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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

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

Adenovirus is a key pathogen in hemorrhagic cystitis associated with bone marrow transplantation.

Late-onset hemorrhagic cystitis (HC) is a well-known complication of bone marrow transplantation (BMT) that is mainly attributed to infection with BK virus (BKV) and adenovirus (AdV). From 1986 through 1998, 282 patients underwent BMT, and 45 of them developed HC. Urine samples tested positive for AdV in 26 patients, of which 22 showed virus type 11. Among patients who underwent allogeneic BMT, logistic regression analysis revealed acute graft-versus-host disease (grade, > or = 2) to be the most significant predictive factor for HC (P < .0001). In addition, a total of 193 urine samples regularly obtained from 26 consecutive patients who underwent allogeneic BMT were examined for BKV, JC virus (JCV), and AdV by means of polymerase chain reaction. Of patients without HC, approximately 30% of the specimens tested positive for BKV (58 samples) and JCV (55 samples), whereas 5 (3%) tested positive for AdV. Of the 3 samples obtained from patients with HC, the numbers of positive results for BKV, JCV, and AdV were 3, 1, and 1, respectively; the numbers of positive results increased to 14 of 17, 9 of 17, and 10 of 17, respectively, when we added another 14 samples obtained from 14 patients with HC (P < .0001, P = .026, and P < .0001, respectively). In conclusion, there was significant correlation between AdV and HC in the patients we studied.

Adenovirus Infections, Human↗
PubMed2001

Modulation of oscillatory neural activities by cholinergic activation of interneurons in the olfactory center of a terrestrial slug.

The neurons in the procerebrum (PC) of the terrestrial slug Limax marginatus show regular oscillation of their membrane potential, and the oscillation has been implicated in olfactory processing. The neural mechanisms for the generation and modulation of the oscillation have been poorly understood. In the present work, we examined the ionic conductances evoked by acetylcholine (ACh) in the PC neurons and the effects of ACh application on the population activities of intrinsic and extrinsic neurons. The PC neurons are categorized into bursting neurons, which are putative local inhibitory neurons, and nonbursting neurons, which likely mediate the input and output of information in the PC. Bath application of ACh augmented the local field potential oscillation in the PC. Perforated patch recording from single PC neurons revealed that ACh has direct excitatory effects on bursting neurons, while it suppresses the activity of nonbursting neurons, possibly via augmented inhibitory synaptic input from bursting neurons. The correlation between the membrane potential of bursting neurons and the frequency of oscillation suggests that bursting neurons are the main determinant of the oscillation frequency. Application of ACh also resulted in a reduction of the oscillation amplitude in the olfactory nerve, suggesting that the frequency modulation in the oscillatory network could change the activities in the follower neurons.

Acetylcholine↗
PubMed2001

A deteriorated triple-helical scaffold accelerates formation of the Tetrahymena ribozyme active structure.

The Tetrahymena group I ribozyme requires a hierarchical folding process to form its correct three-dimensional structure. Ribozyme activity depends on the catalytic core consisting of two domains, P4-P6 and P3-P7, connected by a triple-helical scaffold. The folding proceeds in the following order: (i) fast folding of the P4-P6 domain, (ii) slow folding of the P3-P7 domain, and (iii) structure rearrangement to form the active ribozyme structure. The third step is believed to directly determine the conformation of the active catalytic domain, but as yet the precise mechanisms remain to be elucidated. To investigate the folding kinetics of this step, we analyzed mutant ribozymes having base substitution(s) in the triple-helical scaffold and found that disruption of the scaffold at A105G results in modest slowing of the P3-P7 folding (1.9-fold) and acceleration of step (iii) by 5.9-fold. These results suggest that disruption or destabilization of the scaffold is a normal component in the formation process of the active structure of the wild type ribozyme.

Animals↗
PubMed2001

Influence of age on the results of brachytherapy for early tongue cancer.

PURPOSE: To determine the influence of elder age on the results of brachytherapy for early (T1-2 N0 M0) oral tongue cancer and examine the compatibility of low-dose rate (LDR) with high-dose rate (HDR) brachytherapy. METHODS AND MATERIALS: We analyzed 591 patients treated at Osaka University Hospital between 1967 and 1999. We compared the results of radiotherapy for 156 elderly patients (137 LDR and 19 HDR) 65 years of age or older and 435 patients (383 LDR and 52 HDR) less than 65 years of age. RESULTS: HDR brachytherapy showed the same local control rate as LDR brachytherapy (81% at 3 years). Elderly patients showed a poorer local control rate (75% at 3 years) than the younger group (83% at 3 years)(p = 0.002). Multivariate analysis identified age as the only prognostic factor for local control (p = 0.002). CONCLUSIONS: HDR brachytherapy achieved the same result as LDR brachytherapy. However, the elderly patient showed a higher rate of local recurrence after brachytherapy.

Adult↗
PubMed2001

Clinical significance of antibody against oxidized low density lipoprotein in patients with atherosclerotic coronary artery disease.

OBJECTIVES: This study was designed to establish the clinical significance of antibodies against oxidized low density lipoprotein (anti-Ox-LDL) titer in atherosclerotic coronary artery disease (CAD). BACKGROUND: Oxidative modification of LDL, which plays a key role in the development of atherosclerosis, induces immunogenic epitopes in the LDL molecule, and the presence of anti-Ox-LDL has been demonstrated in human sera. METHODS: Anti-Ox-LDL titer was measured by enzyme-linked immunosorbent assay in 108 patients who had angiographically verified CAD, and 31 patients who had chest pain but no significant CAD, as controls. RESULTS: The anti-Ox-LDL titer was higher (p < 0.01) in patients with multivessel CAD (19.4 +/- 10.1 AcU/ml, n = 68) than in the controls (9.8 +/- 4.1). However, no significant difference was shown between the single-vessel CAD group (15.1 +/- 6.4, n = 40) and the controls, or between the multivessel CAD group and the single-vessel CAD group. The titer was higher in patients with unstable angina (21.5 +/- 11.8 AcU/ml, n = 20, p < 0.01), or in patients with acute myocardial infarction (23.1 +/- 12.0, n = 20, p < 0.01) than in patients with stable-effort angina or old myocardial infarction (12.2 +/- 8.6, n = 68). Multiple logistic regression analysis indicated that the anti-Ox-LDL titer most powerfully discriminated CAD patients from controls (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.07-1.33, p = 0.0006) and acute coronary syndrome from chronic CAD (OR: 1.09, 95% CI: 1.04-1.14, p = 0.0008). CONCLUSIONS: Serum anti-Ox-LDL titer not only can predict a presence of atherosclerotic CAD but also may be a marker of plaque instability. Low density lipoprotein oxidation may play an important role in the development of plaque instability.

Aged↗
PubMed2001

XAFS study on metal endohedral fullerenes.

Structure of metal endohedral fullerenes is studied by XAFS and XANES. The Sc-Sc distance of 2.23(1) A determined from Sc K-edge XAFS supports the formation of a triangular Sc3 cluster in Sc3@C82 as is found by MEM analysis for the X-ray diffraction. Gd L(III)-edge XAFS of Gd@C82 shows that the first and the second neigboring Gd-C distances are 2.51(2) and 2.85(4) A, respectively. The La-La distance of La2@C80 has been determined to be 3.90(1) A at 40 K. This value does not change when increasing temperature [3.90(2) A at 240 K]. The position and the valenece of the Eu atom in Eu@C60 are also discussed based on Eu L(III)-edge XAFS and XANES.

Journal Article↗
PubMed2001

The mechanism of aubstrate eecognition of pyroglutamyl-peptidase I from Bacillus amyloliquefaciens as determined by X-ray crystallography and site-directed mutagenesis.

Pyroglutamyl-peptidase is able to specifically remove the amino-terminal pyroglutamyl residue protecting proteins or peptides from aminopeptidases. To clarify the mechanism of substrate recognition for the unique structure of the pyrrolidone ring, x-ray crystallography and site-directed mutagenesis were applied. The crystal structure of pyroglutamyl-peptidase bound to a transition state analog inhibitor (Inh), pyroglutaminal, was determined. Two hydrogen bonds were located between the main chain of the enzyme and the inhibitor (71:O.H-N:Inh and Gln71:N-H.OE:Inh), and the pyrrolidone ring of the inhibitor was inserted into the hydrophobic pocket composed of Phe-10, Phe-13, Thr-45, Ile-92, Phe-142, and Val-143. To study in detail the hydrophobic pocket, Phe-10, Phe-13, and Phe-142 were selected for mutation experiments. The k(cat) value of the F10Y mutant decreased, but the two phenylalanine mutants F13Y and F142Y did not exhibit significant changes in kinetic parameters compared with the wild-type enzyme. The catalytic efficiencies (k(cat)/K(m)) for the F13A and F142A mutants were less than 1000-fold that of the wild-type enzyme. The x-ray crystallographic study of the F142A mutant showed no significant change except for a minor one in the hydrophobic pocket compared with the wild type. These findings indicate that the molecular recognition of pyroglutamic acid is achieved through two hydrogen bonds and an insertion in the hydrophobic pocket. In the pocket, Phe-10 is more important to the hydrophobic interaction than is Phe-142, and furthermore Phe-13 serves as an "induced fit" mechanism.

Amino Acid Sequence↗
PubMed2001

New 5-HT1A receptor agonists possessing 1,4-benzoxazepine scaffold exhibit highly potent anti-ischemic effects.

A series of new 3-substituted-4-(4-aminobutyl)-1,4-benzoxazepin-5(4H)-one derivatives (1-5) which showed a very high affinity for 5-HT1A receptor with good selectivity over dopamine D2 receptor was synthesized. Among these compounds, 3-chloro-4-[4-[4-(2-pyridinyl)-1,2,3,6-tetrahydropyridin-1-yl]butyl]-1,4-benzoxazepin-5(4H)-one (5: SUN N4057) exhibited remarkable neuroprotective activity in a transient middle cerebral artery occlusion (t-MCAO) model.

Animals↗
PubMed2001

Crystal structure of DNA polymerase from hyperthermophilic archaeon Pyrococcus kodakaraensis KOD1.

The crystal structure of family B DNA polymerase from the hyperthermophilic archaeon Pyrococcus kodakaraensis KOD1 (KOD DNA polymerase) was determined. KOD DNA polymerase exhibits the highest known extension rate, processivity and fidelity. We carried out the structural analysis of KOD DNA polymerase in order to clarify the mechanisms of those enzymatic features. Structural comparison of DNA polymerases from hyperthermophilic archaea highlighted the conformational difference in Thumb domains. The Thumb domain of KOD DNA polymerase shows an "opened" conformation. The fingers subdomain possessed many basic residues at the side of the polymerase active site. The residues are considered to be accessible to the incoming dNTP by electrostatic interaction. A beta-hairpin motif (residues 242-249) extends from the Exonuclease (Exo) domain as seen in the editing complex of the RB69 DNA polymerase from bacteriophage RB69. Many arginine residues are located at the forked-point (the junction of the template-binding and editing clefts) of KOD DNA polymerase, suggesting that the basic environment is suitable for partitioning of the primer and template DNA duplex and for stabilizing the partially melted DNA structure in the high-temperature environments. The stabilization of the melted DNA structure at the forked-point may be correlated with the high PCR performance of KOD DNA polymerase, which is due to low error rate, high elongation rate and processivity.

Amino Acid Sequence↗
PubMed2001

Identification of CRE1 as a cytokinin receptor from Arabidopsis.

Cytokinins are a class of plant hormones that are central to the regulation of cell division and differentiation in plants. It has been proposed that they are detected by a two-component system, because overexpression of the histidine kinase gene CKI1 induces typical cytokinin responses and genes for a set of response regulators of two-component systems can be induced by cytokinins. Two-component systems use a histidine kinase as an environmental sensor and rely on a phosphorelay for signal transduction. They are common in microorganisms, and are also emerging as important signal detection routes in plants. Here we report the identification of a cytokinin receptor. We identified Arabidopsis cre1 (cytokinin response 1) mutants, which exhibited reduced responses to cytokinins. The mutated gene CRE1 encodes a histidine kinase. CRE1 expression conferred a cytokinin-dependent growth phenotype on a yeast mutant that lacked the endogenous histidine kinase SLN1 (ref. 10), providing direct evidence that CRE1 is a cytokinin receptor. We also provide evidence that cytokinins can activate CRE1 to initiate phosphorelay signalling.

Arabidopsis↗
PubMed2001

FK960, a novel potential anti-dementia drug, enhances high K(+)-evoked release of somatostatin from rat hippocampal slices.

We have demonstrated that FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a novel putative anti-dementia drug of piperazine derivative, ameliorates memory deficits in a variety of animal models of dementia in rats and monkeys, and also augments long-term potentiation (LTP) in the mossy fiber-CA3 pathway in guinea-pig hippocampal slices. Our recent studies have further suggested that somatostatin activation could be a primary mechanism of the pharmacological action of FK960. To clarify the mode of action of FK960 on somatostatinergic neurotransmission, FK960 was examined for its effects on somatostatin release from rat hippocampal slices. FK960 significantly enhanced high K(+)-evoked release, but not basal release, of somatostatin with similar concentration-dependency to its LTP augmenting action. On the other hands, FK960 had no effects on the release of neurotransmitters such as acetylcholine, 5-HT, D-aspartate or GABA from hippocampal slices. Our results provide compelling evidence that FK960 exerts specific and facilitatory actions on neural mechanisms involved in the activity-dependent release of somatostatin from nerve terminals of the hippocampus. These results also strengthen the view that FK960 regulates cognitive functions and augments LTP through an activation of the somatostatinergic nervous system in the hippocampus.

Acetylcholine↗
PubMed2001

Downregulation of MDM2 stabilizes p53 by inhibiting p53 ubiquitination in response to specific alkylating agents.

p53 is stabilized in response to DNA damaging stress. This stabilization is thought to result from phosphorylation in the N-terminus of p53, which inhibits p53:MDM2 binding, and prevents MDM2 from promoting p53 ubiquitination. In this report, the DNA alkylating agents mitomycin C (MMC) and methylmethane sulfonate (MMS), as well as UV radiation, stabilized p53 in a manner independent of phosphorylation in p53 N-terminus. This stabilization coincided with decreased levels of MDM2 mRNA and protein, and a corresponding decrease in p53 ubiquitination. Importantly, MDM2 overexpression inhibited the stabilization of p53 and decrease in ubiquitination following MMC, MMS, and UV treatment. This indicates that downregulation of MDM2 contributes to the stabilization of p53 in response to these agents.

Alkylating Agents↗
PubMed2001

The basic helix-loop-helix gene hesr2 promotes gliogenesis in mouse retina.

Members of a subclass of hairy/Enhancer of split [E(spl)] homologs, called hesr genes, are structurally related to another subclass of hairy/E(spl) homologs, Hes genes, which play an important role in neural development. To characterize the roles of hesr genes in neural development, we used the retina as a model system. In situ hybridization analysis indicated that all hesr genes are expressed in the developing retina, but only hesr2 expression is associated spatially with gliogenesis. Each member was then misexpressed with retrovirus in the retinal explant cultures prepared from mouse embryos or neonates, which well mimic in vivo retinal development. Interestingly, hesr2 but not hesr1 or hesr3 promoted gliogenesis while inhibiting rod genesis without affecting cell proliferation or death, suggesting that the cells that normally differentiate into rods adopted the glial fate by misexpression of hesr2. The gliogenic activity of hesr2 was more profound when it was misexpressed postnatally than prenatally. In addition, double mutation of the neuronal determination genes Mash1 and Math3, which increases Müller glia at the expense of bipolar cells, upregulated hesr2 expression. These results indicate that, among structurally related hesr genes, only hesr2 promotes glial versus neuronal cell fate specification in the retina and that antagonistic regulation between hesr2 and Mash1-Math3 may determine the ratios of neurons and glia.

Animals↗
PubMed2001

Synthesis and antifungal activities of novel 1,3-beta-D-glucan synthase inhibitors. Part 1.

Highly potent 1,3-beta-D-glucan synthase inhibitors 10, 11 and 13 have been identified by the chemical modification of the fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. D-Ornithine derivative (10) showed improved antifungal activity in the systemic candidiasis model in mice and reduced hepatotoxicity in vitro, as compared with 1.

Animals↗
PubMed2001

The effects of propofol on NMDA- or nitric oxide-mediated neurotoxicity in vitro.

Acute brain ischemia causes neurotoxic cascades including NMDA receptors and NO. Propofol, an i.v. anesthetic, is thought to have a neuroprotective effect. We investigated the influence of propofol on NMDA/NO neurotoxicity using Shibuta's established model of primary brain cultures. Cortical neurons prepared from E16 were used after 13-14 days in culture. The neurons were exposed to various concentrations of propofol with NMDA or NO-donor. The survival rates of neurons exposed to 30 microM NMDA with or without 300 microM propofol were 12.1 +/- 2.2% and 11.9 +/- 2.2%, respectively. The survival rates exposed to 30 microM NO-donor with or without 300 microM propofol were 11.2 +/- 4.2% and 14.0 +/- 3.9%, respectively. These results suggest that neuroprotective effect of propofol is limited and propofol does not offer advantages over thiopental against NMDA/NO-induced cytotoxicity.

Animals↗
PubMed2001

Regulation of fibronectin expression and splicing in migrating epithelial cells: migrating MDCK cells produce a lesser amount of, but more active, fibronectin.

Previously we have demonstrated that in MDCK epithelial cells not only transforming growth factor-beta (TGF-beta) but also hepatocyte growth factor/scatter factor (HGF/SF) regulates fibronectin (FN) splicing by increasing the ratio of EDA-containing FN (EDA+ FN) mRNA to EDA-minus FN (EDA- FN) mRNA (EDA+/EDA- ratio). EDA+ FN is known to be upregulated in tissues where cells actively migrate, such as those during morphogenesis, wound healing, and tumorigenesis. However, a direct association between cell migration and FN splicing at the EDA region has never been investigated. In this work, we have shown by using an in vitro wound migration assay that migrating epithelial cells regulate FN production and splicing differently compared to nonmigrating cells. Wounds were introduced as migration stimuli into the 10-day-old confluent cell sheet, where the EDA+/EDA- ratio and FN mRNA expression levels were stable. In migrating cells at the wound edge, the FN mRNA level decreased by 0.73-fold and the EDA+/EDA- ratio increased by 1.32-fold when compared with nonmigrating cells apart from the wound edge. HGF/SF significantly stimulated cell migration at the wound edge and concomitantly decreased the FN mRNA level by 0.60-fold and increased the EDA+/EDA- ratio by 1.84-fold in migrating cells. In nonmigrating cells apart from the wound edge, FN mRNA expression and splicing were not influenced by either wound stimulation or HGF/SF. EDA+ FN stimulates cell migration more effectively than EDA- FN and thus is considered to be a more active variant of FN. Taken together, migrating MDCK cells appear to regulate FN mRNA expression and splicing to produce a lesser amount of, but more active, FN.

Animals↗
PubMed2001

Opposing pharmacological actions of cepharanthin on lipopolysaccharide-induced histidine decarboxylase activity in mice spleens.

A biscoclaurin alkaloid preparation, cepharanthin (Ceph), is reported to have opposing pharmacological effects, enhancement or depression, on several cells and tissues, although detailed mechanisms remain unclear. Previously, we reported that Ceph enhanced lipopolysaccharide (LPS)-induced histidine decarboxylase (HDC) activity in mice spleens by consecutive pre-administration. In this study, we examined the pharmacological effects on HDC activity of a single Ceph pre-administration to test the influence of the administration method. Consequently, HDC activities were decreased by a single administration 15 minutes before LPS challenge in ddY and ICR mice spleens. Moreover, to further examine this suppressing effect, we employed genetically mast cell-deficient WBB6F1 W/Wv (W/Wv) mice to avoid the influence of mast cells. In W/Wv mice, HDC activity was enhanced, but not in the congenic WBB6F1 +/+ mice. These findings suggest that mast cells influence the depressant effect on HDC activity by a Ceph single administration in mast cell sufficient mice.

Alkaloids↗