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Y Yamada

Publications and source records attributed to Y Yamada.

At least 163 records · Page 9Linked to original sources
PubMed2001

Dinuclear calcium complex with weakly NH...O hydrogen-bonded sulfonate ligands.

The novel intramolecularly NH...O hydrogen-bonded Ca(II)-aryl sulfonate complex, [Ca2(SO3-2-t-BuCONHC6H4)2(H2O)4]n(2-t-BuCONHC6H4SO3)2n (1), sulfonate anion, (HNEt3)(SO3-2-t-BuCONHC6H4) (2a), (PPh4)(SO3-2-t-BuCONHC6H4) (2b), (n-Bu4N)(SO3-2-t-BuCONHC6H4) (2c), and sulfonic acid, 2-t-BuCONHC6H4SO3H (3), were synthesized. The structures of 1, 2a, and 2b depict the presence of the formation of NH...O hydrogen bonds between the amide NH and S-O oxygen for a series of compounds as determined by IR and 1H NMR analyses both in the solid state and in the solution state. Thus, the NH...O hydrogen bonds with neutral amide groups are available for investigation of the electronic state of the O- anion. The combined data from the IR and 1H NMR spectra indicate that the sulfonic acid, sulfonate anion, and Ca(II) complex have a substantially weak intramolecular NH...O hydrogen bond between the SO3 oxygen and amide NH. In the detailed comparison with the intense NH...O hydrogen bonds for the carboxylate, weak NH...O hydrogen bonds for sulfonate is due to the strong conjugation of the SO3- group with the lower nucleophilicity.

Journal Article↗
PubMed2001

Transcriptional cross-talk between Smad, ERK1/2, and p38 mitogen-activated protein kinase pathways regulates transforming growth factor-beta-induced aggrecan gene expression in chondrogenic ATDC5 cells.

In chondrogenesis, members of the transforming growth factor-beta (TGF-beta) superfamily play critical roles by inducing gene expression of cartilage-specific molecules. By using a chondrogenic cell line, ATDC5, we investigated the TGF-beta-mediated signaling pathways involved in expression of the aggrecan gene (Agc). At confluency, TGF-beta induced Agc expression within 3 h, and cycloheximide blocked this induction, indicating that de novo protein synthesis is essential for this response. At this stage, TGF-beta induced rapid, transient phosphorylation of Smad2, extracellular signal-activated kinase 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (MAPK). Inhibition of the Smad pathways by transfection with a dominant negative Smad4 construct significantly reduced TGF-beta-induced Agc expression, indicating that Smad signaling is essential for this response. Furthermore, an inhibitor of the ERK1/2 pathway, U0126, or inhibitors of the p38 MAPK pathway, SB203580 and SKF86002, repressed TGF-beta-induced Agc expression in a dose-dependent manner, indicating that ERK1/2 or p38 MAPK activation is also required for TGF-beta-induced Agc expression in confluent ATDC5 cells. In differentiated ATDC5 cells, persistently high basal levels of ERK1/2 and p38 MAPK phosphorylation correlated with elevated basal Agc expression, which was inhibited by incubation with inhibitors of these pathways. Whereas Smad2 was rapidly phosphorylated by TGF-beta and involved in the initial activation of Agc expression in confluent cells, Smad2 activation was not required for maintaining the high level of Agc expression. Taken together, these results suggest an important role for transcriptional cross-talk between Smad and MAPK pathways in expression of early chondrocytic phenotypes and identify important changes in the regulation of Agc expression following chondrocyte differentiation.

Aggrecans↗
PubMed2001

Effect of carvedilol on atrioventricular conduction in the ischemic heart.

We compared the effects of carvedilol on atrial-His and His-ventricular conduction with those of propranolol in isolated rat hearts. Hearts were perfused retrograde, and atrial-His and His-ventricular intervals were measured. The effective doses that increased conduction times by 25% were 10(-6) M for atrial-His and 3x10(-6) M for His-ventricular for propranolol, and 8x10(-8) M for atrial-His and 10(-8) M for His-ventricular for carvedilol. Prazosin did not affect the atrial-His and His-ventricular intervals. After ischemia-reperfusion, atrial-His and His-ventricular intervals increased to a greater extent with 10(-6) M carvedilol. To determine the direct membrane effect, we examined the transmembrane action potential in guinea pig papillary muscle. Both drugs decreased the maximum upstroke velocity equally. Our data indicate that carvedilol had a greater effect on atrioventricular conduction in the setting of ischemia-reperfusion than did propranolol. This effect of carvedilol was not due to its alpha-adrenoceptor blocking property or to a direct membrane effect.

Action Potentials↗
PubMed2001

DNA topoisomerase II as the target for the anticancer drug TOP-53: mechanistic basis for drug action.

TOP-53 is a promising anticancer agent that displays high activity against non-small cell lung cancer in animal tumor models [Utsugi, T., et al. (1996) Cancer Res. 56, 2809-2814]. Compared to its parent compound, etoposide, TOP-53 is considerably more toxic to non-small cell lung cancer cells, is more active at generating chromosomal breaks, and displays improved cellular uptake and pharmacokinetics in animal lung tissues. Despite the preclinical success of TOP-53, several questions remain regarding its cytotoxic mechanism. Therefore, this study characterized the basis for drug action. Results indicate that topoisomerase II is the primary cytotoxic target for TOP-53. Furthermore, the drug kills cells by acting as a topoisomerase II poison. TOP-53 exhibits a DNA cleavage site specificity that is identical to that of etoposide. Like its parent compound, the drug increases the number of enzyme-mediated DNA breaks by interfering with the DNA religation activity of the enzyme. TOP-53 is considerably more efficient than etoposide at enhancing topoisomerase II-mediated DNA cleavage and exhibits high activity against human topoisomerase IIalpha and IIbeta in vitro and in cultured cells. Therefore, at least in part, the enhanced cytotoxic activity of TOP-53 can be attributed to an enhanced activity against topoisomerase II. Finally, TOP-53 displays nearly wild-type activity against a mutant yeast type II enzyme that is highly resistant to etoposide. This finding suggests that TOP-53 can retain activity against systems that have developed resistance to etoposide, and indicates that substituents on the etoposide C-ring are important for topoisomerase II-drug interactions.

Antigens, Neoplasm↗
PubMed2001

Multiple variants of receptor-type protein tyrosine phosphatase beta are expressed in the central nervous system of Xenopus.

We have isolated cDNA clones encoding the Xenopus homologue of receptor-type protein tyrosine phosphatase beta (RPTPbeta), and identified 13 forms of the mRNA provably generated by alternative splicing. All the conceptual translates have a carbonic anhydrase-like domain, a fibronectin type III-like repeat and a spacer in the extracellular segment. Eleven of them (designated XRPTPbeta.1-XRPTPbeta.11) also have highly conserved two intracellular PTP domains, whereas the other two variants (sXRPTPbeta.1 and sXRPTPbeta.2) have neither transmembrane nor cytoplasmic segment. There are five peptides that can be inserted in various combinations into the spacer region. Northern and Western blot analyses show central nervous system-specific expression of the XRPTPbeta mRNAs and proteins. Chondroitinase ABC treatment of the brain and spinal cord extracts results in separation of six protein bands on the Western blot, in association with a decrease in the size of major bands, indicating that the major XRPTPbeta variants are chondroitin sulfate proteoglycans. The results of these as well as reverse-transcribed polymerase chain reaction analyses suggest that the amounts of different XRPTPbeta variants are regulated in tissue- and developmental stage-specific manners.

Amino Acid Sequence↗
PubMed2001

Metabolic engineering of plant alkaloid biosynthesis.

Plant alkaloids, one of the largest groups of natural products, provide many pharmacologically active compounds. Several genes in the biosynthetic pathways for scopolamine, nicotine, and berberine have been cloned, making the metabolic engineering of these alkaloids possible. Expression of two branching-point enzymes was engineered: putrescine N-methyltransferase (PMT) in transgenic plants of Atropa belladonna and Nicotiana sylvestris and (S)-scoulerine 9-O-methyltransferase (SMT) in cultured cells of Coptis japonica and Eschscholzia californica. Overexpression of PMT increased the nicotine content in N. sylvestris, whereas suppression of endogenous PMT activity severely decreased the nicotine content and induced abnormal morphologies. Ectopic expression of SMT caused the accumulation of benzylisoquinoline alkaloids in E. californica. The prospects and limitations of engineering plant alkaloid metabolism are discussed.

Alkaloids↗
PubMed2001

A rare case of complete human erythrocyte AMP deaminase deficiency due to two novel missense mutations in AMPD3.

Human erythrocyte AMP deaminase (AMPD3) deficiency is a clinically asymptomatic condition characterized by a 50% increase in steady-state levels of ATP in affected cells. The deficiency in Japanese is associated 75% of the time with the same mutation of R573C, and 25% of the time with other heterogeneous mutations of the AMPD3 gene. The heterozygote frequency was estimated at about 1/30. We previously reported five Japanese individuals who had a complete deficiency of AMPD3. Four were homozygotes for the major mutation of R573C; however, one female did not have the R573C allele. To clarify the mutations in her AMPD3 gene, we analyzed the AMPD3 gene and detected a minor mutation, W450R, derived from the mother and a novel mutation,Q712P, derived from the father. The expression study using AMPD3 cDNA containing both mutations showed that each mutation completely reduced the enzyme activity of AMPD3. As the frequency of carriers heterozygous for these mutations seems to be very low, identifying them may lead to a better understanding of the genetic background of populations in Japan.

AMP Deaminase↗
PubMed2001

Capillary zone electrophoretic chiral discrimination using a cationic cyclodextrin derivative: determination of velocity and association constants of each enantiomer of the amino acid derivative with 6-trimethylammonio-deoxy-beta-cyclodextrin.

A positively charged beta-cyclodextrin possessing a trimethylammonio group, 6-trimethylammonio-6-deoxy-beta-cyclodextrin chloride 1 was prepared by the reaction of an amino derivative 3 with methyl iodide under very mild conditions. The cyclodextrin derivative discriminated between enantiomers of acetylphenylalanine 2 on capillary zone electrophoresis (CZE) analysis, which was possibly due to an electrostatic interaction between the trimethylammonio group of 1 and the carboxylate group of 2, and also due to the inclusion of 2 in a hydrophobic molecular cavity of 1. Double data normalization based on relative electrophoretic velocity of peaks due to indirect response of 1 and also water in an injected sample may be effective for elimination of variation and fluctuation of physical parameters of medium, such as viscosity and ionic strength, in order to determine intrinsic association constants and velocity of the complexes.

Amino Acids↗
PubMed2001

Abnormal activity in the globus pallidus in off-period dystonia.

Pallidotomy was performed in a parkinsonian patient with off-period foot dystonia. Dystonia appeared at the beginning of surgery and disappeared after the first microelectrode penetration of the globus pallidus, perhaps a micropallidotomy effect. Neuronal recording during dystonia revealed that the mean firing rates were low in both the internal and external segments of the globus pallidus, and that firing was irregular in the internal segment of the globus pallidus, compared with firing patterns in offstate parkinsonian patients without dystonia. These firing patterns immediately changed into those of nondystonic, off-state parkinsonism after relief of dystonia These results suggest that off-period dystonia results from the same physiological change in the basal ganglia as that in primary dystonia.

Dystonia↗
PubMed2001

Dyssegmental dysplasia, Silverman-Handmaker type: unexpected role of perlecan in cartilage development.

Dyssegmental dysplasia, Silverman-Handmaker type (DDSH), is a lethal autosomal recessive form of dwarfism with characteristic anisospondylic micromelia. The remarkable similarities in the radiographic, clinical, and chondroosseous morphology of DDSH patients to those of perlecan-null mice led to the identification of mutations in the perlecan gene (HSPG2) of DDSH. Perlecan, a large heparan sulfate proteoglycan, is expressed in various tissues and is a component of all basement membrane extracellular matrices. A chondrodysplasia phenotype caused by the loss of perlecan was unexpected, because cartilage does not have basement membranes. Insertion and splicing mutations in HSPG2 of DDSH were found that were predicted to create a premature termination codon. Immunostaining and biochemical analysis revealed that the mutant perlecan molecules were unstable and not secreted into the extracellular matrix. These results indicate that DDSH is caused by functional null mutations of HSPG2 and that perlecan is essential for cartilage development. Published 2002 Wiley-Liss, Inc.

Cartilage↗
PubMed2001

Neuronal activity in the globus pallidus in chorea caused by striatal lacunar infarction.

Pallidotomy was performed in a patient with hemichorea caused by lacunar infarction in the striatum. Chorea in the lower limb was reduced after a neurosurgical lesion in the medial portion of the sensorimotor territory of the internal segment of the globus pallidus, and chorea in the upper limb disappeared after an additional lesion in the lateral portion of that same area. Intraoperative neuronal recording revealed that mean firing rates were low, and that firing was irregular in the globus pallidus compared with off-state parkinsonian patients. These results suggest that chorea with striatal infarction is driven by phasic neuronal activity with a low firing rate in the globus pallidus and that the neural pathway of chorea has a functional somatotopical organization in the globus pallidus.

Action Potentials↗
PubMed2001

Molecular analysis of Japanese patients with Rett syndrome: Identification of five novel mutations and genotype-phenotype correlation.

Rett syndrome is an X-linked dominant neurodevelopmental disorder that affects females almost exclusively. The recent identification of mutations of the methyl-CpG-binding protein 2 gene (MECP2) in patients with RTT, encouraged us to analyze the gene in 37 Japanese patients divided into classical RTT (14 cases), variant RTT (13 cases), and mentally retarded patients with Rett-like features (10 cases). Mutations in MECP2 were identified from most of the patients with classical and variant RTT (25 of 27 cases). Six reported common mutations were detected in 17 cases, and rare single nucleotide substitutions were found in 3 patients. In addition, one insertion mutation (1189insA) and four deletion mutations including one double deletion mutant (451delG, 100del4, 1124del53 and 881del289 plus 1187del8) were newly identified. In the 10 mentally retarded patients with Rett-like features, however, no mutation was detected in the coding region of MECP2. The finding of MECP2 mutations in 92.5% of patients with RTT indicates that RTT fulfilling the diagnostic criteria are due to genetic alteration.

Amino Acid Substitution↗
PubMed2001

Elevated expression of vacuolar proton pump genes and cellular PH in cisplatin resistance.

V-ATPases are proton-translocating enzymes, which are found not only in numerous intracellular organelles but also in the plasma membranes of many eukaryotic cells. Using differential display, we have identified one of the proton pump subunit genes, ATP6C, as a cisplatin-inducible gene. Northern blot analysis demonstrated that expression of other members of the subunit is inducible by cisplatin treatment. Proton pump gene expression is also upregulated in 3 independent cisplatin-resistant cell lines but not in vincristine- or etoposide-resistant cell lines. Cellular pH was significantly higher in cisplatin-resistant cells than in sensitive parental cells. In vitro DNA-binding activity of cisplatin was markedly increased in acidic conditions, suggesting that the cytotoxicity of cisplatin is modulated by cellular pH. Furthermore, the proton pump inhibitor bafilomycin can synergistically potentiate the cytotoxicity of cisplatin but not of etoposide or camptothecin. These results indicate that cellular pH is one of the critical parameters for effective cancer chemotherapy with cisplatin.

Anti-Bacterial Agents↗
PubMed2001

Transcriptional suppression of Sox9 expression in chondrocytes by retinoic acid.

SOX9 is a transcription factor that is expressed in chondrocytes and regulates expression of chondrocyte phenotype related genes. Expression of these genes is known to be suppressed by retinoic acid (RA). We, therefore, examined whether the Sox9 gene expression is regulated by RA in chondrocytes. RA treatment suppressed Sox9 mRNA expression in primary chondrocytes prepared from newborn mouse rib cartilage within 12 h and this suppression lasted at least up to 24 h. The RA suppression of Sox9 mRNA levels was dose-dependent starting at 0.5 microM with a maximum at 1 microM. Nuclear run-on assays revealed that RA reduced the rate of transcription of Sox9 gene. Finally, Western blot analysis indicated that RA suppressed SOX9 protein levels in these chondrocytes. Furthermore, overexpression of SOX9 reversed RA suppression of Col2a1 enhancer activity. These observations indicate that RA suppresses Sox9 gene expression in chondrocytes at least in part through transcriptional events. J. Cell. Biochem. Suppl. 36: 71-78, 2001.

Animals↗
PubMed2001

Possible involvement of reactive oxygen species in D-galactosamine-induced sensitization against tumor necrosis factor-alpha-induced hepatocyte apoptosis.

Intravenous administration of tumor necrosis factor-alpha (TNF-alpha) (0.5 microg/mouse) caused hepatocyte apoptosis in BALB/c mice when they were sensitized with D-galactosamine (GalN, 20 mg/mouse). Activation of nuclear factor kappa B (NF-kappa B) and expression of apoptotic Bcl-2 family members were not significantly different between livers of mice treated with TNF-alpha alone and GalN + TNF-alpha, indicating that neither activation of NF-kappa B nor expression of Bcl-2 family is involved in the sensitization by GalN against TNF-alpha-induced hepatocyte apoptosis. To identify differentially expressed genes implicated in GalN-induced hepatocyte sensitization, we adopted mRNA fingerprinting using an arbitrarily primed polymerase chain reaction. The present analysis revealed that mRNA expression of extracellular antioxidant, selenoprotein P, was up-regulated in the livers after GalN administration. GalN-induced increase in its protein level was confirmed by Western blotting. Increased expression of this gene was also observed in the liver of mice treated with concanavalin A, but not anti-Fas antibody. mRNA of another antioxidant, glutathione peroxidase-1, was also up-regulated, and lipid peroxides were produced in the liver after GalN administration. Selenoprotein P mRNA level also increased in Huh-7 human hepatoma cells incubated with GalN (5 or 10 mM). Accordingly, formation of reactive oxygen species (ROS) was observed in GalN-treated Huh-7 cells. H(2)O(2) induced up-regulation of selenoprotein P mRNA and sensitized Huh-7 cells to TNF-alpha-induced apoptosis. These results suggest that ROS produced by GalN may play a pivotal role in hepatocyte sensitization toward TNF-alpha-induced apoptosis.

Animals↗