Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemorrhagic cystitis is a potentially life-threatening complication in systemic lupus erythematosus (SLE). No safe, effective and conservative treatment exists for patients who fail to respond to standard therapy. We report a 17-year-old girl with SLE who suffered from severe hemorrhagic cystitis. Initially, she received frequent red blood cell and platelet transfusions, continuous bladder irrigation, and blood clots were evacuated. Numerous kinds of treatment were tried, including electrocoagulation of bleeding foci, prostaglandin E1 bladder instillation, and hyperbaric oxygen. However, she remained severely anemic and thrombocytopenic necessitating daily transfusions of blood products. After intravesical formalin instillation was performed twice, the hematuria ceased completely.
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PMID:Formalin treatment of refractory hemorrhagic cystitis in systemic lupus erythematosus. 987 30

Lupus nephritis results from an acute inflammatory and immunological response to renal immune complex deposition. The acute response is characterized by activation of circulating leukocytes and renal parenchymal cells, triggering the production of pro-inflammatory cytokines and growth factors. In all too many cases, this response is followed by a chronic response, which is characterized by excessive deposition of collagen and other extracellular matrix macromolecules and the development of end-stage renal disease. Mechanisms underlying this chronic response in progressive renal disease are not adequately defined. In this overview, potential roles of reactive oxygen species (ROS) generation and transforming growth factor-beta (TGF-beta) production in the pathogenesis of lupus nephritis are considered. ROS and TGF-beta may be key elements of a pathway leading to persistent and excessive matrix deposition in progressive lupus nephritis. Further studies to define the role of this pathway in lupus nephritis may lead to the development of additional, more specific therapeutic targets to prevent progression of renal disease.
Lupus 1998
PMID:Mechanisms of progression of renal damage in lupus nephritis: pathogenesis of renal scarring. 988 97

We investigated the effects of muscle mass and contraction intensity on the cardiorespiratory responses to static exercise and on the contribution afforded by muscle metaboreflex and arterial baroreflex mechanisms. Ten subjects performed static handgrip at 30% maximal voluntary contraction (MVC) (SHG-30) and one-leg extension at 15% (SLE-15) and 30% (SLE-30) MVC, followed by postexercise circulatory occlusion (PECO). Mean arterial pressure (MAP) and heart rate (HR) responses were greater during SLE-30 than during SHG-30. The difference in MAP was maintained by PECO, and the part of the pressor response maintained by PECO was greater after SLE-30 than after SHG-30 (88.3 +/- 10.6 and 67.8 +/- 12.7%, respectively, P = 0. 02). There were no differences in MAP and HR responses between SHG-30 and SLE-15 trials. Baroreflex sensitivity was maintained during SHG-30 and SLE-15, whereas it was significantly reduced during SLE-30 and recovered back to the resting level during PECO. Minute ventilation and oxygen uptake increased more during SLE-30 than during both SHG-30 and SLE-15 trials. Minute ventilation remained significantly elevated above rest only during PECO following SLE-30. These data suggest that during static exercise the muscle mass and contraction intensity affect 1) the magnitude of the cardiorespiratory responses, 2) the contribution of muscle metaboreflex to the cardiorespiratory responses, and 3) the arterial baroreflex contribution to HR control.
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PMID:Role of muscular factors in cardiorespiratory responses to static exercise: contribution of reflex mechanisms. 988 28

Minoeycline, a semisynthetic tetracycline, is often used to treat acne and rheumatoid arthritis. It has been considered an unlikely drug to be associated with systemic lupus erythematosus; however, many cases of drug-induced lupus related to minocycline have been reported. Some of those reports included pulmonary lupus, but none of the patients described developed respiratory distress. We describe a patient treated with minocycline for 2 years who presented with progressive dyspnea, severe hypoxia, and pulmonary infiltrates necessitating hospitalization and oxygen supplementation.
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PMID:Respiratory distress due to minocycline-induced pulmonary lupus. 1033 77

Alterations in DNA structure by hydroxyl radical modification was characterized by UV spectroscopy, Tm, nuclease S1 digestibility and base modification. In view of indicted role of oxygen free radicals in human diseases, an attempt has been made to precisely compare the antigen binding properties of induced antibodies against hydroxyl radical modified DNA with those of naturally occurring anti-DNA autoantibodies. Antibodies induced against ROS-DNA showed diverse antigen binding characteristics which were comparable with those derived from SLE patients. The immune IgG recognized native DNA, heat denatured DNA, and synthetic polynucleotides in B-/B-like conformations. IgG isolated from SLE sera showed preference for ROS-DNA in competition-inhibition assay. The antigenic diversity of induced antibodies and preference of circulating anti-DNA autoantibodies for ROS-DNA over that of native DNA demonstrates the possible role of modified DNA antigens in the pathogenesis of SLE.
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PMID:Human anti-DNA autoantibodies and induced antibodies against ROS-modified-DNA show similar antigenic binding characteristics. 1036 60

An intricate balance between soluble mediators, released by activated cells of the immune/inflammatory systems, and products of the neuroendocrine system is implicated in the presence of an autoimmune rheumatic disease. Monocytes/macrophages contribute to autoimmune events in rheumatic diseases, such as rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE), mainly acting as antigen-processing and presenting cells in the presence of an autoimmune rheumatic disease. Clinical symptoms such as morning stiffness and gelling, at least in RA, that peak during the late night and early morning, are consistent with the hypothesis that the immune function of activated cells (i.e., Th1 cells and monocytes/macrophages) and their mediators (cytokines and reactive oxygen intermediates) is increased at these times in relation to neuroendocrine pathway rhythmicity. Therefore, monocytes/macrophages seem to be the "link" between the steroid hormone environment (i.e., gonadal hormones) and the immune response effectors. If gonadal hormones, along with cytotoxic agents, do modulate macrophage apoptosis, such an approach might offer an important pathway to the control of autoimmune diseases. In conclusion, on the basis of a more complete understanding of macrophage effector and immunoregulatory activities, on both a local and systemic level, new hopes arise from the possible development of more sophisticated antimacrophage treatments for the management of autoimmune rheumatic diseases.
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PMID:Macrophages as effectors of the immunoendocrinologic interactions in autoimmune rheumatic diseases. 1041 91

Drug-induced lupus is a side effect of deliberate ingestion of various medications, but its etiology, underlying mechanisms, and pathogenesis are puzzling. In vivo metabolic transformation of lupus-inducing drugs to reactive products explains how a heterogeneous set of drugs can mediate the same disease syndrome. Evidence has accumulated that drugs are transformed by extracellular oxidation from reactive oxygen species and myeloperoxidase produced when neutrophils are activated, maximizing the in situ accumulation of reactive drug metabolites within lymphoid compartments. The metabolite of procainamide, procainamide hydroxylamine, displays diverse biologic properties, but no apparent autoimmune effect has been observed. However, when procainamide hydroxylamine was introduced into the thymus of young adult normal mice, a delayed but robust autoimmune response developed. Disruption of central T-cell tolerance by intrathymic procainamide hydroxylamine resulted in the production of chromatin-reactive T cells that apparently drove the autoantibody response in the periphery. Drug-induced autoantibodies in this mouse model were remarkably similar to those in patients with procainamide-induced lupus. Therefore, this system has considerable promise to provide insight into the initiating events in drug-induced lupus and may provide a paradigm for how other xenobiotics might induce systemic autoimmunity.
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PMID:Initiation of autoimmunity by a reactive metabolite of a lupus-inducing drug in the thymus. 1050 46

Heparan sulfate (HS) is the anionic polysaccharide side chain of HS proteoglycans (HSPGs) present in basement membranes, in extracellular matrix, and on cell surfaces. Recently, agrin was identified as a major HSPG present in the glomerular basement membrane (GBM). An increased permeability of the GBM for proteins after digestion of HS by heparitinase or after antibody binding to HS demonstrated the importance of HS for the permselective properties of the GBM. With recently developed antibodies directed against the GBM HSPG (agrin) core protein and the HS side chain, we demonstrated a decrease in HS staining in the GBM in different human proteinuric glomerulopathies, such as systemic lupus erythematosus (SLE), minimal change disease, membranous glomerulonephritis, and diabetic nephropathy, whereas the staining of the agrin core protein remained unaltered. This suggested changes in the HS side chains of HSPG in proteinuric glomerular diseases. To gain more insight into the mechanisms responsible for this observation, we studied GBM HS(PG) expression in experimental models of proteinuria. Similar HS changes were found in murine lupus nephritis, adriamycin nephropathy, and active Heymann nephritis. In these models, an inverse correlation was found between HS staining in the GBM and proteinuria. From these investigations, four new and different mechanisms have emerged. First, in lupus nephritis, HS was found to be masked by nucleosomes complexed to antinuclear autoantibodies. This masking was due to the binding of cationic moieties on the N-terminal parts of the core histones to anionic determinants in HS. Second, in adriamycin nephropathy, glomerular HS was depolymerized by reactive oxygen species (ROS), mainly hydroxyl radicals, which could be prevented by scavengers both in vitro (exposure of HS to ROS) and in vivo. Third, in vivo renal perfusion of purified elastase led to a decrease of HS in the GBM caused by proteolytic cleavage of the agrin core protein near the attachment sites of HS by the HS-bound enzyme. Fourth, in streptozotocin-induced diabetic nephropathy and during culture of glomerular cells under high glucose conditions, evidence was obtained that hyperglycemia led to a down-regulation of HS synthesis, accompanied by a reduction in the degree of HS sulfation.
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PMID:Glomerular heparan sulfate alterations: mechanisms and relevance for proteinuria. 1065 15

Thoracic involvement occurs more frequently in systemic lupus erythematosus than in any other connective tissue diseases, and more than half of patients with the disease suffer from the involvement. Primary intrathoracic manifestations include pleural disease (effusions and/or thickening), acute lupus pneumonitis, subacute interstitial lung disease including bronchiolitis obliterans organizing pneumonia and non-specific interstitial pneumonia with fibrosis, chronic interstitial lung disease of usual interstitial pneumonia, pulmonary hemorrhage, pulmonary vascular disease, small airway disease of bronchiolitis obliterans, and pulmonary arterial hypertension. Secondary intrathoracic manifestations include atelectasis due to diaphragmatic dysfunction, opportunistic pneumonia, drug and oxygen toxicity, aspiration, and pleuropulmonary consequences of cardiac and renal failure.
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PMID:Thoracic involvement of systemic lupus erythematosus: clinical, pathologic, and radiologic findings. 1066 51

We estimated the serum levels of IL-6, TNF-alpha and IL-10, and generation of superoxide radicals, as well as their mutual dependence, in 63 SLE patients at various stages of disease activity. Our results indicate a statistically significant increase of the serum levels studied, and an increase of superoxide anion generation by granulocytes, in correlation with SLE activity. These results indicate that oxygen metabolism and the examined cytokines play an important role in pathogenesis of SLE. The assessment of these parameters can be useful in the estimation of disease activity.
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PMID:Estimation of SLE activity based on the serum level of chosen cytokines and superoxide radical generation. 1070 46


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