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)

We report on two patients (one female 42 years, one male 47 years) suffering from insulin-dependent diabetes mellitus (IDDM) for more than 20 years. Both patients exhibited sclerodactyly and sclerosis of the hands and lower arms as well as swelling and slight contracture of the distal interphalangeal joints. Interestingly, internal organs were not involved and autoantibodies characteristic for scleroderma were missing. Poor utilization and excess of glucose seem to be responsible for the activation of fibroblasts to produce abundant matrix proteins in the skin. Significant therapeutic improvement of the glucose metabolism was able to improve joint contractures or at least to stop the progression of skin changes in our patients. These skin changes should not be misdiagnosed as systemic sclerosis.
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PMID:Scleroderma-like lesions in insulin-dependent diabetes mellitus. 1056 31

The renin angiotensin system (RAS) is now recognized as the body's most powerful hormone system for controlling renal hemodynamics and sodium excretion and, therefore, body fluid volumes and arterial pressure. The discovery of angiotensin converting enzyme inhibitors (ACEi) was a keystone for the understanding of the significance of the RAS since ACEi proved to be effective in controlling hypertension and heart failure and in preventing the development of the vascular injury of chronic diseases like scleroderma and diabetes mellitus. The success of ACEi stimulated the research into inhibitors of other actors of the RAS like renin or angiotensin receptor antagonists. It is not often realized that the discovery of ACEi owes a great deal to basic research in which the venom of a Brazilian viper, Bothrops Jararaca, was instrumental for the discovery of bradykinin by Rocha e Silva and the bradykinin potentiating factor. This article reviews the contribution of the converting enzyme inhibitors for the demonstration of the relevance of the RAS to several human pathologies.
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PMID:Angiotensin converting enzyme: history and relevance. 1070 50

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3[1,25-(OH)2D3], exerts immunosuppressive activity. At a cellular and molecular level, the hormone preferentially targets helper T cell activity (Th1) by inhibiting the secretion of both IL-2 and IFN-gamma by Th1 and by suppressing the secretion pro-Th1 cytokine IL-12 by antigen-presenting cells. The active metabolite further inhibits class II antigen expression and enhances suppressor cell activity. In animal models of autoimmunity, 1,25-(OH)2D3 prevents the development of experimental autoimmune encephalomyelitis, reduces the incidence of diabetes, and attenuates murine lupus. The hormone also prolongs graft survival in animal models of transplantation. In humans, non-classical use of 1,25-(OH)2D3 has led to an anti-proliferative effect in psoriasis, antineoplastic effect in prostate cancer, and immunomodulatory effect in scleroderma. The development of less hypercalcemic analogs might open a new therapeutic area for vitamin D3.
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PMID:1,25-Dihydroxyvitamin D3--a hormone with immunomodulatory properties. 1076 31

We describe 4 women of 43, 73, 84, and 86 years with Raynaud's phenomenon, severe digital necrosis, and high serum levels of anticentromere antibodies without skin thickening or internal organ sclerosis. Investigations revealed no diabetes or arterial vascular disease leading to arterial obstruction. Histologic examination did not show any dermal sclerosis or calcinosis. The intravenous infusions of prostaglandin reversed the ischemic lesions in 3 patients. These cases suggest that the triad Raynaud's phenomenon, anticentromere antibodies and necrosis of digits without sclerodactyly and sclerosis of internal organ should be considered as an entity distinct from scleroderma with sclerosis. For this entity we propose the name RACAND syndrome.
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PMID:Raynaud's phenomenon, anticentromere antibodies, and digital necrosis without sclerodactyly: an entity independent of scleroderma? 1100 18

1. Pericytes are cells of microvessels (arterioles, capillaries and venules) that wrap around endothelial cells. They are most abundant on venules and are common on capillaries. 2. The pericyte population is highly variable between different tissues and organs, probably in a manner reflecting postarteriolar hydrostatic pressures. Pericytes are more abundant in the distal legs and feet, again suggesting a hydrostatic pressure-driven mechanical role for pericytes as protectors of microvessel wall integrity. 3. Pericyte alteration or degeneration is linked directly with microangiopathy in diabetes, scleroderma, hypertension, dementias and, possibly, inappropriate calcification of blood vessels. 4. Pericytes are functionally codependent on endothelial cells. Each cell type influences each others' mitotic rate and probably phenotypic expression. 5. Pericytes are not randomly located around microvessels. Instead, they are located adjacent to or over endothelial cell junctions of venules and especially over gaps between endothelial cells during inflammation. Pericytes are emerging as essential components of the microvessel wall, with metabolic, signalling and mechanical roles to support the endothelial cell.
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PMID:Diversity within pericytes. 1102 80

Involvement of the central nervous system is uncommon in progressive systemic sclerosis, with only 2 reported cases associated with intracerebral hemorrhage detected by neuroimaging. A 55-year-old woman with a 10-year history of scleroderma presented with left occipital lobe hemorrhage manifesting as headache and vomiting. She had no signs of hypertension, diabetes mellitus and hyperlipidemia. CT and MRI, on admission, showed left occipital lobe hemorrhage with ventricular rupture and acute left subdural hematoma. Serial cerebral angiography was performed on day 0, day 7 and day 14, and found no evidence of aneurysm, arteriovenous multiformation or tumor stain in the left occipital lobe. However, the bilateral anterior cerebral arteries showed increasing segmental narrowing suggestive of vasculitis. Histological examination of a section from the brain cortex adjacent to the hemorrhage revealed no evidence of vasculitis, fibrinoid degeneration or amyloid deposition. Focal vasculitis may have occurred secondary to the homorrhagic lesion.
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PMID:[A case of left occipital lobe hemorrhage in a patient with progressive systemic sclerosis: evaluation of cerebral angiography and histology]. 1112 85

Pseudohypertension is the artifactual elevation of blood pressure that occurs secondary to noncompressible blood vessels. It has been described in patients with uremia, diabetes mellitus, and severe atherosclerosis. If unrecognized, the condition may lead to inappropriate and potentially harmful therapy. We report a case of pseudohypertension in a 65-year-old man with diffuse scleroderma. His blood pressure as assessed by conventional sphygmomanometry was at least 240/135 to 145 mm Hg. Intra-arterial blood pressure was found to be 107/52 mm Hg. The severe rise in blood pressure as measured by sphygmomanometry led to the concern of scleroderma renal crisis and potentially harmful therapy. Intra-arterial pressure monitoring confirmed the presence of pseudohypertension, however. This is the first reported case of pseudohypertension in a patient with diffuse scleroderma.
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PMID:Pseudohypertension in a patient with diffuse scleroderma. 1127 2

The purpose of this study is to better characterize graft and patient survival posttransplantation by examining survival according to underlying renal disease for all first-time renal allograft recipients in the United Network for Organ Sharing (UNOS) registry. From 1987 through 1996, the UNOS registry collected data on 23,838 living and 67,183 cadaveric renal transplantations. This investigation included all patients undergoing their first renal transplantation for whom the underlying cause of renal failure could be identified and categorized. Gross 1- and 3-year patient and graft survival according to underlying renal disease are included. In addition, a Cox proportional hazards model was created to analyze the effect of underlying disease on graft and patient survival after adjusting for comorbid conditions, demographics, and type of renal transplant (living versus cadaveric). The association between underlying disease and graft and patient survival is shown. Amyloidosis, sickle cell anemia, scleroderma, and radiation nephritis are associated with poor graft and patient survival. The risk ratio for patient mortality was more than twice that for immunoglobulin A nephropathy for a number of conditions, including analgesic nephropathy, amyloidosis, and both forms of diabetes mellitus.
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PMID:Relationship between underlying renal disease and renal transplantation outcome. 1138 83

Bradykinin is formed by the interaction of factor XII, prekallikrein, and high-molecular-weight kininogen on negatively charged inorganic surfaces (silicates, urate, and pyrophosphate) or macromolecular organic surfaces (heparin, other mucopolysaccharides, and sulfatides) or on assembly along the surface of cells. Catalysis along the cell surface requires zinc-dependent binding of factor XII and high-molecular-weight kininogen to proteins, such as the receptor for the globular heads of the C1q subcomponent of complement, cytokeratin 1, and urokinase plasminogen activator receptor. These 3 proteins complex together within the cell membrane, and initiation depends on autoactivation of factor XII on binding to gC1qR (the receptor for the globular heads of the C1q subcomponent of complement). There is also a factor XII-independent bypass mechanism requiring a cell-derived cofactor or protease that activates prekallikrein. Bradykinin is degraded by carboxypeptidase N and angiotensin-converting enzyme. Angioedema that is bradykinin dependent results from hereditary or acquired C1 inhibitor deficiencies or use of angiotensin-converting enzyme inhibitors to treat hypertension, heart failure, diabetes, or scleroderma. The role for bradykinin in allergic rhinitis, asthma, and anaphylaxis is to contribute to tissue hyperresponsiveness, local inflammation, and hypotension. Activation of the plasma cascade occurs as a result of heparin release and endothelial-cell activation and as a secondary event caused by other pathways of inflammation.
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PMID:Pathways for bradykinin formation and inflammatory disease. 1184 87

NKT cells represent a unique T cell lineage that recognize glycolipid antigens in the context of the non-classical MHC class I molecule CD1d. NKT cells are potent producers of immunoregulatory cytokines, and have been implicated in several different autoimmune diseases in mice and humans, including Type 1 diabetes, experimental autoimmune encephalomyelitis--a mouse model for multiple sclerosis, systemic lupus erythematosus, and scleroderma. This review will cover the evidence for an involvement for NKT cells in these autoimmune diseases, and discuss the potential for therapeutic manipulation of these cells as a means of preventing autoimmune disease in the clinic.
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PMID:NKT cells: potential targets for autoimmune disease therapy? 1214 18


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