Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00001 (DNase I)
 8,324 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The difference in the antigenic determinant size of DNA for sera from patients with SLE and rabbit anti-DNA sera were investigated. Haptenic inhibition studies were carried out by measuring the inhibition of [3H]DNA-antibody binding by three different types of oligonucleotides which were prepared from formic acid-diphenylamine digests, hydrazinolyzed digests and pancreatic DNase digests, respectively. Oligonucleotides from DNase I digests showed potent inhibitory activity with both SLE sera and rabbit sera. However, the inhibitory activities of purine and pyrimidine oligonucleotides were more potent for SLE sera than for rabbit anti-DNA sera. The determinant size estimated for rabbit sera was in the range of tetra-to heptanucleotide, while in SLE sera it was in the range of di-and trinucleotide.
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PMID:Characteristic differences in inhibitory effects of oligodeoxyribonucleotides from DNA on human systemic lupus erythematodes (SLE) sera and rabbit anti-DNA sera. 7 86

Studies were undertaken to determine whether deoxyribonuclease I, (DNase I) once immobilized on activated nylon microspheres, would be capable of degrading circulating DNA in vitro and in vivo in an extracorporeal circulation system in dogs. Nylon microspheres were prepared and after gentle hydrolysis and glutaraldehyde treatment, demonstrated a retention of up to 4.73 mg of Dnase I. In vitro studies showed that DNase I immobilized on microspheres degreded a significant percentage of 125I-native DNA (nDNA) within 15 min. Mongrel dogs were injected with 125I-nDNA and a variation in initial t 1/2 in individual animals was observed. Therefore, for experimental studies, 125I-nDNA was injected and decay was recorded during a control period in which untreated microcapsules were utilized in the extracorporeal system. DNase I microspheres were then introduced into the extracorporeal circuit which resulted in an acceleration of degradation of acid precipitable 125I-nDNA. When 200 mug of unlabeled DNA with 125I-nDNA was injected, a similar augmentation of DNA degradation was noted after extracorporeal circulation over DNase I microcapsules. This effect could not be attributed to release of DNase I from the microspheres since no 131I-DNase was detected in the serum or organs of the dogs at the conclusion of the experiments. 125I-nDNA:anti-DNA complexes were passively injected into dogs and after a similar control period of circulation over untreated microcapsules. DNase I microspheres were introduced. Results showed a rapid acceleration in the degradation rate of 125I-nDNA:anti-DNA complexes precipitable with (NH4)2SO4. Extracorporeal circulation over nylon microspheres resulted in no significant alteration of the host's hematocrit or platelet count, and little residual cellular debris on the microcapsules. These data suggest that DNAase immobilized on nylon microspheres may have a potential role in the specific therapy of systemic lupus erythematosus, when it is desirable to hydrolyze DNA circulating free or in combination with antibody.
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PMID:Degradation of circulating DNA by extracorporeal circulation over nuclease immobilized on nylon microcapsules. 126 66

Distribution on both nuclei and metaphase chromosomes of Ku-proteins, recognized by autoantibodies from a patient with systemic lupus erythematosus, has been studied using a specific monoclonal antibody (mAbH6) that recognizes p70, one Ku-protein. Observation with either a conventional fluorescent microscope or a confocal laser scanning microscope revealed mAbH6-stained p70 antigen localized on both nuclear periphery and nucleoli of human interphase cells. The specific staining of nucleoli with mAbH6 has been confirmed using isolated nucleoli from rat liver in which the staining was seen as fine granules surrounding nucleolar DNA. During mitosis p70 antigen moved away from association with the nuclear envelope region to localization on the periphery of condensed chromosomes with no apparent staining of chromosome interior. The p70 antigen was copurified with DNA fragments by immunoaffinity column chromatography using mAbH6. The mAbH6 staining of both nuclear periphery and nucleoli was lost upon digestion with DNase I at low concentrations. These results suggest that p70 antigen is connected with these nuclear structures through DNA.
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PMID:Immunolocalization of Ku-proteins (p80/p70): localization of p70 to nucleoli and periphery of both interphase nuclei and metaphase chromosomes. 163 39

This report describes the identification of autoantibodies that react with c-myc proteins in the sera of some patients with autoimmune diseases. Sera from nine to 30 patients, including six with systemic lupus erythematosus, one with mixed connective tissue disease, one with dermatomyositis and one with autoimmune haemolytic anaemia, reacted in immunoblotting assays against a truncated human c-myc protein p42 produced by Escherichia coli. Furthermore, these sera exhibited double bands of 58,000 and 60,000 MW in the nuclear fraction of HL-60 cells with the amplified c-myc gene. These bands were the same as those detected by the anti-human c-myc protein monoclonal antibody (MYC-1) by immunoblotting assay. The binding activities to 58,000 and 60,000 MW were not reduced by DNase I digestion with the sera and could be absorbed by a p42-bound affinity column and recovered after elution.
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PMID:Autoantibodies to c-myc nuclear protein products in autoimmune disease. 217 28

The putative cross-reaction of anti-DNA antibodies with "lupus-associated membrane proteins (LAMP)" on the surface of intact Raji cells was examined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analyses. Cell surface proteins of 14, 17, 18, 33 and 34 kDa were detected by monoclonal anti-double-stranded (ds) DNA antibodies and the sera of patients with systemic lupus erythematosus (SLE) in active states, but were not detected by the sera of SLE patients in inactive states, nor in healthy controls. However, pre-treatment of these anti-DNA antibodies with DNase I markedly reduced the reactivity to the cell surface proteins. Judging from the electrophoretic mobility, these proteins were identical with histones, and purified histones inhibited the reaction of anti-DNA antibodies with the cell surface proteins. Moreover, affinity-purified antihistone antibodies could demonstrate histones in the Raji cell surface proteins. Thus, we conclude that "cross-reaction" of anti-DNA antibodies with LAMP is due to DNA-anti-DNA immune complexes which could react with cell surface histones.
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PMID:Interpretation of the cross-reactivity of anti-DNA antibodies with cell surface proteins: the role of cell surface histones. 230 91

The majority of C1q-binding IgG in sera of some patients with systemic lupus erythematosus (SLE) cosediments with monomeric IgG. This study was undertaken to provide definitive proof that the low-molecular weight C1q-binding IgG consists of autoantibodies to C1q. Monomeric C1q-binding IgG was isolated from five SLE plasmas by C1q affinity chromatography and gel filtration. All C1q-binding IgG preparations and their F(ab')2 fragments bound to both C1q and the collagen-like region of C1q by an ELISA. To rule out the possibility that small DNA-antiDNA immune complexes caused this binding activity, Fab' fragments of the C1q-binding IgG preparations were digested with DNase I to degrade any DNA. The Fab' fragments continued to bind to C1q and its collagen-like region after this treatment. C1q-binding IgG was heterogenous on isoelectric focusing. Interaction of C1q-binding IgG with solid-phase C1q was retained in 1 M NaCl, whereas the binding of DNA or heat-aggregated IgG to solid-phase C1q was abrogated or markedly diminished. The association constant of C1q-binding IgG with solid-phase C1q was 2.7 X 10(7) M-1. We conclude that low-molecular weight C1q-binding IgG in the studied patients with SLE consists of autoantibodies to the collagen-like region of C1q.
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PMID:Low-molecular weight C1q-binding immunoglobulin G in patients with systemic lupus erythematosus consists of autoantibodies to the collagen-like region of C1q. 326 24

Antibodies from 5 patients with systemic sclerosis reacted with an antigen localized to the metaphase chromatin, the cleavage furrow and the midbody of anaphase and telophase HEp-2 cells. The titer of antimidbody antibodies ranged from 1:160 to 1:1280. Four patients had systemic sclerosis and one had idiopathic Raynaud's phenomenon. In situ biochemical characterization of the antigen revealed that it was resistant to DNase I, micrococcal nuclease and RNase A, but was sensitive to trypsin treatment. The antigen remained insoluble in 400 mM acetic acid but was extracted from the cells with 400 mM hydrochloric acid. The antibody was not seen in sera from 2500 normal female blood donors, 120 patients with systemic lupus, 60 patients with rheumatoid arthritis, 15 patients with linear scleroderma or 25 patients with Raynaud's disease.
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PMID:An antigen in metaphase chromatin and the midbody of mammalian cells binds to scleroderma sera. 359 98

Antibody to DNA was measured before and after treatment of systemic lupus erythematosus (SLE) sera with bovine pancreatic deoxyribonuclease (DNase I). In 11 of 15 cases of SLE with active renal disease there was a significant increase in DNA-binding after DNase digestion, while no such increase was noted in inactive SLE, normal controls or in patients with nonlupus renal disease. The significant rise in DNA-binding after digestion indicated that DNA had bound in vivo to the anti-DNA in these sera. A striking correlation between the occurrence of these complexes and disease activity was shown. In eight cases of SLE nephritis where serial blood samples were obtained, the greatest increase in DNA-binding after DNase digestion occurred at the time of the severest renal disease. In addition, serum from a case of SLE with acute cerebritis but without evidence of renal disease also had a significant rise in binding during the acute phase. This assay provides proof of the existence of circulating DNA:anti-DNA complexes in some cases of SLE and can also be used to measure an apparently critical parameter of disease activity.
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PMID:DNA:anti-DNA complexes: their detection in systemic lupus erythematosus sera. 469 46

The antigenic determinant of thermally denatured DNA reactive with systemic lupus erythematosus (SLE) sera was examined by hapten inhibition assay. We used oligonucleotides with different chain lengths (2-8) derived from DNase I digests of salmon sperm DNA in Farr's radioimmunoassay with thermally denatured mouse embryo 3H-DNA as antigen, and the effect of dextran sulphate addition to the assay mixture on the inhibitory activity of oligonucleotides was examined. A characteristic oligonucleotide inhibition pattern on DNA binding by SLE sera was observed in the assay system without dextran sulphate. Di-and/or trinucleotide inhibited the binding more effectively than tetra-and/or pentanucleotide. These patterns were also observed in DNA-normal serum interaction. When dextran sulphate was added to the mixture, the inhibition pattern changed; the inhibitory activity of oligonucleotides increased with chain length in both serum groups. The inhibitory potency of di- and trinucleotide was higher on DNA-SLE sera than on DNA-normal sera interaction. The high potency of short-chain oligomers in SLE sera is obviously different from that in experimentally elicited anti-DNA sera suggesting that different mechanism(s) are involved in antibody production in normal individuals and SLE patients.
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PMID:Antigenic structure of DNA: relatively high inhibitory activity of di- and trideoxyribonucleotide derived from DNase digest on the interaction of thermally denatured DNA with systemic lupus erythematosus sera. 616 22

We examined the ability of DNase I to digest DNA that was contained with DNA-anti-DNA immune complexes. IgG isolated from the sera of 20 patients with systemic lupus erythematosus (SLE) and containing antibodies to DNA was incubated with double-stranded DNA to form immune complexes. Excess DNase was added, and digestion of DNA was monitored by the conversion of DNA to TCA soluble products. IgG from 8 of the 20 SLE patients protected DNA from degradation by DNase in direct proportion to the amount of DNA bound to IgG as measured in the Farr binding assay. Using IgG from these sera, we showed that the DNA protected from degradation remained bound to IgG during digestion and was 35-45 base pairs in size. The size of this fragment is the same as that which has been proposed to be the minimal size necessary for monogamous bivalent binding of IgG to DNA. We therefore compared the ability of F(ab')2 and Fab' to protect DNA from DNase digestion and demonstrated that the bivalent F(ab')2 fragments were protective, but that the univalent Fab' fragments were not. These results suggest that some antibodies to DNA that bind to DNA via monogamous bivalent binding can protect a 35-45-base pair DNA fragment from DNase digestion. The implications of this finding are discussed with regard to the in vivo behavior and potential pathogenicity of small DNA-anti-DNA immune complexes.
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PMID:DNA-anti-DNA immune complexes. Antibody protection of a discrete DNA fragment from DNase digestion in vitro. 623 27


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