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T Iwamoto

Publications and source records attributed to T Iwamoto.

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

First results from KamLAND: evidence for reactor antineutrino disappearance.

KamLAND has measured the flux of nu;(e)'s from distant nuclear reactors. We find fewer nu;(e) events than expected from standard assumptions about nu;(e) propagation at the 99.95% C.L. In a 162 ton.yr exposure the ratio of the observed inverse beta-decay events to the expected number without nu;(e) disappearance is 0.611+/-0.085(stat)+/-0.041(syst) for nu;(e) energies >3.4 MeV. In the context of two-flavor neutrino oscillations with CPT invariance, all solutions to the solar neutrino problem except for the "large mixing angle" region are excluded.

Journal Article↗
PubMed2003

Effect of the neuronal nitric oxide synthase inhibitor 7-nitroindazole on the righting reflex ED50 and minimum alveolar concentration during sevoflurane anaesthesia in rats.

BACKGROUND AND OBJECTIVE: The aim was to determine the effect of acute and chronic administration of 7-nitroindazole, a selective neuronal nitric oxide synthase inhibitor, on the righting reflex ED50 and the minimum alveolar concentration during sevoflurane anaesthesia in rats. METHODS: 7-Nitroindazole was acutely (0, 50 and 100 mg kg(-1)) and chronically (0 and 150 mg kg(-1) day(-1), 4 days) administered to rats. After the preparation, the minimum alveolar concentration and the righting reflex ED50 were measured. The concentration of cGMP in the brain, cerebellum and spinal cord was also measured. RESULTS: Acute administration reduced the minimum alveolar concentration (50 mg kg(-1), 58.8% (95% CI: 50.3-67.3%) of the baseline value, P < 0.01; 100 mg kg(-1), 55.8 (46.9-64.7), P < 0.01) and the righting reflex ED50 (50 mg kg(-1), 27.2 (17.2-37.2), P < 0.01; 100 mg kg(-1), 14.3 (6.6-22.0), P < 0.01). Chronic administration did not reduce the minimum alveolar concentration; however, it reduced the righting reflex ED50 (65.3 (52.9-77.7), P < 0.01). Overall, the reduction in minimum alveolar concentration in the acute and chronic protocol did not correlate with that of the righting reflex ED50. 7-Nitroindazole (100 mg kg(-1), acute) reduced the cGMP concentration within the cerebellum by 55.4%; however, it did not decrease concentrations in the brain or spinal cord. CONCLUSIONS: Different mechanisms are responsible for the observed alterations to the minimum alveolar concentration and the righting reflex ED50 following treatment with 7-nitroindazole. The nitric oxide-cGMP pathway might play a less important role in the determination of minimum alveolar concentration than the righting reflex ED50.

Anesthetics, Inhalation↗
PubMed2003

Asymptomatic myocardial ischemia in relation to carotid artery stenosis among patients with aortic aneurysm.

AIM: The prevalence of asymptomatic coronary artery stenosis in relation to carotid artery stenosis is influenced by the underlying disease and has yet to be clarified. METHODS: A total of 124 consecutive Japanese patients with aortic aneurysm, but without symptoms of coronary artery stenosis, were divided into 2 groups on the basis of carotid ultrasonography: the carotid stenosis group (>or=50% luminal diameter narrowing) and the non-stenosis group. Myocardial imaging was performed using thalium-201 chloride and adenosine triphosphate disodium. RESULTS: The mean age and incidence of both cerebrovascular disease and peripheral artery disease were significantly higher in the stenosis group (n=24) than the non-stenosis group (n=100). Defining both fixed and reversible hypoperfusion as positive on the basis of myocardial imaging, a significantly higher number of positive findings were found in the stenosis group (15/24; 62.5%) than in the non-stenosis group (32/100, 32.0%), (Odds ratio: 3.54; p<0.01). The distributions of hypoperfusion defects in the stenosis group were similar to those in the non-stenosis group, but fixed hypoperfusion was more frequently seen in the stenosis group. CONCLUSION: The high prevalence of positive findings in the stenosis group indicates that carotid artery stenosis is frequently associated with coronary artery stenosis even in asymptomatic patients, and could be an indicator for advanced atherosclerosis of the coronary artery. The results confirm that stress myocardial imaging is invaluable in the detection of coronary artery stenosis, particularly in patients with carotid arteriosclerosis.

Aged↗
PubMed2002

Structural implications of placing cationic residues at either the NH2- or COOH-terminus in a pore-forming synthetic peptide.

Restoration of chloride conductance via introduction of an anion-selective pore, formed by a channel-forming peptide, has been hypothesized as a novel treatment modality for patients with cystic fibrosis. Delivery of these peptides from an aqueous environment in the absence of organic solvents is paramount. M2GlyR peptides, designed based on the glycine receptor, insert into lipid bilayers and polarized epithelial cells and assemble spontaneously into chloride-conducting pores. Addition of 4 lysine residues to either terminus increases the solubility of M2GlyR peptides. Both orientations of the helix within the membrane form an anion-selective pore, however, differences in solubility, associations and channel-forming activity are observed. To determine how the positioning of the lysine residues affects these properties, structural characteristics of the lysyl-modified peptides were explored utilizing chemical cross-linking, NMR and molecular modeling. Initial model structures of the a-helical peptides predict that lysine residues at the COOH-terminus form a capping structure by folding back to form hydrogen bonds with backbone carbonyl groups and hydroxyl side chains of residues in the helical segment of the peptide. In contrast, lysine residues at the NH2-terminus form fewer H-bonds and extend away from the helical backbone. Results from NMR and chemical cross-linking support the model structures. The C-cap formed by H-bonding of lysine residues is likely to account for the different biophysical properties observed between NH2- and COOH-terminal-modified M2GlyR peptides.

Animals↗
PubMed2002

Development of a THz spectroscopic imaging system.

We have developed a real-time THz imaging system based on the two-dimensional (2D) electro-optic (EO) sampling technique. Employing the 2D EO-sampling technique, we can obtain THz images using a CCD camera at a video rate of up to 30 frames per second. A spatial resolution of 1.4 mm was achieved. This resolution was reasonably close to the theoretical limit determined by diffraction. We observed not only static objects but also moving ones. To acquire spectroscopic information, time-domain images were collected. By processing these images on a computer, we can obtain spectroscopic images. Spectroscopy for silicon wafers was demonstrated.

Diagnostic Imaging↗
PubMed2002

Antitumor activity of a phenoxazine compound, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one against human B cell and T cell lymphoblastoid cell lines: induction of mixed types of cell death, apoptosis, and necrosis.

PURPOSE: We studied the antitumor activity of 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx), which was synthesized by the reactions of 2-amino-5-methylphenol with bovine hemoglobin, on human B cell lymphoblastoid cell lines, P3HR-1 and Raji derived from African Burkitt's lymphoma, and the human T cell lymphoblastoid cell line Molt-4. We also studied whether Phx might cause apoptosis and necrosis in these cells. METHODS: We evaluated cell viability and apoptosis and necrosis of the cells in the presence of Phx, by using agarose gel electrophoresis, flow cytometry, and fluorescence microscopy. RESULTS: Phx suppressed the viability of P3HR-1, Raji, and Molt-4 cells, though the suppression patterns were different, i.e., Phx suppressed the viability of P3HR-1, Raji, and Molt-4 cells at higher concentrations, while the drug enhanced the viability of Raji cells, but not those of P3HR-1 and Molt-4 cells at lower concentrations. To investigate which type of cell death - apoptosis or necrosis - is induced by Phx, induction of DNA ladder, phosphatidylserine externalization, and propidium iodide-permeable cells were examined in Phx-treated cells. Although Phx did not induce DNA ladder formation, it induced the phosphatidylserine externalization and propidium iodide-permeable cells, suggesting that Phx caused a mixed type of cell death, both apoptosis and necrosis. The population of early stage apoptotic cells was dominant in Raji cells, and that of the late stage apoptotic/necrotic cells was dominant in Molt-4 cells after 72-h treatment with Phx. The population of the early stage apoptotic cells and the late stage apoptotic/necrotic cells was almost equal in P3HR-1 cells in the presence of Phx, though the population of both types of cells increased with time. The nuclear morphological analysis of Phx-treated Raji, P3HR-1, and Molt-4 cells also showed that Phx induces apoptosis. CONCLUSIONS: The present results suggest that Phx shows antitumor activity against human B cell-derived and T cell-derived lymphoblastoid cell lines, in vitro, causing apoptosis and necrosis.

Annexin A5↗
PubMed2002

STAT and SMAD signaling in cancer.

STAT and SMAD often exert opposite biological effects on diverse cellular functions. Recent studies have shown that STAT can interface with SMAD at molecular level and that some novel molecules, such as SOCS (also called CIS) and APRO6 (also called TOB), modulate this signaling. A cofactor p300/CBP might act as a bridging molecule to mediate the interface. Thus, STAT and SMAD signaling pathways may crosstalk each other with interweaved regulatory mechanisms. Interestingly, the importance of all the proteins' function has been shown by the increasing evidence of their involvement in cancer. These recent progresses have been made in attributing novel exciting functions. Accordingly, we would like to review the latest advances of those pathways on a cross-section in cancer signaling.

Animals↗
PubMed2001

Spectroscopic observation of intermediates formed during the oxidative half-reaction of copper/topa quinone-containing phenylethylamine oxidase.

The catalytic reaction of copper/topa quinone (TPQ) containing amine oxidase consists of the initial, well-characterized, reductive half-reaction and the following, less studied, oxidative half-reaction. We have analyzed the oxidative half-reaction catalyzed by phenylethylamine oxidase from Arthrobacter globiformis (AGAO) by rapid-scan stopped-flow measurements. Upon addition of dioxygen to the substrate-reduced AGAO at pH 8.2, the absorption bands derived from the semiquinone (TPQ(sq)) and aminoresorcinol forms of the TPQ cofactor disappeared within the dead time (<1 ms) of the measurements, indicating that the reaction of the substrate-reduced enzyme with dioxygen is very rapid. Concomitantly, an early intermediate exhibiting an absorption band at about 410 nm was formed, which then decayed with a rate constant of 390 +/- 50 s(-1). This intermediate was detected more prominently in the reaction in D2O buffer (pD 8.1) and was assigned to a Cu(II)-peroxy species. The assignment was based on the observation that addition of H2O2 to the substrate-reduced AGAO under anaerobic conditions led to the formation of a new band at about 415 nm, accompanied by partial quenching of absorption bands derived from TPQ(sq). Other intermediates exhibiting absorption bands at about 310 and 340 nm were also observed in the oxidative half-reaction. Kinetics of the disappearance of these latter bands did not correspond with that of the Cu(II)-peroxy band at 410 nm but did well with that of the increase of the 480 nm absorption band due to the reoxidized TPQ. Rapid increase of the absorption in the 320-370 nm region was also observed for the reaction of the substrate-reduced, Ni-substituted enzyme with dioxygen. On the basis of these results, a possible mechanism is proposed for the oxidative half-reaction of the bacterial copper amine oxidase.

Amine Oxidase (Copper-Containing)↗
PubMed2001

Antinociceptive effect of the novel compound OT-7100 in a diabetic neuropathy model.

We previously reported that OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-alpha]pyrimidine) had antinociceptive potency in various animal models. To further characterize this compound, the present study examined the effects of OT-7100 on mechanical hyperalgesia and motor nerve conduction velocity in streptozotocin-induced diabetic rats. OT-7100 significantly increased the nociceptive threshold in the diabetic rat in a dose-dependent manner. Gabapentin (anticonvulsant agent) and insulin strongly increased the nociceptive threshold but gabapentin increased it above normal levels. An aldose reductase inhibitor slightly increased the nociceptive threshold at a high dose. We also measured glucose levels and motor nerve conduction velocity in OT-7100-treated rats. Insulin decreased glucose levels but OT-7100 had no effect on glucose levels or on motor nerve conduction velocity. These results suggest that OT-7100 alleviates hyperalgesia in a diabetic neuropathy model in a different manner from gabapentin or aldose reductase inhibitor and may be a new treatment for the pain associated with peripheral nerve injury.

Acetates↗
PubMed2001

A mechanism of Ca2+ release from Ca2+ stores coupling to the Na+/Ca2+ exchanger in cultured smooth muscle cells.

We previously observed Ca2+ release from intracellular Ca2+ stores caused by reduction in extracellular Na+ concentration ([Na+]o). The purpose of this study was to determine whether lowering [Na+]o can elicit Ca2+ release from Ca2+ stores via the Na+/Ca2+ exchanger and to elucidate the mechanisms related to the Ca2+ release pathway in cultured longitudinal smooth muscle cells obtained from guinea pig ileum. Low [Na+]o-induced Ca2+ release was inhibited by antisense oligodeoxynucleotides for Na+/Ca2+ exchanger type 1 (anti-NCX). Application of anti-NCX to cells attenuated both the number of Ca2+ responding cells and the expression of the exchanger. Moreover, microinjection of heparin, a blocker of inositol 1,4,5-trisphosphate (IP3) receptors, into the cells inhibited low [Na+]o-induced Ca2+ release. These findings suggest that low [Na+]o-induced Ca2+ release occurs through an IP3-induced Ca2+ release mechanism due to changes in the Ca2+ flux regulated by the Na+/Ca2+ exchanger.

Animals↗
PubMed2001

A dot-blot-immunoassay for semen identification using a polyclonal antibody against semenogelin, a powerful seminal marker.

Among various seminal plasma proteins, semenogelin (Sg), produced in the seminal vesicle, has been considered a candidate for demonstrating the presence of semen. Sg consists of two proteins, one 52 kDa (Sg-I) in size, and the other a mixture of 71 and 76 kDa proteins (Sg-II). Recombinant Sg-I and Sg-II proteins were obtained using a baculovirus system and then injected into a rabbit to produce the respective antibodies [Characterization of recombinant precursor proteins of the human seminal plasma sperm motility inhibitor synthesized in insect cells, Int. J. Mol. Med. 2 (1998) 693]. When liquefied seminal plasma was immunoblotted with the anti-Sg-I and Sg-II antibodies, the anti-Sg-II antibody identified a wider range of the polypeptides originating from Sg than did the anti-Sg-I antibody. A dot-blot-immunoassay using anti-Sg-II antibody revealed a clear immunoreactive spot even when the semen was diluted 6400-fold. However, this assay showed that the Sg antigen was undetectable in saliva, urine, vaginal secretions, sweat, nasal secretions and serum. To determine the stability of Sg antigenic activity, filter paper with dried semen stains were kept at 37, 4 and 22 degrees C for 1, 6 and 18 months, respectively, and the Sg antigenic activity was examined. The activity was detectable in an area not less than 0.5 cm x 0.5 cm under all of the above environmental conditions during each period. Finally, semen was mixed with saliva or blood at various volumetric ratios, and used as a source of dried stains. The Sg antigenic activity was detectable in the stains until the ratio of semen to saliva or blood reached 1:8. These results suggest that Sg may be useful as a marker for semen identification.

Adult↗
PubMed2001

Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand.

Glycosphingolipids and their metabolites play important roles in a variety of biological processes. Several signal molecules are localized in a glycolipid-enriched microdomain on the cell surface, and their signals are regulated by the glycolipid composition. However, the function of glycolipids in osteoclastogenesis has not been clearly understood. We found that D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), a glucosylceramide synthase inhibitor, completely inhibits the osteoclast formation induced by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand (RANKL) in a dose-dependent manner. Expression of RANK, the receptor of RANKL, induced by macrophage colony-stimulating factor, was reduced markedly in D-PDMP-treated cells. d-PDMP also inhibited the phosphorylation of the inhibitor of nuclear factor-kappa B and extracellular signal-regulated kinase 1/2 induced by RANKL. In several experiments with the addition of glycolipids to D-PDMP-treated purified bone marrow cells, lactosylceramide (LacCer) strongly affected the differentiation into tartrate-resistant acid phosphatase mononucleated cells, but not positive multinucleated cells. GM3 and GM1 also recovered, but less effectively compared with LacCer. Moreover, exogenous LacCer recovered the reduced expression of RANK and the phosphorylation of inhibitor of NF-kappa B and extracellular signal-regulated kinase 1/2 after stimulation by RANKL at the same level of cells without D-PDMP treatment. Our data suggest that glycosphingolipids, especially LacCer, are necessary for the initiation step of RANKL-induced osteoclastogenesis.

Animals↗
PubMed2001

Tocopherol-associated protein is a ligand-dependent transcriptional activator.

Vitamin E is a term that encompasses a group of potent, lipid-soluble, chain-breaking antioxidants. Structural analysis reveals that molecules having vitamin E activity include four isomers (alpha, beta, gamma, and delta) of both tocopherols and tocotrienols. Alpha-tocopherol has been shown to have the highest biological vitamin E activity in mammalian tissues based on fetal resorption assays, and it reverses vitamin E deficiency symptoms. Although the molecular functions fulfilled specifically by alpha-tocopherol have yet to be fully described, it is unlikely that they are limited to general antioxidant functions. Here we show the functional characterization of alpha-tocopherol associated protein, TAP, which displays significant sequence similarity to the alpha-tocopherol transfer protein. Ligand competition analysis showed that recombinant TAP binds to alpha-tocopherol but not to other isomers of tocopherols. Using GFP fusion protein expression system, we observed that TAP translocates from cytosol to nuclei in alpha-tocopherol-dependent fashion. Transient transfection experiment showed that TAP activates transcription of the reporter gene in alpha-tocopherol-dependent manner. These results suggest that the biological function of alpha-tocopherol is not only as an antioxidant but also as a transcriptional regulator of gene expression via association with a transcription factor TAP.

Amino Acid Sequence↗
PubMed2001

JAK/STAT3-dependent activation of the RalGDS/Ral pathway in M1 mouse myeloid leukemia cells.

The Ras-related GTPase (Ral) is converted to the GTP-bound form by Ral guanine nucleotide dissociation stimulator (RalGDS), a putative effector protein of Ras. Recently, it was proven that Ral regulates c-Src activity and subsequent phosphorylation of its substrate, STAT3. Here, we show that STAT3 inversely regulates activation of Ral through induction of expression of RalGDS. To identify new leukemia inhibitory factor-induced genes, we have performed representational difference analysis using M1 mouse myeloid leukemia cells and cloned RalGDS. The expression of RalGDS and subsequent activation of RalA were clearly suppressed by a dominant negative form of STAT3 and a JAK inhibitor, JAB/SOCS1/SSI-1, indicating that RalGDS/RalA signaling requires the activation of the JAK/STAT3 pathway. An experiment using a Ras inhibitor demonstrated that full activation of RalA also requires activation of Ras. These results suggest a novel cross-talk between JAK/STAT3 and the Ras/RalGDS/Ral signaling pathways through gp130.

Acute-Phase Proteins↗
PubMed2001

Cardiac Na(+)-Ca(2+) exchange: molecular and pharmacological aspects.

The Na(+)-Ca(2+) exchanger (NCX) is one of the essential regulators of Ca(2+) homeostasis in cardiomyocytes and thus an important modulator of the cardiac contractile function. The purpose of this review is to survey recent advances in cardiac NCX research, with particular emphasis on molecular and pharmacological aspects. The NCX function is thought to be regulated by a variety of cellular factors. However, data obtained by use of different experimental systems often appear to be in conflict. Where possible, we endeavor to provide a rational interpretation of such data. We also provide a summary of current work relating to the structure and function of the cardiac NCX. Recent molecular studies of the NCX protein are beginning to shed light on structural features of the ion translocation pathway in the NCX membrane domain, which seems likely to be formed, at least partly, by the phylogenetically conserved alpha-1 and alpha-2 repeat structures and their neighboring membrane-spanning segments. Finally, we discuss new classes of NCX inhibitors with improved selectivity. One of these, 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate (KB-R7943), appears to exhibit unique selectivity for Ca(2+)-influx-mode NCX activity. Data obtained with these inhibitors should provide a basis for designing more selective and clinically useful drugs targeting NCX.

Animals↗
PubMed2001

A mechanistic study of reactions of stable disilenes with haloalkanes.

Mechanisms of the reactions of three tetrakis(trialkylsilyl)disilenes and a tetraaryldisilene with various haloalkanes such as carbon tetrachloride, chloroform, dichloromethane, which gave the corresponding 1-alkyl-2-chlorodisilanes and/or 1,2-dichlorodisilanes, were investigated in detail. As evidenced by an ESR observation of an intermediate radical, these reactions were quite unusual, forming neutral radical pairs from two closed shell molecules at the first step; no similar reactions have been observed between alkenes and haloalkanes. Low oxidation potentials of these disilenes, large negative activation entropies, and solvent effects for the rates are in good accord with the direct halogen abstraction of disilenes from haloalkanes instead of single-electron transfer at the rate-determining first step. The structure--reactivity relationship of the reactions and the Hammond postulate suggest that the transition state structures for the first step are similar to those for the halogen abstraction by silyl radicals, but more product-like.

Journal Article↗