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Biomedical subjects

I Matsunaga

Publications and source records attributed to I Matsunaga.

At least 37 records · Page 2Linked to original sources

Direct involvement of hydrogen peroxide in bacterial alpha-hydroxylation of fatty acid.

We have reported that fatty-acid alpha-hydroxylase partially purified from Sphingomonas paucimobilis required NADH and molecular oxygen. In this study, we found that the reaction was greatly inhibited by catalase. Glutathione and glutathione peroxidase also inhibited alpha-hydroxylation, but superoxide dismutase and mannitol did not. Replacement of NADH and molecular oxygen by hydrogen peroxide increased the alpha-hydroxylation activity. In the presence of hydrogen peroxide, molecular oxygen was not required for the activity. These findings suggest that hydrogen peroxide was essential for bacterial alpha-hydroxylase.

Catalase↗

Relationship between induction of macrophage chemotactic factors and formation of granulomas caused by mycoloyl glycolipids from Rhodococcus ruber (Nocardia rubra).

Mycoloyl glycolipids cause granulomas in the lungs, liver, and spleen of mice, but the mechanism is not fully understood. To understand the role of macrophage chemotactic factors (MCFs) in granuloma formation, we prepared various mycoloyl glycolipids with different carbohydrate moieties: trehalose dimycolate (TDM), glucose mycolate (GM), mannose mycolate (MM), and fructose mycolate (FM) from Rhodococcus ruber, and examined the relationship between their MCF induction in peritoneal macrophages and the extent of granuloma formation. The molecular mass of each glycolipid was confirmed by fast-atom-bombardment mass-spectrometry. TDM or GM caused granulomas in the lungs, spleen, and liver of ICR mice, but MM and FM did not. The culture supernatant of peritoneal macrophages stimulated with TDM or GM increased macrophage migration, whereas MM and FM had no chemotactic activity. The activity of interleukin-1 (IL-1) in the supernatant was increased equally by each glycolipid and was therefore not related to chemotaxis. Tumor necrosis factor-alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were not detected in the four supernatants. The TDM-induced MCF was heat-stable, trypsin-labile, and undialyzable. Furthermore, we separated two MCF active fractions from the supernatant of TDM-stimulated macrophages by gel filtration. These factors acted on macrophages but not on neutrophils. Our results suggested that macrophages recognize the sugar moieties of mycoloyl glycolipids and may, in response, generate a MCF that may play an important role in the macrophage or monocyte recruitment which is essential prior to granuloma formation.

Animals↗

Identification of urinary metabolites of human subjects exposed to o-dichlorobenzene.

o-Dichlorobenzene (o-DCB) has adverse effects on the liver and kidney in animals. It also causes some irritation to the eyes and the upper respiratory system in humans. This study aimed to identify urinary metabolites of human subjects exposed to o-DCB. Urine samples were collected from three male workers exposed to o-DCB and were analyzed using a gas chromatograph-mass spectrometer. 2,3- and 3,4-dichlorophenols and 3,4- and 4,5-dichlorocatechols were detected in all the samples. Some amounts of the four metabolites were presumably present as conjugates, because they increased after heating with hydrochloric acid.

Catechols↗

Load on the low back of teachers in nursery schools.

In order to evaluate the load on the low back of teachers in nursery schools, basic activity, working posture, child-lifting, and desk-lifting were analyzed for eight nursery teachers using video recording. The trunk inclination angle (TIA) was also measured continuously during full workshifts for 20 nursery teachers using an inclination monitor. The nursery teachers in the 0-1 (year) age class more often adopted low working postures, "sitting on the floor" and "kneeling," while teachers in the 4-5 age class more frequently adopted high working postures, "standing" and "sitting on a chair." The mean of TIA among all subjects was 20 degrees. The time spent at a TIA of more than 20 degrees represented 43% of the workshift. The mean and time distribution of TIA did not differ between the age classes. The frequency of trunk-lifting from severe bending forward (TIA > 45 degrees) was 86 times/hour on average. The frequency of trunk-lifting was highest in the 0-1 age class. The number of times of child-lifting was 46 in the 0-1 age class, while it was 1 in the 4-5 age class.

Back↗

Changes in the distribution of short-term exposure concentration with different averaging times.

For 10 workers (16 worker-chemical combinations) exposed to organic solvents, the distributions of 7.5-min time-weighted average (TWA) concentrations, 15-min TWAs, 30-min TWAs, and 60-min TWAs were examined by the Shapiro-Wilk W test and by plotting the TWA values and logarithmic values on probability paper. The hypothesis of normality of 7.5-min TWA and 15-min TWA was rejected for almost all combinations, while the hypothesis of lognormality was rejected only for a few combinations. For 30-min TWAs and 60-min TWAs, the hypothesis of normality was rejected for five and two combinations, respectively, while the hypothesis of lognormality could not be rejected for any of the combinations. The probability plot also showed that TWA values with averaging times of 7.5 to 60 min were approximately distributed in a lognormal manner. Consequently, there was no evidence against using the lognormal distribution to describe the short-term exposure distribution. Results suggest that statistical methods proposed for evaluating exposure conditions based on lognormal distribution can be useful regardless of averaging time. The appropriateness of estimating exposure distribution with different averaging times by Larsen's equations was also examined using 16 combinations. The geometric mean and geometric standard deviation estimated by Larsen's equations were nearly equal to those estimated by the traditional equations' average, but the difference of the two estimates in each case tended to be large when the ratio of the new averaging time to the original one was large.

Chemical Industry↗

Effect of variation of exposure to airborne chlorobenzene on internal exposure and concentrations of urinary metabolite.

OBJECTIVES: This study aimed to develop a physiologically based pharmacokinetic model for chlorobenzene and to investigate the effect of variation in exposure to chlorobenzene on the chlorobenzene concentration in blood and the urinary concentration of 4-chlorocatechol. METHODS: A physiologically based pharmacokinetic model was developed and the simulated results of urinary 4-chlorocatechol concentrations were compared with the values found in experiments and field surveys. The area under the chlorobenzene concentration-time curve in blood (CBBauc) was selected as the measure of internal exposure related to the chronic effect of chlorobenzene. The maximum one-hour time weighted average value of chlorobenzene concentration in blood (CBBmax) was chosen as the measure of internal exposure related to the acute effect of chlorobenzene. The total amount of urinary 4-chlorocatechol (TOTCC) and that excreted during the last four hours (CC(4-8)) or two hours (CC(6-8)) of exposure as well as that excreted during two hours on the next morning (CC(22-24)) were used to represent concentrations of urinary metabolites. The effects of variation of the one-hour time weighted averages of airborne chlorobenzene exposure (CBAs) on the internal exposures and the concentrations of urinary metabolites were investigated with the pharmacokinetic model. RESULTS: The comparison of the simulated results with the observed data showed that the pharmacokinetic model can be used to estimate the urinary concentrations of 4-chlorocatechol. The CBBauc and TOTCC were not affected by changes in both the geometric SD (GSD) of CBAs or the variations in CBAs. The CBBmax varied with changes in both the GSD and CBAs. The CC(4-8) and CC(6-8) did not vary with the GSD, but these concentrations were affected by the change in the CBAs. Although there was little effect of the GSD and CBAs on the CC(22-24), this value highly reflected the exposure over the preceding days. CONCLUSION: To protect workers from the chronic effect of chlorobenzene, it may be sufficient to control the daily average exposure. To protect from the acute effect, however, the short term exposure must be controlled as well. The values of CC(4-8) and CC(6-8) were acceptable for estimating daily average exposure, but the CC(22-24) was not.

Adipose Tissue↗

Physiologically based pharmacokinetic model for acetone.

OBJECTIVE: This study aimed to develop a physiologically based pharmacokinetic model for acetone and to predict the kinetic behaviour of acetone in the human body with that model. METHODS: The model consists of eight tissue groups in which acetone can be distributed: the mucous layer of the inhaled air tract, the mucous layer of the exhaled air tract, a compartment for gas exchange (alveolus of the lung), a group of blood vessel rich tissues including the brain and heart, a group of tissues including muscles and skin that have low perfusion rates, a group of fatty tissues, an organ for metabolism (liver), and a compartment for urinary excretion (kidney). A mucous layer in the model is only the outermost layer of the mucus lining the wall of the air tract during inhalation and exhalation. To check the relevance of the model, the simulated results were compared with the experimental data. Next, simulation was conducted by changing the volume of the mucous layer and the respiratory rate to clarify the effect of these variables. Finally, simulation of an occupational situation was performed. RESULTS: With an appropriate value for the volume of mucous layer, the simulated acetone concentrations in arterial blood, end exhaled air, urine, and fatty tissue were found to agree well with the experimental data. The volume of mucous layer and rate of respiration were critical for the appropriate simulation. The simulated occupational situation fitted the observed regression line in field studies quite well. The simulation also enabled predictions to be made about the characteristic kinetics for water soluble solvents. CONCLUSION: The model is useful for understanding and explaining the kinetics of acetone.

Absorption↗

Idiopathic colonic phlebitis with massive ascites.

We describe a 35-year-old woman with colonic phlebitis of unknown origin accompanied by effusion of serum protein into the peritoneal cavity. Abdominal ultrasonography and computed tomography showed massive ascites and edematous wall thickness of the colon. Laboratory examination of the peritoneal fluid showed a high concentration of protein, probably due to nonselective efflux of serum protein. The main histopathological finding was extensive edema of the submucosa with vasculitis in the colon. This kind of phlebitis with massive ascites, but without systemic involvement, and with the ascitic fluid almost identical to the serum protein level, has not been reported previously.

Adult↗

Separation and partial characterization of soluble fatty acid alpha-hydroxylase from Sphingomonas paucimobilus.

The crude extracts from Sphingomonas paucimobilus containing 2-hydroxy fatty acid-rich sphingolipids were found to oxidize [1-14C]-myristate to 2-hydroxymyristate in the presence of NADH. The myristate-oxidation activity was partially purified about 290-fold from the cell-free extracts by ammonium sulfate fractionation and hydroxylapatite chromatography. When laurate, myristate, and palmitate were used as the substrates, the reaction products were identified as the corresponding 2-hydroxy fatty acids by gas-chromatography (GC), HPLC, and GC-mass spectrometry. The enzyme preparation required NADH and molecular oxygen for its alpha-hydroxylation activity, suggesting that the bacterial alpha-hydroxylation is typical of monooxygenase reactions. Of fatty acids tested, myristate was the most efficient substrate.

Bacteria↗

Approaches for estimating the distribution of short-term exposure concentrations for different averaging times.

Because the distribution of short-term exposure concentrations is approximately log-normal within 1 day, the geometric mean (GM) and geometric standard deviation (GSD) are critical parameters for obtaining the overall view of exposure, but when the averaging time changes, so too do the GM and GSD, though the arithmetic mean (AM) should be fixed. For industrial hygienists the ability to transform the GM and GSD from one averaging time to another is very useful. Three approaches for estimating the GM and GSD for different averaging times were applied to 10 workers (16 worker-chemical combinations). The random approach is based on the assumption that exposure concentrations vary randomly over time. On the other hand, two autocorrelation approaches are based on an assumption that the exposure time series are autocorrelated. This study showed that the random approach tended to lead to positive-biased and negative-biased estimates for the GM and GSD, respectively. The two types of the autocorrelation approach generally gave unbiased estimates, but the dispersions of the estimates became large when the ratio of the new averaging time to the original one was large.

Humans↗

Concentrations of urinary metabolites in workers exposed to monochlorobenzene and variation in the concentration during a workshift.

Urinary concentrations of metabolites of monochlorobenzene were examined in 10 male workers exposed to the compound while synthesising intermediate products for dyes. Their individual exposure concentrations were monitored for the whole workshift and samples of urine were collected at the start and end of the workshift, during it, and during the noon recess. The concentrations of four metabolites, 4-chlorocatechol and o-, m-, and p-chlorophenol, in the urine samples were measured. The investigation was performed on Monday and Tuesday in one week and on Tuesday and Wednesday in another week. The concentrations of 4-chlorocatechol in urine collected during the last four hours and at the end of the workshift were proportional to the eight hour time weighted average exposure to monochlorobenzene. The concentration in urine collected during the noon recess showed a linear correlation with the four hour time weighted average in the morning. Similarly, linear relations were obtained for urinary p-chlorophenol. The ratio (as monochlorobenzene) of p-chlorophenol to 4-chlorocatechol concentrations at the start of the workshift was 0.39 and at the end of the workshift was 0.22. The ratios of the urinary concentrations 15 hours after exposure to those at the end of exposure were 0.24 for 4-chlorocatechol and 0.44 for p-chlorophenol. The present study also showed that variations in exposure at the workplace were reflected by changes in concentrations of urinary metabolites during the workshift.

Adult↗

Autocorrelation of short-term and daily average exposure levels in workplaces.

Based on workplace exposure data for 16 worker-chemical combinations, the degree of autocorrelation in a series of short-term time-weighted average (TWA) exposure concentrations (7.5-min, 15-min, 30-min, and 60-min TWAs) was investigated. For 7.5-min and 15-min TWAs, consecutive values generally exhibited no correlation or positive correlation, but not negative correlation. Consecutive 30-min TWAs and 60-min TWAs showed either positive correlation, negative correlations, or no correlation. Autocorrelation functions displayed various patterns that depended on the exposure time series. The mean of the autocorrelation coefficients across all worker-chemical combinations was similar to an exponential function, which signifies that the degree of autocorrelation, on average, decreased as the interval between two averaging periods increased. Autocorrelation in a series of 8-hr TWAs also was analyzed for 10 worker-chemical combinations. In general, little autocorrelation was observed. Based on this analysis, the authors discuss a sampling strategy that, on average, would minimize the degree of correlation between measurements of short-term TWAs.

Chemical Industry↗

The development of a revolving personal sampler.

The American Conference of Governmental Industrial Hygienists recommends the use of threshold limit value-short-term exposure limit (TLV-STEL) and ceiling limit (TLV-C) as guide-lines to prevent workers from irritation, chronic or irreversible tissue damage, and narcosis caused by intense exposures to hazardous substances for short periods. To evaluate whether a worker's exposure level is within the specified limit, it is desirable to measure every 15-min time-weighted average concentration (15-min TWA) during a workday. The authors developed a revolving personal sampler that can collect consecutive short-term exposure samples. A recovery test of toluene of various concentrations was conducted by using this sampler. Toluene concentrations in the test atmosphere were 10, 50, 100, 200, and 400 ppm. The test results showed that the mean recovery at each concentration was 97.7% to 100.0%, and the coefficient of variation was 0.008 to 0.015. The revolving personal sampler can be used to monitor every 15-min TWA of a worker.

Air Pollutants, Occupational↗

Fluctuations of occupational exposure indices to mixtures.

In workplaces, two or more hazardous substances are often used simultaneously. Daily average exposure to each can vary considerably from day to day, and thus indices (Emix) combining exposures to all substances used must vary in a more complex manner. In this study, we examined the between-days distributions of Emix using occupational data for five workers exposed to two or more organic solvents, and found Emix to be log-normally distributed. To describe the between-days fluctuation of Emix, we propose a new model in which the causes of fluctuation were classified as a Specific Factor and a Common Factor. We also present a new method for estimating the distribution of Emix. The usefulness of our new model and new method is shown by their application to actual data.

Air Pollutants, Occupational↗

[Assessment of occupational exposures to industrial hazardous substances. V. A proposed method for evaluating employee's exposure averages (8-h TWAs) using a single day measurement].

Daily exposure averages (8-h TWAs) to hazardous substances may vary considerably day to day, even though a worker is engaged in the same job. Previously we proposed a method to evaluate a long-term exposure condition with interday fluctuation using some exposure measurements. As it is assumed that 8-h TWAs are log-normally distributed, geometric standard deviation (sigma g) representing true interday fluctuation of 8-h TWAs should be estimated. If a single day's 8-h TWA of a worker is measured, sigma g of his own distribution of 8-h TWAs cannot be estimated. Therefore, to evaluate a long-term condition using a single day's 8-h TWA, representative sigma g in all industrial workplaces must be determined beforehand. To investigate sigma g observed in many industrial workplaces, two days' 8-h TWAs of each worker were measured in a week on 260 workers exposed to 19 hazardous substances. Sg2 (geometric standard deviation estimated by two samples) ranged from 1.00 to 8.22 with a median of 1.47 and a 90% upper limit of 2.47. Transforming Sg2 into sigma g, median and 90% upper limit of sigma g were 1.75 and 2.47, respectively. According to a classification scheme in the proposed method, exposure levels (I to III) were calculated using sigma g of 1.75 and 2.47. A long-term exposure condition to hazardous substances can be evaluated by comparing a single day's 8-h TWA with the exposure levels.

Environmental Monitoring↗

Computed tomographic findings in relation to event-related potentials during visual discrimination tasks in patients with multiple cerebral infarcts.

Event-related potentials were recorded for 29 patients with multiple cerebral infarcts (MCI) (mean age, 65.7 years) during visual discrimination tasks to clarify the relationship between computed tomographic findings (CT) and P300 component. P300 latency in patients with MCI was significantly longer than that of 15 age-matched normal subjects (mean age, 65.4 years), although no significant difference was found in P300 amplitude between the two groups. There was a significant negative correlation between P300 latency and mental status as determined by the Hasegawa's Dementia Scale. Significant correlation was also found between P300 latency and the degree of ventricular dilatation or severity of periventricular lucency (PVL) on CT scan. P300 latency was not significantly correlated with the number of infarcts. P300 latency in patients with MCI thus appears related to the severity of PVLs and degree of ventricular dilatation in addition to mental status.

Cerebral Ventriculography↗

Mycolyl glycolipids stimulate macrophages to release a chemotactic factor.

We have previously reported that mycolyl glycolipids from Nocardia rubra such as glucose or trehalose mycolates induced granuloma formation in mice. The structure of the carbohydrate moiety of the mycolyl glycolipids influenced the granuloma forming activity profoundly. Here, we have examined the macrophage-chemotactic activity in the culture supernatants stimulated with various glycolipids differing in carbohydrate moiety (trehalose 6,6'-dimycolate, or TDM; glucose monomycolate, or GM; mannose monomycolate, or MM; and fructose monomycolate, or FM). A distinctive chemotactic activity was detected with TDM or GM, but, little or none with MM or FM.

Animals↗