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Biomedical subjects

O Inoue

Publications and source records attributed to O Inoue.

At least 73 records · Page 4Linked to original sources

Detection of benzodiazepine receptor occupancy in the human brain by positron emission tomography.

Benzodiazepine receptor occupancy in the brain following oral administration of clonazepam (CZP) with a dose of 30 micrograms/kg in six healthy young men and a further dose of 50 micrograms/kg in one of the subjects was estimated by carbon-11 labeled Ro15-1788 and positron emission tomography (PET). The effects of CZP on the latency of auditory event-related potentials (P300) were also studied. Overall brain 11C uptake was depressed and the % inhibition of 11C uptake in the gray matter of the brain at 30 min after [11C]Ro15-1788 injection was 15.3-23.5% (mean, n = 6) following 30 micrograms/kg CZP when compared with that in the control experiment without any previous treatment. The 11C uptake in the cerebral cortex in the subject who received both doses decreased in a dose-related manner after 30 micrograms/kg and 50 micrograms/kg CZP. The P300 latency was prolonged significantly by 30 micrograms/kg CZP [31.6 +/- 16.3 ms (mean +/- SD, n = 6), P less than 0.05]. The P300 latency in the same subject was prolonged in a dose-related manner by 30 micrograms/kg and 50 micrograms/kg CZP. The technique using [11C]Ro15-1788 and PET permits comparison of the pharmacological effects with the percentage of receptor sites which benzodiazepines occupy in the human brain. P300 also seems to be useful to investigate the pharmacological effects of benzodiazepines.

Adult

Synthesis and evaluation of 11C-PK 11195 for in vivo study of peripheral-type benzodiazepine receptors using positron emission tomography.

The biodistribution of 3H-PK 11195, an antagonist of the peripheral-type benzodiazepine receptors, was studied in mice. High accumulations of radioactivity in the heart, lung, spleen, kidney and adrenal were observed after intravenous injection of tracer amounts of 3H-PK 11195 into the mice. The radioactivity in the heart, lung, spleen, kidney and adrenal was significantly decreased by the coadministration of carrier PK 11195, which indicated that PK 11195 specifically binds to the receptors. No radioactive metabolites were observed in the heart, lung and brain 20 min after intravenous administration of 3H-PK 11195. The accumulation of 3H-PK 11195 in the lung was not affected by pretreatment with either alpha-methyl benzylamine or imipramine, suggesting that 3H-PK 11195 specifically binds to the receptors. The ratios of radioactivity of the kidney, adrenal and spleen to blood increased as a function of time, whereas that of the lung and heart rapidly reached to a steady state. 11C-PK 11195 was synthesized by the N-methylation of desmethyl precursor yielding more than 100 mCi with high specific activity (more than 1.4 Ci/mumol). The labeling and purification procedure was completed within 23 min after the end of bombardment (EOB). The 11C-PK 11195 solution for injection seems to have a high potential for the in vivo study of the peripheral-type benzodiazepine receptors in the living human by means of positron emission tomography (PET).

Animals

Blood cadmium levels in the populations of 3 Chinese cities.

Blood samples were collected from male and female factory workers aged greater than or equal to 16 years (with no occupational exposure to metals including cadmium) in the 3 cities of Hefei (323 subjects), Shenyang (78 subjects), and Jinxi (137 subjects) in China from 1985 to 1987. The samples were analyzed for cadmium in a single laboratory by automated flameless atomic absorption spectrophotometry under strict quality control. The effect of smoking was evident in Hefei, Shenyang and Jinxi, while the effect of aging was not apparent. There were no sex or regional differences in blood cadmium levels in non-smokers in the 3 cities (e.g., 1.2, 1.3 and 1.4 micrograms/l as geometric means in non-smoking women in Hefei, Shenyang and Jinxi, respectively). There was general agreement in blood cadmium levels between the present results and the values reported in the literature, although the latter values were generally based on small study populations.

Adult

Urinary t,t-muconic acid as an indicator of exposure to benzene.

A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit (less than 0.1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5.0 mg/l as a non-corrected value) was higher than the 97.5%-tile values for the non-exposed (1.4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene.

Air Pollutants, Occupational

Excretion of 1,2,4-benzenetriol in the urine of workers exposed to benzene.

Urine samples were collected from 152 workers (64 men, 88 women) who had been exposed to benzene, 53 workers (men only) exposed to a mixture of benzene and toluene, and 213 non-exposed controls (113 men, 100 women). The samples were analysed for 1,2,4-benzentriol (a minor metabolite of benzene) by high performance liquid chromatography. The time weighted average solvent exposure of each worker was monitored by diffusive sampling technique. The urinary concentration of 1,2,4-benzentriol related linearly to the intensity of exposure to benzene both in men and women among workers exposed to benzene, and was suppressed by toluene co-exposure among male workers exposed to a mixture of benzene and toluene. A cross sectional balance study in men at the end of the shift of a workday showed that only 0.47% of benzene absorbed will be excreted into urine as 1,2,4-benzenetriol, in close agreement with previous results in rabbits fed benzene. The concentration of 1,2,4-benzenetriol in urine was more closely related to the concentration of quinol than that of catechol. The fact that phenol and quinol, but not catechol, are precursors of 1,2,4-benzentriol in urine was further confirmed by the intraperitoneal injection of the three phenolic compounds to rats followed by urine analysis for 1,2,4-benzenetriol.

Animals

Hepatitis B virus infection among women in a shoe factory in Korea.

One hundred and sixty five Korean women in a shoe factory in Masan, Korea were evaluated on hepatitis B virus infection by solid-phase radioimmunoassay in 1986. The participants were women of child-bearing ages, mostly in 20's and 30's. About two thirds (105/165) of the subjects had serological evidence of past or present hepatitis B virus infection, and 17% (28/165) were HBsAg-positive. In view of possible risk of vertical transmission of hepatitis B virus, further epidemiological study was considered necessary to establish preventive measures.

Adolescent

[Comparative effects of traditional Chinese medicines (dai-saiko-to, hatimi-zio-gan and byakko-ka-ninzin-to) on experimental diabetes and hyperlipidemia].

In order to clarify the anti-hyperglycemic and anti-hyperlipidemic actions of traditional Chinese medicines, experiments were carried out with experimentally diabetic rats induced by cyproheptadine treatment. The following results were obtained: 1) Dai-saiko-to decreased the blood glucose level at 30, 60 and 120 min after glucose loading in the tolerance test; and the drug tended to increase serum insulin level and increased the ratio (glucose/insulin) at 120 min after the glucose loading. A significant decrease in serum total cholesterol was observed in the high fat diet-treated rats. 2) Hatimi-zio-gan also decreased the blood glucose level at 30 and 120 min after glucose loading. The drug did not lower the serum insulin, but rather increased the glucagon level at 120 min after the loading. The serum lipid level was not reduced by the drug. 3) Byakko-ka-ninzin-to also increased serum glucagon at 120 min, but no change of glucose and lipid in the sera under the above experimental conditions was observed. Such experimental results suggest that Dai-saiko-to might exert an effect that can improve the pathological conditions of diabetes mellitus.

Animals

Hemodynamic evaluation and morphological changes of right ventricular out-flow tract and pulmonary valve after balloon pulmonary valvuloplasty.

Balloon pulmonary valvuloplasty (BPV) was attempted in 38 cases of congenital pulmonary valve stenosis. It was effective and was done without complication in 36 cases, however it was not effective in two cases of pulmonary valve dysplasia. The balloon used was 20-50% larger in diameter than the pulmonary valve annulus. In the seven cases in which the transvalvular pressure gradient was above 100 mmHg on cardiac catheterization, right ventriculography demonstrated that the functional obstruction of the right ventricular outflow tract increased immediately after BPV, however it subsequently improved at one year after the procedure. At between one and three months after BPV, two-dimensional echocardiography demonstrated that the morphological obstruction to the right ventricular outflow tract had diminished. In two cases, localized right ventricular septal hypertrophy with severe pulmonary valve stenosis was observed by two-dimensional echocardiography and right ventriculography, and persisted at one year. In all cases, two-dimensional echocardiography and angiography demonstrated doming pulmonary valves with valve stenosis, which was diminished by BPV. The pulmonary valve morphology was observed by two-dimensional echocardiography in three cases following BPV. In one case, partial relief of pulmonary valve obstruction was seen to be due to commissural splitting and in the other two, to tearing of cusp tissue. Inspection of the pulmonary valve at operation was made in one case who underwent elective surgery for repair of an atrial septal defect which was associated with pulmonary valve stenosis. It demonstrated partial relief of pulmonary valve stenosis by tearing of cusp tissue. In conclusion, BPV is as effective a treatment for congenital pulmonary valve stenosis as open valvulotomy. In our follow-up study, it has shown no apparent complications. The transient obstruction in the right ventricular outflow tract immediately after BPV improved within one month and improved further after three months and one year. However, in the more long-standing cases the localized right ventricular septal hypertrophy persisted and these cases will require, a long term follow-up.

Blood Pressure

[Age-related decrease of 11C-N-methylspiperone in vivo binding to human striatum detected by PET].

The effect of aging on 11C-N-methylspiperone binding to living human striatum was demonstrated using positron emission tomography. The 11 normal volunteers (22 to 72 years old) participated in this study. The uptake of 11C-N-methylspiperone in the brain following intravenous injection was highest in the striatum in individual subject. And the uptake in the striatum only gradually increased until the end of the study. The uptake of 11C-N-methylspiperone in cerebellum peaked within 10 minutes following injection and then rapidly dropped. The association rate constant "k3" was calculated from the slope of the radioactivity-ratio of striatum to cerebellum versus the equivalent time. The equivalent time was calculated from the radioactivity of cerebellum as an input function. The exponential decrease of the k3 value with aging was observed. The k3 value of the youngest subject (22 years old, male) was 0.035/min, while that of the oldest one (72 years old, male) was found to be 0.020/min. These data suggested that the dopaminergic activity through D2 dopamine receptors reduces with aging in human striatum.

Adult

[Valvular regurgitation in patients with Kawasaki disease and in healthy children: a pulsed Doppler echocardiographic study].

Valvular lesions in the acute stage of Kawasaki disease were observed using pulsed Doppler echocardiography. The subjects consisted of 65 patients with Kawasaki disease (2 months-6 2/12 years) who had been followed from the acute stage. The age-matched 113 controls were selected from 661 healthy children (2 months-14 years of age). In the acute stage of Kawasaki disease, tricuspid regurgitation (TR) was detected in 31 (48%), pulmonary regurgitation (PR) in 22 (34%) and mitral regurgitation (MR) in 17 (26%). There was no aortic regurgitation (AR). In the convalescent stage, TR was found in 26 (40%), PR in 20 (31%), and MR in 11 (17%), but no AR was detected. The incidence of each valvular regurgitation between the acute and convalescent stages in patients with Kawasaki disease did not differ significantly. Furthermore, there was no significant difference in the incidence of valvular regurgitation between patients with Kawasaki disease and the normal controls. In nine patients, however, valvular regurgitation in the acute stage had disappeared by the convalescent stage, and two patients had developed a new pansystolic murmur in the acute stage. We estimated the incidence of pathologic valvular involvement in Kawasaki disease to be 11/65 (17%). The incidence of valvular involvement in patients with coronary artery aneurysms was significantly higher than that of patients without coronary artery aneurysms (p less than 0.01). It was concluded that mild and transient valvular regurgitation, which cannot be detected by auscultation, may occur in some patients in the acute stage of Kawasaki disease. These may be caused by acute inflammation of the valve related to coronary artery lesions. In view of the Doppler echocardiographic findings in normal controls, these regurgitations should be distinguished from "physiological" ones.

Acute Disease

Blood lead levels of the general populations of three Chinese cities.

Blood samples were obtained from 537 adults (age greater than or equal to 16 years) living in three cities in China; in Hefei in 1985, and in Shenyang and Jinxi in 1987. The samples were subjected to blood lead (Pb-B) analyses. The subjects were factory workers either in solvent-synthesizing or solvent application plants with no known exposure to metals (including lead). Their smoking and drinking habits were confirmed in medical interviews. Blood lead was significantly higher in smokers than in non-smokers, although no dose-dependency was observed. The Pb-B values in non-smokers were log-normally distributed. The Pb-B among non-smokers was significantly higher in men [104.0 micrograms l-1 (1.428) 87] [geometric mean (geometric standard deviation) number of determinations] than in women [75.5 micrograms l-1 (1.358) 225] when the data from the three cities were combined. There was a significant difference in the Pb-B levels of non-smoking men in the three cities studied, suggesting that regional food habits should be considered as a possible contributory factor of a non-occupational nature. The present findings are compared with observations from Korea and Japan from the viewpoint of environmental health.

China

Mutual metabolic suppression between benzene and toluene in man.

The exposure intensity during a shift and the metabolite levels in the shift-end urine were examined in male workers exposed to either benzene (65 subjects; the benzene group), toluene (35 subjects; the toluene group), or a mixture of both (55 subjects; the mixture group). In addition, 35 non-exposed male workers (the control group) were similarly examined for urinary metabolites to define background levels. A linear relationship was established between the intensity of solvent exposure and the corresponding urinary metabolite levels (i.e. phenol, catechol and quinol from benzene, and hippuric acid and o-cresol from toluene) in each case when one of the three exposed groups was combined with the control group for calculation. Comparison of regression lines in combination with regression analysis disclosed that urinary levels of phenol and quinol (but not catechol) were lower in the mixture group than in the benzene group when the intensities of exposure to benzene were comparable, indicating that the biotransformation of benzene to phenolic compounds (excluding catechol) in man is suppressed by co-exposure to toluene. Conversely, metabolism of toluene to hippuric acid was suppressed by benzene co-exposure. Conversion of toluene to o-cresol was also reduced by benzene, but to a lesser extent. The significance of the present findings on the mutual suppression of metabolism between benzene and toluene is discussed in relation to solvent toxicology and biological monitoring of exposure to the solvents.

Air Pollutants, Occupational

Changes in in vivo binding of 3H-Ro 15-1788 in mouse brain by reserpine.

The effects of reserpine on the in vivo binding of 3H-Ro 15-1788, (Ro 15-1788:ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5a][1,4]benzodiazepine-3-carboxylate) a selective benzodiazepine antagonist, in the mouse brain were investigated. The biodistributions of tracer amounts of 3H-Ro 15-1788 in mice were significantly altered by pretreatment with reserpine (2.5 or 5.0 mg/kg, 24 h before the tracer administration). The time courses of radioactivity in the brain and the blood following i.v. injection of 3H-Ro 15-1788 with carrier Ro 15-1788 were not changed by pretreatment with reserpine, which suggested that the specific binding process might be altered by reserpine. The degree of alteration in the in vivo binding of 3H-Ro 15-1788 seemed to be dependent upon the dose of reserpine and the duration after the treatment of reserpine. The maximum changes in the biodistribution of 3H-Ro 15-1788 were observed at 1 day after injection of reserpine. The body temperature and the brain monoamine contents (dopamine, norepinephrine and 5-hydroxytryptamine) in mice were measured as indicators of pharmacological effects of reserpine, and good relationships to the degree of changes in the biodistribution of 3H-Ro 15-1788 and either the body temperature or brain monoamine contents, were observed. Furthermore, the changes in the biodistribution of 3H-Ro 15-1788 in the reserpinized mice were significantly suppressed by anti-depressant imipramine treatment. These results suggest that it would be possible to detect the in vivo drug interaction with brain benzodiazepine receptors in the living human brain using 11C-Ro 15-1788 and positron emission tomography (PET).

Animals

Determination of catechol and quinol in the urine of workers exposed to benzene.

Time weighted average concentrations of benzene in breathing zone air (measured by diffusive sampling coupled with FID gas chromatography) and concentrations of catechol and quinol in the urine (collected at about 1500 in the second half of a working week and analysed by high performance liquid chromatography) were compared in 152 workers who were exposed to benzene (64 men, 88 women). The concentration of urinary metabolites was also determined in 131 non-exposed subjects (43 men, 88 women). There was a linear relation between the benzene concentrations in the breathing zone and the urinary concentrations of catechol and quinol (with or without correction for urine density) in both sexes. Neither catechol nor quinol concentration was able to separate those exposed to benzene at 10 ppm from those without exposure. The data indicated that when workers were exposed to benzene at 100 ppm about 25% of benzene absorbed was excreted into the urine as phenolic metabolites, of which 13.2%, 1.6%, and 10.2% are phenol, catechol, and quinol, respectively.

Benzene