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Kazuhisa Nakayama,Kim, Won-Sin,Seiji Torii,Masahiro Hosaka,Tsutomu Nakagawa,Jo Ikemizu,Tadashi Baba,Kazuo Murakami 원광대학교기초자연과학연구소 1992 基礎科學硏究誌 Vol.11 No.3
We used the polymerase chain reaction to identify a mouse testis cDNA that represented another member of a growing class of mammalian endoproteases involved in the processing of precursor proteins. This cDNA encoded a 655-residue protein, designated PC4, containing a bacterial subtilisin-like catalytic domain closely related to those of the recently characterized precursor-processing endoproteases, furin, PC1/PC3, PC2, and Kex2. Within this domain, the amino acid sequence of PC4 was 70, 58, 55, and 45% identical with those of mouse furin, mouse PC1/PC3, mouse PC2, and yeast Kex2, respectively. Northern blot analysis indicated that the PC4 mRNA was detectable only in the testes after the 20th day of postnatal development. Moreover, this message was mainly expressed in the round spermatids. These data suggest that PC4 represents a prime candidate for a precursor-processing endoprotease in the testicular germ cells and that its gene expression is regulated during spermatogenesis.
( Norihiro Imai ),( Kenji Ikeda ),( Yuya Seko ),( Yusuke Kawamura ),( Hitomi Sezaki ),( Tetsuya Hosaka ),( Norio Akuta ),( Masahiro Kobayashi ),( Satoshi Saitoh ),( Fumitaka Suzuki ),( Yoshiyuki Suzuk 대한간학회 2013 Gut and Liver Vol.7 No.2
Miriplatin is a novel lipophilic platinum complex that was developed to treat hepatocellular carcinoma (HCC). Although HCC patients frequently have coexisting chronic renal failure, little prospective data are available regarding the clinical toxicity of chemotherapeutic agents used to treat HCC patients with chronic renal failure. In a phase II study, the plasma concentration of total platinum in patients who received miriplatin was very low, and no severe renal toxicity caused by miriplatin injection was reported. Here, we present three cases of HCC with stage 4 chronic renal failure who received transcatheter arterial chemotherapy with miriplatin. All cases were male, ages 72, 84, and 83 years, and had serum creatinine levels of 2.3, 1.6, and 1.9 mg/dL, respectively. Their estimated glomerular filtration rates were 21.9, 20.3, and 22.2 mL/min, respectively. All cases were treated for unresectable HCC with transcatheter arterial chemotherapy with miriplatin. No serious adverse events were observed, and serum creatinine levels did not elevate, even in the patient who experienced renal failure caused by cisplatin administration. These results might suggest that transcatheter arterial chemotherapy with miriplatin can be safely used in HCC patients with chronic renal failure. (Gut Liver 2013;7:246-251)
( Norio Akuta ),( Yusuke Kawamura ),( Yasuji Arase ),( Fumitaka Suzuki ),( Hitomi Sezaki ),( Tetsuya Hosaka ),( Masahiro Kobayashi ),( Mariko Kobayashi ),( Satoshi Saitoh ),( Yoshiyuki Suzuki ),( Kenj 대한간학회 2016 Gut and Liver Vol.10 No.3
Background/Aims: It is important to determine the noninvasive parameters of histological features in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the value of genetic variations as surrogate markers of histological features. Methods: The parameters that affected the histological features of NAFLD were investigated in 211 Japanese patients with biopsy-proven NAFLD. The relationships between genetic variations in PNPLA3 rs738409 or TM6SF2 rs58542926 and histological features were analyzed. Furthermore, the impact of genetic variations that affected the pathological criteria for the diagnosis of nonalcoholic steatohepatitis (NASH) (Matteoni classification and NAFLD activity score) was evaluated. Results: The fibrosis stage of PNPLA3 GG was significantly more progressive than that of CG by multiple comparisons. Multivariate analysis identified PNPLA3 genotypes as predictors of fibrosis of stage 2 or more, but the impact tended to decrease at stage 3 or greater. There were no significant differences among the histological features of the three genotypes of TM6SF2. PNPLA3 genotypes partly affected the definition of NASH by the NAFLD activity score, but TM6SF2 genotypes did not affect the definition of NASH. Conclusions: In Japanese patients with biopsy-proven NAFLD, PNPLA3 genotypes may partly affect histological features, including stage of fibrosis, but the TM6SF2 genotype does not affect histological features. (Gut Liver 2016;10:437-445)
Kazuhisa, Nakayama,Toshio, Watanabe,Tsutomu, Nakagawa,Kim, Won Sin,Masami, Nagahama,Masahiro, Hosaka,Kiyotaka, Hatsuzawa,Kiyomi, Kondoh-Hashiba,Kazuo, Murakami 圓光大學校 基礎自然科學硏究所 1993 基礎科學硏究誌 Vol.12 No.2
Many peptide hormones and neuropeptides are produced from larger, inactive precursors though endoproteolysis at sites usually marked by paired basic residues (primarily Lys-Arg and Arg-Arg), or occasionally by a monobasic residue (primarily Arg). Based upon data concerning processing of prorenin and its mutants around the native Lys-Arg cleavage site expressed in mouse pituitary AtT-20 cells, we present the following sequence rules that govern mono-arginyl cleavages: (a) a basic residue at the fourth (position-4) or the sixth(position-6) residue upstream of the cleavage site is required, (b) at position - 4, Arg ; more favorable than Lys, and (c) at position I, a hydrophobic aliphatic residue is not suitable. These rules are compatible with those proposed by comparison of precursor sequences around mono-arginyl cleavage sites. We also provide evidence that precursor cleavages at mono-arginly and dibasic sites can be catalyzed by the same Kex2-like processing endoprotease, PC1/PC3.
( Yusuke Kawamura ),( Kenji Ikeda ),( Taito Fukushima ),( Yuya Seko ),( Tasuku Hara ),( Hitomi Sezaki ),( Tetsuya Hosaka ),( Norio Akuta ),( Masahiro Kobayashi ),( Satoshi Saitoh ),( Fumitaka Suzuki ) The Editorial Office of Gut and Liver 2013 Gut and Liver Vol.7 No.5
Background/Aims: The aim of this study was to determine the pharmacodynamics of cisplatin following three different treatment procedures for intrahepatic arterial infusion thera-py for hepatocellular carcinoma (HCC). Methods: We divided 13 HCC patients into the following three groups: group A, lone injection of cisplatin (n=3); group B, combined injection of cisplatin and lipiodol, with embolization using small gela-tin cubes (GCs) (n=5); and group C, injection of suspended lipiodol with cisplatin powder, with embolization using small GCs (n=5). In each group, the free cisplatin concentration in the hepatic vein was measured at 0, 5, 10, and 30 minutes. Results: The mean free cisplatin concentrations were as fol-lows. For group A, the mean was 48.58 μg/mL at 0 minute, 7.31 mL at 5 minutes, 5.70 mL at 10 minutes, and 7.15 mL at 30 minutes. For the same time points, for group B, the concentrations were 8.66, 4.23, 3.22, and 1.65 μg/mL, respectively, and for group C, the concentrations were 4.81, 2.61, 2.52, and 1.75 mL, respectively. The mean area under the curve (AUC)0-infinity for the free cisplatin concentration was 7.80 in group A, 2.48 in group B, and 2.27 in group C. The AUC0-infinity for the free cisplatin concentration gradually decreased, from group A to group C. Conclusions: These results indicate that the combination of lipiodol and small GCs may be useful for delaying cisplatin drainage from the liver. (Gut Liver 2013;7:576-584)