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Y Someya

Publications and source records attributed to Y Someya.

At least 19 recordsLinked to original sources
PubMed2001

Ten year progressive ventricular enlargement in schizophrenia: an MRI morphometrical study.

Recent studies of the brain using magnetic resonance imaging (MRI) have suggested progressive structural changes in schizophrenics. However, those studies were conducted over periods of less than 5 years and thus lacked sufficient capacity to determine the course and nature of this process. In this study, MRI scans were obtained in 15 schizophrenics and 12 controls at baseline and after 4- and 10-year follow ups. Volumes of the lateral ventricles were measured. Patients were assessed by the Brief Psychiatric Rating Scale (BPRS) at the same two time points: at baseline and at 10-year follow up. After 10 years, a significant lateral ventricular enlargement was found in patients (mean percentage change: +22.9%) but not in controls (5.1%). Although our results are not in disagreement with the neurodevelopmental hypothesis, they do provide strong evidence that in schizophrenia progressive brain reduction occurs even in its chronic stage.

Adult↗
PubMed2001

Isolation and identification of trans-2- and trans-3-hydroxy-1,8-cineole glucosides from Alpinia galanga.

Three hydroxy-1,8-cineole glucopyranosides, (1R, 2R, 4S)- and (1S, 2S, 4R)-trans-2-hydroxy-1,8-cineole beta-D-glucopyranosides, and (1R, 3S, 4S)-trans-3-hydroxy-1,8-cineole beta-D-glucopyranoside, which are possible precursors of acetoxy-1,8-cineoles as unique aroma components, were isolated from the rhizomes of greater galangal (Alpinia galanga W.). Their structures were analyzed by FAB-MS and NMR spectrometry, and the absolute configulation of each aglycone was determined by using a GC-MS analysis with a capillary column coated with a chiral stationary phase. The composition of the diastereomers of (1R, 2R, 4S)- and (1S, 2S, 4R)-trans-2-hydroxy-1,8-cineole beta-D-glucopyranosides in the rhizomes was determined as 3:7 by a GC-MS analysis after preparing the trifluoroacetate derivatives of the glucosides.

Carbohydrate Sequence↗
PubMed2001

Human TSC-22 gene: no association with type 2 diabetes.

OBJECTIVE: In order to elucidate whether or not genetic variations of TSC-22 (TGF [transforming growth factor]-beta-stimulated clone 22), which was originally identified as a TGF-beta-responsive leucine zipper protein in murine osteoblastic cells, are associated with type 2 diabetes, the genomic organization of the human TSC-22 gene was determined and the association between its polymorphisms and type 2 diabetes was examined. RESULTS: The human TSC-22 gene spans approximately 5 kilobase pairs and is encoded in three exons. Two single nucleotide polymorphisms (SNPs) were identified in the coding region of the first exon, two other SNPs in the first intron, and one SNP in the putative promoter region. There were, however, no significant differences in the frequency of these polymorphisms between patients with type 2 diabetes and non-diabetic control subjects. CONCLUSION: It is unlikely that the TSC-22 gene is a locus responsible for type 2 diabetes.

Aged↗
PubMed2000

Complete nucleotide sequence of the chiba virus genome and functional expression of the 3C-like protease in Escherichia coli.

We cloned the genome RNA of the Chiba virus (ChV; Hu/NLV/Chiba 407/1987/JP) and determined its complete nucleotide sequence. The genome is predicted to be a positive-sense, single-stranded RNA of 7697 bases, excluding a poly(A) tract. Comparison of the nucleotide and amino acid sequences with those of other members of the species Norwalk virus (NV) revealed that ChV belongs to genogroup I NV. The ChV genome contains three open reading frames (ORFs). A large 5'-terminal ORF (ORF1) encodes a polyprotein with 1785 amino acids that are likely processed into functional proteins, including RNA helicase, VPg, protease, and RNA-dependent RNA polymerase. ORF2 encodes the capsid protein with 544 amino acids, and a small 3'-terminal ORF (ORF3) encodes a basic protein with 208 amino acids. The amino acid sequences of five cleavage sites in ORF1 are highly conserved compared with those of other members of NV. When expressed in Escherichia coli, the glutathione-S-transferase (GST) fusion protein of the ChV protease connected via a short peptide containing a human rhinovirus 3C protease cleavage site was cleaved into GST and the protease; however, this cleavage did not occur when the Cys mutation was introduced into the putative active site of the protease. Moreover, the ChV protease recognized and cleaved the predicted proteolytic sites between VPg and protease and between protease and RNA polymerase. Therefore, the ChV protease expressed in E. coli retained an enzymatic activity and a substrate specificity similar to that of the human rhinovirus 3C protease.

3C Viral Proteases↗
PubMed2000

Sustained enhancement of Ca(2+) influx by glibenclamide induces apoptosis in RINm5F cells.

Cytosolic Ca(2+) elevations are known to be involved in triggering apoptosis in many tissues, but the effect of sustained enhancement of Ca(2+) influx on apoptosis in beta cells remains unknown. We have found that the viability of RINm5F cells is decreased dose-dependently by continuous exposure to glibenclamide at concentrations from 10(-7) to 10(-4) M, and that this effect is partially ameliorated by pretreatment with cycloheximide. Electrophoresis of the cells exposed to glibenclamide revealed ladder-like fragmentation characteristic of apoptosis, and which also is suppressed by cycloheximide pretreatment. By using terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, we detected increased DNA fragmentation in the nuclei of the cells exposed to glibenclamide, and staining with Hoechst 33342 and propidium iodide showed a dose-dependent increase in the number of cells with the chromatin condensation and fragmentation in their nuclei that is characteristic of apoptosis. The effects of glibenclamide on cell viability and apoptotic cell death were partially inhibited by treatment with Ca(2+) channel blocker, and by reducing the extracellular Ca(2+) concentration during glibenclamide exposure, suggesting that they may be derived from increased Ca(2+) influx. Furthermore, only the percentage of apoptotic cells, and not that of necrotic cells, increased with the increasing intracellular Ca(2+) concentration during glibenclamide exposure. In conclusion, we have demonstrated that the sustained enhancement of Ca(2+) influx caused by glibenclamide exposure can induce apoptotic cell death in a pure beta cell line.

Animals↗
PubMed2000

Role of the charge interaction between Arg(70) and Asp(120) in the Tn10-encoded metal-tetracycline/H(+) antiporter of Escherichia coli.

We reported that the positive charge of Arg(70) is mandatory for tetracycline transport activity of Tn10-encoded metal-tetracycline/H(+) antiporter (TetA(B)) (Someya, Y., and Yamaguchi, A. (1996) Biochemistry 35, 9385-9391). Arg(70) may function through a charge-pairing with a negatively charged residue in close proximity. Therefore, we mutated Asp(66) and Asp(120), which are only two negatively charged residues located close to Arg(70) in putative secondary structure of TetA(B) and highly conserved throughout transporters of the major facilitator superfamily. Site-directed mutagenesis studies revealed that Asp(66) is essential, but Asp(120) is important for TetA(B) function. Surprisingly, when Asp(120) was replaced by a neutral residue, the R70A mutant recovered tetracycline resistance and transport activity. There was no such effect in the Asp(66) mutation. The charge-exchanged mutant, R70D/D120R, also showed significant drug resistance and transport activity (about 50% of the wild type), although the R70D mutant had absolutely no activity, and the D120R mutant retained very low activity (about 10% of the wild type). Both the R70C and D120C mutants were inactivated by N-ethylmaleimide. Mercuric ion (Hg(2+)), which gives a positive charge to a SH group of a Cys residue through mercaptide formation, had an opposite effect on the R70C and D120C mutants. The activity of the R70C mutant was stimulated by Hg(2+); however, on the contrary, the D120C mutant was partially inhibited. On the other hand, the R70C/D120C double mutant was almost completely inactivated by Hg(2+), probably because the side chains at positions 70 and 120 are bridged with Hg(2+). The close proximity of positions 70 and 120 were confirmed by disulfide cross-linking formation of the R70C/D120C double mutant when it was oxidized by copper-(1,10-phenanthroline). These results indicate that the positive charge of Arg(70) requires the negative charge of Asp(120) for neutralization, probably for properly positioning transmembrane segments in the membrane.

Antiporters↗
PubMed2000

Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography.

Using positron emission tomography (PET) and [11C]N-methylspiperone (NMSP), we examined 5-HT2 receptors in the cortex of schizophrenic patients in whom we previously observed decreased prefrontal D1 receptor binding. The subjects were 10 neuroleptic-naive schizophrenic patients, 7 schizophrenic patients who were drug-free but had previously been treated with neuroleptics, and 12 normal controls. A non-significant trend towards decreased prefrontal [11C]NMSP binding was observed in the neuroleptic-treated patients, suggesting a possible effect of previous neuroleptic treatment on the alteration in cortical 5-HT2 function. However, the neuroleptic-naive patients showed no noticeable difference in cortical [11C]NMSP binding compared to controls. Our results do not rule out the role of 5-HT2 function as a crucial site of therapeutic activity of schizophrenia, but they do suggest that cortical 5-HT2 receptors might not be primarily involved in the pathophysiology of schizophrenia.

Adult↗
PubMed2000

Seizure frequency and bilateral temporal abnormalities: a proton magnetic resonance spectroscopy of temporal lobe epilepsy.

Proton magnetic resonance spectroscopy ((1)H-MRS) was performed in seven healthy volunteers and 17 patients with temporal lobe epilepsy (TLE) to clarify the correlation of the severity of epilepsy with bilateral temporal changes in N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine + phosphocreatine (Cr). Despite unilateral EEG focus, bilateral temporal reduction in NAA /(Cho + Cr) was revealed in patients with intractable seizures. The potential for seizure generation correlated with the NAA /(Cho + Cr) reduction not only on the ipsilateral side but also on the contralateral side. Proton MRS proved to be a useful measurement for obtaining important information about the neuronal changes as well as the lateralization of the epileptogenic focus in TLE patients.

Adult↗
PubMed2000

Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression.

Insulin plays a crucial role in the regulation of glucose-homeostasis, and its synthesis is regulated by several stimuli. The transcription of the human insulin gene, enhanced by an elevated intracellular concentration of calcium ions, was completely blocked by Ca2+/calmodulin-dependent protein kinase inhibitor. The activity of the transcription factor activating transcription factor-2 (ATF-2), which binds to the cAMP responsive elements of the human insulin gene, was enhanced by Ca2+/calmodulin-dependent protein kinase IV (CaMKIV). Mutagenesis studies showed that Thr69, Thr71, and Thr73 of ATF-2 are all required for activation by CaMKIV. CaMKIV-induced ATF-2 transcriptional activity was not altered by activation of cJun NH2-terminal protein kinase (JNK) or p38 mitogen-activated protein (MAP) kinase. Furthermore, when transfected into rat primary cultured islets, ATF-2 enhanced glucose-induced insulin promoter activity, whereas cAMP response element-binding protein (CREB) repressed it. These results suggest a mechanism in which ATF-2 regulates insulin gene expression in pancreatic beta-cells, with the transcriptional activity of ATF-2 being increased by an elevated concentration of calcium ions.

Activating Transcription Factor 2↗
PubMed2000

[Caliciviruses].

Explore the source record for details and available documents.

Acute Disease↗
PubMed1999

The cyclic AMP response element modulator family regulates the insulin gene transcription by interacting with transcription factor IID.

We analyzed a mechanism of transcriptional regulation of the human insulin gene by cyclic AMP response element modulator (CREM) through four cyclic AMP response elements (CREs). We isolated two novel CREM isoforms (CREMDeltaQ1 and CREMDeltaQ2), which lack one of the glutamine-rich domains, Q1 and Q2 respectively, and six known isoforms (CREMtaualpha, CREMalpha, inducible cyclic AMP early repressor (ICER) I, ICER Igamma, CREM-17X, and CREM-17) from rat pancreatic islets and the RINm5F pancreatic beta-cell line. CREM isoforms functioned as efficient transcriptional activators or repressors to modulate insulin promoter activity by binding to all of the insulin CREs. The binding activity of repressors is higher than that of activators and suppressed not only basal activity but also activator-induced activities. Furthermore, CREM activator interacted directly with the transcription factor IID components hTAF(II)130 and TATA box-binding protein (TBP). These results suggest that the activation of the insulin gene transcription by CREM activator is mediated by not only direct binding to the CREs but also by recruiting transcription factor IID to the insulin promoter via its interaction with hTAF(II)130 and TBP. On the other hand, the CREM repressor ICER competitively interrupts the binding of the activators to CREs and does not interact with either TBP or hTAF(II)130; therefore, it might fail to stabilize the basal transcriptional machinery and repress transactivation.

Animals↗
PubMed1999

The MH1 domains of smad2 and smad3 are involved in the regulation of the ALK7 signals.

The biological responses of the transforming growth factor beta (TGF-beta) superfamily are induced by activation of a receptor complex and Smad proteins. We surveyed the TGF-beta superfamily receptors using the degenerate PCR strategy, and found activin receptor-like kinase 7 (ALK7) to be abundantly expressed in fetal rat pancreatic islets. ALK7 is also expressed in adult rat islets and pancreatic beta-cell-derived MIN6 cells. The constitutively active form of ALK7, ALK7(T194D), activated Smad3 and a chimeric Smad protein, Smad3-2, containing the MH1 domain of Smad3 and the MH2 domain of Smad2, and translocated them to nuclei and then induced activation of the human PAI-1 promoter. However, neither Smad2 nor Smad2-3 protein, containing the MH1 domain of Smad2 and the MH2 domain of Smad3 were activated. These results indicate that the ALK7 signal regulates nuclear localization and activation of Smad2 and Smad3, and the MH1 domain of Smad2 has inhibitory effects on the nuclear localization.

Activin Receptors↗
PubMed1999

Enantiomeric purity and odor characteristics of 2- and 3-acetoxy-1, 8-cineoles in the rhizomes of Alpinia galanga willd.

(S)-(+)-O-methylmandelate esters of trans- and cis-1,3, 3-trimethyl-2-oxabicyclo[2.2.2]octan-5- and 6-ols (2- and 3-hydroxy-1,8-cineoles) were prepared, and eight diastereomers were separated. The absolute configuration of the asymmetric carbons of the cineole moiety of each diastereomer was determined by (1)H NMR data according to the Mosher theory. Each mandelate was reduced with LiAlH(4) to obtain optically pure hydroxy-1,8-cineoles, this being followed by acetylation to afford optically pure acetoxy-1, 8-cineoles. These acetates were subjected to chiral GC, using a cyclodextrin column, and the enantiomeric purity of trans- and cis-1, 3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5- and 6-yl acetates in the aroma concentrate from the rhizomes of Alpinia galanga was determined as 93.9 (5S), 19.4 (5R), 63.5 (6R), and 100 (6R) % ee, respectively. The aroma character of each enantiomer was also evaluated by GC-sniffing.

Aluminum Compounds↗
PubMed1999

Novel characteristic for distinguishing Lactococcus lactis subsp. lactis from subsp. cremoris.

Lactococcus lactis strains were examined for their ability to produce gamma-aminobutyric acid (GABA). Results showed that strains of L. lactis subsp. lactis were able to produce this acid, whereas L. lactis subsp. cremoris were not. GABA production thus represents another effective characteristic for distinguishing L. lactis subsp. lactis from L. lactis subsp. cremoris.

Glutamate Decarboxylase↗
PubMed1998

Transcriptional repressors are increased in pancreatic islets of type 2 diabetic rats.

To further clarify the mechanism of impaired insulin gene transcription in the diabetic state, we investigated the expression and function of the transcriptional repressor CREM (CRE modulator) in rat pancreatic islets. The CREM gene generates both transcriptional activators and repressors by alternative splicing and an intronic promoter. We isolated a novel alternatively spliced CREM isoform, CREM-17X, which efficiently represses insulin gene transcription, in addition to the three previously reported repressors. We also compared mRNA levels of insulin and the CREM repressors in pancreatic islets of Wistar and GK (Goto-Kakizaki) rats, the well-characterized spontaneous animal model of type 2 diabetes. The CREM repressor levels are increased, and the expression of insulin mRNA is decreased in GK rats, suggesting that increased CREM repressor expression in pancreatic islets could contribute to the decreased insulin gene transcription that results in impaired insulin secretion in type 2 diabetes.

Animals↗
PubMed1998

Production of gamma-aminobutyric acid by cheese starters during cheese ripening.

Nine mixed-strain starters were examined for their abilities to produce gamma-aminobutyric acid. Six commercial starters were found to produce gamma-aminobutyric acid in a skim milk culture. The bacterium that produced gamma-aminobutyric acid was isolated from the mixed-strain starters, identified as citrate-utilizing Lactococcus lactis ssp. lactis (formerly L. lactis ssp. lactis biovar diacetylactis) and designated as strain 01-7. A cell extract showed glutamate decarboxylase activity, for which the optimum pH was 4.7. In pH-controlled cultivation, gamma-aminobutyric acid was generated at pH 5.0 but not above pH 5.5. Cheeses were prepared experimentally using strain 01-7 to determine the relationship between the pH values and the production of gamma-aminobutyric acid during cheese ripening. gamma-Aminobutyric acid increased linearly in the experimental cheeses as the pH of the cheese decreased. Based on these results, gamma-aminobutyric acid was concluded to be produced by the cheese starters during ripening.

Cheese↗
PubMed1997

Second-site suppressor mutations for the Arg70 substitution mutants of the Tn10-encoded metal-tetracycline/H+ antiporter of Escherichia coli.

The positive charge of the Arg70 residue in the cytoplasmic loop of the Tn10-encoded metal-tetracycline/H+ antiporter (Tet(B)) of Escherichia coli is essential for the tetracycline transport function (Y. Someya and A. Yamaguchi, Biochemistry 35, 9385-9391 (1996)). In this study, we found that the R70A mutation was suppressed by the second-site mutation of Thr171 to Ser. The T171S mutation suppressed any mutations at position 70 regardless of the amino acid residue introduced. The R70A and R70C mutations were also suppressed by the T171A or T171C mutations, but not by the T171Y mutation, indicating that the decrease in the side chain volume at position 171 is essential for the suppression. Tetracycline transport activity of the R70C mutant was stimulated by Hg2+ because mercaptide formed between the SH group of Cys70 and Hg2+ worked as a functional positively-charged side chain. The activity of the R70A/R71C/T171S mutant was also stimulated by Hg2+, whereas those of the R70A/R71C, R71C, and R71C/T171S mutants were not, indicating that the T171S mutation causes the switching of the functional positive charge at position 70 to 71. Since Thr171 is in the middle of the transmembrane helix VI, the switching may be based on a remote conformational effect.

Anti-Bacterial Agents↗