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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
Artikel om en flygolycka 1994 då ett B 52 bombplan kraschade under en flyguppvisning på grund av pilotens riskfyllda flygning.
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
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
