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  • 1
    ISSN: 1432-0428
    Keywords: Incidence ; seasonal variation ; geographical pattern ; sex-difference ; epidemiology ; juvenile-onset ; insulin-dependent ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The incidence, sex, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus (j.i.d.m.) were studied retrospectively on one third of the Danish population 1970–1974. The j.i.d.m. incidence remained fairly constant during the study period, the average being 13.2 per 100000 per year. The total number of boys exceeded the number of girls by 27 per cent. A marked peak of incidence was found at 12–14 years, earlier for females than for males. A seasonal variation in onset (diagnosis) of j.i.d.m. was observed with the lowest number of new cases in May–July. The j.i.d.m. incidence seemed to show socioeconomic differences, being highest in those parts of the survey area with lower status.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Mouse ; experimental diabetes ; streptozotocin ; H-2 system ; sex hormone ; insulitis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five daily injections of streptozotocin (40 mg/kg) produced a delayed but progressively increasing level of hyperglycaemia in long term studies with male Naval Medical Research Institute mice and C3D2F1 (DBA 2 J male × C3H/ Tif female) F1 hybrid mice. The development of hyperglycaemia was paralleled by decreased amounts of pancreatic immunoreactive insulin as well as degranulation and necrosis of pancreatic B cells. Insulitis was found from days 9–25 after the first injection of streptozotocin. Compared with the F1 hybrid strain the parental inbred strains DBA 2 J and C3H/Tif demonstrated a certain resistance to streptozotocin. Development of hyperglycaemia did not differ in four congenic resistant lines of mice on the C57 BL/10 genetic background, indicating that major histocompatibility complex genes are not likely to determine susceptibility to streptozotocin-induced islet B cell damage.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Experimental diabetes mellitus ; glucose intolerance ; virus ; autoimmunity ; immune response genes ; islet-cell-surface antibody ; major histocompatibility locus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Mice with different histocompatibility loci on an identical background genome (congenic resistant lines of mice) were used to study the possible influence of the histocompatibility complex on experimental diabetes. The major histocompatibility complex (H-2) was not found to influence the diabetogenic effect of encephalomyocarditis (EMC) virus. In contrast the glucose intolerance following heterologous and homologous immunization with pancreatic antigens appeared H-2 influenced. Antibodies against cell surface components on viable B-cells were present in serum from mice with glucose intolerance induced by homologous immunization. The results suggest that the susceptibility to experimental autoimmune diabetes in mice is influenced by the H-2 complex.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: HLA ; genetics ; heterogeneity of insulin-dependent diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Three groups of patients with insulin-dependent diabetes mellitus, ascertained by different procedures, were investigated for HLA-A, B, C and D antigens (n=164), and a subset (n=93) for HLA-DR. Both HLA-D/DR3 and D/DR4 were strongly positively associated and D/DR2 was negatively associated with insulin-dependent diabetes. HLA-DR4 was found to be a better marker for insulin-dependent diabetes than Dw4. The HLA-B associations (B8, B15 and B18) were clearly secondary to the increases of HLA-D/DR3 and D/DR 4. The HLA associations did not differ between familial and isolated cases indicating that these two groups may well have a common genetic background. Based on analysis of HLA-haplotype sharing in affected sibling pairs, a simple dominant model of inheritance could be ruled out, and a simple recessive model was found unlikely. The relative risks for the HLA-Dw3,4 and HLA-DR3,4 phenotype were 21.2 and 44.4 respectively and exceeded those of both the HLA-Dw3 and HLA-DR3 (5.6 and 4.3) as well as the HLA-Dw4 and DR4 (10.1 and 10.5) phenotypes. This argues against an intermediate genetic model but further studies are needed to clarify whether there is more than one susceptibility gene for insulin-dependent diabetes mellitus within the HLA-system.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; pancreatic B-cells ; serum cytotoxicity ; serum complement ; islet cell antibodies ; rubidium accumulation ; insulin release ; autoimmunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum from normal blood-donors and juvenile diabetic patients inhibited Rb+ accumulation and stimulated release of 51Cr and insulin in suspensions of dispersed pancreatic islet cells prepared from ob/ob mouse islets, which are rich in B-cells. The effects indicate the presence of a B-cytotoxic factor in human serum. Serum from mouse and fetal calf also inhibited the islet cell accumulation of Rb+. Toxicity was not suppressed by treating serum with protein A-Sepharose and did not correlate with islet cell binding of fluorescent antibodies to human immunoglobulin. Whereas all sera inhibited Rb+ accumulation, 3 of 6 diabetic patient sera, but no blood-donor serum, made the cells fluoresce on exposure to the fluorescent antibodies. Supporting a dependence on complement, toxicity remained after dialysis, but was destroyed by treating serum with zymosan-A or heating at 56 ° for 30 min.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Mouse ; experimental diabetes ; streptozotocin ; sex influence ; sex hormone ; islet cell cytotoxicity in vitro ; lymphocyte transfer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of sex on pancreatic islet B cell susceptibility to streptozotocin was studied in mice given multiple low doses of streptozotocin. Male C3 D2 F1 mice developed a steadily increasing blood glucose level after a lag period of about 3 weeks, in contrast to females who were resistant. Spleen cells from streptozotocin treated female animals produced hyperglycaemia in total body irradiated syngeneic female recipients, but only if the recipients were treated with testosterone. Testosterone treatment of donors did not affect blood glucose levels of recipients. Streptozotocin cytotoxicity in vitro determined by a 51Cr-release assay revealed an increased sensitivity to streptozotocin in dispersed islet cells from adult male animals as compared with cells from adult female mice. The incubation of islet cells from animals of either sex with testosterone, or oestradiol plus progesterone, did not enhance the susceptibility to streptozotocin. Islet cells from sexually immature male or female mice were less susceptible to streptozotocin. The results demonstrate that sex determines susceptibility to streptozotocin in vivo and in vitro.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Experimental diabetes ; mouse ; streptozotocin ; irradiation ; immunosuppression ; morphology ; insulitis ; autoimmunity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five daily injections of streptozotocin (40 mg/kg) produce islet inflammation, necrosis of pancreatic B cells and hyperglycaemia in the mouse. Anti-pancreatic autoimmunity has been suggested as part of the cause of these events. We have studied the possible effect of total-body irradiation in long-term studies (246 days) and report here that insulitis, islet necrosis and insulin depletion are reduced after irradiation. In parallel the level of hyperglycaemia is reduced. It is concluded that immunological mechanisms are to some extent responsible for the development of streptozotocin-induced diabetes.
    Type of Medium: Electronic Resource
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