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M Hirose

Publications and source records attributed to M Hirose.

At least 235 records · Page 13Linked to original sources
PubMed1998

Endothelin-1 stimulates sodium-dependent calcium efflux from bovine adrenal chromaffin cells in culture.

1. The effect of endothelin (ET)-1 on Ca2+ efflux from cultured bovine adrenal chromaffin cells was examined. ET-1 (10(-7) M) significantly increased intracellular free Ca2+ level ([Ca2+]i), 45Ca2+ uptake and catecholamine secretion in the cells. 2. ET-1 stimulated the efflux of 45Ca2+ from the cells preloaded with 45Ca2+ in a concentration-dependent manner (10(-9)-10(-7) M). This stimulatory effect was inhibited by ET(B) receptor antagonist BQ788, but not by ET(A) receptor antagonist BQ123. Selective ET(B) receptor agonists Suc-[Glu9, Ala11.5]-ET-1 and sarafotoxin S6c (SRTX) also stimulated 45Ca2+ efflux from the cells. 3. ET-1, Suc-[Glu9 Ala11.15]-ET-1 and SRTX increased the level of cyclic GMP in the adrenal chromaffin cells. ET-1 induced an increase in the nitric oxide (NO) level in the cells. The stimulatory effects by which ET- increases NO level and 45Ca2+ efflux were inhibited by NG-monomethyl-L-arginine acetate (L-NMMA), a competitive inhibitor of NO synthase. 4. The 45Ca2+ efflux stimulated by ET-1 was inhibited by deprivation of extracellular Na+, but not by deprivation of Ca2+. 5. These results suggest that ET-1 stimulates an extracellular Na+-dependent Ca2+ efflux through the activation of NO synthase in cultured bovine adrenal chromaffin cells.

Adrenal Glands↗
PubMed1998

Insulin-like growth factor I plays a role in gastric wound healing: evidence using a zinc derivative, polaprezinc, and an in vitro rabbit wound repair model.

BACKGROUND: Although the detailed mechanism is unclear, zinc and its derivative, polaprezinc, have been reported to accelerate gastric ulcer healing in vivo. AIM: To investigate the detailed cellular mechanism of polaprezinc on gastric epithelial cells and fibroblasts with special attention to insulin-like growth factor I (IGF-I). METHODS: Isolated rabbit gastric epithelial cells formed a complete monolayer, from which a circular artificial wound with constant size was made. The restoration process was monitored by measuring wound size up to 48 h. Either polaprezinc, IGF-I, fibroblast conditioned medium or neutralized medium conditioned by anti-IGF-I antibody was added at the time of wounding. The expression of mRNA of IGF-I, hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF-alpha) in fibroblasts with or without polaprezinc treatment was tested using reverse transcription polymerase chain reaction (RT-PCR). Gastric epithelial cell proliferation was also examined by bromodeoxyuridine (BrdU) staining. RESULTS: IGF-I and fibroblast conditioned medium treatment accelerated gastric epithelial restoration which included cell migration and proliferation. However, polaprezinc and neutralized conditioned medium treatment did not accelerate epithelial repair. RT-PCR for growth factor mRNA revealed the IGF-I mRNA expression in fibroblasts was increased after treatment with polaprezinc. CONCLUSION: Polaprezinc induced IGF-I production from mesenchymal cells, resulting in stimulation of epithelial cell restoration through a paracrine pathway. IGF-I may play an important role in gastric wound repair.

Animals↗
PubMed1998

Carcinogenicity of antioxidants BHA, caffeic acid, sesamol, 4-methoxyphenol and catechol at low doses, either alone or in combination, and modulation of their effects in a rat medium-term multi-organ carcinogenesis model.

The carcinogenicity of low dietary levels of the antioxidants butylated hydroxyanisole (BHA), caffeic acid, sesamol, 4-methoxyphenol (4-MP) and catechol, known to target the forestomach or glandular stomach, were examined alone or in combination in a 2-year long-term experiment and their modifying effects assessed in a medium-term multiorgan model. In the carcinogenicity study, groups of 30-31 male F344 rats were treated with 0.4% BHA, 0.4% caffeic acid, 0.4% sesamol, 0.4% 4-MP and 0.16% catechol either alone or in combination for up to 104 weeks and then killed. In the medium-term multi-organ model, groups of 10 to 15 male F344 rats were given diethylnitrosamine (DEN), N-methylnitrosourea (MNU), 1,2-dimethylhydrazine (DMH), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) for a total multiple initiation period of 4 weeks (DMBDD treatment). BHA, caffeic acid, sesamol and 4-MP, each at doses of 0.4% or 0.08%, and catechol at doses of 0.16% or 0.032% were administered in the diet either alone or in combination after completion of the initiation regimen. All surviving animals were killed at the end of week 28, and major organs were examined histopathologically. In the carcinogenicity study, slightly increased incidences of forestomach papillomas were found in the sesamol- (15.8%), caffeic acid- (14.8%), catechol- (3%) and 4-MP- (11.5%) treated groups as compared with basal diet (0%), and a significant increase was observed with the five antioxidants in combination (42.9%, P < 0.001). In a medium-term multiorgan carcinogenesis model, incidences of forestomach papillomas and/or carcinomas were increased in each high dose group, but additive or synergistic effects were not found in the combination group. In the low dose case, the incidence of forestomach papillomas was significantly increased only in the combination group. With regard to other organs, the incidence of colon tumors was significantly decreased only in the high dose combination group. The results indicate that even at low dose levels phenolic compounds can exert additive/synergistic effect on carcinogenesis.

Animals↗
PubMed1998

A functional epitope on P-selectin that supports binding of P-selectin to P-selectin glycoprotein ligand-1 but not to sialyl Lewis X oligosaccharides.

P-selectin mediates the adhesion of leukocytes to activated platelets and endothelial cells. To characterize the functional domains of P-selectin for ligand recognition, we established nine hybridoma cell lines secreting anti-rat P-selectin mAb. Among them, the mAb C215 bound both rat and human P-selectins, and inhibited binding of rat and human P-selectins to P-selectin glycoprotein ligand-1 (PSGL-1) from HL-60 cells. In contrast, mAb C215 failed to inhibit the binding of rat and human P-selectin-IgG to sialyl Lewis X (sLe(x)) oligosaccharides. Epitope mapping of mAb C215 using synthetic decapeptides revealed that mAb C215 binds specifically to an eight-residue epitope that spans amino acids 76-83 of rat P-selectin, a region completely conserved by human P-selectin. Synthetic peptides containing the mAb C215 epitope inhibited binding of P-selectin to PSGL-1, but not to sLe(x) oligosaccharides, suggesting that the C215 epitope on P-selectin may directly interact with a particular site on the PSGL-1 core protein essential for interaction with P-selectin, such as sulfated tyrosine residues. Our results suggest the presence of two ligand recognition sites on P-selectin necessary for binding to PSGL-1--one recognizes sLe(x), while the other recognises the PSGL-1 core protein.

Amino Acid Sequence↗
PubMed1998

Isolation of anti-glutathione antibodies from a phage display library.

We have isolated anti-glutathione antibodies from a human synthetic phage antibody scFv library (Nissim,A., Hoogenboom,H.R., Tomlinson,I.M., Flynn,G., Midgley,C., Lane,D. and Winter,G., 1994, EMBO J., 13, 692-698). Glutathione (GSH) conjugates with carrier proteins, such as bovine serum albumin (BSA), keyhole limpet hemocyanin (KLH) and human lysozyme (LZM), were used as antigens. After four cycles of panning and affinity chromatography, clones that recognized GSH-conjugated proteins, but not BSA, KLH or LZM, were isolated. The isolated phage antibodies and the soluble scFv fragments were characterized by immunoblotting, and the nucleotide sequences of the VH segments of selected clones were determined. The binding of several isolates to GSH-BSA was competitively inhibited by GSH in an ELISA. These observations have demonstrated that antibodies against GSH, a tripeptide, can be isolated from the library. We constructed the tertiary models of several scFv fragments and discussed the mechanism of antigen binding sites.

Antibodies, Viral↗
PubMed1998

Heart rate variability during chemical thoracic sympathectomy.

BACKGROUND: Chemical thoracic sympathectomy (CTS) resulted in profound bradycardia in a patient with severe post-therapeutic neuralgia. To clarify the cause of this bradycardia, the authors evaluated heart rate variability using a Poincaré plot, which is a scatter diagram of the current R-R interval plotted against the R-R interval immediately preceding it, in this patient and in others scheduled for CTS or mandibular block (MB). METHODS: Twenty-three patients were scheduled for CTS (n = 13, CTS group) and for MB (n = 10, MB group). Heart rate and the SD of the R-R interval variabilities spreading along the x axis (SDRR) and perpendicularly along the diagonal line of the Poincaré plot (SDdeltaRR) were evaluated before, just after, and 1 h after the block. RESULTS: Neither group had significant changes in heart rate. The MB group showed no significant change in the SD(RR):SDdeltaRR ratio. In the CTS group, however, the SD(RR):SDdeltaRR ratio decreased significantly from 1.72+/-0.20 to 1.23+/-0.11 just after CTS. The previous patient, who had a high SD(RR):SDdeltaRR ratio of 3.45 before CTS, exhibited severe bradycardia (22 beats/min). CONCLUSIONS: The SD(RR):SDdeltaRR ratio decreased after CTS without any significant concomitant change in heart rate. The decrease in the SD(RR):SDdeltaRR. ratio indicates a reduction of cardiac sympathetic activity. However, CTS in patients having high SD(RR):SDdeltaRR ratios can result in profound bradycardia.

Adult↗
PubMed1998

A neurotrophic pyrimidine compound, MS-818, enhances EGF-induced restoration of gastric epithelial wounds in vitro.

MS-818 is a novel synthetic pyrimidine compound that stimulates nerve regeneration and promotes synthesis of various growth factors and differentiation of astrocytes. Effects of MS-818 on gastric epithelial cells were assessed using a wound repair model with primary cultured gastric epithelial cells from rabbits. A round wound with a constant cell-free area was created and the process of restoration was monitored by measuring wound size every 12 h. Cell proliferation was monitored by sequential staining with BrdU. As previously reported, EGF (10 ng/ml) accelerated wound repair by promoting cell migration and proliferation. Although MS-818 alone had no effects, MS-818 (10-100 microM) enhanced EGF-induced acceleration of gastric epithelial restoration, including cell migration and proliferation. Although the detailed mechanism of action of this agent is still unclear, MS-818 might have favorable effects on in vivo gastric mucosal repair.

Animals↗
PubMed1998

Inhibition by E-4031 of the prolongation of the first returning cycle length after overdrive in anesthetized dog hearts.

Prolongation of the functional recovery of the sinoatrial (SA) nodal pacemaker activity after overdrive, "overdrive suppression," is determined by intrinsic pacemaker activity, pacemaker site, and SA conduction. We investigated the effects of E-4031, a blocker of a rapid type of the delayed rectifier K+ current (Ikr) and stimulation of the intracardiac parasympathetic nerves to the SA nodal region (SAP) on the prolongation of the first returning cycle length (1st RCL) after overdrive in autonomically decentralized hearts of open-chest anesthetized dogs. Second and third RCLs also were measured. We determined SA node recovery time (SNRT) and corrected SNRT (CSNRT) after atrial pacing at rates of 120, 150, and 200% of the control rate for 1 min and also determined SA conduction time (SACT) by the constant-atrial-pacing method. E-4031 (0.1-3 micromol/kg i.v.) increased the sinus cycle length (SCL) and SNRT dose dependently. However, E-4031 decreased CSNRT when the pacing rate was low or the number of pacing stimuli was small, although the agent did not induce a significant change in CSNRT when sufficient pacing stimuli were applied. E-4031 decreased SACT dose dependently. After E-4031 treatment. we observed changes in atrial electrical configurations, suggesting the possibility of pacemaker shift. When SAP stimulation increased SCL, SNRT, CSNRT, and SACT, E-4031 selectively inhibited the prolongation of SCL by SAP stimulation but did not affect the prolongation of CSNRT or SACT. These results suggest that functional recovery of the SA nodal pacemaker activity after overdrive is regulated by Ikr at least in part and that Ikr inhibition attenuates prolongation of the SCL but not the 1st RCL induced by parasympathetic nerve activation in the heart in situ.

Anesthesia↗
PubMed1998

Prevention by synthetic phenolic antioxidants of 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)- or activated MeIQx-induced mutagenesis and MeIQx-induced rat hepatocarcinogenesis, and role of antioxidant activity in the prevention of carcinogenesis.

Effects of synthetic phenolic antioxidants 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-butylhydroquinone (TBHQ) and propyl gallate (PG) on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)- or activated MeIQx-induced mutagenesis and rat hepatocarcinogenesis were compared, and the association between antioxidative activity and inhibition of carcinogenesis was examined. When the antimutagenic activity of five antioxidants against MeIQx- or activated MeIQx-induced mutagenesis was compared in the Ames assay using the Salmonella strain TA 98, HTHQ showed the greatest effect, followed by BHA, BHT, PG and TBHQ, in that order. In a rat hepatocarcinogenesis study, 6-week-old male F344 rats were given a single i.p. injection of 200 mg/kg bw of diethylnitrosamine (DEN) and starting 2 weeks later, groups of 15 animals received a diet containing 0.03% MeIQx alone, MeIQx together with each antioxidant at a dietary dose of 0.25%, each antioxidant alone, or basal diet alone for 6 weeks. Three weeks after the DEN injection, animals were subjected to 2/3 partial hepatectomy. Liver tissues obtained at partial hepatectomy were processed for the measurement of 8-hydroxydeoxyguanine (8-OHdG) and lipid peroxidation. The average number and areas of glutathione S-transferase placental form (GST-P) positive foci were increased by the treatment with MeIQx (27.2 +/- 6.5 per cm2 and 3.17 +/- 0.96 mm2/cm2, respectively). A significant decrease in these parameters was found with the simultaneous antioxidant treatment, HTHQ demonstrating the greatest effect, followed by BHA, BHT and TBHQ, and PG. Without MeIQx, a weak increase in the number of foci was observed in the BHT treatment case. Examination of 8-OHdG levels in liver DNA, as well as malondialdehyde (MDA) and 4-hydroxyalkenals, did not reveal any inter-group variation. These results indicate that antimutagenic activity of antioxidants against MeIQx roughly parallels their anticarcinogenic activity, with HTHQ as the most powerful chemopreventor, but that oxidative stress and antioxidative activity may not be responsible for MeIQx-induced hepatocarcinogenesis and its inhibition, respectively.

Animals↗
PubMed1998

Dose dependence of 1-O-hexyl-2,3,5-trimethylhydroquinone promotion of forestomach carcinogenesis in rats pretreated with N-ethylnitrosourethane.

Post-initiation dose-dependent effects of the chemopreventive antioxidant 1-O-hexyl-2, 3, 5-trimethylhydroquinone (HTHQ), a potent inhibitor of heterocyclic amine-induced mutagenesis and carcinogenesis, on the development of forestomach and tongue tumors were investigated in male F344 rats. Groups of 22 rats were treated with 0.01% ethylnitrosourethane (ENUR) as an initiator in the drinking water for 4 weeks, then placed on diet containing 1.0%, 0.5%, 0.25% or 0.125% HTHQ, or basal diet alone for 36 weeks. Further group of 12 rats each were similarly treated with the different doses of HTHQ or given basal diet alone for 36 weeks without prior ENUR treatment. All animals were killed at week 40. Tongue papillary hyperplasia and papillomas tended to be increased in the groups treated with ENUR followed by 0.5-0.125% HTHQ, though there was no effect at the highest dose, in line with increased bromodeoxyuridine labeling indices. In the forestomach, the incidences of papillomas and carcinomas were also significantly elevated only in the group treated with ENUR followed by 0.125% HTHQ. Without ENUR pretreatment, papillary hyperplasia was found in the 1-0.125% HTHQ groups and the labeling index was also increased, though without clear dose dependence. The results indicate that HTHQ may have very weak or weak promotion potential for tongue and forestomach carcinogenesis, but that both minimum and maximum thresholds for active dose levels may exist.

Animals↗
PubMed1998

CNP causes receptor-mediated positive dromotropic effects in anesthetized dog hearts.

No data are available for the direct effect of C-type natriuretic peptide (CNP) on atrioventricular (AV) conduction in mammalian hearts. Thus we studied the dromotropic effects of CNP-22 injected into the AV node artery in autonomically decentralized hearts in open-chest, anesthetized dogs. CNP decreased AV interval (AV conduction time) in a dose-dependent manner with increase in coronary artery blood flow rate in six anesthetized dogs. Isosorbide dinitrate did not affect AV interval, but it increased coronary artery blood flow rate. A guanylyl cyclase-linked natriuretic peptide receptor antagonist, HS-142-1, inhibited the decreases in AV interval and the increases in coronary blood flow rate in response to CNP, whereas propranolol did not affect the positive dromotropic response to CNP. These results demonstrate that CNP decreases AV interval and increases coronary artery blood flow rate mediated by a guanylyl cyclase-linked natriuretic peptide receptor, but not beta-adrenoceptor, in the dog heart.

Animals↗
PubMed1998

Different chronotropic and inotropic effects of EMD 57033 and EMD 53998, Ca2+ sensitizers, on isolated, blood-perfused dog heart preparations.

To investigate whether a Ca2+ sensitizer increases sinus rate, we studied the effects of racemic thiadiazinone, EMD 53998 (a Ca2+ sensitizer with phosphodiesterase inhibitory action) and its (+)-enantiomer EMD 57033 (a relatively pure Ca2+ sensitizer) on isolated, blood-perfused spontaneously beating right atria and paced left ventricles of the dogs. EMD 53998 increased sinus rate dose-dependently, but EMD 57033 did not. Both substances increased atrial and ventricular contractile force. Propranolol did not affect the responses to each substance. These results suggest that the Ca2+ sensitizing action induced by EMD 57033 does not affect pacemaker currents directly.

Animals↗
PubMed1998

Medium-term bioassays for carcinogenicity of chemical mixtures.

Carcinogenic effects of chemical mixtures were examined with a medium-term liver bioassay for carcinogens or a multiorgan medium-term bioassay using male F344 rats. In the medium-term liver bioassay, rats were initially treated with diethylnitrosamine (DEN) at 200 mg/kg body weight, i.p.; after 2 weeks they received chemical mixtures such as 10 different heterocyclic amines at one-tenth or one-hundredth the dose levels used in carcinogenicity studies and the mixtures of 20 different pesticides, each at acceptable daily intake (ADI) levels or a mixture of 100 times ADI levels. All animals were subjected to two-thirds partial hepatectomy at week 3 and were sacrificed at week 8. The number and areas of glutathione S-transferase placental form (GST-P) positive foci (preneoplastic lesions in the liver) were compared between respective groups. When 10 heterocyclic amines were mixed in the diet at one-tenth dose level, clear synergism was observed, but no combined effects were evident with the one-hundredth dose levels. In the pesticide experiment, treatment of rats with the 20-pesticide mixture at the ADI dose level did not enhance GST-P-positive foci. In contrast, a mixture of 100 times the ADI significantly increased those values. In a multiorgan bioassay of 28 weeks, mixtures of 40 high-volume compounds and 20 pesticides (suspected carcinogens) added together at their respective ADI levels did not enhance carcinogenesis in any organs initiated by five different carcinogens (DEN, N-methylnitrosourea, dimethylhydrazine, N-butyl-N-(4-hydroxybutyl)nitrosamine, and dihydroxy-di-n-propylnitrosamine) in combination. The combination effect of low dietary levels of five antioxidants, butylated hydroxyanisole, caffeic acid, sesamol, 4-methoxyphenol, and catechol, were also examined using the multiorgan bioassay. The incidence of forestomach papillomas was significantly increased only in the combination group and the results indicate that combination of the five antioxidants can exert additive/synergistic effects on tumorigenesis in the multiorgan bioassay. These results indicate that chemical mixtures at very low doses did not enhance preneoplastic lesions synergistically but the mixtures at certain doses show synergism in the target organ. The medium-term bioassays are particularly useful tools for this purpose.

Animals↗
PubMed1998

Vascular and non-vascular ligands for L-selectin.

Ligands for L-selectin are expressed not only on vascular endothelial cells but also in the extravascular tissues. In this article, we summarize the current understanding of the "vascular" ligands for L-selectin. We also describe identification of "non-vascular" ligands for L-selectin and discuss their possible biological significance.

Animals↗
PubMed1998

Expression level of G1-cyclins and cell proliferation in human cultured leukemia/lymphoma cell lines.

We observed the expression of wild-type retinoblastoma protein (RB) in all 17 hematologic cultured cell lines tested. However, no p16INK4 expression was detected in any cell line among 16 leukemia/lymphoma cell lines, although an EBV-transformed cell line expressed p16INK4. The expression levels of cyclin D1 and CDK4 varied widely among the cell lines. The correlation coefficient (r2) between doubling time (DT) and cyclin D1 in the 14 cell lines that doubled within 47.2 h was 0.4856, while the r2 between DT and cyclin dependent kinase 4 (CDK4) and that between DT and RB among those cell lines were 0.3761 and 0.0874, respectively. The levels of protein expression in vincristine (VCR)-resistant cell lines was not different from those in corresponding wild-type cell lines. Thus, we concluded that the loss of p16INK4 protein and inactivation of RB protein could be an essential step for oncogenesis of leukemia/ lymphoma, and that cyclin D1 may possibly be a target protein to control cell growth of hematologic cell lines which lack the expression of p16INK4.

Cell Division↗
PubMed1998

Effect of MDR antagonists on the cidal activity of vincristine for cells expressing MDR-1 is superior to those expressing MRP.

In an attempt to identify the target protein, P-GP or mrp, of each MDR antagonist, verapamyl (Ver), dipyridamole (Dip), or cyclosporin A (Cy-A), this study was designed to compare the activity of the three afore-mentioned drugs and to test their combined effect on the cidal activity of vincristine (VCR) in five types of wild and the corresponding VCR-resistant cultured cell lines from human leukemia and lymphoma. Three of the VCR-resistant cell lines are characterized by the overexpression of mdr-1, while two cell lines overexpress mrp. We found that all three antagonists additively to synergistically enhanced the cidal activity of VCR for the five wild-type and VCR-resistant cell lines in a dose dependent manner when used singly. Combinations consisting of a 20% inhibitory concentration (IC20) of VCR plus two antagonists also showed additive to synergistic effects on both wild and VCR-resistant cell lines. It is of interest that the combined effect of IC20 VCR plus MDR antagonists on the three VCR-resistant cell lines expressing mdr-1 was significantly superior to those of the two cell lines expressing the mrp gene. These results suggest that the combined effect of MDR antagonists work better than their single use and that the MDR antagonists work more efficiently in cells showing drug resistance through mdr-1 than in those utilizing mrp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

[A 13-week subchronic oral toxicity study of chlorophyll in F344 rats].

A 13-week subchronic toxicity study of chlorophyll (containing 40% oil) was performed in both sexes of F344 rats by feeding of CRF-1 powder diet containing 0, 0.18%, 0.55%, 1.66% and 5%, and vehicle (oil) alone. No animals died during the administration period and no changes in body weights and food intakes were found in any dosed groups. Some hematological, serum biochemical and histopathological changes were observed for the 5%-treated group, but these did not suggest obvious toxicity. These findings indicate that the treatment with 1.66% chlorophyll in diet for 13 weeks does not cause any changes in rats and the 5% feeding is not obviously toxic.

Animals↗