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Biomedical subjects

K Fujishiro

Publications and source records attributed to K Fujishiro.

At least 73 records · Page 4Linked to original sources

Testicular damage induced by megadoses of pyridoxine.

Pyridoxine hydrochloride, 125 mg/kg, 250 mg/kg, 500 mg/kg or 1,000 mg/kg, daily, was intraperitoneally injected into Wistar male rats and its effects on weights and mature spermatid or sperm counts in the testis and the epididymis were investigated. After six weeks administration, weights of the testis and the epididymis in the 500 mg/kg and 1,000 mg/kg groups dramatically decreased and weights of the epididymis in the 125 mg/kg and 250 mg/kg groups also decreased significantly. Mature spermatid counts in the testis and sperm counts in the epididymis decreased in the 500 mg/kg and 1,000 mg/kg groups, and sperm counts in the tail plus body of the epididymis also decreased in the 250 mg/kg group. From these results, it was elucidated that megadoses of pyridoxine induced testicular damage in rats.

Animals↗

[Effects of ethylene oxide on hepatic microsomal cytochrome P-450: an in vitro study].

The effect of ethylene oxide on rat hepatic microsomal cytochrome P-450 was studied in vitro. Cytochrome P-450, but not b5, was decreased by ethanol. When hepatic microsome was bubbled with ethylene oxide gas, cytochrome P-450 content remained unchanged when compared with CO2 bubbling. The addition of NADPH 1 mM also did not change cytochrome P-450 significantly. The excessive high exposure to 500 mM ethylene oxide also did not affect microsomal cytochrome P-450. These results indicate that ethylene oxide does not destroy directly the hepatic microsomal cytochrome P-450 under these conditions.

Animals↗

[Effects of inhalation of ethylene oxide on female rats].

The effects of systemic toxicity including reproductive toxicity of ethylene oxide on female rats were studied. When Wistar female rats were exposed to 250 ppm of ethylene oxide for six hours a day, five days a week for ten weeks, they showed inhibition of body weight gain and paralysis of the hindlegs. Hematological examination revealed macrocytic and normochromic anemia with high reticulocyte counts. The estrus cycle of the exposed group was prolonged and the percentage of the diestrus stage increased. There was no atrophy in the ovary or the uterus. However, the activity of glutathione reductase in the ovary decreased by 18% and that of glutathione-S-transferase increased by 30%. These results indicate that ethylene oxide has a similar effect on both female and male rats and that the female reproductive system is also affected.

Administration, Inhalation↗

[Excretion of porphyrin and porphyrin precursor during ethylene oxide inhalation].

The effect of chronic inhalation of ethylene oxide on urinary coproporphyrin and delta-aminolevulinic acid were studied. When Wistar male rats were exposed to 500 ppm ethylene oxide three times a week, daily urine volume was increased by 200-300% from the first week to the fifth week of the experimental period. After exposure, daily coproporphyrin excretion and urinary coproporphyrin per mg of creatinine increased by 250% and 141%, respectively. On the other hand, daily excretion of delta-aminolevulinic acid in urine tended to increase but did not increase significantly by creatinine-correction. We think this is the first report of ethylene oxide induced experimental porphyria.

Administration, Inhalation↗

Testicular toxicity and alterations of glutathione metabolism resulting from chronic inhalation of ethylene oxide in rats.

Wistar male rats were exposed to ethylene oxide (EtO) at a concentration of 500 ppm, 6 hr a day, 3 days a week, for 2, 4, 6, or 13 weeks. Testicular toxicity and changes in glutathione metabolism in the testis were investigated. The relative weights of the testes and the epididymes of the EtO-exposed group decreased in a time-dependent manner. Light microscopic examination revealed degeneration and exfoliation of germ cells. Although the severity of damage became apparent over the course of exposure, some seminiferous tubules showed germ cell recovery at 13 weeks compared with 6 weeks. There was no alteration in plasma testosterone concentration. Glutathione reductase (GR) activity decreased during the entire examination period, and recovery from the decrease was not achieved by addition of flavin adenine dinucleotide (FAD). On the other hand, glutathione peroxidase (GPx) activity decreased at 2 weeks, and then increased at 6 and 13 weeks. In spite of alterations in the glutathione redox cycle, the level of reduced glutathione (GSH) in the testes was not affected. Glutathione S-transferase activity, measured with 1-chloro-2,4-dinitrobenzene (CDNB) as substrate, increased at 6 and 13 weeks and, measured with 1,2-epoxy-3-(p-nitrophenoxy)propane, increased at 4, 6, and 13 weeks. These data indicate that chronic inhalation of EtO induces testicular atrophy. Alterations in the glutathione redox cycle and glutathione S-transferase activity might play important roles in the toxicity and the detoxifying mechanism of the testis.

Administration, Inhalation↗

[Variation of glycosaminoglycan in the growth of transplantable tumors derived from a spontaneous ddY mouse mammary tumor].

The components and variations of glycosaminoglycan (GAG) in the growth of transplantable tumors derived from a spontaneous mouse mammary tumor were investigated. A 45-week-old ddY female mouse, obtained from Shizuoka Laboratory Animal Center, was found to have a bean-sized mass at the third mammary gland of the left side. The tumor mass was surgically excised and used for transplantation in the present study. This mammary tumor was histologically found to be Type B-adenocarcinoma. Transplantable mammary tumors consisted of the fibrous or edematous interstitium contained a large amount of GAG components, which was mainly hyaluronic acid (HA), dermatan sulfate (DS) and chondroitin sulfate A/C (ChS). In the analysis of GAG components, HA content was present in a large amount in logarithmic growth phase of transplanted mammary tumors, but it was markedly decreased in stationary phase. On the other hand, the contents of DS and ChS increased in stationary phase of the tumor growth, and these increases corresponded, histologically, with the propagation of the fibrous interstitial tissues.

Adenocarcinoma↗

Pathology of spontaneous malignant fibrous histiocytoma in a Japanese white rabbit.

Spontaneous malignant fibrous histiocytoma (MFH) of the chest wall was found in a 10-year-old male Japanese white rabbit. Histologically, the MFH consisted mainly of areas of storiform, pleomorphic and myxoid patterns. Positive reactions for acid phosphatase (Ac-P), non-specific esterase (N-SE) and beta-glucuronidase (beta-GL) were demonstrated in fibroblast-like, histiocyte-like and giant cells. Moreover, a strongly positive fibronectin (FN) reaction was observed mainly in histiocyte-like and giant cells. In electron microscopy, tumor cells were composed morphologically of various types of cells such as fibroblast-like, histiocyte-like, undifferentiated and giant cells. This case was quite similar to those reported in man or other animals.

Animals↗

[Magnetic resonance imaging of parkinsonism].

We have analyzed magnetic resonance images in 33 patients; 18 patients with Parkinson's disease, 1 patient with diurnally fluctuating progressive dystonia, 1 patient with pure akinesia, 6 patients with multiple system atrophy, 1 patient with flunarizine induced parkinsonism, and 4 patients with unclassified parkinsonism. The MR images were obtained using a 1.5-T GE MR System. A spin-echo pulse sequence was used with a TE of 30 msec and 80 msec and a TR of 2000 msec. No signal abnormalities were seen in any patient with Parkinson's disease but 3 showed slightly decreased signal intensity of the putamen on T2-weighted sequences. Patients with diurnally fluctuating progressive dystonia and pure akinesia evidenced no abnormal findings. All six patients with multiple system atrophy demonstrated decreased signal intensity of the putamen, particularly along their lateral and posterior portions, and an enlarged substantia nigra. Atrophy of the pons and cerebellum was detected in all cases with multiple system atrophy. One case of flunarizine induced parkinsonism showed slightly decreased signal intensity of the putamen. Four cases of unclassified parkinsonism showed decreased signal in the putamen on T2-weighted sequences. Magnetic resonance imaging has the potential to become a useful diagnostic tool in the management of parkinsonism.

Adult↗

The changes of glycosaminoglycan in the growth of urethane-induced mouse mammary tumors.

The changes of glycosaminoglycan (GAG) in the growth of urethane-induced mammary tumors in BALB/c mice were investigated. The artificial mammary tumor was chemically induced by urethane. Successive homo-transplantations of this artificial mammary tumor were successfully achieved at the rate of 100%. Histologically, this artificially induced transplantable mammary tumor (MC) line maintained the characteristics of adenoacanthoma of primary tumors in each successive generation. MC in each generation showed a logarithmic growth beginning from about the 5th day after transplantation, and their growth became slow about the 30th day. Histochemically, GAG components in MC were distributed into the interstitial tissue and into some of the squamous metaplastic epithelial cell layers. Biochemically, GAG components consisted primarily of hyaluronic acid (HA), dermatan sulfate (DS) and chondroitin sulfate (ChS), but there were also small amounts of components which could not be identified. The HA content of MC increased during the logarithmic growth phase and decreased during the stationary phase. However, DS and ChS contents increased during the stationary phase of MC. These increases, histologically, corresponded with propagations in fibrous interstitial tissue. In the final analysis, it is surmised that HA is involved in the take and growth of MC (adenoacanthoma) in mice, while DS and/or ChS are involved in the proliferation of the fibrous interstitial tissue cells of the tumor.

Adenocarcinoma↗

Crystallization and some properties of acetylpolyamine amidohydrolase from Mycoplana bullata.

During the course of investigations on the catabolism of acetylpolyamines by microorganisms, we found that acetylpolyamine amidohydrolase was produced by Mycoplana bullata FERM BP-1845 and isolated the enzyme from the cell-free extract in crystalline form. The enzyme had an apparent molecular weight of 67 kDa and was composed of two identical subunits. The enzyme activity was inhibited by o-oxyquinoline and the crystalline enzyme contained one zinc atom per each subunit. The enzyme had an optimal pH around 8.0 with acetylputrescine as substrate and showed broad substrate specificity and high affinity towards various acetylpolyamines, such as acetylputrescine, acetylcadaverine, acetylspermidine, and acetylspermine.

Actinomycetales↗

[Effects of chronic inhalation of ethylene oxide on the rat testes].

The effects of chronic exposure of ethylene oxide on the testes were investigated. When rats were exposed to 500 ppm, three times a week for 13 weeks, the testes of the exposed group became remarkably atrophic and their DNA content decreased proportionally. However, plasma testosterone concentration did not significantly change. In the testes the activity of glutathione reductase decreased by 45% and glutathione-S-transferase increased by 64%, respectively. These results suggest that ethylene oxide causes a definite toxicity in the testes and the abnormality of glutathione metabolism plays an important role in its toxicity.

Administration, Inhalation↗

Triorthocresyl phosphate poisoning--a review of human cases.

Since the end of the nineteenth century, numerous cases of triorthocresyl phosphate (TOCP) poisoning due to accidental contamination of drink, food or drugs have been reported. Following the ingestion of preparations contaminated by TOCP, gastrointestinal symptoms may occur and after an interval of ten to twenty days, a well-known delayed neurotoxicity gradually develops. In general, the initial symptoms are pain and paresthesia in the lower extremities. In most cases, muscle weakness progresses rapidly developing into a striking paralysis of the lower extremities with or without an involvement of the upper extremities. Severe cases show pyramidal signs. The histopathological findings show axonal degeneration in the peripheral nerves and degenerative changes in the anterior horn cells. Degenerative change also occurs in the lateral and dorsal tracts of the spinal cord. The cardinal therapy is physical rehabilitation.

Axons↗

[Inhibition of delta-aminolevulinic acid dehydratase by styrene and styrene oxide].

Effects of styrene and styrene oxide on delta-aminolevulinic acid dehydratase in rats were investigated, in vivo and in vitro. In the in vivo study, rats were exposed to styrene or styrene oxide intraperitoneally for seven days. delta-Aminolevulinic acid dehydratase in the erythrocyte was inhibited by both styrene and styrene oxide. The inhibition by styrene oxide had a clear dose-response relationship, but that by styrene did not. In the liver, however, these substances did not inhibit delta-aminolevulinic acid dehydratase. In the in vitro study, styrene oxide inhibited delta-aminolevulinic acid dehydratase both in the erythrocyte and in the liver, but styrene failed to inhibit it. These results suggest that styrene is metabolized to styrene oxide, and this metabolite inhibits delta-aminolevulinic acid dehydratase. It is also thought that the discrepancy of inhibition between the erythrocyte and the liver is due to a difference of distribution and metabolism of the substances.

Animals↗

Cumulative toxicity potential of methomyl aerosol by repeated inhalation.

There are few investigations concerning the cumulative toxicity of agricultural chemicals by repeated inhalation. In this study, Wistar male rats were exposed to methomyl powder (mass median aerodynamic diameter, 4.4 microns) for a single 4-hr exposure, or for 4 hr/day, 5 days/week for 3 months. The average exposure concentrations were controlled at 9.9 mg/m3 for the single exposure and at 14.8 mg/m3 for repeated exposures by a dust generator consisting of a continuous fluidized bed with an overflow pipe and a screw feeder. After the repeated exposures, plasma and red cell cholinesterase activities, and lipid concentrations of the rat lungs were measured and histopathological examinations were performed. There was no evidence of cumulative effects on the red cell cholinesterase activity, histopathological changes and lipid concentration in 3-month repeated inhalation.

Aerosols↗

Purification and Characterization of Benzonitrilases from Arthrobacter sp. Strain J-1.

We found two kinds of benzonitrilases, designated benzonitrilases A and B, in a cell extract of Arthrobacter sp. strain J-1 grown on benzonitrile as a sole carbon and nitrogen source. Benzonitrilases A and B were purified approximately 409-fold and 38-fold, respectively. Purified benzonitrilase A appeared to be homogeneous according to the criteria of polyacrylamide gel electrophoresis. Both the enzymes hydrolyzed benzonitrile to benzoic acid and ammonia without forming benzamide as an intermediate. The molecular weights of benzonitrilases A and B were found to be 30,000 and 23,000, respectively. The subunit molecular weight of benzonitrilase A was the same as its molecular weight. The isoelectric points of benzonitrilases A and B were 4.95 and 4.80, respectively. The optimum temperature and pH, respectively, for benzonitrilase A were 40 degrees C and 8.5, and those for benzonitrilase B were 30 degrees C and 7.5. The K(m) values for benzonitrilases A and B were 6.7 mM and 4.5 mM, respectively. Both the enzymes degraded p-tolunitrile, 4-cyanopyridine, and p-chlorobenzonitrile, but they did not attack aliphatic nitriles or amides. Both the enzymes were inhibited by thiol reagents.

Journal Article↗