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)

Commercial 14C-labeled KB cell DNA, widely used to assay sera for anti-DNA antibodies, was chromatographed on benzoylated-naphthoylated-DEAE-cellulose (BNDC) and on hydroxyapatite (HAP). On BNDC, only 25% of the 14C label eluted with 1 M NaC1 (KB fraction I) characteristic of ds-DNA. Fifty-five percent of the label eluted with 50% formamide-1 M NaC1 (KB fraction II) characteristic of ss or denatured DNA. On HAP, however, none of the 14C label eluted with 0.2 M phosphate buffer as anticipated for ss-DNA, but, rather, all of the 14C label eluted with 0.4 M phosphate, characteristic of ds-DNA. after pretreatment with S1 endonuclease of Aspergillus oryzae, which selectively digests ss regions, however, 42% of the 14C label was lost from the 0.4 M phosphate peak. These results indicated that more than half of this 14C-KB-cell DNA preparation was ds-DNA with ss regions which was undetectable by HAP chromatography. 3H-ds-DNA and circular 3H-ss-DNA prepared from T7 and phiX174 bacteriophage, respectively, were found to be chromatographically pure on both BNDC and HAP. None of 10 non-SLE sera (rheumatoid arthritis 3, mixed connective tissue disease 4, scleroderma 1, ulcerative colitis 1, and pulmonary fibrosis with chronic active hepatitis 1), previously believed to contain anti-ds-DNA antibodies on the basis of KB cell DNA testing and detectable antibodies against KB fraction 1 or T7 DNA: all of 10 KB cell DNA positive SLE sera had antibodies against both. Additionally, none of the 10 non-SLE sera had antibodies against KB cell DNA when retested with DNA that had been pretreated with S1 endonuclease. Seven of these 10, however, as well as all 10 SLE sera, had antibodies against phiX174 DNA, KB fraction II DNA and alkali-denatured T7 DNA. The data support the conclusions that 1) false positive tests for anti-ds-DNA antibodies can result from contamination of ds-DNA with ds-DNA having ss regions, and 2) non-SLE sera do not contain antibodies specific for ds-DNA at levels comparable to those found in SLE sera but rather contain high levels of antibodies reacting with ss regions or mixed DNA.
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PMID:Characterization of DNA used to assay sera for anti-DNA antibodies; determination of the specificities of anti-DNA antibodies in SLE and non-SLE rheumatic disease states. 30 90

The NZB/NZW hybrid mouse is an animal model of human systemic lupus erythematosus (SLE). Two breeding schemes were devised using NZB, NZW, B/W, and CBA mice, which permit definitive decisions regarding genetic and/or viral origin of the disease. It is proposed that at least two factors must be involved: (1) a genetic abnormality producing hyper-responsiveness to nucleic acid antigens, and (2) a DNA repair defect which results in liberation of DNA and RNA when cells are lethally injured. Evidence is presented for a DNA repair deficit in human SLE lymphocytes following in vitro irradiation with ultraviolet (UV) light. Lymphocytes from adult New Zealand and control mice were found to lack normal amounts of endonuclease necessary for repairing UV damage.
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PMID:Repair of UV damaged DNA in systemic lupus erythematosus. 115 52

LF was found to bind to deoxyribonucleic acid as assessed by immunofluorescence studies on cell nuclei, affinity chromatography of DNA on immobilized LF, and gel chromatography of an LF-DNA reaction mixture. LF immobilized on Sepharose 4-B was reacted with 125I-labeled DNA in both its double-stranded and single-stranded configurations; dsDNA eluted with a 0.69M NaCl buffer, whereas ssDNA eluted with a 0.25M NaCl buffer. Additional evidence for a preferential reactivity with dsDNA was provided by the enzymatic treatment of preformed dsDNA-LF and ssDNA-LF complexes with S1 endonuclease, and DNAse 1--DNase digestion alone liberated free LF. The interaction of LF with DNA partially inhibited the binding of anti-DNA antibodies from patients with SLE, as assayed in a standard Farr assay. Furthermore, DNA-anti-DNA (labeled with 125I-IgG) complexes could be dispersed in vitro by the addition of LF. It is hypothesized that the release of LF by neutrophils chemotactically attracted to DNA-anti-DNA complexes may act as a feedback loop to modulate the inflammatory response in SLE.
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PMID:Lactoferrin interacts with deoxyribonucleic acid: a preferential reactivity with double-stranded DNA and dissociation of DNA-anti-DNA complexes. 627 82

Immunoprecipitable double-stranded (dsDNA) was previously shown to persist in the circulation of a clinically recognizable subgroup of patients with systemic lupus erythematosus (SLE). Plasma from 10 such patients was subjected to a DNA isolation procedure that used a combination of proteolysis, phenol extraction, and hydroxylapatite adsorption and elution in the presence of urea. The isolated dsDNA was radiolabeled by nick translation and then characterized by isopyknic ultracentrifugation in CsCl under both neutral and alkaline conditions, as well as after digestion with S1-endonuclease. These experiments demonstrated essential identity in nucleotide base composition between the plasma-derived DNA and human genomic DNA. The presence of specific human base sequences in the plasma DNA was demonstrated by finding that authentic human genomic DNA accelerated the renaturation of plasma DNA when compared with the effect of nonhuman, control DNA. The proportion of such sequences in plasma DNA was estimated by attempting to renature the plasma DNA in the presence of human DNA under conditions shown to result in complete renaturation of human DNA in model experiments. In this way, a minimum of 47% of plasma DNA base sequences could be shown also to be present in human genomic DNA. However, an average of 10-20% of the plasma-derived DNA failed to renature under these conditions, a result that was further confirmed by comparing the renaturation of the tritium-labeled plasma DNA specimens, in double-label experiments, with internal controls consisting of 14C-labeled authentic human DNA. Attempts to drive the reaction to completion with human DNA led to a similar conclusion. The relative nonrenaturability of this fraction of plasma DNA did not appear to be attributable to extensive chain breakage, although adequate analysis of this DNA subfraction was limited by reagent availability. It was therefore concluded that, in this group of SLE patients, persistently circulating DNA consisted largely of base sequences also found in human genomic DNA. The additional presence in plasma of a DNA subfraction that differed in its renaturation behavior from human genomic DNA was recognized, although its significance could not be established with certainty.
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PMID:Circulating DNA in systemic lupus erythematosus. Isolation and characterization. 632 28

Although antibodies (Ab) specific for double-stranded (ds) DNA are thought to be involved in the etiopathogenesis of systemic lupus erythematosus (SLE), the fine structure of their DNA targets remains elusive. We have adapted a polymerase chain reaction (PCR)-assisted immunoprecipitation method to define the binding sites in DNA sequences recognized by high affinity anti-dsDNA Ab of SLE patients. SLE sera were used to bind templates from a pool of double-stranded oligonucleotides (ON). A central part of 20 base-pair random sequence was flanked by restriction endonuclease recognition sites and sequences complementary to predefined PCR primers. Immunoselected ON were precipitated, isolated from the immune complexes and then subjected to a further immunoprecipitation step after amplification by PCR. After five cycles of immunoprecipitation and PCR, the resulting ON were cloned. Sequence analysis revealed that sera from SLE patients and two human monoclonal anti-dsDNA Ab obtained from SLE patients preferentially select sequences expected to form non-B-DNA structures. Inhibition studies of the Farr assay confirmed the increased affinity of the selected epitopes for anti-DNA Ab as compared to random B-DNA.
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PMID:Preferential recognition of specific DNA motifs by anti-double-stranded DNA autoantibodies. 762 66

Although systemic lupus erythematosus (SLE) is known to be positively associated with certain major histocompatibility complex (MHC) class I and/or class II antigens, it is not clear whether the MHC genes are the predisposing genes of the disease rather than markers for other closely linked gene(s). Because of the involvement of tumor necrosis factor (TNF) in the inflammation process and localization of the TNF genes in the proximity of the HLA-B locus, we studied the restriction fragment length polymorphism (RFLP) of the TNF-alpha and -beta genes in 20 SLE patients and 23 normal individuals using restriction endonuclease NcoI. The frequency of a 5.5 kb NcoI fragment from SLE patients was significantly higher than that from normal controls. This result suggests that the polymorphic TNF genes may be involved in the pathogenesis of SLE.
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PMID:Restriction fragment length polymorphism (RFLP) analysis in the TNF genes of patients with systemic lupus erythematosus (SLE). 790 14

We undertook an analysis of the B cell repertoire at both the germline and somatic levels. To assess the content and organization of the IgH-V and IgK-V loci in SLE, endonuclease-generated polymorphisms were used to characterize individual variations within the human V gene segments. The results are compatible with the conclusion that this disease is not caused by major abnormalities in the structure, size, or organization of the IgV loci. We propose that hyperproduction and lupus-associated autoantibodies arises through a two-stage mechanism whereby a general activation of the multireactive preimmune B-cell repertoire precedes oligoclonal expansion of selected B cell clonotypes.
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PMID:Human autoantibodies and their genes. 794 33

IgG anti-double stranded DNA antibodies (anti-dsDNA) purified from serum of patients with active systemic lupus erythematosus (SLE), have been found to be cytotoxic to the cultured rat mesangial cells (MC). In the present study, by use of immunofluorescent staining, immunoblotting, radioimmunoprecipitation, and cell cycle analysis, we showed that IgG anti-dsDNA could bind to the membrane of MC. The bound epitope was a 28 kDa protein, which would disappear if the cells were treated in advance with proteinase K (100 micrograms/ml). In addition, binding of MC by 20 micrograms/ml of anti-dsDNA IgG F(ab')2 activated plasma membrane (equivalent to 80 IU/ml of calf thymus double-stranded DNA binding activity) resulted in release of much more 3H-arachidonic acid than binding by 20 micrograms/ml of human IgG F(ab')2 (26.71 +/- 3.75% in the case of anti-dsDNA vs. 4.73 +/- 2.86% in the case of IgG). To understand further the cytotoxic mechanism of anti-dsDNA, we incubated MC with anti-dsDNA, for a variety of periods (from 10 minutes to 24 hours). After incubation, the cells were fixed and stained with hematoxylin-eosin for morphologic observation. Simultaneously, the genomic DNA was extracted and analyzed in 1.8% agarose gel electrophoresis. We found that cell death caused anti-dsDNA followed a process of apoptosis rather than necrosis. These results suggest that binding of anti-dsDNA with MC membrane may activate endonuclease which will fracture the DNA and lead to programmed cell death.
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PMID:Polyclonal IgG anti-dsDNA antibodies exert cytotoxic effect on cultured rat mesangial cells by binding to cell membrane and augmenting apoptosis. 835 8

SLE is dramatically more prevalent in persons of African descent than in other populations. Several genes in the class III region of the MHC have been considered as potential susceptibility loci for this disorder, but the primary association(s) remains unknown. The stress protein gene, hsp70-2, is of special interest in this regard because it encodes a protein functionally relevant to antigen processing and presentation and has itself been identified as a putative susceptibility locus in organ-specific autoimmune diseases in Caucasians. To clarify the relationship of the hsp70-2 gene to SLE in African Americans, genomic DNA from 46 patients and 42 appropriately matched control subjects was analyzed for an RFLP of the hsp70-2 gene using the probe pH2.3 and the restriction endonuclease PstI, which identifies alleles of 8.5 and 9.0 kb. The 8.5-kb hsp70-2 allele was associated with SLE in this population (X2 = 8.2473, p = 0.0044). This association was not due to linkage disequilibrium with the C4A deletion or with HLA-DR3, as has been reported in Caucasians with IDDM. These data suggest that the 8.5-kb hsp70-2 allele may be an independent susceptibility marker for SLE in African Americans.
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PMID:The 8.5-kb PstI allele of the stress protein gene, Hsp70-2: an independent risk factor for systemic lupus erythematosus in African Americans? 865 62

We assessed the polymerase chain reaction (PCR) technique to detect Mycobacterium tuberculosis complex DNA in 48 paraffin-embedded specimens from 32 patients with different variants of cutaneous tuberculosis, and compared the results with those of culture. A 123 bp product of the IS6110 insertion sequence specific of M. tuberculosis complex was amplified and confirmed by digestion with SalI restriction endonuclease. The time required for the procedure was 3 days. Thirty-seven samples (77.1%) were positive for M. tuberculosis complex DNA. No false positive results were obtained in nine negative controls. Of the 20 specimens tested by PCR and culture, the frequency of positivity was 90% for DNA amplification and 65% for culture. In seven cases of lupus vulgaris, the figures were 100% and 57%, respectively. In the 11 specimens culture negative or not microbiologically tested and PCR negative, evidence for tuberculous infection was provided by the correlation of various relative and absolute criteria. These results show that PCR amplification of the IS6110 insertion fragment is a rapid and accurate means for the detection of M. tuberculosis complex DNA in paraffin-embedded skin biopsies from patients with cutaneous tuberculosis, especially in paucibacillary lesions.
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PMID:Detection of Mycobacterium tuberculosis complex DNA by the polymerase chain reaction for rapid diagnosis of cutaneous tuberculosis. 888 65


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