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)

Antibodies reacting with human pancreatic islet cells were found by immunofluorescence in the sera of 51 of 105 children with diabetes mellitus of recent onset. These antibodies were of IgG class, and several of them fixed complement and reacted with pancreatic islets of other species. Thyroid microsomal and/or gastric-parietal-cell antibodies were found in only 10 of the patients with islet-cell antibodies, and none of them had adrenal antibodies. These findings contrast with previous reports which have stressed the rarity of islet-cell antibodies in adult diabetics and their occurrence only in patients with other evidence of autoimmune disease.
 ...
PMID:Islet-cell antibodies in juvenile diabetes mellitus of recent onset. 4 33

20 out of 179 diabetics treated with oral hypoglycaemic agents (O.H.A.) within 3 mo of diagnosis had pancreatic-islet-cell antibodies (ICAb) in their sera at diagnosis or later. 13 of these 20, compared with only 14 of the remaining 159, subsequently required insulin at a mean follow-up of 2 yr 10 mo and 4 yr 11 mo, respectively (p less than 10(-7)). 5 of the 7 ICAb-positive diabetics still continuing on O.H.A. therapy after a mean follow-up of 4 yr 6 mo required maximum or near-maximum combined oral therapy, while only 34 of the 145 ICAb-negative diabetics continuing on O.H.A. did so at a mean follow-up of 5 yr 4 mo (p less than 0.02). In addition, 81 diabetics treated initially with diet for a mean time of 4 yr 7 mo before going on to O.H.A. therapy were studied. All were ICAb-negative when tested at a mean interval of 6 yr 10 mo from diagnosis. By the end of the mean follow-up period of 10 yr 3 mo, 27 were on combined oral therapy and 3 had been transferred to insulin treatment. ICAb-positive diabetics on O.H.A. had a high prevalence of a personal history of organ-specific autoimmune disease, thyrogastric antibodies, a family history of insulin-dependent diabetes and possibly of HLA-B8 comparable to that in insulin-dependent diabetes and higher than that expected in a control population or in diabetics controlled by diet alone. We believe that ICAb-positive diabetes controlled by O.H.A. is an earlier stage in the same disease process (type-I diabetes) that culminates in insulin-dependency.
 ...
PMID:Clinical and pathogenic significance of pancreatic-islet-cell antibodies in diabetics treated with oral hypoglycaemic agents. 6 85

In a study of 972 patients with diabetes mellitus, humoral pancreatic islet-cell antibodies (I.C.Ab.) were detected in highest prevalence in insulin-treated diabetics with (38 per cent) and without (22 per cent) associated overt organ-specific autoimmune disease (A.I.D.) where consideration was not given to the duration of diabetes. They were also detected in 8 per cent of diabetics treated with oral hypoglycemic agents (O.H.A.), but not in diabetics requiring diet alone and in only 0.5 per cent of 434 control subjects. Six per cent of 522 patients with overt organ-specific A.I.D. but not diagnosed to be diabetic had I.C.Ab.s. I.C.Ab.s were present in the sera of 2 per cent of 157 first-degree relatives of I.C.Ab.-positive subjects. In insulin-treated diabetics and, to a lesser extent, in diabetics not requiring insulin, the prevalence of humoral I.C.Ab. was strongly dependent of the duration of the diabetes, being 60 per cent during the first year from diagnosis in the insulin-treated group and falling to 20 per cent at two to five years and to 5 per cent at 10-20 years. The prevalence of I.C.Ab. in insulin-treated diabetics showed no correlation with the patient's age at the time of testing when the duration of diabetes was taken into account. Diabetics who did not require insulin for treatment but who were I.C.Ab.-positive showed a significant tendency to subsequently require insulin and to have a higher prevalence of other autoantibodies than insulin-independent diabetics who were I.C.Ab.-negative. Persistence of I.C.Ab. for more than five years from diagnosis of diabetes was associated with coexistent overt organ-specific A.I.D. and with HLA-B8, A1, and A1 + B8.
Diabetes 1977 Feb
PMID:Pancreatic islet-cell antibodies in diabetes mellitus correlated with the duration and type of diabetes, coexistent autoimmune disease, and HLA type. 32 73

Pancreatic islet cell, thyroid, and gastric antibodies were studied in 116 young insulin-dependent diabetics and 257 relatives. Seventy-four per cent of the diabetics studied within three months of diagnosis had islet-cell antibodies but only 20% of those studied three years or more after diagnosis. Persistence of these antibodies was associated with a high prevalence of thyrogastric autoimmunity, which suggests that some cases have an aetiology similar to that of "polyendocrine" autoimmune disease. Retinopathy or nephropathy, or both, was present in 10 diabetics, who were all members of "autoimmune" families, in which one or more members had organ-specific antibodies. Nine of the 10 healthy relatives with islet-cell antibodies and all families with more than one diabetic were also in this autoimmune group. These data suggest that an autoimmune factor may contribute to juvenile diabetes and that such autoimmune diabetes has a tendency to run in families and may be more likely to cause complications.
 ...
PMID:Autoimmunity in juvenile diabetics and their families. 35 41

Out of 314 patients with coeliac disease, 63 had associated disorders of known or suspected immunological cause (excluding aphthous stomatitis and dermatitis herpetiformis). Autoimmune diseases appeared to occur more often in patients with coeliac disease than in the normal population, 52 such diseases being found in 45 patients. Of individual disorders, diabetes mellitus, thyroid diseases, and ulcerative colitis seemed to be more common than expected. Atopy (asthma and eczema) occurred in 7% of the patients. Most of these immunological disorders developed when the patients were on normal diet. A gluten-free diet and virtually normal jejunum did not prevent their development, and the diet had little ameliorating effect on their course apart from an occasional dramatic improvement in atopic patients.
 ...
PMID:Coeliac disease and immunological disorders. 63 Feb 12

Cultured skin fibroblasts from clinically normal offspring of two parents with non-insulin-dependent diabetes have demonstrated premature senescence as a decreased ability of cells to establish colonies when inoculated at low density (plating efficiency). The present study tested the hypothesis that there is an inherent cellular defect affecting viability of diabetic cells in insulin-dependent diabetes. Four insulin-dependent patients, aged 12 to 19 years, included two with joint contracture, skin changes, and growth failure; one with thyroiditis and past history of nephrosis; and one with a family history of insulin dependency. Ten control subjects, aged 10 to 52 years, had negative family histories and normal oral glucose tolerance tests. Number of cells per confluent dish correlated significantly with donor age (p less than 0.001) at 30 and 40 in-vitro generations. The patients' cells' mean confluent density did not differ from that of five age-matched controls. Plating efficiency correlated with donor age at 30 in-vitro generations ( p less than 0.001); plating efficiency of cells from the youngsters with diabetes was virtually identical to that of control cells at 20, 30, and 40 generations. In this small series of two subjects with in-vivo growth failure, one with associated autoimmune disease and another with familial insulin-dependent disease, cultured fibroblasts demonstrated normal viability and the hypothesis of a cellular growth defect was not confirmed.
Diabetes 1978 Mar
PMID:Insulin-dependent childhood diabetes. Normal viability of cultured fibroblasts. 64 Feb 40

Insulin dependent or type 1 diabetes is an autoimmune disease with a strong genetic susceptibility linked to MHC and non MHC genes. Risk of the disease is 20 fold higher in first degree relatives of patients than in the general population. beta-cell destruction is progressive and marked by the appearance of antibodies to several islet constituents including insulin and glutamate decarboxylase. These markers allow disease prediction specially in children where a population with a 5 years risk approaching 100% can be defined. The intravenous glucose tolerance test can detect a progressive decline of the first phase of insulin secretion, preceding glucose intolerance and hyperglycemia. These screening programs will allow clinical trials currently limited to non specific immuno-suppressive agents such as cyclosporine in patients with preclinical diabetes. In the future, identification of targets and effector mechanisms of auto-immune destruction of the beta-cells will allow the evaluation of more specific approaches at earlier stages of the disease.
 ...
PMID:[Screening of type I diabetes in patients' families]. 129 38

Autoimmune diseases have been studied from the perspective of an abnormal immune response in genetically vulnerable hosts. Although the immune response is responsible for the initiation of autoimmune diseases, the effectors of the disease process likely involves cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). These polypeptides induce a wide variety of inflammatory events which contribute to the destruction of tissue and tissue remodeling in several autoimmune diseases. Blocking IL-1 with its naturally occurring receptor antagonist, the IL-1 receptor antagonist reduces the severity of disease in animal models of inflammation and autoimmune processes. Clinical studies with the IL-1 receptor antagonist will define the role for this cytokine in the pathogenesis of autoimmune diseases such as arthritis, inflammatory bowel disease, type I diabetes and vasculitis.
 ...
PMID:Interleukin-1 and tumor necrosis factor: effector cytokines in autoimmune diseases. 132 Sep 50

Type 1 or insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease of the insulin-producing pancreatic beta-cells which is determined by both genetic and environmental factors. The major histocompatibility complex and the insulin gene region (INS) on human chromosomes 6p and 11p, respectively, contain susceptibility genes. Using a mostly French data set, evidence for linkage of INS to IDDM was recently obtained but only in male meioses (suggesting involvement of maternal imprinting) and only in HLA-DR4-positive diabetics. In contrast, we find evidence for linkage in both male and female meioses and that the effect of the susceptibility gene(s) in the INS region is not dependent on the presence of HLA-DR4.
 ...
PMID:Insulin gene region-encoded susceptibility to type 1 diabetes is not restricted to HLA-DR4-positive individuals. 134 71

Molecular genetic techniques are being widely applied to the study of autoimmune diseases. Major advances have been made in diabetes, rheumatoid arthritis and coeliac disease. Work on experimental models of autoimmune uveitis suggests that similar advances will follow in this field. The application of molecular genetics to the study of immunology has lead to great advances in our understanding of the anatomy of antigen recognition. This work has lead to the identification of some of the structural determinants of antigen binding by MHC molecules and is helping to explain some MHC-disease associations. More recently, molecular studies of the T cell receptor have characterized patterns of T cell receptor expression in humans and have lead to the identification of regions of the T cell receptor critical for antigen recognition. These techniques will hopefully provide insights into the nature of autoimmunity and permit the identification of targets for disease specific immunotherapies. This review describes attempts to corelate MHC structure and function in the context of autoimmunity and discusses some of the strategies for analyzing T cell receptor usage in autoimmune disease.
 ...
PMID:Molecular aspects of autoimmunity: a review. 138 42


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