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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
First-degree relatives of Type 1 (insulin-dependent) diabetic patients are at increased risk for developing clinical diabetes. The presence of islet cell or insulin autoantibodies further identifies relatives at greater risk, but not all immunologic-marker-positive relatives progress to disease. Beta-cell dysfunction, however, seems to be more prevalent than clinical Type 1 diabetes, since stable
To evaluate the possibility of autoimmune processes against pancreatic islets in fetal life, we tested islet cell antibody (ICA) reactivity with 14 fetal pancreata obtained after abortion at the 15th up to the 19th week of gestation. Pancreatic islets positive for a monoclonal proinsulin antibody but non-reactive with ICA negative control serum were found in 9 14 pancreata and all ( 9 9) of them s
A rat islet tumor subclone, RIN-5AH-T2-B, was cultured with 2 mmol/liter of the proliferation-arresting compound sodium butyrate (NaB). Insulin gene expression and glucose-stimulated insulin release were analyzed and compared with logarithmically proliferating and confluent control cells cultured without NaB. Logarithmically proliferating control cells revealed high insulin gene expression. In the
Inbred lymphopenic, diabetes-prone (DP) and non-lymphopenic, diabetes-resistant (DR) BB rats in a specific pathogen-free (SPF) colony were subjected to a cross-intercross breeding experiment which showed diabetes to segregate as a recessive trait. All DP rats, but none of the DR and F1 rats, developed diabetes. In contrast, about 25% of the F2 rats developed diabetes which made it possible to stud
The BB rat spontaneously develops insulin-dependent diabetes mellitus (IDDM) in association with marked insulitis in the islets of Langerhans. Since platelet-activating factor (PAF-acether) is involved in allergic and inflammatory reactions, we tested a PAF antagonist, Ginkgolide B (BN 52021) for potential effects on islet inflammation and diabetes. Diabetes prone BB/Wor rats were treated daily fr
Mechanisms underlying the etiology and pathogenesis of insulin-dependent diabetes mellitus (IDDM) are reviewed. Its natural history and associated autoimmune phenomena indicate that IDDM is a systemic disorder resulting in a specific disappearance of pancreatic β cells. Genetic aspects of the disorder include its linkage to HLA class II gene loci, although the manner in which this produces autoimm
Diabetes-prone (DP) BB rats spontaneously develop insulin-dependent diabetes resembling type 1 diabetes mellitus in man. They also exhibit lifelong T cell deficiency. The segregation of both diabetes and lymphopenia was studied in crosses between this inbred line of rats and the related but nondiabetic and nonlymphopenic inbred diabetes-resistant (DR) BB rat line. Diabetes segregated as a single,
Forty-one assays were analysed at the 3rd International Workshop on the standardisation of islet cell antibodies. Analysis of precision demonstrated assays consistently detecting blind duplicates within one doubling dilution and capable of discriminating one doubling dilution differences in islet cell antibody concentration. Some assays, however, reported duplicates discrepantly by more than seven
Site-specific, high affinity polyclonal antisera are effectively and successfully produced by immunizing rabbits with synthetic peptides. The use of these antisera in subsequent immune analysis is often limited because of non-specific binding. We describe a new and simple method to effectively affinity-purify anti-peptide antibodies. To test our system, rabbits were immunized with model peptides r
Long term effects of in vivo treatment with human rIL-1β on diabetogenesis and thyroid disease were determined in the Biobreeding rat. Administration of high dose (10 μg/kg) IL-1β accelerated the onset of insulin-dependent diabetes mellitus compared to saline-injected controls. High dose treatment resulted in goiter development, pronounced LT, reduced serum T4 levels, and overall growth reduction.
Insulin autoantibodies (IAAs) occur in newly diagnosed human insulin-dependent diabetes mellitus (IDDM) patients, but their presence in BB rats is controversial, possibly due to assay differences or variability in the animals studied. To resolve this controversy, IAAs were measured in well-characterized inbred BB rats both in radioligand assays with 125I-labeled rat insulin I or II, respectively,
Restriction fragment length polymorphism using an HLA‐DQ β‐chain genomic probe showed that 63 children with insulin‐dependent (type 1) diabetes mellitus (IDDM) were all (100%) positive for the BamH1 fragments 12 kb and/or 4 kb compared to 98% (62/63) for HLA‐DR3 and/or 4 and 75% (47/63) for HLA‐B8 and/or 15. The 36 (56%) DR3‐positive children were all 4‐kb‐positive; however, a total of 44 (70%) ch
To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive an-odal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal tryps
