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Shiro Akinaga Tadashi Ashizawa Katsushige Gomi Hiroe Ohno Makoto Morimoto Chikara Murakata Masami Okabe 《Cancer chemotherapy and pharmacology》1992,29(4):266-272
Summary Novel derivatives of K-252a, (8R*,9S*,11S*)-(–)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9,10-tetrahydro-8, 11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo [a,g]-cycloocta[cde]trinden-1-one, an inhibitor of protein kinases and calmodulin-dependent phosphodiesterase, were synthesized and evaluated for their antitumor activity in vitro and in vivo. Of ten derivatives tested, four were active against the P388 murine leukemia i. p.-i. p. system, although K-252a was inactive. Among these derivatives, KT6124 was selected for further biological evaluation studies because its efficacy was the highest. KT6124 was also active against sarcoma 180 and B16 melanoma. It exerted a relatively broad spectrum of antiproliferative activity against 20 human tumor cell lines in vitro. To determine the mechanism(s) of action underlying the antitumor activity of KT6124, we tested the drug for inhibition of protein kinases, including Ca2+-and phospholipid-dependent protein kinase (PKC), in intact A431 human epidermoid carcinoma cells in comparison with the PKC-inhibitory activity of K-252a. KT6124 did not antagonize the action of phorbol 12-myristate 13-acetate (PMA) in A431 cells, whereas K-252a did, suggesting that KT6124 may not act on protein kinases in the cells. The interaction of KT6124 with DNA in living cells was examined by the alkaline elution method. KT6124 apparantly exhibited DNA scission both dose-and time-dependently in the target cells. The DNA breakage was dependent on proteinase K treatment, suggesting its possible interaction with DNA-related enzyme(s). These results indicate that KT6124 exerts antitumor activity by acting on DNA or on DNA-related enzyme(s) in tumor cells rather than via the inhibition of protein kinases. 相似文献
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Yuji Maruyama Shigeo Yamauchi Hidetsugu Ogasawara Hajime Imura Masami Ochi Kazuo Shimizu 《Annals of thoracic and cardiovascular surgery》2006,12(1):60-62
Surgical treatment for subacute pulmonary arterial thromboembolism has previously been considered to be inappropriate. We undertook a pulmonary arterial thrombectomy and removal of a floating right heart thrombus in a patient who had been symptomatic for over a month. The pulmonary arterial pressure, which had been equal to the systemic pressure preoperatively, decreased gradually and almost normalized one month postoperatively. Pulmonary perfusion scintigraphy revealed a dramatic improvement and the patient returned to normal life activities. 相似文献
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Use of Glycopeptidolipid Core Antigen for Serodiagnosis of Mycobacterium avium Complex Pulmonary Disease in Immunocompetent Patients 下载免费PDF全文
Seigo Kitada Ryoji Maekura Naomi Toyoshima Takashi Naka Nagatoshi Fujiwara Masami Kobayashi Ikuya Yano Masami Ito Kazuo Kobayashi 《Clinical and Vaccine Immunology : CVI》2005,12(1):44-51
We report the development of a serodiagnostic method for Mycobacterium avium complex (MAC) disease with an enzyme immunoassay (EIA) with the MAC-specific glycopeptidolipid (GPL) core as the antigen. In this study, we confirmed by EIA that the GPL core antibody was in the sera of immunocompetent patients with MAC disease. The EIA for quantifying the GPL core antibody was evaluated as a clinical tool for serodiagnosis of pulmonary MAC disease. A significant increase in GPL core antibodies (immunoglobulins G, A, and M) was detected in sera of patients with MAC pulmonary diseases when they were compared to patients who were colonized with MAC, patients with Mycobacterium kansasii disease or tuberculosis, and healthy subjects. The sensitivities and specificities of the GPL core-based EIA for diagnosis of MAC pulmonary disease were 72.6% and 92.2%, respectively, for IgG, 92.5% and 95.1%, respectively, for IgA, and 78.3% and 91.0%, respectively, for IgM. The best sensitivity and specificity were obtained by measuring immunoglobulin A antibodies against GPL core antigen. The level of GPL core antibodies reflected disease activity, since it decreased in cured MAC patients who had responded to chemotherapy. Measurement of serum antibodies against GPL core is useful for both diagnosis and assessment of disease activity in MAC disease of the lung. 相似文献
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M. Iwasa Y. Maeno H. Inoue H. Koyama R. Matoba 《International journal of legal medicine》1996,109(1):23-28
We examined whether methamphetamine (MAP) induced apoptotic cell death in vivo. Male Wistar rats were injected intraperitoneally with 25 mg MAP/Kg body weight and were sacrificed at 4, 8 and 24 h. As early as 4 h after a single dose of MAP, DNA ladder bands representing DNA fragmentation into multiples of the internucleosomal DNA length of about 180 by were observed by gel electrophoresis in thymic and splenic DNA. DNA from control rats injected with 1 ml physiological saline/Kg body weight showed no ladder band patterns. The proportion of fragmented DNA from the thymus increased in a time-dependent manner up to 8 h and faint ladder band patterns were observed at 24 h, indicating that cell death via apoptosis occurred at an early stage and then apoptotic bodies were scavenged. DNA fragmentation in the thymus and spleen induced with MAP was also confirmed by the terminal deoxynucleotidyl transferase-mediated dUTPbiotin nick end labeling (TUNEL) method in situ. In control thymus samples, stained cells were numerous in the cortex but sparse in the medulla. At the boundary area between the cortex and medulla, stained cells were seen as a layer. In the MAP-treated rats, stained cells were increased and dispersed equally in the cortex and medulla. In control spleen samples, stained cells were numerous in all areas excluding the germinal centers. Cells at the germinal centers were stained intensively in MAP-treated rat spleen. Light microscopical analyses allowed us to identify lymphocytes during the course of apoptotic cell death. Electron microscopic studies showed morphological landmarks for the process of cellular apoptosis in both organs e.g. lymphocytes with chromatin condensed into crescents at the periphery of the nuclei and apoptotic bodies. These results indicate that MAP induced cell death of the thymic and splenic lymphocytes via apoptosis. 相似文献
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S Ogoshi M Iwasa S Kitagawa Y Ohmori S Mizobuchi Y Iwasa T Tamiya 《JPEN. Journal of parenteral and enteral nutrition》1988,12(1):53-57
The effect of a nucleoside-nucleotide mixture on liver injury of rats induced by D-galactosamine was studied by examining changes in function and histopathology of the liver. Animals with liver damage received total parenteral nutrition with glucose and amino acids supplemented with a nucleoside-nucleotide mixture containing inosine, cytidine, GMP, uridine and thymidine, or with uridine which inhibits galactosamine injury, or with liver cell extract containing flavin adenine dinucleotide and nucleic acid derivatives. As control, animals with liver damage received total parenteral nutrition with glucose and amino acids only. The serum GOT and GPT concentrations were significantly lower in the group supplemented with nucleoside-nucleotide mixture than those in other groups. A large dose (1.2 g/kg) of uridine inhibited liver injury, but a lower dose (0.14 g/kg) did not have any effect, whereas nucleoside-nucleotide mixture containing the same amount of uridine inhibited the injury. Liver cell extract also did not improve liver function. Thus infusion of a physiological and balanced mixture of nucleosides or nucleotides may improve liver function in rats with liver injury. 相似文献
10.
Myocardial protective effect of lidocaine during experimental off-pump coronary artery bypass grafting. 总被引:1,自引:0,他引:1
Kazuhiro Hinokiyama Nobuo Hatori Masami Ochi Tadaaki Maehara Shigeo Tanaka 《Annals of thoracic and cardiovascular surgery》2003,9(1):36-42
Off-pump coronary artery bypass grafting (OPCABG) has recently gained popularity. During OPCABG, patients remain vulnerable to ischemic-reperfusion injury due to a temporary coronary occlusion without any active cardioprotection. Some strategies such as ischemic preconditioning (IP) and an intracoronary shunt have been applied with a view to minimizing the effects of ischemia, but the effects of these strategies remain controversial. This study was carried out to investigate the protective effect of lidocaine against myocardial ischemic-reperfusion injury. Twenty-one pigs were assigned to three groups, each consisting of seven pigs. In the control group, using a left internal thoracic artery (LITA) bypass circuit, the left anterior descending coronary artery (LAD) was occluded for 45 min followed by two hours of reperfusion. In the IP group, five min of occlusion followed by 15 min of reperfusion was performed. In the lidocaine group, 2 mg/kg of lidocaine was administered directly into the LAD just before the LAD occlusion. Infarct size expressed as a percentage of the area at risk was significantly smaller in the lidocaine group (2.7+/-4.2%) than in the control group (79.9+/-6.0%, p<0.001) or the IP group (57.0+/-25.9%, p<0.001). Lidocaine exhibited a potent myocardial protective effect in the present OPCABG model. 相似文献