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Islet cell antibodies are associated with β-cell failure also in obese adult onset diabetic patients

To clarify the utility of islet cell antibodies (ICA) to correctly classify and predict insulin treatment in newly diagnosed diabetic subjects, ICA, body mass index (BMI), glycated hemoglobin (HbA1c), and fasting plasma C-peptide values were evaluated at and 3 years after diagnosis in 233 new, consecutively diagnosed, adult diabetic patients classified as obese or nonobese (National Diabetes Data

Identification of autoantibody epitopes of glutamic acid decarboxylase in Stiff-man syndrome patients

Stiff-man syndrome is a neurologic disorder characterized by progressive rigidity of skeletal muscles. Deficiency of the neurotransmitter γ- aminobutyric acid and autoantibodies to glutamic acid decarboxylase (GAD), the enzyme synthesizing γ-aminobutyric acid, are closely associated with the disorder, although the relevant antigenic epitopes have not been identified. In the present study, sera fro

A novel radioligand binding assay to determine diagnostic accuracy of isoform-specific glutamic acid decarboxylase antibodies in childhood IDDM

Insulin-dependent diabetes mellitus (IDDM) is associated with autoreactivity against GAD but the diagnostic sensitivity (positivity in disease) and specificity (negativity in health) of isoform-specific GAD antibodies have yet to be defined in assay systems suitable for screening large number of samples. One set of IDDM patient (n=10) and control (n=50) standard sera were used to develop quantitat

Molecular biology of IDDM

The clinical onset of insulin-dependent diabetes is associated with several autoimmune phenomena including islet cell antibodies, glutamic acid decarboxylase (the GAD65 isoform) autoantibodies (GAD65Ab) as well as insulin autoantibodies. The molecular cloning of these autoantigens has permitted the development of precise and reproducible antibody immunoassays to identify marker-positive patients a

Analysis of antibody markers, DRB1, DRB5, DQA1 and DQB1 genes and modeling of DR2 molecules in DR2‐positive patients with insulin‐dependent diabetes mellitus

Abstract: HLA‐DR2 is negatively associated with insulin‐dependent diabetes mellitus (IDDM). The aim of the present study was to analyze DR2‐positive patients among 425 consecutively diagnosed unrelated Swedish children with IDDM and in 367 matched controls. HLA‐DRB, ‐DQA and ‐DQB were determined by Taq I restriction fragment length polymorphism analysis. Amplification by polymerase chain reaction

Functional state of the β cell affects expression of both forms of glutamic acid decarboxylase

Glutamic acid decarboxylase (GAD) is a candidate target autoantigen involved in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). The functional state of the B cells has been suggested to play a pathogenic role in IDDM by altering β-cell autoantigen expression. In this study, we investigated expression of GAD-65 and GAD-67 in isolated Sprague-Dawley rat islets cultured at different g

Introducing low-quality feedstocks in bioethanol production: efficient conversion of the lignocellulose fraction of animal bedding through steam pretreatment

BackgroundAnimal bedding remains an underutilized source of raw material for bioethanol production, despite the economic and environmental benefits of its use. Further research concerning the optimization of the production process is needed, as previously tested pretreatment methods have not increased the conversion efficiency to the levels necessary for commercialization of the process.ResultsWe

Weight loss in rats following intraventricular transplants of pancreatic islets

Because of the body's resistance to permanent weight change, obesity remains a major health problem in modern society. It is hypothesized that the regulatory system defending body weight utilizes pancreatic insulin as an indicator of adiposity to the brain. To take advantage of this negative feedback system, we transplanted neonatal (experiment 1) or adult (experiment 2) pancreatic islets containi

Prospective evaluation of β-cell function in insulin antoantibody-positive relatives of insulin-dependent diabetic patients

During the preclinical period of insulin-dependent diabetes mellitus (IDDM), progression to clinical IDDM is characterized by declining β-cell function. Although the presence of insulin autoantibodies (IAA) improves the ability of islet cell antibodies (ICA) to predict subsequent clinical IDDM, few studies have examined the risk of developing IDDM in subjects positive for IAA but negative for both

Differential expression of glutamic acid decarboxylase in rat and human islets

The GABA synthesizing enzyme GAD is a prominent islet cell autoantigen in type I diabetes. The two forms of GAD (GAD64 and GAD67) are encoded by different genes in both rats and humans. By in situ hybridization analysis of rat and human pancreases, expression of both genes was detected in rat islets, whereas only GAD64 mRNA was detected in human islets, Immunocytochemical analysis of rat and human

Autoantibodies in IDDM primarily recognize the 65,000-Mr rather than the 67,000-Mr isoform of glutamic acid decarboxylase

Glutamic acid decarboxylase autoantibodies may aid in rapid screening strategies predicting IDDM before clinical onset. Rat islets contain GAD65 and GAD67 autoantibody targets, but human islets express only GAD65, now confirmed by direct immunoprecipitation from radiolabeled rat and human islets. Because human IDDM involves β-cell-specific autoimmunity, we tested 190 new IDDM patients and 51 healt

Analysis of HLA‐DQA1 and ‐DQB1 genes in Mexican Americans with insulin‐dependent diabetes mellitus

Abstract: Mexican American patients (n = 35) with insulin‐dependent diabetes mellitus (IDDM) and control subjects (n = 39) were HLA‐DQA and DQB typed by the polymerase chain reaction technique combined with allele‐specific oligonucleotide probes. Either DQBl*0302 or DQB1*0201 was present among 91% (32/35) of the patients compared to 67% (26/39) of controls. Either DQA1*0501 or DQA1*0301 was presen

HLA-DQ primarily confers protection and HLA-DR susceptibility in type I (insulin-dependent) diabetes studied in population-based affected families and controls

The association between HLA-DR and -DQ and insulin-dependent diabetes mellitus (IDDM) in a defined high-incidence area was analyzed in a total of 58 population-based patients, representing 77% of IDDM patients with age at onset below 16 years, and in 92 unrelated parents in control families without IDDM. HLA haplotypes were confirmed by analyzing first-degree relatives in both groups. Seven differ

HLA‐DR3, DQ2 homozygosity in two patients with insulin‐dependent diabetes mellitus superimposed with ulcerative colitis and primary sclerosing cholangitis

Abstract. Two unrelated young males with the unusual simultaneous presence of insulin‐dependent diabetes mellitus, ulcerative colitis and primary sclerosing cholangitis are reported. Both patients manifested homozygosity for the DR3‐DQw2 (DQB*0201) HLA genotypes. We believe that homozygosity for this genotype may predispose for this type of multi‐organ autoimmune disease. 1993 Blackwell Publishing

Quantitative assay using recombinant human islet glutamic acid decarboxylase (GAD65) shows that 64K autoantibody positivity at onset predicts diabetes type

At and before onset, most insulin-dependent diabetics (IDDM) have islet GAD65 autoantibodies (GAD65Ab). Since IDDM also occurs in older patients where non-insulin-dependent diabetes is common, we studied GAD65Ab at onset to classify diabetes type. Our quantitative immunoprecipitation assay uses recombinant human islet GAD65 stably expressed in hamster fibroblasts. Electrophoretic mobility was iden