treated patients with insulin-dependent diabetes mellitus, respectively. These findings support the hypothesis that the autoimmune B cell repertoire in patients with organ-specific and systemic autoimmunity is shaped by Ag-driven responses rather than merely reflecting a polyclonal B cell activation.
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PMID:Probing the normal and autoimmune B cell repertoire with Epstein-Barr virus. Frequency of B cells producing monoreactive high affinity autoantibodies in patients with Hashimoto's disease and systemic lupus erythematosus. 284 90

Streptozotocin diabetes in rats is associated with reduced function of the hypothalamo-pituitary-thyroid axis. The structure and hormone secretion of the thyroid and pituitary glands were studied in adult male rats 1 month after streptozotocin injection. The thyroid of diabetic rats was characterized by decreased follicle area and epithelial thickness. By electron microscopy, thyroid epithelial cells were characterized by flattened and almost empty rough endoplasmic reticulum cisternae, scanty exocytotic apical and endocytotic vesicles as well as degenerate mitochondria and rough endoplasmic reticulum. By immunohistochemistry, intracolloidal thyroglobulin and T3 as well as intraepithelial thyroglobulin were reduced. Electron microscopic and immunohistochemical analysis of pituitary glands showed that in diabetic rats thyrotrophs were mostly of type II, and the number of thyrotrophs (type I + type II) was greater than in controls. By radioimmunoassay (RIA), plasma T3, T4, and TSH levels were markedly reduced, and the TSH response to TRH was deficient in diabetic animals. The pituitary TSH concentration was increased, as expected from the morphological data. This study demonstrates severe structural changes in the thyroid and pituitary glands of diabetic rats which are accompanied by marked alterations of their secretory activity.
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PMID:Thyroid and pituitary secretory disorders in streptozotocin-diabetic rats are associated with severe structural changes of these glands. 288 60

Diabetes-prone BB Wistar rats were fed a modified AIN-76 diet providing the following amounts of iodine for 10 wk: 0.2 mg/kg diet (recommended amount); 1.0 mg/kg; 2.0 mg/kg; or 3.0 mg/kg. The thyroids were examined for gross and microscopic changes and sera were assayed for antibodies to triiodothyronine (T3), thyroxine (T4), and thyroglobulin (Tg). The body weights and food consumption of the rats fed 0.2 mg of iodine/kg were significantly lower than those of the animals fed higher amounts. Urinary iodine excretion reflected dietary intakes. The thyroids from animals fed 2.0 and 3.0 mg/kg were significantly (P less than 0.01) larger than those from animals fed 0.2 mg/kg. One rat fed 0.2 mg/kg and 2 rats in each group fed 2.0 and 3.0 mg/kg had extensive lymphocytic thyroiditis. Three rats fed 1.0 mg/kg, 6 fed 2.0 mg/kg and 6 fed 3.0 mg/kg had enlarged thyroids. Two rats fed 0.2 mg/kg, 2 fed 2.0 mg/kg and 6 fed 3.0 mg/kg had detectable Tg antibodies. These data suggest that high iodine intakes increase Tg antibodies, which may be associated with an increase in autoimmune thyroiditis in these animals.
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PMID:Effect of dietary iodine on autoimmune thyroiditis in the BB Wistar rats. 292 47

The effect of Tamm Horsfall protein (THP) of 18 healthy subjects and 14 diabetics on adherence of Escherichia coli (06:K13) 2699 strain to human kidney cells (HUK) was studied. Adhesion of bacteria (without additions: 100 bacteria per cell) was reduced dose-dependently by THP, half maximal inhibition occurring with 250 micrograms THP ml-1. Maximal inhibition (-84% at 1000 micrograms ml-1) exceeded inhibition by alpha-methyl-mannoside (36% at 50 mM), was specific (not reproduced by other glycoproteins, e.g. ovalbumin, mucin or thyroglobulin) and reversible (abolished by washing THP off HUK cells). Anti-adherence property of THP was not abolished by neuraminidase treatment. No significant difference of anti-adherence activity of THP was found between controls and diabetics, despite altered carbohydrate composition of THP in diabetes.
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PMID:Tamm Horsfall glycoprotein interferes with bacterial adherence to human kidney cells. 313 Feb 65

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

The serum thyroglobulin (Tg) concentration was measured in 97 patients with diabetes mellitus (39 males, 58 females). Hyper Tg-nemia which exceeds the normal range (1.0-26.6 ng/ml) was observed in 10 patients (3 out of 21 cases treated with diet alone, 3 out of 50 cases treated with oral hypoglycemic agents, 4 out of 26 cases treated with insulin). There was no significant correlation between concentrations of serum Tg and triiodothyronine (T3), thyroxine (T4), fasting plasma glucose (FPG), and hemoglobin A1c (HbA1c). However, a positive correlation was observed between serum concentrations of Tg and thyroid stimulating hormone (TSH). Patients with diabetes were divided into three groups according to the mode of treatment (Group I; diet alone, n = 21, Group II; oral hypoglycemic agents, n = 50, Group III; insulin, n = 26). No significant difference in the serum Tg concentration was observed among the three groups. They were also divided into two groups; normal Tg-nemia (Group A, n = 87) and hyper Tg-nemia (Group B, n = 10). There was no difference between levels of T3, T4, FPG, and HbA1c in the two groups. The serum TSH concentration measured by double antibody RIA and two site immunoradiometric assay in Group B was significantly higher than that in Group A. These results suggest that hyper Tg-nemia in patients with diabetes could be due to the increased TSH concentration which reflects latent subclinical primary hypothyroidism in them.
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PMID:Serum thyroglobulin concentration in patients with diabetes mellitus. 331 39

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

In order to elucidate whether or not the 'coupling defect' observed in thyroids from diabetic rats is due to a structural defect of intrathyroidal thyroglobulin (Tg), the sedimentation pattern and the stability of the thyroidal soluble iodoproteins were studied in control (C), food restricted (FR), diabetic (D) and insulin-treated diabetic (D+I) rats fed a low iodine diet either with (NID) or without (LID) iodide supplementation and labelled with 125I: acutely, 24 h prior to sacrifice and chronically, by feeding the corresponding diet labelled for 60 days. Diabetes resulted in a decrease of thyroidal weight, an increase of both thyroidal 127I content and concentration and decreased plasma TSH, irrespective of the diet. Insulin treatment reversed these alterations. Food restriction led to an intermediate situation between C and D. The iodoamino acid distribution in the acutely labelled thyroidal soluble iodoproteins showed a significant increase in the percent of organified 125I found as iodotyrosines (MIT and DIT) and a decrease of that found as iodothyronines (T3 and T4) both in D and FR. However, in the isotopically equilibrated groups, no differences were found except in LID-D where a slight increase in DIT and a decrease in T3 was found as compared to the corresponding control. The sedimentation patterns of both acutely and chronically labelled thyroidal soluble iodoproteins from all experimental groups displayed two peaks. The main one, corresponding to Tg, had a slightly lower sedimentation coefficient than the 19 S internal marker run in parallel, while the second one, relatively small, formed probably by dissociation of the main Tg peak, sedimented more slowly (12- 14 S).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intrathyroidal thyroglobulin in streptozotocin-diabetic rats. 352 86

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

The HLA haplotype segregation and autoantibody spectrum in 7 type I (insulin-dependent) diabetic multiplex families of North Indian origin were determined. Of the total of 17 diabetic sibs, 7 shared both haplotypes and 3 shared one haplotype with the proband. No HLA-non-identical sibs were observed. This distribution of haplotypes was non-random (P approximately equal to 0.005). The mode of inheritance was compatible with an autosomal recessive model, while a dominant model was unlikely. Pancreatic islet-cell antibodies were found in 23.5% of affected sibs, but in no healthy family member. A high incidence of other autoantibodies (parietal-cell and thyroglobulin/thyroid microsomal antibodies) was detected in both the diabetic patients (26.3%), and in healthy first-degree relatives (22.2%). These findings emphasize the role of HLA-linked genes and autoimmunity in the pathogenesis of type I diabetes in North India.
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PMID:HLA and autoimmunity in North Indian type I (insulin-dependent) diabetic multiplex families. 372 5


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