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T Yoshimura

Publications and source records attributed to T Yoshimura.

At least 91 records · Page 5Linked to original sources
PubMed2000

Emission and metal- and ligand-centered-redox characteristics of the hexarhenium(III) clusters trans- and cis-[Re6(mu 3-S)8Cl4(L)2]2-, where L is a pyridine derivative or pyrazine.

Preparations of a series of face-capped octahedral hexarhenium(III) clusters having two N-heterocyclic ligands, [Bu4N]2[trans-[Re6(mu 3-S)8Cl4(L)2]] (Bu4N+ = tetra-n-butylammonium cation; L = pyrazine (1a), 4,4'-bipyridine (3a), 4-methylpyridine (5a), 4-(dimethylamino)pyridine (6a)) and their cis analogues (1b, 3b, 5b, and 6b, respectively), and their electrochemical and photophysical properties have been reported. An X-ray crystal structure determination has been carried out for 1a to confirm the trans configuration (C40H80N6S8Cl4Re6, orthorhombic, space group Cmca (No. 64), a = 19.560(5) A, b = 19.494(4) A, c = 18.592(4) A, beta = 115.76(2) degrees, Z = 4). The redox potential of the reversible ReIII6/ReIII5ReIV process of these complexes and previously reported [Bu4N]2[trans- and cis-[Re6(mu 3-S)8Cl4(4-cyanopyridine)2]] (2a and 2b, respectively) and [Bu4N]2[trans- and cis-[Re6(mu 3-S)8Cl4(pyridine)2]] (4a and 4b, respectively) in acetonitrile depends linearly on the pKa of the N-heterocyclic ligands, with the potentials being more negative with basic ligands. The ligand-centered-redox waves for 1a, 1b, 2a, and 2b were observed as split waves (delta E1/2 = 90-140 mV), the extent of the splitting being larger for the cis isomer and largest for the pyrazine complexes. Electronic interaction between the two ligands through the [Re6(mu 3-S)8]2+ core has been suggested. The second ligand-reduction wave was also observed for 3a and 3b, the potential being shifted positively to coalesce with the first reduction wave on addition of the weak proton donor imidazole. This is accounted for by the proton-coupled redox reaction at the free pyridyl site of the 4,4'-bipyridine ligands. All of the complexes show luminescence in acetonitrile at room temperature. While the complexes of pyridine and 4-methylpyridine show photophysical characteristics (lambda em 740-750 nm, phi em 0.031-0.057, tau em 4.2-6.2 microseconds) similar to those (770 nm, 0.039, and 6.3 microseconds, respectively) of [Re6(mu 3-S)8Cl6]4-, emissions of other complexes are significantly weak with lambda em, phi em, and tau em values in the ranges 763-785 nm, 0.0010-0.0017, and 0.013-0.029 microsecond, respectively. Suggestions are given for the excited states localized on the cluster core and the ligand pi* orbitals.

Journal Article↗
PubMed2000

cDNA cloning, purification, and characterization of mouse liver selenocysteine lyase. Candidate for selenium delivery protein in selenoprotein synthesis.

Selenocysteine lyase (SCL) (EC 4.4.1.16) is a pyridoxal 5'-phosphate-dependent enzyme that specifically catalyzes the decomposition of L-selenocysteine to L-alanine and elemental selenium. The enzyme was proposed to function as a selenium delivery protein to selenophosphate synthetase in selenoprotein biosynthesis (Lacourciere, G. M., and Stadtman, T. C. (1998) J. Biol. Chem. 273, 30921-30926). We purified SCL from pig liver and determined its partial amino acid sequences. Mouse cDNA clones encoding peptides resembling pig SCL were found in the expressed sequence tag data base, and their sequences were used as probes to isolate full-length mouse liver cDNA. The cDNA for mouse SCL (mSCL) was determined to be 2,172 base pairs in length, containing an open reading frame encoding a polypeptide chain of 432 amino acid residues (M(r) 47, 201). We also determined the sequence of the N-terminal region of putative human SCL. These enzymes were shown to be distantly related in primary structure to NifS, which catalyzes the desulfurization of L-cysteine to provide sulfur for iron-sulfur clusters. The recombinant mSCL overproduced in Escherichia coli was a homodimer with the subunit M(r) of 47,000. The enzyme was pyridoxal phosphate-dependent and highly specific to L-selenocysteine (the k(cat)/K(m) value for L-selenocysteine was about 4,200 times higher than that for L-cysteine). Reverse transcriptase-polymerase chain reaction and Western blot analyses revealed that mSCL is cytosolic and predominantly exists in the liver, kidney, and testis, where mouse selenophosphate synthetase is also abundant, supporting the view that mSCL functions in cooperation with selenophosphate synthetase in selenoprotein synthesis. This is the first report of the primary structure of mammalian SCL.

Amino Acid Sequence↗
PubMed2000

Important role of local angiotensin II activity mediated via type 1 receptor in the pathogenesis of cardiovascular inflammatory changes induced by chronic blockade of nitric oxide synthesis in rats.

BACKGROUND: The chronic inhibition of NO synthesis by N(omega)-nitro-L-arginine methyl ester (L-NAME) upregulates the cardiovascular tissue angiotensin II (Ang II)-generating system and induces cardiovascular inflammatory changes in rats. METHODS AND RESULTS: We used a rat model to investigate the role of local Ang II activity in the pathogenesis of such inflammatory changes. Marked increases in monocyte infiltration into coronary vessels and myocardial interstitial areas, monocyte chemoattractant protein-1 (MCP-1) expression, and nuclear factor-kappaB (NF-kappaB, an important redox-sensitive transcriptional factor that induces MCP-1) activity were observed on day 3 of L-NAME administration. Along with these changes, vascular superoxide anion production was also increased. Treatment with an Ang II type 1 receptor antagonist or with a thiol-containing antioxidant, N-acetylcysteine, prevented all of these changes. CONCLUSIONS: Increased Ang II activity mediated via the type 1 receptor may thus be important in the pathogenesis of early cardiovascular inflammatory changes in this model. Endothelium-derived NO may decrease MCP-1 production and oxidative stress-sensitive signals by suppressing localized activity of Ang II.

Angiotensin II↗
PubMed2000

Allelic imbalance and mutations of the PTEN gene in ovarian cancer.

The PTEN/MMAC1/TEP1 tumor-suppressor gene, which maps to chromosome 10q23.3, is mutated and homozygously deleted in a variety of human tumors, including endometrioid-type ovarian tumors. We examined 33 primary ovarian cancers and 3 ovarian borderline tumors for allelic imbalance (AI) of the 10q23.3 region using 5 polymorphic markers, including an insertion/deletion-type polymorphic marker identified in intron 4 of the PTEN gene. AI at one or more loci was detected in 12 of 31 (39%) informative ovarian cancers and none of 3 ovarian borderline tumors. The commonly deleted region was mapped between the D10S215 and D10S541 loci, including the PTEN locus. Moreover, the incidence of AI at the PTEN locus (38%) was the highest among the 5 loci examined. Therefore, we searched for mutations in the entire coding region of the PTEN gene by PCR-SSCP and sequencing analyses in these tumors and 7 ovarian cancer cell lines. Mutations were detected in 3 of the 33 (9%) ovarian cancers: 2 cases with double mutations and 1 case with a mutation on 1 allele accompanied by deletions on both alleles in the poly T tract preceding the splice acceptor site in intron 7. An intragenic deletion was detected in 1 of the 7 (14%) ovarian cancer cell lines. PTEN mutations were detected not only in the endometrioid type but also in the serous and mucinous types of ovarian cancer. However, PTEN was not mutated in the 12 tumors that showed AI of the PTEN locus. Our results suggest that the PTEN gene plays an important role in the development of a subset but diverse histological types of ovarian tumors. However, it is possible that another tumor-suppressor gene in the close vicinity of the PTEN gene is also inactivated by AI of the 10q23.3 region.

Chromosome Mapping↗
PubMed2000

Human thioredoxin attenuates hypoxia-reoxygenation injury of murine endothelial cells in a thiol-free condition.

The adult T cell leukemia-derived factor (ADF), or human thioredoxin (hTRX), has a radical scavenging effect similar to that of N-acetyl cysteine (NAC). We have recently shown that ADF/hTRX protects the lung and the heart from ischemia-reperfusion induced injury. To elucidate mechanisms of the protective effect, a hypoxia-reoxygenation (H-R) injury model was developed using a murine endothelial cell line, cultured in a thiol-free medium. In this condition, cells became much more vulnerable to H-R injury. The viability of cells decreased significantly after 1 h of hypoxic incubation followed by 1 h of reoxygenation. The injury was reduced by ADF/hTRX (100 microM) or NAC (10 mM). These two agents also demonstrated an additive protective effect. When cells were cultured in thiol-free medium for 2 h in a normoxic condition, intracellular hydrogen peroxide production was increased, which was associated with a decrease in glutathione level. NAC (10 mM) attenuated these changes whereas ADF/hTRX (100 microM) did not. These results suggest that although both ADF/hTRX and NAC protected cells from H-R injury, the underlying mechanisms are different. Because the cytoprotective effect of ADF/hTRX occurs in the thiol-free condition, it must be mediated via a novel mechanism other than enhancing thiol uptake. The additive cytoprotective effect between ADF/hTRX and NAC suggests that we should combine these two agents clinically.

Acetylcysteine↗
PubMed2000

Prognostic value of Doppler transmittal flow patterns and cardiac natriuretic peptides in patients with chronic congestive heart failure admitted for episodes of acute decompensation.

This study was designed to determine whether the restrictive filling transmitral flow velocity pattern is associated with increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). It was also designed to evaluate the prognostic value of these parameters from patients with chronic congestive heart failure (CHF) admitted for episodes of acute decompensation. We performed Doppler echocardiography, measured plasma levels of ANP and BNP in 33 patients at the time of admission, and assessed the subsequent cardiac mortality for 3 months. Eleven patients (33%) had a restrictive filling pattern of deceleration time (DcT) < 120ms. Plasma ANP and BNP levels were markedly increased in all patients to 189 +/- 145 pg/ml and 865 +/- 559 pg/ml, respectively. Seventeen patients (52%) showed more than 700 pg/ml of plasma levels of BNP. There was a significant correlation of DcT with the plasma ANP level (r = -0.41, P = 0.017), and a better correlation of DcT with the plasma BNP level (r =-0.50, P = 0.003). The combined index of both shorter DcT (< 120 ms) and higher plasma BNP levels (>700 pg/ml) was the best predictor of cardiac mortality by Cox univariate analysis (chi2 = 5.87, P = 0.015). Furthermore, the sensitivity and specificity of this index for the detection of cardiac mortality were 80% and 86%, respectively. In conclusion, the combined analysis of the Doppler transmitral flow velocity pattern and measurement of the plasma BNP level is noteworthy since it is noninvasive and convenient. Moreover, it is extremely useful in predicting the prognosis for patients with chronic CHF admitted for episodes of acute decompensation.

Acute Disease↗
PubMed2000

The influence of traditional Chinese herbal drugs on serum 1, 5-anhydroglucitol levels.

The serum concentration of 1,5-anhydroglucitol (1,5-AG), a polyol which originates mainly in the diet, is used in Japan as a new marker for glycemia. To evaluate the potential interference of 1, 5-AG measurements by traditional Chinese medicines (Kampo), we examined the 1,5-AG content in 32 types of concentrated dosage forms of Kampo using high performance liquid chromatography (HPLC). The 32 types of Kampo were the most frequently used in Japan, two of which, Ninjin-yoei-to (7030 microg/g dry weight) and Kami-kihi-to (6700 microg/g dry weight), contained large amounts of 1,5-AG. Six others contained small amounts of 1,5-AG. Both Ninjin-yoei-to and Kami-kihi-to contain the same ingredient, Polygalae radix, which is a crude form of polygalitol (1,5-AG). To confirm the effects of these Kampo medicines on the serum levels of 1,5-AG, we administered Ninjin-yoei-to (7.5 g/day) for 8 weeks to 18 patients with Type 2 diabetes mellitus (Type 2 DM). The serum level of 1,5-AG increased from 9.8+/-8.9 to 28.1+/-17.5 microg/ml by week 8. Hemoglobin A1c (HbA1c) had not changed by week 8. Thus, an abnormal serum 1,5-AG level may be present in patients taking Kampo which contains Polygalae radix.

Aged↗
PubMed2000

Analysis of glycosidically bound aroma precursors in tea leaves. 1. Qualitative and quantitative analyses of glycosides with aglycons as aroma compounds.

Twenty-six synthetic glycosides constituting aglycons of the main tea aroma compounds ((Z)-3-hexenol, benzyl alcohol, 2-phenylethanol, methyl salicylate, geraniol, linalool, and four isomers of linalool oxides) were synthesized in our laboratory as authentic compounds. Those compounds were used to carry out a direct qualitative and quantitative determination of the glycosides as aroma precursors in different tea cultivars by capillary gas chromatographic-mass spectrometric (GC-MS) analyses after trifluoroacetyl conversion of the tea glycosidic fractions. Eleven beta-D-glucopyranosides, 10 beta-primeverosides (6-O-beta-D-xylopyranosyl-beta-D-glucopyranoside) with aglycons as the above alcohols, and geranyl beta-vicianoside (6-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside) were identified (tentatively identified in the case of methyl salicylate beta-primeveroside) in fresh tea leaves and quantified on the basis of calibration curves that had been established by using the synthetic compounds. Primeverosides were more abundant than glucosides in each cultivar we investigated for making green tea, oolong tea, and black tea. Separation of the diastereoisomers of linalool and four isomers of linalool oxides by GC analyses is also discussed.

Calibration↗
PubMed2000

Mapping quantitative trait loci for circadian behavioral rhythms in SMXA recombinant inbred strains.

SM/J and A/J inbred strain of mice have different characteristics in circadian behaviors such as free-running period (tau), phase relationship (psi) between light-dark cycles and activity rhythms, and amount of wheel-running activity. To determine the genes which affect these behaviors, a quantitative trait locus (QTL) analysis using SMXA recombinant inbred strains derived from SM/J and A/J mice was performed. Concerning tau, two regions on chromosomes (Chrs) 7 and 18 surpassed the genome-wide suggestive level. As for psi, one suggestive QTL was detected on Chr 7. The QTLs which affect daily activity counts under light-dark cycles and constant darkness were mapped to the same chromosomal regions on Chrs 1 and 17, respectively. The provisional QTLs detected in the present study might be useful for understanding the complex mechanism regulating circadian behaviors.

Animals↗
PubMed2000

Alteration in the responsiveness to tumour necrosis factor-alpha is crucial for maximal expression of monocyte chemoattractant protein-1 in human neutrophils.

We previously reported delayed expression of monocyte chemoattractant protein-1 (MCP-1) in human neutrophils cultured with a cytokine-rich crude supernatant of phytohaemagglutinin-stimulated peripheral blood mononuclear cells (PHA-sup). Tumour necrosis factor-alpha (TNF-alpha) contained in the PHA-sup played a key role in this event, but there appeared to be another factor(s) in the same supernatant that co-operated with TNF-alpha for maximal MCP-1 expression. In the present study, we reduced TNF-alpha concentrations in the PHA-sup to minimal levels using anti-TNF-alpha affinity columns (TNF-depleted-sup) and investigated the co-operation between TNF-alpha and TNF-depleted-sup. Nine hours of preincubation with TNF-depleted-sup altered the responsiveness of neutrophils to TNF-alpha and enabled TNF-alpha to increase the level of MCP-1 expression to a maximal level within 4 hr. The priming effect was not due to the increased expression of cell-surface TNF receptors. However, the activation of primed cells by TNF-alpha was clearly through TNF receptor-p55. Finally, the activity in the TNF-depleted-sup that co-operated with TNF-alpha was eluted at 60 000 MW on high-performance liquid chromatography-gel filtration. Thus, delayed neutrophil expression of MCP-1 is regulated by a cytokine-dependent mechanism that induces neutrophils to enter a 'mature' stage.

Antigens, CD↗
PubMed2000

Modulation of activity and substrate specificity by modifying the backbone length of the distant interdomain loop of D-amino acid aminotransferase.

The activity and substrate specificity of D-amino acid aminotransferase (D-AAT) (EC 2.6.1.21) can be rationally modulated by replacing the loop core (P119-R120-P121) with glycine chains of different lengths: 1, 3, or 5 glycines. The mutant enzymes were much more active than the wild-type enzyme in the overall reactions between various amino acids and pyruvate. The presteady-state kinetic analyses of half-reactions revealed that the 5-glycine mutant has the highest affinity (Kd) among all mutant enzymes and the wild-type enzyme towards various amino acids except D-aspartate. The 5-glycine mutant was much more efficient as a catalyst than the wild-type enzyme because the mutant enzyme showed the highest value of specificity constant (kmax/Kd) for all amino acids except D-aspartate and D-glutamate. The kmax/Kd values of the three mutants decreased with decrease in glycine chain length for each amino acid examined. Our findings may provide a new approach to rational modulation of enzymes.

Alanine Transaminase↗
PubMed2000

Evaluation of the clinical relevance of the iceA1 gene in patients with Helicobacter pylori infection in Japan.

BACKGROUND: A novel Helicobacter pylori gene, iceA, has two allelic variants, and the iceA1 strain is associated with peptic ulcer disease. The aims of this study were to evaluate whether the possession of iceA1 gene is associated with gastric cancer or the severity of gastritis. METHODS: Ninety-seven subjects (46 patients with early gastric cancer and 51 control subjects) infected with H. pylori were studied. DNA was extracted from isolated H. pylori strains, and the presence of the iceA1 gene was examined by polymerase chain reaction. The features of gastritis were graded in accordance with the updated Sydney System, using gastric biopsy specimens. RESULTS: iceA1 was found in 61% of patients with gastric cancer and 53% of control subjects (NS). The grade of gastritis in iceA1-positive and -negative gastric mucosa was compared. Higher polymorphonuclear cell infiltration was observed in iceA1-positive subjects (P < 0.05). However, no significant difference was observed in the grades of mononuclear cell infiltration, glandular atrophy, and H. pylori density. CONCLUSIONS: Our results suggest that the iceA1 gene is not associated with the development of gastric cancer in Japan, whereas the iceA1-positive strain may induce more enhanced active gastric inflammation in cagA-positive and vacA s1/m1 strains.

Alleles↗
PubMed2000

Detection and imaging of endogenously produced nitric oxide with electron paramagnetic resonance spectroscopy.

Nitric oxide (NO) represents a new paradigm for second messengers in regulation. Despite the numerous physiological and pathophysiological functions of NO, its importance as an endogenous second messenger and a cytostatic and/or cytotoxic agent was unknown until 1987. Recent developments in detection methods for endogenous NO produced directly or indirectly from NO synthases (NOSs) have enabled major advances in our understanding of the role of NO in biological systems. The spin-trapping technique combined with electron paramagnetic resonance (EPR) spectroscopy is a method for analyzing NO production directly both in vivo and in vitro. Iron complexes with dithiocarbamate derivatives are noteworthy among the spin-trapping reagents for NO because NO has a high affinity for iron complexes. The resultant stable nitrosyl iron complexes exhibit an intense three-line signal at room temperature and an axial signal at low temperature. Besides the facility and wide applicability of this method, its outstanding feature is that noninvasive in vivo measurements are available by using a low-frequency EPR spectrometer. In this article, we review on previous and recent developments of in vitro, in vivo, and ex vivo EPR detection and imaging of endogenously produced NO.

Animals↗
PubMed2000

Prospective study on the relation of cigarette smoking with cancer of the liver and stomach in an endemic region.

BACKGROUND: Smoking has not been confirmed as a risk factor for cancers of the liver and stomach. The authors examined prospectively the relationship between smoking and these cancers in an endemic region. METHODS: The data used were a cohort study on the relationship between lifestyle and health in the region having the highest liver cancer mortality in Japan. Of the cohort members, 4050 males aged > or =40 years were included in the present analysis with a 9-year mean follow-up. Cox proportional hazards regression was used to estimate relative risks (RR) for cancer of the liver, stomach, smoking-related sites and others, while adjusting for age, residence, and alcohol intake. RESULTS: By the end of the study period, 59 cases of liver cancer and 53 cases of stomach cancer were identified. Current smokers, compared to subjects who had never smoked, had a threefold risk of liver cancer (RR = 3.3; 95% CI: 1.2-9.5) and a twofold risk of stomach cancer (RR = 2.2; 95% CI: 0.8-5.7). Sub-cohort analysis showed that adjustment for history of chronic liver disease did not attenuate the risk of liver cancer. Light/medium smokers had almost the same risk of these cancers as heavy smokers, while they showed a relatively low risk of smoke-related cancers. CONCLUSIONS: The present results indicate that smoking is a risk factor of liver and stomach cancer in a population with a high background risk for these cancers. However, causal inferences should be made cautiously due to a lack of information on known risk factors.

Adult↗
PubMed2000

Kinetic and mutational studies of three NifS homologs from Escherichia coli: mechanistic difference between L-cysteine desulfurase and L-selenocysteine lyase reactions.

We have purified three NifS homologs from Escherichia coli, CSD, CsdB, and IscS, that appear to be involved in iron-sulfur cluster formation and/or the biosynthesis of selenophosphate. All three homologs catalyze the elimination of Se and S from L-selenocysteine and L-cysteine, respectively, to form L-alanine. These pyridoxal 5'-phosphate enzymes were inactivated by abortive transamination, yielding pyruvate and a pyridoxamine 5'-phosphate form of the enzyme. The enzymes showed non-Michaelis-Menten behavior for L-selenocysteine and L-cysteine. When pyruvate was added, they showed Michaelis-Menten behavior for L-selenocysteine but not for L-cysteine. Pyruvate significantly enhanced the activity of CSD toward L-selenocysteine. Surprisingly, the enzyme activity toward L-cysteine was not increased as much by pyruvate, suggesting the presence of different rate-limiting steps or reaction mechanisms for L-cysteine desulfurization and the degradation of L-selenocysteine. We substituted Ala for each of Cys358 in CSD, Cys364 in CsdB, and Cys328 in IscS, residues that correspond to the catalytically essential Cys325 of Azotobacter vinelandii NifS. The enzyme activity toward L-cysteine was almost completely abolished by the mutations, whereas the activity toward L-selenocysteine was much less affected. This indicates that the reaction mechanism of L-cysteine desulfurization is different from that of L-selenocysteine decomposition, and that the conserved cysteine residues play a critical role only in L-cysteine desulfurization.

Bacterial Proteins↗
PubMed2000

Three-dimensional structure of 4-amino-4-deoxychorismate lyase from Escherichia coli.

4-Amino-4-deoxychorismate lyase (ADCL) is a member of the fold-type IV of PLP dependent enzymes that converts 4-amino-4-deoxychorismate (ADC) to p-aminobenzoate and pyruvate. The crystal structure of ADCL from Escherichia coli has been solved using MIR phases in combination with density modification. The structure has been refined to an R-factor of 20.6% at 2.2 A resolution. The enzyme is a homo dimer with a crystallographic twofold axis, and the polypeptide chain is folded into small and large domains with an interdomain loop. The coenzyme, pyridoxal 5'-phosphate, resides at the domain interface, its re-face facing toward the protein. Although the main chain folding of the active site is homologous to those of D-amino acid and L-branched-chain amino acid aminotransferases, no residues in the active site are conserved among them except for Arg59, Lys159, and Glu193, which directly interact with the coenzyme and play critical roles in the catalytic functions. ADC was modeled into the active site of the unliganded enzyme on the basis of the X-ray structures of the unliganded and liganded forms in the D-amino acid and L-branched-chain amino acid aminotransferases. According to this model, the carboxylates of ADC are recognized by Asn256, Arg107, and Lys97, and the cyclohexadiene moiety makes van der Waals contact with the side chain of Leu258. ADC forms a Schiff base with PLP to release the catalytic residue Lys159, which forms a hydrogen bond with Thr38. The neutral amino group of Lys159 eliminates the a-proton of ADC to give a quinonoid intermediate to release a pyruvate in accord with the proton transfer from Thr38 to the olefin moiety of ADC.

Amino Acid Sequence↗