Symptoms and signs of workers exposed to benzene, toluene or the combination.
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Biomedical subjects
Publications and source records attributed to O Inoue.
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Carbon-11-labeled N,N-dimethylphenylethylamine ([11C]DMPEA) was synthesized by the reaction of N-methylphenylethylamine with [11C]methyl iodide. This newly synthesized radiotracer was developed for the purpose of in vivo measurement of monoamine oxidase-B activity in the brain using a metabolic trapping method. Initially, biodistribution was investigated in mice. The rapid and high uptake of 11C radioactivity in the brain was observed following intravenous injection of [11C]DMPEA, the peak of which was reached at 1 min, followed by a decrease at 1-5 min and slowly thereafter. The kinetics of [11C]DMPEA in the human brain were determined using positron emission tomography (PET) and showed that 11C radioactivity increased gradually over 60 min following initial rapid uptake of 11C radioactivity, with basal ganglia and thalamus showing high accumulation.
Toluene metabolism was studied in 192 Chinese workers in comparison with that in 130 Japanese and 17 Turks. Time-weighted average concentrations of toluene in the breathing zone of workers were measured utilizing passive dosimeters, and hippuric acid (HA) and omicron-cresol (omicron C) concentrations in shift-end spot urine samples by high-performance liquid chromatography (HPLC) and gas chromatography (GC), respectively. Under similar exposure conditions, male Japanese excreted almost twice as much HA as male Chinese, although such difference was less marked between female Chinese and Japanese. In contrast, the excretion of oC did not differ between the two ethnic groups. The ratio of oC over HA was highest among Turkish workers followed by Chinese, and lowest among Japanese. Possible roles of differences in toxicogenetics as well as in life patterns were discussed.
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In this study the morphological changes in the livers of marmosets inoculated with stool extracts from epidemic non-A, non-B hepatitis patients in India were examined. The histologic changes of epidemic non-A, non-B hepatitis in marmosets consisted mainly of round cell infiltration in the portal tracts, spotty liver cell necrosis, sinusoidal lymphocyte infiltration, and Kupffer cell mobilization. By electron microscopy, liver cells from infected marmosets showed cisternal dilation of the endoplasmic reticulum, irregularly-shaped nucleus, and disorganization of the mitochondrial cristae. In some areas interaction of lymphocytes with hepatocytes was observed. Similar observations have been made in type B hepatitis infection, presumably due to liver cell damage mediated by immune mechanisms. The result of our study is also compatible with the interpretation that the liver cell damage in this experimental model may be mediated by immune mechanisms.
Urine samples were collected from 64 men and 88 women in shoe factories and printing plants at the end of a seven hour day shift in the latter half of a week in spring. Urine samples were also taken from 43 men and 88 women in the same factories but who were not exposed to solvents. Exposure to benzene during the shift was monitored by passive dosimeters. Both phenol in urine and benzene in activated carbon were analysed with FID gas chromatographs. The urinary concentrations of phenol were linearly related to the time weighted average concentrations of benzene in the breathzone air; the variation was so small that those exposed to 10 ppm benzene could be separated from the non-exposed at least on a group basis when the phenol concentration was corrected either for creatinine concentration or for specific gravity. The urinary phenol concentrations corresponding to 10 ppm benzene were 47.5 mg/l (as observed), 57.9 mg/g creatinine, or 46.6 mg/l (specific gravity 1.016).
Using 11C-labeled Ro15-1788 and positron emission tomography, studies of benzodiazepine binding sites in the human brain were performed on four normal volunteers. Rapid and high accumulation of 11C activity was observed in the brain after i.v. injection of [11C]Ro15-1788, the maximum of which was within 12 min. Initial distribution of 11C activity in the brain was similar to the distribution of the normal cerebral blood flow. Ten minutes after injection, however, a high uptake of 11C activity was observed in the cerebral cortex and moderate uptake was seen in the cerebellar cortex, the basal ganglia, and the thalamus. The accumulation of 11C activity was low in the brain stem. This distribution of 11C activity was approximately parallel to the known distribution of benzodiazepine receptors. Saturation experiments were performed on four volunteers with oral administration of 0.3-1.8 mg/kg of cold Ro15-1788 prior to injection. Initial distribution of 11C activity following injection peaked within 2 min and then the accumulation of 11C activity decreased rapidly and remarkably throughout the brain. The results indicated that [11C] Ro15-1788 associates and dissociates to specific and nonspecific binding sites rapidly and has a high ratio of specific receptor binding to nonspecific binding in vivo. Carbon-11 Ro15-1788 is a suitable radioligand for the study of benzodiazepine receptors in vivo in humans.
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Nitrogen-13-labelled beta-phenethylamine[( 13N]PEA) was synthesized by Hofmann rearrangement of [13N]phenylpropionamide prepared from phenylpropionyl chloride and aqueous [13N]ammonia solution. The reaction proceeded rapidly with a fairly good yield. [13N]PEA was isolated using preparative thin-layer chromatography, and organ distribution in mice was studied preliminarily. After i.v. administration of [13N]PEA, high accumulation and long-term retention of the radioactivity were observed in the brain and the heart.
Ethyl 8-fluoro-5,6-dihydro-5-[11C]methyl-6-oxo-4H-imidazo [1,5-a] [1,4]benzodiazepine-3-carboxylate ([11C]RO 15-1788) has been prepared automatically with high specific activity for in vivo visualization or quantitative analysis of brain benzodiazepine receptors. The yield, radiochemical yield, radiochemical purity and specific activity of the product ready for an i.v. injection were 276 +/- 76 mCi, 50.8 +/- 7.8%, 99.3 +/- 0.3% and 2.9 +/- 0.5 Ci/mumol, respectively, taking an average of the latest 3 runs. The time required was about 25 min. Each product was sufficient to carry out three successive clinical studies by positron emission tomography (PET). All the procedures other than evaporation and filtration at the final stage were carried out with specially designed equipment connected to a central control system for radioisotope production.