Stable blood cell counts after one-week storage at room temperature.
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Biomedical subjects
Publications and source records attributed to S Horiguchi.
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One hundred and forty-three workers exposed to one or more of toluene, xylene, ethylbenzene, styrene, n-hexane, and methanol at sub-occupational exposure limits were examined for the time-weighted average intensity of exposure by diffusive sampling, and for biological exposure indicators by means of analysis of shift-end blood for the solvent and analysis of shift-end urine for the corresponding metabolite(s). Urinalysis was also performed in 20 nonexposed control men to establish the "background level." Both solvent concentrations in blood and metabolite concentrations in urine correlated significantly with solvent concentrations in air. Comparison of blood analysis and urinalysis as regards sensitivity in identifying low solvent exposure showed that blood analysis is generally superior to urinalysis. It was also noted that estimation of exposure intensity on an individual basis is scarcely possible even with blood analysis. Solvent concentration in whole blood was the same as that in serum in the case of the aromatics, except for styrene. It was higher in blood than in serum in the case of n-hexane, and lower in the cases of styrene and methanol.
A semiautomated head-space gas chromatographic (GC) method was developed for measuring formic acid in urine. The method consists of heating 1 ml urine sample in a 20-ml air-tight vial in the presence of 1 ml sulfuric acid and 2 ml ethanol at 60 degrees C for 30 min for ethyl esterification and air-liquid equilibrium, followed by automatic injection of 1 ml head-space air into a flame ionization detector GC. The detection limit was 1 mg/l for formic acid. The method was applied to measure formic acid in the shift-end urine samples from 88 workers exposed to methanol at 66.6 ppm (as geometric mean) and in urine samples from 149 nonexposed controls. Methanol concentrations were also determined. Regression analysis showed that urinary formic acid concentrations, as observed or corrected for either creatinine concentration or specific gravity of urine (1.016), correlated significantly with time-weighted average intensities of exposure to methanol vapor. Men excreted significantly more formic acid than women. Comparison with methanol excretion suggested, however, that urinary formic acid is less sensitive than urinary methanol as an indicator of methanol vapor exposure, primarily because the background level for formic acid (26 mg/l as arithmetic mean, or 23 mg/l as geometric mean) is more than ten times higher than the level for methanol (1.9 mg/l as arithmetic mean, or 1.7 mg/l as geometric mean). After theoretical methanol exposure at infinite concentration, the urinary formic acid/methanol ratio should be about 0.4.
Exposure of 34 male workers to combined toluene, styrene and methanol was monitored by personal diffusive sampling of solvent vapours in breathing zone air, analysis of shift-end blood for the 3 solvents and analysis of shift-end urine for hippuric, mandelic and phenylglyoxylic acids and methanol. The exposure of most of the workers was below current occupational exposure limits. Regression analysis showed that a linear correlation exists for each of the 3 solvents between any pairs of the concentrations in air, blood and urine. Namely, toluene, styrene and methanol concentrations in blood obtained at the end of a shift are linearly related to the time-weighted average intensity of exposure to corresponding solvents, and also hippuric, mandelic and phenylglyoxylic acids as well as methanol in shift-end urine. The concentrations of hippuric, mandelic and phenylglyoxylic acids as well as methanol in urine correlated with the respiratory exposure intensity. Comparison of the present results with the exposure--excretion relationship after occupational exposure to the individual solvent showed that no modification in metabolism is induced by the combined exposure when exposure is low, as in the present case.
A diffusive sampling method with water as absorbent was examined in comparison with 3 conventional methods of diffusive sampling with carbon cloth as absorbent, pumping through National Institute of Occupational Safety and Health (NIOSH) charcoal tubes, and pumping through NIOSH silica gel tubes to measure time-weighted average concentration of dimethylformamide (DMF). DMF vapors of constant concentrations at 3-110 ppm were generated by bubbling air at constant velocities through liquid DMF followed by dilution with fresh air. Both types of diffusive samplers could either absorb or adsorb DMF in proportion to time (0.25-8 h) and concentration (3-58 ppm), except that the DMF adsorbed was below the measurable amount when carbon cloth samplers were exposed at 3 ppm for less than 1 h. When both diffusive samplers were loaded with DMF and kept in fresh air, the DMF in water samplers stayed unchanged for at least for 12 h. The DMF in carbon cloth samplers showed a decay with a half-time of 14.3 h. When the carbon cloth was taken out immediately after termination of DMF exposure, wrapped in aluminum foil, and kept refrigerated, however, there was no measurable decrease in DMF for at least 3 weeks. When the air was drawn at 0.2 l/min, a breakthrough of the silica gel tube took place at about 4,000 ppm.min (as the lower 95% confidence limit), whereas charcoal tubes could tolerate even heavier exposures, suggesting that both tubes are fit to measure the 8-h time-weighted average of DMF at 10 ppm.
Stoichiometric conversion of methyl acetate to methanol in vitro was detected when methyl acetate was incubated with blood for 2 to 8 h. The velocity of the reaction was so fast that almost all of methyl acetate disappeared in 8 h. The methanol formation was further confirmed by means of gas-chromatography-mass spectrometry. The capacity to hydrolyze methyl acetate was evenly distributed in cellular and noncellular fractions of blood, but not in urine. The significance of the observation is discussed in relation to biological monitoring of exposure to industrial ester solvents by means of head-space gas-chromatography of blood samples.
An occupational health study was conducted on 45 acetone-exposed male workers in combination with 343 non-exposed men to examine the quantitative relationship between the intensity of acetone vapor exposure and the concentration of acetone in urine. The time-weighted average acetone concentrations were measured by means of diffusive samplers with water as absorbent, whereas urine samples were collected at the end of the shift as well as before the shift on the next morning. Acetone concentration in shift-end urine did not increase when the workers were exposed to acetone up to approx. 15 ppm, and this was followed by a gradual increase at a higher atmospheric acetone concentration, in a manner dependent to acetone vapor concentration. The comparison in acetone concentrations between the urine samples collected at the shift-end and those before the shift of the next morning showed that the levels in two sets of samples were the same among those exposed to 15 or less ppm acetone, whereas acetone in the shift-end samples was significantly higher than the counterpart levels in the pre-shift samples among those exposed to acetone at more than 15 ppm.
Blood and urine samples were collected at the end of an 8-h workshift from 30 male workers exposed to a mixture of n-hexane, ethyl acetate and toluene (each being about 2 ppm as geometric means) and also from 20 nonexposed male workers. Blood samples were analyzed for n-hexane and toluene, and urine samples were analyzed for n-hexane, toluene, 2,5-hexanedione (both with and without hydrolysis) and hippuric acid. Based on the correlation between biological exposure indicators and solvent concentrations in air, sensitivity as an exposure indicator was compared between solvents in blood and solvents or metabolites in urine in terms of the lowest solvent concentration at which the exposed subjects can be statistically separated from the nonexposed. Both n-hexane and toluene in blood were sensitive enough to detect the exposure at 6.1 ppm and 1.4 ppm, respectively. n-Hexane exposure below 2 ppm was detectable also by urinalysis for 2,5-hexadione without hydrolysis. Urinary hippuric acid, however, failed to detect low toluene exposure under the conditions studied. Of additional interest is the fact that toluene in urine correlated significantly with toluene in air, which apparently deserves further study for confirmation.
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A 72-year-old man developed supranuclear ophthalmoplegia, bradykinesia, rigidity, unsteady gait, dementia, dysphagia, retrocollis, grasp reflex and apraxia of eyelid opening. These findings were compatible with progressive supranuclear palsy (PSP). At the age of 66, he presented a peculiar phenomenon characterized by simultaneous tonic contraction of the orbicularis oris muscle (OOM) and the palatal muscles elicited by pronouncing "pa", which resulted in difficulty of voluntary opening of the mouth and the rhinopharynx. Therefore, the respiration air reciprocated between the lung and the closed mouth. The expiratory pressure puffed out the cheeks, while the lips remained tightly closed. While the respiratory movements and the pressure increased by degree, the OOM contracted more strongly in proportion to the pressure. Sixty to ninety seconds after the elicitation, the pressure overcame the contraction of the OOM and the course of the phenomenon was completed. The electromyograms showed that the OOM activity was prolonged after initial voluntary contraction, remaining thus after a tracheostomy for pneumonia at the age of 72, and that it increased in response to the pressure. Apraxia of eyelid opening, one of the other symptoms, resembled this phenomenon in terms of the aspect of difficulty of voluntary mouth opening. The "holding" phase of grasp reflex, yet another symptom, resembled it in the recruitment of the OOM activity. The phenomenon is not common in patients with PSP. However, we concluded that it may be included among the symptoms of PSP because it has similar characteristics to apraxia of eyelid opening and grasp reflex, which are not uncommon in patients with PSP.
The effect of platelet activating factor (PAF) on human paranasal ciliated cells was investigated in vitro. Normal human paranasal sinus mucosa was obtained by surgical procedure and incubated with Eagle's MEM containing 10% FCS in the form of tissue culture. Ciliary activity was viewed at 37 degrees C under an inverted microscope equipped with a thermoregulator and a humidified CO2 chamber, recorded on video tapes and photoelectrically measured. Ciliary inhibition was observed by the treatment with PAF, in a dose dependent manner, at concentrations from 10(-10) M to 10(-6) M. The inhibitory effect of 10(-8) M PAF on ciliary activity was completely blocked when the mucosa was treated with 10(-6) M CV-3988 or 10(-6) M CV-6209 (specific PAF receptor antagonists). By the radioimmunoassay, the concentration of PAF in tissue culture was reduced by half within 12.5 min, and within 60 min it was only 5% of the initial concentration. There was no significant difference in ciliary inhibition between irrigation after a 60 min incubation with 10(-8) M PAF and non-irrigation. These results indicate that PAF inhibited ciliary activity directly and specifically, and induced irreversible damage primarily within the first 60 min after the challenge.
Serum immunoglobulin and complement C3 levels were measured in workers exposed to lead at a secondary lead refinery and a solder factory. In the first survey, significant correlations were found between blood lead and IgA with a correlation coefficient of 0.296, and between blood lead and IgE with a correlation coefficient of 0.314. No other significant correlations were found among the indicators of lead exposure and humoral immunity. In the second survey, no significant correlations were found between blood lead and IgG and IgA. A significantly higher number of subjects with IgE of more than 400 IU/ml was found in the group with blood lead of more than 60 micrograms/100 g.
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Intracisternal administration of PGD2 (5 micrograms) and PGE2 (5 micrograms) induced hypoalgesia in conscious mice in acetic acid writhing test. The hypoalgesia caused by PGD2 was blocked by para-chlorophenylalanine, cyproheptadine or phenoxybenzamine. However, the suppression of writhing responses caused by PGE2 was not blocked at all by these drugs. These results indicate that the actions of PGD2 depend upon serotonin and norepinephrine systems.
The apparent amount of 2,5-hexanedione, a biomarker of n-hexane expsoure in occupational health, in the urine of both exposed and non-exposed subjects varied not only as a function of the pH at which the urine sample was hydrolyzed but also depending on the capillary column used for gas chromatographic (GC) analysis of the urinary hydrolyzates after extraction with dichloromethane. The formation of a compound, identified by gas chromatography-mass spectrometry (GC-MS) as 2-acetylfuran, following acid hydrolysis was a major cause of confounding effects. This compound was hardly separated from 2.5-hexanedione on a capillary column such as DB-WAX, whereas separation could be achieved on a DB-1 capillary column. 2-Acetylfuran was formed when a urine sample was heated at a pH of less than 2 for hydrolysis, and the amount detected in urine did not differ between exposed and non-exposed subjects, indicating that the formation of 2-acetylfuran is independent of n-hexane exposure. When urinary hydrolysis is used, hydrolysis at a pH of less than 0.5, extraction with dichloromethane, and GC analysis on a non-polar capillary column are proposed to be the best analytical conditions for 2,5-hexanedione analysis in biological monitoring of exposure to n-hexane.
The exposure-excretion relationship and possible health effects of exposure to methanol vapor were studied in 33 exposed workers during the second half of 2 working weeks. Urinary methanol concentrations were also determined in 91 nonexposed subjects. The geometric mean value for methanol in urine samples from the latter was less than 2 mg/l (95% upper limit of normal, less than 5 mg/l) when log-normal distribution was assumed. Among the exposed workers, the methanol level in urine samples collected prior to the work shift exceeded the 95% upper limit of normal. The time-weighted average intensity of exposure to methanol vapor was measured using personal sampling devices (in which water severed as an absorbent) in 48 cases of methanol exposure (i.e., 2 of the 33 exposed workers failed to provide urine samples, whereas 17 subjects were examined twice). Methanol concentrations in urine were determined in samples collected at the end of the shift from the 48 exposed cases as well as from 30 nonexposed controls. There was a significant correlation between the exposure to methanol vapor at concentrations of up to 5,500 ppm and the levels of methanol measured in the shift-end urine samples. The calculation indicated that a mean level of 42 mg methanol/l urine (95% confidence range, 26-60 mg/kg) was excreted in the shift-end urine sample following 8 h exposure to methanol at 200 ppm (the current occupational exposure limit). Dimmed vision and nasal irritation were among the most frequent symptoms complained during work. Three cases showing clinical signs of borderline significance were identified.
The concentrations of 2,5-hexanedione (2,5-HD), an n-hexane metabolite, and 2-acetylfuran (2-AF) were measured in urine samples from 123 workers who had predominantly been exposed to n-hexane vapor and 53 workers who had experienced no exposure to solvents. The time-weighted average intensity of exposure to n-hexane vapor was determined by a diffusive sampling method. For biological monitoring of exposure, urine samples were collected late in the afternoon during the second half of a working week and were analyzed in the presence and absence of acid hydrolysis (at pH less than 0.5) for 2,5-HD and 2-AF by gas chromatography on a nonpolar capillary DB-1 column. The urinary 2,5-HD concentration increased as a linear function of the intensity of exposure to n-hexane, showing a correlation coefficient of 0.64-0.77 after acid hydrolysis and that of 0.73-0.83 in the absence of hydrolysis, depending on the correction for urinary density (P less than 0.01 in all cases, with no improvement in the coefficient occurring after the corrections). In contrast, 2-AF levels were independent of n-hexane exposure. The geometric mean 2,5-HD concentration in urine samples from 53 nonexposed men was 0.26 mg/l as observed (i.e., with no correction), 0.19 mg/l after correction for a urinary specific gravity of 1.016, and 0.23 mg/g creatinine after correction for creatinine concentration, and the geometric standard deviation was approximately 2.