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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 595 records · Page 33Linked to original sources

Mechanism of allyl alcohol toxicity and protective effects of low-molecular-weight thiols studied with isolated rat hepatocytes.

Freshly isolated hepatocytes from male rats were incubated with allyl alcohol at concentrations up to 2 mM. Allyl alcohol exerted a dose-dependent toxicity on the cells which was inversely related to cellular glutathione (GSH) content and accordingly influenced by stimulation as well as inhibition of GSH synthesis. The toxicity was prevented by inhibitors of alcohol dehydrogenase and augmented by the aldehyde dehydrogenase inhibitor disulfiram, suggesting that the toxic metabolite was the reactive aldehyde acrolein. The pattern of hepatocellular metabolism of allyl alcohol was monitored by high-pressure liquid chromatography (HPLC) analysis. The results suggest that acrolein, which is formed by the activity of alcohol dehydrogenase, preferentially reacts with cellular GSH to form an aldehyde-GSH adduct which subsequently is metabolized to the corresponding acid. In addition, a thiohemiacetal may be produced and subsequently degraded. In cells depleted of GSH, acrolein may react with essential macromolecules and thereby lead to structural and functional derangement and, eventually, irreversible injury.

1-Propanol↗

Gamma interferon enhances mitogenic responses induced by pokeweed mitogen.

Interferon (IFN)-induced suppression of the lectin-stimulated lymphoproliferative response was studied comparatively with human IFN-alpha, IFN-beta and IFN-gamma, using an equal unit of their antiviral activity ranging from 31.25 to 1000 IU/ml. Both IFN-alpha and IFN-beta inhibited phytohemagglutinin (PHA) and pokeweed mitogen (PWM)-stimulated lymphoblastogenic response similarly in a dose-related fashion, but the IFN-gamma effect was far less. Indeed, the PWM-stimulated lymphocyte blastogenesis in the cultures incubated for 7 days was enhanced in the presence of IFN-gamma at a concentration of 62.5 IU/ml. The enhancing effect was found to be highest at the lowest concentration of IFN-gamma examined. The IFN-gamma induced enhancement of lectin-stimulated blastogenesis was found mainly in the PWM cultures incubated for 7 days but less in cultures incubated for 5 days or in PHA cultures incubated for 3 days, suggesting that the observed effect might be caused by the activation of interleukin production.

Humans↗

Substrate concentration dependency of N-nitrosodimethylamine and N-nitrosomethylbenzylamine metabolism in rat liver.

Metabolism of N-nitrosodimethylamine (NDMA), a hepatocarcinogen, and N-nitrosomethylbenzylamine (NMBeA), an esophageal carcinogen, was comparatively investigated in rat liver. When these nitrosamines (25 micromole/kg) were administered orally to rats, the clearance of NDMA from the serum and liver was faster than that of NMBeA. The metabolic decomposition of NDMA by rat isolated hepatocytes was slower than that of NMBeA at high concentration (0.5 mM). However, at low concentration (6.7 microM) the metabolic decomposition of NDMA was faster than that of NMBeA. The ratio of NDMA demethylation to NMBeA demethylation and debenzylation by hepatic microsomes also changed depending on nitrosamine concentrations (1 microM to 1 mM), and low concentration of NDMA was demethylated rapidly. These results suggest that NDMA is metabolized to a methylating agent more effectively than NMBeA in liver, when carcinogenic doses of nitrosamines are administered.

Animals↗

Plasma free tryptophan concentration in children with attention deficit disorder.

In order to examine the serotonin metabolism in children with attention deficit disorder (ADD), plasma tryptophan, which is the precursor of serotonin, was measured in 10 children with ADD and 12 normal children. The mean plasma total tryptophan level in the children with ADD was not significantly different from that of the normal children. The mean plasma free tryptophan level in the children with ADD was significantly higher than that in the normal children. There tended to be a positive correlation between the plasma free tryptophan level and the Werry-Weiss-Peters Activity Scale in children with ADD. In other words, the more severe the hyperactivity of ADD, the higher the plasma free tryptophan level. The mean ratio of plasma free to total tryptophan levels in the children with ADD was significantly higher than that in the normal children, which means that the children with ADD showed a high amount of free tryptophan in the total tryptophan level. These results suggest that there might be some disturbance in the tryptophan-serotonin metabolism in the brain of a child with ADD.

Attention Deficit Disorder with Hyperactivity↗

Occupation and bladder cancer in Boston, USA, Manchester, UK, and Nagoya, Japan.

Relations between occupational history and the development of cancer of the lower urinary tract ("bladder cancer") were evaluated in Boston, Massachusetts, USA, Manchester, UK, and Nagoya, Japan. Population-based series of incident cases and controls were identified and interviewed in each area. The present analysis was limited to men and was based on 430 cases and 397 controls in Boston, 399 cases and 493 controls in Manchester, and 226 cases and 443 controls in Nagoya. In Boston, elevated risk of bladder cancer was associated with employment related to dyes (relative risk = 2 X 1; 90% confidence interval, 0 X 9-5 X 1), leather (1 X 7; 1 X 1-2 X 6), paint (1 X 5; 0 X 9-2 X 4), or organic chemicals (1 X 6; 1 X 1-2 X 5). In Manchester, elevated risk was associated with 0 X 9-3 X 6). No clear association was observed between occupation and risk in Nagoya. Elevations in risk related to occupation generally were stronger in men under 65 years of age compared to older men. Differences from place to place in associations between occupation and risk may be the result of differences in the exposures to hazardous agents that jobs with the same title involve.

Adult↗

Effects of tinoridine on lipid peroxidation and renin release in the rat renin granule fraction.

This study was carried out to investigate the effect of tinoridine (2-amino-3-ethoxycarbonyl-6-benzyl-4,5,6,7-tetrahydrothieno[2,3-c] pyridine), a non-steroidal anti-inflammatory drug, on the lipid peroxidation and renin release in the renin granule fraction. The renin granule fraction was prepared from the kidney cortex homogenate by a discontinuous sucrose density gradient centrifugation. Incubation of this fraction at 37 degrees C resulted in an increase in lipid peroxide formation, accompanied by increased release of renin from the granules. When the renin granule fraction was incubated with 50 microM tinoridine at 37 degrees C, lipid peroxide formation in this fraction was completely inhibited. Simultaneously, the rate of renin release from the granules was significantly suppressed. Tinoridine, at concentrations from 5 microM up to 100 microM, produced a concentration-dependent inhibition on the simultaneous increases in lipid peroxide formation and renin release induced by 50 microM ascorbic acid in the renin granule fraction. On the other hand, indomethacin, hydrocortisone and prednisolone, which had no ability to inhibit the lipid peroxidation in the renin granule fraction, did not influence the release of renin from the granules. These results suggest that tinoridine suppresses renin release by inhibiting the oxidative disintegration of membranes of renin granules.

Animals↗

Inhibitory action of somatostatin on meiotic maturation of cultured porcine follicular ova.

To investigate the physiological importance of somatotrophin release-inhibiting factor (SRIF), effects in vitro of synthetic SRIF 14 on germinal vesicle breakdown (GVB) of cultured porcine follicular ova were studied. The proportion of ova with GVB decreased gradually and significantly with increasing concentrations of SRIF 14 in the range from 6 X 10(-12) to 6 X 10(-7) M during a 22 h period of culture. The inhibitory effect was apparent for the period between 14 and 22 h in the course of culture but was reversed by a concomitant addition of anti-SRIF to the medium. Neither synthetic oxytocin, vasoactive intestinal polypeptide nor substance P exerted any inhibitory or stimulatory action on GVB. These results suggest a limited but definite inhibitory action of SRIF on GVB of porcine ova.

Animals↗

Case-control study of urinary bladder cancer in metropolitan Nagoya.

We conducted a population-based case-control study of patients with bladder cancer and of controls drawn randomly from the general population of Metropolitan Nagoya and interviewed both groups. The incidence rates of bladder cancer were 2.42 and 7.05/100,000 for females and males, respectively. The analysis, based on 293 patients and 589 controls who were frequency matched for age, sex, and residence, provided the following major findings. Age-adjusted relative risks of 1.89 (1.15-3.10) and 3.53 (1.71-7.27) were found in male and female cigarette smokers, respectively. Significant relative risk was also found in males who drank cocoa. Elevated risk with a dose-response relationship was observed among women who used hair dye and who smoke, but this risk was insignificant, with the disappearance of a dose-response relationship, when it was adjusted for smoking. Age- and smoking-adjusted relative risk of coffee drinking was insignificant with no dose-response relationship. Relative risk of artificial sweetener use was below 1 with adjustment for age and smoking. Intake of alcoholic beverages and cola was insignificantly associated. Reduced risk of significance was suggested for the intake of black tea and matcha (powdered green tea) in females and of fruit juice in males.

Adult↗

[The short-term variability index from abdominal fetal electrocardiogram].

Fetal heart rate monitoring was carried out on 37 patients between 34 and 42 weeks gestation, in 21 patients with direct fetal electrocardiogram (dFECG), and in 16 patients with abdominal fetal electrocardiogram (aFECG). The mean of the absolute beat by beat differences (MABB) and the percentage of beat by beat differences below 1 millisecond (1 msec%) and below 2 milliseconds (2 msec%) were measured from true fetal R-R intervals by a computerized technique. With dFECG, a significant inverse correlation was found between the MABB and the 1 msec% or the 2 msec%. The standard deviation of fetal R-R intervals as the LTV index showed a higher correlation to the MABB than to the 1 msec% or the 2 msec%. These results were similar to those with aFECG. In addition, with aFECG, the effect of fetal rest and activity on the MABB was significant, but the 1 msec% and the 2 msec% were not altered with periods of fetal rest and activity. The influence of the artifact in aFECG signals on the 1 msec% and the 2 msec% was less than on the MABB. The 1 msec% and the 2 msec% were reliable indices of the STV assessment from aFECG.

Abdomen↗

[Correlation between progesterone and plasminogen activator in rat ovaries during the ovulatory process].

The role of progesterone in the action of hCG on follicular rupture is unclear at present. In this present study, we investigated the correlation between the preovulatory increase in progesterone and the periovulatory increase in plasminogen activator (PA) activities was completely suppressed with simultaneous injection with hCG of a minimum effective dose of cycloheximide to block ovulation completely. Suppression of hCG-induced acute rise of preovulatory progesterone after simultaneous injection with hCG of a minimum effective dose of cyanoketone to block ovulation completely, was accompanied by an only partial but significant suppression of hCG-induced increase in PA activities. Furthermore this suppression of PA activities after concurrent injection of cyanoketone with hCG was reversed by a supplementary injection of a dose of progesterone which was enough to restore ovulatory responses completely against the inhibitory action of cyanoketone. These facts suggest that PA in rat ovaries is synthesized de novo and progesterone may be responsible for the increase of PA in rat ovaries during the periovulatory process.

Animals↗

Nature of N-nitrosodimethylamine demethylase in hepatic microsomes of rats.

The nature of enzymes involved in demethylation of N-nitrosodimethylamine (NDMA) was investigated in hepatic microsomes of rats. Compared to the other cytochrome P-450-dependent enzymes. NDMA demethylase had anomalous properties as reported in the literature. However, kinetic analysis suggested a qualitative change in NDMA demethylase induced by phenobarbital (PB) and 3-methylcholanthrene (MC) pretreatment. The inhibition of demethylase by alpha-naphthoflavone in MC-treated microsomes also suggested that cytochrome P-450 species induced by MC are active in demethylating NDMA. The enhancement of NDMA demethylase activity by metyrapone in PB-treated microsomes was greater than in non-treated ones, and was not observed in MC-treated ones. The result is almost the same as in acetanilide hydroxylation, depending on cytochrome P-450. Pyrazole, tranylcypromine, and aminoacetonitrile, which are selective inhibitors of NDMA demethylation, interacted with cytochrome P-450 species to produce type-II spectra, and typical type-II compounds (aniline, imidazole, and nicotinamide) were inhibitors of the NDMA demethylation. Tranylcypromine irreversibly inhibited microsomal monoamine oxidase [EC 1.4.3.4], but not NDMA demethylase. Semicarbazide (a copper- and pyridoxal-containing amine oxidase [EC 1.4.3.6] inhibitor) had no effect on demethylation. From these results it is concluded that NDMA demethylation depends only on cytochrome P-450-dependent monooxygenases.

Aminoacetonitrile↗

Malignant fibrous histiocytomas induced in rats by polymers.

Five polymeric materials (3 polyvinyl chlorides, 1 polyhydroxyethyl methacrylate, and 1 dimethyl polysiloxane) were implanted into subcutaneous (SC) tissues of rats. Subcutaneous tumors developed in all experimental groups. The incidences of the tumors differed however, although the experimental conditions were the same for all these materials. This result indicates that chemical characteristics of the materials may influence the incidence of SC tumors. From the histological and electron-microscopic findings many of these tumors were diagnosed as malignant fibrous histiocytomas.

Animals↗

Indomethacin augments inhibitory effects of interferons on lymphoproliferative response.

Lectin-induced lymphoproliferative response was enhanced by the addition of indomethacin to the culture and in contrast, suppressed by the addition of interferon. However, when indomethacin and interferon were concomitantly present in the lectin-driven cultures, the suppressive effect of interferon on the lymphocyte blastogenesis surpassed the enhancing effect of indomethacin on the response. Furthermore, and unexpectedly, the inhibitory effect on the response due to interferon was definitely augmented in the presence of indomethacin as compared with the response in the absence of indomethacin.

Drug Synergism↗