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Y Shirasu

Publications and source records attributed to Y Shirasu.

At least 73 records · Page 4Linked to original sources
PubMed1986

Isolation and expression in Escherichia coli of a cDNA clone encoding porcine pancreatic elastase.

We have cloned a DNA that is complementary to the messenger RNA that encodes porcine pancreatic elastase 1 from pancreas using rat pancreatic elastase 1 cDNA as a probe. This complementary DNA contains the entire protein coding region of 798 nucleotides which encodes an elastase of 266 amino acids, and 22 and 136 nucleotides of the 5' and 3'-untranslated sequences. When this deduced amino acid sequence was compared with known amino acid sequences, a carboxy-terminal 240 amino acids long peptide was found to be identical with a mature form of porcine pancreatic elastase 1, except for two amino acids. The porcine enzyme contains the same number of amino acid residues as the rat enzyme, and their amino acid sequences are 85% homologous. Taking the above findings together, we conclude that the cloned cDNA encodes a mature enzyme of 240 amino acids including a leader and activation peptide of 26 amino acids. We expressed the cloned porcine pancreatic elastase 1 cDNA in E. coli as a lac-fused protein. The resulting fused protein showed enzymatic activity and immunoreactivity toward anti-elastase serum.

Amino Acid Sequence↗
PubMed1986

Mechanism of potentiation of BPMC toxicity by fenthion pretreatment in mice.

The mechanism of potentiation of 2-sec-butylphenyl N-methylcarbamate (BPMC) toxicity by O,O-dimethyl O-(3-methyl-4-methylthiophenyl) phosphorothioate (fenthion) in mice was investigated in relation to BPMC metabolism in the liver. Simultaneous administration of BPMC and either one of the thiophosphates (fenthion, its sulfoxide and sulfone) in a dose of 1/40 of its LD50 resulted in a 2- to 3-fold potentiation. On the other hand, one hour pretreatment with these thiophosphates in the same dose resulted in a 7- to 9-fold potentiation of BPMC toxicity, but that with fenthion oxon resulted in only a 2-fold potentiation. Plasma levels of BPMC were significantly increased by pretreatment with the thiophosphates, but not by the oxon. In an in vitro study, an inhibition of hepatic microsomal metabolism of BPMC and a decrease of cytochrome P-450 content by thiophosphates were observed at the concentration of 10 microM, but not by 25 microM of oxon. In an in vivo study, an inhibition of hepatic microsomal metabolism of BPMC, aminopyrine and aniline by the thiophosphates pretreatment were observed in doses of 1/40 of their LD50's, but not by the oxon in doses of up to 4/10 of its LD50. Cytochrome P-450 content was decreased by the thiophosphates in doses of 4/10 of their LD50's, but not by the oxon. These results suggested that the inhibition of BPMC metabolism might be, at least in part, the mechanism for the fenthion-induced potentiation of BPMC toxicity and that desulfuration of fenthion might be responsible for the inhibition of BPMC metabolism.

Animals↗
PubMed1985

Effects of vitamin C on tumor induction by diethylnitrosamine in the respiratory tract of hamsters exposed to cigarette smoke.

A large dietary supplement (1%) of vitamin C was given to male Syrian hamsters exposed to cigarette smoke and receiving 12 weekly subcutaneous injections of diethylnitrosamine (DEN) to determine whether or not high doses of vitamin C can prevent the development of tumors by DEN in the respiratory tract. Treatment with DEN developed various types of tumors in the respiratory tract of hamsters and cigarette smoke exposure potentiated the tumor development in the nasal cavity, larynx and trachea. In comparison with the smoke-exposed hamsters treated with DEN, the vitamin C-supplemented hamsters showed significantly lower incidence of nasal cavity tumors and exhibited significantly earlier appearance of tracheal tumors. In addition, the laryngeal tumors also tended to develop earlier in the vitamin C-supplemented hamsters. The results indicate that high doses of vitamin C may inhibit tumor induction by DEN and exposure to cigarette smoke in the nasal cavity, but the development of laryngeal and tracheal tumors appeared to be accelerated by vitamin C supplement.

Animals↗
PubMed1985

Thirteen-week subacute toxicity study of 4-bromophenyl chloromethyl sulfone (BCS) in rats.

Four groups of 12 Wistar SPF rats of both sexes were fed diets containing 4-bromophenyl chloromethyl sulfone (BCS) at the levels of 0, 20, 100 or 500 ppm for 13 weeks to evaluate the subacute toxicity. Males and females in the 500 ppm group showed increases in plasma protein and calcium and a decreased A/G ratio. The values of plasma total cholesterol and uric acid increased in this female group. In addition, significant increases in both absolute and relative weights were seen in the liver, thyroid and adrenal of this group of both sexes, together with the increased kidney weight in males. All males and females in the 500 ppm group had centrilobular hepatocellular swelling of the liver consisting of proliferation of the smooth endoplasmic reticulum. Males of this group also showed increased incidences of hyalin droplet degeneration of the proximal tubular epithelium and focal tubular atrophy of the kidney. The maximum no-effect level of BCS was determined to be 100 ppm (males: 6.25 mg/kg/day, females: 6.80 mg/kg/day).

Animals↗
PubMed1984

Potentiated toxicity of 2-sec-butylphenyl methylcarbamate (BPMC) by O,O-dimethyl O-(3-methyl-4-nitrophenyl)phosphorothioate (fenitrothion) in mice; relationship between acute toxicity and metabolism of BPMC.

Fenitrothion of oral subtoxic dose (100 mg/kg; 4 hr pretreatment) decreased acute oral LD50 of BPMC from 360 to 66 mg/kg in male mice. The treatment prolonged the hexobarbital sleeping time and increased the plasma BPMC concentrations. The BPMC toxicity and its plasma concentrations were significantly reduced by phenobarbital treatment (80 mg/kg/day, 2 days, ip). This treatment diminished the effects of fenitrothion on BPMC toxicity and plasma BPMC concentrations. BPMC was metabolized by mixed-function oxidases of the liver in vitro. The metabolism of BPMC was competitively inhibited by the addition of fenitrothion (5 micrograms/ml). Fenitrothion remained in the liver (7 micrograms/g liver). These results suggest that competitive inhibition of BPMC metabolism by fenitrothion may, at least in part, play a role in inhibition of BPMC detoxication, resulting in potentiation of its toxicity.

Animals↗
PubMed1984

Pharmacokinetic analysis of increased toxicity of 2-sec-butylphenyl methylcarbamate (BPMC) by fenitrothion pretreatment in mice.

The potentiating effect of O,O-dimethyl O-(3-methyl-4-nitrophenyl) phosphorothioate (fenitrothion) on the toxicity of 2-sec-butylphenyl methylcarbamate (BPMC) in male mice was analyzed pharmacokinetically. The animals pretreated by dietary administration of 1000 ppm fenitrothion for 1 week (4.4% of the po LD50 daily) did not show toxic symptoms except for a slight decrease in body weight. In the fenitrothion-pretreated mice, toxicity of fenitrothion was not changed but a fivefold potentiation was observed in po and ip acute lethality and a threefold potentiation of iv lethality of BPMC. Toxic signs after BPMC administration were similar regardless of fenitrothion pretreatment or of route of administration. Fenitrothion pretreatment followed by BPMC administration (20 mg/kg po or 8 mg/kg iv, approximate LD5 in the pretreated mice) significantly increased the plasma BPMC concentration and the total area under the plasma concentration versus time curve (AUC0-infinity). The pretreatment increased the oral AUC0-infinity more greatly than the iv AUC0-infinity (for po, 6.3-fold; for iv, 2.0-fold). The oral systemic availability of BPMC (fraction reaching systemic circulation) was increased by fenitrothion treatment to 3.3-fold. These results suggest that a major cause of the potentiation may be the increase in amount of BPMC in the systemic circulation.

Animals↗
PubMed1984

Potentiation of acute toxicity of 2-sec-butylphenyl N-methylcarbamate (BPMC) by fenthion in mice.

This study was undertaken to determine whether interactions of toxicologic importance might occur during combined exposure of male mice to 2-sec-butylphenyl N-methylcarbamate (BPMC) and O,O-dimethyl O-(3-methyl-4-methylthiophenyl)phosphorothioate (fenthion). The equitoxic coadministration of BPMC and fenthion resulted in only a 1.6-fold potentiation compared to the expected LD50. However, 1 hr oral pretreatment with 3 (1/100 LD50), 7.5, 15, and 30 mg/kg of fenthion resulted in 5-, 9-, 12-, and 15-fold potentiation of the acute oral toxicity of BPMC, respectively. This fenthion pretreatment caused significant increases in the BPMC plasma concentrations and in the area under the concentration-time curve. The increase of the plasma concentrations of BPMC depended upon the fenthion dose and was associated with that of the potency ratio. The pretreatment of fenthion prolonged the hexobarbital sleeping time. The plasma concentrations of BPMC after the administration of a dose of LD2.5 (20 mg/kg) in fenthion-pretreated mice were clearly lower than those of a dose of LD2.5 (195 mg/kg) in nontreated mice. These results suggested that fenthion pretreatment caused the potentiation of the acute toxicity of BPMC partially by the inhibition of detoxification of BPMC.

Administration, Oral↗
PubMed1984

Inhalation chamber with size discriminator for liquid aerosols.

To minimize data variation in inhalation toxicity testing and to evaluate human and animal hazards of inhaled chemicals, a practical inhalation chamber with a size discriminator for mists was developed to provide high concentration liquid aerosols of defined particle sizes. Liquid aerosols generated with an atomizer were separated by an impinging separator which was composed of aerosol jets directed upward against a flat plate. The principle of the separator eliminates particles larger than a calculated cutoff size in micrometer and submicrometer ranges by changing the orifice diameter of the jet nozzle under constant air flow. The mists thus separated are introduced into the space between two concentric cylinders just above the impaction plate. Ten rats can be positioned around the periphery of the chamber wall equidistant from the impaction plate, with their snouts thrust into the inhalation space. Preliminary testing with olive oil and water aerosols using particle cutoff sizes of 1, 3, and 3.3 micron showed that the obtained separation of particles was very clear, although the cutoff point seemed to shift somewhat to smaller values than calculated; the shift was especially evident with water aerosols. The concentrations obtained were more than 1 mg/liter when the cutoff point was selected at 1 micron. The mist at the inhalation space attained a steady concentration and particle size distribution within 2 min of the onset of mist injection, remained over a 4-hr period, and was cleared within 2 min of the cessation of mist generation.

Aerosols↗