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Biomedical subjects

K Fujishiro

Publications and source records attributed to K Fujishiro.

At least 55 records · Page 3Linked to original sources

Effects of inhaled ethylene oxide on the lens glutathione redox cycle in rats.

The effects of chronic ethylene oxide (EtO) inhalation on the lens glutathione redox cycle were investigated. When Wistar male rats were exposed to 500 ppm EtO for 6 h a day, 3 times a week for 13 weeks, glutathione reductase decreased significantly in the lens while glutathione peroxidase did not. Glutathione reductase activity decreased time dependently, by as much as 81% after 13 weeks. In spite of changes in the glutathione redox cycle, reduced and oxidized glutathione levels were not affected. Our results raise the possibility that EtO inhalation may produce a cataract via changes in the glutathione redox cycle.

Administration, Inhalation↗

Preventive effects of methylcobalamin on the testicular damage induced by ethylene oxide.

In this study, the effects of methylcobalamin on testicular damage induced by ethylene oxide (EtO) were studied. When Wistar male rats inhaled EtO at 500 ppm, 6 h a day, 3 days a week, for 6 weeks, testicular damage was observed histopathologically and by some other parameters. Subcutaneous injection of methylcobalamin at 500 micrograms/kg, 5 times/week was found to ameliorate the damage. However, the degree of the methylcobalamin effect differed among the parameters examined in this study. Decrease in testicular weight due to EtO exposure was completely prevented by methylcobalamin, and decrease in testicular mature spermatid count and LDH-X activity was fairly well prevented. The degree of prevention of alteration in the epididymis, such as epididymal weight, epididymal sperm count and sperm abnormality rate, was significant but not complete. EtO caused apparent alterations in glutathione metabolism in the testes, but methylcobalamin did not affect such alterations induced by EtO. From these results, it has been determined that methylcobalamin has definite preventive effects on testicular toxicity of EtO.

Animals↗

Dose dependent effects of inhaled ethylene oxide on spermatogenesis in rats.

Male Wistar rats were exposed to ethylene oxide (EO) at concentrations of 50, 100, or 250 ppm for six hours a day, on five days a week for 13 weeks. Dose effect relations of inhaled EO on spermatogenesis were evaluated from testicular and epididymal weights, histopathological changes and lactate dehydrogenase X (LDH X) activity in the testis, and sperm counts and sperm head abnormalities in the epididymis. At 250 ppm, a decrease in epididymal weights, slight degenerations in the seminiferous tubules, decreased sperm counts, and increased numbers of abnormal sperm heads in the tail of the epididymis were found; these were not seen at lower doses. When the abnormal sperm heads were classified into immature types and teratic types, the number of immature heads increased only at 250 ppm. On the other hand, the teratic type had increased at doses of 50 and 100 ppm EO when compared with the control group. Hence, subchronic inhalation of EO at low concentrations affects spermatogenesis in rats.

Alkylating Agents↗

Correlation of common carotid flow volume measured by ultrasonic quantitative flowmeter with pathological findings.

To evaluate the possibility of quantitatively diagnosing carotid and cerebral atherosclerosis noninvasively, we measured common carotid flow volume in 60 sides (30 patients), using an ultrasonic quantitative flowmeter, and then compared these findings to the severity score of carotid and cerebral atherosclerosis as determined at autopsy. Stenosis decreased common carotid flow volume in the carotid and cerebral arteries. Increases in the severity score varied inversely with reduced flow volume, which was high in inverse correlation (r = -0.696). Patients with flow volumes of 8.5 ml/sec or greater did not have stenosis greater than or equal to 75%, whereas all patients with flow volumes of 6.4 ml/sec or less had stenosis greater than or equal to 50%, with 45% of these having stenosis greater than or equal to 75%. These pathological findings confirm that the common carotid flow volume reflects the degree of carotid and cerebral atherosclerosis present and that the lower limit of common carotid flow volume in healthy subjects is 6.5 ml/sec.

Arteriosclerosis↗

[Effects of ethylene glycol on hepatic microsomal cytochrome P-450].

The effect of ethylene glycol on rat hepatic microsomal cytochrome P-450 was studied in vitro and in vivo. The destruction of cytochrome P-450 was not seen in vitro. The addition of 1 mM NADPH also did not change. When ethylene glycol was added to drinking water at a concentration of 1.0% for 7 days, there was no change in the contents of microsomal protein, cytochrome P-450, b5 and heme. While NADPH-cytochrome C reductase activity of the exposed group did not change, NADH-ferricyanide reductase activity increased significantly.

Animals↗

Isolation and identification of the gene of cholesterol oxidase from Brevibacterium sterolicum ATCC 21387, a widely used enzyme in clinical analysis.

The gene coding cholesterol oxidase (CHOD) from Brevibacterium sterolicum, which is widely used in clinical analysis, has been selected from pUC19-based gene bank in E. coli MM294 by colony-hybridization using synthetic DNA as probe. The gene was identified to encode the protein having the same amino acid sequence as that determined from amino-acid sequence analysis. The expression of the CHOD gene in E. coli was not observed, probably due to the transcription failure. Attempts are being made to express it in various hosts including Streptomyces lividans, Corynebacterium glutamicum, and B. sterolicum itself.

Amino Acid Sequence↗

[Effects of sex difference on the toxicity of ethylene oxide. IV. Anemia].

Wistar male and female rats were exposed to ethylene oxide (EO) at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks simultaneously, and the sex difference of anemia induced by EO was investigated. Hemoglobin concentrations of both the male and female exposed groups were decreased when compared with each control group, and the anemia in the female exposed group was more severe than that in the male exposed group. Absolute spleen weight increased only in the female exposed group. We have already reported that a decrease of the glutathione reductase activity in the erythrocyte plays an important role in the EO-induced anemia. In the present study, the activity in both male and female exposed groups decreased when compared with each control group, and there was no sex difference in the degree of the decrease. From these observations, we concluded that there was a sex difference in the EO-induced anemia.

Anemia↗

[Effects of sexual difference on the toxicity of ethylene oxide. II. Glutathione metabolism and lipid peroxidation in the liver].

Wistar male and female rats were exposed to ethylene oxide (EO) at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks simultaneously, and the effects of EO on the glutathione metabolism and lipid peroxidation in the liver in regards to sexual difference were studied. Although the liver weight of the male exposed group did not alter, that of the female exposed group increased when compared with the control group. This increase was not accompanied with the alteration of protein content per gram of liver in the cytosol fraction and total homogenate. Among the glutathione related enzymes in the liver, the glutathione reductase activity of both male and female exposed groups decreased compared with each control group, and there was no difference in the degree of the decrease. The glutathione peroxidase activity increased only in the male exposed group. The glutathione-S-transferase activity of both male and female exposed groups increased significantly. In the male exposed group, the activity increased greater than that in the female exposed group. In the male exposed group, the lipid peroxide level in the liver increased slightly but not significantly.

Animals↗

[Effects of sexual difference on the toxicity of ethylene oxide. III. The rat hepatic monooxygenase system].

Wistar male and female rats were exposed to ethylene oxide (EO) at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks and the effect of EO on the hepatic monooxygenase system in regards to the sex difference was investigated. Serum GOT of the exposed male rat slightly increased, but that of the female did not change. Contents of microsomal protein and cytochrome P-450 of the male exposed group decreased significantly compared to the male control group, but that of the female exposed group did not change. The change of cytochrome b5, protoheme and NADH-ferricyanide reductase activity of the female exposed group was the same as that of the male. Although NADPH-cytochrome c reductase activity of the male exposed group did not change, that of the female group exposed increased significantly when compared to the female control group. From these observations, we concluded that the effect of EO on the hepatic monooxygenase system was different between male and female.

Animals↗

Chronic inhalation effects of ethylene oxide on porphyrin-heme metabolism.

The effects of chronic ethylene oxide (EtO) inhalation on porphyrin-heme metabolism were investigated. When Wistar male rats were exposed to 500 ppm EtO for 6 h a day, 3 times a week for 13 weeks, hemoglobin content significantly decreased, and a normocytic and normochromic anemia was found. In the liver, cytochrome P-450 and protoheme significantly decreased but wet weight, microsomal protein and cytochrome b5 were not affected. The activity of delta-aminolevulinic acid (ALA) synthase increased while ALA dehydratase did not change. The activity of hepatic ferrochelatase decreased time-dependently. Uroporphyrin increased 37% and coproporphyrin tended to increase in the liver. The concentration of protoporphyrin in the liver and erythrocytes tended to increase. Coproporphyrin excretion in the urine showed a 5-6-fold increase while there was no significant increase in urinary ALA excretion. These results indicate that chronic inhalation of EtO causes alterations of hepatic porphyrin-heme metabolism as well as anemia and may affect mechanisms of adaptation to xenobiotics.

5-Aminolevulinate Synthetase↗

[Effects of sexual difference on the toxicity of ethylene oxide. I. Polyneuropathy].

Male and female Wistar rats were exposed to ethylene oxide (EO) at a concentration of 250 ppm, 6 hours a day, 5 days a week for 17 weeks simultaneously, and the sexual difference in susceptibility of the peripheral nerve to EO was investigated. Both male and female rats of the exposed group showed paresis of the hindlegs, but sexual difference did not affect the degree of this abnormality. In histopathological examinations, axonal degeneration of the myelinated fibers in the peroneal nerve, the nerve to the soleus muscle and in the gracile fascicles of the spinal cord was revealed. The nerve to the soleus muscle degenerated more severely than the peroneal nerve. Sexual difference played no part in the severity of the degenerations in each nerve or in the gracile fascicles. From these observations, we concluded that there was no significant difference in the susceptibility of the peripheral nerve to EO between male and female rats.

Animals↗

Biochemical changes in rat erythrocytes caused by ethylene oxide exposure.

When Wistar male rats were exposed to ethylene oxide (EtO) at a concentration of about 500 ppm, 6 hr a day, 3 days a week for 2, 6, or 13 weeks, hematological examination showed macrocytic, normochromic anemia with a high reticulocyte count. This result raised the possibility that the hemolytic process was responsible for the anemia. Thus, the following possible causes of hemolysis were investigated with erythrocytes obtained from control and EtO-exposed rats. (1) Metabolism in erythrocytes; (a) Hexose monophosphate cycle: The activity of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, or glutathione peroxidase was not affected, but the activity of glutathione reductase (GR) significantly decreased and did not recover by the addition of flavin adenine dinucleotide. Reduced glutathione content also decreased and the glutathione stability test was positive. (b) Embden-Meyerhof pathway: Adenosine triphosphate content did not decrease. (c) Lapoport-Luebering cycle: 2,3-Diphosphoglycerate content was not affected. (2) Membrane alterations: Osmotic fragility was not affected and the activity of acetylcholine esterase in the ghost membranes of the exposed group increased. (3) Hemoglobin stability: The heat test and the isopropanol test were negative. GR has an important function in maintaining the reducing power in erythrocytes, and the decrease in the activity caused by EtO induced an alteration of the glutathione stability. Although the mechanism of EtO-induced anemia could not be clearly explained, the inhibition of GR activity might be related to the anemia.

2,3-Diphosphoglycerate↗

Concentrations of neopterin and biopterin in the cerebrospinal fluid of patients with Parkinson's disease.

The concentrations of neopterin and biopterin in CSF of 18 younger and 10 older, control patients and of 18 patients with Parkinson's disease were measured by high-performance liquid chromatography with fluorescence detection. Both neopterin concentrations and the neopterin to biopterin ratios in CSF were lower in 50-year or younger group than in 51-year or older group. Biopterin concentrations were also decreased but not significantly in the older group. The concentrations of neopterin and biopterin in CSF of patients with Parkinson's disease were lower than those of the age-matched older control group. However, the neopterin/biopterin ratios tended to be lower but not change significantly as compared to the age-matched older control group.

Adolescent↗

Cell line of mouse malignant fibrous histiocytoma with spontaneous metastatic potential.

A new murine malignant fibrous histiocytoma (MFH) cell line was established from a 4-hydroxyaminoquinoline 1-oxide-induced MFH. This cell line was followed by a contiguous sheet, and a confluent monolayer was established after 12 days incubation. These cells could be serially transplanted into the subcutaneous tissue of mice, the success rate becoming 100% after the 9th passage. Transplanted tumors demonstrated rapid growth and displayed a high potential for metastasis to the lung after the 16th passage. And a 100% lung metastasis rate was observed for MFH cells after the 20th passage. Histologically, these metastatic tumors retained features of the primary tumor.

4-Hydroxyaminoquinoline-1-oxide↗

Immunohistochemical study of 4-hydroxyaminoquinoline 1-oxide-induced rat malignant fibrous histiocytoma.

The primary focus of this experiment was on the investigation of localizations of alpha 1-antitrypsin (alpha 1-AT), alpha 1-antichymotrypsin (alpha 1-ACT), fibronectin (FN) and lysozyme (LY) in tumor cells of experimental malignant fibrous histiocytoma (MFH). The induction of MFH was conducted by injecting Fischer 344 rats with 4-hydroxyaminoquinoline 1-oxide (4-HAQO). In 46 out of 50 rats, tumors were generated, all of which were diagnosed as MFH and classified into 5 subtypes, according to their histological properties. The presence of alpha 1-AT, alpha 1-ACT and FN in all MFH tumor cells was observed in the tumor cells of various types. Especially, fibroblast-like, histiocyte-like and Touton and/or Epulis type giant cells showed strong reactivity. However, positive reaction of LY in MHF tumor cells was very weak, or the reaction was negative. These findings are consistent with those of human MFH.

4-Hydroxyaminoquinoline-1-oxide↗