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51.
Shuichiro Ito Tomoko Takayama Hiroyuki Hanzawa Kimihisa Ichikawa Jun Ohsumi Nobufusa Serizawa Tadashi Hata Hideyuki Haruyama 《Journal of biochemistry》2002,131(1):137-143
Binding of Fas ligand to Fas induces apoptosis. The Fas-Fas ligand system plays important roles in many biological processes, including the elimination of autoreactive lymphoid cells. The mouse anti-human Fas monoclonal antibody HFE7A (m-HFE7A), which induces apoptosis, has been humanized based on a structure predicted by homology modeling. A version of humanized HFE7A is currently under development for the treatment of autoimmune diseases such as rheumatoid arthritis. For a deeper understanding of the protein engineering aspect of antibody humanization, for which information on the three-dimensional structure is essential, we determined the crystal structure of the m-HFE7A antigen-binding fragment (Fab) by X-ray crystallography at 2.5 A resolution. The main-chain conformation of the five loops in the six complementarity-determining regions (CDRs) was correctly predicted with root-mean-square deviations of 0.30-1.04 A based on a comparison of the crystal structure with the predicted structure. The CDR-H3 conformation of the crystal structure, which was not classified as one of the canonical structures, was completely different from that of the predicted structure but adopted the conformation which followed the "H3-rules." The results of charge distribution analysis of the antigen-binding site suggest that electrostatic interactions may be important for its binding to Fas. 相似文献
52.
Suhara Y Kittaka A Kishimoto S Calverley MJ Fujishima T Saito N Sugiura T Waku K Takayama H 《Bioorganic & medicinal chemistry letters》2002,12(22):3255-3258
The 2alpha-methyl-, 2alpha-(3-hydroxypropyl)-, and 2alpha-(3-hydroxypropoxy)-derivatives of the 'double side chain' analogue of 1alpha,25-dihydroxyvitamin D(3) were synthesized using Trost A-ring/CD-ring connective strategy. Regarding the requisite A-ring building blocks, a new, high yield and stereoselective route to the 2alpha-methyl compound starting from D-glucose was developed. All three new analogues showed potent HL-60 cancer cell differentiation activity. 相似文献
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54.
Takayama E Seki S Ohkawa T Ami K Habu Y Yamaguchi T Tadakuma T Hiraide H 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(11):5652-5658
Although CD8+ IL-2Rbeta (CD122)+ T cells with intermediate TCR reportedly develop extrathymically, their functions still remain largely unknown. In the present study, we characterized the function of CD8+ CD122+ T cells with intermediate TCR of C57BL/6 mice. The proportion of CD8+ CD122+ T cells in splenocytes gradually increased with age, whereas CD8+ IL-2Rbeta-negative or -low (CD122-) T cells conversely decreased. The IFN-gamma production from splenocytes stimulated with immobilized anti-CD3 Ab in vitro increased with age, whereas the IL-4 production decreased. When sorted CD8+ CD122+ T cells were stimulated in vitro by the anti-CD3 Ab, they promptly produced a much larger amount of IFN-gamma than did CD8+ CD122- T cells or CD4+ T cells, whereas only CD4+ T cells produced IL-4. The depletion of CD8+ CD122+ T cells from whole splenocytes greatly decreased the CD3-stimulated IFN-gamma production and increased the IL-4 production, whereas the addition of sorted CD8+ CD122+ T cells to CD8+ CD122+ T cell-depleted splenocytes restored the IFN-gamma production and partially decreased IL-4 production. It is of interest that CD8+ CD122+ T cells stimulated CD4+ T cells to produce IFN-gamma. The CD3-stimulated IFN-gamma production from each T cell subset was augmented by macrophages. Furthermore, CD3-stimulated CD8+ CD122+ T cells produced an even greater amount of IFN-gamma than did liver NK1.1+ T cells and also showed antitumor cytotoxicity. These results show that CD8+ CD122+ T cells may thus be an important source of early IFN-gamma production and are suggested to be involved in the immunological changes with aging. 相似文献
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Highly divergent sequences of the pollen self-incompatibility (S) gene in class-I S haplotypes of Brassica campestris (syn. rapa) L 总被引:1,自引:0,他引:1
Watanabe M Ito A Takada Y Ninomiya C Kakizaki T Takahata Y Hatakeyama K Hinata K Suzuki G Takasaki T Satta Y Shiba H Takayama S Isogai A 《FEBS letters》2000,473(2):139-144
Self-incompatibility (SI) enables flowering plants to discriminate between self- and non-self-pollen. In Brassica, SI is controlled by the highly polymorphic S locus. The recently identified male determinant, termed SP11 or SCR, is thought to be the ligand of S receptor kinase, the female determinant. To examine functional and evolutionary properties of SP11, we cloned 14 alleles from class-I S haplotypes of Brassica campestris and carried out sequence analyses. The sequences of mature SP11 proteins are highly divergent, except for the presence of conserved cysteines. The phylogenetic trees suggest possible co-evolution of the genes encoding the male and female determinants. 相似文献
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59.
p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1. 总被引:13,自引:1,他引:12 下载免费PDF全文
The Drosophila seven in absentia (sina) gene is required for R7 photoreceptor cell formation during Drosophila eye development, where it functions within the Ras/Raf pathway and targets other proteins for degradation via associations with a ubiquitin-conjugating enzyme. Recently, a mammalian sina homologue was reported to be a p53-inducible gene in a myeloid leukemia cell line. To explore the function of human SINA-homologous (Siah) proteins, expression plasmids encoding Siah-1A were transiently transfected into 293 epithelial cells and GM701 fibroblast cells, resulting in growth arrest without induction of apoptosis. We discovered that BAG-1, a ubiquitin-like Hsp70/Hsc70-regulating protein, is a negative regulator of Siah-1A. Siah-1A was identified as a BAG-1-binding protein via yeast two-hybrid methods. Specific interaction of BAG-1 with Siah-1A was also demonstrated by in vitro binding experiments using glutathione S-transferase fusion proteins and co-immunoprecipitation studies. Siah-1A-induced growth arrest in 293 and GM701 cells was abolished by co-transfection of wild-type BAG-1 with Siah-1A but not by a C-terminal deletion mutant of BAG-1 that fails to bind Siah-1A. Over-expression of BAG-1 significantly inhibited p53-induced growth arrest in 293 cells without preventing p53 transactivation of reporter gene plasmids. BAG-1 also prevented growth arrest following UV-irradiation-induced genotoxic injury without interfering with accumulation of p53 protein or p21(waf-1) expression. BAG-1 functions downstream of p53-induced gene expression to inhibit p53-mediated suppression of cell growth, presumably by suppressing the actions of Siah-1A. We suggest that Siah-1A may be an important mediator of p53-dependent cell-cycle arrest and demonstrate that Siah-1A is directly inhibited by BAG-1. 相似文献
60.
Shinrin-yoku (forest-air bathing and walking) effectively decreases blood glucose levels in diabetic patients 总被引:6,自引:0,他引:6
Y. Ohtsuka Noriyuki Yabunaka Shigeru Takayama 《International journal of biometeorology》1998,41(3):125-127
The influence of ”shinrin-yoku” (forest-air bathing and walking) on blood glucose levels in diabetic patients was examined.
Eighty-seven (29 male and 58 female) non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in the present
study. Shinrin-yoku was performed nine times over a period of 6 years. The patients were divided into two parties. They then
walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications.
The mean blood glucose level after forest walking changed from 179 (SEM 4) mg · 100 ml–1 to 108 (SEM 2) mg · 100 ml–1 (P<0.0001). The level of glycated haemoglobin A1c also decreased from 6.9 (SEM 0.2)% (before the first shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P<0.05). Blood glucose values declined by 74 (SEM 9) mg · 100 ml–1 and 70 (SEM 4) mg · 100 ml–1 after short- and long-distance walking respectively. There was no significant difference between these values. Since the
forest environment causes changes in hormonal secretion and autonomic nervous functions, it is presumed that, in addition
to the increased calorie consumption and improved insulin sensitivity, walking in a forest environment has other beneficial
effects in decreasing blood glucose levels.
Received: 9 July 1997/Accepted: 20 October 1997 相似文献