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Mitsumasa Iwata Shunji Izuta Motoshi Suzuki Kiyohide Kojima Yoshihito Furuhashi Yutaka Tomoda Shonen Yoshida 《Cancer science》1991,82(4):433-439
We examined the mechanisms of the inhibition of DNA synthesis by a new platinum compound, (-)-( R )-2-aminomethylpyrrolidine(1,1-cyclobutane-dicarboxylato)-2-platinum(II) monohydrate (DWA-2114R), a derivative of the antitumor drug cis- diamminedichloroplatinum(II) (CDDP), using prokaryotic and eukaryotic DNA polymerases. Preincubating activated DNA with CDDP or DWA-2114R reduced its template activity for prokaryotic and eukaryotic DNA polymerases in a dose-dependent manner. DWA2114R required six times greater drug concentration and two times longer incubation time to show the same decrease of the template activity compared to CDDP. Treatment of primed pUC118 ssDNA templates with the two drugs followed by second-strand synthesis by prokaryotic and eukaryotic DNA polymerases revealed that DWA2114R bound to DNA in a similar manner to CDDP and these adducts blocked DNA elongation by DNA polymerases of eukaryotes as well as of prokaryotes. With these two drugs, the elongations by E. coli DNA polymerase I (Klenow fragment), T7 DNA polymerase and calf thymus DNA polymerase α were strongly arrested at guanine-guanine sequences (GG). Stop bands were also observed at adenine-guanine sequences (AG) guanine-adenine-guanine sequences (GAG) and mono-guanine sequence (G). Calf testis DNA polymerase β was also arrested efficiently at AG, GAG and G, but much more weakly at GG. This pattern was common to DWA2114R and CDDP. 相似文献
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Yutaka Okishio Tadayoshi Takeuchi Akikazu Fujita Kiyotaka Suenaga Kaori Fujinami Satoru Munakata Tadashi Takewaki Fumiaki Hata 《Journal of Smooth Muscle Research》2005,41(3):163-174
Recently an essential role of interstitial cells of Cajal (ICC) within myenteric plexus (ICC-MY) was suggested in ascending contraction and descending relaxation in the mouse ileum. The role of ICC in these neural reflexes was examined in the distal colonic segments prepared from the wild type and c-kit mutant, W/W(V) mice, in the present study. Localized distension of the segments from the wild type mice by using a small balloon resulted in ascending contraction and descending relaxation. In the segments from the mutant mice, localized distension also induced these neural reflexes similar to those observed in the wild type mice. Immunohistochemical examination demonstrated that ICC-MY and ICC present in muscle layers (ICC-IM) were severely disrupted in the mutant mouse, but only ICC, present within submucosal plexus (ICC-SMP), remained unchanged. In the small strips with ICC-SMP absent prepared from the mutant mouse, electrical field stimulation induced contraction or relaxation in the absence or presence of atropine, respectively. It was suggested that ICC have no important role in the ascending and descending neural reflexes in the mouse distal colon, this is in direct contrast to the role of ICC-MY in the ileum. 相似文献
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目的评估十二指肠-空肠导管(Endoluminal Duodeno-Jejunal Tube,EDJT)在活体猪实验动物模型中减缓体重增加的可行性,及其在中短期生存中的安全性。方法本项研究共用8只45kg重的Yorkshire猪,其中3只置入180emEDJT,1只置入360cm EDJT,另4只猪作为对照组。切开十二指肠,将EDJT导管缝合固定在十二指肠近Vater壶腹起始处。结果评估全部猪的不适反应和体重,每日一次,共7周,未发现严重并发症发生。术后7周3组动物的平均体重变化百分率:对照组、180cm组和360cm组分别是22.5%,6%和-2.8%。EDJT组(180cm组、360cm组)体重增加明显减慢,与对照组相比,有统计学意义(P=0.05)。结论EDJT可以安全使用,无肠梗阻、肠套叠或胰腺炎等并发症发生。EDJT可明显减缓体重增加。 相似文献
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Effect of the free radical scavenger MCI-186 on spinal cord reperfusion after transient ischemia in the rabbit 总被引:4,自引:0,他引:4
Kenichi Hashizume Toshihiko Ueda Hideyuki Shimizu Atsuo Mori Ryohei Yozu 《The Japanese Journal of Thoracic and Cardiovascular Surgery》2005,53(8):426-433
Objective: Paraplegia remains a serious complication of aortic operations. The production of free radicals during reperfusion
after transient ischemia is believed to induce secondary spinal neuronal injury, resulting in paraplegia. The aim of the present
study was to clarify the protective effect and method of administration of antioxidants on the neurological and histological
outcome in the animal model for reperfusion injury after transient spinal cord ischemia. Methods: New Zealand white rabbits underwent surgical exposure of the abdominal aorta that was clamped for 15 minutes to achieve spinal
cord ischemia. Group A animals received two 10 mg/kg doses of 3-methyl-l-phenyl-2-pyrazolin-5-one (MCI-186) at the time of
release of the aortic clamp and 30 minutes later. In group B, MCI-186, 5 mg/kg, was given three times, at the time of aorta
clamp release, 30 minutes and 12 hours later. In group C (control group), one dose of vehicle was administered. Neurological
status was assessed using modified Tarlov’s score until 168 hours after operation. Spinal cord sections were examined microscopically
to determine the extent of ischemic neuronal damage. Results: Groups A and B animals had better neurological function than group C (p(0.001). In contrast, group C animals exhibited paraplegia or paraparesis with marked neuronal necrosis. The number of surviving
neurons within examined sections of the spinal cord was significantly greater in group B than in group C (p(0.001). Conclusion: In a 15-minute ischemia-reperfusion model using rabbits, systemic repetitious administration of MCI-186, a free radical scavenger,
was found to have a protective effect on the spinal cord neurons both neurologically and histologically. We postulate that
the drug minimizes the delayed neuronal cell death for reperfusion injury after transient ischemia by reducing the free radical
molecules. Moreover, it was thought that we could protect delayed neuronal cell death more effectively by administering MCI-18612
hours later. 相似文献
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Makoto Osawa Yutaka Ito Toyohiro Hirai Rie Isozumi Shunji Takakura Yasuhiro Fujimoto Yoshitsugu Iinuma Satoshi Ichiyama Koichi Tanaka Michiaki Mishima 《Liver transplantation》2007,13(4):566-570
Invasive aspergillosis (IA) is a severe complication of liver transplantation. Risk factors for IA after deceased donor liver transplantation (DDLT) have been presented in several reports, but are not well established for living donor liver transplant recipients. Here, a retrospective case-control study was performed. Five cases with IA were investigated after living donor liver transplantation (LDLT) between January 1999 and December 2002 at Kyoto University Hospital. For comparison, living donor liver transplant recipients without IA were taken as controls. These patients had undergone LDLT 1 month before or after each IA case and had the same survival times as the latter. We evaluated the clinical and laboratory findings for both groups up until their demise. Patients with IA after LDLT had a very poor prognosis. By univariate analysis, risk factors for IA were preoperative intensive care unit stay (P = 0.02) and preoperative steroid administration (P = 0.02). Preoperative steroid administration for fulminant hepatitis possibly predisposed to the development of IA after LDLT. 相似文献