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71.
KT5926, a potent and selective inhibitor of myosin light chain kinase 总被引:15,自引:0,他引:15
KT5926, (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3 ,9, 10-tetrahydro-8,11-epoxy, 1H,8H, 11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde] trinden-1-one, was found to be a potent and selective inhibitor of myosin light chain kinase. The compound inhibited both Ca2+/calmodulin-dependent and -independent smooth muscle myosin light chain kinases to a similar extent. The inhibition was not affected by the concentration of calmodulin. Kinetic analyses showed that the mode of inhibition was of the competitive type with respect to ATP (Ki, 18 nM) and of the noncompetitive type with respect to myosin light chain (Ki, 12 nM). These results indicated that KT5926 directly interacted with the enzyme at the catalytic site. KT5926 also inhibited other protein kinases, but with relatively high Ki values; the values for protein kinase C, cAMP-dependent protein kinase, and cGMP-dependent protein kinase were 723, 1200, and 158 nM, respectively. Ca2(+)-ATPase, Na+/K(+)-ATPase, hexokinase, and 5'-nucleotidase were not inhibited by KT5926 at less than 10 microM. The effect of KT5926 on serotonin secretion and protein phosphorylation induced by platelet-activating factor or phorbol ester was examined in rabbit platelets. KT5926 inhibited the phosphorylation of a 20-kDa protein but had no effect on the phosphorylation of a 40-kDa protein, thereby indicating that the compound exerts its selective inhibition of myosin light chain kinase in intact cells. The compound inhibited serotonin secretion induced by platelet-activating factor, but its potency was significantly less than that 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, which inhibited the phosphorylation of both the 20-kDa protein and the 40-kDa protein. Phorbol ester-induced secretion was not suppressed by KT5926. These results provide the evidence that both the 20-kDa protein phosphorylation by myosin light chain kinase and the 40-kDa protein phosphorylation by protein kinase C substantially contribute to the secretion response in platelets. 相似文献
72.
Bunta Kato Koji Yamada Masahiro Horiuchi Toshikazu Hirayama Yasuhiro Hasegawa 《Clinical neurology》2007,47(9):577-580
A 79-year-old woman with a 4-year history of Parkinson's disease was admitted due to unique dyspneic attacks with cyanosis while eating. Dyspneic attacks with cyanosis occurred mainly during actions such as taking meals or rehabilitation. Due to increased tonus of the orbicularis oris muscle, she was unable to open her mouth and breathe out, and finally experienced hypoxemia as revealed by pulse oxymetry. Dystonic hypertonus was relieved by touching the mandible with the fingers, and she was able to open her mouth again. These symptom was compatible with the sensory trick. Based on these findings, we considered that dyspneic attacks were produced by focal oromandibular dystonia. Polysomnography also showed central sleep apnea. We report herein a rare case of Parkinson's disease presenting with respiratory insufficiency caused by focal dystonia and central sleep apnea. 相似文献
73.
Mitsuru Masaki Tadashi Kuroda Naoki Hosen Hisao Hirota Kazuo Terai Yuichi Oshima Yoshikazu Nakaoka Shoko Sugiyama Ryusuke Kimura Satoshi Yoshihara Manabu Kawakami Norishige Iizuka Yasuhiko Tomita Hiroyasu Ogawa Ichiro Kawase Keiko Yamauchi-Takihara 《Journal of the American Society of Echocardiography》2004,17(4):397-398
A 57-year-old man with a history of renal cell carcinoma presented with presyncope. He underwent nephrectomy years earlier followed by HLA-matched allogeneic peripheral-blood stem-cell transplantation. Echocardiographic investigation revealed a solitary right ventricle mass without contiguous vena caval or right atrial involvement. The mass was pathologically confirmed to be metastatic carcinoma in the right ventricular cavity. This case highlights the need to consider an underlying neoplastic syndrome in patients presenting isolated right ventricle mass by echocardiography. 相似文献
74.
Satoshi Suzuki Koji Yasuda Yuji Matsumura Takashi Kondo 《The Japanese Journal of Thoracic and Cardiovascular Surgery》2006,54(5):225-227
We present here a rare case of left-side catamenial pneumothorax, in which endometrial tissue pleura was found on the visceral pleura histologically. A chest roentogenogram confirmed the left pneumothorax, but did not reveal bullae or any associated anomalies, in a 41-year-old woman with three documented episodes of left-side pneumothorax occurring every menstruation. Video-assisted thoracoscopic surgery revealed not only tiny holes in the diaphragm, but also a scattered small brown spots on the visceral pleura. Histological examination of the lung sections revealed the existence of endometrial tissue on the visceral pleura with disrupted pleural elastic fibers. Our case suggests that cyclic erosion of the visceral pleura by the implanted endometrial tissue caused air leakage from the lung, in addition to the most accepted concept that air is aspirated into the thoracic cavity via the abdomen through the acquired fenestration of the diaphragm. 相似文献
75.
Takashi Yamauchi Takafumi Masai Koji Takeda Satoshi Kainuma Yoshiki Sawa Kazuo Abe 《Annals of thoracic and cardiovascular surgery》2007,13(6):410-412
We report a rare case of constrictive pericarditis that stimulated a large mediastinal tumor obstructing the right ventricular inflow tract. A 58-year-old woman was referred to our hospital because of a recent increase of dyspnea and facial edema. Computed tomography revealed severely thickened calcification, including a low-density area, presenting as a mediastinal tumor, compressing the right ventricular inflow tract. A complete resection was performed, and her symptoms dramatically improved. Idiopathic constrictive pericarditis was diagnosed pathologically. 相似文献
76.
Masato Nakajima Koji Tsuchiya Yoshihiro Honda Hiroshi Koshiyama Tatsuho Kobayashi 《General thoracic and cardiovascular surgery》2009,57(12):654-656
Although the causes of stroke are diverse, thromboembolism due to a mobile aortic thrombus is rare. We describe a surgical
case of acute massive pulmonary embolism after critical cerebral infarction associated with a mobile ascending aortic thrombus
in a 52-year-old woman. Concomitant surgical removal of the aortic thrombus and pulmonary embolectomy was performed successfully,
and the patient has been stable without recurrent thromboembolic complications after 18 months of follow-up. 相似文献
77.
Kenji Yamao Atsushi Irisawa Hiroyuki Inoue Koji Matsuda Mitsuhiro Kida Shomei Ryozawa Yoshiki Hirooka Teruo Kozu 《Digestive endoscopy》2007,19(Z1):S180-S205
Standard imaging techniques using a curved linear array echoendocope are summarized to facilitate the attainment of expertise in endoscopic ultrasonography and endoscopic ultrasound‐guided fine needle aspiration, and to promote the widespread use of this diagnostic and therapeutic tool. Typical images of the mediastinal organs, the bilio‐pancreatic systems and neighboring organs by scanning from the esophagus, stomach, duodenal bulb, and descending portion of the duodenum, are shown in a sequential manner. The basic techniques of endoscopic ultrasound‐guided fine needle aspiration are also presented. 相似文献
78.
79.
Naoki Sugawara Koji Arizono Toshiichi Kitajima Hideaki Inoue Yu-Rong Lai 《Archives of toxicology》1997,71(5):336-339
A new mutant, the Eisai hyperbilirubinemic (EHB) rat, shows no inherent expression of the canalicular isoform of the multidrug
resistance protein (cMrp) in the liver. It has defective biliary secretion of organic anions such as bilirubin glucuronides,
bromosulfophthalein (BSP), cysteinyl leukotrienes, glutathione (GSH) and bile acid sulfate and glucuronides. When rats were
injected intravenously with CdCl2, biliary excretion of Cd over 30 min was 0.28% and 0.004% of the total dose in Sprague-Dawley (SD) and EHB rats, respectively.
Six SD rats and five EHB rats were fed a diet containing Cd. Bile Cd was detected at the level of 2 ng/20 min in SD rats,
but not in EHB rats. There was no significant difference of hepatic Cd concentration between SD and EHB rats. Furthermore,
there were no significant differences of renal and intestinal Cd, and hepatic and renal metallothionein (MT) concentrations
between the SD and EHB groups. Biliary excretion of reduced-GSH for 20 min was 1.3 ± 0.3 mg and 3.6 ± 0.9 μg in SD and EHB
rats, respectively. Our results suggest that hepatobiliary excretion of exogenous Cd is mediated mainly via carrier transport,
including a cMrp or GSH carrier, but that the lack of the transport pathway does not contribute to abnormal accumulation of
Cd in the liver.
Received: 12 August 1996 / Accepted 7 November 1996 相似文献
80.
In ovariectomized rhesus monkeys, the electrophysiological manifestation of luteinizing hormone-releasing hormone (LHRH) pulse generator activity was arrested by morphine and reinitiated by naloxone. These responses were noted within 1 and 2 min, respectively, after the intravenous injection of the drugs. Naloxone given alone had no effect. These results support the view that opioids modulate pulsatile gonadotropin release by an action on the hypothalamic LHRH pulse generator. 相似文献