中世高地ドイツ語における数意識の構造 : Iweinをテキストとして

本稿は，第15回西日本言語学会（1985年9月7日，於広島文教女子大学）にて口答発表した内容を改訂・増補したものである

Cardioprotective effects of amlodipine in the ischemic-reperfused heart

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27711/1/0000098.pd

Cardioprotective effects of amlodipine on ischemia and reperfusion in two experimental models

The cardioprotective effect of amlodipine, a longacting dihydropyridine derivative, was studied in 2 experimental models of ischemia and reperfusion.Isolated and blood-perfused feline hearts were made globally ischemic for 60 minutes and then reperfused for 60 minutes. Alterations of left ventricular developed pressure and compliance were monitored in both amlodipine-treated hearts and salinetreated control animals. Changes in perfusion pressure indicated that amlodipine significantly reduced myocardial oxygen consumption and coronary vascular resistance. Furthermore, a progressive increase in resting left ventricular diastolic pressure indicated that amlodipine, administered before the onset of global ischemia, attenuated the development of ischemic contracture. Return of contractile function 60 minutes after reperfusion and maintenance of tissue concentrations of electrolytes were significantly better in the amlodipinetreated group than in the control animals.In intact canine hearts, regional myocardial ischemia was induced for 90 minutes, followed by 6 hours of reperfusion. Although the hemodynamic variables and the size of the region of risk did not differ significantly between treated animals and control animals, the infarct size was significantly smaller in the amlodipine-treated group than in the control animals, and a gradual reduction in coronary blood flow was observed in the control group that was prevented in the amlodipine group. A comparison of these findings with those observed with oxygen radical scavengers also is discussed.A detailed report of these studies was published in The American Journal of Cardiology (1989;64:101I-116I). This review is included here to maintain continuity of the symposium for the convenience of the reader.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28306/1/0000060.pd

Cardioprotective effects of amlodipine in the ischemic-repefused heart

Amlodipine is a a dihydropyridine derivative belonging to the group of pharmacologic calcium entry blocking agents and is characterized as having a slow onset and relatively long duration of action with minimal effects on cardiac electrophysiology and myocardial contractility.The protective effect of amlodipine was studied in isolated blood-perfused feline hearts made globally ischemic for 60 minutes followed by reperfusion for 60 minutes. Ischemic-lnduced alterations of left ventricular developed pressure and compliance were monitored. In 11 control and 7 drug-treated hearts, amloipine produced significant decreases in myocardial oxygen consumption (6.2 +/- 0.4 to 4.4 +/- 0.4 ml oxygen/min/100 g) and coronary vascular resistance, as assessed by changes in perfusion pressure (120 +/- 1 to 100 +/- 4 mm Hg). Amlodipine administered before the onset of global ischemia decreased the development of ischemic contracture as reflected by a progressive increase in resting left ventricular diastolic pressure. The return of contractile function, 60 minutes after reperfusion, improved significantly in the amlodipine-treated group compared with controls, and there was better maintenance of the tissue concentration of Na+, Ca2+ and K+.A canine model of regional myocardial ischemia (90 minutes) followed by 6 hours of reperfusion was used to assess the cardioprotective effects of amlodyrine, 150 [mu]g/kg, administered 15 minutes before reperfusion. Infarct size, expressed as a percentage of the area at risk, was smaller in the amlodipine-treated group (n = 10) than in the control group (n = 10) (34.5 +/- 3.8% vs 45.9 +/- 2.8%, P = 0.027). Risk region size did not differ between groups and both groups were comparable with respect to the hemodynamic parameters of heart rate, blood pressure and rate-pressure product. Amlodipine prevented the gradual reduction in coronary blood flow observed in the control group.It is concluded that amlodipine reduces myocardial ischemic injury by mechanism(s) that may involve a reduction in myocardial oxygen demand as well as by positively influencing transmembrane Ca2+ fluxes during ischemia and reperfusion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27687/1/0000071.pd

Oral Administration of D-aspartate, but not of L-aspartate, Reduces Food Intake in Chicks

In the present study, we determined the effects of oral administration of L- and D-aspartate (L-Asp and D-Asp) on food intake over a period of2haftertheadministration, as well as its effects on the concentration of L- and D-Asp in the brain and plasma. Chicks were orally administered different levels (0, 3.75, 7.5 and 15 mmol/kg body weight) of L-Asp (Experiment 1) and D-Asp (Experiment 2). Administration of several doses of L-Asp linearly increased the concentration of L-Asp, but not of D-Asp, in plasma. Oral L-Asp somewhat modified the levels of L- and D-Asp levels in the telencephalon, but not in the diencephalon. However, food intake was not significantly changed with doses of L-Asp. On the other hand, D-Asp strongly and dose-dependently inhibited food intake over a period of 2 h after the administration. Oral D-Asp clearly increased D-Asp levels in the plasma and diencephalon, but no significant changes in L-Asp were detected. Brain monoamine contents were only minimally influenced by L- or DAsp administration. We conclude that D-Asp may act as an anorexigenic factor in the diencephalon. Key words: brain, D-Aspartate, food intake, L-Aspartate, neonatal chick, plasm

p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells

Colorectal cancer (CRC) cells harboring KRAS or BRAF mutations show a more-malignant phenotype than cells with wild-type KRAS and BRAF. KRAS/BRAF-wild-type CRCs are sensitive to epidermal growth factor receptor (EGFR)-targeting agents, whereas KRAS/BRAF-mutant CRCs are resistant due to constitutive activation of the EGFR-downstream KRAS/BRAF signaling pathway. Novel therapeutic strategies to treat KRAS/BRAF mutant CRC cells are thus needed. We recently demonstrated that the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 exhibit therapeutic potential against KRAS-mutant human pancreatic cancer cells. In this study, we evaluated the therapeutic potential of OBP-301 and OBP-702 against human CRC cells with differing KRAS/BRAF status. Human CRC cells with wild-type KRAS/BRAF (SW48, Colo320DM, CACO-2), mutant KRAS (DLD-1, SW620, HCT116), and mutant BRAF (RKO, HT29, COLO205) were used in this study. The antitumor effect of OBP-301 and OBP-702 against CRC cells was analyzed using the XTT assay. Virus-mediated modulation of apoptosis, autophagy, and the EGFR-MEK-ERK and AKT-mTOR signaling pathways was analyzed by Western blotting. Wild-type and KRAS-mutant CRC cells were sensitive to OBP-301 and OBP-702, whereas BRAF-mutant CRC cells were sensitive to OBP-702 but resistant to OBP-301. Western blot analysis demonstrated that OBP-301 induced autophagy and that OBP-702 induced autophagy and apoptosis in human CRC cells. In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis

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