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Inbred specific pathogen-free diabetes-prone (DP) and diabetes-resistant (DR) BB rats were crossed to produce F1 and intercrossed to produce F2 rats. Diabetes segregates in these crosses as a recessive trait on rat chromosome 4. The weight gain of genetically diabetes-prone rats born to F1 healthy parents was studied to avoid effects of maternal diabetes. The weight gain of the F2 rats was initial
Glutamic acid decarboxylase (GAD) catalyzes the synthesis of γ-aminobutyric acid (GABA), which is known as a major inhibitory neurotransmitter in the central nervous system (CNS), but is also present outside the CNS. Recent studies showed that GAD is the major target of autoantibodies associated with the development of insulin-dependent diabetes mellitus and of the rare stiff man syndrome. Studies
Objective: Coeliac disease is closely associated with the presence of gliadin antibodies and certain HLA class II alleles. The aim of this study was to compare the HLA genotype in gliadin antibody-positive individuals without coeliac disease with that in patients with clinically verified coeliac disease.Design: HLA genotyping was carried out in 65 patients with coeliac disease and the results were
OBJECTIVE - To determine the effects of islet cell antibodies on β-cell function during the first 3 yr after diagnosis in type II diabetic patients. RESEARCH DESIGN AND METHODS - β-cell function in type II diabetic patients with (n = 11, 50 ± 5 yr of age) and without (n = 10, 52 ± 4 yr of age) ICA was followed prospectively and compared with β-cell function in type I adult diabetic patients (n = 1
Islet cell antibodies (ICA), fasting plasma C-peptide, and HbA(1c) were evaluated up to 10 years after diagnosis in 52 patients with diabetes diagnosed in adult age (mean age at diagnosis 53 ± 2 yr, range 21-76 yr) with a high (>20 IU/day) insulin requirement (group A) and in 50 matched control patients with diabetes diagnosed in adult age (mean age at diagnosis 54 ± 2 yr, range 24-73 yr) with low
The BB rat is among the best models of insulin−dependent diabetes mellitus — with onset and pathogenesis closely resembling the human disease. One unusual feature is a severe T−cell lymphopenia, which appears to be inherited as a recessive trait controlled by a single gene, Lyp. Based on genetic analysis of several crosses, we show that development of diabetes involves at least three genes: Lyp, w
A novel sequential Injection Immunoassay (SI I A) method Is described which utilizes Immunomagnetic beads to Investigate short-time antibody binding. The method Is versatile and flexible and may therefore be adapted to many different applications. Initial results for a competitive assay are also presented. The Immunomagnetic bead reactor Is created within the flowing stream by retaining Immunomagn
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The effect of age on ICA and thyrogastric antibodies at diagnosis of IDDM was evaluated in 633 consecutively diagnosed Swedish diabetic patients aged 15-34 yr and in 282 volunteers of the same age. ICAs were present in 61% (383 of 633) of the patients and in 2% (5 of 282) of control subjects. When the initial classification was considered, ICAs were detected in 69% (327 of 473) of patients with ID
GAD is an autoantigen in IDDM. Molecular cloning and specific antibodies allowed us to demonstrate that only the lower Mr GAD64 isoform is expressed in human islets, in contrast to human brain, rat islets, and rat brain, all of which express both GA064 and GAD67. Expression of the human islet GAD64 isoform in COS-7 and BHK cells resulted in an enzymatically active rGAD64, which is immunoreactive w
Previous studies have determined that daily low dose injections of the potent cytokine interleukin-1β (IL-1β) decreased the frequency of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone (DP) BB rats. In contrast, high dose injections induced an earlier than normal onset. In this study we tested whether the effects of daily human recombinant IL-1β injections on leukocyte subsets were as
The goal of the Fourth International Workshop for Standardization of ICA Measurements was to determine the specificity of ICA assays and their ability to distinguish between control sera (n = 57) and sera from IDDM-related individuals-representing relatives of IDDM patients (n = 21), healthy individuals who later developed IDDM (n = 8), or newly diagnosed IDDM patients (n = 23). Results from 28 la
Autoantibodies against the βcell Mr 64,000 protein (p64), recently identified as an isoform of glutamic acid decarboxylase (GAD), are prevalent in patients with insulin-dependent diabetes mellitus (IDDM). Dog islets were found to represent an abundant source of native p64 allowing the study of antigen-antibody interactions in IDDM. A quantitative, standardized assay for p64 antibodies based on dog
The recent development of the flow-injection immunoassay (FIIA), beginning with one of the first publications in 1980 by Lim and Miller, has resulted in a growing field which combines the precise and reproducible timing of flow-injection analysis (FIA) with immunoassays to yield assays which are carried out in a nonequilibrium time frame. These often faster assay methods require small volumes of s
Glutamic acid decarboxylase (GAD; glutamate decarboxylase, L-glutamate 1-carboxy-lyase, EC 4.1.1.15), which catalyzes formation of γ-aminobutyric acid from L-glutamic acid, is detectable in different isoforms with distinct electrophoretic and kinetic characteristics. GAD has also been implicated as an autoantigen in the vastly differing autoimmune disease stiff-man syndrome and insulin-dependent d
A role for the Epstein-Barr virus in initiating Type 1 (insulin-dependent) diabetes mellitus has been proposed since Epstein-Barr virus BOLF1(497-513) AVTPL RIFIVP PAAEY has an 11 amino acid identity with HLA-DQw8 β (49-60) AVTPL GPPAAEY. Rabbit antisera to the BOLF1 (496-515) peptide crossreacted with the homologous DQw8 β (44-63) peptide but not with the related DQw7 β(44-63) peptide, which diff
Daily injections of high dose human recombinant interleukin-1β (IL-1β) accelerated the onset of both insulin-dependent diabetes mellitus and lymphocytic thyroiditis in genetically prone BB rats. In diabetes-resistant BB rats, high dose IL-1β failed to induce diabetes. Additionally, the presence of neutralizing IL-1β antibodies in these rats strongly correlated with inhibition of lymphocytic thyroi
Islet cell cytoplasmic antibodies were determined in 85 individuals 60 to 74 years old with fasting hyperglycaemia, in 65 patients with cystic fibrosis, in 113 patients with pancreatitis, in 21 patients with Turner's phenotype, and in 135 first‐degree relatives of patients with Type 1 (insulin‐dependent) diabetes. Islet cell antibodies were absent in all 60 to 74‐year‐old subjects with fasting hyp
