Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Passive hemagglutination (PHA) and hemolysis (PHL) tests using chromium chloride-treated sheep red blood cells were developed to detect and measure the anti-DNA antibodies. Sonication of native DNA was found to prevent the incidence of non-specific agglutination. Sheep red cells were coated with double-stranded DNA (dsDNA) which had been sonicated and treated with nuclease S1 to digest the single-stranded regions in the DNA. The specificities for dsDNA-coated cells were checked by inhibition studies in PHA test and plaque assay. In clinical studies fairly close correlations were found between the antibodies to DNA and the activity of the disease in patients with systemic lupus erythematosus (SLE). Complement-fixing antibodies were detected in most of SLE patients with active lupus nephritis, but rarely in those in remission. Anticomplementary activity seemed to be negligible in PHL test. These tests are simple and may be useful to the diagnosis and the management of SLE.
 ...
PMID:Passive hemagglutination and hemolysis tests for the detection of anti-DNA antibody. 35 55

DNA samples from control and lupus lymphocytes were studied for DNA integrity and single-strand breaks by agarose gel electrophoresis following digestion with the enzyme S1 nuclease. S1 nuclease digests single-strand gaps in double-stranded DNA. Gel patterns of phytohemagglutinin (PHA)-stimulated control and lupus lymphocyte DNAs were identical in the absence of S1 nuclease incubation. DNA isolated from PHA-stimulated control lymphocytes was relatively resistant to S1 nuclease digestion in 14 of 16 samples. However, 15 of 16 DNA samples from PHA-stimulated lupus lymphocytes demonstrated dramatically greater S1 nuclease digestion than paired control DNAs from lymphocytes analyzed at the same time under the same conditions. Increased S1 sensitivity suggests that more single-strand DNA breaks were found in PHA-stimulated lupus lymphocytes and/or the lupus DNA was more damaged than control DNA. We suggest that structural changes found in DNA from stimulated T lymphocytes of lupus patients are consistent with an endogenous antigen-mediated disorder.
 ...
PMID:Phytohemagglutinin-stimulated lymphocytes from patients with systemic lupus erythematosus demonstrate DNA damage. 194 28

A hemolytic assay was developed with the primary aim of being able to identify human lymphocytes producing anti-dsDNA antibodies found in patients with systemic lupus erythematosus (SLE). The coating of sheep red-blood cells with DNA was performed after precoating the cells with poly-L-lysine. The DNA-SRBC were lysed by anti-DNA antibodies from SLE sera, and the percent hemolysis was found to correlate with the anti-DNA activity demonstrated by the Farr assay (r = 0.87). Single-stranded DNA at the surface of the coated cells could be removed after digestion with nuclease S1. The effect of the digestion was verified by SLE serum specific for single-stranded DNA. With slight modifications, the target cells may be used to determine not only the titer of anti-DNA antibodies but also the complement-consumption and immunoglobulin classes of the anti-DNA antibodies.
 ...
PMID:Immune hemolytic assay for identification of human anti-dsDNA antibodies with DNA-coated red blood cells as target cells. 283 17

Double-stranded DNA fragments of varying sizes were isolated and tested for binding to systemic lupus erythematosus (SLE) antinative DNA antibodies. Fragments of 20-25, 40-50, 90-110, and 160-180 base pairs (bp), along with intermediate-size pieces were isolated by preparative gel electrophoresis of a limited micrococcal nuclease digest of calf thymus DNA. Larger helical polynucleotides of 160-200, 380, 600-1,000, and 1,200 bp were isolated by preparative gel electrophoresis of DNA from chicken erythrocyte nucleosomes and oligonucleosomes. The fragments behaved as base-paired structures as tested by thermal denaturation, resistance to S1 nuclease, and serological assays with antibodies to native or denatured DNA. At a concentration of 0.27 muM, fragments of 20-25 bp were able to react with two SLE sera in competition with native DNA. With these and two other sera, DNA of 40-50 bp was a much more effective competitor. One serum required DNA greater than 180 bp for competition in the concentration range tested. Denatured fragments were much less effective than native fragments. The results emphasize the heterogeneity of SLE antinative DNA antibodies, confirm that secondary structure of the antigen is important for specific binding to these antibodies, and support the suggestion that bivalent binding to one molecule may be important for high functional affinity.
 ...
PMID:Reaction of systemic lupus erythematosus antinative DNA antibodies with native DNA fragments from 20 to 1,200 base pairs. 615 84

Experiments were designed to determine the basis for the strong competitive reaction of denatured DNA with systemic lupus erythematosus (SLE) antinative DNA antibodies. Secondary structure in denatured DNA was reflected in hyperchromicity upon heating and in multiphase kinetics of its digestion by S1 nuclease. Partial digestion by S1 nuclease completely eliminated the ability of denatured DNA to react with antidenatured DNA antibodies, but not its ability to react with SLE sera. S1 nuclease-resistant cores were isolated from extensively digested denatured DNA. These cores had secondary structure, including some stable fold-back helical regions. The cores, from 20 to several hundred base pairs in size, competed with native DNA for binding by SLE sera. Other experiments measured reactions of denatured DNA under conditions that affected its secondary structure content. Its competitive activity decreased as temperature was increased from 0 degrees to 37 degrees C, whereas the activity of native DNA was not altered in this temperature range. With DNA pieces of 90-110 base pairs, native fragments were much more effective than the denatured fragments, in which stable helical structure is less likely to occur than in high molecular weight denatured DNA. Competitive assays with mononucleotides, oligonucleotides, homopolymers, and RNA-DNA hybrids also indicated that two strands of polydeoxyribonucleotide were required for optimal reactions with these SLE serum antibodies. The antibodies can measure stable helical regions in denatured DNA; they may also stabilize short helical regions that occur in an equilibrium of conformational forms.
 ...
PMID:Secondary structure in denatured DNA is responsible for its reaction with antinative DNA antibodies of systemic lupus erythematosus sera. 615 50

An enzyme immunoassay was developed to detect antibodies to native DNA; DNA coating conditions that maximized sensitivity, specificity, and reproducibility were selected. Sera of patients with systemic lupus erythematosus (SLE) were positive more frequently by this immunoassay than by the Crithidia luciliae assay or by counterimmunoelectrophoresis. By enzyme immunoassay, 94% of sera with active SLE and 70% of sera from patients with inactive SLE were positive, as were 16% from those suspected of having SLE, and 2.5% of normal persons. Specificity for native DNA was shown for both SLE and normal sera by inhibition studies and by S1 nuclease treatment of polystyrene-bound native DNA. The enzyme immunoassay correlated more with serum hemolytic complement levels that did the other 2 assays, suggesting that it detects biologically more relevant anti-DNA antibodies than do the other 2 tests.
 ...
PMID:Enzyme immunoassay for antibodies to native DNA. Specificity and quality of antibodies. 633 94

Sera from 20 patients with systemic lupus erythematosus (SLE), selected for elevated titers of antibody to native DNA (nDNA), were examined by indirect immunofluorescence (IF) on tissue culture Hep-2 and rabbit kidney cells. Twelve sera showed a particulate cytoplasmic staining, in addition to nuclear IF. Double IF staining by using a mouse monoclonal anti-nDNA and a human serum containing anti-mitochondrial antibody as probes showed that the cytoplasmic structures recognized by these 12 SLE sera were mitochondria. SLE sera showing mitochondrial staining had high anti-nDNA levels, as assessed by ELISA (3.5 +/- 1.9 O.D.), compared with those not showing this staining pattern (0.8 +/- 0.4 O.D.). Mitochondrial staining was abolished by DNase I pretreatment of the substrates. Liquid phase absorption of serum anti-nDNA with S1 nuclease-treated calf thymus DNA or purified mitochondrial DNA also removed staining. These findings demonstrate that anti-nDNA antibodies from patients with SLE bind to DNA in intact mitochondria. Therefore, mitochondrial IF staining on tissue culture cells in the presence of nuclear staining should be interpreted with caution, because the phenomenon could be entirely related to anti-native DNA. These observations might also provide new insights concerning the nature of immunogenic cellular components stimulating anti-DNA production.
 ...
PMID:Anti-native DNA antibodies from autoimmune sera also bind to DNA in mitochondria. 638 67

The size and structure of viral RNA species synthesized in nuclei isolated during the early phase of productive infection by adenovirus type 2 have been examined by electrophoresis in denaturing polyacrylamide cells and the nuclease S1 assay. The major products of transcription in vitro of early regions 1 and 2 in the adenoviral genome are processed RNA molecules that appear to be correctly spliced in isolated nuclei. Splicing of adenoviral RNA molecules is inhibited when nuclei are preincubated with antibodies from systemic lupus erythematosus patients that immunoprecipitate small nuclear ribonucleoprotein particles. The specificity of these antibodies suggests that ribonucleoprotein particles containing U1 RNA are required for splicing of the adenoviral RNA sequences we have examined.
 ...
PMID:A small nuclear ribonucleoprotein is required for splicing of adenoviral early RNA sequences. 694 Jan 64

A sensitive solid phase microradioimmunoassay has been developed for measurement of antidouble stranded DNA (dsDNA) antibodies. In this procedure, advantage has been taken of the capacity of poly-L-lysine (PLL) to facilitate the binding of pure dsDNA to plastic surfaces. In the absence of PLL, binding did not occur. Diluted sera were incubated in PLL-treated dsDNA-coated microtitration trays and anti-dsDNA Ig measured using affinity purified 125I-anti-Ig of high specific activity. The synthetic DNA, poly dA-dT, was used as a model for dsDNA. In initial experiments, specific anti-DNA binding could not be demonstrated because of high background binding of patient Ig to PLL-treated surfaces. This was reduced by diluting test sera and anti-Ig in buffer containing 2% BGG and 1% BSA. Specificity of the assay for DNA was demonstrated by absorbing the anti-DNA activity on DNA-coated plastic. The binding of systemic lupus erythematosus (SLE) patient serum Ig to poly dA-dT coated trays did not diminish after digestion with nuclease S1, suggesting that the synthetic polymer is an appropriate model for dsDNA. Patient and normal sera were screened for anti-dsDNA activity using poly dA-dT as antigen. None of the 38 normal sera, 23 of 35 active SLE sera, 1 of 25 treated SLE, 4 of 35 rheumatoid arthritis, 3 of 35 scleroderma, and 1 of 13 polymyositis sera demonstrated positive anti-dsDNA activity. The anti-dsDNA values obtained in the radioimmunoassay correlated significantly with those obtained in the Crithidia luciliae assay.
 ...
PMID:A sensitive solid phase microradioimmunoassay for anti-double stranded DNA antibodies. 697 Nov 3

13-cis-Retinoic acid (13-CRA), a water-soluble vitamin A analog and 5'-lipoxygenase inhibitor, was tested in vitro for effects on excess oxidative metabolism and DNA damage in mitogen-stimulated lymphocytes from patients with systemic lupus erythematosus (SLE), because other 5'-lipoxygenase enzyme inhibitors were shown to lower the excess oxidative metabolism in SLE cells. Excess chemiluminescence (CL) was abolished within minutes after the addition of 1 x 10(-6) M 13-CRA in five of five CL-positive mitogen-stimulated SLE lymphocytes, and was lowered in five of eight samples after 48 to 72 h culture. Similarly, low concentrations of 13-CRA for 48-72 h largely prevented the S1 nuclease-sensitive DNA changes/DNA damage observed in CL-positive lupus lymphocytes in vitro. However, 13-CRA did not affect DNA damage in four of four CL-negative lymphocyte samples. 13-CRA, like other retinoic acid compounds, was known to stimulate B-cell activities in vivo and in vitro but effects on dividing lupus T cells had not been studied. 13-CRA further inhibited the diminished PHA-stimulated lupus T-cell growth in tissue culture at a concentration of 9 x 10(-6) M in three of five lupus lymphocyte samples. 13-CRA has positive and negative effects on multiple aspects of the immune system and it is not clear whether 13-CRA will have positive or adverse clinical effects on SLE patients. Close attention to vitamin A and vitamin "supplements" in patients with SLE may answer this question.
 ...
PMID:13-cis-retinoic acid affects oxidation and DNA damage in oxidative-positive SLE lymphocytes but may not be useful for therapy. 843 47


1 2 Next >>