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Biomedical subjects

K Fujishiro

Publications and source records attributed to K Fujishiro.

At least 37 records · Page 2Linked to original sources

Liver injury induced by dichloropropanols--changes in the time course on hematological and blood chemical examinations.

The toxicity of dichloropropanols (DCPs) was investigated by hematological and blood chemical examination. Solutions of two isomers of DCPs, 1,3-dichloro-2-propanol (DC2P) and 2,3-dichloro-1-propanol (DC1P) were dissolved in saline at a concentration of 100 mg/ml and 0.1 ml of each was subcutaneously injected into male Wistar rats weighing about 200 g. Acute changes on transaminases and number of platelets were determined in the time course. 6 hours later, transaminases showed significant increases while the number of platelets significantly decreased in the DC2P-treated group. In the half the of DC2P-treated group, transaminases had increased furthermore at 24 hours, while those in the rest were recovered to the control level. No changes were observed in the DC1P-treated group. These results indicate that there is a prominent hepatotoxicity in DC2P, with the individual diversities to some extent and the hepatic toxicity differs considerably between DC2P and DC1P. Therefore, the monitoring of the working environment and biological monitoring of DCPs should be mandatory, in the workplace where DCPs, especially DC2P, are utilized.

Alanine Transaminase↗

Liver injury and alterations of hepatic microsomal monooxygenase system due to dimethylformamide (DMF) in rats.

The effects of repeated exposure to N, N-dimethylformamide (DMF) on the liver and the hepatic microsomal monooxygenase system were investigated. DMF was administered to Wistar male rats by subcutaneous (s.c.) injection at 0.5 ml/kg body weight daily for 1-17 days. Macroscopically, mild liver swelling was observed and liver weights significantly increased after 3 days of exposure to DMF respectively. Hematological changes were not observed. In exposed rats, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase significantly increased after 3 and 7 days of exposure to DMF. After 17 days of exposure to DMF, transaminases decreased compared to the 7 days. Hepatic microsomal cytochrome P-450 tended to decrease after 3 days of exposure DMF and decreased by 34% after 7 days and 25% after 17 days. Aminopyrine N-demethylase activity depressed significantly while aniline hydroxylase activity showed no change after 3 days of exposure to DMF. These results indicate that DMF alters the hepatic microsomal monooxygenase system. These findings may greatly contribute to the elucidation of the pathogenesis of DMF hepatotoxicity.

Aminopyrine N-Demethylase↗

Interrelation between urinary delta-aminolevulinic acid (ALA), serum ALA, and blood lead in workers exposed to lead.

Using a fluorometric HPLC method, we determined delta-aminolevulinic acid (ALA) in sera and urine samples from 16 lead workers with blood lead levels ranging from 19 to 107 microG/100 ml. The concentration of ALA in serum correlated highly with the urinary ALA concentration (gamma = 0.957 for ALA mg/1; gamma = 0.967 for ALA mg/g creatinine). The ALA concentrations in the serum of lead workers ranged from 11 to 151 micrograms/1 with a mean of 51 micrograms/1. In addition, the concentrations of urinary ALA (mg/g creatinine) and serum ALA micrograms/1) had a strong correlation with blood lead concentrations (gamma = 0.838 and 0.892, respectively). These data indicate that the measurement of serum ALA, as well as urinary ALA, is very useful for the biological monitoring of occupational lead exposure.

Adolescent↗

A study on cerebral nicotine receptor distribution, blood flow, oxygen consumption, and other metabolic activities--a study on the effects of smoking on carotid and cerebral artery blood flow.

We investigated middle cerebral artery flow velocity (MCA-FV) by a noninvasive method to determine whether or not smoking causes an increase in cerebral blood flow (CBF). Furthermore we determined sequentially the changes in CBF caused by smoking in order to evaluate changes in responses at different times in daily activities and the effect from meals. The subjects were 25 healthy individuals ranging in age from 20 to 36 yr. MCA-FV was measured by a transcranial Doppler system. They smoked a filtered cigarette for 5 min at 1 P.M., 3 P.M., 6 P.M., 8 P.M., 10 P.M., 8 A.M., and 11 A.M. Results (1) Smoking caused increases in both common carotid artery flow volume and MCA-FV, and the percentage increase of these parameters showed a good correlation (r = 0.809). (2) MCA-FV increased significantly during the first (by 6.6%) and second halves (by 5.4%) of the smoking period. (3) The change in MCA-FV after meals was slight. (4) Smoking tended to increase MCA-FV during each smoking session but the changes were not significant. The pulsatility index reduced significantly during almost every smoking session. These results lead to the conclusion that smoking reduces vascular resistance in cerebral arteries and increases CBF.

Adult↗

Reversibility of ethylene oxide-induced testicular damage evaluated by the hemiorchiectomy method.

In the present study, we tried to use the hemiorchiectomy method to examine a reversibility of the testicular damage induced by ethylene oxide (EtO). Wistar male rats were exposed to EtO at a concentration of 500 ppm, 6 hours a day, 3 days a week for 8 weeks. Thereafter we evaluated the reversibility after 13-week recovery period. From the result about a propriety of the hemiorchiecyomy method for recovery study, it was suggested that hemiorchiectomy did not affect remaining testis and epididymis after the recovery period and there was no laterality about the testicular damage just after the exposure period. Therefore we concluded that the hemiorchiectomy method could be used for recovery study for EtO-induced testicular damage. The reversibility was evaluated by comparing the damages of hemiorchiectomized testis just after the exposure period and those of remaining testis removed after the recovery period in the same rat. The result indicated that the reversibility of EtO-induced testicular damage may depend on a degree of damage just after the exposure.

Animals↗

[Effects of ethylene oxide inhalation on mice].

Male ddY mice were exposed to ethylene oxide (EO) at a concentration of 400 ppm, 6 hours a day, 3 days a week for 13 weeks and the effects of EO on the hepatic drug metabolizing enzymes were investigated. The liver and spleen weight per body weight did not change. Compared to the control group, the kidney weight of the exposed group increased while the testis weight decreased significantly. Hematological examination showed macrocytic anemia in the exposed group. Contents of microsomal cytochrome P-450 in the exposed group increased twice as much as that in the control group, while microsomal protein, cytochrome b5, protoheme and NADPH-cytochrome C reductase activity did not change. NADH-ferricyanide reductase activity of the exposed group increased significantly. Among the glutathione related enzymes in the liver, glutathione reductase and glutathione peroxidase activities in the exposed group decreased but glutathione-S-transferase activity increased significantly.

Administration, Inhalation↗

[Fulminant hepatitis after the inhalation of dichloropropanols].

A fatal case of acute fulminant hepatitis following exposure to dichloropropanols is reported. A 59-year-old male worker in a chemical plant developed general malaise, nausea and vomiting several hours after cleaning a tank that had contained dichloropropanols. He had no previous history of hepatic dysfunction. On admission, hepatomegaly was prominent. Because of highly elevated levels of GOT and GPT in the serum, reduced prothrombin time and a lowered consciousness level, a diagnosis of fulminant hepatitis was made. Significant decreases of leukocytes and platelets were also observed. Serum creatinine and BUN were slightly elevated. Although plasma exchanges were conducted on the third and fourth day, the liver functions continued to deteriorate. The patient died on the fifth day. Because dichloropropanols could be detected in the blood specimens obtained at the time of admission, we considered that fulminant hepatitis in this case was attributed to dichloropropanols exposure. To our knowledge, this is the first case of fulminant hepatitis after dichloropropanols-exposure.

Administration, Inhalation↗

[Toxicity of dichloropropanols--changes in hematological findings and serum chemistry].

We investigated the toxicity of dichloropropanols (DCPs) in hematological findings and serum chemistry. The solutions of two isomers of DCPs, 1,3-dichloro-2-propanol (DC2P) and 2,3-dichloro-1-propanol (DC1P) were dissolved in saline at the concentration of 100 mg/ml, and 0.1 ml of each solution was subcutaneously injected into male Wistar rats weighing about 200 g. At 6 hours after the injections, in the DC2P group, the number of white blood cells and platelets showed a significant decrease. Transaminases, alkaline phosphatase and lactate dehydrogenase were greatly elevated. Blood urea nitrogen and creatinine also showed a significant increase. There were no changes in the measurements in the DC1P group. These results indicate that there is a prominent hepatotoxicity in DC2P, and that there is a considerable difference in the toxicity present in DC2P and DC1P. Furthermore, in the workplace where DCPs, especially DC2P, is used, the monitoring of the working environment and biological monitoring should be mandatory.

Alkaline Phosphatase↗

Effects of megadoses of pyridoxine on spermatogenesis and male reproductive organs in rats.

Although it has been indicated that many neurotoxicants also cause reproductive toxicity, the reproductive toxicity of megadoses of pyridoxine, which is a neurotoxicant, has not been studied. In this paper, we studied the effects of megadoses of pyridoxine on male reproductive organs. Pyridoxine hydrochloride, 125 mg/kg, 250 mg/kg, 500 mg/kg or 1000 mg/kg, daily, was intraperitoneally injected into Wistar male rats 5 days a week for 2 or 6 weeks, and its effects on the male reproductive organs were investigated. After 2 weeks of administration, absolute weights of the testis in the 500 and 1000 mg/kg epididymis in all the exposed groups and prostate gland in the 1000 mg/kg group decreased, and mature spermatid counts in the testis decreased in the 1000 mg/kg group. After 6 weeks administration, the absolute and relative weights of the testis, epididymis, prostate gland and seminal vesicle decreased in the 500 mg/kg and 1000 mg/kg groups, and mature spermatid counts in the testis and sperm counts in the epididymis decreased in these groups. Among the marker enzymes of the testicular cells, LDH-X activity decreased, and beta-glucuronidase activity, cytochrome P-450 content and cytochrome b5 content increased in the 1000 mg/kg group. Plasma testosterone concentration did not significantly alter in all the exposed groups. From these results, it was concluded that megadoses of pyridoxine affected the spermatogenesis and decreased reproductive organ weights in the rat.

Animals↗

Effects of dimethylformamide on hepatic microsomal monooxygenase system and glutathione metabolism in rats.

The effects of repeated exposure to N,N-dimethylformamide (DMF) on hepatic microsomal monooxygenase system and glutathione metabolism were investigated. DMF was administered to Wistar male rats by subcutaneous (s.c.) injection at 0.5 ml/kg body weight daily for 1 week. Macroscopically, mild liver swelling was observed and liver weights significantly increased after 1 week of exposure to DMF. Hematological changes were not detected. In exposed rats, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, cholinesterase and total cholesterol significantly increased. Hepatic microsomal cytochrome P-450 and protoheme decreased by 34% and 24%, respectively, while microsomal protein and cytochrome b5 were not affected. NADH-ferricyanide reductase activity decreased by 24% while NADPH-cytochrome c reductase activity showed no change. Glutathione reductase (GR) activity showed a significant decrease after the first injection and remained depressed throughout the study, with no change in glutathione peroxidase (GPx) activity. Glutathione S-transferase (GST) activity showed a significant increase at 3 days after DMF treatment and gradually increased by 66% at 1 week. In a subsequent experiment with a single administration of DMF (4 ml/kg), reduced glutathione (GSH) in the liver was decreased by 28% at 8 h, but recovered to control levels by 24 h. These results indicate that DMF alters the hepatic microsomal monooxygenase system and glutathione metabolism. These findings may greatly contribute to the elucidation of the pathogenesis of DMF hepatotoxicity.

Animals↗

Hyperexpression and analysis of choB encoding cholesterol oxidase of Brevibacterium sterolicum in Escherichia coli and Streptomyces lividans.

We examined the expression of choB, encoding cholesterol oxidase of Brevibacterium sterolicum ATCC 21387, in Escherichia coli JM105 and Streptomyces lividans TK23 using various deletion DNA fragments within the 5'-flanking region. The enzyme activity could be detected intracellularly in E. coli only when the 5'-flanking region was reduced to less than 256-bp and choB was transcribed by the lac promoter. A large amount of the enzyme were produced as inactive inclusion bodies when ChoB protein was fused with the NH2-terminal portion of LacZ protein. In contrast, choB with more than 256-bp of the 5'-flanking region was efficiently expressed in S. lividans TK23, and about 85 times as much of the active enzyme (170 U/ml) was secreted into the culture filtrate as with B. sterolicum in flask culture. These results suggest that the promoter of choB exist within 256-bp of the 5'-flanking region and can be efficiently recognized by the RNA polymerase of S. lividans. The characteristics of the enzyme purified from the culture filtrate of the S. lividans transformant and that of B. sterolicum were identical although the NH2-terminal amino acid sequence of the enzyme from the S. lividans transformant was 6 amino acids shorter than that from B. sterolicum.

Biotechnology↗

[Recovery study from anemia and alterations of glutathione metabolism in erythrocytes induced by chronic inhalation of ethylene oxide].

A study was made on the recovery from anemia induced by chronic exposure of ethylene oxide. When rats were exposed to ethylene oxide at a concentration of 500 ppm, 6 h a day, 3 d a week for 13 wk, macrocytic normochromic anemia with a high reticulocyte count was observed. The hematological values were also evaluated 4 and 13 wk after the end of exposure and the values were found to have already recovered at 4 wk. We reported previously that anemia induced by ethylene oxide was accompanied with a decrease in glutathione reductase activity and instability of glutathione. In this study, alterations of glutathione redox cycle after the end of exposure were examined. The recovery in the decrease of glutathione reductase was slow and the speed of recovery seemed to be dependent on the life span of erythrocytes of the rats. The decrease in glutathione content completely recovered at 4 wk after the exposure. It was concluded from these observations that anemia induced by ethylene oxide is reversible.

Administration, Inhalation↗

[A survey of ethylene oxide sterilization in a hospital].

The health and environmental problems of ethylene oxide gas sterilization in a hospital are reported. Eight nurses who had been engaged in the gas sterilization, sometimes operated the auto-sterilizer in an inadequate manner; they exposed more than several hundred ppm of ethylene oxide once or twice a week. The main acute effects on these nurses after massive exposure were headaches, general fatigue and irritation of the eyes and throat. But no signs of polyneuropathy were seen. This survey suggests that there is a great risk of ethylene oxide poisoning while sterilizing instruments in a hospital.

Ethylene Oxide↗

Sequence of gene choB encoding cholesterol oxidase of Brevibacterium sterolicum: comparison with choA of streptomyces sp. SA-COO.

The nucleotide (nt) sequence of the cholesterol oxidase (Cho)-encoding gene (choB) cloned from Brevibacterium sterolicum ATCC21387 was determined. The sequence contained an open reading frame with a G + C content of 64.9 mol% that would encode a protein of 552 amino acids (aa). Comparison of the nt sequence of choB and deduced aa sequence to those of the Cho-encoding gene (choA) of Streptomyces sp. strain SA-COO showed identities of 64% and 58%, respectively. N-terminal aa sequence analysis of the extracellular enzyme of B. sterolicum confirmed that the mature enzyme consisted of 507 aa with a predicted Mr of 54,902, and was preceded by a 45-aa signal sequence.

Amino Acid Sequence↗

[Effects of ethylene glycol on drug metabolizing enzymes in rat liver].

We investigated the effects of ethylene glycol (EG) on the hepatic drug metabolizing enzymes. The exposed group was given 1% EG solution and the control group was provided with distilled water for 2 weeks ad libitum. The body weight of the exposed group was the same as that of the control group. The liver and kidney weight per body weight did not change. The daily drinking volume for the exposed group on the average showed an increase of 13.5% over that of the control group. Hematologically and biochemically, anemia, liver and renal dysfunction were not seen. The content of the hepatic microsomal cytochrome P-450 in the exposed group showed an increase of 17% over that of the control group, but the contents of cytochrome b5, protoheme and the activities of NADPH-cytochrome c reductase, NADH-ferricyanide reductase did not change. The activities of the hepatic cytosolic alcohol dehydrogenase and glutathione reductase, glutathione peroxidase, glutathione-S-transferase also did not change. These results indicate that the hepatic microsomal cytochrome P-450 takes part in the metabolism of EG.

Animals↗