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Volume 115 (2000)
- Issue 6 Pages 323-
- Issue 5 Pages 271-
- Issue 4 Pages 185-
- Issue 3 Pages 123-
- Issue 2 Pages 67-
- Issue 1 Pages 5-
Volume 115, Issue 3
Displaying 1-7 of 7 articles from this issue
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Ryuichi MORISHITA2000 Volume 115 Issue 3 Pages 123-130
Published: March 01, 2000
Released on J-STAGE: September 07, 2011
JOURNAL FREE ACCESSRecent progress in molecular biology has provided new techniques to inhibit target gene expression. Especially, the application of DNA technology such as antisense strategy to regulate the transcription of disease-related genes in vivo has important therapeutic potential. Recently, transfection of cis-element double-stranded (ds) oligodeoxynucleotides (ODN) (= decoy) as a powerful tool in a new class of anti-gene strategies for gene therapy and the study of transcriptional regulation has been reported. Transfection of ds ODN corresponding to cis sequence will result in the attenuation of authentic cis-trans interaction, leading to the removal of trans-factors from the endogenous cis-elements with subsequent modulation of gene expression. This “decoy” strategy is not only a novel strategy for gene therapy as an anti-gene strategy, but also a powerful tool for the study of endogenous gene regulation in vivo as well as in vitro. In this article, we reviewed 1) the mechanisms, and 2) potential applications of decoy strategy.View full abstractDownload PDF (5611K) -
Yukihiko SUGIMOTO2000 Volume 115 Issue 3 Pages 131-141
Published: March 01, 2000
Released on J-STAGE: September 07, 2011
JOURNAL FREE ACCESSProstaglandins exert a wide variety of biological actions through specific receptors. The prostaglandins PGE2 and PGF2α have been suggested to affect many physiological processes. There have been four pharmacologically identified receptor subtypes, EP1 through EP4 for PGE2 and a single receptor type, FP for PGF2α. However, it is yet unknown as to which receptor is involved in each process. To make this clear, we investigated the distribution of these receptors in various sytems and established mice deficient in each receptor and examined their physiology. Finally, we found that these receptors are involved in several processes associated with reproduction physiology. FP-deficient mice are able to become pregnant, but can-not deliver their pups because of the lack of parturition; luteolysis does not occur normally. EP2-deficient mice are able to become pregnant, but their litter sizes are much reduced, which is due to defects in ovulation and fertilization; cumulus cell function is impaired. EP4-deficient mice die within a few days after birth because of patency of the ductus arteriosus; remodeling of cardiovascular system during birth is im-paired. Thus, the E- and F-types of prostaglandins play roles in cumulus function, luteolysis and ductus closure through EP2, FP and EP4, respectively.View full abstractDownload PDF (9232K) -
Hiroyuki MATSUNO2000 Volume 115 Issue 3 Pages 143-150
Published: March 01, 2000
Released on J-STAGE: September 07, 2011
JOURNAL FREE ACCESSThe long-lasting success of PTCA, a common treatment for patients with coronary artery disease, is hampered by acute reocclusion due to thrombus and by late restenosis due to smooth muscle cell (SMC) migration and proliferation. Recently potent antiplatelet agents such as inhibitors of platelet glycoprotein (GP) IIb/ IIIa (αIIb/β3) have become available and are highly effective in humans. We investigated the inhibitory effects of these compounds on vascular stenosis. Administration of an RGD-containing peptide (non-selective αIIb/β3 antagonist) results in reduction of neointima, but selective α IIb/ β3 antagonists have no effect. This effect is due both to an early event, which could be due to the inhibition of secretion of PDGF from activated platelets with blocked α IIb/ β3, and to a late event, by interference with SMC αv/ β3. Moreover, platelet adhesion via GPIb/V/IX is a trigger for thrombus formation. Inhibition of platelet adhesion results in the prevention of thrombus formation and the suppression of neointima. However, this effect was supported by the reduction of SMC proliferation. Therefore, these dual inhibitions markedly reduced vascular stenosis. Finally some low molecular mass heat shock proteins (HSPs) appear to act as molecular chaperones, but their physiological roles have not been fully elucidated. We have investigated the physiological role of p20, a kind of HSP, on platelet function. p20 inhibited platelet aggregation. Our findings may provide the basis for a novel defensive system against thrombus formation.View full abstractDownload PDF (5360K) -
Yoshiyuki INADA, Takehiko NAKA2000 Volume 115 Issue 3 Pages 151-160
Published: March 01, 2000
Released on J-STAGE: September 07, 2011
JOURNAL FREE ACCESSThe nonpeptide angiotensin II (AII) subtype-1 (AT1) receptor antagonist candesartan cilexetil is completely converted to its active form, candesartan, during gastrointestinal absorption. In in vitro studies, candesartan has been found to act as an insurmountable antagonist at the AT1 receptor that dosedependently reduces the maximal contractions induced by AII and, at high concentrations, virtually eliminates the AT1-receptor-mediated effects of AII. Receptor binding studies suggest that insurmountable antagonism may be due to tight binding to the AT1 receptor and slow dissociation from it. The antihypertensive efficacy of candesartan cilexetil has been demonstrated in different animal models of hypertension. Candesartan cilexetil exerts a long-lasting antihypertensive action in spontaneously hypertensive rats in the low dose range of 0.1-10 mg kg. The long-lasting antihypertensive effect of candesartan cilexetil is confirmed by the trough peak ratio in hypertensive patients. It has been demonstrated that administration of AII receptor antagonists is followed by a rise in AII levels, and the increased AII levels result in competition with the antagonist for binding to the receptor. Insurmountable antagonists would seem to be more advantageous since they would block more efficiently in the presence of increasing AII levels than surmountable antagonists. A growing number of studies indicate that candesartan cilexetil provides end-organ protection in addition to lowering blood pressure. The utility of AT1 antagonists may extend beyond treatment of hypertension, chronic heart failure and renal diseases, as suggested by the potential usefulness of ACE inhibitors in the treatment or prevention of many other cardiovascular diseases.View full abstractDownload PDF (2255K) -
Masao SASAMATA, Michael A. MOSKOWITZ, Eng H. LO2000 Volume 115 Issue 3 Pages 161-169
Published: March 01, 2000
Released on J-STAGE: September 07, 2011
JOURNAL FREE ACCESSRecently, we established a novel temporal correlation mapping (TCM) technique in combination with high-resolution functional computed tomography (CT) scanning to analyze the temporal changes in bolus transit dynamics of iodinated contrast agents in focal cerebral ischemia. Based on changes in the temporal dynamics of blood flow, we defined a new kind of penumbra and core in focal ischemia: the hemodynamic penumbra and hemodynamic core. We visualized for the first time a larger hemodynamic core and smaller hemodynamic penumbra in endothelial NOS knockout mice than in wild type mice early after focal ischemia by using the TCM analysis technique. In addition, neuroprotective effects of the water-soluble AMPA receptor antagonist YM872 were for the first time observed in the hemodynamic penumbra after focal ischemia. In conclusion, early TCM analysis could be used to directly and quantitatively evaluate the effects of neuroprotective therapy and the evolution of neuronal damage in the hemodynamic penumbra.View full abstractDownload PDF (8269K) -
2000 Volume 115 Issue 3 Pages b41-b61
Published: March 01, 2000
Released on J-STAGE: September 07, 2011
JOURNAL FREE ACCESSDownload PDF (5188K) -
2000 Volume 115 Issue 3 Pages b63-b80
Published: March 01, 2000
Released on J-STAGE: September 07, 2011
JOURNAL FREE ACCESSDownload PDF (4425K)
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