Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A diabetic syndrome closely resembling human IDDM has been induced in rats of specific pathogen-free origin by a combination of thymectomy and irradiation, with an overall incidence (10 wk postirradiation) in female rats of 34% for acute disease and 47% for islet lesions. Males were slightly more susceptible than females. Clinical features of the syndrome included hyperglycemia, insulinopenia, ketosis, and lipidemia, and corresponding islet pathology ranged from diffuse atrophy to focal atrophy and insulitis. Onset was usually acute, and the disease fatal unless early insulin therapy was initiated. Lymphocytic thyroiditis also was observed in a proportion of thymectomized and irradiated rats (49% in females) over the same period but with no apparent correlation to the occurrence of diabetes. A significant decrease in the incidence of disease was found in thymectomized and irradiated rats of conventional origin when compared with genetically identical specific pathogen-free rats, implicating a role for environmental factors in disease susceptibility. Diabetes inducement also was found to be strain related but not RT1u dependent. Both clinical signs and islet lesions were inhibited by early reconstitution of thymectomized and irradiated animals with syngeneic lymphoid cells from normal donors. Islet lesions and glucose intolerance could be transferred to syngeneic recipients by concanavalin A-activated lymphoid cells from acute diabetic donors. The close similarities between this experimental syndrome induced by immunological manipulation and the clinical condition in humans provide further evidence for an immune-mediated pathogenesis for IDDM.
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PMID:IDDM in rats induced by thymectomy and irradiation. 845 8

Epitope spreading is a process whereby epitopes distinct from and non-cross-reactive with an inducing epitope become major targets of an ongoing immune response. This phenomenon has been defined in experimental and natural situations as a consequence of acute or persistent infection and secondary to chronic tissue destruction that occurs during progressive autoimmune disease. We have investigated the functional significance of this process in the chronic stages of both autoimmune and virus-induced central nervous system (CNS) demyelinating disease models in the SJL/J mouse. During the relapsing-remitting course of experimental autoimmune encephalomyelitis (R-EAE) induced with defined encephalitogenic myelin peptides, CD4+ T cells specific for endogenous epitopes on both the initiating myelin protein (intramolecular epitope spreading) and distinct myelin proteins (intermolecular epitope spreading) are primed secondary to myelin destruction during acute disease and play a major functional role in mediating disease relapses. Similarly, epitope spreading to endogenous myelin epitopes appears to play a major functional role in the chronic-progressive course of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a virus-induced CD4+ T-cell-mediated immunopathology. In TMEV-IDD, myelin destruction is initiated by virus-specific CD4+ T cells which target virus epitopes persisting in CNS-derived antigen-presenting cells. However, the chronic stage of this progressive disease is associated with the activation of CD4+ T cells specific for multiple myelin epitopes. In both models, the temporal course of T-cell activation occurs in a hierarchical order of epitope dominance, spreading first to the most immunodominant epitope and progressing to lesser immunodominant epitopes. In addition, epitope spreading in R-EAE is regulated predominantly by CD28/B7-1 co-stimulatory interactions, as antagonism of B7-1-mediated co-stimulation using anti-B7-1 F(ab) fragments is an effective ameliorative therapy for ongoing disease. The process of epitope spreading has obvious important implications for the design of antigen-specific therapies for the treatment of autoimmune disease since these therapies will have to identify and target endogenous self epitopes associated with chronic tissue destruction.
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PMID:The functional significance of epitope spreading and its regulation by co-stimulatory molecules. 979 64

Children with insulin-dependent diabetes mellitus (IDDM) suffer from a chronic autoimmune beta cell destruction of unknown origin, maybe due to superantigens or retroviral endogenous genes. Recently, a novel endogenous retrovirus designated as IDDMK 22 was proposed to encode for such a candidate autoimmune gene in type 1 diabetes. We therefore analyzed the expression of IDDMK 22 genes in peripheral blood leukocytes and plasma from 55 healthy children and 55 diabetic children including 11 patients with acute disease onset. In our study we applied an improved quantitative and highly specific real-time PCR assay. In contrast to previous data obtained by conventional PCR. IDDMK 22 gene expression did not differ between diabetic and nondiabetic individuals. For this reason, we propose that IDDMK 22 is an ubiquitous endogenous retroviral element in the human genome but not a candidate autoimmune gene for IDDM, especially in childhood-onset disease. Real-time PCR proved to be a highly sensitive and specific method for detection and quantitation of very low amounts of mRNA and will thereby be useful regarding the special demands in pediatric studies dealing with very low amounts of specimen.
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PMID:Quantitation of gene expression by real-time PCR disproves a "retroviral hypothesis" for childhood-onset diabetes mellitus. 1040 Jan 35

The heterogeneity between young- and adult-onset type 1 diabetes (T1D) is well known, but not well understood. We approach this question through mathematical formulation and analysis of the dynamic interactions between the immune cells and the pancreatic islet beta-cells that lead to the beta-cell destruction. Utilizing the perturbation expansion method we investigate the dynamic stability of our system under fast and slow beta-cell turnover limits. We find that if autoimmunity is initiated when the turnover is slow (adult age), a stable steady state can exist with reduced number of beta-cells, where the beta-cell regeneration balances the ongoing autoimmune destruction. This implies that a slow disease process is possible. In contrast, if autoimmunity occurs when the beta-cell turnover is rapid (young age), such a stable state will never be attained and the destruction will progress unabated, leading to an acute disease onset. The major findings of our model are consistent with clinical observations, and it offers an explanation for the dynamic and phenotypic heterogeneity between young- and adult-onset T1D. More importantly, the model analyses point out that pathways regulating beta-cell turnover can be new targets to interfere with the disease process of T1D.
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PMID:Investigation of the age-at-onset heterogeneity in type 1 diabetes through mathematical modeling. 1672 39

Since children with chronic diseases represent a primary target for immunization strategies, it is important that their immunization coverage and timeliness of vaccines is optimal. We performed a study to measure immunization coverage and timeliness of vaccines in children with type 1 diabetes, HIV infection, Down syndrome, cystic fibrosis, and neurological diseases. A total of 275 children aged 6 months-18 years were included in the study. Coverage for diphtheria-tetanus-pertussis (DTP), polio (Pol), and hepatitis B (HBV) vaccines approximated 85% at 24 months, while measles-mumps-rubella (MMR) coverage was 62%. Immunization coverage for seasonal influenza was 59%. The analysis of timeliness revealed that there was heterogeneity among children with different chronic diseases. A proportional hazard model showed that children with HIV infection had the longest time to complete three doses of DTP, Pol, and HBV, and those with neurological diseases received the first dose of MMR later than the other categories. Causes of missing or delayed vaccination mostly included a concurrent acute disease. Children with chronic diseases should be strictly monitored for routine and recommended vaccinations, and health care providers and families should be properly informed to avoid false contraindications.
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PMID:Immunization coverage and timeliness of vaccination in Italian children with chronic diseases. 2141 80