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排序方式: 共有118条查询结果,搜索用时 15 毫秒
51.
Gluteus maximus adipomuscular turnover or sliding flap in the surgical treatment of extensive sacral chordomas 总被引:4,自引:0,他引:4
Two cases with extensive posterior peritoneal defects after high sacral amputation for sacral chordoma are presented. An adipomuscular flap as a modification of the conventional gluteus maximus muscle flap was designed to obliterate an extensive residual posterior peritoneal dead space. The deep adipose tissue beneath the superficial fascia left on the gluteus maximus muscle was effectively used to provide more volume to the flap. The adipomuscular flap was turned over into the posterior peritoneal defect in the first case, and the flap was slid into the cavity in the other case. The adipomuscular flap eventually enabled the successful reconstruction of the posterior peritoneal defect, and the volume of the flap was well maintained behind the rectum, according to the postoperative magnetic resonance imaging findings in both cases. 相似文献
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Design and synthesis of potent beta-secretase (BACE1) inhibitors with P1' carboxylic acid bioisosteres 总被引:2,自引:0,他引:2
Kimura T Hamada Y Stochaj M Ikari H Nagamine A Abdel-Rahman H Igawa N Hidaka K Nguyen JT Saito K Hayashi Y Kiso Y 《Bioorganic & medicinal chemistry letters》2006,16(9):2380-2386
Recently, we reported potent and small-sized beta-secretase (BACE1) inhibitors KMI-420 and KMI-429 in which we replaced the Glu residue at the P4 position of KMI-260 and KMI-360, respectively, with a 1H-tetrazole-5-carbonyl DAP (L-alpha,beta-diaminopropionic acid) residue. At the P1' position, these compounds contain one or two carboxylic acid groups, which are unfavorable for crossing the blood-brain barrier. Herein, we report BACE1 inhibitors with P1' carboxylic acid bioisosteres in order to develop practical anti-Alzheimer's disease drugs. Among them, tetrazole ring-containing compounds, KMI-570 (IC50=4.8 nM) and KMI-684 (IC50=1.2 nM), exhibited significantly potent BACE1 inhibitory activities. 相似文献
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Hirutani Sakiko Shimomae Kazuki Yaguchi Akira Chin Dong Poh Mii Masahiro Igawa Tomoko 《Plant Cell, Tissue and Organ Culture》2020,142(2):435-440
Plant Cell, Tissue and Organ Culture (PCTOC) - Begonia semperflorens-cultorum, known as wax begonia, is one of the most popular Begonia species in which variable commercial cultivars have been... 相似文献
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Tomoyuki Igawa Hiroyuki Tsunoda Taichi Kuramochi Zenjiro Sampei Shinya Ishii Kunihiro Hattori 《MABS-AUSTIN》2011,3(3):243-252
Since the first generation of humanized IgG1 antibodies reached the market in the late 1990s, IgG antibody molecules have been extensively engineered. The success of antibody therapeutics has introduced severe competition in developing novel therapeutic monoclonal antibodies, especially for promising or clinically validated targets. Such competition has led researchers to generate so-called second or third generation antibodies with clinical differentiation utilizing various engineering and optimization technologies. Parent IgG antibodies can be engineered to have improved antigen binding properties, effector functions, pharmacokinetics, pharmaceutical properties and safety issues. Although the primary role of the antibody variable region is to bind to the antigen, it is also the main source of antibody diversity and its sequence affects various properties important for developing antibody therapeutics. Here we review recent research activity in variable region engineering to generate superior antibody therapeutics.Key words: antibody therapeutics, variable region, engineering, affinity, pharmacokinetics, stability, immunogenicity 相似文献
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11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) catalyzes the interconversion of cortisone and cortisol within the endoplasmic reticulum. 11β-HSD1 is expressed widely, most notably in the liver, adipose tissue, and central nervous system. It has been studied intensely over the last 10 years because its activity is reported to be increased in visceral adipose tissue of obese people. Epidermal keratinocytes and dermal fibroblasts also express 11β-HSD1. However, the function of the enzymatic activity 11β-HSD1 in skin is not known. We found that 11β-HSD1 was expressed in human and murine epidermis, and this expression increased as keratinocytes differentiate. The expression of 11β-HSD1 by normal human epidermal keratinocytes (NHEKs) was increased by starvation or calcium-induced differentiation in vitro. A selective inhibitor of 11β-HSD1 promoted proliferation of NHEKs and normal human dermal fibroblasts, but did not alter the differentiation of NHEKs. Topical application of selective 11β-HSD1 inhibitor to the dorsal skin of hairless mice caused proliferation of keratinocytes. Taken together, these data suggest that 11β-HSD1 is involved in tissue remodeling of the skin. This hypothesis was further supported by the observation that topical application of the selective 11β-HSD1 inhibitor enhanced cutaneous wound healing in C57BL/6 mice and ob/ob mice. Collectively, we conclude that 11β-HSD1 is negatively regulating the proliferation of keratinocytes and fibroblasts, and cutaneous wound healing. Hence, 11β-HSD1 might maintain skin homeostasis by regulating the proliferation of keratinocytes and dermal fibroblasts. Thus 11β-HSD1 is a novel candidate target for the design of skin disease treatments. 相似文献
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Two main steps of photodecomposition were observed at the initial stage on the irradiation of ultraviolet light to Kitazin P® in a thin film. One was the isomerization to a thionate, O-benzyl O, O-diisopropyl phosphorothionate, which was gradually hydrolyzed or oxidized to its oxygen analogue. The other step was the cleavage of P-S bond to produce O, O-diisopropyl phosphonate and α-toluenethiol, the latter of which was degraded to produce α-toluenesulfonic acid via dibenzyl disulfide, and finally sulfuric acid and benzoic acid. O, O-Diisopropyl hydrogen phosphorothioate, O, O-diisopropyl hydrogen phosphate and benzyl alcohol were detected as hydrolyzates. Benzyl alcohol was further oxidized to benzoic acid via benzaldehyde. In addition to these compounds, O, O, S-triisopropyl phosphorothiolate, O, O, O-triisopropyl phosphorothionate, O, O, O-triisopropyl phosphate and benzyl isopropyl sulfide were also detected. 相似文献