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71.
K Furukawa M Tagaya M Inouye J Preiss T Fukui 《The Journal of biological chemistry》1990,265(4):2086-2090
Glycogen synthases from Escherichia coli and mammalian muscle differ in many respects including regulation, sugar nucleotide specificity, and primary sequence. To compare the structure of the active sites in these enzymes, the affinity-labeling study of the E. coli enzyme was carried out using adenosine diphosphopyridoxal as the reagent. The E. coli enzyme was inactivated in a time- and dose-dependent manner when incubated with the reagent followed by sodium borohydride reduction. The inactivation was markedly protected by ADP-glucose and ADP, suggesting that the reagent was bound to the substrate-binding site. The stoichiometry of the bound reagent to the enzyme was approximately 1:1. Sequence analysis of the labeled peptide isolated from a proteolytic digest of the modified protein revealed that Lys15 is labeled. Based on the geometry of the reagent, the epsilon-amino group of this residue might be located close to the pyrophosphate moiety of ADP-glucose bound to the E. coli enzyme, like that of Lys38 in the rabbit muscle enzyme, which is labeled by uridine diphosphopyridoxal (Tagaya, M., Nakano, K., and Fukui, T. (1986) J. Biol. Chem. 260, 6670-6676; Mahrenholz, A. M., Wang, Y., and Roach, P. J. (1988) J. Biol. Chem. 263, 10561-10567). The importance of the conserved sequence of Lys-X-Gly-Gly is discussed in connection with the glycine-rich region found in many nucleotide-binding proteins. 相似文献
72.
Tadao Niijima Takashi Umeda Manabu Kuriyama Hiroyuki Ohmori Yohsuke Matsumura Tomoyasu Tsushima Toyoko Tanahashi Jun Yoshimoto Toshihiko Asahi Norimasa Ike Taiichiro Johsen Noritaka Ishido Naoki Mitsuhata Takeshi Uyama Hiroyoshi Tanaka Hideo Ueda Jisaburo Sakatoku Norio Yamamoto Kazuo Nagata Yukitoshi Fujita Masaaki Morioka Kazuo Kurokawa Susumu Kagawa Tomoyuki Ishibe Yasutoshi Himeno Toyofumi Ueda 《Cancer immunology, immunotherapy : CII》1989,30(2):81-85
Summary In order to examine its clinical efficacy, recombinant human interferon- (rIFN-) was instilled intravesically into 51 patients with superficial bladder cancer. Ten patients, who received intermittent intravesical instillation at a dose of (3–36) × 106 U rIFN- on days 1–3 every week, showed no response. Thirty-two patients received intravesical instillation at a dose of (3–36) × 106 U every day for 10–20 days. Eight patients showed partial response, indicating an efficacy rate of 25%. Nine patients received divided doses of 18 × 106 U twice a day every day for 10–20 days. Six patients showed partial response, indicating an efficacy rate of 67%. This value was significantly higher than that obtained by administering divided doses. The response to intravesical instillation therapy with rIFN- varies with treatment protocol. Frequent and longer exposure to rIFN- may induce better regression of superficial bladder cancer. Six incidences of side-effects were found in five cases (9.8%): pollakiuria in one, pain on micturition in two, fever in two, and eruption in one case. All of these side-effects were slight and reversible after drug withdrawal. Laboratory tests showed only a few changes with low severity. Thus, rIFN- is potentially a new drug for instillation therapy of superficial bladder cancer, in view of the absence of adverse effects. 相似文献
73.
Ikuo Saiki Hiroaki Maeda Jun Murata Nobuchika Yamamoto Makoto Kiso Akira Hasegawa Ichiro Azuma 《Cancer immunology, immunotherapy : CII》1989,30(3):151-157
Summary We have investigated the effect of endogenous production of tumor necrosis factor (TNF) induced by the combination of recombinant interferon (rIFN) as a primer followed by GLA-60 as a trigger (rIFN/GLA-60) on murine lung metastases caused by B16-BL6 melanoma. In order to examine the therapeutic effect of endogenous TNF on tumor metastasis, the ability of multiple administrations of rIFN/GLA-60 to induce TNF production was also tested. The multiple administrations of rIFN/GLA-60 at intervals of 2 days were effective for the induction of endogenous TNF in mice but continuous multiple administrations of them for 2–4 days were not. In tumor-bearing mice, the production of endogenous TNF by rIFN/GLA-60 was less than that of normal mice, but treatment 3 days after the surgical excision of primary tumors showed the endogenous TNF production to be similar to that in normal mice. In the experimental lung metastasis model, intravenous administration of rIFN followed by intravenous or intranasal administration of GLA-60 showed potent inhibition of lung metastases of B16-BL6 melanoma, whereas the reverse sequence of administration (GLA-60/rIFN) or administration of a mixture of rIFN and GLA-60, which cannot induce the production of TNF, caused no inhibition of lung metastases. These results indicated that the regression of tumor metastases by rIFN/GLA-60 was mediated by the production of endogenous TNF in addition to the direct effects of both immunostimulants. Furthermore, the administration of rIFN and GLA-60 significantly inhibited the tumor metastases in spontaneous lung metastasis model. These results may provide a promising approach for the treatment of cancer metastasis as a result of its ability to induce endogenous TNF. 相似文献
74.
Cyclic oxyphosphoranes as model intermediates during splicing and cleavage of RNA: ab initio molecular orbital calculations on the conformational analysis. 下载免费PDF全文
Ab initio molecular orbital calculations have been carried out on hydrated adducts of methyl ethylene phosphate as a model intermediate during cleavage of RNA. Upon rotating the apical methoxyl group two kinds of stable conformers and two kinds of rotational transition states are located, the most stable conformation being gs-G where the dihedral angle between the apical methyl group and the basal ring oxygen is calculated to be 76 degrees. In this gs-G conformation one of the lone pairs on the apical oxygen is oriented antiperiplanar to the basal ring ester bond. The torsional energy required to rotate the methyl group about the phosphorus-apical oxygen bond leading to ts-C conformation, where the methyl group is eclipsed with the ring oxygen, is calculated to be 5.2 kcal/mol. Judging from the published substrate's coordinates in the RNase environment, the expected pentacoordinate-intermediate/transition state during the cleavage of RNA appears to be, in fact, the most stable gs-G conformation. 相似文献
75.
清香桂碱D和矮陀陀胺碱A,B的结构 总被引:9,自引:0,他引:9
本文报道从国产清香桂(Sarcococca ruscifolta)和金丝矮陀陀(Pachysandra axillaria)植物中分得的三个胺碱型新甾体生物碱清香桂碱 D 和矮陀陀胺碱 A、B 的化学结构,并首次归属了它们的~(13)C NMR 数据。 相似文献
76.
77.
K Furukawa I J Thampoe H Yamaguchi K O Lloyd 《Journal of immunology (Baltimore, Md. : 1950)》1989,142(3):848-854
After the observation that human mAb 32-27M reacts only with melanoma and astrocytoma cells cultured in the presence of fetal bovine serum, a novel pathway for the uptake of exogenous gangliosides, their further biosynthesis, and expression at the cell surface as novel Ag has been elucidated. The addition of fetal bovine serum to melanoma and astrocytoma cells growing in synthetic medium (insulin-transferrin-selenium) resulted in reactivity with Ab32-27M. As antibody 32-27M detects N-glycolylneuraminic acid (NeuGc)-containing gangliosides, the effect of adding a number of different gangliosides to melanoma and astrocytoma cells cultured in the synthetic medium was studied. Only the addition of NeuGc-GM3 resulted in the development of Ab32-27M reactivity. The identity of the antigenic structures developed after addition of fetal bovine serum or NeuGc-GM3 was determined by analysis of the gangliosides from both samples. The major component detected in melanoma cell lines was shown to be N-acetylneuraminic acid-NeuGc-GD3. Another, slower moving component, present in some melanomas and in astrocytomas may be N-acetylneuraminic acid-NeuGc-GD2. The cell type specificity for these processes can be most readily explained by postulating that all cells can take up exogenous gangliosides but only melanoma and astrocytoma cells have sufficiently high levels of GM3 alpha 2----8-sialyltransferase for the conversion of added NeuGc-GM3 to disialogangliosides to be effective. These results demonstrate a novel pathway for exogenous glycolipid processing that can lead to novel Ag expression but may also play a role in normal glycolipid metabolism and function. 相似文献
78.
Hiroyuki Tsunoda Toshio Ohshima Jun Tohyama Masayuki Sasaki Norio Sakuragawa Frank Martiniuk 《Human genetics》1996,97(4):496-499
We report a missense mutation in an adult Japanese patient with acid alpha-glucosidase (GAA) deficiency. A TC to GT transition
at nucleotides 1585–1586, was identified. This transition resulted in an amino acid substitution of Ser-529 to Val (S529V)
in exon 11. We also have demonstrated that the S529V mutation abolishes the catalytic activity of the enzyme. Our data suggest
that this mutation is the cause of the clinical manifestation known as adult-onset GAA deficiency. The missense mutation described
here is a new mutation, and the first identified in Japanese patients with GAA deficiency.
Received: 23 May 1995 相似文献
79.
80.
可育的抗除草剂溴苯腈转基因小麦 总被引:21,自引:0,他引:21
报道了采用微粒轰击(Microprojectile bom bardm ent) 幼胚将除草剂抗性基因导入小麦(Triticumaestivum L.)的转化研究。实验共使用了13 个小麦品种, 从开花后14~18 d 的籽粒中剥取幼胚, 植物表达质粒含有CaMV 35S启动子控制的除草剂溴苯腈抗性基因bxn 以及筛选标记基因NTPⅡ。采用高压放电基因枪,用质粒DNA 包被的钨粒轰击预培养3 d 的幼胚。在含有卡那霉素类似物geneticin G418sulphate 的MS培养基上, 经过多步骤筛选和分化, 从800 多个幼胚中获得了16 株转化苗。除草剂抗性鉴定和Southern 杂交分析证明, 其中4 株为转基因植物,具有溴苯腈抗性, 并且自交可育。转化工作从分离幼胚到转化苗鉴定完毕, 最短时间为6 个月, 因此, 该方法是一项快速有效的基因导入技术 相似文献