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Biomedical subjects

K Tsuchiya

Publications and source records attributed to K Tsuchiya.

At least 541 records · Page 30Linked to original sources
PubMed1985

Determination of malotilate and its metabolites in plasma and urine.

A method for the determination of malotilate (I), the corresponding monocarboxylic acid (II) and its decarboxylated product (III) in plasma is described. Plasma was extracted with chloroform spiked with internal standard. The residue, dissolved in methanol, was chromatographed on a reversed-phase column with a mobile phase of 60% acetonitrile and 1% acetic acid in water. The sensitivity limit for I, II and III was 50, 25 and 100 ng/ml of plasma, respectively. Compound I in the same plasma extract was also analysed by gas chromatography--electron-impact mass spectrometry. The base peaks m/z 160 for I and m/z 162 for internal standard (IV) were monitored; the sensitivity limit for I was 2.5 ng/ml of plasma. The determination of the metabolites of I, II and its conjugate (V), and isopropyl-hydrogen malonate (VI) in urine by high-performance liquid chromatography is also described. The limit of quantification for VI was 2.0 micrograms/ml, and the overall coefficient of variation of VI was 4.7%. The limit of quantification for II in urine was 0.5 micrograms/ml and that for V was 1.0 micrograms/ml as total II (II + V). The overall precision of the method was satisfactory. The method was used to determine plasma and urine concentrations in four dogs orally dosed with 100, 200 or 400 mg of malotilate.

Animals↗
PubMed1985

Alkylation of amide linkages and cleavage of the C chain in the enzyme-activated-substrate inhibition of alpha-chymotrypsin with N-nitrosamides.

Active-site-directed N-nitrosamides inhibit alpha-chymotrypsin through an enzyme-activated-substrate mechanism. In this work, the activation results in the release--in the active site--of benzyl carbonium ions, which alkylate and inhibit the enzyme. The final ratio of benzyl groups to enzyme molecules is 1.0, but the alkyl groups are scattered over a number of sites. Reduction and alkylation of the inhibited enzyme generate peptides insoluble in most media. Guanidine hydrochloride at 6 M proved a good solvent, and its use as an eluant on G-75 Sephadex permitted separation of the peptides. In the case of 14C-labeled enzyme, such an approach has shown that all of the alkylation occurs on the C chain of the enzyme, the chain of which the active site is constructed. Chemical modification of the peptides with ethylenediamine and N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide rendered them soluble in dilute acid, permitting high-performance liquid chromatographic separation. Model studies have shown that the benzyl carbonium ions are highly reactive, alkylating amide linkages at both oxygen and nitrogen. Alkylation at oxygen produces imidate esters, which are labile centers. Hydrolysis of protein imidates results in a cleavage of the chain at that point, and separation of the peptides formed (followed by analysis) permits their identification. In our inhibition of alpha-chymotrypsin, a major site of O-alkylation has been identified as the carbonyl oxygen of Ser-214. Alkylation at the nitrogen atom of amide linkages generates stable labels; full hydrolysis with 6 N HC1 then leads to N-benzyl amino acids characteristic of those sites. Chromatography of this mixture and also 13C NMR spectroscopy of the intact inhibited enzyme have shown that three major N-alkylations have occurred. Tryptic digestion of the C chain of chymotrypsin, which contains all of the alkylation sites, provides evidence that the stable N sites are principally located between residue 216 and residue 230. These locations are consistent with predictions of alkylation sites based on inspection of a molecular model of chymotrypsin, with special reference to the aromatic binding pocket.

Alkylation↗
PubMed1985

An electron microscopic study of pathogenesis of urinary tract infection caused by Pseudomonas aeruginosa P 9 in mice.

Scanning and transmission electron microscopic examination of the kidney and bladder of mice infected transurethrally with Pseudomonas aeruginosa P 9 revealed that the pyelonephritis is established through two routes, after the organisms reach the pelvis of the kidney via the bladder and ureter. In one route, which appeared to be predominant, the inoculated bacteria invaded the renal parenchyma through exfoliation of the calyceal epithelial cells with subsequent destruction of the basement membrane. Alternatively, the inoculated bacteria retrograded in the collecting tubules and urineferous tubules and propagated in the lumina followed by invasion of the renal parenchyma. In the bladder, the inoculated bacteria increased in number then disappeared within 48 h after exhibiting morphological aberrations such as elongation, bulge and spheroplast formation.

Animals↗
PubMed1984

Bioethics and health care in industrial society.

Due to rapid development, industrial societies must now make a fresh start based on a new idea of society which will enable them to survive the fast approaching 21st century. In this situation, health problems must be dealt with not only by medical science but also by research in other areas such as economics and technology. In fact, we are now in a situation in which problems of health and health care can no longer be solved without cooperation from these other research areas. What is most necessary is a new ethical standard. This can be developed through ideas based on a system of bioethics in which Occidental humanism and Oriental humanism are combined to a substantial degree. I believe that the establishment of this type of bioethics can lead to the successful institutionalization of health, health care and welfare for the 21st century.

Environmental Health↗
PubMed1984

Release of P and K from yeast cells irradiated by vacuum UV below 170 nm.

Yeast cells were irradiated with monochromatic synchrotron radiation (SR) under wet conditions in the wavelength region from 160 to 185 nm at INS-SOR, Tokyo. By the particle-induced X-ray emission (PIXE) method applied to whole cells several elements were found to be released from the irradiated cells at the wavelengths shorter than 170 nm. The most drastic release occurred with phosphorus, followed potassium. Sulphur and calcium were not released over the whole wavelength region studied. It was also revealed that the release of these elements paralleled the cell inactivation. The cause of these element releases upon vaccuum-UV irradiation was inferred in relation to the dissociation of H2O molecules located in the vicinity of the cell surface region.

Particle Accelerators↗
PubMed1984

Studies on prolactin in major psychoses--with reference to prolactin response to stress in schizophrenia.

The serum prolactin concentrations of schizophrenics with delusions or hallucinations, hypomanics, depressives, alcoholics with and without psychotic symptoms were examined. Among them, only the serum prolactin concentrations of alcoholics with psychotic symptoms were significantly higher when compared to the normal controls. In a stress experiment, the alterations of serum prolactin seen in schizophrenics were significantly greater when compared to the normal controls. The results are discussed in connection with the neurochemical mechanisms for the emotional states caused by stress.

Adult↗