Biomedical subjects

Ryo Shibata

Publications and source records attributed to Ryo Shibata.

6 recordsLinked to original sources

PubMed2006

Pitavastatin inhibits lysophosphatidic acid-induced proliferation and monocyte chemoattractant protein-1 expression in aortic smooth muscle cells by suppressing Rac-1-mediated reactive oxygen species generation.

Lysophosphatidic acid (LPA), a product generated during oxidative modification of low-density lipoprotein (LDL) and a major lipid extracted from human atherosclerotic plaques, has been shown to elicit smooth muscle cell (SMC) proliferation and inflammation, thereby being involved in atherogenesis. Recently, statins, an inhibitor of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase, have been reported to reduce the risk of cardiovascular events and slows the progression of atherosclerosis, at least partly, via pleiotropic effects. However, the effect of statin on the LPA-signaling in SMCs remains to be elucidated. In this study, we investigated whether and how pitavastatin could inhibit the LPA-induced proliferation and monocyte chemoattractant protein-1 (MCP-1) expression in cultured human aortic SMCs. LPA dose-dependently increased intracellular reactive oxygen species (ROS) generation in SMCs, which was blocked by diphenylene iodonium (DPI), an inhibitor of NADPH oxidase or pitavastatin. The anti-oxidative property of pitavastatin was prevented by simultaneous treatment of geranylgeranyl pyrophosphate. Furthermore, overexpression of dominant negative Rac-1 mutant was found to inhibit the LPA-induced ROS generation in SMCs. LPA induced Rac-1 activation in SMCs, which was suppressed by pitavastatin or LPA receptor antagonist. Pitavastatin, DPI, and an anti-oxidant N-acetylcysteine inhibited the LPA-induced proliferation and MCP-1 gene expression in SMCs. These results suggest that pitavastatin could block the LPA-induced proliferation and MCP-1 expression in SMCs by suppressing Rac-1-mediated NADPH oxidase-dependent ROS generation. Our present study provides a novel beneficial aspect of pitavastatin; pitavastatin may act as a blocker of the LPA-signaling in SMCs.

Antioxidants↗

PubMed2006

Diffusion accelerates and enhances chirality selection.

The diffusion effect on chirality selection in a two-dimensional reaction-diffusion model is studied by Monte Carlo simulations. The model consists of achiral reactants A which turn into either of the chiral products R or S in a solvent of chemically inactive vacancies V . The reaction contains a nonlinear autocatalysis as well as a recycling process, and the chiral symmetry breaking is monitored by an enantiomeric excess (ee) phi. Without dilution a strong nonlinear autocatalysis ensures chiral symmetry breaking. By diluting a diffusionless system, the ee phi decreases and a racemic state is recovered below a critical concentration c(c) . When the diffusion is allowed, the steady value of phi increases and c(c) decreases. As for the relation between the ee phi and the concentration c , a formula interpolating between the diffusionless (D=0) and the homogeneous (D=infinity) limits is proposed by incorporating the diffusional enhancement of the concentrations of chiral species. Diffusion also accelerates the development of the chiral order, and the time required to establish the order in a system of a size L(2) is inversely proportional to the diffusion constant D as L(2)/D .

Journal Article↗

PubMed2006

Molecular mechanism for elevation of asymmetric dimethylarginine and its role for hypertension in chronic kidney disease.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase. ADMA is generated by protein methyltransferase (PRMT) and is metabolized mainly by dimethylarginine dimethylaminohydrolase (DDAH). ADMA levels are reported to increase in patients with chronic kidney disease (CKD), thereby playing a role in the pathogenesis of accelerated atherosclerosis in this population. However, the precise mechanism underlying ADMA accumulation in these patients is not fully understood. This study investigated the molecular mechanism for the elevation of ADMA levels in CKD, using a rat remnant kidney model that represents progressive CKD. After male Sprague-Dawley rats underwent baseline measurement of BP and renal function, 5/6 subtotal nephrectomy (5/6Nx) and 4/6 nephrectomy were performed. Plasma and urinary levels of ADMA and symmetric dimethylarginine, an inert isomer of ADMA, were measured by HPLC. Expression levels of PRMT genes and DDAH proteins were analyzed by semiquantitative reverse transcription-PCR and Western blotting, respectively. Plasma ADMA levels were elevated in the Nx groups in proportion to the degree of nephrectomy despite marked increases in renal clearance of ADMA. In contrast, renal clearance of symmetric dimethylarginine was decreased and its plasma levels were increased in the Nx groups. Furthermore, both liver and kidney gene expression of PRMT was increased, whereas DDAH protein expression was decreased in the 5/6Nx group. Plasma ADMA levels were correlated with systolic BP levels. Moreover, adenovirus-mediated DDAH gene transfer into the 5/6Nx rats prevented the elevation of BP levels, which was associated with the reduction of plasma and urinary ADMA levels. The results presented here suggest that decreased DDAH levels as well as increased PRMT gene expression could cause the elevation of plasma ADMA levels, thereby eliciting hypertension in CKD. Substitution of DDAH protein or enhancement of its activity may become a novel therapeutic strategy for the treatment of hypertension-related vascular injury in CKD.

Adenoviridae↗

PubMed2005

X-ray telescope onboard Astro-E. III. Guidelines to performance improvements and optimization of the ray-tracing simulator.

We present a detailed study of the performance of the Astro-E x-ray telescope (XRT) onboard the Astro-E satellite. As described in preceding papers the ground-based calibrations of the Astro-E XRT revealed that its image quality and effective area are somewhat worse than that expected from the original design. Conceivable causes for such performance degradation are examined by x-ray and optical microscopic measurements at various levels, such as individual reflectors, sectors, and quadrants of the XRT and their alignments. We can attribute, based on detailed measurements, the degradation of the image quality to a slope error in the individual reflectors and the positioning error of reflectors. As for the deficit of the effective area, the shadowing of x rays within the XRT body is the dominant factor. Error budgets for the performance degradation of the Astro-E XRT are summarized. The ray-tracing simulator, which is needed to construct the response function for arbitrary off-axis angles and spatial distributions of any celestial x-ray sources, has been developed and tuned based on the results of detailed measurements. The ray-tracing simulation provides results that are consistent within 3% with the real measurement except for large off-axis angles and higher energies. We propose, based on knowledge obtained from all the measurements and simulations, several plans for future developments to improve the performance of the nested thin-foil mirrors.

Journal Article↗

PubMed2002

Characterization of the supermirror hard-x-ray telescope for the InFOCmuS balloon experiment.

A hard-x-ray telescope is successfully produced for balloon observations by making use of depth-graded multilayers, or so-called supermirrors, with platinum-carbon (Pt/C) layer pairs. It consists of four quadrant units assembled in an optical configuration with a diameter of 40 cm and a focal length of 8 m. Each quadrant is made of 510 pieces of coaxially and confocally aligned supermirrors that significantly enhance the sensitivity in an energy range of 20-40 keV. The configuration of the telescope is similar to the x-ray telescope onboard Astro-E, but with a longer focal length. The reflectivity of supermirrors is of the order of 40% in the energy range concerned at a grazing angle of 0.2 deg. The effective area of a fully assembled telescope is 50 cm2 at 30 keV. The angular resolution is 2.37 arc min at half-power diameter 8.0 keV. The field of view is 12.6 arc min in the hard-x-ray region, depending somewhat on x-ray energies. We discuss these characteristics, taking into account the figure errors of reflectors and their optical alignment in the telescope assembly. This hard-x-ray telescope is unanimously afforded in the International Focusing Optics Collaboration for muCrab Sensitivity balloon experiment.

Journal Article↗

PubMedDate not supplied

Oral adsorbent AST-120 decreases serum levels of AGEs in patients with chronic renal failure.

Advanced glycation end products (AGEs) are senescent macroprotein derivatives that are formed at an accelerated rate in patients with chronic renal failure (CRF). AGE formation and accumulation in plasma and vascular tissues contribute to accelerated atherosclerosis in this devastating disorder. AST-120 is an oral adsorbent that attenuates the progression of CRF by removing uremic toxins. Recently, AST-120 has been reported to reduce the progression of atherosclerosis as well. However, whether AST-120 decreases serum levels of AGEs and subsequently exerts atheroprotective properties remains to be elucidated. Ten nondiabetic CRF patients were enrolled in this study. All patients were kept on regular therapeutic diet and medications throughout the study. Serum AGE levels before and after AST-120 treatments were measured using enzyme-linked immunosorbent assay. Effects of patient-derived serum on atherosclerosis-related gene expression in cultured human umbilical vein endothelial cells (HUVECs) were analyzed by semiquantitative RT-PCR. Administration of AST-120 (6 g/day) for 3 months significantly decreased serum levels of AGEs in nondiabetic CRF patients, whereas AGE levels remained unchanged in age- and renal function-matched CRF patients without AST-120 treatment (n = 6). Patient serum after AST-120 treatment significantly reduced mRNA levels of receptor for AGEs, monocyte chemoattractant protein-1, and vascular adhesion molecule-1 in HUVECs compared with serum before treatment. Moreover, in vitro, AST-120 was found to adsorb carboxymethyllysine (CML), one of the well-characterized, digested food-derived AGEs. This study suggests that atheroprotective properties of AST-120 can be ascribed, at least in part, to its AGE-lowering ability via absorption of CML.

Administration, Oral↗