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)

For decases certain diseases, such as glomerulonephritis, polyarteritis nodosa, scleroderma and serum sickness, have been linked with autoimmune pathogenesis. During recent years a host of additional diseases traditionally thought to have some genetic predisposition but with obscure etiology have been suspected of being autoimmune in nature. Rheumatoid arthritis, diabetes, myasthenia gravis and thyroiditis are diseases of widely divergent organ systems, yet may well have common pathways of pathology via immune complexing mechanisms. Herein we present evidence supporting the concept that renal artery stenosis (occurring primarily in association with the middle aortic syndrome or after renal transplantation) is of immune etiology. Although the specific antigenic agent is still to be defined there is growing acceptance of the theory that medium and large vessels are subject to autoimmune vasculitis in many aspects similar to the autoimmune affections of small vessels. Several cases are presented. Some of these suggest an immune reaction by the natural history but without evidence of immunochemical reactants in the involved vessels, presumably because active disease was arrested at the time to study. In other cases immunofluorescent preparations demonstrate reactants in the walls of the vessels to document the hypothesis more convincingly.
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PMID:Immunologic considerations in renovascular hypertension. 13 96

Cold non-HLA lymphocyte cytotoxins were found to be principally reactive against B lymphocytes. These antibodies were studied in 1335 patients with a wide range of diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma, Hashimoto's disease, asthma, diabetes, lymphoma, psoriasis, leukemia, multiple sclerosis, and also in healthy donors. Antibodies reactive to B lymphocytes in the cold or warm test conditions were not directed against HLA specificities. Since B lymphocytes differ from T lymphocytes principally in that they have surface immunoglobulin, it is postulated that at least one target antigen of cold lymphocyte cytotoxins is not a virus, infectious agent, or a genetically determined structural antigen, but, rather, simply immunoglobulin.
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PMID:Non-HLA lymphocyte cytotoxins in various diseases. 31 13

Recent observation of a case of idiopathic chronic intestinal pseudo-obstruction and the relationship sometimes suggested in this context with certain systemic diseases, such as scleroderma, led the authors to compare the changes seen in the myenteric plexuses in these different groups of disorders. The intramural plexuses were studied using the technique of B. Smith, in thick frozen section parallel to the lumen and stained using Bielchowsky's method. Plexus innervation was normal in a case of digestive amyloidosis and a case of myxoedema. There were secondary changes in the plexuses in scleroderma. The lesions were very different in our case of idiopathic chronic intestinal pseudo-obstruction (marked decrease in the number of neurones with degenerative changes in the neurones and dendrites, marked schwannosis). A decrease in the number of neurones was seen in a case of severe diabetes. Various mechanisms are discussed. These cases emphasize the great value of B. Smith's technique in the fine study of the intramural plexus innervation of the digestive wall.
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PMID:[Lesions of the myenterix plexuses in idiopathic chronic intestinal pseudo-obstruction and in certain general diseases]. 69 26

For decades certain diseases, such as glomerulonephritis, polyarteritis nodosa, scleroderma and serum sickness, have been linked with autoimmune pathogenesis. During recent years a host of additional diseases traditionally thought to have some genetic predisposition but with obscure etiology have been suspected of being autoimmune in nature. Rheumatoid arthritis, diabetes, myasthenia gravis and thyroiditis are diseases of widely divergent organ systems, yet may well have common pathways of pathology via immune complexing mechanisms. Herein we present evidence supporting the concept that renal artery stenosis (occurring primarily in association with the middle aortic syndrome or after renal transplantation) is of immune etiology. Although the specific antigenic agent is still to be defined there is growing acceptance of the theory that medium and large vessels are subject to autoimmune vasculitis in many aspects similar to the autoimmune affections of small vessels. Several cases are presented. Some of these suggest an immune reaction by the natural history but without evidence of immunochemical reactants in the involved vessels, presumably because active disease was arrested at the time of study. In other cases immunofluorescent preparations demonstrate reactants in the walls of the vessels to document the hypothesis more convincingly.
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PMID:Immunologic considerations in renovascular hypertension. 78 14

Postmortal histologic examinations of the synovial membrane of both knee joints were conducted in 85 selected cases. The following conditions were given priority: diabetes mellitus, advanced renal insufficiency, liver cirrhosis with ascites, chronic insufficiency of the right heart, vericose syndrome of the lower extremities, tumours compressing organs of the pelvis minor as well as a few rare infectious and tumerous diseases. Comparison of the histomorphologic findings revealed consistancies such as pronounced ultravillous branching of the synovial membrane with villous hyalinosis in diabetes mellitus, increased, coarse villi formation in renal insufficiency and liver cirrhosis, edema of the synovial membrane in chronic insufficiency of the right heart and renal insufficiency as well as a number of nonspecific reactions of the synovial membrane in obstruction of venous drainage. In the context of generalized fibrotic processes such as in Ormond's disease and scleroderma, similar reactions of the synovial membrane are pronounced. Arthralgic complaints and secondary arthroses in those systemic diseases not primarily involving joints can be at least partially clarified by histomorphologic findings.
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PMID:[Reaction of synovial membranes in knee joint with primary extra-articular systemic diseases (author's transl)]. 85 62

Reduced peritoneal clearances of creatinine and urate were demonstrated repeatedly in a patient with scleroderma and a patient with diabetes mellitus. Urea clearances were not significantly different from usual values. The findings suggest decreased peritoneal membrane permeability and/or area (if urea clearance is flow limited). Clearances increased to usual values with intraperitioneal isoproterenol in the patient with diabetes. There was no effect of isoproterenol in the patient with scleroderma.
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PMID:Peritoneal clearances in scleroderma and diabetes mellitus: effects of intraperitioneal isoproterenol. 96 10

Small cutaneous vessels, obtained by ear lobe biopsies, were studied in 14 patients with various chronic nephritides and in 10 normal controls. The capillaries in the group of patients with nephritis were found to undergo two main changes: thickening of the adventitia reticularis and perivascular cellular infiltration in an inverse ratio. This infiltration was seen to be made up of mononuclear cells and an increased number of mast cells in various stages of degranulation. Changes in the basement membrane as seen by electron microscopy are not constant. All of the above changes were absent in the controls and are similar to what has been described in previous studies in both experimental and spontaneous pathologic conditions, such as experimental hypertension, diabetes mellitus, scleroderma, rheumatoid arthritis, etc. Small vessel involvement in chronic nephritides could be part of a process of diffuse microvascular damage that includes the kidneys or it may be related to hypertension or to the biochemical changes which follow uremic and pre-uremic states.
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PMID:Peripheral small vessel involvement in chronic nephritides. 118 6

T cell activation is dependent upon calcium influx and protein kinase C activation, with subsequent lymphocyte proliferation dependent upon IL-2. Abnormalities in T cell proliferation, including abnormal calcium influx and defective protein kinase C activation, have been identified in aged mice and humans and many autoimmune diseases including diabetes, lupus and scleroderma. Since UCD line 200 chickens, which spontaneously develop a scleroderma-like disease, have both thymic defects and a diminished peripheral blood lymphocyte response to IL-2, we have further investigated T cell function in these birds. Interestingly, line 200 T cells respond poorly in vitro to a variety of diversely acting T cell mitogens including concanavalin A, phytohemagglutinin and anti-chicken CD3 monoclonal antibody. Moreover, they do not respond well even to phorbol myristate acetate in conjunction with ionomycin. Addition of exogenous IL-2-containing supernatant concurrently with mitogenic stimulation also had no significant effect. Analysis of intracellular free calcium demonstrated that the lymphocytes from diseased birds had a reduced influx of calcium (or release for intracellular stores) following stimulation. These data clearly reflect a unique defect in T cell activation associated with avian scleroderma. Analysis of chicken CD3, CD4 and CD8 expression revealed a 39% decrease in peripheral blood CD4+ cells in scleroderma birds, although this decrease was not sufficient to explain the 80-90% decrease observed in proliferation assays and calcium influx. Our data support the hypothesis that avian scleroderma is mediated via abnormal function of lymphocyte co-stimulatory molecules or intracellular calcium regulators.
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PMID:Avian scleroderma: evidence for qualitative and quantitative T cell defects. 138 34

To detect serum antibodies to GAD in subjects with IDDM, three recombinant mBGAD 67 peptides encompassing the full-length protein were used in an ELISA. In this study 7 of 9 (78%) preclinical IDDM subjects (ICA+ first-degree relatives of a person with IDDM) and 6 of 13 (46%) recent-onset IDDM subjects, but no subjects with Graves' disease (n = 10) or scleroderma (n = 10), nor healthy nondiabetic control subjects (n = 10) had antibodies that reacted with one or more of the recombinant mBGAD peptides. We found no preferential reactivity with any recombinant peptide. Although only 3 preclinical subjects and 1 recent-onset subject had antibodies to all three mBGAD peptides, the results indicate that mBGAD 67 contains at least three B-cell autoepitopes. Compared with an immunoprecipitation assay of native human brain GAD, the ELISA detected 5 of 6 (83%) preclinical and 6 of 6 (100%) recent-onset IDDM subjects. The ELISA should facilitate screening to evaluate the role of autoimmunity to GAD in the development of IDDM.
Diabetes 1992 Sep
PMID:An ELISA for antibodies to recombinant glutamic acid decarboxylase in IDDM. 149 69

The destruction of pancreatic islet beta cells in insulin-dependent diabetes mellitus (IDDM) is thought to be T cell mediated. To directly identify islet-reactive T cells in asymptomatic, "preclinical" IDDM individuals with islet cell antibodies (ICA), proliferation of peripheral blood mononuclear cells (PBMC) was measured in the presence of sonicated fetal pig proislets. Stimulation indices (mean +/- SD) for [3H]thymidine uptake by PBMC cultured with sonicated proislets were: preclinical IDDM subjects (n = 22) 6.10 +/- 6.50, recent-onset IDDM subjects (n = 29) 3.66 +/- 3.35, Graves' disease subjects (n = 6) 2.17 +/- 0.93, scleroderma subjects (n = 4) 1.65 +/- 0.19 and normal control subjects (n = 14) 1.63 +/- 0.62. 68% (15/22) of preclinical IDDM, 41% (12/29) of recent-onset IDDM and 17% (1/6) of Graves' disease subjects had T cell reactivity greater than the mean + 2 SD of controls. T cell reactivity to proislets was tissue specific, and greater in magnitude and frequency than to human insulin. The majority of preclinical subjects with ICA greater than 20 Juvenile Diabetes Foundation (JDF) units (12/15, 80%) or antibodies to a 64-kD islet autoantigen (11/15, 73%) had significant T cell reactivity to proislets. ICA greater than 40 JDF units, a strong prognostic marker for progression to clinical IDDM, was an absolute index of T cell reactivity. Overall, the frequency of T cell reactivity in preclinical subjects, 68% (15/22), was comparable to that of ICA greater than 20 JDF units or 64-kD antibodies. Greater T cell reactivity to proislets in preclinical subjects accords with the natural history of autoimmune beta cell destruction. The direct assay of islet-reactive T cells in peripheral blood may have prognostic significance for the development of clinical IDDM and should facilitate identification of the primary target autoantigen(s).
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PMID:Islet-reactive T cells are a marker of preclinical insulin-dependent diabetes. 155 80


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