| 1. |
- Madsen, O. D., et al.
(författare)
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Cloned cell lines from a transplantable islet cell tumor are heterogeneous and express cholecystokinin in addition to islet hormones
- 1986
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Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 103:5, s. 2025-2034
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Tidskriftsartikel (refereegranskat)abstract
- A liver metastasis (MSL) with a remarkable in vitro proliferation potential has been identified in an NEDH rat carrying a transplantable x-ray-induced islet cell tumor. Two insulin-secreting cell lines, MSL-G and MSL-H, with doubling times of 3-5 d were established by repeated limiting dilution cloning. In vivo inoculation of MSL-G cells induced severe hypoglycemia caused by a small but highly heterogeneous tumor as revealed by immunocytochemistry. Whereas most cells stained for the islet hormones, insulin, glucagon, and somatostatin, clustered cells were discovered to contain cholecystokinin (CCK). Additional in vitro-limiting dilution cloning, followed by immunocytochemical characterization, clearly demonstrated the capacity of single cell clones to simultaneously express the same four hormones. Radioimmunoassays with a panel of site-specific antisera of culture supernatants and purified cell extracts showed the MSL-G2 cells to produce, store, and secrete readily detectable amounts of processed and unprocessed CCK. Gastrin was not detected while coexpression of glucagon and CCK were demonstrated. Mutant clones selected for resistance to 6-thioguanine (frequency, 2 x 10-7) and checked for HAT (hypoxanthine, aminopterin, thymidine) sensitivity retained the capacity for multihormone expression. We propose that the MSL tumor contains pluripotent endocrine stem cells. The MSL tumor and the MSL-G2 cells in particular will allow studies of not only CCK biosynthesis and processing but also of mechanisms involved in tumor and islet cell differentiation.
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| 2. |
- Bjorck, L., et al.
(författare)
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A deletion in a rat major histocompatibility complex class I gene is linked to the absence of β2-microglobulin-containing serum molecules
- 1986
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 83:15, s. 5630-5633
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Tidskriftsartikel (refereegranskat)abstract
- Class I major histocompatibility antigens are composed of a heavy chain that is noncovalently associated with β2-microglobulin (β2m). Most class I molecules are membrane bound, but mouse and rat cDNA clones and genes without a functional code for the transmembrane amino acids have been identified. The membrane-associated class I molecules are important in the control of cell-mediated cytotoxicity, while the function of the soluble molecules remains unclear. Previous studies have shown that β2m circulates in rat serum in three different molecular weight classes. The first is free β2m (M(r), 12,000), the second is about M(r) 70,000, and the third is roughly M(r) 200,000. In an inbred subline of immunodeficient, diabetesprone BioBreeding rats (BioBreeding/Hagedorn), previous work detected two restriction fragment polymorphisms in class I major histocompatibility complex genes, one of them a gene deletion on a 7-kilobase BamHI fragment and the other on a 2-kilobase BamHI fragment. In these rats we have found that the third serum β2m-binding size class is absent. Analysis of F1 and F2 individuals following cross-breeding between Bio-Breeding/Hagedorn rats and genetically related (nondiabetic) control BioBreeding w-subline rats demonstrated that the large-size serum peak of β2m was associated with the presence of the class I restriction fragments.
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| 3. |
- Dyrberg, T., et al.
(författare)
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Patogenesen ved type 1 diabetes.
- 1989
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Ingår i: Ugeskrift for Laeger. - 0041-5782. ; 151:17, s. 1029-1030
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Herold, K C, et al.
(författare)
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Derivation of non-lymphopenic BB rats with an intercross breeding
- 1989
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 3:2, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have suggested that the development of diabetes in the BB rats does not require the expression of T lymphopenia. In order to derive non-lymphopenic diabetic rats and define the relationship between the T cell abnormalities, MHC genotype, and diabetes, we performed a cross between BB/H and diabetes resistant BB/control followed by an intercross of the F1. In the F2, the overall incidence of diabetes and lymphopenia was 30% and 27%, respectively. Lymphopenia was strongly associated with diabetes (p less than 0.001) and was seen in 76% of the diabetic F2's. However, 6 of the diabetic were non-lymphopenic (24%) and 3 of the non-diabetics were lymphopenic (5%). In the non-lymphopenic diabetic animals, all T cell levels were within the normal range, but diabetes occurred at an earlier age than their lymphopenic littermates (p less than 0.001). In contrast to the strong association between the inheritance of lymphopenia and diabetes, no relationship between diabetes and Class I MHC restriction fragment length polymorphisms was found. We conclude: 1) Diabetes and lymphopenia are strongly associated inherited abnormalities in the BB rat and are not associated with Class I RFLP defined genotypes within the RTIu haplotype, 2) Animals in whom diabetes occurs in the absence of lymphopenia can be derived using this breeding approach 3) In our non-lymphopenic rats, diabetes occurred at an earlier age possibly reflecting the restoration of quantitative or qualitative T cell defects found in lymphopenic BB rats.
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| 5. |
- Landin-Olsson, M., et al.
(författare)
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Islet cell and other organ-specific autoantibodies in all children developing Type 1 (insulin-dependent) diabetes mellitus in Sweden during one year and in matched control children
- 1989
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Ingår i: Diabetologia. - 0012-186X. ; 32:6, s. 387-395
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Tidskriftsartikel (refereegranskat)abstract
- The majority (about 90%) of children developing Type 1 (insulin-dependent) diabetes mellitus do not have a first-degree relative with the disease. Nearly all (389/405, 96%) children (0-14 years) in Sweden, who developed diabetes during one year, were therefore studied to compare islet cell, thyroid peroxidase, thyroglobulin, and gastric H+, K+-ATPase antibodies with 321 age, sex, and geographically matched, but non-related, control children. Islet cell (cytoplasmic) antibodies were found in 81% (316/389) of the patients and in 3% (9/321) of the control children (p<0.001). The median islet cell antibody levels were 70 (range 3-8200) Juvenile Diabetes Foundation (JDF) Units in the islet cell antibody positive patients, and 27 (range 17-1200) JDF Units in the control children (NS). Autoantibodies against thyroid peroxidase (8%), thyroglobulin (6%), and gastric H+, K+- ATPase (3%) were all increased in the patients compared with the control children, being 2% (p<0.001), 2% (p<0.01), and 0.3% (p<0.01), respectively. During an observation time of 20-34 months, two of the nine islet cell antibody positive control children developed Type 1 diabetes, after 8 and 25 months respectively, while the others remained healthy and became islet cell antibody negative. None of the islet cell antibody negative control children developed diabetes during the same time of observation. This first investigation of an unselected population of diabetic children and matched control children shows: that islet cell antibodies are strongly associated with newly diagnosed childhood diabetes, that other autoantibodies are more frequent among diabetic children than control children, and that the frequency of islet cell antibodies in the background population of children is higher than previously documented, and could also be transient, underlining that factors additional to islet cell antibodies are necessary for the later development of Type 1 diabetes.
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| 6. |
- Lernmark, A., et al.
(författare)
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Genes and gene products in the development of diabetes mellitus : Concluding remarks
- 1989
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Ingår i: Genes and gene products in the development of diabetes mellitus : proceedings of the 3rd Nordisk Insulin Symposium 'Genes ane gene products in the development of diabetes mellitus'. ICS866 - proceedings of the 3rd Nordisk Insulin Symposium 'Genes ane gene products in the development of diabetes mellitus'. ICS866. - 0444813225 ; , s. 421-428
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Konferensbidrag (refereegranskat)
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| 7. |
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| 8. |
- Madsen, O D, et al.
(författare)
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A two-colour immunofluorescence test with a monoclonal human proinsulin antibody improves the assay for islet cell antibodies
- 1986
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Ingår i: Diabetologia. - : Springer-Verlag New York. - 0012-186X .- 1432-0428. ; 29:2, s. 8-115
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Tidskriftsartikel (refereegranskat)abstract
- The conventional indirect immunofluorescence assay for islet cell antibodies was compared with a two-colour immunofluorescent assay to detect both islet cell antibodies with fluorescein isothiocyanate-labeled rabbit anti-human IgG and pancreatic B cells with a monoclonal human proinsulin antibody and Texas red-labeled sheep anti-mouse IgG. Determinations of end-point titres showed a correlation between the new two-colour immunofluorescent assay and the conventional indirect immunofluorescent assay in 1) selected sera positive for islet cell antibodies and insulin autoantibodies rs = 0.93 (p less than 0.01) or for islet cell antibodies alone rs = 0.99 (p less than 0.005) and 2) sera from children or young adults with newly diagnosed Type 1 (insulin-dependent) diabetes rs = 0.95 (p less than 0.0001). No interference between the monoclonal human proinsulin antibodies and islet cell antibodies with or without insulin autoantibodies or between the two second fluorescent antibodies was detected. It is concluded that the two-colour immunofluorescence assay is advantageous since it is possible to mix the reagents to avoid a more time-consuming and technically complicated assay, the presence of B cells can be confirmed in each section to permit detection of B cell cytoplasmic antibodies and microscopic evaluation is easier and more accurate, particularly in islet cell antibody negative samples.
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