Biomedical subjects

Shinzo Kimura

Publications and source records attributed to Shinzo Kimura.

5 recordsLinked to original sources

PubMed2006

DNA microarray analyses reveal a post-irradiation differential time-dependent gene expression profile in yeast cells exposed to X-rays and gamma-rays.

Ionizing radiation (IR) is the most enigmatic of genotoxic stress inducers in our environment that has been around from the eons of time. IR is generally considered harmful, and has been the subject of numerous studies, mostly looking at the DNA damaging effects in cells and the repair mechanisms therein. Moreover, few studies have focused on large-scale identification of cellular responses to IR, and to this end, we describe here an initial study on the transcriptional responses of the unicellular genome model, yeast (Saccharomyces cerevisiae strain S288C), by cDNA microarray. The effect of two different IR, X-rays, and gamma (gamma)-rays, was investigated by irradiating the yeast cells cultured in YPD medium with 50 Gy doses of X- and gamma-rays, followed by resuspension of the cells in YPD for time-course experiments. The samples were collected for microarray analysis at 20, 40, and 80 min after irradiation. Microarray analysis revealed a time-course transcriptional profile of changed gene expressions. Up-regulated genes belonged to the functional categories mainly related to cell cycle and DNA processing, cell rescue defense and virulence, protein and cell fate, and metabolism (X- and gamma-rays). Similarly, for X- and gamma-rays, the down-regulated genes belonged to mostly transcription and protein synthesis, cell cycle and DNA processing, control of cellular organization, cell fate, and C-compound and carbohydrate metabolism categories, respectively. This study provides for the first time a snapshot of the genome-wide mRNA expression profiles in X- and gamma-ray post-irradiated yeast cells and comparatively interprets/discusses the changed gene functional categories as effects of these two radiations vis-à-vis their energy levels.

Down-Regulation↗

PubMed2004

Dose effect for Japanese due to 232Th and 238U in imported drinking water.

The consumption rate of bottled mineral water in Japan has increased due to changes in eating habits and contamination of water sources. Radioactivity levels of 238U and 232Th in imported mineral water were checked from the viewpoint of internal radiation for Japanese subjects. Concentration ranges of 238U and 232Th in imported bottled mineral water, domestic bottled mineral water, domestic tap water, and domestic soft drinks were as follows: for U, N.D to 7.48 x 10(3), 1.07 to 344, 0.66 to 104, and 3.04 to 46.2 ng dm (ppt); for Th, 0.60 to 5.12, 0.65 to 22.4, 0.64 to 22.1, and 11.0 to 48.5 ng dm, respectively. In some brands of imported bottled mineral water, U concentration was sometimes much higher than domestic bottled mineral water and domestic tap water. The annual effective dose (1.5 x 10(-3) mSv y(-1) estimated from intake of 238U was approximately 7 times higher than that through dietary intake in Japanese. However, the internal dose added by drinking the imported portable water is negligible compared with total annual internal dose. Concentrations of non-radioactive elements were also compared between imported and domestic bottled water. Geometric means of cobalt, arsenic, strontium, cesium, phosphorous, and calcium in imported bottled water were higher compared with those of domestic bottled mineral water and domestic tap water. Maximum values of 11 elements (arsenic, rubidium, strontium, cesium, barium, sodium, magnesium, potassium, calcium, and manganese) were also found in imported bottled water.

Administration, Oral↗

PubMed2003

HMG CoA reductase inhibitor suppresses the expression of tissue factor and plasminogen activator inhibitor-1 induced by angiotensin II in cultured rat aortic endothelial cells.

BACKGROUND: It has been demonstrated that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (HRIs) reduce the incidence of acute cardiovascular events in patients with hyperlipidemia. Recent reports have shown that the protective effects of these drugs against cardiovascular events are also observed in patients without hyperlipidemia, but the mechanism of this favorable effect still remains unclear. In this study, the effects of HRIs on the endothelial regulation of thrombus formation were elucidated. METHODS AND RESULTS: The mRNA and protein expression of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) induced by angiotensin II (Ang II) were evaluated in cultured rat aortic endothelial cells. Pretreatment with simvastatin (0.03-3 microg/ml) significantly inhibited TF and PAI-1 induction by Ang II in a dose- and time-dependent manner. These inhibitions were significantly attenuated by mevalonic acid or geranylgeranyl pyrophosphate. Both Rho inhibitor, C3 exoenzyme, and Rho kinase inhibitor, Y-27632, mimicked the inhibitory effects of simvastatin against TF and PAI-1 induced by Ang II. This result suggested that the Rho/Rho kinase pathway is related to the TF and PAI-1 induction by Ang II. CONCLUSION: It was indicated that simvastatin maintains endothelial cells to be antithrombotic by inhibiting TF and PAI-1 expression via the Rho/Rho kinase pathways in which AngII induces TF and PAI-1 expression. These observations explain, at least partly, the mechanism of the favorable effects of simvastatin in reducing the thrombotic events.

Angiotensin II↗

PubMed2003

Effects of argatroban and heparin on thrombus formation and tissue plasminogen activator-induced thrombolysis in a microvascular thrombosis model.

Effects of (2R,4R)-4-methyl-1-[N(2)-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidine-carboxylic acid monohydrate (argatroban) and unfractionated heparin (UFH) were compared with respect to thrombus formation and tissue-type plasminogen activator (t-PA)-induced thrombolysis in a microvasculature thrombosis model. The antithrombotic activities of anticoagulants were evaluated with respect to the time required for the initiation of thrombus formation (T(i)) and the time required for the thrombus to stop blood flow (T(s)). The effects of anticoagulants administered with t-PA were evaluated by percent stenosis of the vessel and percent area of the thrombus. Argatroban (1-3 mg/kg/bolus) significantly prolonged T(i) and T(s) in a dose-dependent fashion compared to control. Argatroban (3 mg/kg/bolus) significantly prolonged both the T(i) and T(s) more effectively than UFH (100 anti-XaU (a-XaU)/kg/bolus), despite equivalent prolongation of the activated partial thromboplastin time (aPTT). Higher doses of UFH (300-500 a-XaU/kg) were required to significantly prolong T(i) and T(s), but at these doses, UFH caused over-prolongation of aPTT (>180 s), which might consequently cause bleeding complications. Argatroban (0.1-0.3 mg/kg/h) significantly accelerated thrombolysis by t-PA in both a dose- and time-dependent fashion. Although argatroban (0.1-0.2 mg/kg/h) did not significantly prolong the aPTT and bleeding time (BT) as compared with control, it significantly accelerated thrombolysis by t-PA at these doses of lower bleeding risk. Argatroban (0.3 mg/kg/h) significantly enhanced thrombolysis by t-PA, while UFH (12.5 anti-XaU/kg/h) attenuated it again, despite equivalent prolongation of the aPTT and BT. We conclude that argatroban seems to be a more efficient and safer anticoagulant than UFH for the prevention of thrombus formation and acceleration of t-PA-induced thrombolysis.

Animals↗

PubMed2002

Bradykinin enhances in vitro procoagulant and antifibrinolytic properties of rat vascular endothelial cells.

INTRODUCTION: Bradykinin (BK) is a biologically active peptides that exerts a broad spectrum of pathophysiological effects mainly by producing nitric oxide (NO) and prostacyclin from vascular endothelial cells. A direct effect of BK on vascular endothelial cells regarding the expression of the regulatory proteins of coagulation and fibrinolysis has not been fully elucidated. MATERIALS AND METHODS: The effects of BK on the expression of tissue factor (TF), tissue factor pathway inhibitor (TFPI), plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator (TPA) in cultured rat aortic endothelial cells (RAECs) were respectively evaluated by Northern blot and chromogenic assay or enzyme-linked immunosorbent assay (ELISA). RESULTS: BK significantly increased the expression of TF and PAI-1 in both mRNA and protein levels, but it did not affect the expression of TFPI. Although BK tended to increase TPA mRNA expression, the observed increase was not statistically significant. Those effects are considered to be mediated by B(2) receptor, because B(2) receptor antagonist (Hoe 140) suppressed those mRNA inductions by BK. Furthermore, since those mRNA inductions by BK were enhanced by nitro-L-arginine-methyl ester (L-NAME) and attenuated by L-arginine (L-Arg), NO was speculated to negatively contribute to the expressions of TF and PAI-1. CONCLUSION: BK was indicated to modify the property of vascular endothelial cells to be procoagulant and antifibrinolytic. Those effects of BK were considered to be the net of its direct effect and the effect negatively mediated by NO.

Animals↗