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H Maeda

Publications and source records attributed to H Maeda.

At least 19 recordsLinked to original sources
PubMed1992

Hydroxyl radical production by H2O2 plus Cu,Zn-superoxide dismutase reflects the activity of free copper released from the oxidatively damaged enzyme.

To elaborate the catalytic activity of Cu2+ of Cu,Zn-superoxide dismutase (SOD) in the generation of hydroxyl radical (.OH) from H2O2, we investigated the mechanism of inactivation of alpha 1-protease inhibitor (alpha 1-PI), mediated by H2O2 and Cu,Zn-SOD. When alpha 1-PI was incubated with 500 units/ml Cu,Zn-SOD and 1.0 mM H2O2, 60% of anti-elastase activity of alpha 1-PI was lost within 90 min. ESR spin trapping using 5,5-dimethyl-1-pyrroline N-oxide showed that free .OH was indeed generated in the reaction of Cu,Zn-SOD/H2O2; this was substantiated by the almost complete eradication of .OH by either ethanol or dimethyl sulfoxide accompanied by the generation of carbon-centered radicals. .OH production and alpha 1-PI inactivation in the H2O2/SOD system became apparent at 30 min or later. Dimethyl sulfoxide and 5,5-dimethyl-1-pyrroline N-oxide protected inactivation of alpha 1-PI significantly in this system, indicating that alpha 1-PI inactivation was mediated by .OH. SOD activity decreased rapidly during the reaction with H2O2 for the initial 30 min. Time-dependent changes in the ESR signal of SOD showed the destruction of ligands for Cu2+ in SOD by H2O2 within this initial period. Thus we conclude that inactivation of alpha 1-PI is mediated in the H2O2/Cu,Zn-SOD system via the generation of .OH by free Cu2+ released from oxidatively damaged SOD.

Cyclic N-Oxides↗
PubMed1992

Gene structure of human indoleamine 2,3-dioxygenase.

Two genomic DNA clones that encode human indoleamine 2,3-dioxygenase (IDO) were isolated from the human genomic DNA library using the IDO cDNA as a probe, and their restriction maps and partial nucleotide sequences were determined. The human IDO gene spanned 15 kilobase pairs with ten exons. The 5' terminus of the IDO mRNA was 33 nucleotides upstream of the translation initiation codon ATG. The 5' flanking region contained ISRE, X-box, and Y-box like sequences. Southern blot analysis of the human genomic DNA indicated that the human IDO gene was present in a single copy in the genome.

Alternative Splicing↗
PubMed1992

Effects of benzylpiperazine derivatives on the neurotoxicity of 3,4-methylenedioxymethamphetamine in rat brain.

The neurotoxicity of 3,4-methylenedioxymethamphetamine (MDMA) in rat brain was attenuated significantly by coadministration of several benzylpiperazines (p-nitrobenzylpiperazine, p-chlorobenzylpiperazine and 1-piperonylpiperazine), which were weak inhibitors for [3H]6-nitroquipazine binding to the 5-hydroxytryptamine (5-HT) transporter in rat brain. These results suggest that these benzylpiperazines may inhibit the MDMA-induced neurotoxicity by a novel neuropharmacological effect other than 5-HT uptake inhibition.

3,4-Methylenedioxyamphetamine↗
PubMed1992

Antagonism of 3,4-methylenedioxymethamphetamine-induced neurotoxicity in rat brain by 1-piperonylpiperazine.

The effects of 1-piperonylpiperazine and N,alpha-dimethylpiperonylamine, which are weak inhibitors for [3H]5-hydroxytryptamine (5-HT) uptake, on 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity were examined. The reductions of serotonergic parameters in the rat cerebral cortex produced by multiple administration of MDMA (10 mg/kg) were attenuated significantly by coadministration of 6-nitroquipazine (10 mg/kg), paroxetine (10 mg/kg) or 1-piperonylpiperazine (20 mg/kg), but not by N,alpha-dimethylpiperonylamine (20 mg/kg). The present data suggest that 1-piperonylpiperazine might inhibit the MDMA-induced neurotoxicity by effect(s) other than 5-HT uptake inhibition.

3,4-Methylenedioxyamphetamine↗
PubMed1992

Inhibitory effect of oryzacystatins and a truncation mutant on the replication of poliovirus in infected Vero cells.

Poliovirus, a picornavirus family member, requires the processing of its poly-protein by its own cysteine proteinase for replication. Oryzacystatin-I and oryzacystatin-II, proteinaceous cysteine proteinase inhibitors (cystatins) of rice seed origin, were found to inhibit the replication of poliovirus effectively in infected Vero cells in vitro. Truncated oryzacystatin-I, which lacks the NH2-terminal 25 amino acid residues of the intact protein, is an even more effective inhibitor, eliciting its effect at concentrations of less than 0.25 nmol/ml. The low molecular weight cysteine proteinase inhibitors, E-64, E-64C and loxistatin, showed no anti-viral effect at any concentration investigated.

Animals↗
PubMed1992

Antitumor effects of SMANCS on rat mammary tumor induced by 7,12-dimethylbenz[a]anthracene.

We previously found that a high-molecular-weight anticancer agent, polystyrene-co-maleic acid conjugated neocarzinostatin (SMANCS), in which two chains of styrene/maleic acid copolymer are conjugated to the anticancer protein neocarzinostatin (NCS), accumulated more selectively in tumor tissue than in normal tissue and was more stable than NCS in blood. These results indicate that SMANCS should have less systemic toxicity and a better therapeutic effect than NCS. In this study, the antitumor activity and adverse effects of SMANCS were compared with those of NCS by using rat mammary tumor induced by 7,12-dimethylbenz[a]anthracene. When tumors of rats, that had received 7,12-dimethylbenz[a]anthracene (20 mg/kg, one dose, p.o. in oily formulation), became palpable usually after 4-20 weeks, SMANCS treatment was initiated. Thirty days after i.v. administration of SMANCS (0.1 mg/kg 3 times and 0.3 mg/kg 3 times), tumors had shrunk in 35 of 37 rats (a mean weight was about 10% of control value; or decreased to about 30% of the value of before treatment in tumor weight); tumor size had not changed in 1 rat, and in the remaining 1 rat the tumor had enlarged. Thirty days after i.v. administration of NCS, tumors had shrunk in 8 of 14 rats, but the tumor size was unchanged in 1 rat and was enlarged in 5. In the control group, all tumors had enlarged. Development of new tumors was completely prevented by the administration of SMANCS. Histological examination of sequential slices of tumor revealed clear finding of degeneration and tumor encapsulation at 30 days after initial administration of SMANCS, with an accompanying fatty degeneration, but these effects were not observed for tumors treated with NCS. Although red blood cell counts and hemoglobin amounts decreased significantly in rats receiving NCS, no such effects were apparent in the SMANCS group.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Intussusception of an appendiceal mucocele: report of a case.

A 66 year old Japanese female was admitted to our department for the examination and treatment of a mass in the cecum. She had experienced no symptoms or signs other than a positive test result for fecal occult blood. The mass in the cecum was confirmed by barium enema, colonofiberscopy and CT scanning. The presumptive diagnosis was a submucosal tumor of the cecum, however, a laparotomy subsequently revealed intussusception of an appendiceal mass. An ileocaecal resection with an ileocolic anastomosis was therefore performed and the mass was histologically diagnosed as a mucocele of the appendix. This patient is only the 24th case of intussusception of a mucocele of the appendix to be reported in Japan. A review of the available literature on this condition follows the case report.

Aged↗
PubMed1992

Hydroxyl radical generation by red tide algae.

The unicellular marine phytoplankton Chattonella marina is known to have toxic effects against various living marine organisms, especially fishes. However, details of the mechanism of the toxicity of this plankton remain obscure. Here we demonstrate the generation of superoxide and hydroxyl radicals from a red tide unicellular organism, C. marina, by using ESR spectroscopy with the spin traps 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and N-t-butyl-alpha-phenylnitrone (PBN), and by using the luminol-enhanced chemiluminescence response. The spin-trapping assay revealed productions of spin adduct of superoxide anion (O2-) (DMPO-OOH) and that of hydroxyl radical (.OH) (DMPO-OH) in the algal suspension, which was not observed in the ultrasonic-ruptured suspension. The addition of superoxide dismutase (500 U/ml) almost completely inhibited the formation of both DMPO-OOH and DMPO-OH, and carbon-centered radicals were generated with the disappearance of DMPO-OH after addition of 5% dimethyl sulfoxide (Me2SO) and 5% ethanol. Furthermore, the generation of methyl and methoxyl radicals, which are thought to be produced by the reaction of hydroxyl radical and Me2SO under aerobic condition, was identified using spin trapping with a combination of PBN and Me2SO. Luminol-enhanced chemiluminescence assay also supported the above observations. These results clearly indicate that C. marina generates and releases the superoxide radical followed by the production of hydroxyl radical to the surrounding environment. The velocity of superoxide generation by C. marina was about 100 times faster than that by mammalian phagocytes per cell basis. The generation of oxygen radical is suggested to be a pathogenic principle in the toxication of red tide to susceptible aquaculture fishes and may be directly correlated with the coastal pollution by red tide.

Cyclic N-Oxides↗
PubMed1992

Bactericidal activity of alkyl peroxyl radicals generated by heme-iron-catalyzed decomposition of organic peroxides.

To clarify the nature of cytocidal molecular species among the radicals generated in the iron-catalyzed reactions of peroxides (ROOH), we examined the cytocidal effects of these radicals against gram-positive and gram-negative bacteria in the presence or absence of various radical scavengers. Three organic peroxides, t-butyl hydroperoxide (t-BuOOH), methyl ethyl ketone peroxide (MEKOOH), and cumene hydroperoxide, were used. Each radical generated from these peroxides was identified and quantitated by electron spin resonance (ESR) spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The major cytotoxic radical species generated in the mixtures of various peroxides and heme iron, especially methemoglobin, metmyoglobin, or hemin, was the alkyl peroxyl radical (ROO.). Strong bactericidal action against gram-positive bacteria was observed in the peroxide-heme iron system, especially in the case of t-BuOOH and MEKOOH. Killing curves for gram-positive bacteria showed an initial lag period, which may indicate the multihit/multitarget kinetics of cell killing. When the diethylenetriamine pentaacetic acid (DTPA)-Fe2+ complex was used as a catalyst for decomposition of various peroxides, alkyl, alkoxyl, and alkyl peroxyl radicals were identified by spin-trapping analysis. However, study of the time course of alkyl peroxyl radical production in the DTPA-Fe2+ complex system revealed that radical species generated in this system were very short lived: a maximal level was achieved within 1 min and then declined sharply, and no bactericidal activity was observed after 10 min. In contrast, the alkyl peroxyl radical level generated by the organic peroxide-heme iron system remained high for 30 min or longer. The generation of alkyl peroxyl radicals quantified by ESR correlated quite well with the bactericidal effect of the system of peroxide plus iron. In addition, bactericidal activity was completely inhibited by the addition of the spin trap DMPO, as well as of other various radical scavengers (alpha-tocopherol and L-ascorbic acid), into the peroxide-heme iron system, but this effect was not observed with superoxide dismutase, beta-carotene, dimethyl sulfoxide, diphenylamine, or butylated hydroxyltoluene. In view of these results, it is assumed that alkyl peroxyl radicals are the potent molecular species that are cytotoxic against bacteria, whereas alkoxyl radicals (RO.) generated in this system do not affect bacterial viability.

Benzene Derivatives↗
PubMed1992

Reduced lysozyme in solution and its interaction with non-ionic surfactants.

Reduced lysozyme at pH 2.5 bound poly(oxyethylene) alkylethers in two steps and the maximum bound amount Qmax of the surfactant reached as large as 0.5-0.7 mole per mole amino acid residue in the cooperative binding step. Binding isotherms were well superimposed when surfactant concentrations were normalized by respective values of the critical micelle concentration, cmc. In terms of the onset concentrations of the cooperative binding C*, hydrophobicity of reduced lysozyme was quantitatively defined as RT In (cmc/C*) which amounted to 670 J per mole surfactant and was unique to the protein irrespective of the kind of surfactant. Qmax could be used as another measure of the hydrophobicity of the protein. The binding isotherms were evaluated by two methods: equilibrium dialysis and surface tension. Their results were consistent with each other and rather complementary. Reduced lysozymes were molecularly dispersed at pH below 2.5 in 0.01 M NaCl but aggregation took place as pH increased. The aggregates could not be dissociated on dilution nor by the addition of nonionic surfactants but by lowering pH. The irreversible nature of the aggregation was reasonably interpreted with a model based on the 'entangled' arrangement of the beta-sheets, which could account for the irreversible aggregation of unfolded proteins in general.

Animals↗
PubMed1992

Characterization of a mouse/human chimeric monoclonal antibody (C beta 1) to a principal neutralizing domain of the human immunodeficiency virus type 1 envelope protein.

A chimeric mouse-human antibody (C beta 1) was constructed that recognized the principal neutralizing domain (PND) of human immunodeficiency virus type 1 (HIV-1) gp120. The constant (C) immunoglobulin regions (C gamma 1 and C kappa) of a mouse monoclonal antibody, 0.5 beta, were substituted for the human C gamma 1 and C kappa by recombining the DNA modules encoding variable or C regions. The DNA constructs were then transfected into X63 Ag8.653 myeloma cells. A clone with a high production of the chimeric antibody (C beta 1) was selected. This antibody was tested for its biological activity against HIV-1. It bound to the surface of HTLV-IIIB-infected cells and reacted with gp120/160 with equal affinity and specificity to that of the parental 0.5 beta murine monoclonal antibody in a Western blot assay. Neutralization and/or enhancement of HIV infection were evaluated with C beta 1 and 0.5 beta. Both C beta 1 and 0.5 beta neutralized cell-to-cell infection and cell-free virus infection by HTLV-IIIB. Antibody-dependence enhancement of HIV infection was not observed with either C beta 1 or 0.5 beta in the presence or absence of human complement. Antibody-dependent cell-mediated cytolysis (ADCC) and antibody-dependent complement-mediated cytolysis (ACC) were observed with C beta 1 but not with the parental 0.5 beta. These findings suggest that the neutralizing antibodies to PND may neutralize but not enhance HIV infection. Furthermore, the high levels of ACC and ADCC shown against HIV-infected cells by C beta 1 indicate that the clinical application of such monoclonal antibodies may be possible.

Amino Acid Sequence↗
PubMed1992

Study on human erythrocyte thioltransferase: comparative characterization with bovine enzyme and its physiological role under oxidative stress.

Thioltransferase, an enzyme which catalyzes the thiol/disulfide exchange reaction in the presence of GSH, was purified to homogeneity on 15% SDS-PAGE from human (36,000-fold purification) and bovine (23,000-fold) erythrocyte hemolysates. These enzymes had similar properties in their monomeric structures (M(r) = 11,000) and broad specificities for substrates ranging from low-molecular disulfides (S-sulfocysteine, cystamine, and cystine) to protein disulfides (trypsin and insulin). They were highly sensitive to SH-reagents (monoiodoacetic acid and mercuric chloride), but were protected from inactivation by the presence of disulfides (GSSG, cystamine, and cystine). Phosphofructokinase and pyruvate kinase that had been inactivated by disulfides were reactivated effectively by the addition of thioltransferase with GSH. In addition, disulfides in membrane proteins of human erythrocytes that have been oxidatively damaged by diamide treatment were reduced to the SH-free form more effectively by incubation with thioltransferase.

Amino Acids↗
PubMed1992

An autopsy case of infant death due to heat stroke.

We report an autopsy case of infant death due to heat stroke. On a winter day, a 52-day-old female baby was placed under a Japanese electric foot warmer with a coverlet (kotatsu) on an electric carpet warmer in a heated room at home. After about 5 h, the mother noticed that the baby was unconscious and took her to a hospital. Spontaneous respiration, however, was already absent, and the pupils were dilated. The trunk was hot; body temperature was 41.3 degrees C. The skin of the whole body was dry. Autopsy revealed second-degree burn injuries on the left side of the face and the dorsum of the left hand. Numerous marked petechiae and ecchymoses were found in the thymus (capsule and parenchyma), pleurae (visceral and parietal), pericardial cavity (internal and external surfaces), epicardium, and beneath the serosa at the origin of the aorta. In addition, there was congestion in various organs, edema in the brain and lungs, and hemorrhage in the lungs. Histopathologically, macrophages without hemosiderin granules were present in the alveoli. When the heating conditions at the accident were reproduced experimentally, the temperature in the electric kotatsu warmer rose to 50-60 degrees C. Thus, we concluded that misuse of the electric kotatsu caused heat stroke in this infant.

Autopsy↗
PubMed1992

Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture.

Cilostazol, a cyclic AMP phosphodiesterase inhibitor, has been used as an antiplatelet agent. In the present study, we investigated the in vitro effect of cilostazol on DNA synthesis in rat aortic arterial smooth muscle cells (SMCs) in culture stimulated with fetal calf serum (FCS), platelet-derived growth factor (PDGF), insulin, or insulin-like growth factor-I (IGF-I). Micromolar concentrations of cilostazol inhibited [3H]thymidine incorporation into DNA and cell growth as determined by cell number and protein concentration. Treatment with cilostazol increased the intracellular concentration of cyclic AMP, suggesting that the inhibition of SMC proliferation by cilostazol may be mediated through increased levels of cyclic AMP. The results suggested that cilostazol, by interfering with the proliferation of arterial SMCs, may have potential to prevent initiation and progression of atherosclerosis.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

Enhanced tumor localization of monoclonal antibody by treatment with kininase II inhibitor and angiotensin II.

The effect of kininase II inhibitor, enalapril, on the delivery of monoclonal antibody A7 to the targeted tumor was investigated using athymic mice bearing human colon cancer, SW1116. Enalapril alone, which enhances tumor vascular permeability through the kinin-generating cascade, did not increase the uptake of 125I-labeled A7 (125I-A7) in SW1116 due to the systemic hypotension induced by its inhibitory effect on angiotensin converting enzyme. However, with combined angiotensin II (AT-II) and enalapril treatment, a 2-fold increase in the accumulation of 125I-A7 was seen when compared to A7 alone. This marked increase was presumably due to increased tumor vascular permeability induced by enalapril combined with the absence of hypotension due to the actions of AT-II. This approach might be useful in radioimmunodetection and immunotargeting chemotherapy using monoclonal antibody.

Angiotensin II↗