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)

All patients with systemic lupus erythematosus (SLE) (American Rheumatism Association criteria with positive antinuclear antibody titre) and who attended any of the three general hospitals in Leicester over a 10 year period were ascertained using several complementary sources. Eighty seven subjects (26 Asian, 61 white) were identified. The estimated prevalence of SLE in Leicester is 0.4/1000 for Asian and 0.2/1000 for white subjects. Mean age of onset of the disease was 24 years in Asian and 31 years in white subjects, with both groups showing a female preponderance. Proteinuria (greater than 1 g/24 h) was noted in 15 (58%) Asian and 21 (35%) white subjects; neuropsychiatric disease in 10 (38%) Asian and 8 (13%) white subjects; myalgic symptoms with raised muscle enzymes in 9 (35%) Asian and 3 (5%) white subjects. Nineteen (73%) Asian subjects were positive for extractable nuclear antigens as well, at some stage of their disease, compared with 6 (10%) white subjects. Immunosuppressive treatment was required in 12 (46%) Asian and 12 (20%) white subjects, and deaths of seven Asian and five white subjects were attributed to SLE. These findings show that Asian subjects have a higher prevalence of SLE with greater systemic disease and mortality.
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PMID:High prevalence of systemic disease and mortality in Asian subjects with systemic lupus erythematosus. 187 55

We studied the effects of difluoromethylornithine (DFMO), an experimental drug that inhibits the biosynthesis of natural polyamines, on anti-DNA antibody production, immunoglobulin synthesis, proteinuria, and blood urea nitrogen (BUN) in lupus-prone female NZB/W mice. Administration of 1% of the drug in drinking water reduced anti-DNA antibody levels by about 80% of that of untreated mice of the same strain. There was a reduction of IgG and IgA levels in older DFMO treated mice, whereas IgM level was not affected. Proteinuria and BUN were also significantly reduced in treated mice. Moreover, DFMO treatment reduced the concentration of putrescine and spermidine in spleen cells. Our results suggest that polyamine biosynthesis inhibition by DFMO may provide a new approach to the treatment of lupus.
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PMID:Difluoromethylornithine therapy of female NZB/W mice. 202 14

Although many reports have been made on the effectiveness of plasma exchange (PE) in active systemic lupus erythematosus (SLE), but there are no clear-cut criteria of indication for lupus nephritis (LN). In order to determine the criteria for indication of LN, 35 patients with LN treated by PE were studied with respect to renal function (F), proteinuria (P), immunological activity (A) and renal histology. The patients were divided into 4 groups according to the severity of renal function: F1 (stable chronic renal failure (CRF) or stable renal function n = 13), F2 (relapse type n = 9), F3 (rapidly progressive LN; creatinine clearance (Ccr) less than 40 ml/min n = 7) and F4 (acute renal failure; Ccr less than 10 ml/min n = 6). Proteinuria was also studied in 4 groups: P1 & P2 (without nephrotic syndrome (NS], P3 (acute type NS n = 15), and P4 (chronic type NS n = 7). These patients were divided into 3 groups to study immunological activity: A1 (chronic stage n = 6), A2 (relapse stage n = 12) and A3 (active stage n = 17). Comparison was made in each parameter. Renal histological classification according to WHO criteria of LN, activity score (AS) and chronicity score (CS) were evaluated and compared. As a result, the following indication was obtained. 1) ABSOLUTE INDICATION: 1. Rapidly progressive LN with high immunological activity; elevated serum creatinine (SCr) greater than 1.0 mg/dl/month or decreased Ccr from normal renal function to less than 40 ml/min within 1-2 months after onset. 2. Acute type NS within 1 year after onset. 3. histological AS greater than 20. 2) RELATIVE INDICATION: 1. Relapse LN with moderate immunological activity, decreased Ccr from normal function to 40-50 ml/min within 3-6 months, the rise in SCr of greater than 1.0 mg/dl/month. 2. Proteinuria is 1.0-3.5 g/day within 1 year after onset. 3. Such complication as CNS, serositis, thrombocytopenia and leukopenia, steroid resistance and/or severe side effects of steroid. 3) NO INDICATION: 1. CRF or stable renal function (Ccr greater than 50 ml/min). 2. Chronic type NS over 1 years with past history of NS and/or edema. 3. Low immunological activity and mild renal histology.
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PMID:[The criteria for indication of plasma exchange on lupus nephritis]. 221 18

The pathogenesis of renal involvement was studied in murine chronic graft-versus-host disease (GVHD), which is a model for human systemic lupus erythematosus. GVHD was induced by four i.v. injections of lymphocytes from DBA/2 donor mice into (C57BL/10 x DBA/2)F1 hybrids at 3-4-day intervals. Two weeks after the first injection, antibodies were found to have been deposited in the mesangium and along the glomerular basement membrane (GBM) in a linear arrangement, which changed to a granular pattern after 6-8 weeks. In this stage, large electron-dense complexes were present both subepithelially and subendothelially along the GBM. Proteinuria increased up to 11,300 +/- 2140 micrograms/18 h. Indirect immunofluorescence studies and ELISA showed that sera and kidney eluates contained autoantibodies directed against nuclear antigens and GBM component laminin as well as against renal tubular epithelial antigens (RTE). The specificity of the anti-RTE antibodies was further characterized by the use of absorption techniques as well as immunoblotting. The early linear immunofluorescence pattern seems to be associated with glomerular binding of anti-GBM antibodies, while electron-dense complex formation in later stages may be induced by the superimposed deposition of anti-RTE antibodies. Similar phenomena were recently described in Heymann's nephritis in the rat, a model for human membranous nephropathy.
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PMID:Pathogenesis of experimental lupus nephritis: a role for anti-basement membrane and anti-tubular brush border antibodies in murine chronic graft-versus-host disease. 230 29

The renal glomeruli are vulnerable to injury by a number of drugs and other toxic agents. These agents may lead to damage by one of two basic mechanisms: direct, dose-related toxic injury; indirect, immunologically mediated injury, largely dose-independent. Proteinuria is the simplest and most important functional indicator of glomerular injury. It occurs almost immediately in direct toxic injury, but there is a latent period of weeks to months with immunologically mediated processes. Of the two mechanisms, the second is by far the more common in clinical settings. The best studied experimental agent causing direct toxic injury is the aminonucleoside of puromycin. Clinically, perhaps the most important agent is Cyclosporine A. Although this agent is usually thought of primarily as a tubular toxin, it is capable of giving rise to a microangiopathic glomerular lesion similar to that in the hemolytic uremic syndrome. The classic model for immunologic glomerular lesion is Heymann nephritis, which produces a membranous glomerulopathy. Clinically, most drug mediated glomerulopathies also take the form of a membranous nephropathy, usually with a frank nephrotic syndrome. Among the more common offenders are penicillamine, gold salts used in rheumatoid arthritis, and captopril used in hypertension. The other common type of drug-related glomerulopathy occurs as part of a lupus-like syndrome induced by a variety of drugs, including hydralazine, procainamide, and penicillamine. All of these give rise to a variety of antibodies, most prominently antinuclear antibodies, and in the more severe cases there may be lupus-like glomerular lesions as well.
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PMID:Drug-associated glomerulopathies. 294 Jun 67

Respiratory stridor and hoarseness were the predominant presenting symptoms in a 63-year-old woman with an hydralazine induced lupus syndrome. Laryngeal tomograms and direct laryngoscopy were consistent with cricoarytenoid arthritis. Proteinuria, anemia, arthritis, and leukocytoclastic vasculitis, as well as the laryngeal findings, all resolved after withdrawal of hydralazine. Laryngeal manifestations of systemic lupus erythematosus are reviewed.
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PMID:Laryngeal manifestations of drug induced lupus. 359 9

Early reports on SLE were too small in number to determine that pregnancy was contraindicated in patients with renal involvement. Later reports show that patients with lupus nephropathy can have successful pregnancies provided certain preconditions are established. Optimal preconditions include prepregnancy remission of at least 6 months, renal function with serum creatinine 1.5 mg/dl or less or creatinine clearance of 60 ml/min or more or proteinuria of 3 g/24 hr or less. Successful pregnancies have been recorded in some patients with more severe renal impairment. Renal function will remain unchanged in approximately 60% of pregnancies; and although deterioration may occur, it is only severe or permanent in less than 10%. In 26% of patients, mild to severe renal impairment was transient, with recovery to prepregnancy levels of renal function. Proteinuria with good creatinine clearance may not be dangerous. Hypertension or superimposed preeclampsia jeopardizes the outcome. Fetal outcome averaged approximately 70% (range, 41-77%) live births, 17.8% (range, 5.1-40%) spontaneous abortions, 19.7% (range, 3.0-38.5%) prematurity, and 8.2% SGA. Therapeutic abortion is not a modality of treatment of lupus nephropathy. Management of patients with lupus nephropathy is twofold and includes suppression of underlying lupus activity as well as the serial evaluation of chronic renal disease. In chronic lupus nephropathy with inactive SLE maternal and fetal outcome is the same as for pregnant patients with chronic renal disease of other causes. Strict fetal surveillance must be performed to decrease the stillbirth rate. The concomitant increase in prematurity demands the services of a tertiary care neonatal unit. Management necessitates the team approach of the obstetrician, nephrologist, rheumatologist, and neonatologist working in collaboration. The reports which contain large numbers of patients now allow better counseling of these patients who are contemplating pregnancy.
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PMID:Lupus nephropathy and pregnancy. 389 19

We present 11 patients with immunotactoid glomerulopathy, a new syndrome characterized clinically by proteinuria (11/11), microscopic hematuria (9/11) and hypertension (9/11). The patients consisted of six females and five males, aged 25 to 59 years (mean, 44.6). Proteinuria was the presenting feature and the reason for renal biopsy in all patients. The diagnosis of immunotactoid glomerulopathy was established at renal biopsy by the presence of glomerular extracellular microtubules composed of immune reactants. All the biopsies studied by immunofluorescence (10 cases) had glomerular deposits of IgG and C3. In three biopsies studied with IgG subclass specific antisera, only one patient had monoclonal immunoglobulin deposits (IgG3 kappa). In six cases the glomerular deposits were analyzed for light chains. In three the deposits contained kappa only, and three consisted of both kappa and lambda. In two cases the immune aggregates were confined to the mesangium, and in the remaining eight cases, the deposits were present in the mesangium and the glomerular basement membranes. Electron-dense deposits composed of microtubules were present in the same distribution within the glomerulus as the immune reactants. The microtubules had a uniform diameter in each biopsy, but they varied in size from case to case. They were approximately the same size in eight cases (mean, 22.3 +/- 3 [SD] nm). Three cases had much larger microtubules: 34.2 nm, 35.4 nm, and 48.9 nm in diameter. Although the 22.3-nm microtubules resembled amyloid in their appearance, glomerular distribution and random orientation in the tissue, they were more than twice the diameter of amyloid (8.9 nm), and Congo red and thioflavin T stains for amyloid were negative. Similar microtubular structures have been described in patients with cryoglobulinemia, SLE and paraproteinemia, but these diseases were excluded in our patients on clinical, serologic and in some cases histologic grounds. More important, none of our patients had clinical or histochemical evidence of amyloidosis, an entity which may be confused with immunotactoid glomerulopathy on a morphologic basis. Follow-up, from 22 to 94 months (mean, 52.6) was obtained in all 11 patients, and 2 clinical courses were noted. Six patients had progressive deterioration of renal function, with five requiring dialysis. This group had severe hypertension (4/6) and nephrotic-range proteinuria (5/6) at some point in their course. The remaining five patients with stable renal function had proteinuria of less than 2.0 g/24 hr in most cases (4/5), and none had severe hypertension. This dichotomy correlated with the distribution of immunotactoids.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunotactoid glomerulopathy. 401 May

Rabbits immunized with ultraviolet-irradiated DNA (UV-DNA) produced high titers of serum antibody. This experimental model was studied to determine if injection of antigen (UV-DNA) intravenously into immunized animals would induce glomerulonephritis and proteinuria. Proteinuria was observed several days after the start of daily intravenous injections into immunized animals and was sustained as long as injections were continued, but fell to normal values after stopping antigen administration. The kidneys showed glomerulitis sometimes associated with focal proliferative lesions, and immunofluorescence showed rabbit Ig and C3 in glomeruli. By electron microscopy, electron-dense subendothelial deposits were seen. Sucrose density gradient analyses of sera immediately after antigen injections suggested the presence of immune complexes of DNA and antibody since both heavy sedimenting and 7S Ig were detected. After digestion with deoxyribonuclease rabbit Ig could be found only in the 7S sedimenting fractions. Intravenous injection of UV-DNA into normal, nonimmune animals did not produce heavy sedimenting Ig or abnormal sedimentation patterns. These studies with an experimental model might provide insight into pathogenetic mechanisms operating in systemic lupus erythematosus where the importance of DNA-anti-DNA immune complexes have been documented. The studies suggested that gradual accumulation of DNA immune complexes in glomeruli might be one mechanism causing renal functional abnormalities.
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PMID:Experimental renal disease induced by DNA-anti-DNA immune complexes. 455 Apr 91

The pregnant patient with nephrotic syndrome should be carefully evaluated for the presence of chronic renal disease. Proteinuria itself may be associated with an increase in perinatal mortality and in the incidence of small-for-gestational-age infants. Coexistent hypertension and/or renal dysfunction add to the risk of an unsuccessful pregnancy. The use of tocolytic agents in pregnant women with nephrotic syndrome theoretically may be hazardous. The patient with systemic lupus erythematosus may be at particular risk of unsuccessful pregnancy if the disease is active; postponement of conception until a remission of six months or longer has been achieved may be well advised.
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PMID:Nephrotic syndrome and pregnancy. Potential problems for mother and child. 649 72


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