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T Inada

Publications and source records attributed to T Inada.

At least 37 records · Page 2Linked to original sources
PubMed2003

Genetic characterisation of adenovirus type 8 isolated in Hiroshima city over a 15 year period.

AIMS: To investigate the genetic differences among the strains of adenovirus type 8 (Ad8) circulating in Hiroshima city, Japan, and to study their circulation pattern. METHODS: One hundred and twenty nine strains of adenovirus type 8 (Ad8) were isolated in Hiroshima City over a 15 year period (1983-97) from patients with keratoconjunctivitis, and analysed with six restriction enzymes-BamHI, HindIII, PstI, SacI, SalI, and SmaI-to investigate possible relations among the isolates and their genetic variability. Seven hypervariable regions of the hexon gene that carry the type specific epitope were also sequenced to investigate the variation among the genome types. RESULTS: Restriction endonuclease analyses yielded three known genome types (Ad8A, 13 samples; Ad8B, seven samples; and Ad8E, 35 samples) and a novel genome type (Ad8I, 74 samples). Ad8A, Ad8B, and Ad8E were closely related, with 96% homology, whereas Ad8I had only 71% homology. Ad8A, Ad8B, and Ad8E shared 91.8% and 96.4% homology with regard to their amino acid and nucleotide sequences, respectively, with the isolate 1127 (accession no X74663). However, when compared with Ad8A, Ad8B, Ad8E, and isolate 1127, Ad8I shared only 62.7% and 69.9% homology with regard to amino acid and nucleotide sequences, respectively. Ad8A, Ad8B, and Ad8E had a unique 31 amino acid deletion in the hypervariable region 1 of the hexon gene, whereas Ad8I had a 33 residue deletion. The Ad8E strain that circulated from 1984 to 1995 was stable among the study population. Ad8I was isolated from an outbreak of epidemic keratoconjunctivitis in 1995 and was also isolated from sporadic cases until 1997. CONCLUSIONS: These results confirmed that genetic variability occurs in Ad8 in the microenvironment and revealed the emergence of a new genome type (Ad8I).

Adenoviruses, Human↗
PubMed2001

Association of ZNF74 gene genotypes with age-at-onset of schizophrenia.

Because of the manifestation of schizophrenic symptoms in individuals with interstitial deletions of chromosome 22q11.2, genes located in 22q11.2 are positional candidates for schizophrenia susceptibility. We genotyped five polymorphisms at D22S941, D22S944, D22S264, and D22S311, and the COMT gene in the common 3Mbp deletion region associated with 22q11 deletion syndrome in 300 Japanese schizophrenics and 300 controls and identified one patient with 22q11 deletion (Arinami et al., 2001). The results showed a trend of different genotypic distributions in D22S264 between patients with schizophrenia and controls (non-corrected p=0.04). Given this finding, we searched for mutations in the ZNF74 gene, which is located 11.2Kbp centromeric to D22S264. The ZNF74 gene is a member of the KRAB-zinc finger gene family and is expressed in the developing brain. Four polymorphisms, 1150T/C, IVS2a-40G/A, E/K46, and [K/N551;L/F552], were detected. The first three polymorphisms were in almost complete linkage disequilibrium. Case-control comparisons for these polymorphisms resulted in similar genotypic and allelic frequencies in patients and controls. The polymorphisms, however, were significantly associated with age-at-onset of schizophrenia (n<0.0001). Subsequent analyses in another Japanese schizophrenic population (n=169) confirmed an age-at-onset association (p<0.0001). These findings suggest that the ZNF74 gene plays a role as one of the modifying factors for schizophrenia.

Adult↗
PubMed2001

Stromal cells expressing ephrin-B2 promote the growth and sprouting of ephrin-B2(+) endothelial cells.

Ephrin-B2 is a transmembrane ligand that is specifically expressed on arterial endothelial cells (ECs) and surrounding cells and interacts with multiple EphB class receptors. Conversely, EphB4, a specific receptor for ephrin-B2, is expressed on venous ECs, and both ephrin-B2 and EphB4 play essential roles in vascular development. The bidirectional signals between EphB4 and ephrin-B2 are thought to be specific for the interaction between arteries and veins and to regulate cell mixing and the making of particular boundaries. However, the molecular mechanism during vasculogenesis and angiogenesis remains unclear. Manipulative functional studies were performed on these proteins in an endothelial cell system. Using in vitro stromal cells (OP9 cells) and a paraaortic splanchnopleura (P-Sp) coculture system, these studies found that the stromal cells expressing ephrin-B2 promoted vascular network formation and ephrin-B2(+) EC proliferation and that they also induced the recruitment and proliferation of alpha-smooth muscle actin (alpha-SMA)-positive cells. Stromal cells expressing EphB4 inhibited vascular network formation, ephrin-B2(+) EC proliferation, and alpha-SMA(+) cell recruitment and proliferation. Thus, these data suggest that ephrin-B2 and EphB4 mediate reciprocal interactions between arterial and venous ECs and surrounding cells to form each characteristic vessel. (Blood. 2001;98:1028-1037)

Animals↗
PubMed2001

Expression of the glucose transporter gene, ptsG, is regulated at the mRNA degradation step in response to glycolytic flux in Escherichia coli.

We report a novel post-transcriptional control of the ptsG gene encoding the major glucose transporter IICB(Glc). We demonstrate that the level of IICB(Glc) is markedly reduced when the glycolytic pathway is blocked by a mutation in either the pgi or pfkA gene encoding phosphoglucose isomerase or phosphofructokinase, respectively. This down-regulation of ptsG is not exerted at the transcriptional level. Both northern blot and S1 analyses demonstrate that the mutation dramatically accelerates the degradation of ptsG mRNA. The degradation of ptsG mRNA occurs in wild-type cells when alpha-methylglucoside, a non- metabolizable analog of glucose, is present in the medium. The addition of any one of the glycolytic intermediates downstream of the block prevents the degradation of ptsG mRNA. The rapid degradation of ptsG mRNA is eliminated when RNase E is thermally inactivated. We conclude that the glycolytic pathway controls ptsG expression by modulating RNase E-mediated mRNA degradation. This is the first instance in which the glycolytic flux has been shown to affect the expression of a specific gene through mRNA stability.

Citric Acid Cycle↗
PubMed2001

A low-pH culture condition enhances the radiosensitizing effect of wortmannin.

PURPOSE: The radiosensitizing effect of wortmannin on human tumor cells in a low-pH microenvironment was compared with that in a neutral-pH environment. METHODS AND MATERIALS: A172 human glioblastoma cells, A549 human lung adenocarcinoma cells, and HMV-1 human melanoma cells were treated with 20 microM wortmannin 2 h before irradiation, and cell survival was examined. A low-pH microenvironment was simulated by exposing cells to low-pH culture medium for 24 h before wortmannin treatment. The effects of wortmannin on the repair of DNA double-strand breaks (dsbs) after 50-Gy irradiation in both low- and neutral-pH conditions were measured by pulsed-field gel electrophoresis. Expression of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) in low-pH conditions was also compared with that in neutral-pH conditions by Western blot analysis. RESULTS: The radiosensitizing effect of wortmannin was greater in low-pH cultures than in neutral-pH cultures for all cell lines. The fast-rejoining component of DNA dsb repair was inhibited more strongly in low-pH than in neutral-pH conditions, although there was little difference in DNA-PKcs expression between groups. CONCLUSIONS: The low-pH culture condition, which was designed to mimic the microenvironment of the central tumor mass in actively proliferating solid tumors, enhanced the radiosensitizing effect of wortmannin by inhibiting the fast-rejoining component of DNA dsb repair and by prolonging the retention of nonrejoined DNA dsbs.

Adenocarcinoma↗
PubMed2001

Effects of propofol and thiopental on the central nervous system during nociceptive stimulation in cats.

PURPOSE: Nociceptive stimulation may increase central nervous system (CNS) activity during anesthesia. However, it is not known whether propofol and thiopental have a similar inhibitory effect on the CNS during nociceptive stimulation. Therefore, we compared the antinociceptive effects of propofol and thiopental in cats. METHODS: In 12 cats, anesthesia was induced with 4% halothane in oxygen and maintained with 0.5% halothane in oxygen. The cortical electroencephalogram (EEG) and the electrical activity from the midbrain reticular neurons (R-MUA) were measured before and after sciatic nerve stimulation. The cats were then allocated to receive cumulative doses of either propofol (n = 6) or thiopental (n = 6) i.v. at 5-min intervals. Two minutes after each dose, the cortical EEG and the R-MUA were compared before and after sciatic nerve stimulation. RESULTS: Propofol and thiopental depressed the basal R-MUA to a similar degree at each dose. Sciatic nerve stimulation increased the R-MUA, and there were no differences in the maximum R-MUA values between propofol and thiopental. The cortical EEGs after each dose of anesthetic without stimulation showed similar patterns, and the patterns of change with stimulation were also similar for these two anesthetics. CONCLUSION: Propofol and thiopental have similar antinociceptive effects in cats.

Journal Article↗
PubMed2001

Association of a 5-HT(5A) receptor polymorphism, Pro15Ser, to schizophrenia.

Several different lines of evidence suggest that genes involved in serotonergic neurotransmission are factors in the pathogenesis of schizophrenia. For example, 5-HT(5A) knockout mice revealed decreased locomotor response to lysergic diethylamide (LSD), which produces a psychotic-like state in healthy people. Recently, we reported a naturally occurring conservative Pro15Ser substitution in the 5-HT(5A) receptor. Here, we evaluate whether this substitution is associated with schizophrenia in a sample including 249 unrelated Japanese schizophrenia patients and 253 unrelated controls. Patients and controls were genotyped for the Pro15Ser polymorphism by a PCR-RFLP assay. Ser15 allele frequencies were 0.07 in patients with schizophrenia and 0.02 in controls (chi(2) = 17.42, df =1, P < 0.0001). thus, we detected a highly significant association of pro15ser to schizophrenia in a large population of japanese schizophrenia patients and controls. since case-control studies have an inherent potential for false-positive results due to population stratification, this finding is preliminary pending further studies, including studies using the transmission/disequilibrium test to eliminate stratification bias or control loci to assess ethnic matching of cases and controls.

Adult↗
PubMed2001

Olanzapine versus haloperidol in the treatment of patients with chronic schizophrenia: results of the Japan multicenter, double-blind olanzapine trial.

This randomized double-blind trial was conducted to test the efficacy and safety of olanzapine in Japanese patients with schizophrenia. Importantly, this study also represents the first large clinical trial of olanzapine conducted in an Asian population. Patients (n = 182) were randomly assigned to treatment with olanzapine or haloperidol over a period of 8 weeks. The primary analyses included: (i) a test of non-inferiority of olanzapine compared with haloperidol in efficacy using the Final Global Improvement Rating (FGIR); and (ii) comparison between the treatment groups in extrapyramidal symptom severity using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). Olanzapine was comparable to haloperidol in efficacy in treating positive symptoms and significantly superior in treating negative symptoms. Extrapyramidal symptom severity was significantly improved for olanzapine-treated patients versus haloperidol-treated patients. Olanzapine was shown to be more effective and better tolerated than haloperidol in the treatment of Japanese patients suffering from chronic schizophrenia.

Adult↗
PubMed2001

Xenon inhibits but N(2)O enhances ketamine-induced c-Fos expression in the rat posterior cingulate and retrosplenial cortices.

Both nitrous oxide (N(2)O) and xenon are N:-methyl-D-aspartate receptor antagonists that have psychotomimetic effects and cause neuronal injuries in the posterior cingulate and retrosplenial cortices. We investigated the effect of xenon, xenon with ketamine, N(2)O, and N(2)O with ketamine on c-Fos expression in the rat posterior cingulate and retrosplenial cortices, a marker of psychotomimetic effects. Brain sections were prepared, and c-Fos expression was detected with immunohistochemical methods. A loss of microtubule-associated protein 2, a marker of neuronal injury, was also investigated. The number of Fos-like immunoreactivity positive cells by ketamine IV at a dose of 5 mg/kg under 70% N(2)O (128 +/- 12 cells per 0.5 mm(2)) was significantly more than those under 30% (15 +/- 2 cells per 0.5 mm(2)) and 70% xenon (2 +/- 1 cells per 0.5 mm(2)). Despite differences in c-fos immunoreactivity, there was no loss of microtubule-associated protein 2 immunoreactivity in any group examined. Xenon may suppress the adverse neuronal effects of ketamine, and combined use of xenon and ketamine seems to be safe in respect to neuronal adverse effects.

Animals↗
PubMed2001

Propofol depressed neutrophil hydrogen peroxide production more than midazolam, whereas adhesion molecule expression was minimally affected by both anesthetics in rats with abdominal sepsis.

The treatment of sepsis may require mechanical ventilation of the lungs and sedation. Because neutrophils are the most important effector cells for protecting against sepsis, and propofol and midazolam are the most widely used anesthetics for sedation, we studied the effects of these two anesthetics on the neutrophil function during sepsis. Sepsis was induced in rats by cecal ligation and puncture. At either 4 h or 24 h after cecal ligation and puncture, blood and peritoneal neutrophils were obtained, incubated with the test anesthetics, and the hydrogen peroxide (H(2)O(2)) production and CD11b/c expression were determined by flow cytometry. In both early (at 4 h) and late (at 24 h) sepsis, propofol and midazolam depressed H(2)O(2) production by blood and peritoneal neutrophils at clinical concentrations. Propofol caused more depression than midazolam (P < 0.005). In both early and late sepsis, the effect of the anesthetics on the up-regulation of the stimulation-induced CD11b/c expression on blood neutrophils was minimal at clinical concentrations. If these results ultimately become clinically relevant, midazolam may be preferable to propofol for sedation during sepsis.

Anesthetics, Intravenous↗
PubMed2001

No leucine(7)-to-proline(7) polymorphism in the signal peptide of neuropeptide Y in Japanese population or Japanese with alcoholism.

We have screened 200 Japanese workers and 105 Japanese patients with alcoholism for the mutation in the signal peptide of pre-pro-neuropeptide Y resulting in a substitution of proline for leucine at position 7. This polymorphism was reported in the Finnish and Dutch populations recently. None of our subjects displayed the mutation at this site. Therefore, this allele does not play any role in the development of alcoholism in the Japanese population.

Alcoholism↗
PubMed2001

An exact test for the association between the disease and alleles at highly polymorphic loci with particular interest in the haplotype analysis.

The association analysis between the disease and genetic alleles is one of the simple methods for localizing the susceptibility locus in the genes. For revealing the association, several statistical tests have been proposed without discussing explicitly the alternative hypotheses. We therefore specify two types of alternative hypotheses (i.e., there is only one susceptibility allele in the locus, and there is an extension or shortening of alleles associated with the disease) and derive exact tests for the respective hypotheses. We also propose to combine these two tests when the prior knowledge is not sufficient enough to specify one of these two hypotheses. In particular, these ideas are extended to the haplotype analysis of three-way association between the disease and bivariate allele frequencies at two closely linked loci. As a by-product, a factorization of the probability distribution of the three-way cell frequencies under the null hypothesis of no three-way interaction is obtained.

Algorithms↗
PubMed2000

Wortmannin sensitizes human glioblastoma cell lines carrying mutant and wild type TP53 gene to radiation.

The purpose of this paper is to investigate the effect of wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), on TP53 (formerly known as p53) signal transduction initiated by ionizing radiation and radiosensitization in isogenic derivatives of human glioblastoma cells differing in TP53 status. Wortmannin inhibited the accumulation of TP53 and CDKN1A (formerly known as WAF1) after 6 Gy irradiation in A-172/neo cells bearing wild-type TP53. In A-172/Trp248 cells carrying mutant TP53, X-rays induced no significant accumulation of TP53 and slight increase of CDKN1A. There were, consequently, little differences in the expression of TP53 and CDKN1A between A-172/Trp248 cells exposed to 6 Gy alone and wortmannin plus 6 Gy. However, wortmannin sensitized both A-172/neo and A-172/Trp248 cells to radiation. These studies indicate that wortmannin inhibits TP53 upregulation, but this suppression does not account for the radiosensitization by this drug. These results indicate that inhibitors of PI3K-related kinases may present a new class of radiosensitizers, regardless of the TP53 status of tumor cells.

Androstadienes↗
PubMed2000

SsrA-mediated tagging and proteolysis of LacI and its role in the regulation of lac operon.

SsrA RNA of Escherichia coli, also known as 10Sa RNA or tmRNA, acts both as tRNA and mRNA when ribosomes are paused at the 3' end of an mRNA lacking a stop codon. This process, referred to as trans-translation, leads to the addition of a short peptide tag to the C-terminus of the incomplete nascent polypeptide. The tagged polypeptide is then degraded by C-terminal-specific proteases. Here, we focused on endogenous targets for the SsrA system and on a potential regulatory role of SsrA RNA. First, we show that trans-translation events occur frequently in normally growing E. COLI: cells. More specifically, we report that the lacI mRNA encoding Lac repressor (LacI) is a specific natural target for trans-translation. The binding of LacI to the lac operators results in truncated lacI mRNAs that are, in turn, recognized by the SsrA system. The SsrA-mediated tagging and proteolysis of LacI appears to play a role in cellular adaptation to lactose availability by supporting a rapid induction of lac operon expression.

Amino Acid Sequence↗
PubMed2000

A contribution to genome-wide association studies: search for susceptibility loci for schizophrenia using DNA microsatellite markers on chromosomes 19, 20, 21 and 22.

As an initial step for genome-wide association studies, we sought an association between schizophrenia and 34 microsatellite markers on chromosomes 19, 20, 21 and 22 by a case-control design. The samples examined for an association were 168 schizophrenic patients and 146 control subjects in the Japanese population. The allele distribution of the 34 loci differed significantly between Japanese and French populations. Significant deviation from the Hardy-Weinberg equilibrium was observed at D19S209 and D21S1256 in the control subjects. Case-control comparisons of the initial screening revealed a significant difference in allele frequency at D20S95 and a trend of difference at D20S118. To confirm these possible associations, additional samples consisting of 110 schizophrenic patients and 116 control subjects were examined, and an association between D20S95 and schizophrenia was confirmed (corrected P value after Bonferroni correction, 0.00035). D20S95 is located close to the gene (CHGB) encoding chromogranin B. These findings suggest that CHGB could be an important candidate gene involved in the development of schizophrenia.

Case-Control Studies↗
PubMed2000

The yeast nuclear cap binding complex can interact with translation factor eIF4G and mediate translation initiation.

The mRNA cap structure is bound by either the nuclear (CBC) or the cytoplasmic (eIF4F) cap binding complex. Following mRNA export, CBC must be exchanged for eIF4F in the cytoplasm. It is not known how this exchange occurs or how this RNP remodeling event is integrated with mRNA function. Here we report genetic and biochemical evidence that the yeast translation initiation factor eIF4G associates with CBC, and that eIF4E, the eIF4F component that binds both the cap and eIF4G, antagonizes this interaction. Furthermore, we find that CBC can stimulate translation in extracts containing an eIF4G protein deficient for eIF4E binding. These data suggest that eIF4E binding to the eIF4G-CBC complex on newly exported mRNA displaces CBC, and that the first round of translation on mRNA may occur via a different mechanism than subsequent rounds.

Cell Nucleus↗
PubMed2000

[A patient with gastric cancer with para-aortic lymph node metastases surviving for 9 years after effective preoperative chemotherapy and radical operation].

A 63-year-old male patient with type 3 advanced gastric cancer was referred to our hospital. Preoperative examination by CT-scan revealed swollen para-aortic lymph nodes and cancer invasion to the pancreas. The patient was treated pre-operatively with intravenous 5-FU, 500 mg/body/day, continuous infusion for 1 week. Immediately after the chemotherapy, the patient underwent total gastrectomy, splenctomy, left-adrenectomy and resection of the body and tail of the pancreas, along with para-aortic lymph node dissection. Microscopic examination revealed that the tumor was a moderately differentiated tubular adenocarcinoma, which displayed invasion to the pancreas with lymph node metastasis up to the level 3 lymph node. Histologically, the effect of preoperative chemotherapy showed a grade 2 effect on the main tumor, but a grade 3 chemotherapeutic effect was observed at the para-aortic lymph nodes. The patient has subsequently remained disease free for 9 years. In this case, it is considered that the preoperative chemotherapy by 5-FU and potentially curative radical operation yielded a good outcome.

Adenocarcinoma↗