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Biomedical subjects

M Ochiai

Publications and source records attributed to M Ochiai.

At least 199 records · Page 11Linked to original sources
PubMed1985

Appearance of direct-acting mutagenicity of various foodstuffs produced in Japan and Southeast Asia on nitrite treatment.

After nitrite treatment, various kinds of pickled vegetables and sun-dried fishes produced in Japan showed direct-acting mutagenicity on Salmonella typhimurium TA100, inducing 1900-18000 revertants/g. Kimchis, sun-dried fishes, sun-dried squid, soy sauces, fish sauces, bean pastes and shrimp paste produced in Korea, the Philippines and Thailand also showed direct-acting mutagenicity after nitrite treatment. All soy sauces and fish sauces tested contained as much tyramine as 17-1020 micrograms/ml, but very low or undetectable amounts of (-)-(1S,3S)- and (-)-(1R,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids.

Animals↗
PubMed1985

Activation of K-ras and oncogenes other than ras family in rat fibrosarcomas induced by 1,8-dinitropyrene.

Oncogenes of fibrosarcomas of rats, induced by subcutaneous injection of 1,8-dinitropyrene (1,8-DNP), were examined by NIH 3T3 cell transfection assay and Southern blot analysis. Transformants containing rat specific repetitive sequences were obtained with DNAs of 4 fibrosarcomas, 1,8-DNP1, 1,8-DNP2, 1,8-DNP3 and 1,8-DNP7. A transformant, 1,8-DNP2-2, induced by DNA of a fibrosarcoma, 1,8-DNP2, and 7 secondary transformants derived from it contained rat K-ras sequences. Another transformant, 1,8-DNP2-1, induced by the same sarcoma did not have a ras family oncogene. This indicates that the sarcoma, 1,8-DNP2, has at least 2 transforming genes. The transforming genes of 6 other transformants derived from 3 sarcomas did not contain ras family or neu transforming genes.

Animals↗
PubMed1985

Vasodepressor effects of prazosin during insulin-induced hypoglycemia in hypertensive patients.

As both hormonal and hemodynamic alterations similar to those occurring during exercise can also be produced in humans by hypoglycemia, the present study explored changes in hemodynamic parameters during hypoglycemia and the effects of the alpha 1-adrenergic blocker, prazosin, on those responses in hypertensive patients. In the control group, which did not receive prazosin, plasma epinephrine, plasma norepinephrine and plasma renin activity (PRA) all increased along with a rise in blood pressure during hypoglycemia. On the other hand, the blood pressure decreased despite similar increases in plasma catecholamine levels and PRA in the prazosin treated group. The hemodynamic parameters, analyzed using M-mode echocardiography, changed in both the control and prazosin groups during hypoglycemia; stroke volume and cardiac output showed similar increases. However, while the total peripheral resistance did not change significantly in the control group, it decreased in the prazosin group during hypoglycemia. In accord with the changes in total peripheral resistance, the increment in mean-velocity of circumferential fiber shortening (m-Vcf) during hypoglycemia was greater in the prazosin group than in the control. These results suggest that: hypoglycemia stimulates the sympatho-adrenal axis which then releases catecholamines leading to a rise in blood pressure and tachycardia; In contrast, the blood pressure decreases during hypoglycemia in the prazosin group despite an increase in plasma catecholamines, because the alpha-receptors are blocked by prazosin and the unopposed beta-adrenergic effects of the catecholamines are pronounced enough to reduce the total vascular resistance.

Adult↗
PubMed1985

Synthesis and structure-activity relationships of 2-azetidinone-1-sulfonic acid derivatives with a heteroatom-bound substituent at the 4-position.

The synthesis and antibacterial activity of 3-[(Z)-2-alkoxyimino-2-(2-aminothiazol-4-yl)-acetamido] -2-azetidinone-1-sulfonic acid derivatives with a heteroatom-bound substituent at the 4-position are described. The effect of various 4-substituents on the antibacterial activity was examined. Some of these compounds showed excellent antibacterial activity especially against Gram-negative bacteria, including beta-lactamase-producing strains.

Anti-Bacterial Agents↗
PubMed1985

Chemical modification of sulfazecin. Synthesis of 4-(substituted methyl)-2-azetidinone-1-sulfonic acid derivatives.

In expectation of improving the antibacterial activity of sulfazecin by chemical modification at the 3- and 4-positions, a number of 3-[2-(2-aminothiazol-4-yl)-(Z)-2-(substituted oxyimino)-acetamido]-4-(substituted methyl)-2-azetidinone-1-sulfonic acids were synthesized. Among various 4-substituents explored, the carbamoyloxymethyl group was found to provide a good effect to the antibacterial activity of these 2-azetidinone derivatives. An extensive study of structure-activity relationships led to selecting (3S,4S)-3-[2-(2-aminothiazol-4-yl)-(Z)-2-carboxymethoxyiminoace tamido]-4- carbamoyloxymethyl-2-azetidinone-1-sulfonic acid, AMA-1080 (Ro 17-2301), which has highly potent antibacterial activity against Gram-negative bacteria including Pseudomonas aeruginosa, for further biological and subsequent clinical evaluation.

Anti-Bacterial Agents↗
PubMed1985

Nitrosatable precursors of mutagens in vegetables and soy sauce.

Nitrosatable precursors of mutagens that show mutagenicity to Salmonella typhimurium TA100 without S9 mix after treatment with nitrite at pH 3 were found in various foods. From Chinese cabbage, three indole compounds, indole-3-acetonitrile, 4-methoxyindole-3-acetonitrile, and 4-methoxyindole-3-aldehyde, were identified as mutagen precursors. 1-Methylindole and 2-methylindole, which are present in cigarette smoke showed strong mutagen precursor activity. Escherichia coli WP2 uvrA/pKM101 is more sensitive than S. typhimurium TA100 to nitrosatable precursors in soy sauce after treatment with 1-3 mM nitrite. The mutagenicity of soy sauce towards E. coli WP2 uvrA/pKM101 is partly explained by 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (MTCA) and tyramine reported previously. Oral administration of soy sauce and nitrite to male Fischer 344 rats for 2 years induced basal cell proliferation of the forestomach and intestinal metaplasia of the glandular stomach, but did not induce cancers in any organ. 3-Diazotyramine, a mutagenic nitrosation product of tyramine that is present at high concentrations in various foods induced squamous cell carcinomas of the oral cavity of rats when given in their drinking water. The carcinogenesis by N-benzylmethylamine, a nitrosatable precursor and nitrite was prevented by thioproline.

Animals↗
PubMed1985

Evaluation of the affinity of new N atom-containing tumor inhibitors for nucleic acids.

Interaction between new N atom-containing tumor inhibitors (1-9) and nucleic acids has been investigated utilizing the spectroscopic methods efficiently. On the basis of their data, it is well suggested that FNT-4 (4) and benzo[c]phenanthridine alkaloids (6-8) bind to nucleic acids by a fashion involving intercalation of aromatic molecule(s).

Animals↗
PubMed1984

Effect of prostaglandin E1 on fractional distribution of cardiac output and organ blood flow in man: a simultaneous and non-invasive determination using double dose thallium-201 scintigraphy.

Taking advantage of the fact that the distribution of Thallium-201 in an organ almost parallels the blood flow to the organ, we devised a non-invasive method of simultaneously determining blood flow and its distribution in human organs. With this method, we investigated the effect of exogenous prostaglandin E1 (PGE1) on the central and peripheral circulation. Scintigraphy was performed after two injections of 201Tl chloride, one at rest and one after the administration of PGE1 or saline. In eight subjects given PGE1 (0.2 microgram X kg-1 X min-1, iv), blood pressure fell, whereas both heart rate and cardiac output rose. The fractional distribution was increased in the heart (+13.3 +/- 2.98%, mean +/- SD), but decreased in the liver (-10.2 +/- 1.95%) and gastro-intestinal tract (-7.09 +/- 2.65%). No significant change was observed in the kidneys or leg. The blood flow in all these organs was increased. In the six control subjects given saline, there was no change in these central and peripheral haemodynamics. Thus, the intravenous infusion of PGE1 in man causes uneven blood flow distribution in heart, liver, kidney, gastro-intestinal organs and leg muscles, despite increased blood flow to all these organs. The method used in this study is relatively non-invasive and useful in evaluating organ blood flow in man, and seems to be widely applicable to physiological and pharmacologic research.

Alprostadil↗
PubMed1984

Presence of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids and tyramine as precursors of mutagens in soya sauce after nitrite treatment.

Soya sauce showed marked direct-acting mutagenicity toward Salmonella typhimurium TA 100 after nitrite treatment. Three precursors showing mutagenicity after nitrite treatment were isolated from soya sauce. Their structures were determined to be (-)-(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid [(-)-(1S,3S)-MTCA], its stereoisomer (-)-(1R,3S)-MTCA and tyramine. The numbers of revertants of TA 100 induced by 1 mg each of (-)-(1S,3S)-MTCA, (-)-(1R,3S)-MTCA and tyramine, after nitrite treatment, were 17 400, 13 000 and 3 900, respectively, without S9 mix. The amounts of MTCA isomers and tyramine in various Japanese soya sauces showing mutagenicity after nitrite treatment were 82-678 and 17-2 250 micrograms/mL, respectively. Most soya sauces produced in the USA showed weaker mutagenicity than those produced in Japan and contained lower, if not undetectable, amounts of the three precursors of mutagens. The mutagenicity of MTCA isomers and tyramine accounted for 16-61 and 1-35%, respectively, of the mutagenicity of the soya sauces after nitrite treatment. The mutagen(s) produced from (-)-(1S,3S)-MTCA with nitrite was a minor product(s), the major product being the non-mutagen, (-)-(1S,3S)-1-methyl-2-nitroso-1,2,3,4-tetrahydro-beta-carboline-3-carbo xylic acid [(-)-(1S,3S)-MNTCA], but the mutagen 4-(2-aminoethyl)-6-diazo-2,4-cyclohexadienone, produced from tyramine with nitrite, was one of the major products.

Carbolines↗
PubMed1983

Presence of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid, a precursor of a mutagenic nitroso compound, in soy sauce.

After treatment with nitrite, Japanese soy sauce was strongly mutagenic to Salmonella typhimurium TA100 without S9 mixture. Two precursors of the mutagen were isolated from Japanese soy sauce, and these were identified as (-)-(1S,3S)-1-methyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid [(-)-(1S,3S)-MTCA] and its stereoisomer (-)-(1R,3S)-MTCA. After treatment with nitrite, 1-mg samples of these compounds induced 17,400 and 13,000 revertants of TA100, respectively, without S9 mixture. Quantitative analysis of various kinds of soy sauces produced in Japan showed the presence of 82-678 micrograms of MTCA per ml. The mutagenicities of these compounds with nitrite accounted for 16-61% of the total mutagenicity of soy sauce with nitrite. Most soy sauces produced in the United States were less mutagenic than those produced in Japan and little, if any, of these two precursors of the mutagen was found in them. A major reaction product of (-)-(1S,3S)-MTCA and nitrite was a compound having a nitroso substitution at position N-2, but this compound was not mutagenic. Thus, the mutagen(s) formed from (-)-(1S,3S)-MTCA and nitrite was a minor product(s), and its specific mutagenic activity must be very high.

Biotransformation↗