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)

A patient with a 20-year history of clinical systemic lupus erythematosus (SLE) who later developed multiple myeloma is described. SLE was diagnosed on the basis of a butterfly rash, photosensitivity, nondeforming arthritis, pleuropericarditis, and alopecia. However, the patient has never had LE cells, antinuclear antibody, or depressed complement. The patient was treated with intermittent courses of corticosteroids over a 20-year period with good results. Multiple myeloma, diagnosed by bone marrow biopsy, has responded favorably to therapy with L-phenylalanine mustard and prednisone.
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PMID:Multiple myeloma complicating the course of seronegative systemic lupus erythematosus. 63 92

In the course of examining polymorphonuclear leukocyte (PMN) chemotaxis in patients with systemic lupus erythematosus (SLE), we have found a previously undescribed serum inhibitor of complement (C5)-derived chemotactic activity. Serum from a 25-yr-old Black female with untreated SLE, when activated with zymosan, failed completely to attract either her own or normal PMN. Incubation of normal PMN with the patient's serum did not affect their subsequent random motility or chemotactic response toward normal zymosan-treated serum (ZTS). The patient's serum, however, did inhibit the chemotactic activity of normal ZTS and of column-purified C5-derived peptide(s), but had no effect on the chemotactic activity of either the synthetic peptide, N-formylmethionyl leucyl-phenylalanine or a filtrate prepared from a culture of Escherichia coli (bacterial chemotactic factor). The inhibitory activity in the patient's serum resisted heating at 56 degrees C for 30 min and could be separated from C5-derived chemotactic activity in the patient's ZTS (or normal ZTS that had been incubated with the patient's serum) by chromatography on Sephadex G-75. Despite its effect on C5-derived chemotactic activity, the patient's serum did not influence two other C5-derived biologic activities: PMN lysosomal enzyme-releasing activity and PMN-aggregating activity. Chromatography of the patient's serum (65% ammonium sulfate pellet) on Sephadex G-200 yielded three distinct peaks of inhibitory activity. Two were heat labile and exhibited other properties of the previously described chemotactic factor inactivators of normal human serum. The third and most active peak, however, resisted heating at 56 degrees C for 30 min, eluted with an apparent mol wt of 50,000-60,000, and acted specifically on C5-derived chemotactic activity. This uniquely specific, heat-stable inhibitor of C5-derived chemotactic activity has been found thus far in serum from 4 of 11 patients with active SLE and may account, in part, for altered host defenses against infections caused by pyogenic microorganisms.
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PMID:A specific inhibitor of complement (C5)-derived chemotactic activity in serum from patients with systemic lupus erythematosus. 65 35

Cytidine deaminase activity (CD) in the neutrophil culture supernatants (PMN SUP) of 27 patients with systemic lupus erythematosus (SLE) was measured using a spectrophotometric method. Compared with the controls (5.449 +/- 1.358 U/5 x 10(6) PMN), the CD activity in the spontaneous culture supernatants of PMN was significantly increased in active (10.003 +/- 2.637 U/5 x 10(6) PMN) but not in inactive (5.358 +/- 1.624 U/5 x 10(6) PMN) SLE. However, after stimulation with N-formyl-methionyl-leucyl-phenylalanine (FMLP, 1 x 10(-7) M), the ratio of enzyme activity between stimulated and spontaneous PMN supernatants was decreased in active SLE (0.794 +/- 0.178) compared with normal controls (1.300 +/- 0.225). In contrast, the enzyme activity in the cytoplasm of either stimulated or non-stimulated PMN was not different among these three groups. These results suggest that CD of PMN is releasable and can be enhanced by chemotactic factor stimulation in normal PMN. The increased spontaneous release of CD by active SLE PMN is one of the indicators for the disease activity in these patients.
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PMID:Increased spontaneous release of cytidine deaminase by polymorphonuclear neutrophils of patients with active systemic lupus erythematosus. 139 73

Priming effect of monocyte culture supernatant on polymorphonuclear neutrophils (PMN)-chemiluminescence (CL) was studied in patients with systemic lupus erythematosus (n = 11) and mixed connective tissue disease (n = 4). In normal controls, N-formyl-methionyl-leucyl-phenylalanine (FMLP) induced PMN-CL was enhanced when PMN were previously incubated for 15 minutes with monocyte culture supernatant (MS) or T lymphocyte culture supernatant (TS) or T lymphocyte culture supernatant (TS). The enhancing effect of MS on PMN-CL was greater than that of TS. This enhancing effect of MS was inhibited by adding of dexamethasone (1 microgram/ml) during the culture. Recombinant human TNF also enhanced PMN-CL as well as MS. When compared the enhancing effects of MS between patients and normal controls, that of patients under corticosteroid therapy (average prednisolone dose 39.5 mg/day) was reduced significantly. Thus, we concluded that the cytokines from monocyte contributed PMN phagocytosis of invading microorganisms, and that this monocyte-mediated PMN phagocytosis was suppressed partly by corticosteroids in collagen disease.
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PMID:[A study of enhancing effects of monocyte culture supernatant on polymorphonuclear neutrophils-chemiluminescence--comparison between normal controls and collagen disease patients]. 143 49

Polyclonal antibodies to double stranded DNA (dsDNA) purified from pooled serum samples of patients with systemic lupus erythematosus (SLE) exerted cytotoxic effects on cultured rat mesangial cells. At concentrations from 5 to 150 IU/ml, antibodies to dsDNA inhibited the incorporation of thymidine labelled with 3H into rat mesangial cells in a dose response manner after three days of culture. In contrast, normal human IgG (1 mg/ml), heat aggregated human IgG (1 mg/ml), N-formyl-methionyl-leucyl-phenylalanine (1 x 10(-7) mol/l), tumour necrosis factor alpha (16 U/ml), lipopolysaccharides (1 microgram/ml), 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) (20 ng/ml), interleukin 1 beta (10 U/ml), and 20% v/v phytohaemagglutinin stimulated mononuclear cell supernatant showed no significant effect on these cells. Anticardiolipin antibody, another autoantibody purified from the serum of patients with SLE, also inhibited the proliferation of rat mesangial cells but to a lesser extent. In the presence of antibodies to dsDNA (100 IU/ml), the mesangial cells became spherical and clustered together, which was very different from the original stellate appearance. These autoantibodies also depolarised the membrane potential of mesangial cells. Antibodies to dsDNA decreased the syntheses of prostaglandin E2, 6-keto-prostaglandin F1 alpha and thromboxane B2 by mesangial cells. In an in vivo study, the antibodies to dsDNA showed a strong affinity for the glomeruli when intravenously injected into rats. These results suggest that the nephrotropic antibodies to dsDNA can directly damage the glomerular mesangial cells in addition to the formation of immune complexes with DNA which may cause kidney inflammation and tissue destruction.
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PMID:Effect of antibodies to double stranded DNA, purified from serum samples of patients with active systemic lupus erythematosus, on the glomerular mesangial cells. 155 Mar 97

Systemic lupus erythematosus (SLE) is an autoimmune disease manifested by the production of autoantibodies which leads to an array of clinical symptoms. Among these autoantibodies, anti-DNA antibodies play a major role, since resulted DNA/anti-DNA immune complexes(IC) cause glomerulonephritis and other autoimmune local lesions in SLE. In this report, spectrotypes of anti-DNA antibodies of IgG, IgA and IgM classes, and IC were studied by isoelectric focusing. The size of IC was also studied. Anti-DNA autoantibodies in the sera of SLE patients were found mainly in IgG class, however, those of IgA and IgM classes were detected as minor subpopulations. By electrofocusing, both IgA and IgM anti-DNA antibodies were focused to relatively restricted acidic regions. In contrast, IgG anti-DNA antibodies were focused to two distinct pH regions; one was the acidic region similar to that IgA and IgM antibodies migrated (pH 3.2 to 6.0), and the other to far basic region between pH range of 7.8 and 10.0. IC was focused to the same basic region as a fraction of IgG migrated. Anti-DNA antibodies of IgG class, especially those focused to alkaline pH region (cationic antibodies) bound to phenylalanine (PH) column with high affinity. From these results, it was inferred that anti-DNA antibodies of IgG classes, especially those having high basic charge (cationic antibodies) showed a tendency to form IC and that the cationic antibodies may participate in the pathogenesis of tissue injury, especially of glomerulonephritis, in SLE.
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PMID:[Analysis of anti-DNA antibody in sera from patients with systemic lupus erythematosus by isoelectric focusing with respect to autoantibody isotype and immune complex]. 155 62

Normal and lupus PMN show an enhancement in superoxide production in vitro when stimulated with lupus serum. When N-formyl-methionyl-leucyl-phenylalanine (FMLP) was used, lupus PMN showed an O2- production of 2.1 nmol/min/10(7) cells, which is 5.2 times the response of normal PMN stimulated by FMLP. Our results show the existence of serum factors in SLE patients that can stimulate O2- production by PMN. Lupus neutrophils showed an increased response to membrane stimuli such as FMLP, capable of triggering the cell respiratory burst. Lupus neutrophils appeared more responsive to membrane stimuli. The serum and cellular factors seemed to indicate an increase rate of superoxide production by PMN in lupus patients, which could be relevant factors in the development of vasculitis and tissue damage.
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PMID:Increased superoxide production by polymorphonuclear leukocytes in systemic lupus erythematosus. 165 9

The platelet glycoprotein (GP) IIb-IIIa complex figures prominently as an immunogen in autoimmune (idiopathic) thrombocytopenic purpura (ITP). 2E7 is a human monoclonal IgM autoantibody, derived from splenocytes of a patient with ITP, that recognizes a specific octapeptide amino acid sequence, Phe-Asp-Gly-Tyr-Trp-Gly-Tyr-Ser, on the heavy chain of GPIIb. This represents the first precise identification of an epitope on GPIIb-IIIa recognized by a human antibody. In this study, we have isolated total mRNA from 2E7, synthesized the corresponding cDNA using reverse transcriptase, and amplified the immunoglobulin mu and kappa chain cDNA by the Taq 1 polymerase chain reaction (PCR) using specific primers. The 2E7 mu chain variable region is encoded by a VH3 gene segment that is 98% homologous to the germline gene VH1.9III, a D-gene that is not homologous to any of the germline D-genes reported to date, and a JH6 gene segment that is essentially germline. The heavy-chain sequence, save for the unique D-gene, is similar to that of a number of human autoantibodies. The 2E7 kappa variable region is encoded by a Vk1 gene segment linked to a Jk1 gene segment. The Vk1 sequence of 2E7, with the exception of one nucleotide, is identical to that of autoantibody HF2-1/17, a prototype of SLE-associated anti-DNA autoantibodies bearing the 16/6 idiotype. The single base substitution results in a relatively conservative exchange of Asp for Glu at position 70 of the protein sequence. Despite this near identity in sequence, 2E7 does not bind to either single-stranded or double-stranded DNA. From these results, we conclude that specificity of 2E7 is likely to reside in either or both the D-JH region (CDR3) of the mu chain and the Jk region (CDR3) of the kappa chain. In addition to the identification of a novel D-gene, we also provide evidence that the 2E7 VHIII gene is probably a prototype of a VHIII subfamily, that the germline Vk1 gene shared by 2E7 and autoantibodies of the 16/6 idiotype probably represents a separate Vk family, and that this Vk gene cannot itself attribute specificity for DNA.
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PMID:Nucleotide sequence of the human autoantibody 2E7 specific for the platelet integrin IIb heavy chain. 171 98

We initiated this study to determine whether three structurally related bifunctional alkylating agents could induce the expression of a presumptive human DNA repair gene. The gene chosen for this study is known to encode the ribosomal phosphoprotein PO, but ironically may also share functions related to DNA repair. We now show by Northern analysis that PO is induced by L-phenylalanine mustard, 4-hydroperoxycyclophosphamide and mechlorethamine, which are DNA-damaging agents commonly used as chemotherapeutic antitumor agents. In further support of its involvement in DNA repair is the finding of a 30- to 50-fold constitutive overexpression of the PO gene in human tumor cell lines that are Mer-, cells which lack O6-methylguanine methyltransferase activity, when compared to Mer+ cell lines. This constitutively elevated level of PO in Mer- cell lines, which are thus DNA repair defective for O6-alkyguanine lesions, was not observed for other genes tested, including the human ribosomal gene S17 whose mRNA steady-state levels were uniformly the same in both Mer- and Mer+ cells. Taking these data together, it appears that increased levels of PO are somehow linked to DNA repair, and increased expression of PO may compensate for the decreased O6-methylguanine DNA methyltransferase activity in Mer- cells. Furthermore, the PO gene has also been shown to be overexpressed in colorectal tumors and polyps and the sera of some systemic lupus erythematosus patients contain antibodies against PO. The titer of the anti-PO antibodies rises significantly during lupus psychosis.
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PMID:Expression of ribosomal phosphoprotein PO is induced by antitumor agents and increased in Mer- human tumor cell lines. 174 17

To elucidate the phagocytic activity of polymorphonuclear leukocytes (PMN) in systemic lupus erythematosus (SLE), we assayed the luminol dependent chemiluminescence of PMN (PMN-CL) of 30 patients with SLE, and evaluated the effects of disease activities and corticosteroid (steroid) therapy on the PMN-CL. The PMN-CL of active SLE patients (n = 10) before steroid therapy increased significantly compared to normal controls when stimulated with phorbol myristate acetate (PMA) (p less than 0.05). On the contrary it decreased significantly when stimulated with opsonized zymosan (OZ) (p less than 0.01). The PMN-CL of SLE patients under steroid therapy (average prednisolone dose, 40.4 mg/day) revealed a tendency to decrease according to the increase of total steroid dose. It was correlated with the total steroid dose for the preceding 12 or 16 weeks, when stimulated with formyl-methionylleucyl-phenylalanine and PMA. However it was not related with the current steroid dose. Thus the increase of PMN-CL by PMA stimulation as well as the decrease by OZ stimulation seems to be a characteristic phenomenon in SLE. The PMN phagocytic activity in SLE will be suppressed after more than 12 weeks therapy of large doses of steroid.
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PMID:[Effects of disease activities and corticosteroid therapy on the chemiluminescence of peripheral polymorphonuclear leukocytes in patients with systemic lupus erythematosus]. 207 52


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