Hiroshi Mori

Aichi Cancer Center, Ōsaka, Ōsaka, Japan

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Publications (17)26.89 Total impact

  • [Show abstract] [Hide abstract] ABSTRACT: In the present study, we investigated the effects of some anti-asthmatic drugs on the production of the CC chemokine, macrophage inflammatory protein-1α (MIP-1α), in response to lipopolysaccharide (LPS) by peripheral blood mononuclear cells (PBMC). MIP-1α production was induced by LPS in a concentration-dependent fashion and reached the maximum at 10 µg/ml LPS (27.5±2.3 ng MIP-1α/106 PBMC). At a submaximal concentration of LPS (1 µg/ml), the release of MIP-1α increased with time and reached the maximum 24 h after LPS stimulation. Actinomycin D and cycloheximide inhibited MIP-1α production completely, but glucocorticoids did not completely inhibit MIP-1α production, with a maximum inhibition of 70%. We examined the effect of β-stimulants and phosphodiesterase inhibitors, which upregulate intracellular cyclic AMP levels, on MIP-1α production. When PBMC were treated with β-stimulants alone, β-stimulants showed a slightly inhibitory effect on MIP-1α production. However, the coadministration of roliplam significantly potentiated the inhibitory effect of β-stimulants on MIP-1α production. Moreover, db-cAMP suppressed MIP-1α production dose-dependently. The above data indicate that the production of MIP-1α is regulated by cyclic AMP and that cyclic AMP could provide a useful target for therapeutic treatment in asthmatic diseases and other diseases where MIP-1α is involved in their etiology.
    No preview · Article · Apr 1998 · Pharmacology
  • [Show abstract] [Hide abstract] ABSTRACT: Previously, we reported that the 5-fluorouridine derivative, 2',3',5'-tris-O-[N-(2-n-propyl-n-pentanoylglycyl]-5-fluorouridine dine (UK-21), is a newly synthesized lowly immunosuppressive and potent antitumor drug in comparison with other fluorouridine derivatives such as B-fluorouracil (5-FU), 5-fluorouridine (5-FUR) and 5-fluorodeoxyuridine (5-FUDR). In order to elucidate the molecular mechanism of antitumor activity of UK-21, we compared the effect of the four drugs on cell proliferation, cell cycle progression and macromolecular syntheses. When KB cells were subjected to a colony-forming inhibition assay designed to expose the cells to the drugs for 4-96 h and wash out, UK-21 and 5-FUR inhibited the colony formation at concentrations ranging from 0.01 to 0.1 mu M, whereas 1-100 mu M was needed for the cytotoxicity of 5-FU and 5-FUDR. By exposure for 24-48 h, all these drugs inhibited cell growth and caused accumulation of the cells in S or G(2) phase at almost the same concentrations of 0.32-8 mu M. These results suggest that the cytotoxic effects of UK-21 and 5-FUR are irreversible, while those of 5-FU and 5-FUDR are reversible. To confirm this, KB cells were treated with UK-21 and/or 5-FU for 1 h, and continued to be cultured for 1-7 days, resulting in the inhibition of the cell growth by UK-21 in a dose-dependent manner at concentrations of 10-100 mu M, but not by 5-FU even at 100 mu M. UK-21, 5-FUR and 5-FU showed a linear relationship between exposure time and IC50 in the colony formation assay with a slope of almost -1, but 5-FUDR did not, suggesting that UK-21, 5-FUR and 5-FU are cell cycle non-specific inhibitors, while 5-FUDR is a cell cycle-specific inhibitor. UK-21 and 5-FUR, but not 5-FU and 5-FUDR inhibited the incorporation of [H-3]uridine into the acid insoluble fraction, while UK-21 and 5-FUDR, but not inhibited the incorporation of results suggest that irreversible cytotoxic effects of UK-21 like 5-FUR are exerted through inhibition of RNA synthesis.
    No preview · Article · Jun 1997 · Anti-Cancer Drugs
  • Hiroichi Nagai · Yuko Takaoka · Hiroshi Mori · Kenji Kawada
    [Show abstract] [Hide abstract] ABSTRACT: KE-298 is a new immunomodulatory agent with a chemical structure similar to that of D-penicillamine. We compared the effects of KE-298 on type II collagen-induced arthritis (CIA) in mice with those of prednisolone. KE-298 at a dose of 25 mg/kg showed only a decrease in the progression of foot pad swelling. At doses of 50 and 100 mg/kg, however, KE-298 inhibited the severity and development of the collagen-induced arthritis index, the progression of foot pad swelling, bone damage and histopathological changes. These inhibitory effects were more pronounced at the dose of 50 mg/kg than at 100 mg/kg. KE-298 also significantly inhibited the delayed-type hypersensitivity (DTH) response to type II collagen, but did not affect the production of anti-type II collagen IgG antibody in arthritic mice. To determine the inhibitory mechanism of KE-298, we studied the effect of KE-298 on IL-1β and TNF-α production in mice. We found that KE-298 inhibited bacterial lipopolysaccharide (LPS)-induced IL-1β production at doses of 50 and 100 mg/kg. It inhibited the production of TNF-α at the dose of 50 mg/kg, but not at 100 mg/kg. In summary, at appropriate dosages, KE-298 inhibited CIA and TNF-α production in mice. KE-298 also inhibited the DTH reaction to type II collagen and LPS-induced IL-1β production in a dose-related fashion. These findings suggest that these effects of KE-298 are closely related to its immunomodulatory action.
    No preview · Article · Jan 1996 · Pharmacology
  • [Show abstract] [Hide abstract] ABSTRACT: Biphasic skin reactions, with peaks at 1 and 24 h after epicutaneous challenge with antigen (immediate phase response: IPR and late phase response: LPR, respectively), were induced in ddY, ICR, Balb/c and Balb/c-nu/nu mice passively sensitized with monoclonal IgE antibody 24 h before. In WBB6F1-W/Wv mice, which lack mast cells, only the LPR was observed. The IPR was characterized by a rapid increase in capillary permeability and the LPR by skin thickening with significant infiltration of eosinophils and other inflammatory cells in Balb/c mice. Histamine H1 receptor antagonists, including diphenhydramine and homochlorcyclizine, and the allergic histamine release inhibitors, tranilast and amlexanox, clearly inhibited the IPR, but not the LPR. Prednisolone and dexamethasone, however, inhibited both. Prednisolone also inhibited the LPR in WBB6F1-W/Wv mice. These results indicate that IgE antibody-dependent biphasic skin reactions consist of a mast cell- and histamine-dependent IPR and a mast cell-independent LPR.
    No preview · Article · Mar 1995 · Biological & Pharmaceutical Bulletin
  • [Show abstract] [Hide abstract] ABSTRACT: The effects of AH 21-132, a type III and IV phosphodiesterase (PDE) inhibitor, on allergic reactions in the airway were studied by comparing them with the effects of rolipram, a type IV PDE inhibitor, and aminophylline, a non-selective PDE inhibitor. The following results were obtained: 1) AH 21-132, rolipram and aminophylline inhibited the antigen-induced contraction of isolated guinea pig tracheal muscle in vitro. 2) AH 21-132 and aminophylline inhibited antigen-induced histamine release from human lung tissue fragments. 3) Antigen-induced accumulation of inflammatory cells including eosinophils and macrophages in mice bronchoalveolar lavage fluid was clearly inhibited by AH 21-132 and rolipram, but not by aminophylline. 4) AH 21-132, rolipram and aminophylline inhibited immediate phase bronchoconstriction induced by either an intravenous or an aerosol challenge of antigen in guinea pigs. 5) AH 21-132 and rolipram inhibited the aeroantigen challenge-induced late phase increase in the airway resistance in guinea pigs, but aminophylline did not. These results suggest that AH 21-132 has an anti-allergic effect in the airway and that these actions may be beneficial for the treatment of allergic bronchial asthma.
    No preview · Article · Feb 1995 · The Japanese Journal of Pharmacology
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    [Show abstract] [Hide abstract] ABSTRACT: We have developed an experimental model for exercise-induced asthma (EIA) using conscious guinea pigs. Respiratory resistance (Rrs) was measured before and after exercise (running). When a 0.05% lipopolysaccharide (LPS) was inhaled by guinea pigs which had been pretreated with a corticosteroid biosynthesis inhibitor metyrapone (50 mg/kg, i.v.), Rrs significantly increased 24 h after exercise. Metyrapone had no effect, however, on the LPS-induced increase in the numbers of macrophages, eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF). In order to examine the role of airway inflammation, the effects of murine recombinant interleukin-5 (mrIL-5) and platelet activating factor (PAF) were investigated in guinea pigs. The exercise-elicited increase in Rrs was observed 24 h later than the treatment with mrIL-5 in metyrapone-treated animals. The number of macrophages, eosinophils and neutrophils increased in the BALF of mrIL-5-treated animals. In contrast, a 0.05% PAF aerosol caused an increased number of eosinophils in BALF, but did not affect Rrs after exercise in either metyrapone-treated or non-treated animals. Moreover, to evaluate the value of this model as a pharmacological tool, the effect of ketotifen and prednisolone on the exercise-induced increase in Rrs was investigated. Prior administration of ketotifen and prednisolone showed a tendency to prevent, or clearly inhibited, the exercise-induced increase in Rrs in animals treated with the combination with LPS and metopyrone.
    Full-text · Article · Feb 1995 · Biological & Pharmaceutical Bulletin
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    Hiroshi Takeda · Hiroshi Mori · Takahiro Hiroi · Jun Saito
    [Show abstract] [Hide abstract] ABSTRACT: We studied five new Antartic achondrites, MacAlpine Hills (MAC) 88177, Yamato (Y)74357, Y75274, Y791491 and Elephant Moraine (EET)84302 by mineralogical techniques to gain a better understanding of the mineral assemblages of a group of meteorites with an affinity to Lodran (stony-iron meteorite) and their formation processes. This group is being called lodranites. These meteorites contain major coarse-grained orthopyroxene (Opx) and olivine as in Lodran and variable amounts of FeNi metal and troilite etc. MAC88177 has more augite and less FeNi than Lodran; Y74357 has more olivine and contains minor augite; Y791491 contains in addition plagioclase. EET84302 has an Acapulco-like chondritic mineral assembladge and is enriched in FeNi metal and plagioclase, but one part is enriched in Opx and chromite. The EET84302 and MAC88177 Opx crystals have dusty cores as in Acapulco. EET84302 and Y75274 are more Mg-rich than other members of the lodranite group, and Y74357 is intermediate. Since these meteorites all have coarse-grained textures, similar major mineral assemblages, variable amounts of augite, plagioclase, FeNi metal, chromite and olivine, we suggest that they are related and are linked to a parent body with modified chondritic compositions. The variability of the abundances of these minerals are in line with a proposed model of the surface mineral assemblages of the S asteroids. The mineral assemblages can best be explained by differing degrees of loss or movements of lower temperature partial melts and recrystallization, and reduction. A portion of EET84302 rich in metal and plagioclase may represent a type of component removed from the lodranite group meteorites. Y791058 and Caddo County, which were studied for comparison, are plagioclase-rich silicate inclusions in IAB iron meteorites and may have been derived by similar process but in a different body.
    Preview · Article · Dec 1994 · Meteoritics
  • [Show abstract] [Hide abstract] ABSTRACT: Our previous studies indicated that a newly synthesized 5-fluorouridine derivative, 2',3',5'- tris- O-[ N-(2- n-propyl- n-pentanoyl)glycyl]-5-fluorouridine (UK-21), revealed its antitumor activity by being converted to 5-fluorouridine (5-FUR) and showed a low level of immunological side effects. However, the bioavailability of UK-21 given orally did not seem to be good. In the present study, we focused on the antitumor and immunosuppressive activities of UK-21 given i.p. to mice. UK-21 suppressed the growth of L-1210, P388 and EL4 leukemias inoculated i.v. into corresponding syngeneic mice and both the growth of Lewis lung carcinoma transplanted s.c. and its subsequent metastasis to the lung. UK-21 showed antitumor activity at doses almost 10 times lower than those of 5-fluorouracil (5-FU). The side effects of UK-21, especially on immune functions, were examined in comparison with those of 5-FUR, 5-FU, and cyclophosphamide (CY) at doses producing comparable antitumor activity. The suppressive effect of UK-21 on IgM and IgG antibody formation in mice immunized with ovalbumin was clearly weaker than that of 5-FUR, 5-FU, and CY. The suppressive effect of UK-21 on thymus weight was markedly weaker than that of 5-FU and CY. The reduction of WBC counts induced by UK-21 was also lower than that produced by any other agent. The results reported herein suggest the strong possibility of UK-21 being developed as a novel anticancer drug with cytotoxic mechanisms different from those of 5-FU. Our study also points to the chemical modification of 5-FUR as a feasible way of developing new anticancer drugs.
    No preview · Article · Jun 1994 · Cancer Chemotherapy and Pharmacology
  • Hiroshi Takeda · Hiroshi Mori · Donald D. Bogard
    [Show abstract] [Hide abstract] ABSTRACT: Previous investigations of mineral chemistry and RbSr and SmNd ages indicated that clast,84 from eucrite Yamato 75011 had preserved the pristine nature of its initial crystallization during an early stage of the HED parent body. Microscale mineralogy and39Ar-40Ar ages of this clast, however, revealed local disturbance of micrtextures and partially reset ages. This evidence suggests that, in addition to initial crystallization and rapid cooling, the Y75011,84 clast experienced shock deformation, reheating of short duration at higher temperature, and brecciation. These characteristics suggest two or more impact events. Fe-rich olivine filling fractures in pyroxene may have been introduced during the accompanying shock fracturing. The inferred39Ar-40Ar degassing ages for Y75011 matrix and clast,84 are3.94 ± 0.04 Ga and3.98 ± 0.03 Ga, respectively. The suggested degassing age for a clast from Y790020, believed to be paired with Y75011, is ∼ 4.03 Ga, but could be younger. We consider it likely that all three samples experienced a common degassing event3.95 ± 0.05 Ga ago, but we cannot rule out two or more events spaced over a ∼ 0.1 Ga interval. Higher temperature extractions of the two clast samples show significantly older apparent ages up to ∼ 4.5 Ga and suggest that the time/temperature regime of this event was not sufficient to degas Ar totally. Most likely, the K-Ar ages were reset by thermal metamorphism associated with one or more impact events associated with shock fracturing, formation of Fe-rich olivine veins, and/or meteorite brecciation. The pyroxene annealing that commonly occurs in many eucrites is likely to be a much earlier process than the impact-produced textural changes and reset K-Ar ages observed in these meteorites. The existence of mineralogical and chronological evidence for metamorphism in an otherwise pristine eucrite suggests that the HED parent body experienced an extensive degree of early cratering.
    No preview · Article · Mar 1994 · Earth and Planetary Science Letters
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    [Show abstract] [Hide abstract] ABSTRACT: Mineralogy of kirschsteinite exsolution in olivine from Antarctic meteorite LEW86010 has been studied by single crustal X-ray diffraction technique. The LEW86010 olivine crystals have exsolution lamellae of kirschteinite about 15 microns wide. Determination of crystallographic orientation of exsolved kirschsteinite in an olivine grain has been made. Weak reflections of exsolved kirschsteinite share common crystallographic orientation with the host olivine. The cell dimensions of the exsolved phase (a - 4.87 plus or minus 0.05A, b - 11.14 plus or minus 0.10A, c - 6.36 plus or minus 0.05A) and intensities were in well accord with those of kirschsteinite previously reported. Oriented section perpendicular to the a axis shows exsolution lamellae in two directions parallel to (031) and (031). The lamellae are up to 10 microns in width and spacings between them are usually 50-100 microns.
    Preview · Article · Jan 1993
  • [Show abstract] [Hide abstract] ABSTRACT: We have previously reported that 2',3',5'-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21), a derivative of 5-fluorouridine (5-FUR), and 1-{6-[N-(2-n-propyl-n-pentanoyl)-glycyl]amino-n-hexylcarbamoyl}-5-fluorouracil (UK-25), a derivative of 5-fluorouracil (5-FU), exert their antitumor activity in mice bearing Meth A or EL4 tumor, while their immunosuppressive effects are mild. In the present study, we examined the effects of these compounds on Sarcoma-180 (S-180), P388, L1210, and Lewis lung carcinoma (LLC) in mice by p.o. administration and on Meth A tumor by i.p.-administration. UK-21 given p.o. showed an antitumor effect against S-180, but it showed virtually no antitumor effects against P388, L1210 and LLC. UK-21 given i.p., on the other hand, strongly inhibited the growth of Meth A tumor at a far lower dose than that for oral administration. The bioavailability of UK-21 given p.o. was suspected to be poor. UK-25 given p.o., in contrast, showed the antitumor effect on all of the tumors employed. The bioavailability of UK-25 given p.o. seemed to be comparable to those of other drugs. These results suggest that UK-21 has the potential for development as a parenterally applicable anticancer drug, and UK-25 has the potential as an oral one.
    No preview · Article · Aug 1992 · The Japanese Journal of Pharmacology
  • [Show abstract] [Hide abstract] ABSTRACT: We studied the biological activities of several 5-fluorouridine (5-FUR) and 5-fluorouracil (5-FU) derivatives to find novel antitumor drugs with lower immunosuppressive effects. We examined 5-FUR and 5-FU derivatives acylated with (2-n-propyl-n-pentanoyl)glycine (KN-539). Among the examined compounds, we found satisfactory activities in a derivative of 5-FUR, 2',3',5'-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21), and a derivative of 5-FU, 1-{6-[N-(2-n-propyl-n-pentanoyl)glycyl]amino-n-hexylcarbamoyl}-5-fluorouracil (UK-25). UK-21 (0.05-0.2 mmole/kg, p.o., 10 days) and UK-25 (0.1-0.4 mmole/kg, p.o., 10 days) suppressed Meth A and E.L.4 tumor growths in the corresponding syngeneic hosts (BALB/c mice and C57BL/6 mice, respectively) without decreasing body weight and blood leukocyte count. UK-21 and UK-25 suppressed the proliferation of KB tumor cells in vitro (IC50: 3.0 x 10(-11) M and 4.4 x 10(-7) M, respectively) at concentrations almost equivalent to those of 5-FUR and 5-FU, respectively. These results suggest that UK-21 and UK-25 express their antitumor activity as 5-FUR and 5-FU, respectively. Neither UK-21 nor UK-25 suppressed thymus weight and humoral antibody production against sheep red blood cells (SRBC) in ddY mice, although 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and 5-FU suppressed them in their respective therapeutic dose ranges for tumors. Thus, UK-21 and UK-25 are expected to develop into anticancer drugs with lower immunotoxicological effects.
    No preview · Article · Mar 1992 · The Japanese Journal of Pharmacology
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    [Show abstract] [Hide abstract] ABSTRACT: Polished thin sections of lunar meteorites EET87521 and Y793274, possibly derived from a mare region of the moon, have been analyzed for the mineral chemistries and textures. Basaltic components in both objects contain strongly zoned Fe-Ca-rich pyroxenes like those found in the VLT basalts. A mesostasis portion found in a basaltic clast of EET87521 consists of ilmenite, minor Cr-Ti spinel mantled by fayalite Fo10-prime, and fine-grained mixtures of hedenbergite and fayalite in contact with a silica mineral. Mg-rich materials are rare in EET87521 but abundant in Y793274. The latter contains the most Mg-rich clast found in lunar samples with orthopyroxene and ilemnite, a gabbroic clast with finely exsolved pigeonite, olivine, and plagioclase, and pyroxene clasts intermediate between those in the basaltic and the Mg-rich clast types. A pyroxene fragment in EET87521 shows exsolution lamellae of augite about 300 nm wide, which is consistent with mare basalt origin.
    Preview · Article · Jan 1992
  • [Show abstract] [Hide abstract] ABSTRACT: The new lunar meteorite MAC88105 has been studied by mineral-chemical techniques and was compared with the Yamato lunar meteorites. Clast types and pyroxene compositions of MAC88105 indicate that evidence for a pairing with any known lunar meteorites is unlikely. Clast-laden vitric breccia and comminuted mineral fragments in glassy matrix are common components as in other lunar meteorites, but granulitic clasts are not as common as in other lunar meteorites. The large and common granulite-like meta-igneous clasts still preserve lath-shaped plagioclase crystals with fine-grained olivine and pyroxenes in the interstices. Pyroxenes with mg number = Mg × 100/(Mg + Fe) between 70-48 mol% are common, but more Mg-rich pyroxenes and plutonic pyroxenes from nonmare pristine crustal rocks are rare. One basaltic clast contains pyroxenes with zoning trends more Mg-rich than the above mg range and than those of the VLT basalts common in lunar meteorites. MAC88105 preserves true glass in the matrix as observed by a transmission electron microscope (TEM). The preservation of glassy materials indicates that MAC88105 had a metamorphic annealing history different from other lunar meteorites.
    No preview · Article · Nov 1991 · Geochimica et Cosmochimica Acta
  • Hiroshi Mori · Hiroshi Takeda
    [Show abstract] [Hide abstract] ABSTRACT: A transmission electron microscopic (TEM) study was conducted to investigate the stress-induced transformation mechanisms of pigeonites from two achondrites. In pigeonites from the Allan Hills 77257 ureilite, abundant lamellae of orthopyroxene-pigeonite intergrowth accompanied by minor amounts of blebby augite precipitates were observed. In pigeonites from the Juvinas eucrite, some stacking faults running through the (001) augite lamellae were observed although most of the stacking faults terminated at the host-lamella interface. High resolution TEM observation shows the fringe offset produced by the stacking fault in the Juvinas pigeonites. The magnitude of the mismatch parallel to [001] is approximately c/4, which is related to the formation of the partial edge dislocation near the host-lamella interface. The partial dislocation is imaged as an edge dislocation with an (002) extra-plane. Three partial dislocation mechanisms with distinct displacement vectors are proposed in order to explain the stress-induced transformation textures observed in the achondritic pyroxenes. Further study will be required to determine unequivocally the mechanism of atomic displacements during stress-induced transformation. However, regardless of the actual mechanism of transformation, it is not difficult to convert orthopyroxene to clinopyroxene or vice versa by this transformation from the structural point of view. Low-Ca pyroxenes are deformed without a stress-induced transformation by slip at high temperature and geologically reasonable strain rates. However, meteoritic pyroxenes can be deformed by stress-induced transformation even at high temperature because preterrestrial impact processes will produce a deformation condition with high strain rates. Deformation at high strain rates and high temperature is very important when we interpret the microtexture of meteoritic pyroxenes.
    No preview · Article · Feb 1988 · Physics and Chemistry of Minerals
  • Hiroshi Mori · Hiroshi Takeda
    [Show abstract] [Hide abstract] ABSTRACT: Transmission electron microscopy was used to find microtextures suggestive of the origin of orthopyroxenes of bronzite composition from three diogenites: Johnstown, Ibbenburen and Allan Hills ALPHA 77256. Sub-boundaries decorated with thick augite lamellae up to 100 microns in length were found in all three orthopyroxenes, and suggests either dislocation recovery processes during mild deformation or annealing at high subsolidus temperature. It is conjectured that during or after crystallization at high temperatures deep in the crust, diogenitic pyroxenes may have experienced mild deformation conditions at substantial static pressures and temperatures. Alternatively, several meteoritic impacts may have caused the destruction of a part of the diogenitic layer, with a large impact finally excavating the parental mass seen in the Johnstown specimen.
    No preview · Article · Apr 1981 · Earth and Planetary Science Letters
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    Hiroshi Takeda · Toshiyuki Baba · Hiroshi Mori · Jun Saito
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