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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
Background: The impact of a change in mitral regurgitation (MR) following TAVR is unknown. We studied the impact of baseline MR and early post-procedural change in MR on survival following TAVR. Methods: The SWEDEHEART registry included all TAVRs performed in Sweden. Patients were dichotomized into no/mild and moderate/severe MR groups. Vital status, echocardiographic data at baseline and within 7
Diabetes-prone BB rats were examined before, during, and after clinical onset of diabetes for the occurrence of circulating islet cell surface antibodies (ICSAs) with a specific binding to islet β-cells. The presence of ICSA was assessed by incubating serum immunoglobulin fractions with normal Wistar rat islet cells and identifying cell-bound immunoglobulins by indirect immunofluorescence and by a
A BamHI 3.7-kilobase (kb) fragment detected by an HLA-DQ β-chain complementary DNA (cDNA) probe and negatively associated with insulin-dependent diabetes mellitus (IDDM) was cloned and sequenced to localize the polymorphism to BamHI sites in intervening sequences of an HLA-DQ β-chain gene. A probe of the first intervening sequence (IVS 1) showed the BamHI 3.7-kb fragment in 6 of 17 HLA-DR3/4 contr
