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Biomedical subjects

Y Tamura

Publications and source records attributed to Y Tamura.

At least 127 records · Page 7Linked to original sources
PubMed2000

Induction of mammalian cell transformation and genotoxicity by 2-methoxyestradiol, an endogenous metabolite of estrogen.

2-methoxyestradiol (2-MeOE(2)) is an endogenous metabolite of 17beta-estradiol and a proposed inhibitor of tumor growth and angiogenesis. However, 2-MeOE(2) is also an inhibitor of microtubule assembly and other microtubule inhibitors, e.g. colcemid and diethylstilbestrol, induce aneuploidy and cell transformation in cultured mammalian cells. To assess the in vitro carcinogenicity and related activity of 2-MeOE(2), the abilities of this metabolite to induce cell transformation and genetic effects were studied simultaneously using Syrian hamster embryo (SHE) fibroblasts. Growth of these cells was reduced by treatment with 2-MeOE(2) at 0.1-1.0 microg/ml in a concentration-dependent manner. Treatment of SHE cells with 2-MeOE(2) at 0.3 or 1.0 microg/ml for 2-48 h also resulted in a concentration- and treatment time-related increase in the mitotic index and the percentage of multinucleated cells. Treatment with 2-MeOE(2) at 0.1-1.0 microg/ml for 48 h induced a statistically significant increase in the frequencies of morphological transformation of SHE cells in a concentration-dependent manner. A statistically significant increase in the frequencies of somatic mutations at the Na(+)/K(+) ATPase or hprt locus was also observed in cells treated with 2-MeOE(2) for 48 h at 0.1 or 0.3 microg/ml, respectively. Treatment of SHE cells with 2-MeOE(2) at 0.3 or 1.0 microg/ml for 24 h induced chromosome aberrations, mainly breaks, exchanges and chromosome pulverization. The incidence of chromosome aberrations was not affected by co-treatment with alpha-naphthoflavone, an inhibitor of 2-hydroxylase that inhibits oxidative conversion of 2-MeOE(2) to 2-hydroxyestradiol, but the incidence was slightly increased by co-treatment with L-ascorbic acid. Numerical chromosomal changes in the near diploid range and in the tetraploid and near tetraploid ranges were also detected in 2-MeOE(2)-treated cells. These findings indicate that 2-MeOE(2) has cell transforming and genotoxic activities in cultured mammalian cells and potential carcinogenic activity.

2-Methoxyestradiol↗
PubMed2000

Properties of quadruplex oligonucleotides with anti-HIV-1 activity.

A phosphorothioate oligonucleotide composed of deoxyguanosine and thymidine was identified as an inhibitor of HIV-1 infection at an early stage of the HIV-1 replication cycle in vitro. The phosphodiester and phosphorothioate chimeric oligonucleotides were found to be potent inhibitors of several steps of HIV-1 infection: the interaction with CD4 and the chemokine receptor, the reverse transcriptase activity, and the integrase activity. To elucidate the mechanism of the anti-HIV-1 function of these oligonucleotides in terms of their structure, we focussed on their G-serial sequences and investigated the characteristics of their solution structures. These oligonucleotides were proved to be able to adopt G-quadruplex structures by UV and CD measurements. We presume that the anti-HIV-1 activities of these oligonucleotides are consequently attributable to G-quadruplex formation.

Anti-HIV Agents↗
PubMed2000

Effective suppression of HIV-1 gene expression by a mammalian tRNA 3' processing endoribonuclease and external guide sequence oligozymes.

We examined the suppression of virus expression by cleavage of the HIV-1 RNA gene using a mammalian tRNA 3' processing endoribonuclease and an External Guide Sequence Oligozyme (EGS) in vivo. We constructed an EGS expression vector that used the tRNA(met) promoter as an expression cassette for EGS. The EGS expression vector was targeted to the upstream region of gag, region. The EGS expression vector was co-transfected into COS cells with the HIV-1 gene plasmid vector. As compared with the EGS non-expressing cells and the EGS expressing cells, the EGS expressing cells with the targeted gag start codon had a clearly decreased amount of the HIV-1 gag p24 protein. The EGS expressing cells with the targeted gag start codon showed effective suppression of HIV-1 gene expression. Thus, these studies describe novel gene targeting agents for the inhibition of gene expression and antiviral activity.

Animals↗
PubMed2000

The beneficial effect of mesalazine on esophageal ulcers in intestinal Behcet's disease.

Intestinal Behcet's disease in a 19-year-old girl was diagnosed because of the history of recurrent oral aphthous ulcers and typical endoscopic findings of esophageal and ileal ulcers. Her symptoms (e.g., dysphagia and retrosternal pain) were gradually relieved by treatment with prednisolone and total parenteral nutrition. However, about one month later, oral and esophageal ulcers appeared again. Mesalazine was added. Oral and esophageal ulcers healed promptly, and have not relapsed for about one year. Although mesalazine appears to act locally in the small intestine and colon, the therapeutic effect of mesalazine in this case may be explained by the systemic antiinflammatory effect. This case suggests that mesalazine is an effective drug and is a good candidate in the treatment of intestinal Behcet's disease, especially accompanied with esophageal involvement.

Adult↗
PubMed2000

Molecular cloning of rat NK target structure--the possibility of CD44 involvement in NK cell-mediated lysis.

The nature of target molecules of natural killer (NK) cell-mediated lysis remains to be elucidated. As we previously reported, mAb 109 recognizes one of the tumor-associated antigens, designated as 109 antigen (Ag), expressed on the cell surface of rat fibrosarcomas W31 and W14, which are transformants of WFB (rat fetal fibroblast cell line) with H-ras oncogene. 109Ag was thought to be a target structure of NK cells since mAb 109 inhibited NK cell-mediated lysis against W31 and W14. Here, we demonstrate by molecular cloning that 109Ag is identical to rat CD44. Immunoprecipitation and immunoblotting studies also showed that mAb 109 and anti-rat CD44 mAb OX-50 recognize the same protein of W31 cell lysates with an 86 kDa molecular size. CD44 was suggested to be a target structure of NK cell-mediated lysis; however, rat CD44 cDNA transfection alone into CD44 null cell lines did not result in up-regulation of target cell susceptibility to NK cell-mediated lysis. Our results therefore indicated that CD44 may play a crucial role as one of the target structures in our rat fibrosarcoma system though the cell surface expression of CD44 alone does not affect NK susceptibility of the target cells.

Animals↗
PubMed2000

Serial changes in serum VEGF and HGF in patients with acute myocardial infarction.

The time course of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) release in patients with acute myocardial infarction (AMI) is unknown. Blood samples were obtained at the time of admission and 3, 7, 14 and 21 days later in 32 patients with AMI and 30 control patients. Serum VEGF and HGF, as well as C-reactive protein (CRP) and amyloid A protein (SAA), were determined. Both serum VEGF and HGF levels on admission in patients with AMI were higher than control values and peaked on day 7. VEGF levels in patients with preinfarction angina were higher than in patients with no preinfarction angina, whereas the HGF level did not differ. Both CRP and SAA levels peaked on day 3, and the CRP level on day 3 correlate with both VEGF and HGF levels on day 7. We hypothesized that the serum VEGF level is associated with preinfarction ischemia and the increase in VEGF and HGF on day 7 of AMI may represent a response to acute inflammation.

Aged↗
PubMed2000

Identification of a sequential B-cell epitope on major allergen (Cry j 1) of Japanese cedar (Cryptomeria japonica) pollen in mice.

BACKGROUND: Japanese cedar (Cryptomeria japonica; CJ) pollinosis is one of the most common allergic diseases in Japan. B cell epitopes on Cry j 1, a major allergen of CJ pollen, have been analyzed by the specific monoclonal antibodies to Cry j 1, and most of these epitopes may be conformational, but no previous report has addressed the analysis of sequential epitope mapping with synthetic peptides. The main purpose of the present study is to identify IgE and IgG B cell epitopes on Cry j 1 by using a synthetic peptide approach in mice. METHODS: We synthesized 35 overlapping peptides that cover the entire length of Cry j 1 and examined whether mouse IgE and IgG antibodies produced by immunization with Cry j 1 reacted to the Cry j 1 peptides. RESULTS AND CONCLUSION: We found that mouse IgE and IgG antibodies reacted strongly to Cry j 1 peptide No. 15 ((141)GVEPVHPQDGDALTLRTATN(160)), though those antibodies did not react with other peptides. IgE and IgG antibody binding to peptide No. 15 was completely inhibited by Cry j 1 and the peptide. To determine the minimum epitope in peptide No. 15, we conducted an ELISA inhibition test. IgE and IgG antibody binding to peptide No. 15 was inhibited by smaller peptides of this peptide. We found the core of the epitope to be (145)VHPQDGDA(152).

Allergens↗
PubMed2000

Protection of mitochondrial functions against oxidative stresses by isoflavans from Glycyrrhiza glabra.

Isoflavan derivatives, glabridin (1), hispaglabridin A (2), hispaglabridin B (3), 4'-Omethylglabridin (4) and 3'-hydroxy-4'-O-methylglabridin (5), isolated from Glycyrrhiza glabra, were investigated for their ability to protect liver mitochondria against oxidative stresses. Mitochondrial lipid peroxidation linked to respiratory electron transport and that induced non-enzymatically were inhibited by these isoflavans. Hispaglabridin A (2) strongly inhibited both peroxidations and 3'-hydroxy-4'-O-methylglabridin (5) was the most effective at preventing NADH-dependent peroxidation. 3'-Hydroxy-4'-O-methylglabridin (5) protected mitochondrial respiratory enzyme activities against NADPH-dependent peroxidation injury. Dihydroxyfumarate-induced mitochondrial peroxidation was also prevented by this isoflavan. Isoflavans from G. glabra were shown to be effective in protecting mitochondrial function against oxidative stresses.

Animals↗
PubMed2000

Plasma and platelet plasminogen activator inhibitor-1 in patients with acute myocardial infarction.

Several studies have demonstrated an increased level of plasma plasminogen activator inhibitor-1 (PAI-1) in patients with coronary artery disease (CAD). However, the concentration of PAI-1 in platelets, which accounts for more than 90% of the blood PAI-1, is unknown in these patients. The present study evaluated the concentrations of PAI-1 and several fibrinolytic factors in the plasma and platelets of patients with CAD and the serial changes in patients with acute myocardial infarction (AMI). All 72 subjects had coronary angiography and were divided into 3 groups: CAD(-) group without coronary artery stenosis or myocardial ischemia (n=20), CAD(+) group with either stable angina pectoris (n=18) or old myocardial infarction (n=12) with coronary artery stenosis, and the AMI group admitted within 24h of symptom onset who underwent successful percutaneous transluminal coronary angioplasty (n=22). The concentrations of plasma PAI-1, tissue plasminogen activator (t-PA), and t-PA x PAI-1 complex were similar in the CAD(-) and CAD(+) groups, but were greater on day 1 in the AMI group compared with the 2 CAD groups. There were no significant differences between the 3 groups in the plasma concentrations of thrombin antithrombin III complex (TAT), alpha2-plasmin inhibitor-plasmin complex (PIC), beta-thromboglobulin (beta-TG), and platelet factor 4 (PF-4). The platelet PAI-1 concentrations did not differ between the CAD(-) and CAD(+) groups, but was greater on day 1 in the AMI group compared to the CAD groups. The platelet beta-TG and PF-4 were similar between the 3 groups. In the AMI group, both the plasma and platelet PAI-1 concentrations were greater on day 1, but the plasma PAI-1 rapidly decreased by day 5 and remained low on day 28 compared with day 1. The platelet PAI-1 concentration gradually decreased by day 5 and was further decreased by day 28. The serial changes of the plasma t-PA and t-PA PAI-1 complex during the course of AMI were similar to those of the plasma PAI-1. A positive correlation was found between the plasma and platelet PAI-1 in all 72 patients, but not in the AMI group alone. These results suggest that the PAI-1 that has accumulated in platelets at the onset of AMI might be released in large amounts into the plasma, resulting in an increase in thrombus formation.

Aged↗
PubMed2000

[Pharmacological aspects of mammalian hibernation: central thermoregulation factors in hibernation cycle].

Hibernation in mammalians such as hamsters is a physiological state characterized by an extreme reduction of various functions such as body temperature and metabolism. Under such severe conditions, the central nervous system (CNS) activity is maintained at a functionally responsive level. Although hibernation is an interesting behavioral state, the physiological mechanisms of the introduction to and/or the arousal from hibernation have not been clearly defined. Intracerebroventricularly (i.c.v.) injected adenosine produces hypothermia in various animals. The effect of adenosine is generated by A1-receptors and is caused by the suppression of the thermogenesis center of the posterior hypothalamus. At on ambient temperature of 5, i.c.v. injected N6-cyclohexyladenosine (CHA) adenosine A1-receptor agonist induces profound hypothermia in hamsters. Although the time course of the descent of body temperature coincided with that of entry into natural hibernation, the effect was not antagonized by 8-cyclopentyltheophyllin (CPT), an adenosine A1-receptor antagonist. However, i.c.v. injection of CPT elevated the body temperature and interrupted hibernation, albeit the deep-phase (post-entry 30 h) was unaffected. This result suggests that a different system may suppress the thermogenesis center in the deep hibernation phase. Interestingly, i.c.v. injected thyrotropin releasing hormone (TRH) elevated the body temperature in both hibernation phases in hamsters. These findings suggest that the central adenosine and TRH play important roles in thermoregulation and that the new thermogenesis system, activating in low-body temperature, is induced in naturally hibernating animals.

Adenosine↗
PubMed2000

Cadmium induces expression of metallothionein in rat dental pulp.

Metallothionein (MT) is a metalloprotein with high affinity for certain heavy metals. In the present study, the ability of cadmium (Cd) to induce the synthesis of MT in dental pulp was investigated. Rats were injected subcutaneously with CdCl2 (1.5 mg Cd/kg) daily for 7 days. Expression of the MT gene was demonstrated by reverse transcription polymerase chain-reaction techniques. The results indicate that Cd induced MT in dental pulp of rat incisor and this may be involved in the cellular defense mechanism against Cd toxicity.

Animals↗
PubMed2000

Characterization of a vitamin B12 compound in the edible purple laver, Porphyra yezoensis.

The edible purple laver, Porphyra yezoensis, contained 51.49+/-1.51 microg of vitamin B12 compounds per 100 g dry weight of the laver (mean +/- SEM, n = 4). A vitamin B12 compound was purified from the lyophilized purple laver and partially characterized. The silica gel 60 TLC and reversed-phase HPLC patterns of the purified pink-colored compound were identical to those of authentic vitamin B12, but not to those of vitamin B12 analogues inactive for humans.

Biological Availability↗
PubMed2000

Rapid and direct detection of clostridium chauvoei by PCR of the 16S-23S rDNA spacer region and partial 23S rDNA sequences.

Clostridium chauvoei causes blackleg, which is difficult to distinguish from the causative clostridia of malignant edema. Therefore, a single-step PCR system was developed for specific detection of C. chauvoei DNA using primers derived from the 16S-23S rDNA spacer region and partial 23S rDNA sequences. The specificity of the single-step PCR system was demonstrated by testing 37 strains of clostridia and 3 strains of other genera. A 509 bp PCR product, which is a C. choauvoei-specific PCR product, could be amplified from all of the C. chauvoei strains tested, but not from the other strains. Moreover, this single-step PCR system specifically detected C. chauvoei DNA in samples of muscle from mice 24 hr after inoculation with 100 spores of C. chauvoei, and in clinical materials from a cow affected with blackleg. These results suggest that our single-step PCR system may be useful for direct detection of C. chauvoei in culture and in clinical materials from animals affected with blackleg.

Animals↗
PubMed2000

Decrease of nitric oxide end-products during coronary circulation reflects elevated basal coronary artery tone in patients with vasospastic angina.

The aim of this study was to investigate the role of nitric oxide (NO) in the coronary circulation and its relation to basal coronary artery tone in patients with vasospastic angina (VSA). We evaluated the level of nitric oxide end-products (NOx; nitrite + nitrate) in coronary circulation blood using an HPLC-Griess system for nine patients with VSA and nine control patients. All of the patients with VSA experienced focal spasm in the proximal to middle segments of the left anterior descending coronary artery (LAD) in response to intracoronary injection of ergonovine maleate. The luminal diameter of the coronary artery was measured in each patient by quantitative coronary arteriography. Blood samples for NOx measurement were obtained from the coronary sinus (NOxV) and the ostium of the left coronary artery (NOxA). The NOx difference, calculated from the coronary venous-arterial difference in NOx, was close to zero for the control patients whereas it was clearly negative for the patients with VSA. In addition, the NOx difference in the patients with VSA showed a negative correlation with basal coronary artery tone (r = -0.91, p < 0.01) and a positive correlation with the dose of ergonovine required for spasm provocation (r = 0.77, p < 0.05). These results indicate that increased basal coronary artery tone and higher susceptibility to ergonovine in patients with VSA would be a consequence of coronary endothelial dysfunction as is indicated by NOx.

Adult↗
PubMed2000

Anti-human immunodeficiency virus type 1 of a two-strand-system targeted to the polypurine tract.

The polypurine tract (PPT) is highly conserved among the known human immunodeficiency virus (HIV)-1 strains, and is a possible target for triplex formation. We show the effects of triple-helix formation by assays of primer extension inhibition in vitro, using a two-strand-system (FTFOs) targeted to the PPT of HIV-1. The two-stranded composition of a triple-helix is thermodynamically and kinetically superior to the three-strand-system. The FTFOs inhibited the RT activity in a sequence-specific manner, i.e., the triplex actually formed at the PPT and blocked the RT. The FTFOs containing the phosphorothioate groups at the antisense sequences showed greater 3'-exonuclease resistance. In the observation of the FITC-DsDGloopT5-37 with MOLT-4 cells by a confocal laser scanning microscope, diffuse fluorescence was apparently observed in the cytoplasm and nucleus. However, weak fluorescence was observed within the cytoplasm and nucleus of MOLT-4 cells treated with the antisense phosphorothioate oligonucleotides (S-ODN-gag-AUG). In HIV-1 infected MOLT-4 cells, the FTFOs containing the phosphorothioate groups at the antisense sequence sites and guanosine rich parts within the third Hoogsteen base pairing sequence inhibit the replication of HIV-1 more effectively than the antisense oligonucleotides, indicating sequence-specific inhibition of HIV-1 replication.

Amino Acid Sequence↗
PubMed2000

[A case of prostate cancer treated with combined androgen-blockade].

A 62-year-old man was admitted to our hospital because of urinary retention. A digital rectal examination revealed an enlarged, elastic, and hard prostate with an irregular surface. Prostatic biopsy was done and the pathological diagnosis was moderately differentiated adenocarcinoma. He was diagnosed as stage D2 by bone scan and MRI. We gave him 250 mg of fosfestrol intravenously for 13 days. Afterward, he underwent orchiectomy castrate and was given flutamide for two years. His condition has improved and he has experienced no relapse.

Adenocarcinoma↗
PubMed2000

[Statistics of the operations at the Department of Urology, Tone Chuo Hospital during a six-year period (June 1993-May 1999)].

A clinical statistic survey was made on the operations performed at the Department of Urology, Tone Chuo Hospital between June 1993 and May 1999. The total number of operations was 1296, consisting of 97 (7.5%) operations of the kidney, 67 (5.2%) operations of the ureter, 190 (14.7%) operations of the bladder, 454 (35.0%) operations of the prostate, 63 (4.9%) operations of the urethra, 92 (7.1%) operations of the penis, 149 (11.5%) operations of the scrotum and 184 (14.2%) other operations. With the aging society, the number of operations for those over 60 years old has exceeded 60%.

Adolescent↗