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)

The prevalence and activity of human herpesvirus-6 in patients with collagen vascular diseases (CVD) was determined. One hundred and fifty patients with CVD (56 with systemic lupus erythematosus-SLE, 92 with rheumatoid arthritis-RA, 1 with Sharp's syndrome and 1 with atypical polyclonal lymphoproliferation-APL and rheumatoid features) were screened serologically (IFA and ELISA) for antibodies against human herpesvirus-6 (HHV-6), Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Virus isolation was attempted from peripheral blood lymphocytes (PBL) of 25 persons with various disorders. PBL were grown in tissue culture and tested with standard HHV-6-positive antisera for viral antigen expression. Supernatants of the patient's lymphocyte cultures were used to infect HSB2 cells, and virus infection in these cells was proven by IFA, in situ hybridization and by electron microscopy. Fifty-five percent of the SLE patients, 6.5% of the RA patients and both patients with Sharp's syndrome or with APL had antibody titers indicative of active HHV-6 infection. Virus cultures were positive in 9 of the 25 attempts with establishment of stable virus lines. These patients were 5 with SLE or UCVD, and one each with RA, CFS, APL as well as one healthy control. Reactivated and chronic active HHV-6 infections are frequent in SLE like EBV in RA. The role of these viruses in the pathogenesis of the diseases or in their reactivation still needs further investigation.
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PMID:Isolation of human herpesvirus-6 (HHV-6) from patients with collagen vascular diseases. 165 47

A-36-year old Japanese female who had been suffered from systemic lupus erythematosus (SLE) and treated with prednisolone for 3.5 years developed de novo acute promyelocytic leukemia (APL) without preleukemic state. She had a short period of complete remission in leukemia but she died with recurrence of leukemia. While malignant tumors including lymphoid malignancy have been shown to develop occasionally in the course of SLE, acute myelogenous leukemia (AML) following SLE is a very rare condition. Although combination of SLE and AML may be incidental, review of the literatures revealed some interesting insight into the pathogenesis of SLE and AML.
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PMID:[Acute promyelocytic leukemia developed in the course of systemic lupus erythematosus: a case report]. 207 34

Much progress has recently been made in understanding the biochemistry and physiology of endogenous fibrinolysis. As a result, a better understanding of the mechanisms and clinical consequences of disordered fibrinolysis has emerged. Increased fibrinolytic activity is an uncommon but important cause of hemorrhagic disease. Congenital disorders of fibrinolysis which cause bleeding include increased plasma plasminogen activator activity and deficiency of alpha-2 antiplasmin. Acquired disorders associated with increased fibrinolytic activity and bleeding include liver cirrhosis, amyloidosis, acute promyelocytic leukemia, some solid tumors, and certain snake envenomation syndromes. Increased fibrinolysis is important to recognize because epsilon-aminocaproic acid (EACA) may be required to prevent or control bleeding. Diminished fibrinolytic activity has been associated with a variety of thrombotic disorders, but a direct cause-and-effect relationship has yet to be established. Congenital abnormalities of fibrinolysis associated with thrombosis include plasminogen deficiency, decreased endothelial generation of plasminogen activator activity, and certain abnormal fibrinogens. Thrombosis in these disorders is effectively managed with warfarin. Diminished fibrinolysis has also been reported in "idiopathic" venous thrombosis, oral contraceptive-induced and post-operative venous thrombosis, coronary artery disease, cerebrovascular disease, systemic lupus erythematosus, and thrombotic thrombocytopenic purpura, but the significance of abnormal fibrinolysis in these disorders is uncertain. Large, prospective studies of fibrinolytic variables as risk factors for vascular and thrombotic disease are needed to determine whether pharmacologic augmentation of impaired fibrinolysis could be useful in the prevention or treatment of these disorders.
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PMID:Clinical disorders of fibrinolysis: a critical review. 252 71

The prescription drugs procainamide (PA) and hydralazine (HYD) are associated with the induction of autoimmunity and a clinical syndrome called drug-induced lupus. Since PA- and HYD-induced autoantibodies are directed primarily against histones and histones are prime acceptors of poly (ADP-ribose) (PADPR), we have investigated the effects of PA and HYD on the activity of poly (ADP-ribose) polymerase (PADPRP). Control substances, with structures similar to PA and HYD but not known to induce lupus, included N-acetylprocainamide (NAPA) and the amino acids phenylalanine, tryptophan and proline, and their amide derivatives. Wil-2 cells were incubated in 0.5-50 microM PA, NAPA and HYD, which included therapeutic concentrations of these drugs. The mean enhancement of incorporation of [3H]-nicotinamide adenine dinucleotide (NAD) into PADPR was 1.84 (P = 0.005) with PA, with HYD 1.48 (P = 0.029), and with NAPA 1.38 (P = 0.036). This increase was suppressed by 3-aminobenzamide, an inhibitor of PADPRP activity. Little or no increase in [3H]-NAD incorporation was observed with equivalent concentrations of phenylalanine, phenylalaninamide or tryptophan. However, a 1.29-fold increase was noted with 0.5 microM tryptophanamide, a 1.26-fold increase with 0.5 microM prolinamide and a 1.4-fold increase with 50 microM proline. PA increased PADPRP activity in B- and T-cell lines but not in promyelocytic leukemia or epithelial cell lines. Since poly (ADP-ribosylation) is important in the cellular response to various agents, the increased ADP-ribosylation of intracellular molecules may be a key event in the induction of autoantibodies.
Lupus 1993 Jun
PMID:Effect of procainamide and hydralazine on poly (ADP-ribosylation) in cell lines. 769 Feb 94

The Ku autoantigen is a heterodimer of 70- and 80-kD proteins recognized by autoantibodies from patients with systemic lupus erythematosus and related diseases that is the DNA-binding component of a DNA-dependent protein kinase. The catalytic activity of DNA-dependent protein kinase is carried by a 350-kD subunit (p350). In light of the recently described role of Ku in repairing double-strand DNA breaks, we investigated the regulation of Ku and p350 levels in neutrophils, a terminally differentiated cell type destined to undergo apoptosis. Since the appearance of double-strand DNA breaks is characteristic of apoptosis, we were interested in the possibility that Ku might oppose programmed cell death. Analysis of peripheral blood cells by flow cytometry using anti-Ku and anti-p350 monoclonal antibodies revealed that neutrophils were unstained, whereas resting (G0) lymphocytes were positive. The absence of Ku in mature neutrophils was confirmed by Western blotting and enzyme-linked immunosorbent assay for Ku antigen. In contrast, the human promyelocytic leukemia line, HL-60, which undergoes differentiation toward neutrophils after dimethylsulfoxide treatment, was positive for Ku and p350. In view of the short lifespan of neutrophils and the prolonged half-life of Ku and p350 (> 5 d), these data suggested that Ku was actively degraded during myeloid differentiation. Analysis of HL-60 cells by flow cytometry revealed that Ku staining was bimodal. Cells in G1/G0, S, or G2/M were all stained positively, whereas cells with a subdiploid DNA content characteristic of apoptosis were Ku negative. Similar results were obtained with phytohemagglutin-stimulated human lymphocytes. These data suggest that the Ku antigen is actively degraded in both myeloid cells destined to undergo apoptosis and apoptotic lymphocytes, raising the possibility that degradation of Ku may help to prevent the inappropriate repair of fragmented nuclear DNA during apoptosis.
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PMID:Absence of autoantigen Ku in mature human neutrophils and human promyelocytic leukemia line (HL-60) cells and lymphocytes undergoing apoptosis. 775 97

This prospective study is an attempt to address the issues of whether or not antiphospholipid antibodies (aPL) constitute a significant risk factor for pregnancy in individuals with systemic lupus erythematosus (SLE) and whether or not combination therapy of high-dose prednisolone (PSL) and low-dose acetylsalicylic acid (ASA) offers efficient control. Antibodies against six phospholipids were measured in sera of patients with stable SLE who had no severe complications before pregnancy, and were followed up during subsequent pregnancies. Four of 12 patients with SLE demonstrated aPL-positivity. Six of 8 patients without aPL had appropriate-for-date (AFD) live babies, the remaining two suffering intrauterine fetal death (IUFD) in the first trimester, one having a chromosome abnormality. Two aPL-positive patients treated only with 5-15 mg/day PSL during pregnancy ended in IUFD in the second trimester. In contrast, the other two patients treated with high-dose PSL and low-dose ASA each had AFD live babies at 38 weeks gestation. The results suggest that APL is a crucial risk factor in pregnancy with stable SLE. Combination therapy of high-dose PSL and low-dose ASA may enable aPL-positive patients with SLE to have AFD live babies.
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PMID:A prospective study on pregnancy risk of antiphospholipid antibodies in association with systemic lupus erythematosus. 776 81

We have presented a working hypothesis showing the possible interrelations between proliferative, aproliferative and autoimmune disorders that may follow infection with lymphotropic herpesviruses. Aproliferative disorders in this context may also indicate immune or hematopoietic deficiency. Although this hypothesis can currently be best documented with the lymphotropic viruses (herpesviruses as well as similarly HTLV and HIV), the model may apply as well--with certain variations--to other viral infections such as with hepatitis virus B or C with acute or chronic infectious diseases, post-infectious arthritis, aplastic anemia, and other autoimmune liver diseases, as well as neoplastic diseases (hepatocellular carcinoma, chronic lymphocytic leukemia). The working hypothesis as depicted in Figure 2 permits a preview of which combinations of symptoms may occur in an individual disease independent of its initial classification and what clinical testing should be done respectively, and it also permits certain prognostic considerations. The above-mentioned transitions or combinations of various disease patterns have been repeatedly described in the medical literature (to refer to only a few examples: APL and MPD, HD and MDS, SLE and aplastic anemia, SLE and Kikuchi's disease; 23, 80-83). Finally the hypothesis can ideally serve as the basis for future planning of clinical research.
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PMID:A unifying concept of viral immunopathogenesis of proliferative and aproliferative diseases (working hypothesis). 789 76

Antiphospholipid antibodies (aPL) present in systemic lupus erythematosus and the primary antiphospholipid syndrome are a well-known risk factor for thrombosis. Most of them require the presence of a cofactor, beta 2-glycoprotein I for anticardiolipin antibodies, prothrombin for lupus anticoagulant. These aPL are of the "immune" type. APL are also found in various non-immunological conditions, in which repeated endothelial or membranous damages appear to be frequent, but thromboses are rare. Most of these aPL are cofactor-independent, except those induced by chlorpromazine, and might belong to "natural" antibodies.
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PMID:[Antiphospholipid antibodies: cause of thrombosis or an epiphenomenon?]. 853 23

Anticardiolipin antibodies and the lupus anticoagulant are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. Because the aPTT is unreliable in patients with lupus anticoagulant and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests, such as ELISA for IgG, IgA, and IgM anticardiolipin antibodies and the dRVVT (followed by cephalin correction for confirmation) for lupus anticoagulant, should be immediately ordered when suspecting antiphospholipid syndrome in persons with otherwise unexplained thrombotic or thromboembolic events or fetal wastage syndrome. The laboratory diagnosis of APL-T syndrome is summarized in Figure 1.
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PMID:The antiphospholipid-thrombosis syndromes. Fact, fiction, confusion, and controversy. 804 99

We determined prospectively the prevalence of avascular osteonecrosis (AON) by magnetic resonance imaging (MRI) of both lower limbs in a group of 40 systemic lupus erythematosus (SLE) patients, and correlated the results with their serum antiphospholipid antibody (APL Ab) status and their glucocorticoid (GC) intake. APL Ab were detected by anticardiolipin ELISA and by lupus anticoagulant assays. Cumulated prednisolone doses were computed by chart review. The prevalence of AON was 37.5%, with most patients being asymptomatic despite involvement of multiple sites. The number of epiphyseal, metaphyseal and diaphyseal AON sites per patient did not differ between APL Ab-positive and APL Ab-negative patients nor between patients with high and low APL Ab titres. By contrast, a striking correlation was found between the prevalence and severity of AON and GC therapy. In conclusion, this prospective MRI study indicates that the prevalence of AON in SLE patients correlates strongly with GC therapy, but not with APL Ab status.
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PMID:Magnetic resonance imaging-detected avascular osteonecrosis in systemic lupus erythematosus: lack of correlation with antiphospholipid antibodies. 961 98


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