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)

To determine brain functional abnormality in systemic lupus erythematosus (SLE) patients with psychiatric symptoms, we evaluated 12 active SLE patients with or without psychiatric symptoms by means of [18F]2-fluoro-2-deoxy-D-glucose positron emission tomography (PET), magnetic resonance imaging and neuropsychological testing. Patients with psychiatric symptoms showed significantly poorer performance in tests which subserved attentional function. The PET study revealed that the psychiatric patients had significantly decreased regional cerebral metabolic rates for glucose in the prefrontal, inferior parietal and anterior cingulate regions. Prefrontal, inferior parietal and anterior cingulate dysfunction may be related to attentional deficits that are involved in various psychiatric symptoms in SLE. PET is an invaluable tool to reveal such brain functional abnormality seen in SLE patients with psychiatric symptoms.
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PMID:Decreased regional cerebral metabolic rate for glucose in systemic lupus erythematosus patients with psychiatric symptoms. 1039 47

The presence of insulin receptor antibodies is a rare cause of insulin resistance. Patients usually have a combination of hyperglycemia, insulin resistance, acanthosis nigricans, and autoimmune features. We report a patient with systemic lupus erythematosus and severe insulin resistance due to insulin receptor antibodies. The most striking aspect of the clinical presentation is the resistance to insulin therapy, with our patient unresponsive to doses of up to 154,075 units in a day. While on a low-dose glucocorticoid therapy, the patient had clinical improvement, and glucose levels subsequently became normal even without insulin and glucocorticoid.
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PMID:Insulin receptor antibodies and insulin resistance. 1041 83

The present study was undertaken to investigate whether active induction of systemic lupus erythematosus (SLE) in non-obese diabetic (NOD) mice could affect their development of insulin-dependent diabetes mellitus (IDDM). NOD mice were immunized with a human IgM mAb carrying the 16/6 idiotype (MIV-7) or with control human IgM. The mice were bled monthly and tested for SLE-associated autoantibodies in the serum and for the presence of leukopenia, thrombocytopenia, proteinuria and immunoglobulin deposits in the kidneys. The development of diabetes was determined by a blood glucose level exceeding 15 mM on two consecutive weekly determinations and by the presence of insulitis in the pancreas. The NOD mice immunized with MIV-7 developed high and persistent levels of autoantibodies, including anti-DNA, anti-histones and anti-cardiolipin, untreated mice and those immunized with normal human IgM did not produce these autoantibodies. The MIV-7-immunized mice also manifested an elevated erythrocyte sedimentation rate, leukopenia, thrombocytopenia and significant proteinuria, as well as deposits of Ig in their kidney glomeruli. Thus, NOD mice immunized with MIV-7 developed both autoantibodies and clinical features of SLE. The MIV-7-treated mice, however, showed a significantly lower incidence of IDDM (25%vs. 90%, P<0.003), accompanied by amelioration of the insulitis. The present study indicates that the induction of SLE by idiotypic immunization can protect NOD mice from developing IDDM, pointing to the importance of immune dysregulation in shift from one autoimmune disease to another.
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PMID:Inhibition of diabetes in NOD mice by idiotypic induction of SLE. 1044 Nov 67

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

Emphysematous cystitis (EC) is a rare condition in which gas-forming organisms are active in the bladder wall and lumen. Most of the cases have been described in patients suffering from diabetes mellitus due to glucosuria and subsequent anaerobic fermentation of glucose. To our knowledge this condition has never been described in association with systemic lupus erythematosus (SLE). We report here the first case of EC during the course of a chronic lupus cystitis (LC) in a woman suffering from SLE and type-I diabetes mellitus.
Lupus 2000
PMID:Lupus cystitis: a possible additive risk factor for emphysematous cystitis in diabetes mellitus: discussion about one case. 1119 30

With donor and recipient matched at the major histocompatibility complex (MHC) locus, peripheral lymphoid tissue transplantation can be carried out without producing a graft-versus-host reaction or graft-versus-host disease (GVHD), thus correcting profound T cell immunodeficiencies of neonatally thymectomized mice. This analysis set the stage for clinical application of bone marrow transplantation (BMT) to provide for the first time cure of a human disease. With successful BMT, we cured immunologic deficiencies of a patient with XL severe combined immunodeficiency; thereafter we were the first to employ BMT to cure aplastic anemia. BMT regularly corrects immune and hematologic deficiencies caused by fatal irradiation without producing GVHD if the bone marrow (BM) used for the transplants has been purged of postthymic T cells. Over two decades in conjunction with Ikehara et al., we have shown that lethal total body irradiation (TBI) plus allogeneic BMT prevents or cures many organ-specific and systemic experimental autoimmune diseases. Animal models successfully treated by BMT include type I diabetes in nonobese diabetes (NOD) mice, type II diabetes in insulin-insensitive, glucose intolerant, diabetes mellitus (KK/Ay) mice, and autoimmune lupus erythematosus (LE) and glomerulonephritis in New Zealand Black x New Zealand White first generation hybrid (NZB x NZW)F1 females. El-Badri extended Ildstad's original research showing a high frequency of survival with a normal functioning immune system after stable mixed chimerism is produced by mixed BMT in C57BL/6 (normal long-lived black strain) mice transplanted with T cell-depleted marrow (TCDM) from BALB/c ("normal" long-lived strain) allogeneic donors and C57BL/6 syngeneic donors. We showed that osteoblasts act as facilitator cells for allogeneic BMT and promote engraftment of allogeneic hematopoietic stem cells. Wang et al. then showed that the autoimmunities and fulminating renal disease of BXSB (C57BL x SB cross and selective lupus-like systemic autoimmunity) male mice was prevented and could be cured by transplantation using TCDM from both BALB/c (resistant) and BXSB (susceptible) strains given to BXSB recipients after lethal TBI. This treatment produced mixed BMT and a stable mixed chimerism, increased longevity, corrected all manifestations of autoimmunity, and cured fulminant glomerulonephritis in these recipients. These studies generated a new perspective on the potential usefulness of BM and stem cell transplants to cure major diseases that can possibly be treated by BMT. Mixed BMT from TCD BALB/c and BXSB mice cured autoimmunities and fulminant glomerulonephritis in BXSB mice. LE disease plus coronary vascular disease that occurs in (NZW x BXSB)F1 mice, along with idiopathic thrombocytopenic purpura, is also cured in lethally irradiated (NZW x BXSB)F1 mice by BMT from C57BL/6 donors. Furthermore, hemolytic anemia, autoimmune phenomena, and hyalinizing glomerular renal disease of New Zealand Black (NZB) mice were prevented or cured by stem cell transplants using purified stem cells from MHC-matched DBA/2 donors or NZB donors. Consequently, we reasoned that autoimmunities reside in stem cells. More recently, we found that transplants of both BM cells and bones can completely and permanently prevent otherwise highly resistant autoimmune diseases of MRL/lpr lpr mice and an autoimmune polyarthritis of NZB/Kn mice. Ildstad concluded that lethal preparative measures would not be acceptable for preparations to treat autoimmune diseases, so we now employ a gentle method for producing stable mixed chimerism described by Sharabi and Sachs to achieve mixed marrow transplantation and mixed hematopoietic chimerism. Other diseases we are approaching using this gentle manipulation include two forms of diabetes: insulin-dependent diabetes mellitus (IDDM) type I in NOD mice and non-insulin-dependent diabetes mellitus (NIDDM) type II in KK/Ay mice, atherosclerosis of apolipoprotein-E + kno
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PMID:Progress toward production of immunologic tolerance with no or minimal toxic immunosuppression for prevention of immunodeficiency and autoimmune diseases. 1083 46

The primary antiphospholipid antibody syndrome (PAPS) has been described in patients with a history of fetal loss, thrombocytopenia and arterial or venous thrombosis. In PAPS, a prothrombotic state is mediated by antiphospholipid antibodies (aPLs) leading to disseminated thromboembolic vascular occlusion. Today, the presence of aPLs in the serum is considered as a distinct risk factor for recurrent stroke in young adults. Some PAPS patients develop a multi-infarct-syndrome with a stepwise decline of higher cortical functions. We report on a 55-year-old man suffering from progressive dementia and PAPS, in whom cerebral glucose metabolism and blood flow were examined by positron emission tomography (PET). Cerebral atrophy and moderate signs of leukaraiosis were detected in magnetic resonance imaging (MRI), whereas the PET scans showed a considerable diffuse impairment of cortical glucose metabolism combined with a reduced cerebral perfusion in the arterial border zones. These findings indicate that PAPS-associated vascular dementia is accompanied by a cortical neuronal loss, presumably caused by a small-vessel disease with immune-mediated intravascular thrombosis. This case shows that pathological findings in PAPS are congruent to cerebral changes of metabolism and blood flow in systemic lupus erythematosus (SLE).
Lupus 2000
PMID:Cerebral blood flow and glucose metabolism in multi-infarct-dementia related to primary antiphospholipid antibody syndrome. 1134 Nov 10

Neuropsychiatric systemic lupus erythematosus (SLE) is frequently associated with deficits in brain glucose metabolism, even if morphological imaging by magnetic resonance imaging (MRI) shows no abnormalities. In these patients it is unclear whether or not the changes of brain metabolism measured by F-18-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) may progress to lesions of cerebral structure. We describe a 20-year-old woman with SLE who presented with depression, headache and impairment of memory. Initially, a cranial MRI was negative, but FDG-PET revealed significant hypometabolism in the frontal and parieto-temporo-occipital regions on both sides as well as hypermetabolism in the nuclei caudati. Within two months the patient developed an acute confusional state, seizures, visual disturbances and cranial MRI became positive showing hyperintensities at the basal ganglia and the temporo-occipital regions. Focal cerebral symptoms responded to treatment with high dose corticosteroids and brain lesions in MRI disappeared. However, a second FDG-PET showed persistent hypometabolism at frontal regions in accordance with the persistence of subclinical depression. To our knowledge, this is the first SLE case report showing that functional brain lesions visualized by FDG-PET may be a risk factor for subsequent structural brain damage seen in MRI. Thus, FDG-PET may help to verify cerebral involvement of SLE earlier than MRI.
Lupus 2000
PMID:Alterations of cerebral glucose metabolism indicate progress to severe morphological brain lesions in neuropsychiatric systemic lupus erythematosus. 1087 34

Diabetic ketoacidosis and moderate degree of hyperglycemia can be managed by glucose-insulin-potassium (GIK) regimen. The GIK regimen is also useful in the treatment of acute myocardial infarction (AMI). But, the exact mechanism(s) of the beneficial action of GIK regimen is not known. I suggest that glucose-insulin can suppress the secretion and antagonize the harmful effects of tumor necrosis factor alpha (TNF alpha) and macrophage migration inhibitory factor (MIF). If this is true, it suggests that GIK regimen may be useful in septicemia and septic shock, and other inflammatory conditions such as ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus and cancer, conditions in which TNF alpha and MIF appear to play a major role.
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PMID:Newer uses of glucose-insulin-potassium regimen. 1120 54

Antimalarial therapy has a long and successful track record in the management of patients with mild SLE. Medium to long term use of hydroxychloroquine, alone or in combination with mepacrine, ameliorates lupus and may reduce the relapse rate. Recent guidelines for monitoring hydroxychloroquine have reduced the need for frequent visual checks. Antimalarials have other beneficial effects on lipid and glucose metabolism as well as having weak anticoagulant activity. They should be considered for most patients with mild lupus.
Lupus 2001
PMID:Antimalarial therapy: a panacea for mild lupus? 1131 43


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