Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In December 1987, we investigated an increased number of cases of herpetic whitlow in medical intensive care unit nurses who routinely gloved for secretion contact. One particular brand of vinyl examination glove had been used in the medical intensive care unit. Restriction endonuclease mapping established the similarity of employee isolates with one patient isolate of herpes simplex virus type I. When initial viral assay demonstrated 2.5% to 10% penetration of herpes simplex virus type I across unused gloves, an evaluation of glove quality was undertaken. In a 300-mL watertightness test, seven brands of vinyl gloves failed 4% to 28% (average, 11.1%; 132/1200), while seven brands of latex gloves failed 0% to 2.6% (average, 1.4%; 24/1750). The brand of vinyl glove that had been in use in the medical intensive care unit failed 28% of the time. Watertight gloves were then tested for permeability to herpes simplex virus type I. None of the latex gloves failed (n = 1726), while only 10 of the vinyl gloves failed (n = 1068, 0.95%). Extreme variability in glove quality was observed. However, gloves made from intact vinyl may provide similar protectiveness as those made from intact latex. As the demand for gloves increases, emphasis should be placed on the production of plentiful, better quality latex and vinyl gloves.
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PMID:Latex and vinyl examination gloves. Quality control procedures and implications for health care workers. 255 79

Hepatic angiosarcoma (HA) is an uncommon neoplasm associated with known etiologic factors in 25% to 42% of cases. It is, however, one of the most common sarcomas found in the liver. The aim of this study was to find was to find mutations in the K-ras-2 oncogene in sporadic and Thorotrast (TT)-induced HA. Point mutations in K-ras-2 were sought in archival, formalin-fixed tissue blocks from 24 patients with angiosarcoma. Of these, 19 cases were sporadic and 5 were TT-induced. Mutational analysis was performed by topographic microdissection with PCR amplification followed by genotyping. Specific mutations were determined by two independent methods: (a) direct sequencing of the PCR product confirmed by rePCR and by using a different sequencing primer, and (b) PCR-based selective enrichment of mutant DNA by endonuclease digestion followed by heteroduplex DNA analysis using denaturing gradient gel electrophoresis. Eleven K-ras-2 point mutations were detected in 7 of 24 (29%) tumors, including 5 of 19 (26%) sporadic HA and 2 of 5 (40%) TT-induced HA. There were seven G:C > A:T and four G:C > T:A mutations. All seven mutated tumors contained a codon 12-aspartate amino acid substitution. In addition, a second codon 12-cysteine mutant cell population was present in one of two codon 12-aspartate mutated TT-induced HA and in three of five codon 12-aspartate sporadic tumors. Of these four tumors, three contained both aspartate and cysteine mutations and were composed of multiple nodules; the fourth was a single mass. Seventeen tumors had multiple nodules; whereas 5 had a K-ras-2 mutation, 12 were wild-type. The molecular pathology of both sporadic and TT-induced HA is characterized by a high rate of K-ras-2 mutations characteristic of oxidative damage (ie, G:C > A:T and G:C > T:A mutations) resulting in two mutated population sets: codon 12 GGT > GAT and GGT > TGT (glycine to aspartic acid and cysteine). This is, to date, the first study to characterize the K-ras-2 gene mutations within human sporadic and TT-induced HA by direct sequence analysis and denaturing gradient gel electrophoresis. These data further support the hypothesis linking adduct-forming vinyl chloride exposure to HA containing a much higher frequency of K-ras-2 mutations and a mutational spectrum characteristic of chloroethylene oxide, a carcinogenic metabolite of vinyl chloride.
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PMID:Sporadic and Thorotrast-induced angiosarcomas of the liver manifest frequent and multiple point mutations in K-ras-2. 901 Apr 58

Seventeen strains of Streptococcus pyogenes were isolated from 17 patients in the Dermatological Ward of Gunma University Hospital in Japan between June 1994 and March 1995. Of these 17 strains, 14 were isolated from the pus of skin infections, two from blood, and one from ascitic fluid. The strains showed the same minimum inhibitory concentrations; 4 mg/L of minomycin, 4 mg/L of ofloxacin and 16 mg/L of fosfomycin. T-antigen typing of the strains indicated they were T11 type. The restriction endonuclease digestion patterns of chromosomal DNA from the 17 strains were all identical. The vinyl sheet covering the bed on which the patients were treated was found to be contaminated with S. pyogenes. This strain showed identical characteristics to the strains derived from the patients. These results suggest that S. pyogenes was transmitted to patients in the Dermatological Ward from the surface of the vinyl sheet covering the bed.
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PMID:Streptococcus pyogenes hospital-acquired infection within a dermatological ward. 981 92

Two human carcinogens that have been extensively studied are vinyl chloride and benzene. The active metabolites used in this study are chloroacetaldehyde (CAA) and para-benzoquinone (pBQ). Each forms exocyclic adducts between the N1 and N6 of A, the N3 and N4 of C and the N1 and N2 of G. Only CAA has been found to form the N2,3 adduct of G. CAA and pBQ adducts differ structurally in size and in the number of added rings, pBQ adding two rings to the base, while etheno bases have a single five-membered ring. The mechanism of repair of these two types of adducts by human enzymes has been studied in our laboratory with defined oligodeoxynucleotides and a site-specific adduct. The etheno derivatives are repaired by DNA glycosylase activity; two mammalian glycosylases are responsible: alkylpurine-DNA-N-glycosylase (APNG) and mismatch-specific thymine-DNA glycosylase. The former repairs 1,N6-ethenoA (epsilon A) as rapidly as the original substrate, 3-methyladenine, while the latter repairs 3,N4-ethenoC (epsilon C) more efficiently than the G/T mismatch. Our finding that there are separate enzymes for epsilon A and epsilon C has been confirmed by the use of tissue extracts from an APNG knockout mouse. As pBQ is much less efficient than CAA in modifying bases, the biochemical studies required total synthesis of the nucleosides. Furthermore, the pBQ adduct-containing oligomers are cleaved, to various extents by a different class of enzyme: human and bacterial N-5'-alkylpurine (AP) endonucleases. The enzyme incises such oligomers 5' to the adduct and generates 3'-hydroxyl and 5'-phosphoryl termini but leaves the modified base on the 5'-terminus of the 3' cleavage fragment ('dangling base'). Using active-site mutants of the human AP endonuclease, we found that the active site for the primary substrate, abasic (AP) site, is the same as that for the bulky pBQ adducts. There appears to be no clear rationale for the widely differing recognition and repair mechanisms for these exocyclic adducts, as shown for the repair of the same types of modification on different bases (e.g. epsilon A and epsilon C) and for completely unrelated lesions (e.g. AP site and pBQ adducts). Another important variable that affects the rate and extent of repair is the effect of neighbouring bases. In the case of epsilon A, this sequence-dependent repair correlates with the extent of double-strandedness of the substrate, as demonstrated by thermal stability studies.
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PMID:Mammalian enzymatic repair of etheno and para-benzoquinone exocyclic adducts derived from the carcinogens vinyl chloride and benzene. 1062 24