Seiichi Inayama
Keio University
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Featured researches published by Seiichi Inayama.
Nature | 1983
Masaharu Noda; Hideo Takahashi; Tsutomu Tanabe; Mitsuyoshi Toyosato; Sho Kikyotani; Yasuji Furutani; Tadaaki Hirose; Hideaki Takashima; Seiichi Inayama; Takashi Miyata; Shosaku Numa
The nicotinic acetylcholine receptor (AChR) from the electroplax of the ray Torpedo californica is composed of five subunits present in a molar stoichiometry of α2βγδ (refs 1–3) and contains both the binding site for the neurotransmitter and the cation gating unit (reviewed in refs 4–6). We have recently elucidated the complete primary structures of the α-, β- and δ-subunit precursors of the T. californica AChR by cloning and sequencing cDNAs for these polypeptides7,8. Here, we report the whole primary structure of the γ-subunit precursor of the AChR deduced from the nucleotide sequence of the cloned cDNA. Comparison of the amino acid sequences of the four subunits reveals marked homology among them. The close resemblance among the hydrophilicity profiles and predicted secondary structures of all the subunits suggests that these polypeptides are oriented in a pseudosymmetric fashion across the membrane. Each subunit contains four putative transmembrane segments that may be involved in the ionic channel. The transmembrane topology of the subunit molecules has also been inferred.
FEBS Letters | 1986
Toshihide Nukada; Tsutomu Tanabe; Hideo Takahashi; Masaharu Noda; Tadaaki Hirose; Seiichi Inayama; Shosaku Numa
The primary structure of the α‐subunit of the adenylate cyclase‐stimulating G‐protein (Gs) has been deduced from the nucleotide sequence of cloned DNA complementary to the bovine cerebral mRNA encoding the polypeptide. Comparison of the amino acid sequences of the α‐subunits of Gs and transducin reveals that some of the highly conserved regions show sequence homology with elongation factor‐Tu and ras p21 proteins and correspond to functional regions of guanine nucleotide‐binding proteins.
FEBS Letters | 1986
Shunsuke Noguchi; Masaharu Noda; Hideo Takahashi; Kiyoshi Kawakami; Toshiko Ohta; Kei Nagano; Tadaaki Hirose; Seiichi Inayama; Masaru Kawamura; Shosaku Numa
DNA complementary to the Torpedo californica electroplax mRNA coding for the β‐subunit of (Na+ + K+)‐ATPase has been cloned by screening a cDNA library with an oligodeoxyribonucleotide probe. Nucleotide sequence analysis of the cloned cDNA has revealed that this polypeptide consists of 305 amino acid residues (including the initiating methionine). The transmembrane topology and the potential N‐glycosylation sites of this polypeptide are discussed.
Journal of Neurochemistry | 1985
Minoru Kimura; Hidetoshi Inoko; Motoya Katsuki; Asako Ando; Tadayuki Sato; Tadaaki Hirose; Hideaki Takashima; Seiichi Inayama; Hideyuki Okano; Ken Takamatsu; Katsuhiko Mikoshiba; Yasuzo Tsukada; Itaru Watanabe
Abstract: The gene expression of myelin basic proteins (MBPs) in shiverer mutant mice was investigated by the Northern and Southern hybridization techniques. In the control mice RNA molecules from the brains which were about 2,300 nucleotides in length were hybridized to cDNA of 1.8 kb encoding for a mouse MBP, but RNA from the brains of 3‐week‐old shiverer mutant mice contained no detectable amount of MBP transcripts hybridizing to this probe. Moreover the shiverer mutant mice lost several restriction fragments that hybridized to the same probe in the control mice when each of the five restriction enzymes, i.e., HindIII, PstI, PvuII, AccI, and StuI, was used. These data suggest that the shiverer mutation may correspond to the deletion of a large portion of MBP exon(s) in the gene, and this deletion causes inefficient transcription leading to the depletion of MBPs in the myelin and the dysmyelination observed in these mice.
Angiology | 1984
Yasuhiro Hosoda; Koichi Kawano; Fumihiro Yamasawa; Toshiharu Ishii; Tetsuichi Shibata; Seiichi Inayama
Collagen and elastin in the arterial wall are thought to show some age-dependent changes, and to relate with development of the arteriosclerotic lesion. Both aortas and the pulmonary trunks were collected from 137 autopsy cases. Biochemical determination of collagen and elastin content was carried out. Collagen and elastin of the aorta and the pulmonary artery showed no significant age-dependent changes. Elastin content of the pulmonary artery increases with age in the adult. This paper seems to be the first report of simultaneous estimation of collagen and elastin content of both the aorta and the pulmonary artery.
Bioorganic & Medicinal Chemistry | 2001
Soko Kasai; Hideko Nagasawa; Mao Yamashita; Mie Masui; Hideki Kuwasaka; Tomoko Oshodani; Yoshihiro Uto; Taisuke Inomata; Shigenori Oka; Seiichi Inayama; Hitoshi Hori
We designed, based on the molecular orbital (MO) calculation, synthesized, and evaluated the biological activities of the new antimetastatic hypoxic cell radiosensitizer, 2-nitroimidazole-acetamide, TX-1877, and its analogues. Each analogue has an electron-affinic imidazole group, an acetamide group and a certain hydrophilic group to control its biological effect, toxicity, and pharmacokinetics. In in vitro radiosensitization assay, most TX-1877 analogues, which have an electron affinity (EA) of more than 0.9 eV and partition coefficient (P) of more than 0.021, showed satisfactory enhancement ratios (ER > 1.60) at doses of I mM. On the other hand, imidazole analogues, such as TX-1908 (EA = 0.67 eV), TX-1910 (EA = -0.34 eV) and TX-1931 (EA = -0.37 eV), which have low electron affinities, had an ER of 1.31 or less. TX-1877 and KIN-806 effectively inhibited tumor regrowth when administered with irradiation in vivo at a dose of 0.4 mg/g. Tumor lung metastasis was inhibited by treatment with either TX-1877 or KIN-806 without irradiation at a dose of 0.4 mg/g. TX-1877 reduced markedly the mean number of metastatic lung nodules in comparison with KIN-806. Moreover, TX-1877 and KIN-806 enhanced macrophage and helper T lymphocyte infiltration for 3 weeks after drug treatment. TX-1877 shows a high EA value and has the C2 of HOMO localizing on N-methylamide and the C2 of LUMO localizing on 2-nitroimidazole group. The MO data might be useful for designing a bifunctional hypoxic cell radiosensitizer. TX-1877 and its analogues are potential antimetastatic hypoxic cell radiosensitizers, which would improve the efficiency of radiotherapy and quality of life in cancer treatment.
Bioorganic & Medicinal Chemistry | 1997
Hitoshi Hori; Cheng-Zhe Jin; Masatoshi Kiyono; Soko Kasai; Mariko Shimamura; Seiichi Inayama
We designed, synthesized, and evaluated haloacetylcarbamoyl-2-nitroimidazoles, including chloro (KIN-1800, TX-1835, and TX-1836) and bromo derivatives (TX-1844, TX-1845, and TX-1846), as potential hypoxic cell radiosensitizers with antiangiogenic activities. To establish biological function owing to the haloacetylcarbamoyl group in the side-chain, we compared their in vitro radiosensitizing activities with those of their parent 2-nitroimidazoles without haloacetylcarbamoyl groups: misonidazole (MISO), TX-1831, and TX-1832, respectively. Both tert-butoxy substituted derivatives. TX-1835 and TX-1845, were more potent radiosensitizers than TX-1831. The p-tert-butylphenoxy-substituted derivatives, TX-1836 and TX-1846, and the methoxysubstituted derivatives, KIN-1800 and TX-1844, were stronger radiosensitizers than TX-1832 and MISO. We examined the anti-angiogenic activities of these 2-nitroimidazole derivatives containing haloacetylcarbamoyl group by the rat lung endothelial (RLE) cell proliferation assay and chick embryo chorioallantoic membrane (chick CAM) angiogenesis assay and showed that haloacetylcarbamoyl-2-nitroimidazoles were more potent angiogenic inhibitors than the corresponding desacetylcarbamoyl-2-nitroimidazoles. The in vivo chick CAM angiogenesis assay showed that the strong bromoacetylcarbamoyl-2-nitroimidazole radiosensitizers, such as TX-1845 and TX-1846, were the strongest angiogenic inhibitors among them. We concluded that the bromoacetylcarbamoyl-2-nitroimidazole radiosensitizers, such as TX-1845 and TX-1846, are promising as anti-angiogenic hypoxic cell radiosensitizers.
Nucleic Acids Research | 1988
Yoshio Inokuchi; Ann B. Jacobson; Tadaaki Hirose; Seiichi Inayama; Akikazu Hirashima
We report the nucleotide sequence of the Group IV RNA bacteriophage SP. The entire sequence is 4276 nucleotides long. Four cistrons have been identified by comparison with the related Group III phage Q beta. The maturation protein contains 449 amino acids, the coat protein contains 131 amino acids, the read-through protein contains 330 amino acids and the replicase beta-subunit contains 575 amino acids. SP is 59 nucleotides longer than Q beta. We have analyzed both sequence and structural conservation between SP and Q beta and shown that the sequences for the coat and central region of the replicase are strongly conserved between the two genomes. We also show that the S and M replicase binding sites of Q beta are strongly conserved in SP. Interestingly, the base composition of SP and Q beta differ significantly from one another, and most of the differences can be accounted for by a strong preponderance of U in the third position of each codon of Q beta relative to SP. We also compare conserved hairpins associated with potential coat protein and replicase binding sites.
Immunogenetics | 1987
Kikuo Tsukamoto; Michio Yasunami; Akinori Kimura; Hidetoshi Inoko; Asako Ando; Takaaki Hirose; Seiichi Inayama; Takehiko Sasazuki
We determined the nucleotide sequences of cDNA clones and part of a genomic clone for the DQwl~ gene from the HLA-Dw12 haplotype. The sequencing analysis revealed that the DQwle gene from Dw12 is organized in six exons, as is the mouse A;~ gene. Moreover, one cDNA clone which lacked a region corresponding to exon 5 and potentially encoding a smaller DQ~ molecule was obtained. This suggested that there was an alternative splicing event in the DQwla gene. These observations account for some of the four DQ~ spots in the Dw12 haplotype in twodimensional polyacrylamide gel electrophoresis (2DPAGE) analysis. Comparison of the deduced amino acid sequences of the DQ~ chain from the Dw12 haplotype with that from the Dw2 haplotype indicated that substitutions were located predominantly in the fi 1 domain. Three genetic subregions, DR, DQ, and DP, are mapped within the HLA-D region, which controls immune response, disease susceptibility, and both primary and secondary mixed lymphocyte culture reaction (MLR) in man (van Rood et al. 1981, Sasazuki et al. 1983, Stastny et al. 1983, Thorsby and Piazza 1975, Shaw et al. 1980). They encode class II molecules which are highly polymorphic heterodimers of c~ and/3 chains. HLA-Dw2 and Dw12 homozygous cells are indistinguishable by DR and DQ serotyping; they both type as DR2 and DQwl, but yet stimulate a primary MLR (Sone et al. 1985). HLA-Dw2 and -Dw12 haplotypes show different features in immune responsiveness to streptococcal cell wall antigen (SCW), to antigen from Mycobacterium leprae (ML), and to schistosomal antigen (Sj). The Dw2 haplotype is associated with low responsiveness to SCW (Nishimura and Sasazuki 1983) and ML (Kikuchi et al. 1985), whereas the Dw12 haplotype is strongly associated with low responsiveness to Sj (Ohta et al. 1983). The low responsiveness is thought to be determined by an immune
British Journal of Cancer | 2003
Mariko Shimamura; Hideko Nagasawa; H Ashino; Y. Yamamoto; T Hazato; Yoshihiro Uto; Hitoshi Hori; Seiichi Inayama
Tumour angiogenesis is initiated by angiogenic factors that are produced in large amounts by hypoxic tumour cells. The inhibition of this step may lead to tumour-specific antiangiogenesis because normal tissues are not usually hypoxic. On the other hand, blocking a biological function of endothelial cells is known to result in angiogenic inhibition. To produce a tumour-specific and powerful antiangiogenesis, we determined whether potent angiogenic inhibition could be achieved by inhibiting the production of angiogenic factors by hypoxic tumour cells and simultaneously blocking certain angiogenic steps in endothelial cells under normoxia. We focused on the 2-nitroimidazole moiety, which is easily incorporated into hypoxic cells and exhibits its cytotoxicity as hypoxic cytotoxin. We designed and synthesised 2-nitroimidazole derivatives designated as KIN compounds, and investigated their antiangiogenic activities under normoxia using a chick embryo chorioallantoic membrane. KIN-841 (2-nitroimidazole 1-acetylhydroxamate) showed a potent angiogenic inhibition in a dose-dependent manner. This compound inhibited the proliferation of bovine pulmonary arterial endothelial (BPAE) cells more strongly than that of tumour cells, such as Lewis lung carcinoma (3LL) cells, under normoxia. The inhibition of cell proliferation by KIN-841 under hypoxia increased about five-fold compared to that under normoxia. Moreover, under hypoxia, KIN-841 significantly decreased the excessive production of vascular endothelial cell growth factors induced by 3LL cells as determined by tritium-labelled thymidine ([3H]thymidine) incorporation into BPAE cells and by ELISA. Intraperitoneal administration of KIN-841 suppressed 3LL-cell-induced in vivo angiogenesis in the mouse dorsal air sac system. These results indicate that the regulation of the production of angiogenic factors by hypoxic tumour cells is a useful target for tumour-specific angiogenesis inhibition, and that KIN-841, which causes simultaneous direct inhibition of endothelial cell function and production of angiogenic factors by hypoxic tumour cells, is a very potent inhibitor of tumour-specific angiogenesis. Thus, the potential for clinical use of KIN-841 as an antitumour drug is very high.