UMLS:C0011849 - FACTA Search

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

The study of peptide binding to HLA class II molecules has mostly concentrated on DR molecules. Since many autoimmune diseases show a primary association to particular DQ molecules rather than DR molecules, it is also important to study the peptide-binding properties of DQ molecules. Here we report a biochemical peptide-binding assay for the type I diabetes-associated DQ8, i.e. DQ (alpha1*0301, beta1*0302), molecule. Affinity-purified DQ8 molecules were tested in peptide-binding assays using a radiolabelled influenza haemagglutinin (Ha) peptide encompassing positions 255-271(Y) as an indicator peptide. The Ha 255-271(Y) peptide bound to DQ8 in a pH-dependent fashion showing optimal binding around pH 5. The association kinetics were relatively slow and the resulting complexes were heat labile. The specificity of peptide binding to DQ8 was investigated in competitive inhibition experiments with a panel of 43 peptides of different lengths and sequences. The DQ8 molecules showed a different pattern of peptide binding compared to a previously studied DQ2 molecule. Peptides derived from thyroid peroxidase, HLA-DQ(alpha1*0301), HLA-DQ(alpha1*0302), retinol receptor and p21ras were among the high-affinity binders, whereas peptides derived from myelin basic protein were among the low-affinity binders. The sequence of the high-affinity peptides conformed with a previously published peptide-binding motif of DQ8.
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PMID:A peptide-binding assay for the disease-associated HLA-DQ8 molecule. 965 24

Previous studies have shown that in vitro thyroid peroxidase (TPO) iodide oxidation activity is decreased and thyroid T4-5'-deiodinase activity is increased 15 days after induction of experimental diabetes mellitus (DM). In the present study we used thyroid histoautoradiography, an indirect assay of in vivo TPO activity, to determine the possible parallelism between the in vitro and in vivo changes induced by experimental DM. DM was induced in male Wistar rats (about 250 g body weight) by a single i.p. streptozotocin injection (45 mg/kg), while control (C) animals received a single injection of the vehicle. Seven and 30 days after diabetes induction, each diabetic and control animal was given i.p. a tracer dose of 125I (2 microCi), 2.5 h before thyroid excision. The glands were counted, weighted, fixed in Bouin's solution, embedded in paraffin and cut. The sections were stained with HE and exposed to NTB-2 emulsion (Kodak). The autohistograms were developed and the quantitative distribution of silver grains was evaluated with a computerized image analyzer system. Thyroid radioiodine uptake was significantly decreased only after 30 days of DM (C: 0.38 +/- 0.05 vs DM: 0.20 +/- 0.04%/mg thyroid, P < 0.05) while in vivo TPO activity was significantly decreased 7 and 30 days after DM induction (C: 5.3 and 4.5 grains/100 micron 2 vs DM: 2.9 and 1.6 grains/100 micron 2, respectively, P < 0.05). These data suggest that insulin deficiency first reduces in vivo TPO activity during short-term experimental diabetes mellitus.
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PMID:Autoradiographic thyroid evaluation in short-term experimental diabetes mellitus. 968 52

We report a 79-year-old woman case of slowly progressive IDDM (SPIDDM) with rheumatoid arthritis (RA) and Hashimoto disease. High titer of anti-glutamic acid decarboxylase antibody (GAD) with a value of 16,400 U/ml (normal value: less than 5 U/ml) and deteriorated secretion of insulin, and clinical course led to the diagnosis of SPIDDM. Both anti-islet cell and anti-insulin antibodies were negative. One year prior to the diagnosis, at 78 years of age, she was newly diagnosed with NIDDM and had been medicated with sulfonylurea and voglibose, resulting her glucose levels well-controlled. Four months before admission, a gradual increase of plasma glucose was noticed, while oral hypoglycemic agents were fully administrated. On admission, her glycemic control was revealed as follows; a fasting blood glucose level of 458 mg/dl and an HbA1 C level of 14.3%. Urinary CPR was 22.5 micrograms day. Her insulin secretion was proved not to be induced with intravenous glucagon injection. Hyperinsulinemic euglycemic glucose clamp test showed the normal glucose uptake ratio; 9.5 mg/kg/min. Moderate doses of subcutaneous insulin (20 units daily) were effective on her diabetes control. She was newly diagnosed with Hashimoto disease that required thyroid hormone replacement 50 micrograms per day after having developed NIDDM. High titer of anti-thyroglobulin antibody (46.9 U/ml) and anti-thyroid peroxidase antibody (81.5 U/ml) were observed. The patient had been medicated for RA with anti-inflammatory drugs since her early seventieth. Rheumatoid factor was elevated to 127.7 IU/L and, anti-nuclear antibody (x 80) and anti-DNA antibody (x 80) were present. It may be of interest that a specific phenotype of HLA; A24 (9) and DR9 recognized to be susceptible to IDDM was detected in the high-elderly onset SPIDDM. Taken together HLA typing with her history of both RA and Hashimoto disease, our case may provide the information to the mechanism of pathogenesis of SPIDDM. Furthermore, to out knowledge, this is the first case of SPIDDM in the aged; 75-year-old or more.
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PMID:[Slowly progressive IDDM with rheumatoid arthritis and Hashimoto disease in high elderly]. 977 59

By coupling 3-(2-mercaptoethyl)quinazoline-2,4(1H,3H)dione (MECH) to divinyl sulfone activated agarose, a novel thiophilic matrix was obtained which allows the binding of immunoglobulins from different sources. In contrast to other thiophilic gels, antibodies are bound at low ionic strength and can easily be desorbed in intact form by elution with dilute alkali. The potential of using the MECH-gel was demonstrated by the purification of antibodies from human and animal (goat, rabbit, mouse) sera. The functional integrity of the purified antibodies was established with cytoplasmic islet cell antibodies from the sera of patients with type I diabetes and autoantibodies against thyroid peroxidase from patients with Graves' and Hashimoto's disease.
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PMID:A simplified procedure for the isolation of immunoglobulins from human serum using a novel type of thiophilic gel at low salt concentration. 983 92

Some type 2 diabetic subjects develop secondary failure to sulphonylurea treatment and require insulin therapy. To test the diagnostic sensitivity and specificity of epitopes of GAD65 autoantibodies (GAD65Ab) for insulin requirement, in patients with latent autoimmune diabetes of the adult, we studied 569 adult subjects with a clinical diagnosis of type 2 diabetes mellitus. All the patients had been initially treated with hypoglycemic agents and/or diet for at least 1 yr. The presence of GAD65Ab (61/569, 10.7%) depended on insulin therapy (P<0.0001), low BMI (P<0.0001), and low basal C-peptide (P = 0.01). The majority of GAD65Ab-positive subjects (47/61, 77%) had antibodies directed to both middle (GAD65-MAb) and COOH-terminal (GAD65-CAb) epitopes. However, GAD65-CAb were more frequent in insulin-treated subjects (92% of GAD65Ab+ individuals) than in subjects treated with hypoglycemic agents and/or diet (18.2% of GAD65Ab+ individuals), while the exclusive presence of GAD65-MAb was more frequent in subjects treated with hypoglycemic agents and/or diet (81.8% vs. 8%) (P<0.0001). The presence of GAD65-CAb had a diagnostic specificity for insulin requirement as high as 99.4% (compared with 96.9% of GAD65Ab as measured in the traditional radiobinding assay) and identified a subgroup of patients with low BMI, low basal C-peptide values, and a need for insulin therapy. Subjects carrying only GAD65-MAb were phenotypically indistinguishable from GAD65Ab-negative patients. Patients positive for GAD65-M+CAb, but not those positive for GAD65-MAb only, showed an increased risk for thyroid autoimmunity, as revealed by the presence of thyroid peroxidase autoantibodies. Our study demonstrates that the use of epitope-specific antibody assays improves the diagnostic specificity of GAD65Ab, and that the presence of GAD65Ab binding to COOH-terminal epitopes is strongly associated with a need for insulin requirement.
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PMID:Autoantibody recognition of COOH-terminal epitopes of GAD65 marks the risk for insulin requirement in adult-onset diabetes mellitus. 1063 4

Impairment of thyroid function has been described in up to 50% of the patients after external irradiation of the neck region as well as after mantle irradiation. In order to assess radiation-induced alterations in cultured thyroid cells, the occurrence of apoptosis and necrosis as well as the expression of thyroid peroxidase (TPO) and of two members of the 70 kD heat shock family, HSP-73 and HSP-72, were analysed following gamma irradiation. Human thyroid epithelial cells (TEC) were purified from surgical tissue specimens, were cultured and irradiated with a single dose of 5 Gy or 50 Gy using Co60 as radioactive source. Analysis was performed 1, 3 and 5 day(s) after irradiation. Apoptosis and necrosis were assessed by DNA staining with propidium iodide and FACS analysis. TPO and HSP expression by SDS-PAGE and Western blotting. The cell viability of TEC was not affected by irradiation and there was no induction of HSP-72, a sensitive indicator of acute cellular stress. Interestingly, the expression of TPO, a key enzyme of thyroid hormone synthesis, decreased significantly in irradiated TEC, while HSP-73 expression remained unchanged. Decreased expression of TPO with a resulting suppression of thyroid hormone synthesis could contribute to an early development of thyroid dysfunction following irradiation. Thus, analysis of thyroid function, even early after external radiation therapy of the neck or after total body irradiation, seems to be indicated.
Exp Clin Endocrinol Diabetes 2000
PMID:Decreased thyroid peroxidase expression in cultured thyrocytes after external gamma irradiation. 1082 22

Autoimmune type 1 diabetic patients show a high prevalence of thyroid peroxidase (TPO), parietal cell (PCA), anti-adrenal (AAA) and anti-endomysium antibodies (EmA-IgA), which may be accompanied with clinical disease. We studied the grade of associated organ-specific autoimmunity and the pattern of prevalence of TPO and PCA by age, gender, duration, age at onset of diabetes, and HLA DR haplotype in 783 type 1 diabetic patients, consisting of 286 children and 497 adults (M/F: 389/394), with a mean diabetes duration of 11.8 +/- 10.1 years. The relationship between islet cell (ICA), glutamic acid decarboxylase-65 (GADA) and thyro-gastric auto-antibodies was also investigated. TPO were present in 21.6%, PCA in 18.3%, AAA in 2.2% and EmA-IgA in 2.1% of the patients. The presence of TPO is determined by gender (p < 0.0001), age (P = 0.0008), and PCA status (p = 0.029). The presence of PCA is only influenced by age (p = 0.0027) and TPO status (p = 0.0155). Patients with ICA+ > or = 3 years had a higher prevalence of thyro-gastric auto-antibodies (p = 0.045) than ICA- subjects. Also, PCA were more prevalent in GADA+ than GADA- patients (p = 0.005). We observed an association between HLA DR5 and PCA (p = 0.0012). Dysthyroidism was more prevalent in TPO+ than TPO- subjects (p < 0.0001). PCA+ subjects had a higher prevalence of iron deficiency anaemia (p = 0.0099) and pernicious anaemia (p < 0.0001) than PCA- patients. In conclusion, particularly type 1 diabetic patients with persisting ICA > or = 3 years or with GADA, show a high prevalence of thyro-gastric auto-antibodies. Based on antibody-positivity we observed a high prevalence of thyroid disease, iron deficiency anaemia and pernicious anaemia, which can compromise the health of the diabetic patient.
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PMID:[Diabetes mellitus type 1 and associated organ-specific autoimmunity]. 1100 7

Gliadin antibody (GA) tests used in screening for coeliac disease (CD) frequently yield positive GA results without accompanying CD in cases of diabetes mellitus type 1 (DM-1). To enlighten this phenomenon we screened 848 DM-1 patients for IgA- and IgG-GA. Subsequently, 16 out of 19 high titre GA patients (6 with CD) were compared with 37 low titre DM-1 patients matched for sex, age and disease duration, for autoimmune and immunogenetic markers. Chronic thyroiditis and thyroid peroxidase (TPO) antibody positivity were more frequent in the GA-positive than in the GA-negative sub-group (38 vs. 2.7%, p = 0.003, and 69 vs. 27%, p < 0.00, respectively). The tissue transglutaminase (tTg) IgA titres correlated with CD but not with GA. tTg IgG titres were lower in GA-positive individuals (p = 0.0012). GA-positivity correlated with a higher titre of factor XIII IgA antibodies (p < 0.001). GA-positive DM-I patients were characterised by a distinct immunogenetic profile; the risk of HLA DQB1*02 was lower among GA-positive patients than among GA-negatives (OR 0.4, preventive fraction 0.43). All CD patients were HLA DRB1*03-DQB1* 02-positive, but none of the five patients with normal biopsies. GA-positive patients instead had HLA DRB1*13 in 37.5% as compared to 8.6% in GA-negative (OR 6.4, etiologic fraction 0.32). Thus, the occurrence of positive GA in DM-1 is correlated to TPO antibody positivity, thyroiditis and factor XIII IgA antibodies, but inversely correlated to tTg IgG, and seems to be associated with another HLA haplotype than that previously found to be associated with CD.
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PMID:Gliadin antibodies in adult insulin-dependent diabetes--autoimmune and immunogenetic correlates. 1119 Dec 81

The objective of the present study was to determine the prevalence of autoimmune thyroid disease in Indian children with type 1 diabetes mellitus by the assay of antibodies to thyroid peroxidase and thyroglobulin. The study population consisted of 35 children with type 1 diabetes mellitus and 32 healthy age- and sex-matched control children. Thyroid peroxidase antibodies (TPO) were determined by ELISA and thyroglobulin antibodies (TGA) by passive hemagglutination. Thyroid function tests and tests of glycemic control were also performed. These assays were repeated after six months and one year. TPO were observed in 19 (54.3%) patients compared to three (10%) controls, and TGA in 11 (31.4%) patients and none of the controls. Both these observations were statistically significant with p=0.0002 for TPO and 0.0016 for TGA. The prevalence of these antibodies was not different in boys and girls and did not change with the duration of diabetes. All patients who were positive for TGA were also positive for TPO. Thyroid function tests were abnormal in one patient who was found to have Hashimoto's thyroiditis. There is a definite need to screen all diabetic children for thyroid antibodies and carefully follow up those patients in whom these antibodies are positive.
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PMID:Autoimmune thyroid disease in Indian children with type 1 diabetes mellitus. 1130 45

Five percent of all pregnant women and 25% of pregnant women with insulin-dependent diabetes mellitus (IDDM) develop postpartum thyroiditis (PPT) during the first year after delivery. PPT has significant morbidity and can be predicted prenatally by the presence of thyroid peroxidase (TPO) antibody. Our objective was to estimate the cost-effectiveness of screening pregnant women for the TPO antibody versus the current strategy of no screening test or an alternative strategy of a thyroid-stimulating hormone (TSH) test 6 weeks postpartum. We performed cost-effectiveness analysis using a decision tree model that accounted for cases of PPT detected, medical outcomes of screening, and costs of screening and care. Hypothetical cohorts of 1000 pregnant women with uncomplicated pregnancies and 1000 pregnant women with IDDM were used to determine direct medical costs, quality-adjusted life years, and cases of PPT detected. The cost of testing 1000 pregnant women for TSH at the 6 week postpartum visit was $75,000, with an effectiveness of 995.2 quality-adjusted life years resulting in a cost-effectiveness ratio of $48,000 per quality-adjusted life year. Checking a TPO antibody was more effective (995.5 quality-adjusted life years) but also more expensive ($93,000). The incremental cost-effectiveness ratio of the TPO antibody strategy was $60,000 per quality-adjusted life year. Results were most sensitive to changes in the test characteristics, incidence of disease, and percentage of women with PPT who were symptomatic. A separate analysis for women with IDDM resulted in an incremental cost-effectiveness ratio of $13,000 per quality-adjusted life year for the TSH strategy and $32,000 per quality-adjusted life year for the TPO strategy. Screening for PPT is likely to be reasonably cost-effective and should be considered for inclusion as part of routine pregnancy care.
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PMID:Cost-effectiveness of prenatal screening for postpartum thyroiditis. 1157 Oct 94

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