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Featured researches published by Akihiko Takasaki.


Proceedings of the National Academy of Sciences of the United States of America | 2008

Comprehensive screening for antigens overexpressed on carcinomas via isolation of human mAbs that may be therapeutic

Gene Kurosawa; Yasushi Akahori; Miwa Morita; Mariko Sumitomo; Noriko Sato; Chiho Muramatsu; Keiko Eguchi; Kazuki Matsuda; Akihiko Takasaki; Miho Tanaka; Yoshitaka Iba; Susumu Hamada-Tsutsumi; Yoshinori Ukai; Mamoru Shiraishi; Kazuhiro Suzuki; Maiko Kurosawa; Sally Fujiyama; Nobuhiro Takahashi; Ryoichi Kato; Yoshikazu Mizoguchi; Mikihiro Shamoto; Hiroyuki Tsuda; Mototaka Sugiura; Yoshinobu Hattori; Shuichi Miyakawa; Ryoichi Shiroki; Kiyotaka Hoshinaga; Nobuhiro Hayashi; Atsushi Sugioka; Yoshikazu Kurosawa

Although several murine mAbs that have been humanized became useful therapeutic agents against a few malignancies, therapeutic Abs are not yet available for the majority of the human cancers because of our lack of knowledge of which antigens (Ags) can become useful targets. In the present study we established a procedure for comprehensive identification of such Ags through the extensive isolation of human mAbs that may become therapeutic. Using the phage-display Ab library we isolated a large number of human mAbs that bind to the surface of tumor cells. They were individually screened by immunostaining, and clones that preferentially and strongly stained the malignant cells were chosen. The Ags recognized by those clones were isolated by immunoprecipitation and identified by MS. We isolated 2,114 mAbs with unique sequences and identified 21 distinct Ags highly expressed on several carcinomas. Of those 2,114 mAbs 356 bound specifically to one of the 21 Ags. After preparing complete IgG1 Abs the in vitro assay for Ab-dependent cell-mediated cytotoxicity (ADCC) and the in vivo assay in cancer-bearing athymic mice were performed to examine antitumor activity. The mAbs converted to IgG1 revealed effective ADCC as well as antitumor activity in vivo. Because half of the 21 Ags showed distinct tumor-specific expression pattern and the mAbs isolated showed various characteristics with strong affinity to the Ag, it is likely that some of the Ags detected will become useful targets for the corresponding carcinoma therapy and that several mAbs will become therapeutic agents.


Journal of Biological Chemistry | 1999

Identification of the Calmodulin-binding Domain of Neuron-specific Protein Kinase C Substrate Protein CAP-22/NAP-22 DIRECT INVOLVEMENT OF PROTEIN MYRISTOYLATION IN CALMODULIN-TARGET PROTEIN INTERACTION

Akihiko Takasaki; Nobuhiro Hayashi; Emiko Yamauchi; Hisaaki Taniguchi

Various proteins in the signal transduction pathways as well as those of viral origin have been shown to be myristoylated. Although the modification is often essential for the proper functioning of the modified protein, the mechanism by which the modification exerts its effects is still largely unknown. Brain-specific protein kinase C substrate, CAP-23/NAP-22, which is involved in the synaptogenesis and neuronal plasticity, binds calmodulin, but the protein lacks any canonical calmodulin-binding domain. In the present report, we show that CAP-23/NAP-22 isolated from rat brain is myristoylated and that the modification is directly involved in its interaction with calmodulin. Myristoylated and non-myristoylated recombinant proteins were produced inEscherichia coli, and their calmodulin-binding properties were examined. Only the former bound to calmodulin. Synthetic peptides based on the N-terminal sequence showed similar binding properties to calmodulin, only when they were myristoylated. The calmodulin-binding site narrowed down to the myristoyl moiety together with a nine-amino acid N-terminal basic domain. Phosphorylation of a single serine residue in the N-terminal domain (Ser5) by protein kinase C abolished the binding. Furthermore, phosphorylation of CAP-23/NAP-22 by protein kinase C was also found myristoylation-dependent, suggesting the importance of myristoylation in protein-protein interactions.


European Journal of Medicinal Chemistry | 2000

Spirostanols obtained by cyclization of pseudosaponin derivatives and comparison of anti-platelet agglutination activities of spirostanol glycosides.

Akihiko Tobari; Mutsumi Teshima; Junich Koyanagi; Masami Kawase; Hiroshi Miyamae; Kenji Yoza; Akihiko Takasaki; Yoich Nagamura; Setsuo Saito

Naturally occurring saponins 3 and 4 have a normal type F ring and alpha-arranged CH(3)-21 group. Treatments of pseudosaponin peracetates 18 and 19 derived from 3 and 4, respectively, with alcoholic KOH, followed by acidification with acetic acid, gave spirostanols 20 and 22 having iso type F rings as major products. Structural analyses of sapogenins and saponins derived from pseudo derivatives 11, 12, 18 and 19 were performed by comparisons of their 1H-NMR spectral data and the X-ray analytical data of 3-O-p-bromobenzoyl sarsasapogenin 7, 3-O-acetyl diosgenin 13 and saponin 20. The mechanisms of ring-closure reaction of the side chain at C-22 of pseudosapogenins and pseudosaponins were deduced using stereomodels of the spirostanols derived from 11 under various reaction conditions. Inhibitory activities of saponin diglycosides 3, 4, 20, 21 and 25 on human platelet agglutinations induced by ADP and ristocetin were compared.


American Journal of Physical Medicine & Rehabilitation | 2010

Analysis of protein expression profile in the cerebellum of cerebral infarction rats after treadmill training.

Kenmei Mizutani; Shigeru Sonoda; Nobuhiro Hayashi; Akihiko Takasaki; Hidehiko Beppu; Eiichi Saitoh; Kan Shimpo

Mizutani K, Sonoda S, Hayashi N, Takasaki A, Beppu H, Saitoh E, Shimpo K: Analysis of protein expression profile in the cerebellum of cerebral infarction rats after treadmill training. Objective:To investigate the relation between protein expression changes in the cerebellum and improvement of motor coordination in rats with cerebral infarction. Design:The rat group with treadmill training (n = 10) were compared with the rat group without treadmill training (n = 10) after 2.5 hrs of transient middle cerebral artery occlusion. Motor performance measured by the rotarod test and alteration of protein expression using two-dimensional electrophoresis based on proteomics in the cerebellum were examined. Results:In behavioral evaluation, the mean latency until falling from the rotating rod in the group with treadmill training was significantly longer (P < 0.01) than that in the group without treadmill training 24 days after surgery. As for protein expression, it was revealed by proteome analysis and Western blotting that the expression of the two protein spots, 25-kDa synaptosomal-associated protein and glial fibrillary acidic protein, were significantly enhanced in the cerebellum of rats with treadmill training than that in rats without a treadmill training. Conclusions:The 25-kDa synaptosomal-associated protein and glial fibrillary acidic protein may be related to the underlying mechanisms of improvement of motor coordination and exercise-induced angiogenesis, that is, remodeling of synaptic connections and proliferation of astroglial cells, respectively.


Journal of Immunological Methods | 2009

Methods for comprehensive identification of membrane proteins recognized by a large number of monoclonal antibodies

Gene Kurosawa; Mariko Sumitomo; Yasushi Akahori; Kazuki Matsuda; Chiho Muramatsu; Akihiko Takasaki; Yoshitaka Iba; Keiko Eguchi; Miho Tanaka; Kazuhiro Suzuki; Miwa Morita; Noriko Sato; Mototaka Sugiura; Atsushi Sugioka; Nobuhiro Hayashi; Yoshikazu Kurosawa

In order to isolate monoclonal antibodies (mAbs) that bind to tumor-associated antigens (Ags) we developed the following strategy. Using the phage-display Ab library we isolated a large number of mAbs that bind to the surface of human tumor cells. The mAbs were individually screened by immunostaining, and clones that preferentially and strongly stained the malignant cells were chosen. Thereafter, the Ags recognized by the mAbs were identified. For identification of the Ags by MS candidate molecules had to be purified either by immunoprecipitation or by affinity chromatography. We isolated several hundred mAbs that showed cancer-specific staining patterns. In order to identify the Ags that were recognized by the numerous mAbs within a short time we developed two methods. Using the GFC [grouping of clones by flow cytometry (FCM)] method many Abs could be grouped by comparing the staining patterns of FCM. Members in each group turned out to bind to the same molecule in many cases. After a candidate Ag was revealed, the polypeptide corresponding to its extracellular portion was prepared and used for identification of clones that bound to the Ag among all the mAbs by SITE (simultaneous identification of clones through three dimensional ELISA) method. Both methods can be generally applicable to various kinds of membrane proteins and the mAbs against them.


Protein Expression and Purification | 1998

An Expression System of Rat Calmodulin Using T7 Phage Promoter inEscherichia coli

Nobuhiro Hayashi; Akihiko Takasaki; Koiti Titani; Hisaaki Taniguchi


Archive | 2004

Acquisition of antibody to cell surface antigen and method for identification of the antigen

Yasushi Akahori; Susumu Hamada; Nobuhiro Hayashi; Hitoshi Kurosawa; Yoshikazu Kurosawa; Keiji Miura; Kazuhiko Morino; Tomoyuki Morino; Yoshikazu Morita; Atsushi Sugioka; Mariko Sumitomo; Kazuhiro Suzuki; Akihiko Takasaki; 惠二 三浦; 万里子 住友; 篤 杉岡; 宣宏 林; 美和 森田; 和彦 森野; 智幸 森野; 進 浜田; 泰 赤堀; 和宏 鈴木; 昭彦 高崎; 仁 黒澤; 良和 黒澤


Archive | 2007

METHOD OF CLASSIFYING ANTIBODY, METHOD OF IDENTIFYING ANTIGEN, METHOD OF OBTAINING ANTIBODY OR ANTIBODY SET, METHOD OF CONSTRUCTING ANTIBODY PANEL AND ANTIBODY OR ANTIBODY SET AND USE OF THE SAME

Atsushi Sugioka; Mototaka Sugiura; Yasushi Akahori; Nobuhiro Hayashi; Akihiko Takasaki; Miwa Morita; Gene Kurosawa; Mariko Sumitomo; Susumu Tsutsumi; Keiko Ogawa; Kazuki Matsuda; Chiho Muramatsu; Noriko Satou; Masachika Azuma; Yoshinori Ukai; Kazuhiro Suzuki; Yoshikazu Kurosawa; Miho Tanaka; Mamoru Shiraishi


Archive | 2006

Anti-IgSF4 Antibody and Utilization of the Same

Yoshikazu Kurosawa; Yasushi Akahori; Nobuhiro Takahashi; Atsushi Sugioka; Nobuhiro Hayashi; Akihiko Takasaki; Kazuhiro Suzuki; Miwa Morita; Gene Kurosawa; Sari Fujiyama; Susumu Tsustumi; Keiko Ogawa; Kazuki Matsuda; Chiho Muramatsu; Yoshitaka Iba; Mariko Sumitomo; Masachika Azuma; Yoshinori Ukai; Kazuhiro Morishita


Journal of Molecular Biology | 2004

Myristoylation-regulated Direct Interaction Between Calcium-bound Calmodulin and N-terminal Region of pp60v-src

Nobuhiro Hayashi; Chisako Nakagawa; Yutaka Ito; Akihiko Takasaki; Yuji Jinbo; Yoshinori Yamakawa; Koiti Titani; Keiichiro Hashimoto; Yoshinobu Izumi; Norio Matsushima

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Kazuki Matsuda

Fujita Health University

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Miwa Morita

Fujita Health University

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Yoshikazu Kurosawa

National Institute of Radiological Sciences

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