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Biomedical subjects

M Kozuka

Publications and source records attributed to M Kozuka.

At least 37 records · Page 2Linked to original sources
PubMed1995

Antitumor agents, 154. Cytotoxic and antimitotic flavonols from Polanisia dodecandra.

Three flavonols, 5,3'-dihydroxy-3,6,7,8,4'-pentamethoxyflavone [1], 5,4'-dihydroxy-3,6,7,8,3'-pentamethoxyflavone [2], and quercetin 3-O-beta-D-glucopyranosyl-7-O-alpha-L-rhamnopyranoside [3], were isolated from Polanisia dodecandra. Compound 1 showed remarkable cytotoxicity in vitro against panels of central nervous system cancer (SF-268, SF-539, SNB-75, U-251), non-small cell lung cancer (HOP-62, NCI-H266, NCI-H460, NCI-H522), small cell lung cancer (DMS-114), ovarian cancer (OVCAR-3, SK-OV-3), colon cancer (HCT-116), renal cancer (UO-31), a melanoma cell line (SK-MEL-5), and two leukemia cell lines (HL-60 [TB], SR), with GI50 values in the low micromolar to nanomolar concentration range. This substance also inhibited rubulin polymerization (IC50 = 0.83 +/- 0.2 microM) and the binding of radiolabeled colchicine to tubulin with 59% inhibition when present in equimolar concentrations with colchicine. Compound 2 also showed cytotoxicity against medulloblastoma (TE-671) tumor cells with an ED50 value of 0.98 microgram/ml. Compound 1 appears to be the first example of a flavonol to exhibit potent inhibition of tubulin polymerization and, therefore, warrants further investigation as an antimitotic agent.

Antineoplastic Agents↗
PubMed1995

Inhibitory effect of natural carotenoids on Epstein-Barr virus activation activity of a tumor promoter in Raji cells. A screening study for anti-tumor promoters.

As a screening study for anti-tumor promoters, 51 carotenoids with diverse structures were examined for their inhibitory effects on the Epstein-Barr virus activation activity of 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. The results showed that most of the carotenoids exhibited inhibitory activity, and in general, no cytotoxicity on Raji cells was observed in the assay. Among the carotenoids, beta-cryptoxanthin, lutein, and lactucaxanthin showed the strongest inhibitory activity, superior to the well known anti-tumor promoter, beta-carotene. Heteroxanthin, peridinin, and halocynthiaxanthin showed cytotoxicity at the high concentration (1000 molar ratio per TPA), but indicated a strong inhibitory effect at the lower concentrations, which were only weakly toxic (500 and 100 molar ratios). Based on these results, the essential moiety for the activity of carotenoids was considered to be the 3-hydroxy-epsilon-end group.

Antineoplastic Agents, Phytogenic↗
PubMed1995

Inhibitory effects of cucurbitane triterpenoids on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumor. II.

To search for possible anti-tumor-promoters, we carried out a primary screening of twenty-four 29-nor-cucurbitacin glucosides isolated from the roots of Cayaponia tayuya (Cucurbitaceae) using an in vitro synergistic assay system. Of these glucosides, cayaponosides B (5), B3 (7), D (8), D3b (22) and C2 (23) exhibited significant inhibitory effects on Epstein-Barr virus (EBV) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, 5 and 23 exhibited remarkable anti-tumor-promoting effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Animals↗
PubMed1995

Inhibitors of skin-tumor promotion. XIII. Inhibitory effects of euglobals and their related compounds on Epstein-Barr virus activation and on two-stage carcinogenesis of mouse skin tumors. (2).

One hundred and fifteen synthesized mono, di, and trihydroxybenzamide and thiobenzamide derivatives having structures related to euglobals were examined for their inhibitory effects on Epstein-Barr virus (EBV) activation by 12-O-tetradecanoylphorbol-13-acetate (TPA) as a primary screening test for anti-tumor-promoters. In general, 3-acyl-2,4,6-trihydroxybenzamide and 3-acyl-2,4,6-trihydroxythiobenzamide derivatives exhibited strong or moderate activities, and the latter compounds were less cytotoxic than the former. Meanwhile, little or no activity was observed with mono and dihydroxybenzamide and dihydroxythiobenzamide derivatives. Structural requirements for the activities of these compounds have been discussed in detail. Among the above compounds, compounds 36 and 73, which were significantly active on the inhibition of EBV activation, were investigated using a two-stage mouse skin carcinogenesis test induced by 7,12-dimethylbenz[a]anthracene (DMBA) and TPA. The results of the in vivo test showed that both compounds have a stronger inhibitory effect than that of the well-known anti-tumor-promoter, glycyrrhetic acid. These results suggested that the two compounds might be valuable as anti-tumor-promoters in chemical carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Anti-tumor-promoting activities of euglobals from Eucalyptus plants.

To search for possible anti-tumor-promoters (chemopreventive agents), we carried out a primary screening of 21 euglobals (acylphloroglucinol-monoterpene or -sesquiterpene structures) isolated from the juvenile leaves of five species of Eucalyptus plants using an in vitro synergistic assay system. Of these compounds, euglobal-G1--G5 (1-5), -Am-2 (15) and -III (16) exhibited significant inhibitory effects on Epstein-Barr virus (EBV) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). Furthermore, the effects of compounds 1 and 16 on the cell cycle of Raji cells were also examined by a flow cytometer, and both compounds 1 and 16 exhibited strong inhibition on the effect of the cell cycle induced by TPA. These two euglobals (1 and 16) exhibited remarkable anti-tumor-promoting effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Inhibitory effects of cucurbitane triterpenoids on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

To search for possible anti-tumor-promoters, we carried out a primary screening of 21 cucurbitane triterpenoids using an in vitro assay system. Of these triterpenoids, scandenoside R6 (6), 23,24-dihydrocucurbitacin F (14), 25-acetyl-23,24-dihydrocucurbitacin F (15), 2-O-beta-D-glucopyranosyl-23,24-dihydrocucurbitacin F (17) and cucurbitacin F (18) exhibited significant inhibitory effects on Epstein-Barr virus (EBV) activation induced by the tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Further, compounds 14 and 17 exhibited remarkable anti-tumor-promotion effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Animals↗
PubMed1994

Euglobal-In-1, a new euglobal from Eucalyptus incrassata.

From the juvenile leaves of Eucalyptus incrassata, a new euglobal having an acylphloroglucinol-sesquiterpene structure, euglobal-In-1 (1), has been isolated along with the known euglobal-III (2) and -V (3). The structure and stereochemistry of 1 were established by spectroscopic methods.

Antigens, Viral↗
PubMed1994

[Anti-tumor promoting activities of kampo prescriptions. II. Inhibitory effects of souseiryu-to on two-stage carcinogenesis of mouse skin tumors and mouse pulmonary tumors].

To search for possible anti-tumor promoters, we carried out a primary screening of fourteen kampo prescriptions utilizing their possible inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation which is induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). In these prescriptions, shouseiryu-to exhibited the most significant inhibitory effect on the EBV-EA activation. Furthermore, two-stage carcinogenesis of mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) and TPA, and mouse pulmonary tumors induced by 4-nitroquinoline-N-oxide (4NQO) and glycerol were strongly inhibited to shouseiryu-to.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Effects of RS-8359 on reduced local cerebral glucose utilization in the rat subjected to transient forebrain ischemia.

Changes in local cerebral glucose utilization (LCGU) of the postischemic rat brain were investigated using the rat four-vessel occlusion model. Following 20 or 30 min of ischemia, LCGUs of the cerebral cortices, striatum and hippocampus were decreased at 1 and 3 days postischemia, but were recovered at 7 days postischemia. Effects of repeated administration of RS-8359, (+-)-4-(4-cyanoanilino)-7-hydroxycyclopenta(3,2-e)pyrimidin e, (30 mg/kg x 2/day, p.o., 4 days) were examined at 3 days postischemia following 20 min of ischemia. Compared with the sham-operated group, the LCGUs of 22 out of 34 structures examined in the ischemic-control group were significantly reduced. In the RS-8359-treated group, however, significant reduction was observed in only 9 structures. Compared with the ischemic-control group, RS-8359 significantly ameliorated the reduction of LCGU in 12 structures. These results suggest that RS-8359 has beneficial effects on reduced glucose metabolism in the postischemic brain.

Animals↗
PubMed1994

Effect of smear layer removal agent and/or fluoride on the surface of dentin.

A study was conducted to observe the effectiveness of an EDTA-based agent, Tubulicid Red, and a polyacrylic acid-based agent, Dentin Conditioner, for removal of the smear layer from a prepared dentin surface, with or without a fluoride dentin reinforcing agent, using the dye penetration test and scanning electron microscopy (SEM). Bovine mandibular first and second incisors were used. After removal of the enamel, the smear layer on the dentin surface was treated with 38% H3PO4, Tubulicid Red, Dentin Conditioner, 1% NaF, 1% SnF2, Tubulicid Red (including 1% SnF2), Dentin Conditioner (including 1% NaF) and Dentin Conditioner (including 1% SnF2). In the dye penetration test, Dentin Conditioner (including 1% SnF2) was the most effective agent for preventing dye penetration. SEM evaluation of the dentin surface after treatment with the smear layer removal agents and/or fluorides showed that the smear layer was removed by H3PO4 and Dentin Conditioner. However, dentinal plugs remained after treatment with Dentin Conditioner alone. The other agents left some layers on the dentin surface.

Acid Etching, Dental↗
PubMed1993

Inhibitory effects of 3-nitrophloroglucinecarboxylic acid derivatives on Epstein-Barr virus early antigen induction.

The inhibitory effects of two series of 3-nitrophloroglucinecarboxylic acid derivatives, 3-nitro-2,4,6-trihydroxythiobenzamides (II) and 3-nitro-phloroglucinecarboxylates (III), on Epstein-Barr virus early antigen (EBV-EA) induction were examined using Raji cells. Some of them strongly inhibited the induction, N-nonyl and O-decyl derivatives being the most potent inhibitors among the thioamides and esters, respectively. These results suggest the possibility that these two 3-nitrophloroglucinecarboxylic acid derivatives may be listed as novel inhibitors of tumor promotion.

Antigens, Viral↗
PubMed1993

Antitumor agents, 138. Rotenoids and isoflavones as cytotoxic constitutents from Amorpha fruticosa.

Eight cytotoxic compounds have been isolated from the CHCl3 extract of Amorpha fruticosa. One compound, 6'-O-D-beta-glucopyranosyldalpanol [10], is a new cytotoxic rotenoid. Another known rotenoid, 12 alpha beta-hydroxyamorphigenin [6], was first shown to exhibit extremely potent cytotoxicity (ED50 < 0.001 microgram/ml) in six neoplastic cell lines. In addition to these compounds, three isoflavones (afrormosin [1], 7,2',4', 5'-tetramethoxyisoflavone [2], 8-methylretusin [3]) and five rotenoids (amorphispironone [4], amorphigenin [5], dalpanol [7], 12a beta-hydroxydalpanol [8], and tephrosin [9]) were isolated. Compound 8 was isolated for the first time as a natural product from this plant. The structures of these compounds were established on the basis of spectral data; some were further confirmed by X-ray crystallographic analysis.

Antineoplastic Agents, Phytogenic↗
PubMed1993

Studies on inhibitors of skin tumor promotion, XII. Rotenoids from Amorpha fruticosa.

As a part of screening studies for chemopreventive agents (anti-tumor-promoters), six North American plants belonging to the Amorpha genus were tested using an in vitro assay system. Of these plants, Amorpha fruticosa exhibited strong inhibitory effects on Epstein-Barr virus early antigen (EBA-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Also six rotenoids, amorphispironone [1], tephrosin [2], amorphigenin [3], 12a-hydroxyamorphigenin [4], 12a-hydroxydalpanol [5], and 6'-O-D-glucopyranosyldalpanol [6], were isolated from the leaves of A. fruticosa. Among these retenoids, 1 and 2 exhibited remarkable inhibitory effects of EBV-EA activation induced by TPA. Further, 1 and 2 exhibited significant anti-tumor-promotion effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These investigations suggested that these rotenoids might be valuable anti-tumor-promoters.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Changes in glucose utilization in the rat brain after transient forebrain ischemia.

BACKGROUND AND PURPOSE: Although several local cerebral glucose utilization (LCGU) studies using rat forebrain ischemia models have been performed to date, none that investigate long-term postischemic changes in LCGU throughout the brain have been reported. We investigated postischemic changes throughout the brain over 14 days using a rat forebrain ischemia model. METHODS: Cerebral ischemia was produced using the rat four-vessel occlusion model. After 30 minutes of ischemia cerebral blood flow was restored, and LCGU in 34 structures in the brain was evaluated at 1, 3, 5, 7, and 14 days after ischemia. RESULTS: LCGU changes were characterized and could be divided into two major patterns, type 1 and type 2. In type 1, LCGU was reduced remarkably at 1 and 3 days, and it returned to near the control level at 5 days. In type 2, LCGU was reduced mildly at 1 day and returned to near the control level at 3 days. Included in type 1 were the severely ischemic structures such as the cerebral cortices and striatum. Included in type 2 were the less severely ischemic structures such as the midbrain, cerebellum, and pons and medulla oblongata. Drastic changes in LCGU took place not only in gray matter but also in white matter, and the patterns of LCGU changes were similar in both regions. Atypical changes in LCGU were observed in the hippocampal CA1 and substantia nigra pars reticulata. In both structures, LCGU was remarkably increased around 7 days after ischemia. CONCLUSIONS: There are two major patterns of LCGU changes after transient forebrain ischemia. LCGU changes in the hippocampal CA1 and substantia nigra pars reticulata are atypical.

Analysis of Variance↗
PubMed1993

Local cerebral glucose utilization in rats with decerebrate rigidity and effects of centrally acting muscle relaxants, diazepam and tizanidine.

Local cerebral glucose utilization (LCGU) was investigated in rats with decerebrate rigidity using the [14C]2-deoxyglucose (2DG) method in order to identify the site responsible for the rigidity. LCGU was increased in the medial vestibular nucleus, the fastigial nucleus, the interpositus nucleus and the dentate nucleus during decerebrate rigidity. Diazepam and tizanidine, centrally acting muscle relaxants, reduced the increase of LCGU in the vestibular and cerebellar nuclei. These results suggest that the vestibular and cerebellar nuclei are the possible sites responsible for the development of decerebrate rigidity and the action of some centrally acting muscle relaxants.

Animals↗
PubMed1993

Constituents of rosaceous plants. I. Structure of new triterpenoids from Cowania mexicana.

In our search for possible anti-tumor-promoters, we carried out an investigation of the leaves and branches of Cowania mexicana D. DON (Rosaceae). Two new cucurbitane type triterpenes, 15-oxo-cucurbitacin F (3) and 15-oxo-23,24-dihydrocucurbitacin F (4), were isolated together with cucurbitacin F (1) and 23,24-dihydrocucurbitacin F (2). These triterpenes were inhibitorss of Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate, a well-known tumor-promoter. The structures of 3 and 4 were determined from 2D-NMR spectral data and difference NOE experiments.

Anticarcinogenic Agents↗
PubMed1993

[Scanning electron microscopic study on inner ear barotrauma: in the guinea pig with one eustachian tube occluded].

In order to investigate the mechanism of inner ear barotrauma, guinea pigs, with one eustachian tube occluded, were subjected to compression and decompression between 1 absolute pressure and 2 absolute pressures in a high pressure chamber. The authors divided the animals into three groups according to the speed of compression and decompression. Each group contained 10 guinea pigs. Morphological changes in the cochlear sensory hairs were examined by means of scanning electron microscope. On the occluded side, hair cells were damaged more frequently and more severely by rapid compression than by rapid decompression. There was no difference in the degree of damage produced by slow decompression and rapid decompression. On the control side, slight or moderate damage to hair cells was observed mainly as a result of rapid decompression. These findings led us to hypothesize that, in the setting of normal eustachian tube function, inner ear barotrauma would generally be caused by the relative positive pressure in the middle ear cavity that occurs during decompression. Furthermore, animals deprived of eustachian tube function would not have sufficient endurance for rapid compression and would sustain inner ear barotrauma far more readily, and of far greater severity, with rapid compression than would animals with normal eustachian tube function. The difference may be due to the presence of another pressure transmission pathway to the inner ear. The mechanism of cochlear sensory hair damage due to atmospheric pressure changes is presumed to be distortion of the reticular lamina and cuticular plate caused by the difference in pressure between cortilymph (perilymph) and the subtectorial space (endolymph) resulting in injury to stereocilia.

Animals↗