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941.
H Kambe H Ito Y Kimura T Okochi H Yamamoto T Hashimoto K Tagawa 《Journal of biochemistry》1992,111(6):722-725
Gelsolin is a Ca(2+)-regulated actin-modulating protein found in a variety of cellular cytoplasm and also in blood plasma. Affinity separation of human plasma gelsolin was successfully accomplished by eluting the protein with a low concentration of nucleoside polyphosphate from immobilized Cibacron Blue F3GA (1, 2). This finding was followed by the demonstration that the protein had one class of ATP binding site with Kd = 2.8 x 10(-7) M, which saturated at an ATP/gelsolin ratio of 0.6 in the absence of Ca2+ (3). To obtain further information on the nucleotide binding properties of gelsolin, binding studies were done in the presence of EGTA with GTP, ADP, and GDP by equilibrium dialysis. Incubation of plasma gelsolin with GTP resulted in binding of 0.6 mol of GTP per mol of protein with a dissociation constant of 1.8 x 10(-6) M, indicating that ATP binds to gelsolin with higher affinity than GTP. Neither ADP nor GDP at up to 100 microM appreciably bound to gelsolin at a physiological salt concentration. Then, the effects of divalent metal ions on the ATP binding to plasma gelsolin were examined. Gelsolin bound to ATP with Kd = 2.4 x 10(-6) M in a solution containing 2 mM MgCl2, whereas micromolar free Ca2+ concentrations inhibited ATP binding. Furthermore, addition of Ca2+ rapidly reversed the preformed nucleotide binding to gelsolin, suggesting that Ca2+ binding to gelsolin leads to a conformational change which disrupts a nucleotide binding fold in the protein molecule. 相似文献
942.
Masaya Hayakawa Maho Tokuda Kensei Kaneko Koichiro Nakamichi Yukie Yamamoto Tatsuya Kamijo Honoka Umeki Reimi Chiba Ryo Yamada Mitsuya Mori Kosuke Yanagiya Ryota Moriuchi Masahiro Yuki Hideo Dohra Hiroyuki Futamata Moriya Ohkuma Kazuhide Kimbara Masaki Shintani 《Applied and environmental microbiology》2022,88(18)
943.
Kei-ichi Morita Takuya Naruto Kousuke Tanimoto Chisato Yasukawa Yu Oikawa Kiyoshi Masuda Issei Imoto Johji Inazawa Ken Omura Hiroyuki Harada 《PloS one》2015,10(11)
Gorlin syndrome (GS) is an autosomal dominant disorder that predisposes affected individuals to developmental defects and tumorigenesis, and caused mainly by heterozygous germline PTCH1 mutations. Despite exhaustive analysis, PTCH1 mutations are often unidentifiable in some patients; the failure to detect mutations is presumably because of mutations occurred in other causative genes or outside of analyzed regions of PTCH1, or copy number alterations (CNAs). In this study, we subjected a cohort of GS-affected individuals from six unrelated families to next-generation sequencing (NGS) analysis for the combined screening of causative alterations in Hedgehog signaling pathway-related genes. Specific single nucleotide variations (SNVs) of PTCH1 causing inferred amino acid changes were identified in four families (seven affected individuals), whereas CNAs within or around PTCH1 were found in two families in whom possible causative SNVs were not detected. Through a targeted resequencing of all coding exons, as well as simultaneous evaluation of copy number status using the alignment map files obtained via NGS, we found that GS phenotypes could be explained by PTCH1 mutations or deletions in all affected patients. Because it is advisable to evaluate CNAs of candidate causative genes in point mutation-negative cases, NGS methodology appears to be useful for improving molecular diagnosis through the simultaneous detection of both SNVs and CNAs in the targeted genes/regions. 相似文献
944.
Ohashi Y Kawakami H Shigeta Y Ikeda H Yamamoto N 《International journal of biometeorology》2012,56(5):903-914
We investigated relationships between the flowering phenology of Prunus yedoensis "Somei-yoshino" (cherry blossom) and the local temperatures in Japan. Our observations were carried out across the Okayama Plain, which included Okayama City (about 700,000 inhabitants), from the winter of 2008 to the spring of 2009. Local air temperature (AT) and the globe temperature (GT) were recorded at the tree height. The flowering dates (FDs) of P. yedoensis were earliest in the central commercial area (located at the center of the plain), followed by the north residential area (further inland), and finally the south residential area (seaward). The recorded FDs were related to the period-averaged daily maximum/minimum AT and GT, and the phenologically effective AT and GT defined in this study. Of these parameters, the phenologically effective GTs correlated most with the FDs. Since the GT is determined by AT, solar and infrared radiations, and wind speed, our previous result suggests that a combination of these three components surrounding the tree is more important for budding and flowering than is AT alone. The supposition is supported by the flowering of P. yedoensis being the latest at the coastal region of the Okayama Plain where the AT were higher than at the inland region, excluding the urban area; it is probably caused by stronger winds there than at the other sites. 相似文献
945.
Yoshihisa Nakada Thomas D. Aicher Yvan Le Huerou Timothy Turner Scott A. Pratt Stephen S. Gonzales Steve A. Boyd Hiroshi Miki Toshihiro Yamamoto Hiroshi Yamaguchi Koki Kato Shuji Kitamura 《Bioorganic & medicinal chemistry》2010,18(7):2785-2795
A series of diacylethylenediamine derivatives were synthesized and evaluated for their inhibitory activity against DGAT-1 and pharmacokinetic profile to discover new small molecule DGAT-1 inhibitors. Among the compounds, N-[2-({[1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]carbonyl}amino)ethyl]-6-(2,2,2-trifluoroethoxy)pyridine-3-carboxamide 3x showed potent inhibitory activity and excellent PK profile. Oral administration of 3x to mice with dietary-induced obesity resulted in reduced body weight gain and white adipose tissue weight. 相似文献
946.
Kensuke Kobayashi Minaho Uchiyama Hirobumi Takahashi Hiroshi Kawamoto Satoru Ito Takashi Yoshizumi Hiroshi Nakashima Tetsuya Kato Atsushi Shimizu Izumi Yamamoto Masanori Asai Hiroshi Miyazoe Akio Ohno Mioko Hirayama Satoshi Ozaki Takeshi Tani Yasuyuki Ishii Takeshi Tanaka Takanobu Mochidome Kiyoshi Tadano Osamu Okamoto 《Bioorganic & medicinal chemistry letters》2009,19(11):3096-3099
The synthesis and biological evaluation of new potent opioid receptor-like 1 (ORL1) antagonists are presented. Conversion of the thioether linkage of the prototype [It is reported prior to this communication as a consecutive series.: Kobayashi, K.; Kato, T.; Yamamoto, I.; Shimizu, A.; Mizutani, S.; Asai, M.; Kawamoto, H.; Ito, S.; Yoshizumi, T.; Hirayama, M.; Ozaki, S.; Ohta, H.; Okamoto, O. Bioorg. Med. Chem. Lett., in press] to the carbonyl linker effectively reduces susceptibility to P-glycoprotein (P-gp) efflux. This finding led to the identification of 2-cyclohexylcarbonylbenzimizole analogue 7c, which exhibited potent ORL1 activity, excellent selectivity over other receptors and ion channels, and poor susceptibility to P-gp. Compound 7c also showed satisfactory pharmacokinetic profiles and brain penetrability in laboratory animals. Furthermore, 7c showed good in vivo antagonism. Hence, 7c was selected as a clinical candidate for a brain-penetrable ORL1 antagonist. 相似文献
947.
948.
Hiraoka K Yamamoto S Otsuru S Nakai S Tamai K Morishita R Ogihara T Kaneda Y 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(7):4297-4307
Immunization with dendritic cells (DCs) using various Ag-loading approaches has shown promising results in tumor-specific immunotherapy and immunoprevention. Fused cells (FCs) that are generated from DCs and tumor cells are one of effective cancer vaccines because both known and unknown tumor Ags are presented on the FCs and recognized by T cells. In this study, we attempted to augment antitumor immunity by the combination of DC-tumor FC vaccination with immunostimulatory oligodeoxynucleotides containing CpG motif (CpG ODN). Murine DCs were fused with syngeneic tumor cells ex vivo using inactivated hemagglutinating virus of Japan (Sendai virus). Mice were intradermally (i.d.) immunized with FCs and/or CpG ODN. Coadministration of CpG ODN enhanced the phenotypical maturation of FCs and unfused DCs, and the production of Th1 cytokines, such as IFN-gamma and IL-12, leading to the induction of tumor-specific CTLs without falling into T cell anergy. In addition, immunization with FCs + CpG ODN provided significant protection against lethal s.c. tumor challenge and spontaneous lung metastasis compared with that with either FCs or CpG ODN alone. Furthermore, among mice that rejected tumor challenge, the mice immunized with FCs + CpG ODN, but not the mice immunized with FCs or CpG ODN alone, completely rejected tumor rechallenge, indicating that CpG ODN provided long-term maintenance of tumor-specific immunity induced by FCs. Thus, the combination of DC-tumor FCs and CpG ODN is an effective and feasible cancer vaccine to prevent the generation and recurrence of cancers. 相似文献
949.
Enhancement of the endotoxin recognition pathway by ventilation with a large tidal volume in rabbits
Moriyama K Ishizaka A Nakamura M Kubo H Kotani T Yamamoto S Ogawa EN Kajikawa O Frevert CW Kotake Y Morisaki H Koh H Tasaka S Martin TR Takeda J 《American journal of physiology. Lung cellular and molecular physiology》2004,286(6):L1114-L1121
Ventilation with a small tidal volume (V(t)) is associated with better clinical outcomes than with a large V(t), particularly in critical settings, including acute lung injury. To determine whether V(t) influences the lipopolysaccaharide (LPS) recognition pathway, we studied CD14 expression in rabbit lungs and the release of TNF-alpha by cultured alveolar macrophages after 240 min of ventilation with a large (20 ml/kg) vs. a small (5 ml/kg) V(t). We also applied small or large V(t) to lungs instilled with 50 microg/kg of LPS. The alveolar macrophages collected after large V(t) ventilation revealed a 20-fold increase in LPS-induced TNF-alpha release compared with those collected after small V(t) ventilation, whereas TNF-alpha was undetectable without LPS stimulation. In animals ventilated with a large V(t), the expression of CD14 mRNA in whole lung homogenates and the expression of CD14 protein on alveolar macrophages, assessed by immunohistochemistry, were both significantly increased in the absence of LPS stimulation. A large V(t) applied to LPS-instilled lungs increased the pulmonary albumin permeability and TNF-alpha release into the plasma. These results suggest that mechanical stress caused by a large V(t) sensitizes the lungs to endotoxin, a phenomenon that may occur partially via the upregulation of CD14. 相似文献
950.
Taoka H Yamamoto Y Sakurai N Fukuda M Asakawa Y Kurasaki A Oharaseki T Kubushiro K 《Human cell》2010,23(4):126-133
We compared the detection rate of cervical neoplasias between a liquid-based cytology (LBC) method using SurePath and the conventional method. We also studied the feasibility of human papillomavirus (HPV) typing by linear array assay. Cytological specimens from 1551 Japanese women were prepared using the conventional and SurePath methods; the cytological and histological results from biopsy samples were compared. HPV typing using an HPV linear array assay was carried out on residual specimens using the SurePath method. The cytodiagnostic results showed a concordance rate of 85.3% (Κ= 0.46) between the two methods. The sensitivity of lesions histopathologically diagnosed as CIN1 or above was not significantly different between the two methods (P = 0.575-1.000). The receiver operating characteristic curve analysis of the detectability in CIN2 or above revealed no significant difference between the two methods (P = 0.096). Among the 44 patients who underwent HPV typing using a linear array assay, 33 samples were eligible for HPV testing and were stored at ambient temperature. In conclusion, the SurePath and conventional methods have equivalent abilities for detecting cervical lesions. After preparation for cytological diagnosis, use of the remaining cells from the SurePath specimens to perform HPV typing using the linear array method could be feasible. 相似文献