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T Tamura

Publications and source records attributed to T Tamura.

At least 91 records · Page 5Linked to original sources
PubMed2001

CYP2C19 genotype and pharmacokinetics of three proton pump inhibitors in healthy subjects.

PURPOSE: To predict the CYP2C19 genotype-dependence in anti-Helicobacter pylori (H. pylori) therapy when lansoprazole or rabeprazole was used instead of omeprazole as a proton pump inhibitor (PPI). METHODS: A comparative pharmacokinetic study with each PPI was designed as an open, randomized, and crossover study of 18 Japanese healthy volunteers who were classified into the homozygous, heterozygous extensive metabolizer and the poor metabolizer based on the CYP2C19 genotype determined by PCR-RFLP method. Each subject received a single oral dose of 20 mg omeprazole, 30 mg lansoprazole, or 20 mg sodium rabeprazole, with at least 1 week washout period between treatments. Plasma concentrations of PPIs and their metabolites were monitored until 12 h after medication. RESULTS: Pharmacokinetic profiles of omeprazole and lansoprazole were well correlated with the CYP2C19 genotype. The heterozygous extensive metabolizer was slightly different from the homozygote, but there was no statistically significant difference. The CYP2C19 genotype dependence found for lansoprazole was not obvious compared with omeprazole. As for rabeprazole, the pharmacokinetic profile was independent of the CYP2C19 genotype. CONCLUSIONS: CYP2C19 genotype dependence will be found in the anti-H. pylori therapy even when lansoprazole is used as the PPI.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects.

PURPOSE: To evaluate the MDR1 genotype frequency in the Japanese population and to study the relationship between the MDR1 genotype and the pharmacokinetics of digoxin after single oral administration in healthy subjects. METHODS: The MDR1 genotype at exon 26 was determined in 114 healthy volunteers by polymerase chain reaction-restriction fragment length polymorphism. The serum concentration-time profile of digoxin was examined after single oral administration at a dose of 0.25 mg. RESULTS: It was found that 35.1 % (40/114) of subjects were homozygous for the wild-type allele (C/C). 52.6% (60/114) were compound heterozygotes with a mutant T-allele (C3435T) (C/T), and 12.3% (14/114) were homozygous for the mutant allele (T/T). There was no effect of gender or age on the distribution. The serum concentration of digoxin after a single oral administration increased rapidly, attaining a steady state in all subjects; however, it was lower in the subjects harboring the T-allele. AUC0-4 h values (+/-SD) were 4.11 +/- 0.57, 3.20 +/- 0.49. and 3.27 +/- 0.58 ng h/ml, respectively, with a significant difference between C/C and C/T or T/T. CONCLUSIONS: The serum concentration of digoxin after single oral administration was lower in the subjects harboring a mutant allele (C3435T) at exon 26 of the MDR1 gene.

Adult↗
PubMed2001

TBP-interacting protein TIP120A is a new global transcription activator with bipartite functional domains.

BACKGROUND: We previously identified a TBP (TATA-binding protein)-interacting protein 120A (TIP120A) from rat liver nuclear extracts. TIP120A is thought to be a unique global transcription factor that can interact with TBP and can stimulate all classes of eukaryotic transcription. RESULTS: We produced various truncation proteins of TIP120A to delineate its functional domains. TIP120A binds to TBP in the acidic amino acid-rich N-terminal region and in the leucine-rich C-terminal region. These regions exhibited an ability to stimulate basal transcription in vitro. In addition, these two regions overlap with domains that facilitate nonspecific DNA-binding of RNA polymerase II. The sequences of these two regions are significantly conserved among TIP120A homologues of eukaryotes. CONCLUSIONS: TIP120A is a bipartite transcription factor, and both N-terminal and C-terminal regions exhibit TBP-binding activity and stimulate the basal transcription ability.

Amino Acid Sequence↗
PubMed2001

Comparison of phosphocreatine concentration in the human masseter and medial pterygoid muscles by 31P-CSI.

The aim of this study is to compare phosphocreatine (PCr) concentrations of human masseter and medial pterygoid muscles by a recently developed localized magnetic resonance spectroscopy (MRS) method, chemical shift imaging (CSI). The characteristic spectra of phosphorous metabolites including PCr and beta-ATP from the superficial part of the masseter (SM) and the deep part of the masseter (DM) and the medial pterygoid muscles (MPt) from 11 volunteers, 20-27-year-old were obtained. The study clearly demonstrated higher PCr/beta-ATP in the SM and MPt than in the DM both in mean values (P < 0.01) and in individual subjects. The results indicate that SM and MPt are power producers. There were no significant differences in the mean values of the PCr/beta-ATP ratios in SM and MPt, however, the PCr/beta-ATP ratios varied individually and the subjects could be divided into three distinct groups: values of MPt higher than SM (group A, 4 subjects); values of MPt almost equal to SM (group B, 3 subjects); and values of MPt lower than SM (group C, 4 subjects). There appears to be a close relationship between the PCr content as determined in the groups here and occlusal guidance.

Adenosine Triphosphate↗
PubMed2001

Coronary flow reserve in angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors.

AIMS: Reduced coronary flow reserve has been reported in patients with traditional risk factors, in particular hyperlipidaemia, despite angiographically normal coronary arteries. However, it is recognized that traditional risk factors do not explain the presence of coronary atherosclerosis in a large proportion of patients. The aim of this study was to assess whether coronary flow reserve is preserved in the myocardium supplied by normal coronary arteries in patients with one-vessel coronary artery disease without traditional risk factors. METHODS AND RESULTS: Positron emission tomography using [13N]ammonia was performed at baseline and after intravenous dipyridamole administration (0.56 mg x dl(-1)over 4 min) in 30 subjects: six patients with ischaemia on effort, no myocardial infarction, and isolated left anterior descending coronary artery stenosis without traditional risk factors (coronary artery disease patients without risk factors, aged 59+/-13), five patients with ischaemia on effort, no myocardial infarction, and isolated left anterior descending coronary artery stenosis with multiple risk factors (coronary artery disease patients with risk factors, aged 69+/-7), 11 age-matched controls (aged 58+/-6), and eight healthy young volunteers (aged 34+/-4). Myocardial blood flow calculated in the myocardium supplied by normal coronary arteries in the coronary artery disease patients was compared with those of the two control groups. Coronary flow reserve was defined as the ratio of hyperaemic blood flow after dipyridamole infusion to baseline blood flow. Although coronary flow reserve in the coronary artery disease patients with risk factors was significantly lower than that in the age-matched controls (1.62+/-0.37, 2.58+/-0.71, P=0.0428), coronary flow reserve in the coronary artery disease patients without risk factors was similar to that in the age-matched controls (2.54+/-0.17 vs 2.58+/-0.71, P=ns). CONCLUSION: Coronary flow reserve is preserved in regions supplied by angiographically normal coronary arteries with one-vessel coronary artery disease without traditional risk factors.

Adult↗
PubMed2001

Rhein, an active metabolite of diacerein, down-regulates the production of pro-matrix metalloproteinases-1, -3, -9 and -13 and up-regulates the production of tissue inhibitor of metalloproteinase-1 in cultured rabbit articular chondrocytes.

OBJECTIVE: Diacerein has proved to be effective in the treatment of osteoarthritis (OA). However, the precise action mechanism of diacerein on OA is not yet fully understood. Therefore, we investigated the effects of rhein, an active metabolite of diacerein, on the production of promatrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase-1 (TIMP-1) in rabbit articular chondrocytes. DESIGN: Confluent rabbit chondrocytes were treated for 24 or 48 h with rhein, naproxen or dexamethasone in the presence of recombinant human IL-1alpha (rhIL-1alpha). ProMMP-9/progelatinase B in the culture medium was monitored by gelatin zymography, and proMMP-1/procollagenase 1, proMMP-3/prostromelysin 1, proMMP-13/procollagenase 3 and TIMP-1 were analysed by Western blot analysis. The steady-state levels of proMMP mRNAs were examined by Northern blot analysis. Total MMPs activity was also determined using FITC-labeled casein. RESULTS: Rhein suppressed the rhIL-1alpha-induced production of proMMPs-1, -3, -9 and -13 in a dose-dependent manner (0.1-30 microM). The suppressed production of proMMPs-1 and -3 was accompanied by a decrease in the steady-state levels of their mRNAs. Interestingly, rhein increased the production of TIMP-1. These observations were further supported by the fact that rhein decreased the apparent total activity of MMPs in the culture medium. CONCLUSION: We have demonstrated that rhein, an active metabolite of diacerein down-regulates the gene-expression and production of proMMPs and up-regulates the TIMP-1 production. The therapeutic effects of diacerein on OA may be due, at least in part, to the chondroprotective effect of rhein, its active metabolite.

Animals↗
PubMed2001

Effects of cilostazol on late lumen loss and repeat revascularization after Palmaz-Schatz coronary stent implantation.

BACKGROUND: Cilostazol is an antiplatelet agent that increases the intracellular concentration of cyclic adenosine monophosphate by inhibiting phosphodiesterase III; it has been shown to reduce neointimal hyperplasia in animal balloon injury models. METHODS: One hundred thirty patients who underwent elective stenting (Palmaz-Schatz stent) were randomly assigned to cilostazol treatment 200 mg/d (n = 65) or to ticlopidine treatment 200 mg/d (n = 65). Angiographic follow-up was performed at 6 months, and clinical follow-up was continued up to 1 year. RESULTS: One sudden death and one myocardial infarction resulting from subacute occlusion were observed in the ticlopidine group. Drug adverse effects were observed in 3 patients in the cilostazol group, as opposed to 6 patients in the ticlopidine group. In the intention-to-treat analysis, 56 patients (61 lesions) in the cilostazol group and 58 patients (58 lesions) in the ticlopidine group were assessed with quantitative coronary angiography. Late loss in the cilostazol group was smaller (0.58+/-0.52 mm vs. 1.09+/-0.65 mm, P<.0001) than in the ticlopidine group. The restenosis rate was lower in the cilostazol group than in the ticlopidine group (16% vs. 33%, P = .044). The target vessel revascularization rate at 1 year was 23% in the cilostazol group and 42% in the ticlopidine group (P =.03). CONCLUSIONS: The results of this study suggest that cilostazol may be a safe medication that is effective in preventing restenosis after stent implantation.

Cilostazol↗
PubMed2001

Re-evaluation of the metabolism of oral doses of racemic carbon-6 isomers of formyltetrahydrofolate in human subjects.

The racemic mixture, [6RS]-5-formyltetrahydrofolate, is widely used clinically. In human subjects, orally-administered pure unnatural C-6 isomers, [6R]-5-formyltetrahydrofolate and [6S]-5,10-methenyltetrahydrofolate, were recently shown to be metabolized to the natural isomer, [6S]-5-methyltetrahydrofolate. We re-analysed the data from human studies published during the past four decades in which oral doses (< or =10 mg) of racemic mixtures of these folates were used. We re-evaluated the data to determine whether these racemic mixtures are only 50 % bioactive or, as we now predict, more than 50 % bioactive. Our analyses indicate that, in human subjects, oral doses of the racemic mixture of the two formyltetrahydrofolates are 20-84 % more bioactive than would be predicted. These data are consistent with the following pathway: chemical conversion of these folates to 10-formyltetrahydrofolate; oxidation of 10-formyltetrahydrofolate to 10-formyldihydrofolate; subsequent enzymic conversion of 10-formyldihydrofolate to dihydrofolate by 5-amino-4-imidazolecarboxamide ribotide transformylase; and finally the well-established metabolism of dihydrofolate to [6S]-5-methyltetrahydrofolate. An additional review of the literature supports the in vivo oxidation of 10-formyltetrahydrofolate occurring to a certain extent, as 10-formyl-folic acid is rapidly formed after the administration of folic acid (pteroylglutamic acid) or 5-formyltetrahydrofolate in human subjects. The dogma that an oral dose of the unnatural C-6 isomer of 5-formyltetrahydrofolate is not bioactive in human subjects does not withstand scrutiny, most probably due to the previously unrecognized in vivo oxidation of 10-formyltetrahydrofolate. This discovery unveils new folate metabolism in human subjects.

Administration, Oral↗
PubMed2001

Development of real-time image sequence analysis for evaluating posture change and respiratory rate of a subject in bed.

An image sequence analysis technique was developed to evaluate posture change and respiratory rate of a subject in bed without any physical contact. Although the image sequence analysis requires many calculations, the system can perform them in real time. The system consisted of a CCD video camera and a PC equipped with a high-speed image processor. To evaluate the system, we tested it on five subjects at a nursing home. The system evaluated 99.4% of the movements of subjects during the total monitoring time (about 61 hours). The waveform was flat when the subject was out of view of the video camera. The system has the possibility of evaluating not only posture changes and respiratory rate. but also sleeping patterns.

Adult↗
PubMed2001

Phase I and pharmacological study of paclitaxel given over 3 h with cisplatin for advanced non-small cell lung cancer.

BACKGROUND: To establish the toxicities and maximum tolerated dose of paclitaxel given over 3 h in combination with cisplatin, to determine the pharmacokinetic profiles of these two drugs and to observe their antitumor activity, we conducted a combination phase I study in non-small cell lung cancer. METHODS: Patients received paclitaxel doses of 150-210 mg/m2 given over 3 h and cisplatin doses of 60-80 mg/m2 as a 1 h infusion 2 h after the end of the paclitaxel infusion. RESULTS: A total of 25 patients with previously untreated non-small cell lung cancer were enrolled. Granulocytopenia was the most frequent hematological toxicity and the most prominent non-hematological toxicity was sensory dominant neuropathy. Two of six patients experienced dose limiting toxicities (leukopenia, infection and neuropathy) at a dose of paclitaxel 210 mg/m2 and cisplatin 60 mg/m2, which was considered the maximum tolerated dose. There were seven partial responses among 24 evaluable patients, for an overall response rate of 29%. The median survival time was 341 days and the 1 year survival rate was 45.8%. As the paclitaxel pharmacokinetic parameters in this study were consistent with those of our previous single agent study, we found no significant drug-drug interaction between the 3 h infusion paclitaxel and cisplatin. CONCLUSION: The recommended doses for further study are determined to be paclitaxel 180 mg/m2 and cisplatin 80 mg/m2. This is a well-tolerated and active regimen for non-small cell lung cancer. In view of the promising survival outcome, further evaluation in prospective randomized trials versus other regimens is warranted.

Adult↗
PubMed2001

A dose escalation study of paclitaxel and carboplatin in untreated Japanese patients with advanced non-small cell lung cancer.

BACKGROUND: The combination of paclitaxel (225 mg/m(2), 3-h infusion) and carboplatin (area under the curve 6) is widely used for non-small cell lung cancer in the USA. In Japan, however, the recommended dose for single-use paclitaxel in 3-h infusion is 210 mg/m(2) and the optimal dose of this agent in combination with carboplatin has not been established. This dose escalation study was designed to determine the maximum tolerated dose of paclitaxel in 3-h infusion plus carboplatin at a fixed dose of area under the curve 6 for Japanese patients with advanced, untreated non-small cell lung cancer. METHODS: Between October 1999 and May 2000, 19 patients were enrolled and 18 of these patients were evaluable for toxicity. Chemotherapy consisted of carboplatin area under the curve 6 and an escalated dose of paclitaxel on day 1 every 3-4 weeks. The initial dose of paclitaxel was 175 mg/m(2) and was increased by 25 mg/m(2) at each dose level. RESULTS: Neutropenia was the major toxicity observed, but was not dose related. Febrile neutropenia was not observed. No grade 3 or more peripheral neuropathy, myalgia or arthralgia was reported. The maximum tolerated dose was not determined even at the highest paclitaxel dose level (225 mg/m(2)) in this study. Partial responses were observed in six of the 19 patients (31.6%). CONCLUSION: We conclude that paclitaxel at 225 mg/m(2) in 3-h infusion and carboplatin area under the curve 6 can safely be given to Japanese patients with non-small cell lung cancer.

Adult↗
PubMed2001

A phase I/II study of cisplatin and vinorelbine chemotherapy in patients with advanced non-small cell lung cancer.

BACKGROUND: A combination of cisplatin and vinorelbine chemotherapy is effective in cases of advanced non-small cell lung cancer, but the optimum administration schedule for both drugs has not yet been defined. The aim of this study was to determine the maximum dose of vinorelbine that can be tolerated while receiving a fixed dose of cisplatin every 3 weeks and to observe the response in Japanese patients with advanced non-small cell lung cancer who had not previously received chemotherapy. METHODS: Cisplatin was given at a dose of 80 mg/m2 on day 1. Vinorelbine was administered on days 1 and 8 at a starting dose of 25 mg/m2 that was then increased by 5 mg/m2 increments. This treatment was repeated every 3 weeks. RESULTS: Twenty-one patients received a total of 54 chemotherapy cycles consisting of three different vinorelbine dosages. Toxicity and efficacy were evaluated in all of the patients. The main dose-limiting toxicity was neutropenia. Grades 3-4 leukopenia and neutropenia were observed in 57% and 86% of all cycles, respectively. These conditions were reversible and did not result in death from toxicity. The most severe non-hematological toxicity symptom was a grade 3 infection and reaction at the site of injection. The maximum tolerated dose of vinorelbine was 35 mg/m2. The objective response was noted in one of six patients at dose level 1, in four of 12 patients at dose level 2 and in two of three patients at dose level 3. CONCLUSION: The recommended doses were 80 mg/m2 for cisplatin and 30 mg/m2 for vinorelbine. The combination of cisplatin and vinorelbine repeated every 3 weeks is well tolerated and has shown promising anti-tumor activity against non-small cell lung cancer.

Adult↗
PubMed2001

Acute canine model for drug-induced Torsades de Pointes in drug safety evaluation-influences of anesthesia and validation with quinidine and astemizole.

An acute in vivo model for drug-induced torsades de pointes (TdP) for use in safety evaluation of drugs was developed using dogs with acute complete atrioventricular (AV) block. In order to study the effects of anesthetic agents on the inducibility of TdP, arrhythmias were induced by programmed electrical stimulation (PES) before and after cumulative intravenous administration of quinidine under anesthesia with sodium pentobarbital, halothane, or isoflurane. Both prolongation of the QTc and the incidence of TdP were greatest in dogs anesthetized with halothane and were smallest in those given pentobarbital, suggesting that halothane is the most suitable anesthetic for this TdP model. To further validate this model, astemizole was administered intravenously to other dogs under halothane anesthesia. Astemizole at 0.3 mg/kg caused slight prolongation of the QT interval but did not induce any arrhythmias. At 1 mg/kg, however, TdP were induced in 5 of 10 animals and in an additional 2 animals at 3 mg/kg. Single and multiple ectopic beats preceded the induction of TdP, and the ectopic beats were observed in a dose-dependent manner. The plasma concentrations of quinidine in dogs with TdP were equivalent to or less than quinidine levels in humans with TdP, while those of astemizole were higher in dogs. In conclusion, this acute canine model of TdP with halothane anesthesia, complete AV block, PES, and simultaneous measurements of plasma drug concentration would be valuable for assessing the risk of drugs, especially I(Kr) blockers, to induce TdP in humans.

Acute Disease↗
PubMed2001

Revival of the genus Lentzea and proposal for Lechevalieria gen. nov.

The genus Saccharothrix is phylogenetically heterogeneous on the basis of analysis of almost complete 16S rDNA sequences. An evaluation of chemotaxonomic, morphological and physiological properties in the light of the molecular phylogeny data revealed that several species are misclassified. Saccharothrix aerocolonigenes NRRL B-3298T and Saccharothrix flava NRRL B-16131T constitute a lineage distinct from Saccharothrix and separate from Lentzea. The genus Lechevalieria gen. nov. is proposed for these species. Lechevalieria aerocolonigenes comb. nov. is the type species and S. flava is transferred as Lechevalieria flava comb. nov. Although Lentzea albidocapillata, the type species of the genus Lentzea, was transferred recently to the genus Saccharothrix, the revival of Lentzea is clearly supported by molecular phylogenetic and chemotaxonomic data. The description of the revived genus is emended to include galactose, mannose and traces of ribose as diagnostic whole-cell sugars and MK-9(H4) as the principal menaquinone and elimination of tuberculostearic acid as a diagnostic component in the fatty acid profile. Saccharothrix waywayandensis NRRL B-16159T, S. aerocolonigenes NRRL B-16137 and 'Asiosporangium albidum' IFO 16102 are members of the amended genus Lentzea on the basis of phylogenetic and chemotaxonomic properties. S. waywayandensis is transferred to Lentzea as Lentzea waywayandensis comb. nov., while the new species Lentzea californiensis sp. nov. and Lentzea albida sp. nov. are described for S. aerocolonigenes NRRL B-16137 and 'A. albidum' IFO 16102, respectively. Nucleotide signatures in the 16S rDNA sequences are defined that are diagnostic for the genera Lechevalieria, Lentzea and Saccharothrix.

Actinomycetales↗
PubMed2001

A new genus of the order Actinomycetales, Virgosporangium gen. nov., with descriptions of Virgosporangium ochraceum sp. nov. and Virgosporangium aurantiacum sp. nov.

Four motile spored strains were isolated from soil samples collected in Japan. The cultures formed long, narrow sporangia on short sporangiophores directly on the substrate mycelium. The sporangia develop singly or in clusters above the surface of the substrate. Each sporangium contains a single row of six or more motile spores. Glutamic acid, glucosamine, glycine, alanine and 3-OH-diaminopimelic acid are present in the cell wall; the whole-cell sugars are 3-O-methylmannose, rhamnose, mannose, arabinose, galactose, xylose and glucose; and the predominant menaquinones are 10(H4), 10(H6) and 10(H8). The diagnostic phospholipid is phosphatidylethanolamine. The acyl type of the muramic acid is glycolyl. The G+C content is 71 mol%. Mycolic acids are absent. The chemotaxonomic data indicate that these strains belong to the family Micromonosporaceae. Analysis of 165 rDNA sequences suggested that these organisms fall into a distinct clade within the family Micromonosporaceae for which a new genus, Virgosporangium gen. nov., is proposed containing the species Virgosporangium ochraceum sp. nov. (strains YU655-43T, YU793-41 and YU794-41) and Virgosporangium aurantiacum sp. nov. (strain YU438-5T).

DNA, Ribosomal↗
PubMed2001

Phylogenetic analysis of the genus Actinoplanes and transfer of Actinoplanes minutisporangius Ruan et al. 1986 and 'Actinoplanes aurantiacus' to Cryptosporangium minutisporangium comb. nov. and Cryptosporangium aurantiacum sp. nov.

The phylogenetic structure of the genus Actinoplanes was determined by comparative 16S rDNA sequence analysis of the type strains of all validly described Actinoplanes species and other strains of Actinoplanes. Actinoplanes minutisporangius IFO 15962T and 'Actinoplanes aurantiacus' IFO 13967 were placed outside the family Micromonosporaceae and appeared to be closely related to the genus Cryptosporangium. On the basis of their morphological and chemotaxonomic characteristics and phylogenetic analysis, these strains were reclassified into the genus Cryptosporangium. DNA-DNA hybridization revealed that these strains differed from the species previously described in this genus. Therefore, the transfer is proposed of Actinoplanes minutisporangius Ruan et al. 1986 and 'Actinoplanes aurantiacus' IFO 13967 to the genus Cryptosporangium as Cryptosporangium minutisporangium comb. nov. and Cryptosporangium aurantiacum sp. nov.

Actinomycetales↗