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K Buschard

Publications and source records attributed to K Buschard.

123 records · Page 7Linked to original sources

Is the diabetogenic effect of streptozotocin in part thymus-dependent?

Following a single injection of 200 mg streptozotocin/kg BW, 25 out of 25 normal mice became diabetic, whereas 12 ( = 20%) out of 50 athymic nude mice did not develop diabetes. In a multiple dosage experiment, where the same total dose was given over a 5 days period, 14 normal and 15 athymic nude mice all became diabetic, but nude mice had significantly lower blood glucose values. These results support our previous suggestion that a thymus dependent immune reaction is, in part, responsible for the diabetogenic effect of streptozotocin.

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Passive transfer of virus induced diabetes mellitus with spleen cells.

The study describes passive transfer of diabetes mellitus by transplantation of spleen cells from donor mice infected with a diabetogenic encephalomyocarditis virus. Inbred normal C57 mice were used as both donors and recipients, and other recipients were C57 athymic, nude mice. Transplants were made in two series after 12 and 22 days duration of infection of the donors, respectively. All recipients became diabetic. The possibility of virus transfer with the spleen cell transplant is discussed, and found to be highly improbable. The fact that passive cellular transfer can be effected points to a decisive significance of the thymus dependent lymphocyte system in the pathogenesis of the primary diabetes.

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T-lymphocytes transfer streptozotocin induced diabetes mellitus in mice.

Diabetes mellitus induced by low dose treatment with streptozotocin in BALB/c mice was passively transferred to syngeneic recipients with a predominantly T-lymphocyte fraction of spleen cells. This fraction was prepared by density centrifugation and passage through an antimouse immunoglobulin coated column. Variation in numbers of injected cells in the range of 10(3) to 10(7) showed that the smaller cell numbers gave the highest blood sugar values. Athymic nude recipients of BALB/c background also developed diabetes following similar transplants. A preliminary result was that the highest blood sugars were seen after transplantation of T-lymphocytes treated by low dose irradiation (200 R). This may reflect a specific effect on T-suppressor lymphocytes.

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Incidence, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus in Denmark.

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%. 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.

Adolescent↗

Passive transfer of streptozotocin induced diabetes mellitus with spleen cells. Studies of synogeneic and allogeneic transfer to normal and athymic nude mice.

This study shows passive transfer of streptozotocin induced diabetes mellitus in mice. Transplants of spleen cells from BALB/c mice, streptozotocin treated for 5 days, induced diabetes in normal BALB/c recipients. Treatment of transplants with anti-theta and complement resulted in a significant decrease in the degree of diabetes. Athymic nude mouse recipients of BALB/c background also developed diabetes after transpant of spleen cells from both syngenic and allogenic (C-7/Bl/6) donors. It is concluded that passive transfer of chemically induced diabetes in mice is practicable, in both syngeneic and allogeneic combinations, and that thymus derived lymphocytes are significant in this process.

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Culture of isolated pancreatic islets: its applications for transplantation purposes.

The aim of this study was to assess the curative effects of long-term stored islets, when transplanted into diabetic recipients. For this purpose mouse pancreatic islets, either freshly isolated or cultured for 10 days, were allografted intraperitoneally into noninbred mice or into nude mice, all made diabetic by means of a streptozotocin injection. When implanted into nude mice, which lack a cell-mediated immune response, cultured islets were equally effective as were freshly isolated islets, in reducing the hyperglycemia. When fresh or cultured islets were allografted into diabetic NMRI mice there was only a short and transient reduction of the blood sugar, suggesting that no reduction of the antigenicity of the islets had occurred after 10 days of culture. The culture system, however, may serve as a purification step, after which only functionally competent islets remain.

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Restitution of streptozotocin induced diabetes mellitus in nude mice with pancreatic grafts from the rat.

Transplants of 1-3 rat pancreases have proven to restitute streptozotocin induced diabetes in athymic nude mice. One out of 9 diabetic nude mice showed restitution following subcutaneous implantation of 1 rat pancreas. Three out of 6 nude mice were restituted by 2-3 grafts. Implants of rat submandibular gland did not restitute nude mice similarly treated with streptozotocin. The model seems of interest in studies of inter-species transplantation of pancreas.

Animals↗

The inability of a diabetogenic virus to induce diabetes mellitus in athymic (nude) mice.

The effect of a known diabetogenic M-strain encephalomyocarditis (EMC)-virus in athymic nude mice (lacking the thymus-dependent lymphocyte system), and in heteroxygous littermates and homozygous normal mice of the background strain (C57/B16) was investigated. While by 3 weeks 4 out of 4 surviving virus-inoculated littermates and 9 out of 9 inoculated normal mice developed diabetes mellitus, none of the 7 surviving virus-inoculated nude mice became diabetic. Virus was isolated from all inoculated animals, including non-diabetic nude mice. It is concluded that it is the response of the thymus-dependent lymphocyte system evoked by the virus rather than the virus itself that leads to damage to the insulin producing cell.

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Gluten-free diet prevents diabetes in NOD mice.

BACKGROUND: Epidemiological as well as animal studies have shown that environmental factors such as nutrition contribute to the development of diabetes. In this study we investigated whether the early introduction of a gluten-free diet can influence the onset and/or incidence of diabetes, as well as insulitis and the number of gut mucosal lymphocytes, in non-obese diabetic (NOD) mice. METHODS: Gluten-free and standard Altromin diets (with the same milk protein and vitamin content) were given to breeding pairs of NOD mice as well as to the first generation of NOD female mice, which were then observed for 320 days. RESULTS: A substantially lower diabetes incidence (chi(2)=15.8, p=0.00007) was observed in NOD mice on the gluten-free diet (15%, n=27) compared to mice on the standard diet (64%, n=28). In addition, mice on the gluten-free diet developed diabetes significantly later (244+/-24 days SEM) compared to those on the standard diet (197+/-8 days, p=0.03). No differences in the number of CD3(+), TCR-gammadelta(+), IgA(+), and IgM(+) cells in the small intestine were observed. CONCLUSION: We showed that gluten-free diet both delayed and to a large extent prevented diabetes in NOD mice that have never been exposed to gluten.

Animal Feed↗

Morphological effects of sodium fusidate (fusidin) on pancreatic islet cells: an electron microscopic study.

Fusidic acid has been shown to prevent the lymphocyte co-stimulatory activities of cytokines and seems--in preliminary trials--clinically effective as an immunoregulatory drug e.g. in insulin-dependent diabetes mellitus. A toxic effect of fusidic acid may however be suspected since a previous study showed a significant dilatation of rough endoplasmic reticulum in cultured pancreatic islet cells from normal rats. In this study we examined the ultrastructural effects of the sodium salt of fusidic acid (fusidin) on cultured rat islet cells (treatment period 3-5 days), and of islet cells from rats receiving fusidin for 6 days. Electron microscopically, fusidin treatment in vitro (3 to 30 micrograms/ml) showed a significant dilatation of the rough endoplasmic reticulum of islet cells. No dose dependent changes were found. In the in vivo model no changes were demonstrated in concentrations of fusidin up to 9.64 micrograms/ml of homogenated pancreatic tissue. It is concluded that treatment with fusidin gives no detectable ultrastructural changes in vivo.

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