Biomedical subjects

Yasuhiro Yamada

Publications and source records attributed to Yasuhiro Yamada.

67 records · Page 4Linked to original sources

PubMed2002

Characterization of virginiamycin S biosynthetic genes from Streptomyces virginiae.

Streptomyces virginiae produces -butyrolactone autoregulators (virginiae butanolide, VB), which control the biosynthesis of virginiamycin M1 and S. A 6.3-kb region downstream of the virginiamycin S (VS)-resistance operon in S. virginiae was sequenced, and four plausible open reading frames (ORFs) (visA, 1,260 bp; visB, 1,656 bp; visC, 888 bp; visD, 1209 bp) were identified. Homology analysis revealed significant similarities with enzymes involved in the biosynthesis of cyclopeptolide antibiotics: VisA (53% identity, 65% similarity) to -lysine 2-aminotransferase (NikC) of nikkomycin D biosynthesis, VisB (66% identity, 72% similarity) to 3-hydroxypicolinic acid:AMP ligase of pristinamycin I biosynthesis, VisC (48% identity, 59% similarity) to lysine cyclodeaminase of ascomycin biosynthesis, and VisD (43% identity, 56% similarity) to erythromycin C-22 hydroxylase of erythromycin biosynthesis. Northern blotting as well as high-resolution S1 analysis of the ORFs revealed that they were transcribed as two bicistronic transcripts, namely 3.0-kb visB-visA and another 2.7-kb visC-visD transcript, with promoters locating upstream of visB and visC, respectively. Transcription of the two operons was observed only 1 h after the VB production, which was 2 h before the virginiamycin production. Furthermore, prompt induction of the transcription was observed as a result of external VB addition, suggesting that the expression of the two operons was under the control of VB.

Ammonia-Lyases↗

PubMed2002

Synergistic induction of apoptosis by acyclic retinoid and interferon-beta in human hepatocellular carcinoma cells.

Acyclic retinoid, a synthetic retinoid analog, as well as interferon alfa (IFN-alpha) and IFN-beta induce apoptosis in hepatocellular carcinoma (HCC) cells and are used clinically in the prevention of HCC. Here, we show that acyclic retinoid acts synergistically with IFNs in suppressing the growth and inducing apoptosis (as characterized by DNA fragmentation and chromatin condensation) in 5 human HCC cell lines (JHH7, HuH7, PLC/PRF/5, HLE, and HLF). This synergism was only observed when cells were pretreated with the acyclic retinoid, whereas natural retinoic acids (all-trans and 9-cis retinoic acid) were ineffective. This promotion may be due to up-regulation of type 1 IFN receptor (IFNR) expression by the retinoid. Accordingly, incubation with antitype 1 IFNR antibody abolished the synergy. Enhanced IFNR expression was accompanied by increased expression and DNA-binding activity of STAT1, an intracellular signal transducing molecule of IFNR, and increased induction of 2', 5'-oligoadenyl-5'-triphosphate synthetase, which is a target gene of STAT1. Acyclic retinoid did not have any effects on the growth of normal human hepatocytes (Hc) probably because of a lack of IFNR and STAT1 up-regulation. In conclusion, these results provide a rationale for combined biochemoprevention of HCC using acyclic retinoid and IFN-beta.

Antineoplastic Agents↗

PubMed2002

Dietary silymarin suppresses 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats.

The modifying effect of dietary administration of a polyphenolic antioxidant flavonoid silymarin isolated milk thistle [Silybum marianum (L.) Gaertneri] on 4-nitroquinoline 1-oxide (4-NQO)-induced tongue tumorigenesis was investigated in male F344 rats. Based on the results in pilot studies showing that silymarin treatment together with 4-NQO significantly reduced the occurrence of tongue dysplasia and gavaged with silymarin significantly elevated the phase II detoxifying enzymes' activities in the liver and tongue, the effects of dietary feeding of silymarin on tongue carcinogenesis were investigated in a long-term experiment, where rats were initiated with 4-NQO and fed silymarin containing diets during or after 4-NQO exposure. At 5 weeks of age, all animals except those treated with silymarin alone and untreated rats were given 20 p.p.m. 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 1 week before 4-NQO administration, animals were fed the experimental diets containing silymarin (100 and 500 p.p.m.) for 10 weeks, and then maintained on a basal diet for 24 weeks. Starting 1 week after the cessation of 4-NQO exposure, the experimental groups given 4-NQO and a basal diet were fed the experimental diets containing 100 or 500 p.p.m. silymarin for 24 weeks. At week 34, feeding of 500 p.p.m. silymarin during the promotion phase significantly inhibited the incidence of tongue carcinoma, when compared with 4-NQO alone group (20% versus 64%, P = 0.019). Dietary silymarin decreased the cell proliferating activity and increased apoptotic index of tongue carcinoma. The treatment with silymarin decreased the polyamine content and prostaglandin (PG) E(2) level in the tongue mucosa. Thus, the results indicate that feeding of silymarin (500 p.p.m.) during the promotion phase of 4-NQO-induced rat tumorigenesis exerts chemopreventive ability against tongue squamous cell carcinoma through modification of phase II enzymes activity, cell proliferation, and/or PGE(2) content.

4-Nitroquinoline-1-oxide↗

PubMed2002

Modifying effects of dietary capsaicin and rotenone on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.

The effects of dietary administration of capsaicin and rotenone on 4-nitroquinoline 1-oxide (4-NQO)-induced tongue tumorigenesis were investigated in male F344 rats. In pilot studies, gavage with capsaicin and rotenone elevated the phase II enzymes glutathione S-transferase (GST) and quinone reductase (QR), in the liver and tongue. Also, a 10 week period of feeding of 500 p.p.m. capsaicin or rotenone together with 4-NQO exposure inhibited the occurrence of tongue dysplasia. Subsequently, a long-term study was conducted to test the protective effects of both compounds on 4-NQO-induced tongue carcinogenesis. One group was treated with 4-NQO alone (20 p.p.m. in drinking water for 8 weeks) and four other groups received the carcinogen treatment plus diets containing 500 p.p.m. test compounds for 10 weeks (initiation phase) or for 28 weeks (post-initiation phase). At the termination of the study (38 weeks), feeding of rotenone during the initiation phase, but not during the post-initiation phase, was found to significantly reduce the incidence of tongue squamous cell carcinoma (53% vs. 16%, 70% reduction, P b=e 0.0250) and severe dysplasia (80% vs. 42%, 70% reduction, P = 0.028). Capsaicin feeding during either the initiation or promotion phase and rotenone feeding during the promotion phase also reduced the frequency of tongue carcinoma without statistical significance. The treatment with two compounds especially rotenone lowered cell proliferation activity in the tongue, elevated phase II enzymes' activities of the liver and tongue, and increased the apoptotic index of tongue carcinoma. Although our results suggest that rotenone feeding during the initiation stage prevented 4-NQO-induced tongue carcinoma, chronic intravenous exposure of rotenone reproduces several features of human Parkinson's disease in rats (Nat. Neurosci., 3, 1301-1306, 2000), suggesting that additional studies to confirm the safety of rotenone are warranted.

4-Nitroquinoline-1-oxide↗

PubMed2002

Chemopreventive effects of a flavonoid antioxidant silymarin on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder carcinogenesis in male ICR mice.

The modifying effects of dietary administration of a flavonoid antioxidant, silymarin, a mixture of three flavonoids isolated from milk thistle seeds, on N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN)-induced urinary bladder carcinogenesis were examined in male ICR mice. Animals were divided into 5 groups, and groups 1 to 3 were given OH-BBN (500 ppm) in drinking water for 6 weeks. Mice in group 2 were fed a diet containing 1000 ppm silymarin for 8 weeks during the initiation phase starting 1 week before OH-BBN exposure, and mice in group 3 were fed the diet for 24 weeks during the postinitiation phase. Animals in group 4 were given only the test compound, and those in group 5 were given the basal diet alone throughout the experiment. Animals were sacrificed at the end of week 32. The frequency of bladder lesions, cell proliferation and cell cycle progression activity estimated in terms of the 5-bromodeoxyuridine (BrdU) labeling index or cyclin D1-positive cell ratio were compared among the groups. Administration of silymarin in the initiation or postinitiation phase significantly decreased the incidences of bladder neoplasms and preneoplastic lesions. Dietary exposure to this agent significantly reduced the labeling index for BrdU and the cyclin D1-positive cell ratio in various bladder lesions. These findings suggest that silymarin is effective in preventing OH-BBN-induced bladder carcinogenesis in mice.

Administration, Oral↗

PubMed2002

Induction of apoptosis by sulindac in azoxymethane-induced possible colonic premalignant lesions in rats.

We have reported that beta-catenin-accumulated crypts (BCAC), which do not have the appearance of aberrant crypt foci (ACF) are possible colonic premalignant lesions in rats. Suppression of the occurrence and advancement of such lesions should have critical relevance to cancer prevention. This study examined whether sulindac, a chemopreventive nonsteroidal anti-inflammatory drug is able to induce apoptosis in such premalignant lesions. At 6 weeks of age, rats groups 1 - 3 were given azoxymethane (AOM) (15 mg/kg-body weight) once weekly for 3 weeks. Two groups were given sulindac in the diet (200 and 400 ppm), starting at 9 weeks of age. The rats were sacrificed at the termination, and the colons were carefully examined. The incidence and crypt multiplicity of BCAC and ACF were significantly less than those of the control group. The effect of sulindac on the expression of BCAC was greater than that on ACF. Exposure to sulindac significantly increased the apoptotic index (terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL)-positive cells) in BCAC. However, no significant increase of the index was found in the case of ACF. These results suggest that the chemopreventive effect of sulindac in rats is related to the induction of apoptosis in premalignant lesions. Our results also provide additional evidence that BCAC are premalignant lesions in colon carcinogenesis in rodents.

Animals↗

PubMed2002

L-tryptophan-L-kynurenine pathway metabolism accelerated by Toxoplasma gondii infection is abolished in gamma interferon-gene-deficient mice: cross-regulation between inducible nitric oxide synthase and indoleamine-2,3-dioxygenase.

L-Tryptophan degradation by indoleamine 2,3-dioxygenase (IDO) might have an important role in gamma interferon (IFN-gamma)-induced antimicrobial effects. In the present study, the effects of Toxoplasma gondii infection on IDO were investigated by using wild-type and IFN-gamma-gene-deficient (knockout) (IFN-gamma KO) mice. In wild-type C57BL/6J mice, enzyme activities and mRNA levels for IDO in both lungs and brain were markedly increased and lung L-tryptophan concentrations were dramatically decreased following T. gondii infection. In contrast, these metabolic changes did not occur in T. gondii-infected IFN-gamma KO mice or in uninfected IFN-gamma KO mice. The levels of inducible nitric oxide synthase (iNOS) induction in infected IFN-gamma KO mice were high in lungs and low in brain compared to those in infected wild-type mice. The extent of increased mRNA expression of T. gondii surface antigen gene 2 (SAG2) induced in lungs and brain by T. gondii infection was significantly enhanced in IFN-gamma KO mice compared to wild-type mice on day 7 postinfection. Treatment with N-nitro-L-arginine methyl ester, an iNOS inhibitor, increased the levels of SAG2 mRNA in brain but not in lungs and of plasma L-kynurenine after T. gondii infection. This in vivo study provides evidence that L-tryptophan depletion caused by T. gondii is directly mediated by IFN-gamma in the lungs, where iNOS is not induced by IFN-gamma. This study suggests that there is an antitoxoplasma mechanism of cross-regulation between iNOS and IDO and that the expression of the main antiparasite effector mechanisms for iNOS and/or IDO may vary among tissues.

Animals↗

PubMed2002

Inhibitory Effects of Chlorogenic Acid on Azoxymethane-induced Colon Carcinogenesis in Male F344 Rats.

Modifying effects of chlorogenic acid (CA) on carcinogen-induced large bowel carcinogenesis was examined in rats. A total of 150 male F344 rats, 4 weeks old, were divided into 5 groups. At 6 weeks of age, groups 1-3 were given subcutaneous injections of AOM (15 mg/kg body weight) once a week for three weeks. Group 2 was given the diet mixed with CA at the dose of 250 ppm during the initiation phase (5 weeks), and group 3 was exposed to the same diet during the post-initiation phase (32 weeks). Group 4 received the diet with CA throughout the experiment. Group 5 was maintained on the basal diet alone and served as a control. At the termination of the experiment (36 weeks after the start), the incidence of colon tumors in group 2 and 3 demonstrated a tendency for decrease as compared with group 1 although this did not attain significance At this time, the multiplicity of colon tumors of group 2 was significantly smaller than in group 1. In this study, the anti-proliferating cell nuclear antigen (PCNA) indices for non-neoplastic cells of the colon mucosae in groups 2 and 3 were also smaller than in group 1. The data suggest that CA has chemopreventive potential against colon carcinogenesis in rats like that showen in a hamster model with use of methylazoxymethanol acetate.

Journal Article↗

PubMed2000

Inhibitory Effects of Dietary Monoglucosyl-rutin on Azoxymethane-induced Colon Carcinogenesis in Rats.

The dietary effect of monoglucosyl-rutin (M-R), a flavonoid, on azoxymethane (AOM)-induced colon carcinogenesis was investigated in two experiments with 5 week old, F344 male rats. In the first experiment (5 weeks study), effects of MR on AOM (15 mg/kg body weight 3 times weekly)-induced formation of aberrant crypt foci (ACF) in five groups were assessed. In this experiment, group 3 given 500 ppm M-R with AOM had a significantly smaller number of ACF containing 4 or more aberrant crypts than group 1 with AOM alone, and groups 2 and 3 given 100 ppm or 500 ppm M-R respectively had significantly lower BrdU labeling indices in the epithelial cells of large bowel than group 1. For the second experiment, rats were divided into 8 groups. Groups 1-5 were given AOM as in the first experiment. Groups 2-5 were fed diets containing 100ppm or 500ppm M-R for 4 weeks in the initiation phase or 36 weeks in the post-initiation phase. Group 6 was given 500ppm M-R throughout the experiment, and group 7 was kept on the basal diet and served as a control. At the termination of the experiment (40 weeks after the start), groups 2-5 had significantly smaller numbers of positive cells with anti-proliferating cell nuclea antigen (PCNA) antibody than group 1. Furthermore, group 5 treated with 500ppm M-R for 36 weeks demonstrated tendencies for decrease in the incidence and multiplicity of colon tumors. These data suggest that M-R has the potential to inhibit AOM-induced colon carcinogenesis.

Journal Article↗

PubMed1998

Screening and identification of a novel lipase from Burkholderia sp. YY62 which hydrolyzes t-butyl esters effectively.

Fatty acid esters composed of sterically hindered alcohol are very poor substrates for known lipases. In order to obtain a novel lipase, t-butyl octanoate (TBO) was selected as a model substrate to screen for bacteria-producing lipase(s) which can preferentially hydrolyze bulky esters. Of 279 strains isolated from 350 soil samples based on the ability to grow with TBO as a sole carbon source, one strain (YY62) was chosen for its strong TBO-hydrolyzing activity. Strain YY62 is a Gram-negative motile rod and was identified as Burkholderia sp. from the taxonomic characters and phylogenetic analysis of 16S rDNA nucleotide sequences. Using the activity ratio between TBO and p-nitrophenyl acetate as a measure for preference to bulky esters, we confirmed that the lipase of strain YY62 was 100-fold superior to commercial lipases in terms of TBO-hydrolyzing activity.

Journal Article↗

PubMedDate not supplied

Preventive effect of fermented brown rice and rice bran against colon carcinogenesis in male F344 rats.

Epidemiological and preclinical studies demonstrate that nutrition plays an important role in the etiology of cancer. It has been reported that rice components, especially rice germ plays a key role in prevention of cancer. The experiments described here examined the potential anticancer properties of brown rice fermented by Aspergillus Oryzae (FBRA) in male F344 rats using inhibition of the formation of azoxymethene (AOM) induced aberrant crypt foci (ACF) and tumors in the colon as the measure of preventive efficacy. The agent was administered at 2.5 and 5% levels in the diet during the initiation phase (during and until 1 week after carcinogen treatment) and/or post-initiation phase (beginning 1 week after carcinogen treatment) of carcinogenesis. In the ACF and tumor studies, rats were sacrificed 5 or 40 weeks after the initiation of AOM treatment (15 mg/kg body weight, once weekly for 3 weeks), respectively. Colonic ACF and tumors were evaluated histopathologically. Administration of 2.5 and 5% FBRA in the diet continuously during initiation and post-initiation period significantly inhibited the ACF formation in rats treated with AOM, compared with rats treated with AOM alone (99+/-24.1 and 79+/-18.4 vs. 139.5+/-27.7, respectively). In addition, administration of 5% FBRA in the diet during the post-initiation phase significantly suppressed the incidence (44 vs.18%) and multiplicity (0.93+/-0.96 vs. 0.18+/-0.40) of colon adenocarcinomas as compared to those given the control diet. In addition, 5% FBRA in the diet during post-initiation phase caused significant inhibition of cell proliferation in the colonic mucosa as compared to the group fed the control diet (81% reduction, p<0.05). These observations demonstrated for the first time that FBRA inhibits colon tumor development in rats, and suggest that it is a promising dietary supplement for prevention of human colon cancer.

Animals↗

PubMedDate not supplied

Promoting effects of high-fat corn oil and high-fat mixed lipid diets on 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis in F344 rats.

Epidemiological studies and laboratory animal model assays suggest that a high intake of dietary fat promotes mammary carcinogenesis as well as colon tumorigenesis. Fat intake in the United States traditionally includes high amounts (30% of total caloric intake) of saturated fatty acids (SFAs) compared to polyunsaturated fatty acids (PUFAs). A recent study suggested that a high-fat mixed-lipid diet (HFML), which simulates the mixed-lipid and high SFAs composition of the average American diet, strongly promotes rat colon carcinogenesis, even when compared to another high-fat diet containing PUFA-rich corn oil. On the other hand, some reports suggest that a high-fat diet rich in n-6 PUFAs promotes mammary carcinogenesis more strongly than a high-fat diet rich in SFAs. Therefore, the present study was designed to compare the effects of HFML, high-fat corn oil diet (HFCO) that is rich in n-6 PUFAs, and a low-fat corn oil diet (LFCO) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female F344 rats. At 7 weeks of age, female F344 rats intended for carcinogen treatment received a gavage of DMBA at a dose level of 65 mg/kg of body weight. Beginning 1 week after carcinogen treatment, groups of rats were then maintained on experimental diets containing LFCO, HFCO or HFML. All rats were evaluated weekly by palpation of mammary tumors and sacrificed 20 weeks after the DMBA treatment. Palpable tumors of mammary glands were detected at the 8, 11, and 19 weeks in the HFCO, HFML and LFCO groups, respectively. Histopathological observation revealed that the incidence and number of mammary tumors in the HFCO group were significantly higher than in the LFCO group. Rats on the HFML diet tended towards a higher incidence and number of mammary tumors compared with the LFCO group, although the correlation was not statistically significant. These results suggest that, for this animal model, both the HFCO and HFML diets promote DMBA-induced mammary carcinogenesis when compared to the LFCO diet, and that the HFCO diet is more tumor-promotional than the HFML diet.

9,10-Dimethyl-1,2-benzanthracene↗

PubMedDate not supplied

Preventive effect of fermented brown rice and rice bran on diethylnitrosoamine and phenobarbital-induced hepatocarcinogenesis in male F344 rats.

Epidemiological and preclinical studies have suggested that nutrition plays an important role in the etiology of cancer. Our group previously demonstrated that rice germ or fermented brown rice has a preventive effect on colorectal carcinogenesis. The experiment described here was examined for the potential anticancer properties of brown rice fermented by Aspergillus Oryzae (FBRA) in male F344 rats using inhibition of diethylnitrosoamine (DEN) and phenobarbital (PB)-induced hepatocarcinogenesis as the measure of preventive efficacy when this agent was administered at 5% and 10% levels in diet during initiation phase (during and until 1 week after carcinogen treatment) or post-initiation phase (beginning 1 week after carcinogen treatment) of the carcinogenesis. Rats were sacrificed 20 weeks after the initiation of DEN treatment (200 mg/kg body weight, once weekly for 3 weeks). Expression of liver tumors was evaluated histopathologically. Administration of 10% FBRA in the diet during the initiation phase significantly decreased the incidence (43% vs. 8%) and multiplicity (0.5+/-0.6 vs. 0.1+/-0.3) of hepatocellular carcinoma (HCC) as compared to those given the control diet. In addition, 5% and 10% of FBRA in the diet during post-initiation phase significantly decreased the incidence of HCC (43% vs. 15% and 9%, respectively) and multiplicity of hepatocellular adenoma (4.7+/-3.7 vs. 2.1+/-2.2 and 2.4+/-1.4, respectively) and HCC (0.5+/-0.6 vs. 0.2+/-0.4 and 0.1+/-0.3, respectively). These data prove that FBRA has an inhibitory effect on the hepatocarcinogenesis in rats. FBRA could be a promising chemopreventive agent for human liver as well as colorectal neoplasia.

Adenoma↗