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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In summary, our bone marrow chimeras studies suggest that there are two defects in the BB rat associated with diabetes and/or lymphopenia, one residing at the level of the bone marrow lymphoid stem cell and the other within the T-cell differentiative environment, apparently postthymic. Our neonatal thymus transplantation studies and the adult thymus transplantation studies of others suggest a third defect in the BB rat, within the thymus itself, but this defect appears not to be responsible for the development of either the diabetes or the T lymphocytopenia. Rather, the thymic defect appears to control, at least in part, the lymphocyte hyporesponsiveness characteristic of the diabetes-prone BB rat. The role of the RT6 T-cell differentiation antigen in the etiopathogenesis of diabetes in this animal model remains unclear.
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PMID:The spontaneously diabetic BB rat: sites of the defects leading to autoimmunity and diabetes mellitus. A review. 219 61

Transplantation of bone marrow cells from nonobese diabetic (NOD) mice, a model for type 1 diabetes mellitus, to C3H/HeN mice, which express I-E alpha molecules and have aspartic acid at residue 57 of the I-A beta chain, induced insulitis followed by overt diabetes in the recipient C3H/HeN mice more than 40 weeks after bone marrow transplantation. When cyclosporin A, which perturbs T-cell functions, was injected intraperitoneally into [NOD----C3H/HeN] chimeric mice daily for 1 month, the chimeric mice developed insulitis and overt diabetes within 20 weeks following bone marrow transplantation. Transplantation of bone marrow cells from (NZW x BXSB)F1 mice, which develop lupus nephritis, myocardial infarction, and idiopathic thrombocytopenic purpura, into C3H/HeN or C57BL/6J mice induced in the recipient strains both lupus nephritis and idiopathic thrombocytopenic purpura more than 3 months after transplantation. Transplantation of a stem-cell-enriched population from (NZW x BXSB)F1 mice into normal mice also induced autoimmune disease in the recipients. These results indicate that both systemic autoimmune disease and organ-specific autoimmune disease originate from defects that reside within the stem cells; the thymus and environmental factors such as sex hormones appear to act only as accelerating factors.
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PMID:Organ-specific and systemic autoimmune diseases originate from defects in hematopoietic stem cells. 223 44

Alloxan diabetes (sucrose blood concentrate greater than or equal to 14 mmol/l decreased the life time of blood lymphocytes and increased the migration of these cells from lymphatic organs in BALB/c male mice. The proliferation pools of lymphoblasts and prolymphocytes in the thymus of diabetic mice were depressed, but in the lymphatic nodes remained unchanged. It has been shown that in lymphoid cells of the thymus of mice with diabetes the generation time and the time of G1- and G2-phase were significantly increased, but the time of the S-phase of the life cycle of these cells was normal. Proliferation of the lymphoid cells in lymphatic nodes was insulin-dependent. It has been shown that in the prolymphocytes of lymphatic nodes from diabetic mice the duration of the G1-phase was significantly decreased.
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PMID:[Kinetics of lymphocytes in mice with alloxan diabetes]. 227 95

Antibodies to an Mr 64,000 protein from human or rat islets have been detected at high frequency in newly diagnosed insulin-dependent diabetic patients. In this study, we show that the antigenic and amphiphilic properties of the rat islet Mr 64,000 protein resemble that of the human protein. We have analyzed the expression of the Mr 64,000 protein in populations of pancreatic beta and non-beta cells and in selected rat tissues by immunoprecipitation of [35S]methionine-radiolabeled proteins with sera from diabetic patients or from healthy control individuals. When islet cell populations enriched in beta or non-beta cells were tested for the expression of the Mr 64,000 antigen, the protein was primarily observed in the beta cells. On analyzing preparations of islets, liver, kidney, thyroid, adrenal, pituitary, spleen, and thymus, the protein could only be detected in islets. The protein was also characterized in terms of its subcellular localization by Percoll density gradient centrifugation and was recovered in a fraction enriched in the plasma membrane marker, 5'-nucleotidase. These results are consistent with a beta cell-restricted plasma membrane expression of the protein and support the hypothesis that this protein is a target antigen of beta cell-specific autoimmunity in insulin-dependent diabetes.
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PMID:Cellular and subcellular localization of an Mr 64,000 protein autoantigen in insulin-dependent diabetes. 240 61

The nonobese diabetic (NOD) mouse has recently been introduced as a model for insulin-dependent diabetes mellitus. The role of regulatory T cells in the development of antipancreatic autoimmunity in this model remains unclear. To evaluate the presence of suppressive phenomena, we used disease transfer by spleen cells from diabetic NOD mice into preirradiated adult recipients as a model for accelerated disease. Suppressor phenomena were detected by testing the protection afforded by lymphoid cells from nondiabetic NOD mice against diabetes transfer in irradiated recipients. Transfer of diabetes was delayed by reconstituting recipients with spleen cells from nondiabetic NOD donors. The greatest protection against diabetes transfer was conferred by spleen cells from 8-wk-old nondiabetic female NOD mice. Depletion experiments showed that the protection was dependent on CD4+ cells. Protection was also detected within thymic cells from nondiabetic NOD mice and protection conferred by spleen cells was abrogated by thymectomy of nondiabetic female, but not male, NOD donors at 3 wk of age. These findings indicate that suppressive CD4+ T cells that are dependent on the presence of the thymus may delay the onset of diabetes in female diabetes-prone NOD mice.
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PMID:T cell-mediated inhibition of the transfer of autoimmune diabetes in NOD mice. 252 54

The maternal and fetal endocrine pancreas were investigated in the diabetic BB rat on day 21 of pregnancy. The maternal pancreas of the diabetic rat contained practically no insulin-positive B cells. The A and D cell mass were also decreased, while plasma glucagon and somatostatin levels were normal or increased, confirming previous data. Six of 11 diabetic rats had B-cell-specific surface antibodies (ICSA), whereas only 1 of 10 nondiabetic rats was ICSA-positive. The volume density of insulin-positive cells was decreased in the fetal pancreas of diabetic BB rats compared to fetuses of nondiabetic rats, but the volume density of glucagon- and somatostatin-positive cells remained normal. The B cells of these fetuses were ultrastructurally less granulated and showed signs of increased cellular activity. Plasma insulin levels were decreased while plasma glucagon and somatostatin concentrations were normal. ICSA were not detected in fetuses of nondiabetic and diabetic rats. There were no differences in the histology of the spleen and thymus between both groups of fetuses. Metabolic characterization of the growth-retarded fetuses of diabetic rats revealed, besides lower plasma insulin concentrations, increased branched chain amino acid levels, and normal plasma Sm/IGF-I levels. The main conclusions from this study are: (1) Severe maternal diabetes decreases the pancreatic insulin-positive cell mass and plasma insulin levels in the fetus, but not the A and D cell mass and function; (2) ICSA are not detectable in fetal plasma; (3) the influence of maternal BB rat diabetes on fetal endocrine pancreas and metabolic environment resembles that of severe streptozotocin-induced diabetes.
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PMID:Maternal and fetal endocrine pancreas in the spontaneously diabetic BB rat. 256 32

Diabetes prone BB-rats develop an insulin-dependent diabetes mellitus between postnatal day 60 and 120 in a high incidence. Moreover, even before onset of the diabetes, these animals are deficient in the RT6+ subset of T lineage cells. We here put forward evidence that the export of cells from the thymus is normal in these rats, suggesting a maturational block in the periphery. We show furthermore by Southern blot analysis that diabetes prone BB-rats possess the RT6a gene which is not grossly altered in comparison to that of diabetes resistant strains.
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PMID:Evidence for normal thymic export of lymphocytes and an intact RT6a gene in RT6 deficient diabetes prone BB-rats. 257 57

The thymus of diabetes prone BB rats (DP) was studied and compared with diabetes resistant (DR) BB rats and normal WAG rats. Thymuses were obtained from 4-5 week old animals, i.e. before the onset of disease. Analysis included specific immune histology using a panel of monoclonal antibodies directed against markers both on thymocytes and stromal cells. No striking differences were observed between the three groups with regard to the expression and distribution of the various T cell markers. There was however a marked difference for thymic class II MHC antigen expression between the various groups. Whereas WAG rats displayed a regular class II MHC pattern both in the cortex and the medulla, both DR and DP rats showed large areas in the cortex where there was no class II MHC staining. The lack of expression of class II MHC antigens in these 'holes' was associated with a complete absence of epithelial cells in that area. Also in the medulla of DP and DR thymuses 'holes' in the keratin-stroma were observed. The stromal aberrations in these auto-immune prone rats are discussed in the context of the deficient T cell system in these animals.
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PMID:Defects in the thymic epithelial stroma of diabetes prone BB rats. 262 36

Bio-Breeding rat T lymphocytes proliferate poorly in response to alloantigen. Transplantation of Bio-Breeding rats with fetal thymus tissue from diabetes resistant rats leads to an improvement in the T cell proliferative response, but only if the thymus contains bone marrow-derived, radiation-resistant thymic antigen presenting cells of the diabetes-resistant phenotype. The current study provides evidence that thymus transplantation leading to the restoration of Bio-Breeding T cell proliferative function can also significantly reduce the incidence of insulitis and prevent the development of diabetes. It appears that a defect in the bone marrow-derived thymic APC population contributes to an abnormal maturation of Bio-Breeding T lymphocytes which in turn predisposes animals to insulitis and diabetic disease.
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PMID:Thymus transplantation and disease prevention in the diabetes-prone Bio-Breeding rat. 265 88

We looked for cells that reacted with monoclonal antibodies against rat insulin-like growth factor II (IGF-II). We found them in human fetal kidneys in the 14th week of gestation and in adult adrenal medullas but not in human liver, pancreas, pituitary gland, or thymus. Every pheochromocytoma in a group of 20 had IGF-II-like immunoreactive cells, as did three out of four ganglioneuroblastomas (one of which was heterotransplantable in athymic nude mice) and one carotid body tumor. Using the electron microscope we localized the immunoreactivity in pheochromocytoma cells to their neurosecretory granules of the non-catecholamine type. We failed to find any IGF-II-reactive cells among the pancreatic islet cell tumors, neuroblastomas, medullary carcinomas of the thyroid, retinoblastomas, and Wilms' tumor we studied. One line of human neuroblastoma cells did show some immunoreactivity after treatment with dbcAMP. Additionally, the rat pheochromocytoma cell line PC12 and its subline PC12h occasionally produced a few immunostained cells. These results strongly indicate that human IGF-II is primarily produced in paraganglionic tissues and tumors.
Diabetes Res Clin Pract 1989
PMID:IGF-II-like immunoreactivity in human tissues, neuroendocrine tumors, and PC12 cells. 268 Mar 64


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