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Biomedical subjects

H Matsumoto

Publications and source records attributed to H Matsumoto.

At least 19 recordsLinked to original sources
PubMed1992

Regulation of endothelin-1 synthesis in cultured guinea pig airway epithelial cells by various cytokines.

To study regulatory mechanisms influencing the synthesis and release of ET-1, a potent bronchoconstrictor, epithelial cells from guinea pig tracheas were cultured to test various cytokines for the synthesis of ET-1 and its precursor, big ET-1. Cytokines tested were divided into 4 groups, based on their potential modes of action. IL-8, TNF alpha and TGF beta transiently increased the synthesis of ET-1, while EGF, PDGF and GM/CSF promoted proliferation of ET-1 synthesizing cells. IL-1 enhanced the synthesis of ET-1 precursor without mitogenesis, whereas IL-2, IL-6 and IGF-1 induced both the synthesis of big ET-1 and mitogenesis. These observations suggest that cytokines involved in damage, inflammation and repair of the airway epithelial layer regulate the synthesis and release of ET-1 by multiple mechanisms, thereby influencing airway muscle tone.

Animals↗
PubMed1992

Cloning and disruption of the cefG gene encoding acetyl coenzyme A: deacetylcephalosporin C o-acetyltransferase from Acremonium chrysogenum.

Acetyl CoA: deacetylcephalosporin C o-acetyltransferase(DCPC-ATF) catalyses the final step in the biosynthesis of cephalosporin C (CPC) in Acremonium chrysogenum. The gene encoding DCPC-ATF, cefG, has been isolated from an A. chrysogenum genomic library using a DCPC-ATF cDNA probe. Nucleotide sequence analysis revealed that cefG contains two short introns of 79bp and 65bp. The gene was found to be closely linked to the cefEF gene encoding deacetoxycephalosporin C synthetase/deacetylcephalosporin C synthetase, which catalyses the preceding two steps in the pathway. The two genes are separated by a 1114 bp segment from which they are divergently transcribed. Introduction of the cloned cefG gene to A.chrysogenum resulted in an increased level of DCPC-ATF activity. A plasmid carrying a cefG gene interrupted in the coding region by a selectable marker for resistance to hygromycin B was constructed and used to disrupt the cefG locus in A.chrysogenum. The cefG-disrupted strains were found to lack the ability to produce CPC, and accumulated its precursor, deacetylcephalosporin C in the culture broth. Southern hybridization analysis confirmed that the disruption resulted from a gene replacement event at the cefG locus.

Acetyltransferases↗
PubMed1992

3-O-alkylascorbic acids as free radical quenchers. 3. Protective effect on coronary occlusion-reperfusion induced arrhythmias in anesthetized rats.

Structural modification of ascorbic acid by substitution of the 3-hydroxy group with lipophilic moieties has allowed the development of agents for treating reperfusion injury. These ascorbic acid derivatives inhibited lipid peroxidation, and some of them also reduced coronary reperfusion-induced arrhythmias in anesthetized rats. We found that 3-O-[(dodecylcarbonyl)methyl]ascorbic acid (8) was protective against reperfusion injury without directly influencing hemodynamics. 2-O-Octadecylascorbic acid (19) and 5,6-O-dodecylideneascorbic acid (15) also exhibited a marked effect on reperfusion injury, but significantly reduced the arterial blood pressure and heart rate in rats.

Anesthesia↗
PubMed1992

Discriminative affinity labelling of opioid receptors by enkephalin and morphiceptin analogues containing 3-nitro-2-pyridinesulphenyl-activated thiol residues.

The thiol groups of leucinthiol, cysteamine and cysteine incorporated into opioid peptides enkephalin and morphiceptin were activated by the 3-nitro-2-pyridinesulphenyl (Npys) group to form mixed disulphides highly reactive to a free thiol. Enkephalin analogues containing Npys-leucinthiol or -cysteine at positions 4, 5 and 6 exhibited high affinities for both mu and delta receptors, while morphiceptin analogues containing Npys-cysteine at positions 4 and 5 showed relatively weak affinity only for mu receptors. When these S-activated opioid peptides were incubated with rat brain membrane preparations, it was found, by binding assay using radiolabelled and non-labelled [D-Ala2,MePhe4,Gly-ol5]enkephalin, that they label mu opioid receptors in a dose-dependent manner. The concentrations required to label half of the receptors were 0.2-2 microM for enkephalins and 10-30 microM for morphiceptins. These results suggested that the thiol group labelled by S-activated enkephalins and morphiceptins is present in the ligand binding site of receptor protein, but not in GTPase-binding protein.

Affinity Labels↗
PubMed1992

Carbohydrate profiles shown by a lectin and a monoclonal antibody correlate with metastatic potential and prognosis of human lung carcinomas.

The expression of two carbohydrate markers--namely, 4C9 antigen, which is an Lex antigen, and the Dolichos biflorus agglutinin (DBA) binding site, which is an N-acetylgalactosamine marker--was examined histochemically in tumors and adjacent nontumorous tissues of 102 cases of human lung carcinomas. In nontumorous tissues, the DBA binding site was expressed more frequently than 4C9 antigen, and the DBA binding site had a tendency to be expressed more significantly than in tumor cells. Adenocarcinomas and well-differentiated tumors had a tendency to more cell surface staining. Patients with tumors that expressed DBA binding sites but not 4C9 antigen (4C9-, DBA+) had fewer metastasis and significantly better prognoses than patients with tumors of other carbohydrate profiles. Better prognosis of patients with 4C9-, DBA+ tumors was observed in those with blood group A antigen and those without it, and the better prognosis also was observed in patients with Stage I and IIIA disease.

Adolescent↗
PubMed1992

Molecular cloning of acetyl coenzyme A: deacetylcephalosporin C o-acetyltransferase cDNA from Acremonium chrysogenum: sequence and expression of catalytic activity in yeast.

Acetyl CoA: deacetylcephalosporin C o-acetyltransferase(DCPC-ATF) catalyses the final step in the biosynthesis of cephalosporin C, the conversion of deacetylcephalosporin C to cephalosporin C. A cDNA encoding DCPC-ATF has been isolated from a cDNA library of a cephalosporin C producing fungus Acremonium chrysogenum using oligonucleotide probes based on N-terminal amino acid sequences of the enzyme. The cDNA contains a single large open reading frame for a putative precursor consisting of 12 amino acid(AA) leader peptide of unknown function, 274 AA large subunit and 126 AA small subunit at the carboxyl end. The cDNA was expressed in yeast exhibiting a functional DCPC-ATF activity. It was also indicated that the leader peptide was not essential for expression of the enzyme activity. The primary structure of DCPC-ATF shows significant homology with those of acetyl CoA: homoserine o-acetyltransferase in Saccharomyces cerevisiae and Ascobolas immersus.

Acetyltransferases↗
PubMed1992

Pituitary adenylate cyclase activating polypeptide provokes cultured rat chromaffin cells to secrete adrenaline.

Pituitary adenylate cyclase activating polypeptide (PACAP) provoked the rat chromaffin cells to secrete adrenaline. Within 20 min, the amount of adrenaline secreted by PACAP (10(-8) M) was as much as that caused by acetylcholine (10(-4) M). PACAP, but not acetylcholine, induced a long-term (over 120 min) increase in secretion of adrenaline. PACAP also activated adenylate cyclase and elevated cytosolic Ca2+ concentration. Furthermore, we found immunoreactive PACAP and PACAP binding sites in the rat adrenal medulla. These results suggest that PACAP has an important role in stimulating secretion of adrenaline in the adrenal medulla.

Adrenal Cortex↗
PubMed1992

Mutations affecting regulation of the anabolic argF and the catabolic aru genes in Pseudomonas aeruginosa PAO.

The nucleotide sequence required for a fully functional promoter and operator of the Pseudomonas aeruginosa argF gene (argFpo), the arginine-repressible gene for anabolic ornithine carbamoyltransferase, was defined within a 160 bp region. The streptomycin (Sm) resistance genes strAB of plasmid RSF1010 were fused to argFpo. This construct in P. aeruginosa strain PAO conferred resistance to Sm. Mutants of strain PAO were selected which were resistant to Sm in the presence of arginine due to constitutive expression of argFpo-strAB. These mutants were designated argR. They were unable to grow or grew poorly on arginine or ornithine as the sole carbon and nitrogen source. This growth defect (Aru-/Oru- phenotype) was correlated with a reduced level of N-succinylornithine aminotransferase, an enzyme participating in the major aerobic pathway for arginine and ornithine catabolism in this organism. The argR mutants were classified into four groups by transduction analysis and three argR mutations were mapped on the PAO chromosome. argR9901 and argR9902 were co-transducible with car-9 (at 1 min) and thus close to the oru-310 locus; argR9906 was localized in the oruI (= aru) gene cluster (67 min). Some aru mutants, which have been isolated previously and which produce very low amounts of all enzymes in the arginine succinyltransferase pathway, were unable to repress the argF gene in an arginine medium. Thus, P. aeruginosa PAO appears to have multiple genes that are involved in the regulation of both the anabolic argF and the catabolic aru genes.

Arginine↗
PubMed1992

Potentiation of the antitumor activity of 5-trifluoromethyl-2'-deoxyuridine by the use of depot forms of the parent compound.

5-Trifluoromethyl-2'-deoxyuridine (CF3dUrd), an antitumor agent, is known to be short-lived in human plasma. Since its rapid elimination from the bloodstream seems to have descouraged the clinical evaluation of this drug, we explored the potential use of masked derivatives of CF3dUrd as "depot" forms of the parent compound. First, we observed that the toxicity of CF3dUrd against HeLA cells in culture was 10(4) times greater for a 24-h treatment as compared with a 1-h treatment at identical concentrations of the drug, which suggests the importance of using a prolonged treatment period. In fact, the divided dosing of CF3dUrd to L1210-bearing mice was markedly more effective than its single administration. 5'-O-Hexanoyl-, N3-p-butylbenzoyl-, 5'-O-benzyloxy-methyl-, and 3'-O-benzyl-CF3dUrd were found to be effective in maintaining the CF3dUrd concentration in plasma. The oral doses of these agents required to achieve 50% growth inhibition (ED50) in mice bearing sarcoma 180 tumors were 19, 34, 10, and 13 mg kg-1 day-1, respectively, whereas that of CF3dUrd was 63 mg kg-1 day-1. The ED50 values for these compounds were inversely correlated with the residence time of CF3dUrd in plasma. The therapeutic indices of these compounds, calculated as the dose producing a 50% inhibition of body-weight gain (IB50) divided by the ED50 value (1.89, 1.21, 1.40, and 2.15, respectively), were significantly higher than that of CF3dUrd (0.78). Consequently, these depot forms of CF3dUrd, particularly 3'-O-benzyl-CF3dUrd, are expected to be more useful than the parent compound as antitumor agents.

Animals↗
PubMed1992

A correlation study between blink reflex habituation and clinical state in patients with Parkinson's disease.

The neurologic states and activities of daily life of patients with Parkinson's disease were evaluated using a rating scale with subitems, and subsequently the neurologic disturbance scores and the daily activity impairment scores were obtained. Subjects consisted of 19 normal controls, and 55 ambulatory patients without marked dyskinesia who were on various anti-parkinsonian drugs. Blink reflex was elicited by paired electrical stimulation over the supraorbital nerve. The interval time between the conditioning stimulation and the test stimulation was set at 200 ms, and 5 serial ipsilateral maximal R2 amplitudes on the stimulated side were measured. The mean of the paired maximal R2 amplitude ratio (test/conditioning), expressed as a percentage, was defined as the habituation index. The habituation indices in normal controls and those with Parkinson's disease were 17.1 +/- 7.6 and 51.9 +/- 29.3, respectively (P less than 0.01). The degree of akinesia, rigidity, balance/gait and dysarthria was positively correlated with the habituation index (P less than 0.01), while tremor was not. On the whole the habituation index was found to have a significant correlation not only with the neurologic disturbance score but also with the daily activity impairment score (P less than 0.01).

Activities of Daily Living↗
PubMed1992

Sequence determination and characterization of a phospholipase A2 isozyme from Trimeresurus gramineus (green habu snake) venom.

In addition to phospholipase A2-I (PLA2-I) reported previously (ODA et al., 1991, Toxicon 29, 157), a new PLA2 named PLA2-II was isolated from Trimeresurus gramineus (green habu snake) venom, and its amino acid sequence was determined by sequencing the native protein and the peptides produced by enzymatic (Achromobacter protease I and clostripain) cleavages of the carboxamidomethylated derivative of the protein. The protein consisted of 122 amino acid residues and His-47, Asp-48, and Asp-98 which have been assumed to be essential for PLA2 activity were conserved. Its sequence similarity to PLA2-I was 79%, with 26 residual differences. In contrast to the unique presence of Phe-28 in PLA2-I, PLA2-II contains Tyr-28 as seen in most of other PLA2s. There was no significant difference between the dissociation constants of PLA2-I and PLA2-II for Ca2+. Secondary structure compositions of PLA2-II were similar to those of PLA2-I and Crotalus atrox PLA2. A striking difference was found between these isozymes in contractile activity of isolated smooth muscle preparation of guinea-pig ileum. PLA2-II was over ten times more potent than PLA2-I, although its lipolytic activity toward egg-yolk was even slightly weaker (73%) than that of PLA2-I. The difference in contractile activities of PLA2-I and PLA2-II could be assumed to be due to discriminative lipid recognition brought about by different amino acid residues at the 58th position (Asp for PLA2-I and Asn for PLA2-II).

Alcaligenes↗
PubMed1992

Cerebrospinal fluid endothelin-1 in Alzheimer's disease and senile dementia of Alzheimer type.

We have measured the endothelin-1 concentrations in the cerebrospinal fluid samples from 5 patients with Alzheimer's disease (AD), 6 patients with senile dementia of Alzheimer type (SDAT) and 7 patients with other diseases without dementia (disease control: DC). The cerebrospinal fluid endothelin-1 level was significantly lower in AD than in DC. No correlation was observed between cerebrospinal fluid endothelin-1 concentration and any other factors such as age, duration from onset, systolic blood pressure, cerebrospinal fluid protein level or plasma endothelin-1 concentration in AD or SDAT. These results suggest a possible alteration of the endothelin-1 system in the central nervous system in Alzheimer's disease.

Age Factors↗
PubMed1992

Collaborative study using the preincubation Salmonella typhimurium mutation assay for airborne particulate matter in Japan. A trial to minimize interlaboratory variation.

A collaborative study has been performed over a period of 3 years to develop a suitable method for monitoring the mutagenicity of airborne particulate matter. The study was organized with 8 laboratories and performed in the following steps: (1) selection of a suitable technique for each process involved in the mutagenicity monitoring, (2) developing a tentative protocol by combining systematically the selected techniques, (3) evaluation of the protocol by intra- and inter-laboratory studies, (4) modification of the protocol according to the evaluation, and (5) evaluation of the modified protocol by conducting an interlaboratory study. We found a suitable method for mutagenicity monitoring of particles in the atmosphere. Airborne particles were sampled with a high-volume sampler, the samples were stored at -80 degrees C, extracted by sonication using dichloromethane, solvent-exchanged, and assayed by the preincubation method using Salmonella typhimurium TA98 and TA100. The observed mutagenic activity was normalized with that of an internal standard. Round robin tests revealed that the method resulted in excellent reproducibility. The coefficient of variation for mutagenic activities of airborne particulate samples collected in various districts of Japan were in the range of 14.7 +/- 6.6% to 19.6 +/- 4.0% for strains TA98 and TA100 with and without metabolic activation. We also found that the plate incorporation method was equivalent to the preincubation method for airborne particulate extracts.

Air Pollutants↗
PubMed1992

Gastric cytoprotective anti-ulcerogenic actions of hydroxychalcones in rats.

The preventive effects of hydroxychalcone derivatives on ulcer formation induced by severe necrotizing agents such as 60% ethanol in 150 mM HCl (HCl-ethanol) and 0.2 N NaOH in rats were examined. Among the compounds tested, 2',4'-dihydroxychalcone gave the strongest activity in both experimental models and protected the gastric mucosa from the insult of either necrotizing agent at oral doses ranging from 1 to 10 mg/kg, as evidenced by a dose-related reduction in the ulcer index. The mucosal protective activity of 2',4'-dihydroxychalcone was not affected by pretreatment with indomethacin (5 mg/kg, s.c.). To investigate the detailed mechanism of the mucosal protective action of 2',4'-dihydroxychalcone, its inhibitory effects on the decrease in the hexosamine content from the gastric mucus induced by HCl-ethanol were studied by using it in combination with a dye, Alcian blue. As a result, 2',4'-dihydroxychalcone at an oral dose of 10 mg/kg inhibited the decrease in the dye-recovery from the gastric mucus induced by HCl-ethanol. PGE2 at an oral dose of 0.1 mg/kg exhibited a similar action. These results established that 2',4'-dihydroxychalcone is a potent cytoprotective agent similar to PGE2 effectively preventing gastric ulcer formation induced by strong necrotizing agents and seems to suggest that this compound protects the stomach against its own peptic secretions by reinforcement of gastric resistances. In fact, 2',4'-dihydroxychalcone prevented ulcer formation induced by water-immersion stress in rats and also showed a marked enhancement of the healing of acetic acid-induced gastric ulcers in rats.

Animals↗
PubMed1992

HIV-1 reverse transcriptase inhibitor from Phyllanthus niruri.

An aqueous extract of Phyllanthus niruri (Euphorbiaceae) inhibited human immunodeficiency virus type-1 reverse transcriptase (HIV-1-RT). The inhibitor against HIV-1-RT in this plant was purified by combination of three column chromatographies, Sephadex LH-20, cellulose, and reverse-phase high-performance liquid chromatography. The inhibitor was then identified by nuclear magnetic resonance (NMR) spectra as repandusinic acid A monosodium salt (RA) which was originally isolated from Mallotus repandus. The 50% inhibitory doses (ID50) of RA on HIV-1-RT and DNA polymerase alpha (from HeLa cells) were 0.05 microM and 0.6 microM, respectively, representing approximately a 10-fold more sensitivity of HIV-1-RT compared with DNA polymerase alpha. RA was shown to be a competitive inhibitor with respect to the template-primer while it was a noncompetitive inhibitor with respect to the substrate. RA as low as 10.1 microM inhibited HIV-1-induced cytopathogenicity in MT-4 cells. In addition, 4.5 microM of RA inhibited HIV-1-induced giant cell formation of SUP-T1 approximately 50%. RA (2.5 microM) inhibited up to 90% of HIV-1 specific p24 antigen production in a Clone H9 cell system.

Antigens, Viral↗
PubMed1992

Duodenal reflux through the pylorus induces gastric adenocarcinoma in the rat.

We investigated whether duodenal reflux through the pylorus is involved in the development of gastric cancer. Male Wistar rats weighing 230-250 g were subjected to three types of operative procedures: (i) allowing reflux through the pylorus; (ii) allowing reflux through a gastrojejunal stoma; and (iii) gastrotomy. No carcinogens were given, and the animals were killed 50 weeks after surgery. No cancers were detected in any of the 18 animals with gastrotomy. In contrast, seven (41%) of 17 animals with reflux through the pylorus and four (31%) of 13 animals with reflux through the stoma had adenocarcinoma. Differences in the incidence between both reflux groups and the gastrotomy group were significant (P < 0.01 and P < 0.05 respectively). All of the adenocarcinomas developed in the pyloric mucosa near the pylorus in the animals with reflux through the pylorus, and in the oxyntic mucosa near the stoma in those with reflux through the stoma. Adenocarcinomas appeared as a polyploid mass with or without slight central erosion. Most of the adenocarcinomas were of the well-differentiated tubular type, and the others were of the mucinous type. No differences in either the histologic type or depth of invasion of the adenocarcinoma were recognized between the two duodenogastric reflux groups. Precancerous or paracancerous lesions, such as adenoma, adenocystic proliferation, and stomal pseudopyloric metaplasia, were more frequently found in the same region as the adenocarcinomas. These findings suggest that duodenogastric reflux in the rat has potent carcinogenic activities not only in the oxyntic mucosa through the stoma, but also in the pyloric mucosa through the pylorus.

Adenocarcinoma↗
PubMed1992

Transient unilateral reverse ventilation/perfusion mismatch in a patient with lung cancer.

The authors report a transient, unilateral reverse ventilation/perfusion (V/P) mismatch in a patient with squamous cell lung cancer. The right lung was well perfused but not ventilated (unilateral reverse V/P mismatch). However, lung imaging performed 3 days later demonstrated the absence of both perfusion and ventilation (V/P match). Reverse V/P mismatch may be a transient process.

Carcinoma, Squamous Cell↗