Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:The spontaneously diabetic BB rat: sites of the defects leading to autoimmunity and diabetes mellitus. A review. 219 61

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.
 ...
PMID:[Kinetics of lymphocytes in mice with alloxan diabetes]. 227 95

We asked in a retrospective analysis whether patients with diabetes mellitus or impaired glucose tolerance are at increased risk for morbidity and mortality after high-dose therapy followed by an autologous bone marrow transplantation. Nine patients with diabetes mellitus (n = 7) or impaired glucose tolerance (n = 2) were identified who had been treated with high-dose therapy and autologous bone marrow transplant for lymphoid malignancies. At the start of the pretransplant conditioning all patients had a Karnofsky score of at least 80 and no clinically demonstrable organ dysfunction. One patient with diabetes mellitus type I (DM I) was transplanted without any complications. The patients with diabetes mellitus type II (DM II) or an impaired glucose tolerance had complications of life-threatening infections (in 6/8), acute renal insufficiency (in 3/8), liver abnormalities with elevated liver enzymes or liver failure (in 4/8) and congestive heart failure (in 1/8). Although the complications observed are not infrequent in the transplant setting, because of the good performance status before BMT and the absence of clinically demonstrable organ impairment before transplantation, it is our impression that the presence of diabetes mellitus or glucose intolerance might be an important co-factor in the morbidity of these patients.
 ...
PMID:Diabetes mellitus or an impaired glucose tolerance as a potential complicating factor in patients treated with high-dose therapy and autologous bone marrow transplantation. 229 95

BioBreeding Worcester diabetes-prone (BBdp) rats develop insulin-dependent autoimmune-driven diabetes mellitus spontaneously and intravenous administration of 1 x 10(7) p.f.u. of lymphocytic choriomeningitis virus (LCMV) to young adult mice prevents disease. The virus is lymphotropic, binding to and replicating in such cells. BBdp rats fail to generate virus-specific major histocompatibility complex-restricted cytotoxic T lymphocyte (CTL) responses when challenged with this dose or other doses of LCMV, Pichinde virus or vaccinia virus. Yet such rats clear virus effectively and show no evidence of persistent infection. Associated with this clearance of virus and establishment of immunity is the production of neutralizing antibodies. In contrast, diabetes-resistant (BBdr) rats generate virus-specific CTL responses. Furthermore LCMV binds to fewer lymphoid cells of BBdr rats (in comparison to those of BBdp rats) and replicates in fewer lymphocytes (by one order of magnitude) from these rats. Thus, unlike mice in which CTLs play a dominant role in the control of LCMV infection, BBdp rats do not overcome this infection via CTLs. In addition, both the BBdp rats and their BBdr counterpart may provide useful models for determining whether or how individual lymphocyte subsets function in the induction of CTL responses, for the analysis of virus-induced immunosuppression and for the use of viruses or their products as therapeutic modalities.
 ...
PMID:Cytotoxic T lymphocytes do not control lymphocytic choriomeningitis virus infection of BB diabetes-prone rats. 232 8

Elimination or inactivation of lymphoid tissue in the pancreatic islet preparation achieves prolongation of islet-allograft survival. In this study we examined the effect of gamma-irradiation on mouse islet-allograft survival. In a B6AF1 isograft model, irradiation up to 2400 rad did not induce deterioration of islet function over 200 days, but greater doses caused cessation of graft function between 83 and 186 days. When DBA/2 crude islets were transplanted into B6AF1 recipients, all nonirradiated allografts were acutely rejected. Marked prolongation of allograft survival was achieved by islet irradiation with doses between 800 and 12,000 rad. With higher doses, significant numbers of allografts survived beyond the controls, but many lost function between 78 and 180 days, with none surviving greater than 200 days. Irradiation with 16,000 rad caused acute radiation damage. Because most secondary islet allografts in recipient mice that lost primary islet-graft function between 84 and 195 days survived greater than 100 days, late functional loss was probably due to the radiation injury. Combined use of recipient treatment with cyclosporin A and graft irradiation (2400 rad) achieved prolongation of DBA/2 islets in B6AF1 mice.
Diabetes 1989 Jan
PMID:Effect of gamma-irradiation on mouse pancreatic islet-allograft survival. 249 98

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.
 ...
PMID:T cell-mediated inhibition of the transfer of autoimmune diabetes in NOD mice. 252 54

Protection by thymosin fraction 5 (TF5) from subdiabetogenic-dose streptozotocin (STZ)-induced type I diabetes in CD-1 mice was investigated. Mice which received multiple subdiabetogenic-dose (35 mg/kg) injections of STZ became hyperglycemia within two weeks. Hyperglycemia was also induced in those treated with low dose of TF5 (0.01 mg/day) in addition to STZ, though it was somewhat mild. In contrast, animals given STZ plus high dose of TF5 (0.1 mg/day) remained normoglycemic throughout the whole observation period (within 4 weeks). In the pancreatic islets from these animals, histologically, the well-granulated beta cells were observed and the infiltration of lymphoid cells was absent or mild. These results suggest that the administration of TF5 prevents the induction of insulitis and hyperglycemia in the subdiabetogenic-dose STZ-treated mice.
 ...
PMID:Protection by thymosin fraction 5 from streptozotocin-induced diabetes in mice. 265 87

Anti-islet cell-mediated immunity in the Bio-Breeding/Worcester (BB/Wor) rat was studied by measuring the cytotoxic activity of splenic lymphoid cells from diabetes-prone (DP) rats receiving either oral cyclosporine (Cy-A, 10 mg/kg/d) or olive oil vehicle (DP control) from age 40 to 105 d. Splenic cells were incubated with concanavalin A (Con-A) for 16 h, then used as effector cells in cytotoxicity assays with 51Cr labeled cells from a rat islet cell line (RIN) as targets. Lysis of RIN cells (% 51Cr release) by Con-A-activated splenic cells from control DP rats increased from age 40 d (5.4 +/- 1.6%) to 105 d (32.7 +/- 1.8%). This increase was significantly less in Cy-A-treated DP rats (14.5 +/- 3.2%) and remained low at 15 d after stopping Cy-A (14.8 +/- 2.5%). Diabetes developed in control DP rats between 74 and 120 days of age, and in none of the Cy-A-treated DP rats by age 105 d, nor for 15 d after stopping Cy-A. The Con-A-activated splenic cells responsible for lysis of RIN cells also lysed normal rat islet cells and had the functional and phenotypic properties of natural killer (NK) cells. In contrast to the lower Con-A-inducible NK cell cytotoxic activity in Cy-A-treated DP rats, basal NK cell activity and monoclonal antibody-defined NK cell subsets were increased in the Cy-A-treated DP rats. Therefore, Cy-A had inhibited the ability of NK cells to respond to cytotoxic activation despite their increased numbers. To investigate the mechanism(s) of the protective effect of Cy-A, we examined the direct effects of Cy-A in vitro. Cy-A (100 ng/ml) inhibited completely Con-A activation of DP splenic cells cytotoxic to islet cells, and this was accompanied by a similar inhibition of interleukin-2 (IL-2) production. Also Cy-A (300 ng/ml) inhibited partially (approximately 65%) IL-2 activation of DP splenic cells cytotoxic to islet cells. In addition, Cy-A inhibited the cytotoxic effects of DP cells previously activated by Con-A, and 300 ng/ml Cy-A produced a maximum inhibition of 47 +/- 5%.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Mechanisms of cyclosporine protection against spontaneous diabetes mellitus in the BB/W or rat. 266 95

To overcome the limitations of in situ studies during the chronic spontaneous autoimmune process leading to insulin cell destruction and diabetes in non-obese diabetic (NOD) mice, we have developed a model of acute transfer of diabetes into healthy syngeneic newborns. The injection of 20 x 10(6) T cells from adult diabetic mice produced synchronous insulitis within 3 weeks and diabetes within 4-5 weeks in young recipients, at a time when non-injected control mice do not even exhibit histological changes in their pancreases. Sequential studies of pancreases from T cell-transferred mice showed that lymphoid infiltration was preceded by a strong tissue expression of Ia antigen which was restricted to the vessel-associated cells limiting the islet of Langerhans, and which might play a role in the recruitment of circulating T cells inside the islets. Acute destruction of most of the insulin-producing cells, leading to diabetes, could take place within a few days after insulitis had begun. A majority of the inflammatory cells were T lymphocytes, approximately 30% of which expressed interleukin 2 receptors. L3T4+ T cells largely predominated at the early phase of islet invasion whereas the proportion of Ly-2+ T cells substantially increased later when beta cell destruction occurred. In contrast, only a minority of B cells and macrophages participated to the inflammatory process. These data are in keeping with previous demonstrations that both T cell subsets contribute to the autoimmune disease. Furthermore, they suggest that beta cell injury is mediated through a cytotoxic process, which requires the sequential involvement of L3T4+ (helper) and Ly-2+ (cytotoxic) T cells.
 ...
PMID:Syngeneic T cell transfer of diabetes into NOD newborn mice: in situ studies of the autoimmune steps leading to insulin-producing cell destruction. 268 73

Walter & Eliza Hall Institute nonobese diabetic (NOD/Wehi) mice exhibit a low incidence of spontaneous diabetes mellitus, but one large dose of cyclophosphamide (CY) can lead to a rapid progression to overt diabetes. Macrophages and Lyt-2+ and L3T4+ cells have been demonstrated to be involved in beta-cell destruction in this model. The role of a specific subset of T-lymphocytes expressing a particular T-lymphocyte-receptor segment was examined in CY-induced diabetic NOD mice with a mouse anti-V beta 8 T-lymphocyte-receptor monoclonal antibody (F23.1). After administration of CY, only 4 of 51 treated mice became hyperglycemic compared to 23 of 47 untreated mice, 13 of 26 mice treated with an isotype-matched control ascites, and 4 of 6 mice given antibody-negative ascites. Insulitis was significantly reduced in the F23.1-treated group, and immunocytochemistry revealed the absence of V beta 8 expression on cells in the lymphoid organs and insulitis of these mice. This investigation revealed that V beta 8+ cells were implicated in CY-induced diabetes in NOD/Wehi mice.
Diabetes 1989 Nov
PMID:Prevention of cyclophosphamide-induced diabetes by anti-V beta 8 T-lymphocyte-receptor monoclonal antibody therapy in NOD/Wehi mice. 269 77


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>