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N Oya

Publications and source records attributed to N Oya.

12 recordsLinked to original sources

Radiosensitization efficacy of KU-2285, RP-170 and etanidazole at low radiation doses: assessment by in vitro cytokinesis-block micronucleus assay.

Since the cytokinesis-block micronucleus assay is very sensitive at low radiation doses, we used it to investigate the in vitro sensitizing effects of two new hypoxic cell sensitizers (KU-2285, a fluorinated 2-nitroimidazole and RP-170, a 2-nitroimidazole nucleoside analogue) at 1-3 Gy in comparison with etanidazole. Exponentially growing EMT6 cells were treated with the drugs under aerobic or hypoxic conditions for 40 min prior to and during irradiation, after which the drugs were removed and cytochalasin B (2 micrograms/ml) was added to the medium. The number of micronuclei in binucleate cells was counted after 42 h of culture. Under aerobic conditions the three compounds at 5 mM had no sensitizing effect. Under hypoxic conditions the sensitizer enhancement ratio (SER) at 5 mM was 3.8 for KU-2285, 3.2 for RP-170, and 2.3 for etanidazole, while the oxygen enhancement ratio was 2.9. When the cells were pretreated under hypoxic conditions with drugs at 5 mM but then irradiated under aerobic conditions, KU-2285 and RP-170 had a sensitizing effect whereas etanidazole did not. The sensitizers were also tested at 0.5 and 1 mM, and the SER values were compared with those obtained at high doses (15-30 Gy) using a colony assay. The SER at low doses was higher than that at high doses for 1 and 5 mM KU-2285 and 5 mM RP-170, while the SERs were similar for all concentrations of etanidazole and the lower concentrations of KU-2285 and RP-170. These results might suggest the potential usefulness of KU-2285 and RP-170 in clinical radiotherapy.

Animals

Pharmacokinetics of fluorinated 2-nitroimidazole hypoxic cell radiosensitizers in murine peripheral nervous tissue.

We have previously reported that KU-2285, a 2-nitroimidazole with a fluorinated N1-substituent (-CH2-CF2CONH(CH2)nOH, n = 2), was a promising hypoxic cell radiosensitizer. In this study the pharmacokinetics of KU-2285 and its related compounds (n = 3 and n = 4) were compared with those of etanidazole (a 2-nitroimidazole with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds (n = 3 and n = 4) to assess the effects of incorporation of a CF2 group. The lipophilicity of the fluorinated compounds was higher than that of etanidazole, as measured by the octanol/water partition coefficient. As the number of CH2 groups increased, the lipophilicity of the compounds in both the KU-2285 and etanidazole series increased. The brain tissue levels of the fluorinated compounds were as low as those of the etanidazole derivatives, while the biological half-lives of the fluorinated compounds in peripheral nervous tissues were shorter than those of related non-fluorinated compounds.

Animals

A new single base substitution in a Japanese phenylketonuria (PKU) patient.

DNA analysis on phenylalanine hydroxylase (PAH) gene was performed in four Japanese PKU patients. By the Southern analysis, three patients were confirmed to be homozygous for haplotype 4, and the other one was homozygous for haplotype 2. Sequence analysis on the mutant PAH gene of this haplotype 2 patient, who was born to first-cousin parents, disclosed it to be a C-to-T transition in exon 7. This transition causes the substitution of Arg261 codon to a termination codon.

Base Sequence

Muscular form of glycogenosis type II (Pompe's disease).

An 11-year-old boy who was previously thought to have progressive muscular dystrophy was studied clinically, biochemically, and histologically. He was seen initially with an amyotonic syndrome with no clinical evidence of heart disease. Light and histochemical examination showed vacuolar degeneration and abnormal accumulation of glycogen in the muscular fibers. Electron microscopy showed aggregates of glycogen granules surrounded by a well-defined membrane, as in previously reported cases of type II glycogenosis. Enzymatic study disclosed that acid alpha-glucosidase was deficient in muscle, liver, and heart tissue, although neutral alpha-glucosidase was present within normal ranges. Measurement of acid and neutral alpha-glucosidase activity in muscle from the patient and his sisters and in urine from them and their parents indicated that his sisters are heterozygotes and his parents probably are heterozygotes. The disease was transmitted as an autosomal-recessive trait.

Child

Properties of the alpha-glucosidase from various human tissues in relation to glycogenosis type II (Pompe's disease).

The physico-chemical and electrophoretical properties of alpha-glucosidases from various human tissues and urine have been studied. There were some differences among Peak I enzymes (neutral alpha-glucosidases) obtained from liver, heart, muscle, kidney and urine. These differences are based on different effects of tris(hydroxymethyl)aminomethane and various thermostabilities of the Peak I enzymes. Electrophoretically, the Peak I enzyme activity at pH 6.5 from control tissues displayed a two-banded pattern except in kidney and urine. In the patient with the adult form of Pompe's disease the faster band of the Peak I enzyme from heart and muscle was not found and the slower band of the Peak I enzyme from liver was more cathodic. The results are discussed in relation to glycogenosis type II (Pompe's disease).

Copper