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M Matsuo

Publications and source records attributed to M Matsuo.

At least 235 records · Page 13Linked to original sources
PubMed1996

Conflict situation increases serotonin release in rat dorsal hippocampus: in vivo study with microdialysis and Vogel test.

The release of serotonin (5-hydroxytryptamine, 5-HT) in the dorsal hippocampus was measured using an in vivo microdialysis method in rats subjected to the Vogel type conflict test. The conflict situation significantly increased 5-HT release in the dorsal hippocampus. Midazolam (0.75 and 1.5 mg/kg i.p.) suppressed the dosage-dependently this increased 5-HT release, an inhibition closely associated with the attenuation of conflict behavior. These findings suggest that the activation of serotonergic neuronal activity in the dorsal hippocampus is linked to mediation of anxiety-related behavior.

Animals↗
PubMed1996

Histological changes in rat embryonic blood cells as a possible mechanism for ventricular septal defects produced by an N-phenylimide herbicide.

An N-phenylimide herbicide, S-53482, inhibits protoporphyrinogen oxidase, an enzyme common to chlorophyll and heme biosynthesis, and produces embryolethality, teratogenicity [mainly ventricular septal defects (VSD) and wavy ribs], and growth retardation in rats. In order to elucidate the mechanism of the developmental toxicity, in particular VSD, effects of the herbicide on rat embryonic blood cells were investigated histologically at the light and electron microscopic levels at 6, 12, 24, 36, and 48 h after oral administration of the chemical to pregnant rats on day 12 of gestation, the most sensitive day for toxicity. Electron and light microscopy demonstrated mitochondrial lesions, including abnormal iron deposits that were probably due to inhibition of heme biosynthesis, in erythroblasts derived from the yolk sac. Subsequently, degeneration of these erythroblasts occurred followed by erythrophagocytosis. Histologically hearts from exposed embryos had a thin ventricular wall, which may reflect a compensatory reaction to a loss of embryonic blood cells. Thus, the herbicide may induce VSD due to hematological dysfunction caused by the inhibition of heme biosynthesis rather than by direct injurious effects on the heart.

Animals↗
PubMed1996

(2E,4E)-N-(4-(1H-indol-3-yl)piperidin-1-yl)alkyl-5-(substituted phenyl)-2,4-pentadienamides as antiallergic agents with antihistaminic and anti slow-reacting substance (SRS) activities.

As an extension of our study aiming to discover a novel compound with dual activities against histamine and slow-reacting substance (SRS), we synthesized two types of indolylpiperidine derivatives, 3 and 4-20. Testing for in vivo antianaphylactic activity and for in vitro anti-SRS activity revealed that (2E,4E)-5-(3,5-dimethoxy-4-hydroxyphenyl)-N-(2-(4-(1H-indol-3-yl)+ ++piperidin-1- yl)ethyl)-2,4-pentadienamide (11) exhibited potent dual activities with ED50 = 0.89 mg/kg and IC50 = 1.43 microM, respectively. However, the plasma concentration of unchanged 11 was very low when administered orally in guinea pigs. This result can be explained by fast formation of a glucuronic acid conjugate.

Amides↗
PubMed1996

Difference between normal and WHHL rabbits in susceptibility to the adrenal toxicity of an acyl-CoA:cholesterol acyltransferase inhibitor, FR145237.

The adrenal toxicity of an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, FR145237, was investigated using Japanese White (normal) and low density lipoprotein (LDL) receptor deficient Watanabe heritable hyperlipidemic (WHHL) rabbits. In the normal rabbits, severe necrosis of the cells in the zona fasciculata and reticularis was observed 24 hr after intravenous injection of 3.2 mg/kg of FR145237, whereas no morphological changes could be found in the adrenal cells of the WHHL rabbits in spite of a higher plasma concentration of the drug. Since most of the FR145237 (87%) in the plasma of the WHHL rabbits was recovered in the LDL fraction 1 hr after intravenous injection of the drug (3.2 mg/kg), it was hypothesized that the delivery of the drug to the adrenal cells may be limited by the LDL receptor deficiency. However, the concentration of FR145237 in the adrenal gland of the WHHL rabbits (13.3 microg/g) was identical to that in the normal rabbits (13.6 microg/g). These results suggest that the susceptibility of the adrenal cells of the WHHL rabbits to the toxicity of FR145237 truly differs from that of normal rabbits, and that the WHHL rabbit may be a useful animal model for the investigation of the mechanisms of the adrenal toxicity of ACAT inhibitors.

Adrenal Cortex↗
PubMed1996

Species difference in protoporphyrin IX accumulation produced by an N-phenylimide herbicide in embryos between rats and rabbits.

There was a remarkable species difference in developmental toxicity exhibited by S-53482, an N-phenylimide photobleaching herbicide, between rats and rabbits. S-53482 showed embryolethality, teratogenicity, and growth retardation in rats. In contrast, no developmental toxicity was shown in rabbits. The herbicidal activity of S-53482 is due to the photodynamic action of accumulated protoporphyrin IX (PPIX) as a result of inhibition of protoporphyrinogen oxidase (PPO), which is one of the key enzymes in porphyrin biosynthesis common to both plants and animals as part of chlorophyll and heme synthesis. Some plant PPO inhibitors were reported to inhibit mammalian PPO. Therefore, in a search for a possible link between developmental toxicity and enzyme inhibition, PPIX accumulations presumably resulting from PPO inhibition in rat and rabbit embryos were investigated. The results demonstrated that PPIX concentration was increased in rat embryos by 2 orders of magnitude when compared to that of nontreated embryos. On the other hand, no PPIX was accumulated in rabbit embryos even by treatment with a high dose level of S-53482. It was concluded that the species difference in PPIX accumulation corresponded very well to that of the developmental toxicity exhibited by S-53482.

Animals↗
PubMed1996

A common mutation in methylenetetrahydrofolate reductase gene among the Japanese population.

Hyperhomocysteinemia has been reported as an independent risk factor for atherosclerotic cerebrovascular and coronary heart diseases. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes responsible for hyperhomocysteinemia. The C to T transition of the MTHFR gene at nucleotide position 677 results in decreasing the enzymatic activity and increasing the plasma homocysteine level. We studied the distribution of the MTHFR gene mutation among the Japanese population. The subjects were 129 Japanese males (aged 40-59 years). The allele frequency of the mutation was 0.38. The frequencies of the three genotypes were as follows: +/+, 11%; +/-, 54%; -/-, 35% (+ and-indicate the presence and absence of the mutation, respectively). We also studied the frequency of the MTHFR gene mutation in the middle-aged Japanese males with hypertension to investigate the possibility that this mutation is related to essential hypertension. The normotensive and hypertensive subjects were identical in the distribution of the mutated allele and the frequencies of the three genotypes. Furthermore, the prevalence of hypertension in each genotype group was same, although the mean diastolic pressure of the group with homozygous mutation was significantly higher than that of other groups (p < 0.05). Therefore, we concluded that there was no significant relationship between the MTHFR gene mutation and hypertensive subjects studied in this study.

Adult↗
PubMed1996

Comparison of insertion rate of L1 retroposon into intron 30 of the neurofibromatosis type 1 gene in seven Asian and Pacific populations.

The allele frequency of a L1 retroposon insertion into intron 30 of the neurofibromatosis type 1 (NF1) gene was determined by analyzing amplified fragment lengths in seven Asian or Pacific population; namely, Japanese, Chinese. Indian, Malay, Filipino, Indonesian and New Guinean. Nearly 100 chromosomes from each group were analyzed. The presence of the L1 insertion was identified by the appearance of an abnormally large PCR-amplified product. The insertion frequency varied from 0.45 to 0.75, depending on the population group. Malay and Indonesian populations were found to have the highest insertion frequencies (0.75 and 0.72, respectively), while the wild-type genotype was more prevalent in Indians. The lowest insertion frequency (0.45), observed in Indians, was nearest to that reported in Westerners (0.35). The different L1 insertion frequencies found in Asian and Pacific groups reflect a major divergence in these human populations. Japanese and Chinese populations showed the highest heterozygosity (0.50), suggesting the usefulness of this polymorphism in linkage analysis in these populations.

Alleles↗
PubMed1996

A research to develop a predicting system of mammalian subacute toxicity. II. Single dose detailed toxicity studies.

"Single dose detailed toxicity study" in rats was conducted with 6 chemical substances to establish a predicting system of subacute toxicity of non-congeneric industrial chemicals. In the detailed examinations, new and previously reported biological parameters were developed and utilized for the establishment and confirmation of the correlations for both qualitative and quantitative prediction of target organs and effects in repeated dose toxicity studies of non-congeners; the new parameters were concerned with liver, kidneys and blood and the established relating equations for prediction had a correlation coefficient of 0.83 (liver), 0.49 (kidneys) and 0.94 (blood), while the old parameters effectively confirmed the previous correlations. The serial changes in the study gave a biological explanation to the established relationships between acute and subacute toxicities in terms of extrapolation.

Animals↗
PubMed1996

A research to develop a predicting system of mammalian subacute toxicity. I. Prediction of subacute toxicity using the biological parameters of acute toxicities.

Predicting equations of subacute toxicity were developed by analyzing rat acute and subacute toxicity data of 56 chemicals of various structures. Minimum or 10% effect level in acute or subacute toxicity was estimated as a "biological parameter". Good regression equations were established between the geometrical means ("combined parameters") of any two of the parameters of acute and subacute toxicities and introduction of log P to the equations improved the correlations with a statistically significant multiple regression coefficient. The lowest predicted effect level of the subacute toxicity, which is selected from the data calculated by the above several correlations, can predict the upper limit of the no observed effect level. In recent years, for research and development of new chemical substances, it becomes one of the important factors that these have a lower environmental load in nature. Eventually, it becomes essential to evaluate not only their acute effects on human or environments, but also their chronic influences when they are to be exposed for a long period of time, and the cost for such verification is becoming a breaking factor for research and development. Thus, the development of a new technique which estimates the environmental load of a chemical substance including toxic effects on human with lower cost is now being attempted. For example, the development of in vitro new alternative methods using cultured cells, the utilization of a data base or software which relates mammalian and environmental toxicities and so on are internationally carried forwards. As for the latter, quantitative structure-activity relationship (QSAR) techniques have been applied practically to decide appropriate toxicity tests needed for regulatory purposes by EPA/TSCA, ITC/TSCA and FDA/FDAA in the USA. In addition, it was concluded recently in a joint meeting of EU and US-EPA that the approach by QSAR techniques was useful to specify the new chemical substances which are to be required toxicological examinations. In these QSAR techniques, however, while there are some considerations about common mechanisms of toxicity among chemicals with a similar structure (Congeneric chemicals, Congeners) for establishing of correlation formulas, for chemicals with various structures (Non-congeneric chemicals, Non-congeners) there often lack such common considerations. In addition, biological or physiological factors which are basic toxic indices are often ignored. In a previous study, we researched acute and subacute oral toxicities of industrial common chemicals in rats and reported the followings; 1) their subacute toxicological spectrum in target organs/tissues and morphologic changes was very limited and specific, 2) the important targets were liver, kidneys, blood (spleen) and stomach and these are considered the sites of dominant exposure due to the kinetics of chemical substances, 3) the morphological changes were hepatocellular hypertrophy, deposition of substance in renal tubules, extramedullary hematopoiesis in spleen and mucous lesion in stomach, and these are implying adaptation such as induction of drug-metabolizing enzymes, overload to renal function, anemia from erythrocyte destruction, and direct reaction, respectively, 4) there seems to occur a series of direct and adaptive reactions to exclude the "foreign compounds" which do not show any specific biological activities, 5) it is also considered that there is a possibility to establish a correlation between toxicological findings or target organs/tissues of both acute and subacute toxicities by their continuity. Therefore, in the present study, a predicting equation of subacute (28-day repeated dose) toxicity is attempted to develop from acute (single dose) toxicity data by considering both common mechanisms and biological factors for non-congeneric industrial chemical substances.

Animals↗
PubMed1996

Leukotriene B4 and C4 in cerebrospinal fluid from children with meningitis and febrile seizures.

Concentrations of immunoreactive leukotriene C4 (LTC4) and leukotriene B4 (LTB4) in the cerebrospinal fluid from 18 patients with aseptic meningitis, including 2 patients with encephalitis and 4 patients with febrile seizures, were measured by a sensitive and specific radioimmunoassay; these results were compared with those from control subjects. The concentrations of both LTC4 and LTB4 were elevated significantly in patients with meningitis (LTC4: 115.6 +/- 47.7 pg/ml; LTB4: 1,603.0 +/- 273.5 pg/ml; n = 18) compared to controls (LTC4: 83.2 +/- 21.6 pg/ml; LTB4: 1,219.3 +/- 161.5 pg/ml; n = 12; P < .05 and P < .01, respectively). However, there was no significant increase in LT levels in patients with febrile seizures. These findings suggest that LTs may play an important role in the inflammatory response induced by viral infections of the central nervous system.

Child↗
PubMed1996

Cytotoxicity of phosphatidylcholine hydroperoxides is exerted through decomposition of fatty acid hydroperoxide moiety.

The cytotoxicity of phosphatidylcholine hydroperoxides synthesized regioselectively and stereoselectively was examined in human umbilical vein endothelial cells. Phosphatidylcholine hydroperoxides were readily incorporated into cells, after which the contents declined gradually. Phosphatidylcholine with an arachidonic acid hydroperoxide residue was toxic to cells, while phosphatidylcholine with a linoleic acid hydroperoxide residue had no effect. The toxicity of phosphatidylcholine with arachidonic acid hydroperoxide disappeared after the reduction of the hydroperoxide by triphenylphosphine. Phosphatidylcholine with arachidonic acid hydroperoxide that had decomposed partially upon standing at room temperature was much more toxic than the pure hydroperoxide. 4-Hydroxynonenal, known widely as a toxic secondary product in the lipid peroxidation of polyunsaturated fatty acids, was detected in the decomposition mixture of phosphatidylcholine hydroperoxide. Phosphatidylcholine hydroperoxide incorporated into cells did not show toxicity when the hydroperoxide-containing medium was changed to growth medium after a short time. On the other hand, the phosphatidylcholine hydroperoxide was toxic in cells treated with the lipophilic free radical generator, 2,2'-azobis(2,4-dimethylvaleronitrile). In addition, cells were damaged by long-term treatment in medium containing phosphatidylcholine hydroperoxide and its decomposition products. These results suggest that the toxicity of phosphatidylcholine hydroperoxides is exerted by toxic compounds arising from the decomposition of the hydroperoxide moiety.

Arachidonic Acid↗
PubMed1996

Research to develop a predicting system of mammalian subacute toxicity, (3). Construction of a predictive toxicokinetics model.

A new predictive toxicokinetics model was developed to estimate subacute toxicity (target organs, severity, etc.) of non-congeneric industrial chemicals, where the chemical structures and physico-chemical properties are only available. Thus, a physiological pharmacokinetics model, which consists of blood, liver, kidney (these were experimentally found as major toxicological targets), muscle and fat compartments, was established to simulate the chemical concentrations in organs/tissues with pharmacokinetic parameters by means of Runge-Kutta-Gill algorithm. The pharmacokinetic parameters, i.e. absorption rate, absorption ratio, hepatic extraction ratio of metabolism and renal clearance were calculated by using separately established Quantitative Structure-Pharmacokinetics Relationship equations. The developed predictive model was then applied to simulations of 43 non-congeneric industrial chemicals. The chemical concentrations in organs/tissues after single oral administration were simulated, and their maximum concentrations (Cmax's) and area under the concentration-time curves (AUC's) were calculated. Fast Inverse Laplace Transform was newly applied for the purpose of simulation of 28-day repeated dose toxicity. Simulated concentrations of 28 days repeated dose were, however, found to be the same as those of simple repetitions of a single administration per day because of the short half-lives of non-congeneric industrial chemicals. A comparison of subacute toxicity data with Cmax's and AUC's in a single dose scenario suggested that the organs/tissues with relatively high concentrations of tested chemical substances were the most sensitive targets within a chemical. Chemical concentrations in liver, for instance, were correlated with the severity of hepatotoxicity among the chemicals. It was also suggested that to improve and widen the present approach, data of metabolite and reactivity of non-congeneric industrial chemicals to organs/tissues, receptors, etc. should be incorporated into the model.

Adipose Tissue↗
PubMed1996

Heparin-induced thrombocytopenia in hemodialysis patients.

This study was conducted to determine the incidence of heparin-induced thrombocytopenia (HIT), an important complication in heparin therapy, in 154 hemodialysis patients, with characterization of the subtypes using an enzyme-linked immunosorbent assay. The etiology of the immunologic type of HIT is suggested to involve the binding of a specific antibody for platelet factor 4-heparin complex to platelets and their consequent activation. The 154 consecutive patients were newly treated with hemodialysis due to chronic or acute renal failure between January 1993 and July 1995. Heparin-induced thrombocytopenia was suspected in six patients (3.9%), and its presence was confirmed by platelet aggregation testing. Five of the patients with HIT had anti-platelet factor 4-heparin complex antibody detected by the enzyme-linked immunosorbent assay and were diagnosed with immunologic HIT. The patient who did not have the antibody was thought to have another type of HIT.

Acute Kidney Injury↗
PubMed1996

Non-linear accumulation of 8-hydroxy-2'-deoxyguanosine, a marker of oxidized DNA damage, during aging.

Damage to DNA seems to be involved in aging and the etiology of age-associated degenerative diseases. The purpose of this study is to examine changes in DNA damage during aging. An oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (8-OHdG), is a proposed biomarker for DNA damaged by oxidative stress. The content of 8-OHdG in nuclear DNA isolated from brain, heart, liver, and kidneys of male Fischer 344 rats of different ages was measured, 8-OHdG can be detected selectively and sensitively at the fmol level by high performance liquid chromatography-electrochemical detection at an applied potential of +350 mV. The amount of 8-OHdG, expressed as the ratio to deoxyguanosine in nuclear DNA, in heart, liver, and kidney remained steady from 2 to 24 months and then increased progressively. The content of 8-OHdG in the DNA in brain showed no changes from 2 to 27 months, but was significantly higher in 30 month-old rats. There was a significant 2-fold increase in the amount of 8-OHdG in the nuclear DNA of all organs tested in 30 month-old rats as compared to 2-24 month-old rats. These results indicate that the accumulation of 8-OHdG in the DNA of rat organs begins at ages above 24 months.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

Extensive white matter involvement in hemorrhagic shock and encephalopathy syndrome.

Reported is a case of hemorrhagic shock and encephalopathy syndrome (HSE) with extensive white matter involvement. A three year old, previously healthy boy was presented with an acute onset of fever, loss of consciousness and convulsions. He had disseminated intravascular coagulation, metabolic acidosis, non-ketotic hypoglycemia and hepatorenal dysfunction. The computed tomography (CT) scan of his head on the second day of illness demonstrated symmetric, extensive low-density areas in the cerebral and cerebellar white matter. The child died on the 13th hospital day. A post-mortem histopathological examination of the liver revealed centrilobular necrosis and infiltration of fatty acid droplets. The concentrations of serum 2',5'-oligoadenylate synthetase and urinary neopterin were markedly elevated, indicating excessively activated cell-mediated immunity. This overproduction of inflammatory cytokines might play an important role in the pathogenesis of the brain lesion as well as in other clinical and laboratory manifestations. The patient had a decreased serum level of alpha l-antitrypsin, which may have been associated with the development of uncontrolled inflammation and coagulation disorder.

Brain↗
PubMed1996

Transient relaxation of plasmid DNA in Escherichia coli by fluoroquinolones.

We examined the influence of fluoroquinolones (norfloxacin, enoxacin, ofloxacin, levofloxacin, and sparfloxacin) on DNA supercoiling of plasmids in Escherichia coli cells by analysis with agarose gel electrophoresis in the presence of chloroquine. All the fluoroquinolones tested immediately induced DNA relaxation. The relaxed DNA was re-supercoiled, and the process was sensitive to chloramphenicol, suggesting that newly synthesized proteins participate in the reaction. The concentrations of fluoroquinolones required for DNA relaxation were much higher than those required for cell killing. The bactericidal effect of fluoroquinolones is apparently related to mechanisms other than DNA relaxation.

Anti-Infective Agents↗
PubMed1996

Inhibition of leukotriene synthesis by honokiol in rat basophilic leukemia cells.

The effects of honokiol, a diphenyl compound extracted from a Chinese herbal medicine, on leukotriene (LT) synthesis were evaluated in rat basophilic leukemia (RBL) cells. The production of LTC4 and LTB4 stimulated by the Ca2+ ionophore A23187 was measured in RBL-1 cells by high-performance liquid chromatography. Honokiol inhibited the production of LTC4 and LTB4 stimulated by A23187 in RBL-1 cells. Honokiol did not inhibit either phospholipase A2 activity, measured by the release of 3H-arachidonic acid (AA), or LTC4 synthase and LTA4 hydrolase activities, measured with LTA4-free acid as substrate. The synthesis of LTC4 and LTB4 from AA in RBL-1 cell lysates in the presence of Ca2+ was inhibited by honokiol. These results indicate that honokiol blocks LT synthesis by inhibiting 5-lipoxygenase activity. Honokiol also inhibited immunoglobulin E-mediated production of these LTs in RBL-2H3 cells, which was measured by a specific radioimmunoassay (RIA). These results suggest that honokiol may exhibit antiallergic actions by inhibiting LT synthesis in immediate-type hyperreactivity.

Animals↗