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)

Estradiol metabolism in 10 patients with systemic lupus erythematosus (SLE) and 29 normal controls was studied by measurement of urinary metabolites after injection of labeled 3H-estradiol. Patients with SLE manifested increased 16-hydroxylation of estrone. Diseases men differed from diseases women to the extent that only 16 alpha-hydroxyestrone was elevated in men, whereas women had elevations of both 16 alpha-hydroxyestrone and estriol. These data suggest that patients with SLE have abnormal patterns of estradiol metabolism, leading to increased estrogenic activity.
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PMID:Alterations of estrogen metabolism in systemic lupus erythematosus. 50 72

Citrated samples from 100 patients on i.v. heparin and 20 normal patients were tested with three batches each of three activated partial thromboplastin time (APTT) reagents: Thrombosil I (Ortho); Automated APTT (Organon Teknika) and Actin FSL (Baxter). The ratio of APTT over the geometric mean normal APTT for each heparinized sample was calculated. One batch of reagent arbitrarily chosen as a reference gave the ratios APTRREF (y). The remaining reagents to be standardized against the reference system gave the ratios APTRTEST (x). The best correlation between systems was given by log vs log x. Standard curves were prepared from the APTT ratios of the 20 normal patients and 65 of the heparinized samples. On plotting log APTRTEST vs log APTRREF the y intercept was close to zero so x was expressed in terms of y using; log x = HSI. log y, where HSI (Heparin Sensitivity Index) = slope. The APTRTEST results of the remaining 35 heparinized samples were transformed using; APTRTRANS = (APTRTEST)HSI.APTRTRANS was then compared to APTRREF to determine whether the transformation brought the results closer to the reference. We conclude that although some improvement was found by using the transform, it was not possible to mathematically relate APTT results due to a high degree of variation between results using different reagents. A standard APTT reagent for the monitoring of heparin therapy is recommended. A separate APTT reagent may be required for the screening of factor deficiencies and lupus anticoagulants.
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PMID:An attempt to standardize APTT reagents used to monitor heparin therapy. 133 84

Antibodies to extractable nuclear antigens (ENA) are frequently demonstrated in the serum of patients with cutaneous lupus erythematosus. To gain a better understanding of the influence of sex hormones on cutaneous lupus, we investigated the in vitro binding of anti-ENA antibodies to cultured human keratinocytes. Estradiol-beta augmented the binding of anti-RNP, anti-SS-A/Ro, and anti-SS-B/La antibodies to cultured cells, but produced no enhancement of the binding of anti-Sm antibodies. In addition, we examined the effects of 16-alpha-hydroxyestrone, a highly estrogenic metabolite, on the binding of anti-ENA antibodies to cultured cells. This agent did not produce any augmentation of binding. Based on these experiments, we discuss the influence of estradiol on cutaneous lupus.
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PMID:Stimulation of anti-RNP antibody binding to cultured keratinocytes by estradiol. 192 44

A case is presented of a 37-year-old Japanese woman who presented to the hospital with arthralgia of the extremities and erythema of the hypothenar and thenar extremities. Also present were pain, swelling of the extremities, general malaise, and erythematous lesions. Abnormal laboratory findings included an elevated erythrocyte sedimentation rate, proteinuria, and weakly positive antinuclear antibodies. A biopsy from the erythematous lesion of the palm revealed mild inflammation of the lymphocytes around dermal small vessels. In addition, the lupus band test was positive in uninvolved skin sites. A month prior to the onset of symptoms, the patient had begun taking an oral contraceptive (OC) that contained 0.5 mg of etynodil acetate and 0.1 mg of mestranol. All symptoms disappeared within 2 weeks of discontinuation of OC use and the laboratory findings returned to normal. This is assumed to be a case of drug-induced lupus erythematosus. Estradiol has been demonstrated to play a significant role in the development of skin lesions in lupus erythematosus, and the estrogen in OCs may trigger a lupus episode. However, this is only the 4th case of OC-induced lupus reported from Japan.
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PMID:Oral contraceptive-induced lupus erythematosus in a Japanese woman. 205 Sep 10

A strong association between anti-SS-A/Ro and anti-SS-B/La antibodies and skin lesions has been well documented in subacute cutaneous lupus erythematosus and neonatal lupus erythematosis in which 70 to 80% of patients are female. In order to better understand the mechanisms of the influence of sex hormones on cutaneous lupus, we designed immunopathological in vitro experiments to evaluate the effects of estradiol and other sex steroids on the binding of SS-A/Ro- and SS-B/La-specific antibodies to cultured human keratinocytes from neonates. Cultured human keratinocytes incubated with antisera specific for SS-A/Ro or SS-B/La Ag were fixed with either acetone or paraformaldehyde and then analyzed in indirect immunofluorescent assays or by FACS analysis to detect cell surface IgG binding as an indirect measure of SS-A/Ro and SS-B/La Ag expression on the cell surface of keratinocytes. Estradiol (10(-5) to 10(-7) M) augmented binding of antiserum probes on the surface of cultured keratinocytes, with 10(-7) M estradiol showing the highest induction of cell surface binding of antisera specific for SS-A/Ro plus SS-B/La Ag (24.5% of cells were positive). In contrast, dihydrotestosterone, testosterone, and progesterone showed no augmentation. The augmentation by estradiol was partially inhibited by the antiestrogen nafoxidine. Estradiol augmented the relative incidence and absolute number of small or cuboidal cells binding antibodies specific for SS-A/Ro and SS-B/La Ag, whereas the number and incidence of larger differentiated cells binding anti-SS-A/Ro and anti-SS-B/La decreased significantly in cell cultures stimulated with estradiol. Flow cytometric analysis utilizing monospecific anti-SS-A/Ro or anti-SS-B/La sera showed that estradiol induced binding of anti-SS-A/Ro in 13.1% of cultured keratinocytes, of anti-SS-A/La in 14.4%, and of sera specific for both Ag in 21.4%. This direct association between estradiol and the augmentation of binding to the cell surface of human keratinocytes of IgG from antisera specific for SS-A/Ro and SS-B/La Ag may be a trigger factor of immunologic damage in lupus and may be important in the different sex rates observed in skin manifestation of subacute cutaneous and neonatal lupus erythematosis.
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PMID:Estradiol enhances binding to cultured human keratinocytes of antibodies specific for SS-A/Ro and SS-B/La. Another possible mechanism for estradiol influence of lupus erythematosus. 245 17

Heterogeneity of the CD4 antigen epitopes has been occasionally reported in healthy subjects, in patients affected by autoimmune diseases, such as Graves' disease and systemic lupus erythematosus (SLE), and recently also in HIV-infected subjects. A 63-year-old woman was admitted to the hospital because of dyspnea, autoimmune thrombocytopenia and serum antinuclear autoantibodies. The clinical course and X-ray films of the chest were consistent with idiopathic pulmonary fibrosis. The evaluation of peripheral blood lymphocyte subsets showed low CD4+ cells by use of OKT4 (Ortho Mune) monoclonal antibody (30%, normal range 35-45) and normal values of the same CD4+ subset by use of OKT4A (Ortho Mune) and Leu3a (Becton Dickinson) monoclonal antibodies (48%, normal range 45-55), which are specific for a different epitope of CD4 molecule. These differences indicate that the patient is heterozygous for the OKT4 epitope deficiency on CD4+ lymphocytes surface. The routine use of a panel of monoclonal antibodies, such as OKT4, OKT4A, Leu3a, which recognize different CD4 epitopes, is suggested in order to perform an accurate evaluation of CD4+ lymphocyte subset in patients affected by immune-mediated disorders other than Graves' disease and SLE.
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PMID:[Heterogeneity of epitopes of the CD4 molecule in a female patient with idiopathic pulmonary fibrosis]. 248 2

The Ortho activated partial thromboplastin time (APTT) reagent, Thrombosil 1 (TS), was compared to the General Diagnostics automated APTT reagent (GD). TS produced more precise results over a 38-day period of testing a normal control plasma, indicating that the upper limit of the normal range could be more precisely set with TS. This normal range was better represented if the normal values with both reagents were logarithmically transformed before calculating the mean +/- 2 SD. TS was more sensitive to plasma which had been heparinized in vitro. This was also demonstrated in vivo by the testing of 100 plasmas from heparinized patients. On testing of in-vitro dilutions of normal plasma with factor-deficient plasmas, TS was more sensitive to decreasing levels of factors VIII, IX and XI but less sensitive to decreasing factor XII. This was demonstrable in vivo in 71% of cases with plasmas from factor-deficient patients. GD was more sensitive to the lupus anticoagulant in most cases.
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PMID:A comparison of two APTT reagents which use silica activators. 255 32

An anti-C1q capture method kit (C1q-immunoglobulin G [IgG]) (Ortho Diagnostics, Inc., Raritan, N.J.) for measuring circulating immune complexes (CIC) was evaluated. The kit showed poor diagnostic sensitivity (P less than 0.005) for identifying CIC in patients with systemic lupus, rheumatoid arthritis, and bacterial endocarditis, as compared with polyethylene glycol-IgG and Raji cell tests (12, 24, and 24 positive, respectively, of 31 patients). Of the patients who were positive with the C1q-IgG test, 25% showed discrepancies when their results were compared with the polyethylene glycol-IgG and C1q-binding test results. Gel filtration chromatography of two of these discrepant sera showed the only peak of C1q-IgG activity to be associated with monomeric IgG (molecular weight, less than 200,000). We concluded that the kit method may be measuring substances other than CIC in some sera, because molecules of C1q attached to IgG should exhibit a molecular weight of greater than 500,000.
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PMID:Evaluation of anti-C1q capture assay for detecting circulating immune complexes and comparison with polyethylene glycol-immunoglobulin G, C1q-binding, and Raji cell methods. 295 87

Responses of pulmonary perivascular infiltrates to immunosuppressive therapy with cyclophosphamide (CY) were evaluated in the MRL/MpJ-lpr/lpr (MRL/1) mouse, a model for the study of systemic lupus erythematosus. Male and female mice were divided into the following groups: controls injected with saline; intact mice receiving CY; castrated CY-treated mice; castrated, hormone implanted, CY-treated mice. CY treatment began at 30 days of age and animals were killed at 60 days of age. Lungs were fixed-inflated to 26 cm H2O pressure with glutaraldehyde-formaldehyde fixative. The pulmonary perivascular response to immunosuppressive therapy was graded depending on the extent of infiltrates surrounding 15 pulmonary vessels per animal. Intact males treated with CY alone had almost complete clearing of perivascular infiltrates, whereas intact females did not respond to therapy. Castrated CY-treated males showed a decreased response to CY compared to intact CY-treated males. Castrated, estradiol-implanted males had no response to CY therapy. Estradiol interfered with the therapeutic response to CY in male MRL/1 mice.
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PMID:Sex hormones modulate the response of pulmonary perivascular inflammation to cyclophosphamide therapy in MRL/MpJ-lpr/lpr mice. 338 81

Humans with SLE were studied with regard to their ability to metabolize estradiol and testosterone. Significant abnormalities in the patterns of metabolism of both classes of sex steroids were found. Estradiol hydroxylation at C-16 was more extensive in both males and females with SLE -- leading to more estrogenic metabolites; and testosterone oxidation was elevated in patients with SLE resulting in a decrease in total androgens. Some normal first degree relatives of patients with SLE also had abnormalities of estradiol hydroxylation.
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PMID:Abnormal estrogen and androgen metabolism in the human with systemic lupus erythematosus. 710 69


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