Search PubMed⌕ Search

Biomedical subjects

Akira Miyazaki

Publications and source records attributed to Akira Miyazaki.

At least 19 recordsLinked to original sources
PubMed2006

Polymer-surfactant layered heterostructures by electropolymerization of phenosafranine in Langmuir-Blodgett films.

Langmuir-Blodgett (LB) films of the water-soluble dye phenosafranine (PS) have been prepared by its adsorption from aqueous dye solution to an arachidic acid (AA) monolayer at the air-water interface. Atomic force microscopy (AFM) images of the LB films revealed the effect of change in pH of deposition on the degree of complexation of AA with the PS dye. Well-defined circular islands and holes were observed which disappeared with the increase in pH. Polarized absorption studies indicated that the dye molecules are oriented uniaxially with their long axis titled at a constant angle to the surface normal of the LB film. Within the restricted geometry of the LB film, the PS dye was electropolymerized to form a two-dimensional film of poly(phenosafranine) sandwiched between arachidic acid layers. The film was characterized by IR spectroscopy, cyclic voltammetry, and AFM. X-ray diffraction studies reveal the presence of a layer structure in the AA-PS LB film before and after polymerization. The polymer film showed highly anisotropic electrical conductivity of ca. 10 orders of magnitude. This indicates the formation of two-dimensional polyPS layers between arachidic acid layers resulting in a layered heterostructure film having alternate conducting and insulating regions. Also, the conductivity of the polyPS prepared from LB film was found to be approximately 2.5 times higher than the conductivity of polyPS prepared by solution polymerization method.

Anisotropy↗
PubMed2006

Magnetic and electronic properties of palladium nanoparticles coated with pi-conjugated tetrathiafulvalenes derivative.

Magnetic and electronic properties are investigated for Pd nanoparticles coated with a TTF-derivative (EDT-TTF(SCH(3))(SC(10)H(20)SH)) and octadecanethiol organic mixed monolayer. The temperature-independent spin susceptibility and spin concentration of Pd decrease upon the increasing proportion of the TTF-derivative in the organic layer. With the introduction of the derivative, the ESR broad signal originating from the interior of the Pd nanoparticles tends to vanish following the appearance of sharp signals due to the TTF radical. The presence of the TTF molecules enhances the charge transfer from the core Pd nanoparticles. The electronic state of the Pd nanoparticles changes as a consequence of the contributions of both the quantum-size effect and the charge-transfer effect between the Pd core, TTF-derivative, and alkanethiol.

Journal Article↗
PubMed2006

Dynamic and collective electrochemical responses of tetrathiafulvalene derivative self-assembled monolayers.

Electroactive tetrathiafulvalene (TTF)-containing alkanethiol self-assembled monolayers (SAMs) were designed and synthesized to elucidate the relationship between electrochemical responses and film structures. Two TTF derivative molecules having one alkanethiol chain (1) and two alkanethiol chains (2) were utilized to modulate the molecular packing arrangements in the SAMs, and the formation and structure of the SAMs were characterized by surface plasmon resonance spectroscopy (SPR). SPR measurements in various contacting media demonstrated loose packing of SAM 1 and close packing of SAM 2 due to the different space fillings of the molecules. Two successive one-electron redox waves were observed for both SAMs by cyclic voltammetry. The peak widths of the redox waves were strongly dependent on the oxidation states of the TTF moieties, the packing arrangement of the SAMs, and the contacting medium. We found that TTF-based SAMs exhibited collective electrochemical responses induced by dynamic structural changes, depending on the degree of freedom for the component molecules in the SAMs. These results imply that the molecular design, taking into account the electrochemical responses, extends the available range of molecular-based functionalities in TTF-based SAMs.

Journal Article↗
PubMed2006

Impact of increased plasma serotonin levels and carotid atherosclerosis on vascular dementia.

Serotonin (5-HT), a potent vasoconstrictor in the large cerebral arteries, is considered to play a key role in atherothrombosis and to be implicated in ischemic cerebrovascular events followed by delayed neuronal death. The present study aims at evaluating the relationship between plasma levels of 5-HT and vascular dementia (VaD) caused by stroke or atherosclerotic small vessel disease. Carotid artery intima-media thickness (IMT), plaques, plasma 5-HT levels and atherosclerotic parameters were determined in 20 patients with VaD and 40 age-matched controls. Age, gender, body mass index, systolic and diastolic blood pressure, fasting plasma glucose levels and serum levels of insulin, triglycerides, high-density lipoprotein cholesterol, leptin, adiponectin and interleukin-6 and plasma levels of plasminogen activator inhibitor-1 were not significantly different between the two groups. Serum levels of insulin-like growth factor-1 (IGF-1) were significantly lower in VaD patients than in controls. Plasma 5-HT levels, serum levels of hepatocyte growth factor (HGF), low-density lipoprotein (LDL) cholesterol and high-sensitive C-reactive protein (hs-CRP), max IMT and plaque frequency were significantly greater in VaD patients than in controls. There was a significant positive correlation of max IMT with 5-HT or HGF levels. Multiple logistic regression analysis revealed that increased plasma levels of 5-HT and carotid plaque prevalence had significantly independent association with VaD as compared with serum levels of IGF-1, HGF, LDL cholesterol and hs-CRP. These results suggest that increased plasma levels of 5-HT and carotid atherosclerotic plaques may be involved in the pathogenesis and progression of VaD.

Aged↗
PubMed2006

Combined small cell carcinoma with pulmonary blastoma and adenocarcinoma: case report and clonality analysis.

We describe a rare tumor occurring in the left pulmonary lobe of a 71-year-old Japanese man. The tumor, which was resected by left lower lobectomy, measured 65 x 50 x 50 mm. Histologic examination revealed papillary adenocarcinoma in small cell carcinoma, and chondrosarcoma. Also, the blastemal cells were located between the small cell carcinoma and the chondrosarcoma, and intermingled with both components. In blastemal cells, some glands resembled a well-differentiated fetal adenocarcinoma. The tumor was diagnosed as combined small cell carcinoma with pulmonary blastoma and papillary adenocarcinoma according to the 2004 WHO classification. Immunohistochemically, the small cell carcinoma expressed TTF-1, pancytokeratin, CD56, synaptophysin, and S100 protein, while blastemal cells expressed vimentin, desmin, smooth muscle actin, CD56, and S100 protein. To investigate whether the tumor was clonal or not, p53 gene mutation of each tumor component was analyzed by laser-captured microdissection, polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. Despite the histologic complexity, all components showed the same mutation at exon5 of the p53 gene. These results indicate that the tumor was clonal and arose from a relatively primitive cell, and that p53 mutation occurred before histologic metamorphosis or differentiation.

Aged↗
PubMed2006

A selective ACAT-1 inhibitor, K-604, suppresses fatty streak lesions in fat-fed hamsters without affecting plasma cholesterol levels.

BACKGROUND: Acyl-coenzyme A:cholesterol O-acyltransferase-1 (ACAT-1), a major ACAT isozyme in macrophages, plays an essential role in foam cell formation in atherosclerotic lesions. However, whether pharmacological inhibition of macrophage ACAT-1 causes exacerbation or suppression of atherosclerosis is controversial. METHODS AND RESULTS: We developed and characterized a novel ACAT inhibitor, K-604. The IC(50) values of K-604 for human ACAT-1 and ACAT-2 were 0.45 and 102.85 micromol/L, respectively, indicating that K-604 is 229-fold more selective for ACAT-1. Kinetic analysis indicated that the inhibition was competitive with respect to oleoyl-coenzyme A with a K(i) value of 0.378 micromol/L. Exposure of human monocyte-derived macrophages to K-604 inhibited cholesterol esterification with IC(50) of 68.0 nmol/L. Furthermore, cholesterol efflux from THP-1 macrophages to HDL(3) or apolipoprotein A-I was enhanced by K-604. Interestingly, administration of K-604 to F1B hamsters on a high-fat diet at a dose of >or=1mg/kg suppressed fatty streak lesions without affecting plasma cholesterol levels. CONCLUSIONS: K-604, a potent and selective inhibitor of ACAT-1, suppressed the development of atherosclerosis in an animal model without affecting plasma cholesterol levels, providing direct evidence that pharmacological inhibition of ACAT-1 in the arterial walls leads to suppression of atherosclerosis.

Animals↗
PubMed2006

Extracellular-added ADP-ribose increases intracellular free Ca2+ concentration through Ca2+ release from stores, but not through TRPM2-mediated Ca2+ entry, in rat beta-cell line RIN-5F.

Intracellular ADP-ribose is an activator of TRPM2, which is a Ca2+-permeable channel and mediates H2O2-induced cell death, in the TRPM2-expressing rat beta-cell line RIN-5F. We examined the effect of extracellular-added ADP-ribose on intracellular Ca2+ concentration in RIN-5F cells. ADP-ribose induced Ca2+ release from the thapsigargin-sensitive Ca2+ store, but not Ca2+ entry across the plasma membrane. A phospholipase C (PLC) inhibitor and a non-specific IP3 receptor inhibitor blocked its Ca2+ release. H2O2-induced Ca2+ entry through TRPM2 was not affected by extracellular ADP-ribose. These findings suggest that extracellular-added ADP-ribose induces Ca2+ release through the PLC-IP3 pathway and does not act as a TRPM2 activator.

Adenosine Diphosphate Ribose↗
PubMed2006

Ndrg4 enhances NGF-induced ERK activation uncoupled with Elk-1 activation.

Ndrg4 is expressed predominantly in the early postnatal rat brain and may be related to neural cell differentiation. PC12 cell lines stably expressing increased levels of Ndrg4 protein display enhanced NGF-induced phosphorylation of MEK and ERK. In contrast, the Ndrg4-C2-overexpressed PC12 cell lines showed attenuated NGF-promoted phosphorylation of Elk-1, which is a nuclear target of ERK. A reporter assay also indicated that Ndrg4-C2 suppresses Elk-1-mediated transcriptional activation and SRE reporter expression. The suppressive effect of Ndrg4-C2 on NGF-induced activation of Elk-1 was abolished by colchicine but not by cytochalasin D, suggesting that microtubules are involved in the reduced activation of Elk-1 by Ndrg4. Ndrg4 may play a role in supporting the activation of ERK and its target proteins needed for neuronal differentiation and in reducing the activation of Elk-1 implicated in cell growth.

Animals↗
PubMed2006

Pressure effect on bulk weak ferromagnets: (BDH-TTP)[M(isoq)2(NCS)4] (M = Cr(III), Fe(III); isoq = Isoquinoline).

The pressure dependence of the magnetic properties of weak ferromagnets (BDH-TTP)[M(isoq)2(NCS)4] [BDH-TTP = 2,5-bis(1',3'-dithiolan-2'-ylidene)-1,3,4,6-tetrathiapentalene; M = Cr, Fe; isoq = isoquinoline] is discussed. These salts form two-dimensional magnetic sheets, where ferrimagnetic chains of donor cation radical (S = 1/2) and anion [S = 3/2 (Cr), 5/2 (Fe)] are antiferromagnetically connected by weak donor-donor and anion-anion interchain S...S contacts. Under ambient pressure, both the Cr and Fe salts undergo a weak ferromagnetic transition at Tc = 7.6 K, below which a spontaneous magnetization emerges along the direction perpendicular to the sheets. The application of the pressure elevates the transition temperatures up to 16.6 and 11.6 K at 9 kbar for M = Cr and Fe, respectively. As the pressure increases, the remanent magnetization M(r) decreases, whose pressure dependence for the Cr salt is larger than that for the Fe salt. This difference indicates that the spin-canting angle of the Cr salt is reduced because of the increase of antiferromagnetic interaction by applied pressure, in contrast to the Fe salt, where single-ion anisotropy contributes less. The quantitative analysis of the magnetization curves of the Cr salt using the mean-field approximation reveals that the intermolecular exchange interaction increases as the pressure increases, among which the interchain anion-anion interaction has the highest pressure sensitivity. This result is consistent with the temperature dependence of the crystal structure showing that the thermal contraction in the distances of interchain anion-anion S...S contacts is the most remarkable in intrachain S...S contacts. The large pressure dependence of the transition temperature of these salts is therefore explained as a result of the fact that the interchain interactions, the anion-anion interaction in particular, are strengthened by applied pressure.

Journal Article↗
PubMed2006

Intracellular-produced hydroxyl radical mediates H2O2-induced Ca2+ influx and cell death in rat beta-cell line RIN-5F.

The melastatin-related transient receptor potential channel TRPM2 is a Ca(2+)-permeable channel that is activated by H(2)O(2), and the Ca(2+) influx through TRPM2 mediates cell death. However, the responsible oxidants for TRPM2 activation remain to be identified. In the present study, we investigated the involvement of hydroxyl radical on TRPM2 activation in TRPM2-expressing HEK293 cells and the rat beta-cell line RIN-5F. In both cell types, H(2)O(2) induced Ca(2+) influx in a concentration-dependent manner. However, the addition of hydroxyl radical, which was produced by mixing FeSO(4) and H(2)O(2), to the cells, did not increase intracellular Ca(2+) concentration. Interestingly, when H(2)O(2) was added to the cells under intracellular Fe(2+)-accumulated conditions, Ca(2+) influx was markedly enhanced compared to H(2)O(2) alone. In addition, the H(2)O(2)-induced Ca(2+) influx was reduced by hydroxyl radical scavengers and an iron chelator. Under intracellular Fe(2+)-accumulated conditions, H(2)O(2)-induced RIN-5F cell death through TRPM2 activation was also markedly enhanced. Hydroxyl radical scavengers and an iron chelator suppressed the RIN-5F cell death by H(2)O(2). These results strongly suggest that the intracellular hydroxyl radical plays a key role in the activation of TRPM2 during H(2)O(2) treatment, and TRPM2 activation mediated by hydroxyl radical is implicated in H(2)O(2)-induced cell death in the beta-cell line RIN-5F.

Adenosine Triphosphate↗
PubMed2006

Human acyl-CoA:cholesterol acyltransferase (ACAT) and its potential as a target for pharmaceutical intervention against atherosclerosis.

Acyl-CoA:cholesterol acyltransferase (ACAT) catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty-acyl-coenzyme A. At the single-cell level, ACAT serves as a regulator of intracellular cholesterol homeostasis. In addition, ACAT supplies cholesteryl esters for lipoprotein assembly in the liver and small intestine. Under pathological conditions, the accumulation of cholesteryl esters produced by ACAT in macrophages contributes to foam cell formation, a hallmark of the early stage of atherosclerosis. Several reviews addressing various aspects of ACAT and ACAT inhibitors are available. This review briefly outlines the current knowledge on the biochemical properties of human ACATs, and then focuses on discussing the merit of ACAT as a drug target for pharmaceutical interventions against atherosclerosis.

Acyl Coenzyme A↗
PubMed2006

Human urotensin II as a link between hypertension and coronary artery disease.

Hypertension is a well-known risk factor for atherosclerosis, but the molecular mechanisms that link elevated blood pressure to the progression of atherosclerosis remain unclear. Human urotensin II (U-II), the most potent endogenous vasoconstrictor peptide identified to date, and its receptor (UT receptor) are involved in the etiology of essential hypertension. In patients with essential hypertension, U-II infused into the forearm brachial artery has been shown to induce vasoconstriction. Recent studies have demonstrated elevated plasma U-II concentrations in patients with essential hypertension, diabetes mellitus, atherosclerosis, and coronary artery disease. U-II is expressed in endothelial cells, macrophages, macrophage-derived foam cells, and myointimal and medial vascular smooth muscle cells (VSMCs) of atherosclerotic human coronary arteries. UT receptors are present in VSMCs of human coronary arteries, the thoracic aorta and cardiac myocytes. Lymphocytes are the most active producers of U-II, whereas monocytes and macrophages are the major cell types expressing UT receptors, with relatively little receptor expression in foam cells, lymphocytes, and platelets. U-II accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. In human endothelial cells, U-II promotes cell proliferation and up-regulates type 1 collagen expression. U-II also activates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and plasminogen activator inhibitor-1 in human VSMCs, and stimulates VSMC proliferation with synergistic effects observed when combined with oxidized low-density lipoprotein, lysophosphatidylcholine, reactive oxygen species or serotonin. These findings suggest that U-II plays key roles in accelerating the development of atherosclerosis, thereby leading to coronary artery disease.

Animals↗
PubMed2005

In situ STM study of potential-dependent height change of a tetrathiafulvalene derivative embedded in alkanethiol self-assembled monolayers on Au(111).

Electroactive tetrathiafulvalene thiol islands embedded in an n-alkanethiol SAM matrix were studied under potential control using in situ scanning tunneling microscopy. Unlike previously studied stochastic switching, the apparent height of the island could be intentionally controlled in the present system by choosing the appropriate potential and the island size. The dependence of the height change on the potential and the size is explained as structural change of the island induced by the charging effect of the electroactive moiety.

Journal Article↗
PubMed2005

Human urotensin II accelerates foam cell formation in human monocyte-derived macrophages.

Human urotensin II (U-II), the most potent vasoconstrictor peptide identified to date, and its receptor (UT) are involved in hypertension and atherosclerosis. Acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) converts intracellular free cholesterol into cholesterol ester (CE) for storage in lipid droplets and plays an important role in the formation of macrophage-derived foam cells in atherosclerotic lesions. We examined the effects of U-II on ACAT-1 expression and CE accumulation in human monocyte-derived macrophages. U-II increased ACAT activity in a concentration-dependent manner after 7 days in monocyte primary culture. Immunoblotting analysis showed that U-II at 25 nmol/L increased ACAT-1 protein expression level by 2.5-fold, which was completely abolished by anti-U-II antibody, selective UT receptor antagonists (urantide and 4-aminoquinoline), a G-protein inactivator (GDP-beta-S), a c-Src protein tyrosine kinase inhibitor (PP2), a protein kinase C (PKC) inhibitor (rottlerin), a mitogen-activated protein kinase kinase (MEK) inhibitor (PD98059), or a Rho kinase (ROCK) inhibitor (Y27632). Northern blotting analysis indicated that among the 4 ACAT-1 mRNA transcripts (2.8-, 3.6-, 4.3-, and 7.0-kb), the 2.8- and 3.6-kb transcript levels were selectively upregulated by approximately 1.7-fold by U-II (25 nmol/L). Further, U-II (25 nmol/L) significantly increased acetylated LDL (acetyl-LDL)-induced CE accumulation in monocyte-derived macrophages but not scavenger receptor class A (SR-A) function as assessed by endocytic uptake of [(125)I]acetyl-LDL. Our results suggest that U-II may play a novel role in the formation of macrophage-derived foam cells by upregulating ACAT-1 expression via the UT receptor/G-protein/c-Src/PKC/MEK and ROCK pathways but not by SR-A, thus contributing to the relatively rapid development of atherosclerosis in hypertension.

Cell Division↗
PubMed2005

Serotonin acts as an up-regulator of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-macrophages.

Acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT-1) converts intracellular free cholesterol into cholesterol ester for storage in lipid droplets and plays an important role in the formation of macrophage-derived foam cells in atherosclerotic lesions. Serotonin (5-HT), a potent vasoconstrictor that is released from activated platelets, increases uptake of oxidized low-density lipoprotein (LDL) by macrophages, leading to foam cell formation, and contributes to the development of atherosclerotic plaque. However, it is not yet known whether 5-HT affects ACAT-1 expression in human monocyte-macrophages as the molecular mechanism of enhanced foam cell formation by 5-HT remains unclear. We examined the effects of 5-HT on ACAT-1 expression during differentiation of cultured human monocytes into macrophages. Expression of ACAT-1 protein but not 5-HT2A receptor increased in a time-dependent manner. 5-HT increased ACAT activity in a concentration-dependent manner after 7 days in primary monocyte culture. Immunoblotting analysis showed that 5-HT at 10 microM increased ACAT-1 protein expression level by two-fold, and this effect was abolished completely by a 5-HT2A receptor antagonist (sarpogrelate), its major metabolite (M-1), a G protein inactivator (GDP-beta-S), a protein kinase C (PKC) inhibitor (rottlerin), a Src family inhibitor (PP2), or a mitogen-activated protein kinase (MAPK) kinase inhibitor (PD98059). Northern blotting analysis indicated that among the four ACAT-1 mRNA transcripts (2.8-, 3.6-, 4.3-, and 7.0-kb), the levels of the 2.8- and 3.6-kb transcripts were selectively up-regulated by approximately 1.7-fold by 5-HT (10 microM). The results of the present study suggested that 5-HT may play a crucial role in macrophage-derived foam cell formation by up-regulating ACAT-1 expression via the 5-HT2A receptor/G protein/c-Src/PKC/MAPK pathway, contributing to the progression of atherosclerotic plaque.

Cells, Cultured↗
PubMed2005

Lipopolysaccharide stimulation converts vigorously washed dendritic cells (DCs) to nonexhausted DCs expressing CD70 and evoking long-lasting type 1 T cell responses.

A great variety of in vitro culture protocols for human monocyte-derived dendritic cells (mo-DCs) has been used to generate DCs suitable for use in immunotherapy. It is thought that activated DCs undergo one-way differentiation into "exhausted" DCs. In the present study, we contrived an in vitro method for facilitating expression of CD70 by mature DCs. This was achieved by vigorous washing of mo-DCs before exposure to lipopolysaccharide (LPS). Unexpectedly, these mature DCs retain expression of some interleukin (IL)-12 family members after extended periods and maintain their ability to stimulate type 1 T cell responses. In contrast, DCs exposed to IL-4 before LPS stimulation or LPS-stimulated DCs not exposed to washing stress before activation failed to express CD70 and did differentiate into exhausted DCs. It is interesting that DCs expressing CD70 (CD70+ DCs) induced interferon-gamma production from purified, allogeneic CD8+ T cells through a direct CD27-CD70 interaction. This is evidence for a pathway resulting in generation of CD8 T effectors by B7-independent mechanisms. These data suggest that exposure of immature DCs to LPS stimulation contributes to their terminal differentiation into CD70+ DCs, which have potent ability to prolong type 1 T cell responses through alternative pathways.

Adoptive Transfer↗
PubMed2005

d-Electron-induced negative magnetoresistance of a pi-d interaction system based on a brominated-TTF donor.

A new pi-d interaction system (EDT-TTFBr2)2FeBr4 (EDT-TTFBr2 = 4,5-dibromo-4',5'-ethylenedithiotetrathiafulvalene) and its nonmagnetic anion analogue (EDT-TTFBr2)2GaBr4 based on a brominated TTF-type organic donor are investigated. The salts featured by quasi-1D pi-electronic systems are metallic with metal-insulator transitions taking place at about 20 and 70 K for the FeBr4- and GaBr4- salts, respectively, where the low-temperature insulating state is associated with charge ordering or a Mott insulator followed by an antiferromagnetic transition at lower temperatures. The FeBr4- salt is featured with an antiferromagnetic transition of the anion d spins at a Neel temperature (TN) = 11 K, which is significantly high despite its long anion-anion Br-Br contact, suggesting the importance of the pi-d interaction in the magnetism. The surprisingly strong pi-d interaction, ca. -22.3 K estimated from the magnetization curve, evidences the usefulness of the chemical modification of the donor molecule with bromine substitution to achieve strong intermolecular interaction. The antiferromagnetic state of the anion d spins affects the transport of the conducting pi electrons through the strong pi-d interaction, as evidenced by the presence of a resistivity anomaly of the FeBr4- salt at TN. Below TN, the FeBr4- salt shows negative magnetoresistance that reaches -23% at the highest magnetic field investigated (B=15 T), whereas only a small positive magnetoresistance is observed in the pi-electron-only GaBr4- salt. The mechanism of the negative magnetoresistance is explained by the stabilization of the insulating state of the pi electrons by the periodic magnetic potential of the anion d spins in the FeBr4- salt, which is modified by applying the external magnetic field.

Journal Article↗