Transformation of o-toluate in Pseudomonas putida isolate 1065 and Rhizopus japonicus ATCC 24794.
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Biomedical subjects
Publications and source records attributed to G Engelhardt.
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From Bacillus sphaericus ATCC 12123 an aryl acylamidase (EC 3.5.1.13) was purified to homogeneity by ion exchange chromatography, gel filtration, and polyacrylamide gel electrophoresis. The enzyme is inducible by various phenylamides of the acylanilide, phenylcarbamate, and methoxysubstituted phenylurea type. It has a molecular weight of 75,000. Enzyme activity was inhibited by sulfhydryl reagents, several metal ions, and 3,4-dichloroaniline (a product of linuron degradation). A requirement for divalent metal ions in enzyme activity could not be demonstrated. In the presence of 6 M urea an irreversible inactivation of the enzyme occurred. The hydrolysis of L-alanine-4-nitroanilide was competitively inhibited by puromycin.
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N, O-dimethylhydroxylamine was identified as a degradation product of linuron formed in the presence of extracts of Bacillus sphaericus ATCC 12123 by characterization of its dinitrophenyl derivative.
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Linuron [3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea] induces the formation of an enzyme (acylamidase) responsible for the degradation of a large variety of different herbicides and fungicides of the acylanilide and phenylurea type. The former type is degraded at a rate at least 10 times higher than the latter.
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Recently there have been reports of liver and kidney tumors in rodents following long-term exposure to di(isononyl) phthalate (DINP). Mechanistic studies suggested that the liver tumors were a consequence of peroxisomal proliferation, whereas the kidney tumors (found only in male rats) were associated with induction of alpha(2u)-globulin. Because both peroxisomal proliferation and alpha(2u)-globulin are considered to be non-genotoxic carcinogenic processes, it seemed appropriate to investigate the genotoxic potential of DINP. Additional studies were also conducted on di(isodecyl) phthalate (DIDP), a structurally related substance that also induces peroxisomal proliferation, although it has not been tested in a carcinogenicity bioassay. The DINP was tested in Salmonella, in vitro cytogenetics and mouse micronucleus assays, whereas DIDP was evaluated in a mouse micronucleus test. All of these tests produced negative results, i.e. neither phthalate was mutagenic in any of the test systems. These data are consistent with results of other published and unpublished genotoxicity tests and provide support for the hypothesis that the liver and kidney tumors induced by DINP were the result of non-genotoxic processes.
The effect of meloxicam, a new non-steroidal anti-inflammatory drug, on spontaneous osteoarthrosis of the ankle joint in Crl: CDBR rats was investigated. The drug was administered in the feed at doses of 0.4, 0.6 and 0.8 mg/kg/day over a period of 2 years to 50 males and 50 females per dose. 100 male rats and 100 female rats were used as controls. Histological examination revealed osteoarthrotic changes of varying degrees of severity in the hip, knee and ankle joints of both treated and untreated animals. The incidence and severity of these changes was greatest in the ankle joints. There was little difference between treated and untreated animals as regards the site, incidence, severity and histological appearance of the osteoarthrotic changes. At the doses tested, meloxicam does not affect the processes involved in spontaneous osteoarthrosis in the rat and can therefore be regarded as chondroneutral in this species.
Chinese hamsters and rats were exposed to an average concentration of 817 ppm and 820 ppm n-butyl acrylate (acrylic acid n-butyl ester), respectively for 4 days. In both animal species, the exposure led to distinct signs of toxicity; four of ten male Chinese hamsters died during the exposure period. The chromosome analysis carried out in the bone marrow of the animals after the 4-day inhalation did not indicate any chromosome-damaging effect of n-butyl acrylate. Under the experimental conditions chosen the percentage of metaphases damaged was always in the same range as that of the controls for both Chinese hamsters and rats.