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Biomedical subjects

Y Ohno

Publications and source records attributed to Y Ohno.

At least 613 records · Page 34Linked to original sources

An international study of smoking and bladder cancer.

The effects of smoking cigarettes and other forms of tobacco on the development of cancer of the lower urinary tract (bladder cancer) were evaluated in Boston, Massachusetts, Manchester, United Kingdom and Nagoya, Japan. Population-based series of incident cases and controls were identified and interviewed in each area. The present analyses were based on 592 cases and 533 controls in Boston, 553 cases and 731 controls in Manchester, and 290 cases and 588 controls in Nagoya. Smokers of cigarettes had about twice the incidence of bladder cancer as nonsmokers. In men the strength of the association between cigarette smoking and bladder cancer was similar in the 3 study areas. The strength of the association varied somewhat from area to area among women. Bladder cancer risk increased with frequency of cigarette smoking and with deep inhaling. In Boston men who smoked 2 or more packs of cigarettes per day and inhaled deeply had nearly 7 times the risk of nonsmokers. Ex-smokers had a level of risk between that of current smokers and nonsmokers. However, there was no clear relationship between risk and age at which cigarette smoking began, time since discontinuation among ex-smokers and use of filters. Over-all, there was little difference in bladder cancer risk between men who had and who had not smoked pipes but pipe smoking did appear to be associated with risk among men who had never smoked cigarettes. Cigar smoking was unrelated to bladder cancer.

Adolescent↗

Dexamethasone suppression test in autistic children.

A dexamethasone suppression test (DST) was carried out on autistic and other handicapped children to investigate the function of the hypothalamo-pituitary adrenal axis (HPA-axis). The subjects were 19 autistic children consisting of 11 relatively well-developed and eight poorly-developed children. The control groups were 26 normal volunteers, 19 patients with schizophrenia and 15 children with mental retardation (MR) or minimal brain dysfunction (MBD). The DST procedures followed the Carroll method. As a result, all of the normal volunteers and 19 schizophrenic patients showed normal response (suppressor). Nine of the 11 well-developed autistic children exhibited suppressor, while all of the poorly-developed children showed an abnormal response (non-suppressor). Nine of the 10 children with MR and all of the five children with MBD were suppressor. These results suggest that there might be a dysfunction in the HPA-axis of the poorly-developed autistic children.

Adolescent↗

Renal aminopyrine demethylation in several species determined by a sensitive radiometric method.

Renal microsomal aminopyrine demethylation activities of several species were measured by a sensitive radiometric method using [dimethylamino-14C-]aminopyrine as a substrate and 2,4-dinitrophenylhydrazine as a trapping agent for the formaldehyde formed. The activity was highest in hamsters (0.75 nmol min-1 mg-1 protein) and that in rabbits, rats, mice, and guinea-pigs was 19.7, 7.0, 4.5 and 3.7%, respectively, of the hamster values. These species differences did not correlate with species differences in cytochrome P-450 content or in NADPH cytochrome c reductase activity. Aminopyrine demethylation activities in sliced renal tissues of several species were also compared. This activity was also found highest in hamsters (0.54 nmol min-1 g-1 wet tissue) and the activities in rabbits, rats, and guinea-pigs were 9.2, 1.8 and 2.5%, respectively, of the hamster values.

Aminopyrine↗

Stimulant effects of W-7, a calmodulin-antagonist, on renin release from rat kidney cortical slices.

Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin-antagonist, on renin release was examined using rat kidney cortical slices. Although the amounts of renin release from the slices were stable during incubation of 3 consecutive 15 min periods in Krebs-Ringer bicarbonate solution (pH 7.4), the addition of W-7 to the incubation medium resulted in a concentration-dependent increase in renin release from the slices. The stimulant effect of W-7 on renin release was abolished by the removal of calcium from the incubation medium. These results suggest that the inhibition of the calcium-calmodulin system leads to the stimulation of renin release from rat kidney cortical slices.

Animals↗

Renal microsomal N-nitrosodimethylamine demethylase determined by a sensitive radiometric method.

Renal microsomal N-nitrosodimethylamine (NDMA) N-demethylation was measured in several species by a sensitive radiometric method using [14C]NDMA as a substrate and 2,4-dinitrophenylhydrazine (DNPH) as a trapping agent of the [14C]formaldehyde formed. The activities were the highest in mice and lowest in hamsters. The activities in rats could not be detected. Among several strains of mice studied the DDY strain was the highest in its activities. Although nicotinamide adenine dinucleotide supported NDMA demethylation by about 32% of nicotinamide adenine dinucleotide phosphate in kidney and only 16% in liver, other properties (pH profiles, km values, and effects of inhibitors) exhibited almost similar results in liver as compared to kidney.

Animals↗

Evidence for existence of somatostatin-like immunoreactivity with molecular heterogeneity in porcine ovaries.

Measurement of somatostatin (SRIF) by RIA in porcine ovarian tissues after removal of the follicular fluid revealed the existence of immunoreactive (IR) SRIF at concentrations of 2.2 +/- 0.6 ng/g wet weight (mean +/- SD). On gel chromatographic analysis of ovarian extracts one major and two minor components with SRIF-like immunoreactivities have been detected. The major component comprised 59.5 +/- 15.1% of the total IR-SRIF and was coeluted with synthetic tetradecapeptide (SRIF 14). The two other components seemed to have almost the same molecular weights as synthetic octacosapeptide (SRIF 28) (25.1 +/- 10%) and pro-somatostatin (15.4 +/- 5.5%), respectively. It is concluded that SRIF in porcine ovaries is heterogeneous, comprising SRIF 14 as a major component, as well as larger forms of SRIF which probably represent SRIF precursors.

Animals↗

Foreign-body tumorigenesis in rats by various kinds of plastics--induction of malignant fibrous histiocytomas.

Five kinds of plastics (3 polyvinyl chlorides, 1 polyhydroxyethyl metacrylate and 1 dimethyl polysiloxane) were implanted into subcutaneous tissues of Wistar rats of both sexes. Subcutaneous tumors developed in all experimental groups. The incidences of the tumors, however, differed from each other, although these materials were tested on the same experimental condition. This result indicates that chemical characters of the materials may influence the incidence of subcutaneous tumors. Histologically, most of these subcutaneous tumors were mesenchymal tumors with spindle cells arranged in a storiform pattern, with sheets of histiocyte-like cells or pleomorphic giant cells. Electron microscopy showed mixture of fibroblastic cells, histiocytic cells and undifferentiated cells in these tumors. From these histological and electron microscopical findings, many of the tumors were diagnosed as malignant fibrous histiocytomas.

Animals↗

Effects of metal-containing drugs taken simultaneously with clioquinol upon clinical features of SMON.

In order to explore the effects of metals upon the subsequent onset of several clinical events in SMON, a retrospective cohort study was attempted. Study subjects were 216 "exposed" patients and 149 "unexposed" patients. "Exposure" was defined as the simultaneous ingestion of metal-containing drugs with clioquinol before the onset of neurological disorders. These two cohorts were identified from 531 patients among 832 patients, collected by the nationwide survey in 1975 and 1976. Effects provoked by ingestion of five metals (alminum, calcium, magnesium, copper and bismuth) were evaluated by relative risks with and without adjustment of the total amount of clioquinol ingested. Adjusted relative risks were estimated by maximum likelihood method. Significance of relative risk was determined by its 95% confidence interval. Following major findings emerged from the present analysis. (1) Simultaneous ingestion of Al-, Ca-, Mg-, Cu- or Bi-containing drugs with clioquinol significantly reduced the risk of developing motor disturbances. (2) Risk of developing visual disturbances were favorably modified by Al-containing drugs. (3) Clinical severity was significantly reduced by ingestion of Al-, Ca-, Mg- or Bi-containing drugs. (4) About 2-fold increase in risk of unfavorable clinical course was demonstrated by Al-containing drugs. (5) Onset of both green-fur on the tongue and relapse appeared unrelated to the metal-containing drugs ingested. (6) Combined ingestion of two kinds of metal-containing drugs with clioquinol appeared to yield more favorable effects than single ingestion of metal-containing drugs. (7) Al- or Bi-containing drugs demonstrated the strongest association with clinical features of SMON, followed by the drugs containing Mg or Ca. Cu-containing drugs had little association.

Clioquinol↗

Effects of dietary fats and phytosterol on serum fatty acid composition and lipoprotein cholesterol in rats.

The effects of dietary fats and phytosterol on the fatty acid composition and lipoprotein cholesterol in serum were studied in female rats, with the following results. (1) The addition of 1% cholesterol to the 20% butter diet decreased the ratio of polyunsaturated fatty acid (PUFA) to saturated fatty acid (SFA) in serum. This phenomenon was negated when there was an intake of cod liver oil and wheat germ oil. (2) When cholesterol was added to the 20% butter diet, the serum total cholesterol increased 3.7-fold, due to an increase in the lower density lipoprotein (LDL + VLDL). (3) The addition of 5% phytosterol to the 10% butter-cholesterol diet reduced the total cholesterol level and increased the ratio of cholesterol in high density lipoprotein (HDL) to the cholesterol in LDL + VLDL. Although a 10% cod liver oil addition also reduced the total cholesterol level, the ratio of HDL/LDL + VLDL was similar to that of the 10% butter-cholesterol diet. (4) A direct relationship was found between the concentration of oleic acid (18:1) in serum and the total cholesterol level (r = 0.947) and also the level of LDL + VLDL-cholesterol (r = 0.935). These results show that cod liver oil, wheat germ oil, and phytosterol induce an increase in the PUFA/SFA ratio, promote hypocholesterolemia, and change lipoprotein concentration. However, there were indications that no relationship exists between the change in the total cholesterol level and the change in the ratio of HDL/LDL + VLDL, and that the increase of total cholesterol and LDL + VLDL-cholesterol was consistent with the increase of oleic acid in serum.

Animals↗

N-acetylcysteine and sodium 2-mercaptoethane sulfonate as sources of urinary thiol groups in the rat.

Increasing the urinary output of free thiol groups protects against cyclophosphamide-induced bladder toxicity. In the present study, intact rats, isolated perfused kidneys, and freshly isolated cells from various rat organs are used to compare the efficacy of N-acetylcysteine and sodium 2-mercaptoethane sulfonate (mesna) as sources of urinary thiols. In intact rats given a single i.v. dose of mesna, urinary thiol output is approximately 10-fold higher than in rats given an equimolar dose of N-acetylcysteine. this is partly due to the fact that N-acetylcysteine is rapidly absorbed by various types of cells, whereas mesna is transported selectively to the kidney, and partly to different renal handling of the two compounds. The results suggest that mesna is a more favorable drug than N-acetylcysteine for increasing urinary thiol excretion.

Acetylcysteine↗

Development of adenocarcinomas after transplantation of rat glandular stomachs treated in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG).

Glandular stomachs of fetal and newborn Wistar rats were transplanted s.c. after treatment in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at concentrations of 10, 5 and 1 microgram/ml for 2 h. Eleven adenocarcinomas developed from 118 MNNG-treated transplants, whereas no adenocarcinomas developed from 28 untreated transplants. The incidence of adenocarcinomas in fetal glandular stomach (9/46) was significantly different (p less than 0.01) from that in glandular stomach of newborn rats (2/67). Various types of mesenchymal tumors also developed from untreated (9/28) and MNNG-treated (20/118) transplants.

Adenocarcinoma↗

New method for quantitative measurement of N-nitrosodimethylamine formation in the whole mouse.

A simple method for the quantitative estimation of the formation of N-nitrosodimethylamine (NDMA) in mice has been developed. Mice were frozen in liquid nitrogen and homogenized. NDMA was then extracted and analyzed by a gas chromatograph equipped with a thermal energy analyzer. In normal mice NDMA (100 nmole) administered orally was rapidly metabolized and recovery of NDMA was about 10% after 60 min. However, when pyrazole (300 mg/kg) was injected i.p. to mice 60 min before the administration of NDMA, more than 80% of the administered NDMA could be recovered within 60 min. This result suggested that in pyrazole pretreated mice the accurate amount of NDMA formed could be estimated. Therefore the NDMA formation was measured in the pyrazole pretreated mice. When 0.25 mumole of aminopyrine and from 0.25 to 2.0 mumole of sodium nitrite were simultaneously administered orally, the amount of the NDMA formation in 20 min was found to be from 8.2 to 60.3 nmole. These values are equal to about from 30 to 200 micrograms/kg of body weight which are nearly daily doses expected to cause the carcinogenic effect on mice or rats. This method of measuring NDMA in pyrazole pretreated mice appears to be useful for investigating the in vivo formation of NDMA quantitatively.

Aminopyrine↗

Effect of phenobarbital and 3-methylcholanthrene on the hepatic microsomal metabolism of N-nitrosodimethylamine, N-nitrosomethylbutylamine and N-nitrosomethylbenzylamine.

The effect of phenobarbital (PB) and 3-methylcholanthrene (MC) pretreatment on dealkylations of N-nitrosodimethylamine (NDMA), N-nitrosomethylbutylamine (NMBuA) and N-nitrosomethylbenzylamine (NMBeA) was investigated in rat hepatic microsomes. PB increased the demethylation and the debutylation of NMBuA and the debenzylation of NMBeA. MC increased the debutylation of NMBuA and the debenzylation of NMBeA. However, MC decreased the demethylation of NMBeA. The demethylation of NDMA was not changed by the pretreatment of the inducers. These results suggest that the dealkylations of these nitrosamines are catalyzed by several enzymes, which probably depend on different cytochrome P-450 species.

Animals↗