Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.30.2 (endonuclease)
18,621 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

Inhibition of endonuclease by d-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) is discussed as a possible therapeutic principle of the antiinflammatory action in polyarthritis. Infections by 'slow viruses" and mycoplasma have to be considered as possible etiologic factors for rheumatoid arthritis. The incorporation of the viral or mycoplasmatic DNA into the genetic material of the host cell depends on the function of endonucleases, which can be inhibited by naproxen. The advantages and the drawbacks of this type of mechanism of action are discussed.
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PMID:[Naproxen, a 'specific" antirheumatic drug?]. 117 77

Oxidative stress is strongly implicated in a number of diseases, such as rheumatoid arthritis, inflammatory bowel disorders, and atherosclerosis, and its emerging as one of the most important causative agents of mutagenesis, tumorigenesis, and aging. Recent progress on the genetics and molecular biology of the cellular responses to oxidative stress, primarily in Escherichia coli and Salmonella typhimurium, is summarized. Bacteria respond to oxidative stress by invoking two distinct stress responses, the peroxide stimulon and the superoxide stimulon, depending on whether the stress is mediated by peroxides or the superoxide anion. The two stimulons each contain a set of more than 30 genes. The expression of a subset of genes in each stimulon is under the control of a positive regulatory element; these genes constitute the OxyR and SoxRS regulons. The schemes of regulation of the two regulons by their respective regulators are reviewed in detail, and the overlaps of these regulons with other stress responses such as the heat shock and SOS responses are discussed. The products of Oxy-R- and SoxRS-regulated genes, such as catalases and superoxide dismutases, are involved in the prevention of oxidative damage, whereas others, such as endonuclease IV, play a role in the repair of oxidative damage. The potential roles of these and other gene products in the defense against oxidative damage in DNA, proteins, and membranes are discussed in detail. A brief discussion of the similarities and differences between oxidative stress responses in bacteria and eukaryotic organisms concludes this review.
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PMID:Oxidative stress responses in Escherichia coli and Salmonella typhimurium. 177 27

Analysis of polymorphic systems, demonstrating differences among ethnic groups, provides a valuable tool for biology and medicine. Blast-1 is a member of the immunoglobulin superfamily and an activation-associated glycoprotein expressed on the surface of mononuclear cells. Blast-1 demonstrates DNA polymorphism in healthy controls and patients with rheumatoid arthritis (RA). The sizes of polymorphic restriction endonuclease fragments of genomic DNA encoding Blast-1 were 2.4 and 1.9 kb. In normal controls, the frequency of the homozygote for the 2.4 kb fragment (L-L) was 0.69 and 0.47, and that for the 1.9 kb fragment (S-S) was 0.04 and 0.11 in Caucasians and Japanese, respectively. The frequency of the heterozygote for both fragments (L-S) was 0.27 and 0.42 in Caucasians and Japanese, respectively. The frequencies of the L and S alleles were 0.83 and 0.17 for Caucasians, respectively, and were 0.68 and 0.32 for Japanese, respectively. The difference in the allele frequency between Caucasians and Japanese was significant. In Japanese patients with RA, the frequency of L-L, L-S and S-S types was 0.45, 0.45 and 0.10, respectively. Lung fibrosis in Japanese RA patients was associated with an increase in the L-S and S-S types and a decrease in the L-L type. The present study indicates that the investigation for gene polymorphisms of Blast-1 among distinct ethnic groups is important because Blast-1 appears to be a genetic marker for the manifestation associated with RA.
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PMID:Restriction fragment length polymorphism of a lymphocyte surface antigen, Blast-1, in Japanese and Caucasians, and in patients with rheumatoid arthritis. 197 77

We used restriction endonuclease digestion of leukocyte DNA to assess the structural integrity of an N-acetylglucosamine beta 1----4 galactosyltransferase (GalTase)-associated (GTA) protein kinase gene in rheumatoid arthritis (RA) patients. This analysis provides evidence that the gross structure of the GTA protein kinase gene locus remains intact in patients with defective galactosylation and that this gene locus is polymorphic both in normal individuals and in patients with RA, although no polymorphisms unique to RA patients were observed. Initial data on the expression of this gene indicate that comparable levels of GTA protein kinase messenger RNA are present in the lymphocytes of normal individuals and RA patients, irrespective of whether lymphocytes were obtained from patients with decreased or normal levels of galactosylation.
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PMID:Polymorphism and expression of the galactosyltransferase-associated protein kinase gene in normal individuals and galactosylation-defective rheumatoid arthritis patients. 212 2

DNA samples from 78 patients with classical or definite rheumatoid arthritis (RA) and 132 healthy controls were analysed by the Southern blotting method, using two DNA probes: the first to the immunoglobulin mu heavy-chain switch region (S mu), in conjunction with the SstI restriction endonuclease, and the second to the D14S1 region, in conjunction with the HindIII restriction endonuclease. The homozygous phenotype for the 6.9 kb S mu fragment was decreased in the patient group (7.8%) compared to controls (19.1%) (P = 0.04). The homozygous phenotype for the 10.3 kb D14S1 fragment was increased in the patient group (38.5%) compared to controls (21.2%) (P = 0.02). The increase was more pronounced in the DR4-positive patients (51.2%) (P versus DR4-positive controls = 0.009). These results suggest that genes on chromosome 14 are involved in the genetics of RA.
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PMID:The association of DNA variants at or near the IgH locus with rheumatoid arthritis. 290 Aug 53

The DR1 and DRw10 beta 1 chain genes were isolated from each of 2 individuals with rheumatoid arthritis who were heterozygous for these class II major histocompatibility complex specificities. The sequences of the DR1 beta 1 chains from both patients were identical, differing from previously reported DR beta 1 chains of individuals without RA by 2 amino acid substitutions, at positions 85 (Val-Ala) and 86 (Gly-Val), and by a silent mutation at the last nucleotide of codon 78 (C-T), resulting in the loss of a Pst I restriction endonuclease site. Identical DRw10 beta 1 chain genes were found in both patients. These were shown to encode the epitope recognized by monoclonal antibody 109d6. This antibody also recognizes an epitope on the DRw53 beta 2 chain of the DR4 haplotype. The third diversity regions of the DR1 beta (amino acids 67-74) and the DRw10 beta 1 chains (amino acids 67-73) were identical, respectively, with those of the DR4 (Dw14) beta 1 and beta 2 chains, raising the possibility that in these patients, the third diversity regions of the two DR beta 1 chain genes present in trans are conformationally equivalent to the cis-encoded third diversity regions of the DR4 (Dw14), DR beta 1, and beta 2 chains. The nucleotide sequences of the DQ beta complementary DNA clones were identical to that of the DQw1 beta chain, and no DR beta 2 complementary DNA clones were identified.
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PMID:Class II major histocompatibility complex gene sequences in rheumatoid arthritis. The third diversity regions of both DR beta 1 genes in two DR1, DRw10-positive individuals specify the same inferred amino acid sequence as the DR beta 1 and DR beta 2 genes of a DR4 (Dw14) haplotype. 293 Jun

The genetic origin of Rheumatoid Arthritis (RA) is largely unknown. The purpose of this investigation was to assess the potential genetically determined involvement of the immunoglobulin (Ig) heavy chain variable region (VH) locus in the pathogenesis of RA. We tested the hypothesis of whether there is a genetic linkage between a structural abnormality of the VH gene complex and autoantibody hyperproduction in RA. We used restriction endonuclease generated polymorphism with human VH gene-family-specific probes to examine genomic DNA from a RA family and from unrelated RA patients from both the Tunisian and the European populations. The use of DNA samples from these ethnic origins permitted a further evaluation of the polymorphism of the human VH locus. While we found that the polymorphism of the VH locus was lower in the Tunisian population, we could not detect a restriction site polymorphism pattern restricted to RA. Together, our results do not support the involvement of major abnormalities of the Ig VH locus as a primary source in the development of RA.
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PMID:Polymorphism of the human immunoglobulin heavy chain locus in rheumatoid arthritis. 918 12

Diclofenac (DCLF) is a nonsteroidal anti-inflammatory drug that is widely used for the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and acute muscle pain conditions. Toxic doses of DCLF can cause nephrotoxicity in humans and experimental animals. However, whether this DCLF-induced nephrotoxicity involves apoptotic cell death in addition to necrosis is unknown. The goals of this investigation were to determine whether DCLF-induced nephrotoxicity involves oxidative stress and apoptotic type genomic DNA fragmentation, and if so, whether DCLF-induced oxidative stress and DNA fragmentation cause apoptotic cell death in mouse kidneys. Male ICR mice (CD-1; 25-45 g), fed ad libitum, were administered nephrotoxic doses of DCLF (100, 200, 300 mg/Kg, po) and sacrificed 24 h later. Blood was collected to evaluate renal injury (BUN), lipid peroxidation (MDA: malondialdehyde levels), and superoxide dismutase (SOD) activity (a marker of oxidative stress). Kidney tissues were analyzed both quantitatively and qualitatively to determine the degree and type of DNA damage, and evaluated histopathologically for the presence of apoptotic characteristics in the nucleus of diverse types of kidney cells. Results show that diclofenac is a powerful nephrotoxicant (at 100, 200, and 300 mg/kg: 4.7-, 4.9-, and 5.0-fold increases in BUN compared to the control, respectively) and a strong inducer of oxidative stress (significant increase in MDA levels). Oxidative stress induced by DCLF was also coupled with massive kidney DNA fragmentation (100, 200, and 300 mg/kg: 3-, 8-, and 10-fold increases compared to control, respectively). A dose-dependent increase in MDA levels and SOD activity was also observed, which indicated a link between oxidative stress and nephrotoxicity. Qualitative analysis of DNA fragmentation by gel electrophoresis showed a DNA ladder indicative of Ca2+-Mg2+-endonuclease activation. Histopathological examination of kidney sections revealed numerous apoptotic nuclei across proximal and distal tubular cell linings. Collectively, these data for the first time suggest that DCLF-induced nephrotoxicity may involve production of reactive oxygen species leading to oxidative stress and massive genomic DNA fragmentation, and these two free radical mediated events may ultimately translate into apoptotic cell death of kidney cells in vivo, and reveal a DNA-active role for DCLF.
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PMID:Diclofenac induced in vivo nephrotoxicity may involve oxidative stress-mediated massive genomic DNA fragmentation and apoptotic cell death. 1144 Aug 26

Interleukin (IL)-10 is an important multifunctional cytokine with both anti-inflammatory and immunoregulatory effects in rheumatoid arthritis (RA). In the present study, we evaluated the frequency and potential impact of IL-10 promoter polymorphisms on susceptibility to and severity of RA in Polish in - patients with a high disease activity (mean DAS 28 C-reactive protein 5.25). DNA was obtained from 244 RA patients and 106 healthy controls. The -592C/A and -1082G/A IL-10 gene polymorphisms were amplified by polymerase chain reaction with restriction endonuclease mapping. The frequency of the IL-10-592CA, -592AA genotypes (respectively: 30% vs 5% and 7% vs 0%) and allele -592A (37% vs 5%) were significantly higher in RA patients as compared with a control group. We did not find any association of the IL-10-592C/A genotype distribution with disease parameters, except for an increased ESR (erythrocyte sedimentation rate) in patients with the -592CC genotype as compared with those with -592CA or -592AA genotypes (P = 0.01). The frequency of the IL-10-1082GG genotype was lower (P = 0.0001), and that of the IL-10-1082GA genotype was higher (P = 0.009) in RA patients comparing with the control group. In RA patients with -1082GA or -1082AA genotypes the time duration of the disease (P = 0.03), Health Assessment Questionnaire (HAQ) Score (P = 0.04) and PLT count (P = 0.001) were significantly increased as compared with subjects with -1082GG genotype. Presented findings indicate that IL-10-592C/A and IL-10-1082G/A polymorphisms may be considered genetic risk factors for RA susceptibility and severity.
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PMID:Interleukin-10 gene promoter polymorphism in Polish rheumatoid arthritis patients. 2047 82


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