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Biomedical subjects

K Yoshihira

Publications and source records attributed to K Yoshihira.

At least 37 records · Page 2Linked to original sources

Studies in the guinea-pig stomach on the formation of N-nitrosomethylurea, from methylurea and sodium nitrite, and its disappearance.

The formation of N-nitrosomethylurea (NMU) from methylurea (MU) and sodium nitrite in the guinea-pig stomach and the disappearance of NMU from the stomach were studied using a previously described method for NMU determination (Yamamoto et al. Fd Chem. Toxic. 1986, 24, 247). Guinea-pigs were used since they have only glandular stomachs and the pH of the gastric juice (1-2) is similar to that of humans. NMU was relatively stable in the isolated gastric contents of this species. When 2 mumol NMU was injected into the pylorus-ligated stomach of fasting guinea-pigs, about 50 and 37% of the NMU remained at 20 and 30 min, respectively. Some 19 and 42% remained 30 min after NMU was given orally by stomach tube to fasting and feeding guinea-pigs, respectively. NMU was detected in most blood samples irrespective of the administration procedure, but it disappeared rapidly from the blood after iv injection. Nitrite disappeared rapidly from the pylorus-ligated stomach, residual nitrite being less than 20% of the dose in 2.5 min. when 7.5 mumol MU and 15 mumol NaNO2 were co-injected into the ligated stomach, 3.1 mumol NMU was detected 10 min after the injection, followed by a gradual decrease. When MU and NaNO2 were given orally to the animals, 0.7-1.0 mumol NMU was detected in the stomach 10 min after the treatment. Thus NMU was shown to be formed readily in the stomach of the guinea-pig and to be absorbed from the stomach into the blood.

Animals↗

Gas chromatographic determination of tetramethylsuccinonitrile in poly(vinyl chloride) products in contact with food.

A method is described for the determination of tetramethylsuccinonitrile (TMSN) in poly(vinyl chloride) (PVC) products in contact with food. TMSN was extracted from PVC with dichloromethane, steam distilled, extracted from the distillate with dichloromethane, then determined with a gas chromatograph equipped with a nitrogen-phosphorus detector and a 6-ft. glass column packed with Chromosorb W coated with 5% Thermon 1000 plus 0.5% phosphoric acid. Recoveries between 98.3 and 100.6% were obtained in the range of 0.5-12.5 ppm of TMSN by the use of nitrobenzene as an internal standard. The detection limit was 0.05 ppm of TMSN in 1 g of PVC products. The highest residue to TMSN found in PVC products in contact with food was 13.9 ppm.

Chromatography, Gas↗

Structure-activity relationship of thirty-nine cytochalasans observed in the effects on cellular structures and cellular events and on actin polymerization in vitro.

The effects of twenty-three natural cytochalasans and sixteen synthetic derivatives on actin-distribution and alteration in morphology of C3H-2K cells, inhibition of lymphocyte capping, and inhibition of actin filament elongation were compared. The effects on cellular level and the in vitro effects showed positive correlation and the structure-activity relationship observed is discussed.

Actins↗

Quantitative determination of the superoxide radicals in the xanthine oxidase reaction by measurement of the electron spin resonance signal of the superoxide radical spin adduct of 5,5-dimethyl-1-pyrroline-1-oxide.

Reactivities of biologically active compounds with superoxide radicals were examined by measurement of electron spin resonance (ESR) spectra of 5-hydroperoxy-2,2-dimethyl-1-pyrrolidinyloxyl formed from 5,5-dimethyl-1-pyrroline-1-oxide and the superoxide radicals generated by xanthine-xanthine oxidase system. Quantitative determination of the superoxide radicals was performed by comparing the intensity of the spin adducts with that of 4-hydroxy-2,2,6,6-tetramethyl-pipperidinooxyl whose spin concentration was determined. Methyl viologen enhanced the formation of this spin adducts, while, rutin and luteoskyrin prevented it.

Cyclic N-Oxides↗

Mutagenicity of natural naphthoquinones and benzoquinones in the Salmonella/microsome test.

The mutagenicities of naturally occurring naphthoquinones and benzoquinones were tested by the pre-incubation method with Salmonella typhimurium strains TA98, TA100 and TA2637, which all contain plasmid pKM101. 6 of the 16 naphthoquinones tested, i.e., plumbagin, naphthazarin, 2-hydroxy-naphthoquinone, vitamin K3 (menadione), juglone and 7-methyljuglone, were mutagenic to strain TA2637 with metabolic activation. Except for juglone and 7-methyl-juglone, these compounds also had slight mutagenic effects on strain TA98 with S9 mix. All the mutagenic naphthoquinones contain one or two hydroxyl and/or methyl substituents. The naphthoquinone mompain, which has four hydroxyl groups, was not mutagenic. Unsubstituted beta-naphthoquinone, naphthoquinones with a prenyl side chain and all bi-naphthoquinone derivatives tested were non-mutagenic. None of the 13 benzoquinones examined was mutagenic to any of the strains used with or without metabolic activation. These results show that natural naphthoquinones are mutagenic when they have only one or two hydroxyl and/or methyl substituents.

Animals↗

Chemical and toxicological studies on bracken fern, Pteridium aquilinum var. latiusculum. VIII. The inability of bracken extracts containing pterosins to cause cattle bracken poisoning.

Methanol extracts of bracken frond and rhizomes prepared using a metallic extraction vessel, were proved incapable of producing bracken poisoning in calves. Nevertheless, they contained appreciable quantities of pterosins and pterosides. Thus the poisonous principle(s) in bracken responsible for the toxicological effects are not associated with these major sesquiterpenoids of the plant.

Animals↗

Correlation between effects of 24 different cytochalasins on cellular structures and cellular events and those on actin in vitro.

To compare the effects of cytochalasins on the cellular level with those on the molecular level, 24 cytochalasins, 20 natural compounds and 4 derivatives, were used. The following effects were tested for each of 24 cytochalasins; (a) four high dose (2-20 muM) effects on the cellular level: rounding up of fibroblastic cells, contraction of actin cables, formation of hairy filaments containing actin, and inhibition of lymphocyte capping; (b) a low dose (0.2-2 muM) effect: inhibition of membrane ruffling; and (c) two in vitro effects: an inhibition of actin filament elongation (the high affinity effect [low dose effect] in vitro) and an effect on viscosity of actin filaments(the low affinity effect [high dose effect] in vitro). These results indicated that there are almost the same hierarchic orders of relative effectiveness of different cytochalasins between low and high dose effects and between cellular and molecular effects. From the data obtained with the 24 cytochalasins, we have calculated correlation coefficients of 0.87 and 0.79 between an effect in vivo, inhibition of capping, and an effect in vitro, inhibition of actin filament elongation, as well as between inhibition of capping and another effect in vitro, effect on viscosity of actin filaments, respectively. Furthermore, a correlation coefficient between the high affinity effect and the low affinity effect determined in vitro was calculated to be 0.90 from the data obtained in this study. The strong positive correlation among low and high dose effects in vivo and those in vitro suggests that most of the effects caused by a cytochalasin, irrespective of doses or affected phenomena, might be attributed to the interaction between the drug and the common target protein, actin. In the course of the immunofluorescence microscope study on cytochalasin-treated cells using actin antibody, we have found that aspochalasin D, a 10-isopropylcytochalasin, strongly induced the formation of rodlets containing actin in the cytoplasm of the treated fibroblasts. In contrast, the other cytochalasins, including cytochalasin B, cytochalasin C, cytochalasin D, and cytochalasin H, were found to induce the formation of nuclear rodlets. Both cytoplasmic and nuclear rodlets found in the cytochalasin-treated cells were similar in ultrastructures to those induced by 5 to 10 percent (vol/vol) dimethyl sulfoxide in the same type of cells.

Actins↗

Viscometric analysis of effects of cytochalasins on in vitro polymerization and depolymerization of microtubules.

Nineteen cytochalasins including 6 natural cytochalasins, 2 natural aspochalasins, 7 natural chaetoglobosins and 4 their acetates were investigated by viscometry to examine their effects on in vitro polymerization and depolymerization of microtubules. Cytochalasin A was proved as an only active cytochalasin, confirming the studies of Himes et al., and others showed very weak or no noticeable effects. This results indicate that a wide range of effects of cytochalasins are not related to interactions with microtubules.

Animals↗