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Jun Agata Nobuyuki Ura Hideaki Yoshida Yasuyuki Shinshi Haruki Sasaki Masaya Hyakkoku Shinya Taniguchi Kazuaki Shimamoto 《Hypertension research》2006,29(11):865-874
Angiotensin II receptor blockers (ARBs) are widely used for the treatment of hypertension. It is believed that treatment with an ARB increases the level of plasma angiotensin II (Ang II) because of a lack of negative feedback on renin activity. However, Ichikawa (Hypertens Res 2001; 24: 641-646) reported that long-term treatment of hypertensive patients with olmesartan resulted in a reduction in plasma Ang II level, though the mechanism was not determined. It has been reported that angiotensin 1-7 (Ang-(1-7)) potentiates the effect of bradykinin and acts as an angiotensin-converting enzyme (ACE) inhibitor. It is known that ACE2, which was discovered as a novel ACE-related carboxypeptidase in 2000, hydrolyzes Ang I to Ang-(1-9) and also Ang II to Ang-(1-7). It has recently been reported that olmesartan increases plasma Ang-(1-7) through an increase in ACE2 expression in rats with myocardial infarction. We hypothesized that over-expression of ACE2 may be related to a reduction in Ang II level and the cardioprotective effect of olmesartan. Administration of 0.5 mg/kg/day of olmesartan for 4 weeks to 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) significantly reduced blood pressure and left ventricular weight compared to those in SHRSP given a vehicle. Co-administration of olmesartan and (D-Ala7)-Ang-(1-7), a selective Ang-(1-7) antagonist, partially inhibited the effect of olmesartan on blood pressure and left ventricular weight. Interestingly, co-administration of (D-Ala7)-Ang-(1-7) with olmesartan significantly increased the plasma Ang II level (453.2+/-113.8 pg/ml) compared to olmesartan alone (144.9+/-27.0 pg/ml, p<0.05). Moreover, olmesartan significantly increased the cardiac ACE2 expression level compared to that in Wistar Kyoto rats and SHRSP treated with a vehicle. Olmesartan significantly improved cardiovascular remodeling and cardiac nitrite/ nitrate content, but co-administration of olmesartan and (D-Ala7)-Ang-(1-7) partially reversed this anti-remodeling effect and the increase in nitrite/nitrate. These findings suggest that olmesartan may exhibit an ACE inhibitory action in addition to an Ang II receptor blocking action, prevent an increase in Ang II level, and protect cardiovascular remodeling through an increase in cardiac nitric oxide production and endogenous Ang-(1-7) via over-expression of ACE2. 相似文献
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Keishi Kashibuchi Kyoichi Tomita Jack A Schalken Haruki Kume Takumi Takeuchi Tadaichi Kitamura 《International journal of urology》2007,14(9):789-794
OBJECTIVES: To determine the value of the loss of expression of E-cadherin and cadherin associated molecules as useful markers for both prognosis and chemosensitivity in bladder cancer patients who have undergone radical cystectomy. PATIENTS AND METHODS: In 55 paraffin embedded specimens of radical cystectomy at our hospital from 1982 to 2000, the expression of E-cadherin, alpha-, beta- and gamma-catenin was examined by immunohistochemical staining. To evaluate the prognostic significance of these molecules, Kaplan-Meier survival curves were constructed and a statistical analysis was calculated by a log-rank test. A multivariate test (tumor stage, tumor grade, lymph node metastasis, configuration, the expression of E-cadherin, alpha-, beta- and gamma-catenin) was performed to detect prognostic markers. RESULTS: Normal expression was found in 33 cases (60.0%) for E-cadherin, 29 (52.7%) for alpha-catenin, 31 cases (56.4%) for beta-catenin, and 31 cases (56.4%) for gamma-catenin. The expression patterns for E-cadherin, alpha-, beta- and gamma-catenin were significantly correlated with each other (P < 0.01). Survival analysis showed a significant difference between normal and aberrant expression in each staining. A multivariate analysis revealed that the expression of alpha- catenin was an independent prognostic factor (P = 0.0191). In 23 patients that received adjuvant chemotherapy, there was a significant difference in survival between the normal and aberrant expression of alpha-catenin, but not other molecules. CONCLUSION: Alpha-catenin may not only be a good prognostic marker, but also one of key molecules that determine the chemosensitivities in patients with invasive bladder cancer. 相似文献
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Tamikuni Komatsu Masayuki Nomura Youzou Kakudate Syuzou Fujiwara R. B. Heimann 《Macromolecular chemistry and physics.》1995,196(9):3031-3040
Dehydrochlorinated poly(vinylidene chloride) proved to be a conjugated polyene-polyene polymer. Shock compression of the polymer formed a large portion of graphite and trace amounts of diamond and of an unknown carbon. The unknown carbon belongs to the hexagonal crystal system and possesses the cell dimension α0 = 0.338 nm. A comparison with known carbynes was made in terms of the crystalline parameters. 相似文献
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Hisao Komatsu Junko Nogaya Masaaki Ueki Satoshi Yokono Kenji Ogli 《Clinical and experimental pharmacology & physiology》1994,21(6):495-499
1. We previously reported that volatile anaesthetics produce incidences of a transient opisthotonus in mice, a sign of CNS stimulation. This study was performed to investigate mechanisms by which enflurane-induced opisthotonus (EIO) occurs. 2. The effects of pretreatment of N-methyl-d-aspartate (NMDA) antagonists dizocilpine (MK-801; DIZ) and ketamine (KET), GABAA antagonists picrotoxin (PIC), pentylenetetrazol (PTZ) and glycine antagonist strychnine (STR) on the incidence of EIO were determined. Prior to exposure to 2.0% enflurane in air, male ddN mice were given intraperitoneal injections of 0.2 mL saline (control), 0.5–5.0 mg/kg DIZ, 20–80 mg/kg KET, 2.9 mg/kg PIC, 40.0 mg/kg PTZ and 0.75 mg/kg STR. After the injection, the behavioural state of the mice was observed for 20 min (the pre-enflurane period). During the exposure to enflurane the time for immobilization, that is, anaesthetic induction time (IT), and the incidence of EIO were measured. 3. Dizocilpine (1.0–5.0 mg/kg) and KET (80 mg/kg) significantly (P<0.01) reduced both the incidence of EIO and IT in a dose-dependent manner. During the pre-enflurane period DIZ produced incidences (5–40%) of transient seizures in a dose-dependent manner, while KET did not induce them at all. The two GABAa antagonists had no detectable effect on the EIO. Strychnine significantly enhanced the EIO. These CNS stimulants resulted in a 3–10% incidence of transient seizure and/or opisthotonus during the pre-enflurane period, but there was no correlation between DIZ-induced seizure and EIO. 4. These results suggest that the EIO is mediated by the NMDA and the STR-sensitive glycine receptors, but not the GABAA receptor. We speculate that DIZ acts on the NMDA-receptor and/or disrupts the balance between the inhibitory and the excitatory systems. 相似文献
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A total number of 427 patients with tetralogy of Fallot who underwent corrective surgery between 1960 and March 1990, in whom 211 patients who survived the surgery over 10 years were evaluated for the follow-up studies. Hemodynamic and cardiac function studies were carried out in 101 patients at the mean interval of 15.7 years (ranges 2 to 21 years). Three methods indicated that patients with muscle resection and pulmonary valvulotomy without patch enlargement (NP) had worse results than the groups with RV patch below valve (RP) and with transannular patch (TP). Also, Holter ECG revealed ventricular arrhythmias in patients with NP were more common than the groups with RP and TP. Sixteen patients (13 with NP, 2 with TP and one with RP) were required reoperation for residual ventricular shunt in 13, residual pulmonary stenosis in 11 and tricuspid regurgitation in 2. All of these 16 patients survived operation and obtained excellent clinical status. It is concluded that patients with TOF after corrective surgery should be carefully followed with short term interval to prevent sudden death and postoperative complications. 相似文献
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Yoshiharu Kikawa Akio Nakai Yosuke Shigematsu Masakatsu Sudo Kimitaka Kato Shinichi Haruki 《Pediatric nephrology (Berlin, Germany)》1990,4(4):343-344
Leukotriene B4 (LTB4) production in polymorphonuclear leucocytes (PMN) was examined in ten children with steroid-responsive nephrotic syndrome (SRNS) before, during, and after steroid administration. Comparison of LTB4 production was made in 14 children with non-inflammatory disease who were not receiving steroid therapy. No significant change was noted in PMN LTB4 biosynthesis in children with SRNS throughout any phase of the disease. Furthermore, there was no significant difference in LTB4 biosynthesis in PMN between SRNS patients before steroid therapy and patients with non-inflammatory disease. These findings suggest that inhibition of LTB4 production is not involved in the mechanism underlying steroid action in SRNS. 相似文献
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