Biomedical subjects

M Matsumoto

Publications and source records attributed to M Matsumoto.

At least 19 recordsLinked to original sources

PubMed1992

Influence of oxidative stress on induced tolerance to ischemia in gerbil hippocampal neurons.

We investigated whether reversible oxidative stress induced by the administration of the superoxide dismutase inhibitor, diethyldithiocarbamate, could induce tolerance to subsequent cerebral ischemia in gerbil hippocampal neurons. Mature male gerbils received intraperitoneal injections of diethyldithiocarbamate (1.0 g/kg), which led to reduced superoxide dismutase activity and increases in thiobarbituric acid-reactive substance in the brain. Cerebral ischemia was produced by occluding the bilateral common carotid arteries for 5 min, either 2 or 4 days after diethyldithiocarbamate injection. One week after ischemia, samples from each brain were stained with hematoxylin-eosin to evaluate ischemic neuronal damage in the hippocampal CA1 sector. Diethyldithiocarbamate treatment 4 days before ischemia had significant protective effects against cerebral ischemia, while diethyldithiocarbamate 2-day pretreatment and vehicle treatment failed to show neuroprotection. Biochemical examinations showed a clear induction of heat shock protein 72 and a significant increase in manganese-containing superoxide dismutase in the hippocampus in animals treated with diethyldithiocarbamate 4 days prior to ischemia. These results suggested that the oxidative stress caused by diethyldithiocarbamate could induced tolerance to ischemia in the gerbil brain, and that the increase in the biosynthesis of manganese-containing superoxide dismutase and heat shock protein 72 could provide a biochemical explanation of the tolerance induced under these conditions.

Animals↗

PubMed1992

Purification and characterization of a novel growth factor (FF-GF) synthesized by a rat hepatoma cell line, FF101.

A rat hepatoma cell line, FF101, established in serum-free, protein-free medium, synthesizes a growth factor(FF-GF). FF-GF was purified by gel filtration chromatography, cation-exchange chromatography and isoelectric focusing. Purified FF-GF was revealed as a single band on SDS-gel electrophoresis and its molecular weight was estimated to be 70 KDa. FF-GF stimulated DNA synthesis of various cells from different origins. The growth-promoting activities of FF-GF were abolished by treating with protease, dithiothreitol, acid and heating, whereas its activity was not inhibited by antibodies against acidic and basic fibroblast growth factors. These results indicate that FF-GF is a novel growth factor.

Animals↗

PubMed1992

Vitamin E inhibits protein oxidation in skeletal muscle of resting and exercised rats.

It is well known that exercise induces lipid peroxidation in skeletal muscle and that vitamin E prevents exercise-induced lipid damage. In this study we show for the first time, an increase in protein oxidation in skeletal muscle after a single bout of exercise, related to an exercise-induced decrease in lipophilic antioxidants, and substantial protection against both resting and exercise-induced protein oxidation by supplementation with various isomers (alpha-tocopherol, alpha-tocotrienol) of vitamin E.

Animals↗

PubMed1992

Effect of local cyanide perfusion on rat striatal extracellular dopamine and its metabolites as studied by in vivo brain microdialysis.

To investigate in vivo effects of energy failure on functions of dopaminergic neurons, we administered 0 (control), 0.2, 1 or 2 mM sodium cyanide (NaCN) dissolved in Ringer's solution for 60 min into the rat striatum through a brain microdialysis membrane. During NaCN perfusion, a transient and concentration-dependent increase in dopamine (DA) levels in the dialysate was observed. The maximum DA level during 2 mM NaCN perfusion was found to be 63-fold higher than the control levels. Leves of 3,4-dihydroxyphenylacetic acid and homovanillic acid were continuously lowered during and after NaCN perfusion. These data suggest that suppression of ATP production by NaCN induces an abrupt and remarkable increase in dopamine release from the nerve terminal in the striatum.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Opposite effect between intercalator and minor groove binding drug on the higher order structure of DNA as is visualized by fluorescence microscopy.

Fluorescence microscopy is applied to obtain the information on the change of the higher-order structure of giant DNA molecules in an aqueous solution. Using T4 DNA, it becomes clear that ethidium bromide, an intercalator, tends to extend the DNA, whereas minor groove binding drugs such as 4',6-diamidino-2-phenylindole and Hoechst 33258 tend to contract the DNA. These changes of higher-order structure have been quantitatively evaluated as the changes in persistent length together with the change of contour length. It is also confirmed that the persistent length obtained by use of fluorescence microscopy is reliable enough comparing with those reported for the shorter DNA by use of light scattering.

Bacteriophage T4↗

PubMed1992

Expression of heme oxygenase and its RNA in mouse liver after injection of heme and splenectomy.

Heme is known to activate the HO (heme oxygenase) gene in cultured cells, but little is known about the effect of heme on the HO gene in intact organisms. The expressions of HO and its RNA in mouse liver were measured using mouse HO cDNA and HO antibody after injection of heme or splenectomy. The antibody was prepared against a beta-galactosidase-HO hybrid protein made in Escherichia coli. The HO mRNA level increased to a maximum 15 h after heme injection. In contrast, expression of HO was maximal about 45 h after heme injection. Essentially the same results were obtained in mice after splenectomy. These results suggest that the HO gene in mouse liver was activated by the injection of heme and splenectomy.

Animals↗

PubMed1992

Flow cytometric analysis of nuclear DNA content of duct cell carcinoma of the pancreas.

BACKGROUND: This study was designed to evaluate the efficacy of nuclear DNA content analysis in determining the prognosis of carcinoma of the pancreas. METHODS: Resected and paraffin-embedded specimens from 72 patients with duct cell carcinoma of the pancreas were examined, and flow cytometry was used to explore the relationship between DNA ploidy and TNM classification or histologic grade. RESULTS: DNA aneuploidy was found histologically in 42.9%, 56.8%, and 71.4% of Grade 1, 2, and 3 tumors, respectively. DNA ploidy showed a statistically significant correlation with T category and retroperitoneal invasion. The cumulative survival rate of patients with retroperitoneal invasion was shorter than that of those without retroperitoneal invasion. Among the patients with retroperitoneal invasion, those with DNA aneuploidy had a significantly shorter survival time than did those with DNA diploidy. CONCLUSIONS: The DNA ploidy pattern, in combination with the presence or absence of retroperitoneal invasion, appears to be useful in predicting the prognosis for duct cell adenocarcinoma of the pancreas.

Adult↗

PubMed1992

The primary structure of the alpha subunit of a starfish guanosine-nucleotide-binding regulatory protein involved in 1-methyladenine-induced oocyte maturation.

Starfish-oocyte maturation induced by 1-methyladenine (MeAde) was inhibited by microinjection of pertussis toxin (PTX). The inhibition appeared to result from PTX-catalyzed ADP-ribosylation of a 39-kDa guanosine-nucleotide-binding regulatory protein (G protein) in the oocyte. These results strongly support the hypothesis that the MeAde-induced signals operate via a membrane receptor and are carried by the PTX-sensitive G protein. When PTX-injected oocytes were treated with dithiothreitol, 85% of them reinitiated meiosis, suggesting that dithiothreitol did not act on the MeAde receptor. We constructed a cDNA library from the immature ovary of starfish, Asterina pectinifera, and screened it with the cDNA of the alpha subunit of an inhibitory rat G protein (Gi-2). A positive cDNA clone contained an open reading frame of 1062 bases which had 74% identity with the rat Gi-2 cDNA. The deduced amino acid sequence was 85% and 89% identical to rat Gi-2 and rat Gi-1, respectively. The alpha subunit of the G protein purified from cortices of starfish oocytes was digested by trypsin and the resulting four peptides were microsequenced. Comparison of these amino acid sequences with the predicted one indicated that the isolated cDNA clone encoded the alpha subunit of the PTX-sensitive G protein in oocytes. The C-terminal sequence, KNNLKDCGLF, was identical to that of Gi, suggesting that the cysteine residue is the site of ADP-ribosylation.

Adenine↗

PubMed1992

Biological activities and quantitative structure-activity relationships of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones as aldose reductase inhibitors.

A series of spiro[imidazolidine-4,4'(1'H)-quinazoline]- 2,2'5(3'H)-triones were prepared and tested for aldose reductase inhibitory activity. The 6'-halogenated derivatives were found to be highly potent in vitro inhibitors of male rabbit lens aldose reductase and in vivo inhibitors of polyol accumulation in the sciatic nerves of galactosemic rats. Of these, (4R)-6'-chloro-3'-methylspiro[imidazolidine-4,4'(1'H)-quinazoline] -2,2',5(3'H)-trione (67) showed the most potent in vitro and in vivo activities. An oral dose of 3 g/kg of compound 67 caused neither death nor behavioral abnormality in the preliminary acute toxicity study using mice and rats. Compound 67 was selected as a candidate for further evaluation. The quantitative structure-activity relationships in this series are also discussed.

Aldehyde Reductase↗

PubMed1992

Alpha 2-adrenoceptor modulation of 5-HT biosynthesis in the rat brain.

The purpose of the present study is to clarify the modulation of the biosynthesis of serotonin (5-HT) via the alpha 2-adrenoceptors in the brain. For this purpose, 5-hydroxytryptophan (5-HTP) accumulation was determined using an HPLC-ECD system in the presence of the inhibition of aromatic L-amino acid decarboxylase. Administration of alpha 2-adrenoceptor agonist, clonidine, produced a reduction of the in vivo 5-HTP accumulation in both the rat hippocampus and dorsal raphe nucleus. In addition, alpha 2-adrenoceptor antagonist, idazoxan, increased the 5-HTP accumulation in both the hippocampus and the dorsal raphe nucleus. In rats with catecholaminergic neurons denervated by pretreatment with 6-hydroxydopamine, clonidine failed to produce a reduction of 5-HTP accumulation in the dorsal raphe nucleus. On the other hand, hippocampal 5-HTP accumulation was decreased significantly. Brain tryptophan levels were unaffected by either clonidine or idazoxan. These results suggest that alpha 2-adrenoceptors might modulate serotonin biosynthesis and this modulation might be related to the neuroanatomical differences in the rat brain.

5-Hydroxytryptophan↗

PubMed1992

Effect of clonidine on the release of serotonin from the rat hippocampus as measured by microdialysis.

The purpose of the present study is to clarify the effect of clonidine on the release of serotonin from the rat hippocampus in vivo. For this purpose, endogenous serotonin release was measured by brain microdialysis. Potassium-evoked serotonin release from the hippocampus of freely moving rats was significantly inhibited when clonidine (10(-5) M) was added to the perfusion solution, while the 5-hydroxyindoleacetic acid output remained unchanged. In catecholaminergically denervated rats, clonidine (10(-5) M) also inhibited the potassium-evoked serotonin release from the hippocampus and the 5-hydroxyindoleacetic acid output was unaffected by clonidine. These results suggest that the inhibitory effect of clonidine on serotonin release from the hippocampus might reflect the activation of alpha 2-adrenoceptors which are localized on the serotonergic nerve terminals.

Animals↗

PubMed1992

D-galactosamine-induced cell damage enhances specific binding of prostaglandin E1 to rat hepatocytes.

Specific bindings of [3H]prostaglandin E1 ([3H]PGE1), 125I-glucagon and [3H]norepinephrine to D-galactosamine (GalN)-treated rat hepatocytes in primary culture were investigated. After a two hour-treatment with GalN (1 and 10mg/ml), hepatocytes showed an enhanced specific binding to [3H]PGE1, whereas 125I-glucagon binding was little affected and [3H]norepinephrine binding was strongly diminished. Scatchard plot analysis indicated an increase of binding sites of [3H]PGE1. This unusual manner of [3H]PGE1 binding is suggested to indicate a special property of PGE1 receptor and may be associated with the cytoprotective effect of prostaglandins.

Alprostadil↗

PubMed1992

Synergistic inhibition of human gastric carcinoma cell growth by 1-beta-D-arabinofuranosylcytosine and hydroxyurea or 2'-deoxyguanosine in vitro.

The cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in combination with hydroxyurea (HU) or 2'-deoxyguanosine (GdR) on human gastric carcinoma MK-1 cells and colon carcinoma HT-15 cells was studied. Synergistic interaction between ara-C and HU on MK-1 cells and HT-15 cells, or ara-C and GdR on MK-1 cells was shown using the combination index method. HU increased the accumulation of ara-C triphosphate (ara-CTP) in the acid-soluble pool and diminished the cellular deoxyCTP (dCTP) pool. HU had no effect on the incorporation of ara-C into DNA and RNA. These results indicate that HU-induced elevation in ara-CTP and decrease in dCTP are the basis for synergy among ara-C and HU in MK-1 cells. GdR diminished cellular dCTP slightly, but it decreased the accumulation of ara-CTP in the acid-soluble pool and did not increase the incorporation of ara-C into DNA. On the other hand, ara-C increased cellular deoxyGTP (dGTP) level in the presence of GdR. These results indicate that synergy between ara-C and GdR is mediated through increased cellular dGTP which might inhibit DNA synthesis directly.

Carcinoma↗

PubMed1992

[US findings of junctional parenchymal defect of the kidney].

Junctional parenchymal defect (JPD) is a triangular or linear hyperechoic structure in the anterosuperior or posteroinferior surface of the kidney. The intermediate septum is a band-like cortex, running obliquely in the central echo complex. Some authors have suggested that these structures result from partial fusion of the embryonic parenchymatous masses called renunculi (renunculi theory). In a prospective study of 600 adult patients, the anterosuperior JPD of the right kidney was most frequently identified on ultrasonography (33.5%). The incidence of JPD did not depend on sex or age, and intermediate septum was frequently associated with JPD (71.4%). These data are compatible with the renunculi theory. The prominent septum of Bertin was located in the same position on the intermediate septum in the majority of cases (96.7%). Therefore, we suggest that the typical prominent septum of Bertin may be an incomplete intermediate septum. In order to differentiate JPD from pathologic conditions such as cortical scar or hyperechoic tumor, it is necessary to identify its characteristic location and shape.

Adult↗

PubMed1992

Determination of nitroxynil in cow milk by reversed-phase high-performance liquid chromatography with dual-electrode coulometric detection.

A sensitive and specific method is described for the determination of nitroxynil (fasciolicide) residues in cow milk. The milk samples were extracted with acetone and acetonitrile, following clean-up using a simple liquid-liquid extraction step. Nitroxynil was separated from the matrix peaks by reversed-phase high-performance liquid chromatography and detected using dual-electrode coulometric detection. The mobile phase was a mixture (20:80, v/v) of acetonitrile and 0.05 M potassium dihydrogenphosphate with the pH adjusted to 4.0. The flow-rate was 1 ml/min at 40 degrees C. The applied potentials of detectors 1 and 2 were maintained at -0.7 and +0.2 V, respectively. Average recoveries (n = 5) of nitroxynil from milk samples spiked at concentrations of 0.01 and 0.1 micrograms/ml were found to be 92.0% and 97.0% with coefficients of variation of 6.2% and 2.2%, respectively. The detection limit of nitroxynil in milk was 0.7 ng/ml. During the analysis of 30 raw cow milk and 140 market milk samples, nitroxynil was detected at a level of 4 ng/ml in one raw cow milk sample.

Animals↗

PubMed1992

[Preliminary specification of X-ray CT for lung cancer screening (LSCT) and its evaluation on risk-cost-effectiveness].

In Japan mass screening for lung cancer is widely performed by chest X-ray film of 10 x 10 cm, with sputum cytology for high-risk groups. However, the effectiveness of the present mass screening program for lung cancer has been less than expected, although some date have shown improvement of the survival rate as a result of mass screening. We propose a new X-ray CT method of screening for lung cancer called Lung Cancer Screening CT (LSCT). The preliminary specifications for LSCT are as follows: scan speed is within 10 sec for a 40 cm length with a 1 cm slice thickness, and the absorption dose for lung is less than 1 cGy. A computer-assisted diagnostic system is necessary for image reading. The risk-benefit analysis of LSCT indicates that Japanese men and women over 45 years old can be screened in 1992 and thereafter. The cost per person.year of LSCT screening is estimated to be 1.4 x 10(6) yen for a population incidence rate of 50 x 10(-5) person/year and average life expectancy of 30 years. In 1992 the above condition will be satisfied by men aged 55 years old and above, but not by women of any age. We believe that LSCT should be developed further and tested in the high-risk group of men with an incidence rate of 100 x 10(-5) persons/year or more.

Adult↗

PubMed1992

Release of newly synthesized platelet-activating factor (PAF) from human polymorphonuclear leukocytes under in vivo conditions. Contribution of PAF-releasing factor in serum.

The behavior of platelet-activating factor (PAF) produced in stimulated human polymorphonuclear leukocytes (PMN) was investigated in the presence of serum under conditions close to those existing in vivo. When the cells were stimulated in the presence of the serum obtained from a PAF acetylhydrolase (PAF-AH)-deficient Japanese subject, over 60% of synthesized PAF was detected in the extracellular medium by bioassay, scintillation proximity RIA and selected ion monitoring/gas chromatography/mass spectrography analysis. The release of PAF from PMN after stimulation with FMLP and A23187 was also observed in the presence of normal serum treated with acid to inactivate PAF-AH. The heterogeneity of the molecular species of extracellular PAF was similar to that of intracellular PAF produced in stimulated PMN in the presence of PAF-AH-deficient serum, ruling out the possibility that a specific molecular species of PAF was preferentially released from the cells in the presence of the serum. As these data suggested the occurrence of PAF-releasing factor(s) in the serum, an attempt was made to partially purify this factor from PAF-AH-deficient serum and acid-treated normal serum by ammonium sulfate fractionation and column chromatography with DEAE-Cellulofine and Sepharose CL-6B. The molecular mass of PAF-releasing factor revealed on a TSK gel G3000 SW HPLC column was 240 kDa, which was different from that of albumin. The binding assay, newly developed for this study, revealed that the PAF-binding activity of PAF-releasing factor is stronger than that of albumin, and that the PAF-releasing factor forms a complex with PAF at low concentration (10(-9) M). PAF bound to this factor was difficult to be hydrolyzed by serum PAF-AH. On the other hand, the PAF/PAF-releasing factor complex had aggregatory activity toward washed rabbit platelets. These observations suggest that certain protein(s) releases and carries the PAF newly synthesized by PMN in blood plasma/serum. Thus it appears that PAF functions as an autacoid in vivo, along with other mediators.

Calcimycin↗

PubMed1992

Analysis of the close relationship between human astrocytoma-specific antigens detected by murine monoclonal antibodies and c-kit proto-oncogene product.

Tyrosine-specific phosphorylated proteins found exclusively on the cell surface of human astrocytomas were previously identified with murine monoclonal antibodies, designated as GA-17, GB-4 and GC-3. The purpose of this study was to further characterize the antigens and investigate the relationship between them and c-kit protooncogene product. We demonstrated that the antigens had protein kinase activity. Moreover, GA-17 reacted with c-kit protein expressed on the membrane of A172 human glioblastoma cells.

Antibodies, Monoclonal↗