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Diabetes segregates as a single locus in crosses between inbred BB rats prone or resistant to diabetes

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,

Assessment of precision, concordance, specificity, and sensitivity of islet cell antibody measurement in 41 assays

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

A novel affinity purification method to isolate peptide specific antibodies

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

IL-1β modulation of spontaneous autoimmune diabetes and thyroiditis in the BB rat

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.

Lack of systematically found insulin autoantibodies in spontaneously diabetic BB rats

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,

HLA Heterozygosity in Insulin‐Dependent Diabetes is Most Frequent at the DQ Locus

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

Immunoreactive trypsin(Ogen) in the sera of children with recent-onset insulin-dependent diabetes and matched controls

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

Change in mitral regurgitation severity impacts survival after transcatheter aortic valve replacement

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

Spontaneously diabetic BB rats have age-dependent islet β-cell-specific surface antibodies at clinical onset

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

Molecular cloning of a polymorphic DNA endonuclease fragment associates insulin-dependent diabetes mellitus with HLA-DQ

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

Detection of islet cell autoantibodies in newly diagnosed diabetic patients using insulin-producing Syrian hamster cells.

An insulin-producing cell line, Clone-16, of hamster origin, was characterized for islet hormone production and for reactivity with islet cell surface (ICSA) and islet cell cytoplasmic (ICA) antibodies in sera from children with newly diagnosed insulin-dependent (Type 1) diabetes mellitus (IDDM). The Clone-16 cells have a doubling time of about 50-60 hr. The cells produced 63 ± 3 ng (mean ± SD) im

Prolonged incubation in the two-colour immunofluorescence test increases the prevalence and titres of islet cell antibodies in Type 1 (insulin-dependent) diabetes mellitus

The conventional indirect immunofluorescence test of islet cell antibodies was recently improved by the development of a two-colour immunofluorescence assay using a monoclonal proinsulin antibody to detect islet B cells. The aim of this study was to test whether in this new assay the prevalence and titre of ICA were affected by the time of incubation carried out in the presence of aprotinin (Trasy

Islet cell and 64k autoantibodies are associated with plasma IgG in newly diagnosed insulin-dependent diabetic children

There is a high prevalence of islet cell antibodies (ICA) and autoantibodies detected against an islet cell protein of M(r) 64,000 at the time of clinical diagnosis of insulin-dependent diabetes (IDDM). In view of the biphasic immune response after antigen presentation, the purpose of this study was to determine the presence of ICA and antibodies against the 64,000 islet antigen after separation o

A simple assay for the detection of antibodies to endocrine islet cell surface antigens

A simple and sensitive immunoradiometric assay for the detection of islet cell surface antibodies (CIRMA) has been developed. Live, transformed islet cells derived from a liver metastasis of a transplantable islet cell tumor were grown in removable microtiter wells and incubated with antibody. Cell-bound antibodies were quantitated using 125I-labelled second antibodies. The assay was used to detec