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991.
Chondroitin sulfate E repeating octasaccharide was effectively synthesized in a stereocontrolled manner by adopting an acetamide-type disaccharide unit. In the tetrasaccharide synthesis we isolated a characteristic glycosyl imidate as a reactive intermediate. An acetamide auxiliary involves the glycosylation mechanism. 相似文献
992.
Murayama Y Shinomura Y Oritani K Miyagawa J Yoshida H Nishida M Katsube F Shiraga M Miyazaki T Nakamoto T Tsutsui S Tamura S Higashiyama S Shimomura I Hayashi N 《Journal of cellular physiology》2008,216(1):135-143
CD9 is a member of the tetraspanins, and has been shown to be involved in a variety of cellular activities such as migration, proliferation, and adhesion. In addition, it has been known that CD9 can associate with other proteins. Here we demonstrated the physical and functional association of CD9 with epidermal growth factor receptor (EGFR) on MKN-28 cells. Double-immunofluorescent staining and immunoprecipitation demonstrated the complex formation of CD9-EGFR and CD9-beta(1) integrin, and that both complexes are colocalized on the cell surface especially at the cell-cell contact site. Anti-CD9 monoclonal antibody ALB6 induced a dotted or patch-like aggregation pattern of both CD9-EGFR and CD9-beta(1) integrin. The internalization of EGFR after EGF-stimulation was significantly enhanced by the treatment with ALB6. CD9 can associate with EGFR in hepatocellular carcinoma cells (HepG2/CD9) and Chinese hamster ovary cancer cells (CHO-HER/CD9), which were transfected with pTJ/human EGFR/CD9. Furthermore expression of CD9 specifically attenuated EGFR signaling in CHO-HER/CD9 cells through the down regulation of surface expression of EGFR. These results suggest that CD9 might have an important role that attenuates EGFR signaling. Therefore, CD9 not only associates EGFR but also a new regulator, which may affect EGF-induced signaling in cancer cells. 相似文献
993.
Sekiya M Osuga J Yahagi N Okazaki H Tamura Y Igarashi M Takase S Harada K Okazaki S Iizuka Y Ohashi K Yagyu H Okazaki M Gotoda T Nagai R Kadowaki T Shimano H Yamada N Ishibashi S 《Journal of lipid research》2008,49(8):1829-1838
Hormone-sensitive lipase (HSL) regulates the hydrolysis of acylglycerol and cholesteryl ester (CE) in various organs, including adipose tissues. However, the hepatic expression level of HSL has been reported to be almost negligible. In the present study, we found that mice lacking both leptin and HSL (Lep(ob/ob)/HSL(-/-)) showed massive accumulation of CE in the liver compared with Lep(ob/ob)/HSL(+/+) mice, while triacylglycerol (TG) accumulation was modest. Similarly, feeding with a high-cholesterol diet induced hepatic CE accumulation in HSL(-/-) mice. Supporting these observations, we detected significant expression of protein as well as mRNA of HSL in the liver. HSL(-/-) mice showed reduced activity of CE hydrolase, but not of TG lipase, in the liver compared with wild-type mice. Furthermore, we confirmed the expression of HSL in viable parenchymal cells isolated from wild-type mice. The hepatocytes from HSL(-/-) mice showed reduced activity of CE hydrolase and contained more CE than those from HSL(+/+) mice even without the incubation with lipoproteins. Incubation with LDL further augmented the accumulation of CE in the HSL-deficient hepatocytes. From these results, we conclude that HSL is involved in the hydrolysis of CE in hepatocyes. 相似文献
994.
S Y Tamura E A Goldman P W Bergum J E Semple 《Bioorganic & medicinal chemistry letters》1999,9(17):2573-2578
Rigid benzolactam P3-P2 dipeptide mimics were designed and prepared as potential inhibitors of blood coagulation factor Xa. Methoxy substitution of the tetrahydrobenzazepinone scaffold led to potent and selective inhibitors. The synthesis and biological activities of these derivatives are reported herein. 相似文献
995.
A novel class of Na+ and Ca2+ channel dual blockers with highly potent anti-ischemic effects 总被引:1,自引:0,他引:1
Annoura H Nakanishi K Uesugi M Fukunaga A Miyajima A Tamura-Horikawa Y Tamura S 《Bioorganic & medicinal chemistry letters》1999,9(20):2999-3002
A series of novel arylpiperidines (4a-d) which have highly potent blocking effects for both neuronal Na+ and T-type Ca2+ channels with extremely low affinity for dopamine D2 receptors were synthesized. Among these compounds, 1-(2-hydroxy-3-phenoxy)propyl-4-(4-phenoxyphenyl)-piperidine hydrochloride (4c; SUN N5030) exhibited remarkable neuroprotective activity in a transient middle cerebral artery occlusion (MCAO) model. 相似文献
996.
Recent studies on the metabolic activities of genus Rhodococcus have shown rhodococci to be of important use in industrial, pharmaceutical and environmental biotechnology. The increasing economic significance of Rhodococcus encourages renewed efforts to characterize their genetic systems, as Rhodococcus genetics are still poorly understood. The goal of this study is to adapt a transposon system for use in creating random mutagenesis in Rhodococcus erythropolis. A plasmid carrying IS1415, a member of IS21 family identified from Rerythropolis, has been constructed and designated as pTNR. pTNR is a non-replicating transposon tool introduced into target cells by electroporation. During its transposition, the transposable-marker gene is separated from the open reading frames (istAB) of IS1415, which should avoid secondary transposition. Transposition of pTNR into wild-type R. erythropolis created mutagenesis with a high efficiency of 1.23x10(6)mutants per microgram plasmid DNA. However, it could also be transposed into other Rhodococcus spp. at lower frequencies in comparison with that of R. erythropolis. It has been indicated by Southern hybridization that the generated kanamycin-resistant mutants were resulted from single transposition event of pTNR. The results also revealed that the transposable-marker gene of pTNR was randomly inserted into the chromosomal DNA of R. erythropolis. The affected DNA regions carrying the transposed DNA element could be conveniently recovered for further characterization using a plasmid rescue procedure. Sequence data of the insertion sites of 40 random mutants analyzed indicated that transposition of pTNR generated 6-bp direct target duplications in 36 cases, while in the remaining four mutants; it generated 5- or 7-bp target duplications (two cases each). This study concluded that pTNR could be served as an efficient genetic tool for construction of random mutagenesis system in Rhodococcus species. 相似文献
997.
Mutations in human coagulation factor IX cause an X-linked bleeding disorder Hemophilia B, which can be classified as severe, moderately severe and mild based on the plasma levels of factor IX among affected individuals with respect to normal factor IX activity assayed in the patients' plasma (<1%, 2-5%, 6-30%, respectively). Recently, we identified hemophilia B to be a disease with mutations showing clinical variation and speculated that this phenotypic heterogeneity might be a replacement-specific property. Here, we have analyzed the differences in sequence and structural properties among identical mutations with varying phenotypes (IMVPs) by comparing with mutations with uniform phenotypes (MUPs), with recurring reports in Haemophilia B mutation database. Classification of mutations into IMVPs and MUPs has been done based on rigorous systematic evaluation of the clotting activity each mutation is associated with. IMVPs (n = 51) occur in less conserved mutant sites with more tolerated substitutions compared to MUPs (n = 100). A preponderance of CpG site mutations and Arg as the mutated residue in IMVPs compared to Cys in MUPs was observed. Hence, a CpG site substitution at less conserved Arg site might have an increased propensity of expressing variable phenotypes. The changes in intrinsic properties associated with the mutation are less drastic for IMVPs than for MUPs, though no significant differences were observed in structural properties. Based on this study and available literature we speculate that modifier genes at other loci, epigenetic interactions and environment may serve individually or cumulatively to bring about the clinical variation implicating hemophilia B to be deviation from classical Mendelian disorder with complete penetrance. We demonstrate that phenotypic heterogeneity appears to be site-specific also owing to the lesser conservation of the mutant site. 相似文献
998.
Shinagawa N Yamazaki K Tamura Y Imai A Kikuchi E Yokouchi H Hommura F Oizumi S Nishimura M 《Cancer immunology, immunotherapy : CII》2008,57(2):165-174
Background and purpose Immunization with heat shock proteins, gp96, elicits specific protective immunity against parent tumors. However, it is marginally
effective as a therapeutic tool against established tumors. In the present study, we evaluated the efficacy and mechanism
of immunotherapy with bone marrow-derived dendritic cells (DCs) pulsed with tumor-derived gp96 against murine lung cancer.
Methods Mice were transplanted subcutaneously with ovalbumin (OVA)-transfected Lewis Lung Cancer (LLC-OVA) cells and immunized with
gp96 derived from LLC-OVA, DCs, or DCs pulsed with gp96 derived from LLC-OVA.
Results The antitumor effect was significantly enhanced in the mice immunized with DCs pulsed with gp96 derived from LLC-OVA, compared
to mice immunized with gp96 or DCs (P < 0.05). The antitumor effect was significantly dependent on natural killer (NK) cells and CD8+ cells and partially dependent on CD4+ cells. Analysis by laser confocal microscopy demonstrated that gp96 was shown on the cell surface at 15 min, and after 30 min
internalized in the endosomes and not in the endoplasmic reticulum or lysosomes. OVA-specific+ CD8+ cells were more readily recruited into the draining lymph nodes and higher CD8+ cytotoxic T cell activity against LLC-OVA was observed in splenocytes from mice immunized with DCs pulsed with gp96 derived
from LLC-OVA. Re-challenge of the surviving mice with LLC-OVA tumors after the initial tumor inoculation showed dramatic retardation
in tumor growth.
Conclusion In conclusion, immunotherapy of DCs pulsed with tumor-derived gp96 against murine lung cancer is effective through immune
response of CD8+ cytotoxic T lymphocytes and NK cells. 相似文献
999.
Nishinoaki M Asakura T Watanabe T Kunizaki E Matsumoto M Eto W Tamura T Minami M Obata A Abe K Funaki J 《Bioscience, biotechnology, and biochemistry》2008,72(2):587-590
An Aspergillus saitoi protease preparation, Molsin, was found to contain beta-glucosidase as well as protease activities. Application of Molsin to soybean curd improved its functionality by converting the contained isoflavone glycosides to their aglycones through beta-glucosidase, and also modified the rheological property into a creamy consistency through protease. The enzymatically modified soybean curd was characterized by a ductility flow having no particular rupture point. 相似文献
1000.