Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Population and family studies show that predisposition to type I diabetes (IDDM) is multifactorial, and that polymorphisms in the MHC region contribute substantially to the susceptibility to IDDM. In the present study the association of polymorphisms in the CD4 and the delta subunit of CD3 with IDDM were examined in a Belgian population. We observed that the frequency of the CD A4/A4 genotype and of the CD3 91 allele were significantly increased P = 0.0077) and decreased (P = 3.8 x 10(-5), respectively, in IDDM compared with controls. These results therefore suggest that CD4, CD3 or neighbouring genes might contribute to IDDM susceptibility. These results are, however, preliminary and cannot be considered as established until re-tested in a new population.
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PMID:Possible association of CD3 and CD4 polymorphisms with insulin-dependent diabetes mellitus (IDDM). 808 9

An experimental ascending urinary tract infection was induced by transurethral instillation of Escherichia coli in streptozotocin (STZ)-induced diabetic mice, in which bactericidal capacity of the perineal exudating neutrophils had been damaged. The local immune response in uninfected diabetic mice and the response time fluctuation of local immune responses in diabetic mice following infection were compared with those in normal mice, and the nature of induced changes in the local immune response was determined. The diabetic model was prepared by a single administration of 280 mg/kg of STZ after it had been fasted for 15 hours. The mouse was then fasted an additional 2 hours to induce the diabetic state. Compared with the normal mice, the diabetic mice prepared using this method were found to have a significant suppression of the bactericidal capacity of the perineal exudating neutrophils, 3 weeks after induction of diabetes. The study of the cellular distribution in uninfected urinary tract tissue demonstrated a reduction in CD4-positive T cell distribution in bladder submucosa of diabetic mice at 3 weeks after induction of diabetes (diabetic group), compared with that in the normal mice (control group). In the diabetic group, probably in order to compensate for the reduction in CD4-positive T cell distribution in the bladder submucosa, the distribution of macrophages was increased in the bladder epithelium, compared with the control group. This finding suggested that diabetic mice are thought to have protective mechanisms against infection different from those of normal mice in the uninfected state. The study of the response time fluctuation of local immune response at the infected sites demonstrated infiltration of macrophages was the same grade as that of neutrophils in the control and the diabetic group. However, in the diabetic group, a marked infiltration of macrophages was recognized when compared with the control group in the early phase of infection. These findings suggested that macrophages aid in protection against infection when damage to the bactericidal capacity of neutrophils results in insufficient elimination of microorganisms. On the other hand, infiltration of T and B cells was weaker in the diabetic group, than in the control group.
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PMID:[Study on local immune response in diabetic mice, in which bactericidal capacity of the neutrophils had been damaged--Escherichia coli induced experimental urinary tract infection]. 808 53

Precise definition of the role of both CD4 and CD8 T-cell subsets from NOD mice in the adoptive transfer of diabetes has been complicated by the possibility that endogenous T-cells may be recruited. Two newly created NOD congenic stocks, NOD.NON-Thy-1a and NOD/LtSz-scid, have been used as T-cell donors and recipients, respectively, to eliminate contributions from endogenous T-cells and thus to define the requirement for transferred T-cell subsets as a function of underlying diabetes development in the NOD donor. Total T-cells and T-cell subsets prepared from either prediabetic or diabetic NOD.NON-Thy-1a donors were adoptively transferred into 6-wk-old NOD-scid/scid recipients that were monitored for diabetes development. Both flow cytometric and histological analysis of recipient spleen and pancreas after adoptive transfer showed lymphocytes of donor (Thy1.1+) origin exclusively. Total T-cell and enriched CD4+ T-cell preparations from both diabetic and young prediabetic donors transferred diabetes to NOD-scid/scid recipients. However, the mean time to diabetes onset was doubled when CD4+ lymphocytes were isolated from prediabetic versus diabetic donors, and these transfers were complicated by the generation of small but significant numbers of CD8+ cells over time. Enriched CD8+ populations alone were unable to transfer disease. More rigorous exclusion of CD8+ cells by means of anti-CD8 MoAb treatment in vivo of the recipients of enriched CD4+ cells demonstrated a significant difference in the diabetogenic potency of CD4+ lymphocytes from diabetic versus nondiabetic donors. Diabetes was adoptively transferred to 58% of the recipients of enriched CD4+ lymphocytes from diabetic donors. In contrast, none of the recipients of enriched CD4+ lymphocytes from young prediabetic donors developed diabetes after MoAb treatment in vivo. The ability of a T-cell population to produce severe insulitis and sialitis in NOD-scid/scid recipients of T-cells closely paralleled its ability to induce diabetes. In an effort to suppress insulitis by suppression of macrophage migration to the islets, NOD-scid/scid mice were treated with silica in conjunction with adoptive transfer of T-cells from diabetic donors. Chronic silica treatment failed to deplete tissue macrophages and did not prevent diabetes development after transfer of unfractionated T-cells. Evidence is discussed indicating that the age-associated differences in ability of CD4+ T-cells to adoptively transfer diabetes in the absence of the CD8+ T-cells subset is a function of prior, chronic exposure of the CD4+ lymphocytes to beta-cell antigens in the donor.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes 1993 Jan
PMID:Adoptive transfer of diabetes into immunodeficient NOD-scid/scid mice. Relative contributions of CD4+ and CD8+ T-cells from diabetic versus prediabetic NOD.NON-Thy-1a donors. 809 6

Non-obese diabetic (NOD) mice were injected with a rat monoclonal antibody to CD4 from birth every two weeks through 6 months of age. These animals gained weight normally but < 11% of their spleen T cells were CD4+, compared with 28% of CD4+ in controls injected with polyclonal rat IgG. The reduction in CD4 cell percentage was associated with a reduction in the number of cells in the thymus and spleen following the injection. CD4+ cells which survived the injections were nevertheless able to enter cell cycle when stimulated by Con A. None of the CD4-treated NOD mice became diabetic by 6 months of age and none of the animals studied histologically at this time had insulitis. At 9 months of age (three months after stopping the CD4 injections) the mice made antibody to human IgG. At 1 year of age most of the male mice had insulitis, although none of the male or female mice had become spontaneously diabetic. Two thirds of animals injected with cyclophosphamide at 16 months became diabetic within 3 weeks. The results confirm that treatment with CD4 antibody in the first 6 months suffices to reduce the incidence of diabetes in NOD mice. The treatment does not prevent the subsequent development of insulitis in injected mice and does not prevent the accumulation of cells capable of causing overt diabetes after cyclophosphamide injection.
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PMID:Prevention of diabetes but not insulitis in NOD mice injected with antibody to CD4. 810 7

Myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) may play an important role in the function and/or dimensions of the left ventricle. We present an autopsied case of HCM followed for 10 years. A 68-year-woman with HCM underwent trans-aortic myectomy of the interventricular septum in 1979. A significant amount of round cell infiltration, myocardial fibrosis and disarray were observed in the resected specimen. She experienced repeated admissions due to diabetes mellitus and congestive heart failure, and died of renal failure in 1989. An autopsy revealed extensive myocardial fibrosis and significant cell infiltration in the ventricular myocardium. The infiltrating cells were almost all lymphocytes, and the ratio of CD4 to CD8 was 3.8. This ratio was different from that of typical viral myocarditis. This case suggests that there may be an undefined inflammatory process causing fibrosis in HCM, in addition to the ischemia due to intramural small coronary artery stenosis.
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PMID:An autopsy case of hypertrophic cardiomyopathy with pathological findings suggesting chronic myocarditis. 820 86

The nonobese diabetic mouse is a relevant model for insulin-dependent diabetes mellitus which results from the destruction of pancreatic beta cells by mononuclear cells infiltrating the islets of Langerhans. Other organs such as salivary glands display inflammatory infiltration. Using immunohistochemical and flow cytometry analyses, we have studied the expression of diverse homing and adhesion molecules in salivary glands and the pancreas in nonobese diabetic mice. In salivary glands, ICAM-1 was expressed by endothelial and dendritic cells within the lymphocytic infiltration. HEV-like structures expressing PNAd were observed in the areas of lymphocytic infiltration whereas MAdCAM-1 was absent. Lymphocytes infiltrating salivary glands expressed LFA-1 and Pgp-1 although Mel-14 Ag was absent. In infiltrated islets, ICAM-1 was expressed by endothelial cells, dendritic cells, and mononuclear cells. We confirm the presence of HEV-like structures expressing MAdCAM-1 and PNAd in inflamed islets. With regard to peripheral lymphocytes, the proportion of CD4 and CD8 cells expressing Mel-14 was decreased in the infiltrated islets, whereas the expression of LFA-1, Pgp-1, and LPAM-1/2 was increased. B lymphocytes exhibited up-regulation of LPAM-1/2. Moreover, the proportion of CD4, CD8, and B lymphocytes expressing CD69 was increased in the pancreas. These results indicate that first, infiltration of islets of Langerhans results at least partly from modifications of adhesion molecule expression in the pancreas, which allow extravasation of mononuclear cells into the islets via at least three different pathways; and second, that activated cells are concentrated in the infiltrates as compared with peripheral lymphoid organs.
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PMID:Expression of homing and adhesion molecules in infiltrated islets of Langerhans and salivary glands of nonobese diabetic mice. 820 21

The nonobese diabetic (NOD) mouse is a model for human Type 1 diabetes mellitus. Pancreatic beta-cell destruction in NOD mice is mediated by an autoimmune process which can be accelerated by cyclophosphamide (CP). We studied the phenotype of lymphocytes from central, peripheral and regional lymphoid tissues in prediabetic NOD and C3H mice before and after a single large dose of CP. All lymphoid organs showed a greatly diminished cell number and most alterations appeared early after CP and were transient, but an aggressive insulitis was not seen in NOD mice until 14 d after injection. The pancreatic islets in C3H mice remained intact and were not infiltrated. NOD female mice, which are most prone to spontaneous and CP-induced diabetes, exhibited the most unusual lymphoid kinetics after treatment with CP. Their thymus and spleen showed the least relative drop in total cell number and the most rapid rate of recovery. The thymus of these mice was also found to have an increased proportion of CD3+ thymocytes while CD4/CD8 double positive thymocytes decreased 7 d after CP. At 14 d after CP the number of IL-2R+ thymocytes had surpassed that of normal levels. The most dramatic observation was the rapid recovery and overshoot in the number of pancreatic lymph node cells of female NOD mice which coincided with aggressive insulitis.
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PMID:The effect of cyclophosphamide treatment on lymphocyte subsets in the nonobese diabetic mouse: a comparison of various lymphoid organs. 821 26

Successful pancreas transplantation requires the suppression of both allograft rejection and recurrence of autoimmune disease. In order to study treatments to suppress these two responses, separate models were developed for pancreas allograft rejection and autoimmune disease. In the first model, the diabetic state was induced with streptozotocin in CBA mice prior to the transplantation of pancreas grafts from BALB/c donors. In the absence of autoimmune disease, control mice rejected their grafts in 26 days (median). Antibody treatments (anti-lymphocyte serum and anti-CD4) significantly prolonged allograft survival beyond this time, but not to the extent we have previously reported in the heart graft model. NOD/Lt mice spontaneously developed autoimmune diabetes, and recurrence of disease was seen in isografts at 9.5 days (median). Antibody treatments significantly delayed disease recurrence, with anti-CD4 being the most effective. Heart allografts (CBA donors) in NOD/Lt recipients were rejected within 17 days (median), and the anti-CD4 treatment had a moderate effect in delaying graft survival (median 28 days). Anti-lymphocyte serum did not prolong graft survival. Thus antibody treatment was effective in delaying both rejection and the recurrence of autoimmune disease in segmental pancreas grafts. However, the same doses were not effective in delaying heart rejection in the NOD/Lt model, so it would appear that treatments which inhibit autoimmune disease may not prevent allograft rejection.
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PMID:Immunosuppressive antibody treatment prolongs graft survival in two murine models of segmental pancreas transplantation. 822 1

Various studies have provided evidence that peripheral T-cells from the diabetes-prone BB-DP rat are abnormal in function and cell surface phenotype. These characteristics have often been interpreted as indicators of immaturity and/or short life span. In this study, we describe a CD4-dependent signaling abnormality in BB-DP peripheral T-cells. In spite of the fact that CD4 plays a critical role in thymocyte development, the abnormal signaling does not appear to influence thymocyte development at the stage when the T-cell receptor is rearranged and the recombinase enzymes RAG-1 and RAG-2 transcripts are downregulated. Therefore, if a maturation defect leading to the seeding of the periphery with immature T-cells occurs in the BB-DP rat, it does not preclude the initial selection of the self major histocompatibility complex-restricted T-cell repertoire.
Diabetes 1994 Jan
PMID:Peculiar T-cell signaling does not preclude positive selection in the diabetes-prone BB rat. 826 16

Inflammatory cells invading islets are thought to be mediators of islet destruction in spontaneous autoimmune diabetes mellitus. Thus methods were developed to isolate and characterize in situ islet inflammatory cells from 75-95-day-old prediabetic and diabetic BB rats. Islet inflammatory cells were structurally examined using single- and double-colour flow cytometry. Functional studies consisted of cytolytic assays using normal rat islet target cells and in situ islet or spleen effector cells. Structural data reveal natural killer cells to be the major cell population (70%) of total immune cells present in inflamed islets during prediabetes. At diabetes onset, the natural killer cell population remained at a high level (47%), but an increasing population of T cells (40%) was noted also. Analyses of T-cell subsets before and after diabetes onset revealed CD4+ T cells as predominant (50-55% of total T cells) with double-negative (CD4-CD8-) T cells (25-30%) and CD8+ T cells (15-20%) also present in significant quantities. Activated T cells accounted only for a minority of T cells (< 3%). Functional studies indicate that in situ islet-derived cytolytic effector cells are more potent killers (ten-fold) of normal islet target cells than are splenic effector cells. These data suggest that in situ islet inflammatory cells (a) can be quantitatively studied both structurally and functionally; (b) express structural phenotypes differing substantially from splenic mononuclear cell populations; (c) are considerably more cytolytic than splenic effectors; and (d) should prove informative in determining the most significant autoimmune functional events prior to and during islet beta-cell destruction.
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PMID:Quantitative phenotypic and functional analyses of islet immune cells before and after diabetes onset in the BB rat. 827 Jan 29


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