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M Hirose

Publications and source records attributed to M Hirose.

At least 163 records · Page 9Linked to original sources
PubMed1999

Crystal structure of hen apo-ovotransferrin. Both lobes adopt an open conformation upon loss of iron.

The three-dimensional crystal structure of hen apo-ovotransferrin has been solved by molecular replacement and refined by simulated annealing and restrained least squares to a 3.0-A resolution. The final model, which comprises 5312 protein atoms (residues 1 to 686) and 28 carbohydrate atoms (from two monosaccharides attached to Asn(473)), gives an R-factor of 0.231 for the 11,989 observed reflections between 20.0- and 3.0-A resolution. In the structure, both empty iron binding clefts are in the open conformation, lending weight to the theory that Fe(3+) binding or release in transferrin proceeds via a mechanism that involves domain opening and closure. Upon opening, the domains rotate essentially as rigid bodies. The two domains of the N-lobe rotate away from one another by 53 degrees, whereas the C-lobe domains rotate away each another by 35 degrees. These rotations take place about an axis that passes through the two beta-strands, linking the domains. The domains of each lobe make different contacts with one another in the open and closed forms. These contacts form two interdomain interfaces on either side of the rotation axis, and domain opening or closing produces a see-saw motion between these two alternative close-packed interfaces. The interdomain disulfide bridge (Cys(478)-Cys(671)), found only in the C-lobe, may restrict domain opening but does not completely prevent it.

Amino Acid Sequence↗
PubMed1999

Chemoprevention of heterocyclic amine-induced carcinogenesis by phenolic compounds in rats.

Chemopreventive effects of synthetic and naturally occurring antioxidants on heterocyclic amine (HCA)-induced rat carcinogenesis and mechanisms of inhibition were assessed. In a medium-term liver bioassay, combined treatment with 0.03% 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and synthetic antioxidants such as 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), BHA, BHT, tert-butylhydroquinone (TBHQ) and propyl gallate, each at a dose of 0.25%, and troglitazone at doses 0.5 and 0.1%, potently inhibited development of glutathione S-transferase placental form (GST-P) positive foci as compared with MeIQx alone values. Of these antioxidants, HTHQ showed the greatest activity. Green tea catechins tended to inhibit GST-P positive foci development, while quercetin, rutin, curcumin, daidzin, ferulic acid and genistin all exerted significant enhancing effects. HTHQ also inhibited 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colon carcinogenesis in a two stage colon carcinogenesis model using 1,2-dimethylhydrazine (DMH) as an initiator. Immunohistochemically detected PhIP-DNA adduct positive nuclei in the colon induced by continuous oral treatment with 0.02% PhIP for 2 weeks decreased by the combined treatment with 0.5 or 0.125% HTHQ. Methoxyresorfin O-demethylase activity in rat liver microsomes in vitro was clearly inhibited by the addition of HTHQ, BHA, BHT, TBHQ or propyl gallate, with particularly strong inhibition being observed in HTHQ. However, the CYP1A2 level in rat liver increased after oral treatment with HTHQ for 2 weeks. These results indicate that synthetic antioxidants, HTHQ in particular, is a very strong chemopreventor of HCA-induced carcinogenesis. It is suggested that depression of metabolic activation rather than antioxidant activity is responsible for the observed effect. However, other mechanisms, including the effects on phase II enzymes cannot be ruled out.

Animals↗
PubMed1999

Abortive expansion of the cumulus and impaired fertility in mice lacking the prostaglandin E receptor subtype EP(2).

Female mice lacking the gene encoding the prostaglandin (PG) E(2) receptor subtype EP(2) (EP(2)(-/-)) become pregnant and deliver their pups at term, but with a much reduced litter size. A decrease in ovulation number and a much reduced fertilization rate were observed in EP(2)(-/-) females without difference of the uterus to support implantation of wild-type embryos. Treatment with gonadotropins induced EP(2) mRNA expression in the cumulus cells of ovarian follicles of wild-type mice. The immature cumuli oophori from wild-type mice expanded in vitro in response to both follicle-stimulating hormone and PGE(2), but the response to PGE(2) was absent in those from EP(2)(-/-) mice. Cumulus expansion proceeded normally in preovulatory follicles but became abortive in a number of ovulated complexes in EP(2)(-/-) mice, indicating that EP(2) is involved in cumulus expansion in the oviduct in vivo. No difference in the fertilization rate between wild-type and EP(2)(-/-) mice was found in in vitro studies using cumulus-free oocytes. These results indicate that PGE(2) cooperates with gonadotropin to complete cumulus expansion for successful fertilization.

Abortion, Spontaneous↗
PubMed1999

Tumor-promoting activities of hydroquinone and 1,1-dimethylhydrazine after initiation of newborn mice with 1-methyl-1-nitrosourea.

To clarify the suitability of a newborn-mouse carcinogenesis assay to detect tumor-promoting activities of carcinogens, the non-genotoxic hydroquinone (HQ) and genotoxic 1,1-dimethylhydrazine (UDMH) were administered to mice during the promotion stage after treatment with 1-methyl-1-nitrosourea (MNU) (20 mg/kg body wt, single intraperitoneal injection) at day 9 after birth. Initiated males and females thus received either HQ at 0.8% in basal diet, or UDMH, at 20 mg/kg body wt once weekly by subcutaneous injection, from day 14 until the end of the experiment at 30 weeks of age. Uninitiated newborn mice, given an injection of the vehicle (0.01 M citrate buffer (pH 5.5), 20 mg/kg body wt), also received HQ or UDMH in the same way. Histopathologically, focal proliferative lesions were found in the livers of male mice and in the lungs of both male and female mice in the MNU-treated groups. HQ significantly increased the incidence and multiplicity of altered hepatocellular foci, the combined incidence of hepatocellular adenomas and carcinomas in males and the incidence and multiplicity of lung adenomas and the combined incidence of lung adenomas and carcinomas in female mice. In addition, four out of eleven MNU + HQ-treated male mice developed lung carcinomas, showing a significant elevation in multiplicity. UDMH also exhibited a tendency to increase the incidence and multiplicity of lung adenomas in female mice. Thus tumor-promoting effects of HQ or UDMH were apparently exerted in the target organs and the MNU-initiated two-stage newborn-mouse carcinogenesis assay may be useful for detection of genotoxic or non-genotoxic carcinogenicity.

Adenoma↗
PubMed1999

Tumor-promoting activity of 2,6-dimethylaniline in a two-stage nasal carcinogenesis model in N-bis(2-hydroxypropyl)nitrosamine-treated rats.

The potential promotion activity on nasal carcinogenesis of 2,6-dimethylaniline (DMA), an alpha2-adrenergic agonist metabolite of xylazine which is used for food-producing animals as a sedative agent, was examined. Male F344 rats received diet containing 0 or 3000 ppm DMA for 52 weeks after initiation with N-bis(2-hydroxypropyl)nitrosamine (DHPN). Histopathological assessment showed the incidence of carcinomas in the DHPN+DMA group (33%) to be significantly elevated as compared with that for the DHPN-alone group (5%). Incidences and/or multiplicity of epithelial hyperplasias and dysplastic foci were also increased in the DHPN+DMA group. These lesions were exclusively observed in the olfactory mucosa. The lowest plasma levels of DMA in tumor- and dysplastic foci-bearing rats were 0.05 and 0.20 microg/ml, respectively. These results indicate that DHPN acts as an appropriate initiator for nasal carcinogenesis and that DMA exerts a tumor-promoting effect on the olfactory mucosa in the rat nasal cavity.

Adenoma↗
PubMed1999

Carcinogenic risk assessment of MeIQx and PhIP in a newborn mouse two-stage tumorigenesis assay.

A newborn mouse two-stage tumorigenesis assay was evaluated as a possible alternative to chronic rodent carcinogenicity bioassays by investigating the carcinogenicity of two major heterocyclic amines, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). One week after birth, Crj:CD-1 mice of both sexes were subcutaneously administered N-nitrosobis(2-oxopropyl)amine (BOP) at a dose of 50 mg/kg as an initiation treatment and starting 2 weeks thereafter they were fed diets supplemented with MeIQx at concentrations of 300, 30, 3 or 0 ppm or PhIP at 200, 50, 10 or 0 ppm for 23 weeks. Animals in all groups predominantly developed tumors of the lung and liver. Pulmonary adenomas and adenocarcinomas were observed in all groups with high incidences, without any significant differences between the groups. MeIQx and PhIP did not influence the multiplicity except in the group given 10 ppm PhIP where it significantly increased the number of pulmonary adenomas (P < 0.05). Similarly, hepatocellular adenomas and carcinomas were found in all groups with high incidences, and again MeIQx and PhIP did not increase their incidences or multiplicities. Although adenomas and carcinomas in the nasal cavity, and acinar cell foci in the pancreas were infrequently found, none of these incidences were increased with the MeIQx or PhIP treatments. These results thus suggest that the tumor-promoting effects of MeIQx or PhIP may be rather weak, if present, as far as this newborn two-stage model is concerned, and the possibility that the dose of BOP was too high to detect the tumor-promoting effects of MeIQx or PhIP by masking them cannot be completely ruled out.

Animals↗
PubMed1999

Effect of cigarette smoke on the mutagenic activation of environmental carcinogens by rodent liver.

In order to assess the effect of cigarette smoke (CS) on metabolic enzymes, male hamsters and rats were exposed for two weeks to smoke produced in a Hamburg type II smoking machine. The livers were then used for Ames liquid incubation and western immunoblot assays. Mutagenic activities of seven heterocyclic amines (HCAs) in Salmonella typhimurium TA98 in the presence of rat or hamster liver S9 were elevated up to 3.7 times above controls (including sham smoke control). Enhancement of mutagenic activities of PhIP and aflatoxin B(1) was observed only in CS-exposed hamster, whereas no significant alteration of mutagenicity was observed with 2-aminofluorene, benzo[a]pyrene, and 3'-hydroxymethyl-N, N-dimethyl-4-aminoazobenzene in strain TA98 or with six N-nitrosodialkylamines in strain TA100. 7,8-Benzoflavone and/or furafylline considerably inhibited the mutagenic activation of IQ and Trp-P-1 in the presence of liver S9 from untreated hamsters and sham smoke- or CS-exposed hamsters and rats, indicating the predominant involvement of hamster cytochrome P450 (CYP) 1A enzymes in the metabolic activation of HCAs. In addition, the data suggest that CS-exposure may selectively induce hepatic CYP1A1/1A2 isoforms. Western immunoblot analyses of liver microsomes using anti-rat CYP antibodies revealed that CS-exposure increased the levels of hamster CYP1A2 (3.9-fold) and rat CYP1A2 (3.0-fold) and CYP1A1, without significant change in the levels of CYP2E1 and CYP2B and 3A isoforms in each species. The presently observed selective induction of HCA activation and CYP isozymes due to CS supports the idea that CS may contribute to enhancing effects on initiation by carcinogens which are metabolically activated by hepatic CYP1A1/1A2. In conjunction with results observed for smokers, the present findings indicate that the hamster is a good animal for studies with CS, and that cigarette smoking in combination with intake of heating protein-rich foods as a life style may markedly contribute to the human carcinogenesis by HCAs.

Amines↗
PubMed1999

Failure of phenethyl isothiocyanate to inhibit hamster tumorigenesis induced by N-nitrosobis(2-oxopropyl)amine when given during the post-initiation phase.

The chemopreventive influence of phenethyl isothiocyanate (PEITC) during the post-initiation stage was investigated in the N-nitrosobis(2-oxopropyl)amine (BOP)-initiated hamster tumorigenesis model. A total of 120 female 5-week-old hamsters were divided into six groups. Animals in groups 1-3, each consisting of 30 hamsters, were injected twice, subcutaneously, with BOP 7 days apart to effect initiation. Starting 1 week after the second BOP injection, hamsters in groups 1 and 2 were fed diets supplemented with 6 micromol/g and 3 micromol/g of PEITC, respectively, for 51 weeks. Animals in group 3 received a basal diet as an initiation positive control. Animals in groups 4-6, each consisting of ten hamsters, were given 6 micromol/g or 3 micromol/g of PEITC alone, or were non-treated, matched negative controls for groups 1-3. At the termination of experimental week 52, the incidences and multiplicities of neoplastic lesions in the target organs including the pancreas, lung, liver and kidney were found to be comparable among the BOP-treated groups. The values for pancreatic adenocarcinomas as well as dysplastic lesions tended to increase although without statistical significance. Taken together with our previous finding that PEITC dramatically inhibited the initiation phase of BOP-induced pancreatic and lung tumorigenesis in hamsters, it can be concluded that PEITC specifically exerts chemopreventive effects only when given concomitantly with the carcinogen.

Adenocarcinoma↗
PubMed1999

Promoting effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone on rat glandular stomach carcinogenesis initiated with N-methyl-N'-nitro-N-nitrosoguanidine.

The modifying effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a mutagenic by-product in chlorinated water, on the development of glandular stomach cancers were investigated in Wistar rats. A total of 120 males, 6 weeks of age, were divided into six groups. After initiation with 100 ppm N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) solution and 5% NaCl diet for 8 weeks, 30 rats each in groups 1-3 were given MX in the drinking water at concentrations of 30, 10, or 0 ppm for the following 57 weeks. Ten animals each in groups 4-6 were administered the MX without prior carcinogen exposure. There were no statistical significant differences in final body weights between the groups. The incidences and multiplicities of adenocarcinomas in the glandular stomachs were significantly higher (P < 0.05) in the initiated 30 ppm MX group than those in the MNNG/NaCl group. The incidences of atypical hyperplasias in the glandular stomachs were also significantly increased (P < 0.05 or 0.01) by the MX treatments. With their multiplicity, the effects were clearly dose dependent. Interestingly, the 30 ppm MX alone itself induced atypical hyperplasias in the pylorus, although the incidences and severity were low. Moreover, MX showed a tendency to enhance the development of intrahepatic cholangiocellular tumors and thyroid follicular cell tumors in the MNNG-treated animals. The results of the present study thus indicate that MX exerts promoting effects when given during the postinitiation phase of two-stage glandular stomach carcinogenesis in rats.

Adenocarcinoma↗
PubMed1999

Activated stellate (Ito) cells possess voltage-activated calcium current.

We previously reported stellate (Ito) cells possess voltage-activated Ca2+ current. The activation of stellate cells has been indicated to contribute to liver fibrosis and the regulation of hepatic hemodynamics. The aim of this study was to investigate the relationship between voltage-activated Ca2+ current and activation of stellate cells. Voltage-activated Ca2+ current in stellate cells isolated from rats were studied using whole-cell patch clamp technique. L-type voltage-activated Ca2+ current was hardly detected in stellate cells cultured for less than 9 days. Ca2+ current was detected 12.5 and 69% of cells at the 10th and 14th day of culture, respectively. BrdU incorporation indicated cell proliferation was recognized over 50% of cells at the 3rd and 5th day of culture, respectively, then decreased significantly in a time-dependent manner. On the other hand, the expression of alpha-smooth muscle actin indicated cell activation increased from 7th day of culture and collagen type I mRNA appeared remarkably in cells cultured for more than 10 days. In this study, we concluded L-type voltage-activated Ca2+ current was recognized in activated stellate (myofibroblast-like) cells.

Actins↗
PubMed1999

Alternative structural state of transferrin. The crystallographic analysis of iron-loaded but domain-opened ovotransferrin N-lobe.

Transferrins bind Fe3+ very tightly in a closed interdomain cleft by the coordination of four protein ligands (Asp60, Tyr92, Tyr191, and His250 in ovotransferrin N-lobe) and of a synergistic anion, physiologically bidentate CO32-. Upon Fe3+ uptake, transferrins undergo a large scale conformational transition: the apo structure with an opening of the interdomain cleft is transformed into the closed holo structure, implying initial Fe3+ binding in the open form. To solve the Fe3+-loaded, domain-opened structure, an ovotransferrin N-lobe crystal that had been grown as the apo form was soaked with Fe3+-nitrilotriacetate, and its structure was solved at 2.1 A resolution. The Fe3+-soaked form showed almost exactly the same overall open structure as the iron-free apo form. The electron density map unequivocally proved the presence of an iron atom with the coordination by the two protein ligands of Tyr92-OH and Tyr191-OH. Other Fe3+ coordination sites are occupied by a nitrilotriacetate anion, which is stabilized through the hydrogen bonds with the peptide NH groups of Ser122, Ala123, and Gly124 and a side chain group of Thr117. There is, however, no clear interaction between the nitrilotriacetate anion and the synergistic anion binding site, Arg121.

Animals↗
PubMed1999

Usefulness of newly designed pigtail catheter with multiple side holes by reducing incidence of ventricular ectopy.

This study was designed to determine whether a newly designed 5 Fr pigtail catheter of Jet Balance with multiple side holes reduces the incidence of ventricular ectopy during left ventriculography. To examine the catheter movement in vitro, we injected a colored glycerin solution by an injector through 5 Fr Jet Balance catheter and 6 Fr conventional pigtail catheter suspended in a water filled, glass container. A recoil of the catheter caused by injection was observed for a 6 Fr conventional catheter; however, no catheter movement was observed when a 5 Fr Jet Balance was used. To evaluate clinical usefulness of the 5 Fr Jet Balance, we compared the number of incidence of ventricular ectopy during left ventriculography between 5 Fr Jet Balance and 6 Fr conventional pigtail catheters. In 104 consecutive patients who underwent left ventriculography, a 5 Fr Jet Balance was used in 55 patients (5 Fr Jet Balance group), and a 6 Fr conventional pigtail in 49 patients (6 Fr conventional pigtail group). The 5 Fr Jet Balance group had a significantly lower incidence of VPB (21.8% vs. 42.9%, P = 0.02), ventricular tachycardia (1.9% vs. 14.3%, P = 0.02), and multiple VPB (9.0% vs. 34.7%, P = 0.001), respectively, than the 6 Fr conventional pigtail group. In conclusion, a 5 Fr Jet Balance pigtail catheter is useful and safe as regard to the incidence of ventricular ectopy during left ventriculography. Cathet. Cardiovasc. Intervent. 48:220-225, 1999.

Aged↗
PubMed1999

The relationship between decrease in Cx32 and induction of P450 isozymes in the early phase of clofibrate hepatocarcinogenesis in the rat.

To examine the relationship between the decrease in connexin 32 (Cx32) and induction of P450 isozymes in the early phase of clofibrate hepatocarcinogenesis, a total of 20 male F344 rats were initiated with a single intraperitoneal injection of 150 mg/kg of diethylnitrosamine (DEN) or given the saline vehicle alone and starting 2 weeks later given diet containing 0.18, 0.09, and 0% clofibrate for 6 weeks. All animals were subjected to two-thirds partial hepatectomy at week 3 and killed at week 8. Absolute and relative (ratios to body weight) liver weights were significantly increased in the DEN + clofibrate groups compared with the DEN-alone group. Diffuse hepatocellular hypertrophy with granular cytoplasmic eosinophilia characterized by a marked increase in peroxisomes and smooth endoplasmic reticulum, was observed in the clofibrate treated rats. Induction of cytochrome P450 (CYP) 4A1 and 2B1/2 was noted in the DEN + clofibrate groups, this being most marked in the CYP 2B1 case. Immunohistochemically, positive immunostaining for anti-CYP 4A1 and CYP 2B1 were observed diffusely and centrilobularly, respectively. The numbers and areas of Cx32-positive spots per hepatocyte in the centrilobular areas in the treated rats were significantly decreased in an essentially dose-dependent manner, but no changes were observed in periportal areas. The numbers and areas of foci positive for glutathione S-transferase placental form (GST-P) were decreased in a dose dependent manner in the clofibrate treated groups. These results suggest that the CYP 2B1/2 induction and Cx32 decrease in centrilobular hepatocytes, similarly to those thought to be involved in the hepatic promotion mechanism of phenobarbital, may also play important roles in clofibrate actions in the liver, in addition to its causation of oxidative DNA injury.

Animals↗
PubMed1999

Cardiac effects of propofol and its interaction with autonomic nervous system in isolated, cross-circulated canine atria.

PURPOSE: The effects of propofol on sinoatrial pacemaker activity and myocardial contractility and its interaction with the autonomic nervous system were investigated in isolated, cross-circulated right atrial canine preparations. METHODS: An isolated right atrial preparation was perfused with heparinized arterial blood from an anesthetized support dog and changes in atrial rate and atrial contractile force were recorded. RESULTS: Propofol (30-1000 microg) and thiopental (30-1000 microg), injected into the sinus node artery of the isolated atrium, induced dose-dependent decreases in atrial rate and contractile force. The negative chronotropic and inotropic effects of propofol were greater than those of thiopental. The propofol-induced negative chronotropic and inotropic responses were not inhibited by atropine. Propofol had no effects on the cardiac responses to acetylcholine, norepinephrine, and the intracardiac parasympathetic nerve stimulation which activates ganglionic nicotinic acetylcholine receptors. CONCLUSION: These results indicate that: (a) propofol directly depresses sinoatrial pacemaker activity and myocardial contractility, (b) the negative chronotropic and inotropic effects of propofol do not involve activation of muscarinic receptors, and (c) propofol has little interaction with the autonomic nervous system at the effector site.

Journal Article↗
PubMed1999

Prevalence of calf diarrhea caused by bovine group A rotavirus carrying G serotype 8 specificity.

One hundred and seventeen rectal fecal specimens were collected in 1995 and 1996 from calves with diarrhea in Kagoshima Prefecture in Japan. The bovine group A rotavirus was detected by enzyme immunoassay in 43 of 117 specimens and isolated from 33 of the 43 specimens that were positive. G serotype, P serotype, and P genotype of 33 isolates were identified by reverse transcription-polymerase chain reaction, and 20 of 33 isolates (60.6%) were identified as G serotype 8. Thus, we discovered that calf diarrhea caused by bovine group A rotavirus carrying G serotype 8 specificity was prevalent in this research area during this research period. To our knowledge, this is the first report on the prevalence of calf diarrhea caused by the bovine group A rotavirus carrying G serotype 8 specificity.

Animals↗
PubMed1999

DNA flow cytometric quantification and DNA polymorphism analysis in the case of a complete mole with a coexisting fetus.

PURPOSE: Our purpose was to investigate whether DNA flow cytometric quantification and DNA polymorphism analysis are useful for cytogenetic diagnosis in the case of a complete hydatidiform mole that coexists with a living fetus. METHODS: Flow cytometric analysis of the nuclear DNA content and polymerase chain reaction (PCR) amplification of the minisatellite locus with the MCT118 probe were performed on the tissues (fetus, placenta and mole) obtained at the initial evacuation. RESULTS: DNA histograms of placental, fetal, and molar tissues showed diploid peaks. PCR products demonstrated that the allele of the mole was homozygous and inherited solely from the husband and that the mole differed genetically from the fetus and the placenta. CONCLUSIONS: These results suggested that DNA flow cytometry and DNA polymorphism analysis may be useful for the cytogenetic diagnosis of a complete hydatidiform mole and a coexisting fetus.

Adult↗
PubMed1999

Ammonia, hydrogen peroxide, and monochloramine retard gastric epithelial restoration in rabbit cultured cell model.

Ammonia (NH3), hydrogen peroxide (H2O2) and monochloramine (NH2Cl) produced by Helicobacter pylori infection might be responsible for mucosal injury. The aim of this study was to evaluate the role of NH3, H2O2, and NH2Cl in the restoration of rabbit primary cultured gastric mucosal cells with a wound repair model. Artificial wounds were made in confluent monolayer gastric epithelial cell sheets by mechanical denudation, and changes in the size of the cell-free area were analyzed quantitatively. Cell proliferation was assessed by bromodeoxyuridine staining. In controls, the wound healed within 48 hr. However, mucosal cell repair was inhibited by treatment with NH3, H2O2, and NH2Cl in a dose-dependent manner. These results indicate that NH3, H2O2, and NH2Cl retarded the wound healing, which included epithelial cell migration and proliferation of gastric mucosa. Therefore, it is suggested that NH3, H2O2, and NH2Cl delays the healing process of peptic ulcers.

Ammonia↗