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Biomedical subjects

H Tokuda

Publications and source records attributed to H Tokuda.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cancer chemopreventive activity of phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, from Polygonum lapathifolium.

To search for cancer chemopreventive agents from natural resources, many phytochemicals have been screened using the in vitro synergistic assay indicated by the inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by 12-O-tetradecanoylphorbol-13-acetate (TPA). Two phenylpropanoid esters of sucrose, vanicoside B and lapathoside A, were isolated from the aerial part of Polygonum lapathifolium as inhibitors on the EBV-EA induction. These compounds also exhibited significant anti-tumor-promoting effects on mouse two-stage skin carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA, as an initiator) and TPA as a promoter. Further, vanicoside B exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors initiated with an NO donor, NOR-1.

Animals↗
PubMed2001

Anti-tumor promoting effects of multiflorane-type triterpenoids and cytotoxic activity of karounidiol against human cancer cell lines.

Forty-nine multiflorane-type triterpenoids consisting of 11 compounds isolated from the seeds of Trichosanthes kirilowii (Cucurbitaceae) and 38 of their derivatives have been evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate in Raji cells as a primary screening test for anti-tumor promoters. All of the compounds tested showed an inhibitory effect against EBV-EA activation, and among which 43 were revealed to possess remarkable activity with potencies either comparable to or stronger than that of glycyrrhetic acid, a known natural anti-tumor promoter. Their structure-activity relationship is discussed. Evaluation of the cytotoxic activity of karounidiol (27) against human cancer cell lines exhibited cytotoxicity especially against a human renal cancer.

Anticarcinogenic Agents↗
PubMed2001

Cancer chemopreventive activity of carotenoids in the fruits of red paprika Capsicum annuum L.

Capsanthin and related carotenoids isolated from the fruits of red paprika Capsicum annuum L. showed potent in vitro anti-tumor-promoting activity with inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Among them, capsanthin diester and capsorbin diester showed strong inhibitory effects. Furthermore, capsanthin , capsanthin 3'-ester and capsanthin 3,3'-diester , major carotenoids in paprika, exhibited potent anti-tumor-promoting activity in an in vivo mouse skin two-stage carcinogenesis assay using 7, 12-dimethylbenz[a]anthracene as an initiator and TPA as a promoter.

Animals↗
PubMed2001

Cancer chemopreventive agents, serratane-type triterpenoids from Picea jezoensis.

Seven serratane-type triterpenoids isolated from the cuticle of Picea jezoensis (Sieb. et Zucc.) Carr. jezoensis (Pinaceae) and the stem bark of Picea jezoensis (Sieb. et Zucc.) Carr. hondoensis (Mayer) Rehder (Pinaceae) were studied their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). All compounds showed strong inhibitory effects on the EBV-EA activation, being stronger than that of oleanolic acid, which exerts on cancer preventive activity in animal carcinogenesis models. Among these compounds, 13alpha, 14alpha-epoxy-3beta-methoxyserratan-21beta-ol and 3beta-methoxy-21alpha-hydroxyserrat-14-en-29-al were investigated for the inhibitory effects in a two-stage mouse skin carcinogenesis test on mouse skin using 7,12-dimethylbenz[a]anthracene as initiator and TPA as promoter. 13alpha,14alpha-Epoxy-3beta-methoxyserratan-21beta-ol was found to exhibit the excellent anti-tumor promoting activity in the in vivo carcinogenesis test.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Mutant of LolA, a lipoprotein-specific molecular chaperone of Escherichia coli, defective in the transfer of lipoproteins to LolB.

The outer membrane-specific lipoproteins of Escherichia coli are released from the inner membrane as a water-soluble complex with LolA and then transferred to the outer membrane receptor, LolB. LolA thus plays a critical role in the sorting and outer membrane localization of lipoproteins. To dissect the LolA function, the highly conserved residues were subjected to random mutagenesis, followed by selection for a growth defect. LolA(R43L), one of mutants thus constructed, possessed Leu in place of Arg at position 43 and caused accumulation of the LolA(R43L)-lipoprotein complex in the periplasm. LolA(R43L) was as active as wild-type LolA as to the release of lipoproteins from spheroplasts. In marked contrast, the transfer of lipoproteins from LolA(R43L) to LolB was completely inhibited, indicating that Arg at position 43 of LolA is involved in the lipoprotein transfer reaction.

Amino Acid Sequence↗
PubMed2001

Lipoprotein sorting signals evaluated as the LolA-dependent release of lipoproteins from the cytoplasmic membrane of Escherichia coli.

Escherichia coli lipoproteins are anchored to either the inner or outer membrane through fatty acyl chains covalently attached to an N-terminal cysteine. Aspartate at position 2 functions to retain lipoproteins in the inner membrane, although the retention is perturbed depending on the residue at position 3. We previously revealed that LolCDE and LolA play critical roles in this lipoprotein sorting. To clarify the sorting signals, the LolA-dependent release of lipoprotein derivatives having various residues at positions 2 and 3 was examined in spheroplasts. When the residue at position 3 was serine, only aspartate at position 2 caused the retention of lipoproteins in spheroplasts. We then examined the release of derivatives having aspartate at position 2 and various residues at position 3. Strong inner membrane retention occurred with a limited number of species of residues at position 3. These residues were present at position 3 of native lipoproteins having aspartate at position 2, whereas residues that inhibited the retention were not. It was also found that a strong inner membrane retention signal having residues other than aspartate at position 2 could be formed through the combination of the residues at positions 2 and 3. These results indicate that the inner membrane localization of native lipoproteins is ensured by the use of a limited number of strong inner membrane retention signals.

Aspartic Acid↗
PubMed2001

Cancer chemopreventive agents, 4-phenylcoumarins from Calophyllum inophyllum.

In a search for anti-tumor-promoting agents, we carried out a primary screening of ten 4-phenylcoumarins isolated from Calophyllum inophyllum L. (Guttiferae), by examining their possible inhibitory effects on Epstein--Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All of the compounds tested in this study showed inhibitory activity against EBV, without showing any cytotoxicity. Calocoumarin-A (5) showed more potent activity than any of the other compounds tested. Furthermore, calocoumarin-A (5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The results of the present investigation indicate that some of these 4-phenylcoumarins might be valuable as potential cancer chemopreventive agents (anti-tumor-promoters).

Animals↗
PubMed2001

Dietary administration of citrus nobiletin inhibits azoxymethane-induced colonic aberrant crypt foci in rats.

The modifying effects of dietary feeding of a polymethoxyflavonoid nobiletin isolated from Citrus unshiu on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in male F344 rats. We also assessed the effects of nobiletin on cell proliferation activity of ACF using a monoclonal antibody MIB-5. Rats were given subcutaneous injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce ACF. They also received the experimental diet containing 0.01% or 0.05% nobiletin for 5 weeks, starting one week before the first dosing of AOM. AOM exposure produced 139 +/- 35 ACF/rat at the end of the study (week 5). Dietary administration of nobiletin caused significant reduction in the frequency of ACF: 70 +/- 15 (50% reduction, p<0.001) at a dose of 0.01% and 63 +/- 10 (55% reduction, p<0.001) at a dose of 0.05%. Nobiletin feeding significantly lowered MIB-5-index in ACF. Also, dietary administration of nobiletin significantly reduced prostaglandin E2 content in the colonic mucosa. These findings might suggest possible chemopreventive ability of nobiletin, through suppression of cell proliferating activity of ACF, in the development of ACF.

Administration, Oral↗
PubMed2001

Inhibitory effects of 6-O-acylated L-ascorbic acids possessing a straight- or branched-acyl chain on Epstein-Barr virus activation.

6-O-Acylated L-ascorbic acids possessing a straight- or branched-acyl chain of varying length from C(4) to C(18) have been synthesized and evaluated their anti-tumor promoting effects on the activation of the Epstein-Barr virus early antigen. The derivatives having a straight- or branched-acyl chain of C(6) to C(11) carbon atoms exhibited marked effects.

Anticarcinogenic Agents↗
PubMed2001

Cancer chemopreventive activity of 3,5,6,7,8,3',4'-heptamethoxyflavone from the peel of citrus plants.

Nobiletin and 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT), isolated from the peel of Citrus plants, were examined for the anti-tumor-initiating activity on two-stage carcinogenesis of mouse skin tumors induced by a nitric oxide donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexenamide, as an initiator and 12-O-tetradecanoylphorbol-13-acetate as a promoter. HPT exhibited the remarkable anti-tumor-initiating effect on mouse skin and it suggested the possibility of HPT being a chemopreventive agent against nitric oxide (NO) carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Hip fracture prevention trial using hip protectors in Japanese nursing homes.

A method to protect the hips during falls could effectively reduce the incidence of hip fractures. We report the results of the first hip protector trial in Japan, performed between July 1996, and September 1999. One hundred and sixty-four elderly female residents of nursing homes, with Activities of Daily Living above the wheelchair level, agreed to participate in this study. Among them, 88 were randomly selected to wear a hip protector and 76 controls did not. All falls and resulting injuries were recorded daily. In anthropometric measurements and ultrasonic bone evaluation, no significant differences were found between the two groups, except in height. During an average of 377 days, the wearers and the non-wearers fell a total of 131 and 90 times, respectively. Among the wearers, there were two non-hip fractures and one hip fracture, so the annual hip fracture rate was calculated at 1.2%, against 8 hip fractures among the non-wearers, or 9.7% per year. The hip fracture rate was significantly lower among the wearers than non-wearers, while the annual number of falls per subject and the distribution of fallers remained the same. According to Cox's proportional hazard regression analysis, the effect of the hip protector on hip fracture prevention was independent of anthropometric data, ultrasonic bone assessment values or number of falls. Moreover, even after limiting the subjects to fallers only, the annual hip fracture rate in non-wearers was higher than in wearers (19.8% vs 2.0%) and the annual hip fracture rate per fall in wearers was lower than that in non-wearers (0.8% vs 8.2%). It was thus concluded that the hip protector is a beneficial device for the prevention of hip fractures.

Accidental Falls↗
PubMed2001

Anti-tumor promoting diterpenes from the stem bark of Thuja standishii (Cupressaceae).

Three new labdane-type diterpenoids, labda-8(17),13-dien-15,12R-olid-19-oic acid (1), 12S-hydroxylabda-8(17),13(16),14-trien-19-oic acid (2) and 13-ethoxylabda-8(17),11,14-trien-19-oic acid (3), along with known diterpenoids, trans-communic acid (4), totarol (5), 12-methoxyabieta-8,11,13-trien-11-ol (6), and 7 alpha,8 alpha-epoxy-6 alpha-hydroxyabieta-9(11),13-dien-12-one (7) were isolated from the stem bark of Thuja standishii. The structures of 1--3 were established by spectroscopic methods and chemical conversion. These compounds together with standishinal (8), 12-hydroxy-6,7-seco-abieta-8,11,13-trien-6,7-dial (9) and 6 alpha-hydroxysugiol (10) were tested for their inhibitory effects on Epstein--Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. Compound 10 showed strong inhibitory effect on EBV-EA induction (100% inhibition at 1000 mol ratio/TPA), and compounds 2 and 6 showed moderate inhibitory effects on EBV-EA induction. In addition, 15-oxolabda-8(17),11Z,13E-trien-19-oic acid (11) was found to exhibit the anti-tumor promoting activity in two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene and TPA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2001

Cancer chemopreventive agents. New depsidones from Garcinia plants.

In a search for cancer chemopreventive agents from natural sources, chemical constituents of two kinds of Garcinia plants, Garcinia neglecta and Garcinia puat, collected in New Caledonia, were examined. Five new depsidones, garcinisidone-B (2), -C (3), -D (4), -E (5), and -F (6), were isolated, and their structures were determined by spectrometric analyses. Inhibitory effects of these depsidones on EBV-EA activation induced by TPA in Raji cells were also demonstrated.

Anticarcinogenic Agents↗
PubMed2001

Abietane diterpenoids from the cones of Larix kaempferi and their inhibitory effects on Epstein-Barr virus activation.

Four known (1-3, 8) and four new abietane diterpenes, 15-hydroxy-8alpha,14alpha,12alpha,13alpha-diepoxyabietan-18-oic acid (4), 7alpha,8alpha,13beta,14beta-diepoxyabietan-18-oic acid (5), 18-nor-abieta-8,11,13-triene-4alpha,7alpha,15-triol (6), and abieta-8,11,13-triene-7alpha,15,18-triol (7) were isolated from the CHCl3 extract of the cones of Larix koempferi. A known compound, 13,14-seco-13,14-dioxoabiet-13-en-18-oic acid (8) was isolated from natural sources for the first time. Their structures were determined by chemical and spectroscopic methods including 1D and 2D NMR techniques. The absolute stereostructure of 5 was determined by X-ray crystallographic analysis. The inhibitory effects of these compounds on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), were examined as a primary screening for antitumor promotors.

Abietanes↗
PubMed2001

Lignans as anti-tumor-promoter from the seeds of Hernandia ovigera.

Seven lignans (2-8) isolated from the seeds of Hernandia ovigera L. (Hernandiaceae) were tested for their inhibitory effects on Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells. Using a primary screening test, all the lignans showed inhibitory activity with IC50 470-590 mol ratio/32 pmol TPA. The data demonstrated that these lignans might be valuable anti-tumor-promoters.

Anticarcinogenic Agents↗
PubMed2001

Chemopreventive activity of isoquinoline alkaloids from Corydalis plants.

Eighteen isoquinoline alkaloids including protoberberines (1-12), benzophenanthridines (13-16) and an aporphine (17) isolated from plants of Corydalis species (Fumariaceae) were tested for inhibitory effects on Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells. In a primary screening test, all of the isoquinoline alkaloids showed inhibitory activity with the IC50 values being in the range of 140-410 mol ratio/32 pmol TPA. The data demonstrate that these isoquinoline alkaloids might be valuable as anti-tumor promoters.

Alkaloids↗
PubMed2001

A virtual therapeutic environment with user projective agents.

Today, we see the Internet as more than just an information infrastructure, but a socializing place and a safe outlet of inner feelings. Many personalities develop aside from real world life due to its anonymous environment. Virtual world interactions are bringing about new psychological illnesses ranging from netaddiction to technostress, as well as online personality disorders and conflicts in multiple identities that exist in the virtual world. Presently, there are no standard therapy models for the virtual environment. There are very few therapeutic environments, or tools especially made for virtual therapeutic environments. The goal of our research is to provide the therapy model and middleware tools for psychologists to use in virtual therapeutic environments. We propose the Cyber Therapy Model, and Projective Agents, a tool used in the therapeutic environment. To evaluate the effectiveness of the tool, we created a prototype system, called the Virtual Group Counseling System, which is a therapeutic environment that allows the user to participate in group counseling through the eyes of their Projective Agent. Projective Agents inherit the user's personality traits. During the virtual group counseling, the user's Projective Agent interacts and collaborates to recover and increase their psychological growth. The prototype system provides a simulation environment where psychologists can adjust the parameters and customize their own simulation environment. The model and tool is a first attempt toward simulating online personalities that may exist only online, and provide data for observation.

Behavior, Addictive↗