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Biomedical subjects

N Matsunuma

Publications and source records attributed to N Matsunuma.

At least 19 recordsLinked to original sources
PubMed1999

Tissue and organ expression of catalase in acatalasemic beagle dogs.

Acatalasemic Beagle dogs which were maintained in our laboratories showed no sign of catalase activity at all in the erythrocytes, and glutathione peroxidase and superoxide dismutase were at normal levels. Immunoblotting analysis demonstrated that no catalase protein is detectable in their erythrocytes. On the other hand, catalase activity was detected in other tissues and organs, albeit at varying, lower levels than in normal dogs. Quantitative immunoblotting analysis consistently demonstrated that the catalase protein is expressed in the liver and kidneys of acatalasemic dogs in proportion to the activity in these organs. The catalase mRNA expressions in the blood, liver and kidneys in acatalasemic dogs were almost the same as those in normal dogs. These results suggested that catalytically normal catalase protein is translated from mRNA in the tissues and organs including erythrocytes, but in erythrocytes this enzyme protein is disposed of by an unknown mechanism.

Acatalasia↗
PubMed1996

Rapid induction of more malignant tumors by various genotoxic carcinogens in transgenic mice harboring a human prototype c-Ha-ras gene than in control non-transgenic mice.

In this study, we investigated the carcinogenic response of transgenic mice carrying the human prototype c-Ha-ras gene, namely Tg rasH2/CB6F1 mice, to various genotoxic carcinogens and compared it with that of control non-transgenic CB6F1 mice (non-Tg mice). The present studies were conducted as the first step in the evaluation of the Tg rasH2/CB6F1 mouse as a model for the rapid carcinogenicity testing system. Short-term (< or = 6 months) rapid carcinogenicity tests of various genotoxic carcinogens, 4-nitroquinoline-1-oxide, cyclophosphamide, N,N-diethylnitrosamine, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine and methylazoxymethanol, revealed that Tg rasH2/CB6F1 mice are more susceptible to these genotoxic carcinogens than control non-Tg mice. Tg rasH2/CB6F1 mice developed tumors more rapidly compared with non-Tg mice. Malignant tumors were observed only in the carcinogen-treated Tg rasH2/CB6F1 mice, but not in non-Tg mice treated with the same carcinogens. Each carcinogen induced tumors in corresponding target tissues of the Tg rasH2/CB6F1 mice. Only a very few lung adenomas but no other tumors were seen as spontaneous tumors during the 6 months of carcinogenicity tests. These results demonstrate that more rapid onset and higher incidence of more malignant tumors can be expected with high probability after treatment with various genotoxic carcinogens in the Tg rasH2/CB6F1 mice than in control non-Tg mice. The Tg rasH2/CB6F1 mouse seems to be a promising candidate as an animal model for the development of a rapid carcinogenicity testing system.

4-Nitroquinoline-1-oxide↗
PubMed1995

Age-related changes in the susceptibility to clofibric acid, a hypolipidemic agent, of male rat liver.

Age-related changes in the susceptibility to clofibric acid were investigated in male F344 rats of 8, 52, and 117 weeks old. Hepatomegaly, decrease of serum total cholesterol and triglyceride, increase of the total cytochrome P-450 contents, induction of the activities of microsomal omega-hydroxylation and peroxisomal beta-oxidation, proliferation of smooth endoplasmic reticulum and peroxisomes were detected in 8- and 52-week-old rats. In 117-week-old rats clofibric acid treatment resulted in decrease of serum total cholesterol, elevation of the activities of microsomal and peroxisomal enzymes, and slight proliferation of peroxisomes. These results suggest that the susceptibility of the male F344 rat liver to clofibric acid decreases in 117-week-old rats, though the effect is still recognizable.

Administration, Oral↗
PubMed1994

Vascular mineralization in the monkey brain.

Mineralization of various degrees was found in the brains of 79 (59%) of 134 cynomolgus monkeys (Macaca fascicularis). There was no age dependency in the incidence or severity, nor were there any abnormalities in growth, weight gain, or neurologic signs, although a slight sex difference was observed. The lesions, which were basophilic and intensely positive for periodic acid-Schiff or von Kossa stain, occurred in the vascular walls of the globus pallidus in two types: globoid bodies with prominent concentric lamellar structures in and around the arteriolar and venular wall (type A) and fine granules in the media of small or medium-sized arteries (type B). Electron microscopic examination revealed dense deposits in the degenerated media of small or medium-sized arteries or the thickened walls of the arterioles. X-ray microanalysis demonstrated the presence of calcium, phosphorus, iron, zinc, magnesium, and aluminum.

Animals↗
PubMed1994

Comparative study of goitrogenic actions of 3-substituted 1, 2, 4-triazoles in rats.

Antithyroid actions of 3-amino-1, 2, 4-triazole (ATZ), 3-mercapto-1, 2, 4-triazole (MTZ) and 3-nitro-1, 2, 4-triazole (NTZ), which are substituents on the 3-position of 1, 2, 4-triazole (TZ), and those of the parental compound, were compared in rats. After administration of either ATZ, MTZ, or NTZ, the thyroids of rats were enlarged with decreasing of colloid content and a proliferation of the follicular epithelia. The serum concentration of 3, 5, 3'-triiodothyronine and thyroxine decreased, while that of thyroid-stimulating hormone increased. ATZ, MTZ, and NTZ inhibited thyroid peroxidase activity both in vivo and in vitro. These antithyroid actions were the most remarkable in case of MTZ and were the least in case of NTZ. TZ had no effect on the thyroid function in vivo and in vitro. The results of Lineweaver-Burk analysis on the effect to lactoperoxidase activity indicated that ATZ, MTZ, and NTZ showed competitive inhibition. These results suggest that both MTZ and NTZ have goitrogenic effects on the thyroid through antiperoxidase action, such as ATZ. Thus, the 3rd carbon position of TZ is thought to be important for induction of goiter in rats. A comparison of the relationship between substituent on the 3-position of TZ and antithyroid activity shows that a mercapto moiety has more potent antithyroid action than an amino and a nitro moiety. It is concluded that the differences in antithyroid activity of TZ derivatives depend on the potency of the substituents.

Animals↗
PubMed1993

Spontaneous globoid mineralization in the cerebellum of rats.

Cerebellar globoid mineralization in two rats was examined by light and electron microscopy, and by X-ray microanalysis. The mineralization was round to oval in shape; it varied in size and was positive for the periodic acid-Schiff and von Kossa reactions. Ultrastructurally, a concentric lamellar structure was prominent in moderately electron-dense depositions. Elemental analysis revealed the presence of large amounts of calcium and phosphorus, and small amounts of zinc, potassium and aluminum.

Animals↗
PubMed1992

Species difference in susceptibility to phorbol myristate acetate-induced leukopenia and lung injury: rat vs. dog.

Phorbol myristate acetate (PMA) was administered intravenously in a single dose to rats (400 micrograms/kg) and in a single and repeated doses to dogs (40 micrograms/kg). Severe leukopenia was observed in both species. The leukopenia in rats was due to a decreased number of both lymphocytes and neutrophils while the leukopenia in dogs was mainly due to a decreased number of neutrophils. The rats recovered from leukopenia much faster than the dogs. The dog which received a single injection developed focal fibrosis in the lungs. Rats showed only slight localized hemorrhage in the lungs, although the rats received a ten-fold larger dose of PMA than the dogs. Lungs of dogs which received multiple injections revealed severe hemorrhagic lesions in most alveoli. Lung lesions induced by PMA are thought to be mediated by activated leukocytes. This suggests that the severity of lung lesion correlates with the degree and duration of neutropenia. In conclusion, intravenous administration of PMA caused lung damage in rats and dogs. However, rats show much less sensitivity to PMA than dogs, resulting from the different response of leukocytes to PMA.

Animals↗
PubMed1989

Preliminary dose finding study for subacute toxicological study of pravastatin sodium in monkeys.

Pravastatin sodium was orally administered to cynomolgus monkeys at dosage levels of 50, 200 and 800 mg/kg/day for 7 successive days. Excretion of diarrhea and/or loose stool were observed in the more than 50 mg/kg dose group, but the changes are quite mild. Animals of the 800 mg/kg dose group showed vomiting, diarrhea and/or excretion of soft stool and reduction of cholesterol content in serum. In conclusion, it is estimated that the no effective level is less than 200 mg/kg because no abnormalities were observed except for only very slight excretions of diarrhea and/or loose stool, and that the effective dose is 800 mg/kg in which vomiting was observed.

Administration, Oral↗
PubMed1989

Subacute toxicological study in monkeys treated orally with pravastatin sodium for 5 weeks.

Pravastatin sodium was administered orally to cynomolgus monkeys at dosage levels of 50, 100, 200 and 400 mg/kg/day for 5 successive weeks. Five animals of 200 mg/kg and 400 mg/kg dose groups were sacrificed during the study period, because these animals deteriorated in general condition and/or showed remarkable changes in serum biochemical examination. Pathological examination revealed hepatic and/or renal disturbance in these animals. These changes are thought to be the cause of deterioration of general condition or changes in serum biochemical examination. All other animals were terminated at the end of the study period. In the animals of the 100 mg/kg dose group, only one animal showed hepatic and renal disorder similar in nature to the changes in the animals sacrificed during the study period. No animals in the 50 mg/kg dose group showed toxic findings in any examination.

Administration, Oral↗
PubMed1989

Long term oral administration study of pravastatin sodium to beagles for 104 weeks.

Pravastatin sodium was successively given for 104 weeks to beagles orally at doses of 5 and 25 mg/kg/day. A decrease in serum cholesterol levels was observed at week 4 and thereafter. No other abnormal findings were obtained in any animals in general conditions, hematological and biochemical examination, various function tests, and pathological examinations. The no-effect dose level in beagles receiving pravastatin sodium orally for 104 weeks is toxicologically estimated to be more than 25 mg/kg/day.

Animals↗
PubMed1988

Enhancing effect of phenobarbital sodium on Tyzzer's disease in mice.

Tyzzer's disease in mice was aggravated by phenobarbital sodium (PB) given consecutively after bacterial inoculation. In PB-treated mice, mortality rate and severity of liver lesions were higher with more prominent bacterial propagation in hepatocytes as compared with non-treated ones, suggesting that PB had an enhancing effect on metabolic activities of host hepatocytes resulting in increased intracellular growth of bacteria.

Animals↗
PubMed1983

[4-way bred rats as experimental animals].

The present study is an attempt to utilize hybrids among several inbred strains of rats as useful animals for the studies of effectiveness and toxicology on drugs., Four-way crosses were made among the LEW, WM, F344 and DRY strains of rats, and their characteristics were examined. From the breeding data of diallel crosses among these four strains and reciprocal crosses among their F1 hybrids, the mating type indicating the highest reproductivity was (LEW X WM) F1 X (F344 X DRY) F1. These four-way crosses were designated as LWFD. The reproductivity of this mating type was exceedingly higher than those of four strains. In order to examine the susceptibility to thiamine hydrochloride, the acute toxicity test was practiced in inbred strains, F1 hybrids and four-way crosses. As a result, in spite of highly heterogeneous population, the LWFD did not show a peculiar response in comparison with four strains and their F1 hybrids. Furthermore, hematological and clinico-biochemical values of the LWFD did not show a large variability as presumed. From these results, it is suggested that hybrids such as four-way crosses among inbred strains can be used as useful animals for the studies of effectiveness and toxicology on drugs.

Animals↗
PubMed1979

[Effect of proximate environment on drug susceptibility of mice (author's transl)].

The present study was performed in order to elucidate the effect of proximate environment on drug susceptibility of mice. Three experiments were carried out independently. In the first experiment, mongrel and ddS mice produced under an unsatisfactory control of proximate environment were purchased, and acute toxicity tests of thiamine hydrochloride (B1HCl) and isonicotinic acid hydrazide (INAH) were practiced at two different conditioned rooms. In the second experiment, ddY mice produced under the conventional environment controlled to a certain extent were purchased, and the toxic effect of B1HCl was examined under the similar environment. In the third experiment, the sensitivity to B1HCl of RFVL mice produced under the strict barrier system was tested at the severe air-conditioned room. LD50 and their fLD50 values were calculated by Litchfield-Wilcoxon's method, and the variance analyses were carried out. The severer the environmental control after the purchase of mice turned to the higher the drug sensitivity. This respect was more remarkable in INAH of which the toxic response is appeared slowly compared with B1HCl. Furthermore, seasonal variation was found in LD50 values. However, seasonal effect differed from rearing and experimental conditions. In the third experiment which these proximate environments were controlled severely, seasonal variation was very small. From the results of these experiments, it was defined that the use of animals produced under the satisfactory rearing condition and severe environmental control are necessary for animal experiments.

Air Conditioning↗