著者

Naoki KANEKO Rie YAMAMOTO Taka-Aki SATO Koichi TANAKA

出版者

日本学士院

雑誌

Proceedings of the Japan Academy, Series B (ISSN:03862208)

巻号頁・発行日

vol.90, no.3, pp.104-117, 2014-03-11 (Released:2014-03-11)

参考文献数

41

被引用文献数

10 51 1

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Proteolytic processing of the amyloid precursor protein (APP) by β-secretase and γ-secretase leads to the generation and deposition of amyloid β (Aβ) in Alzheimer’s disease (AD). N-terminally or C-terminally truncated Aβ variants have been found in human cerebrospinal fluid and cultured cell media using immunoprecipitation and mass spectrometry. Unfortunately, the profile of plasma Aβ variants has not been revealed due to the difficulty of isolating Aβ from plasma. We present here for the first time studies of Aβ and related peptides in human plasma. Twenty-two Aβ-related peptides including novel peptides truncated before the β-secretase site were detected in human plasma and 20 of the peptides were identified by tandem mass spectrometry. Using an internal standard, we developed a quantitative assay for the Aβ-related peptides and demonstrated plasma dilution linearity and the precision required for their quantitation. The present method should enhance the understanding of APP processing and clearance in AD progression.

著者

Naoki KANEKO Akinori NAKAMURA Yukihiko WASHIMI Takashi KATO Takashi SAKURAI Yutaka ARAHATA Masahiko BUNDO Akinori TAKEDA Shumpei NIIDA Kengo ITO Kenji TOBA Koichi TANAKA Katsuhiko YANAGISAWA

出版者

日本学士院

雑誌

Proceedings of the Japan Academy, Series B (ISSN:03862208)

巻号頁・発行日

vol.90, no.9, pp.353-364, 2014-11-11 (Released:2014-11-11)

参考文献数

37

被引用文献数

8 103

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Alzheimer’s disease (AD) is the most common and devastating dementia. Simple and practical biomarkers for AD are urgently required for accurate diagnosis and to facilitate the development of disease-modifying interventions. The subjects for the study were selected on the basis of PiB amyloid imaging by PET. Forty PiB-positive (PiB+) individuals, including cognitively healthy controls (HC), and mild cognitive impairment and AD individuals, and 22 PiB-negative (PiB−) HC participated. Employing our novel highly sensitive immunoprecipitation-mass spectrometry, we measured plasma amyloid β-proteins (Aβs; Aβ1-40 and Aβ1-42) and Aβ-approximate peptides (AβAPs), which were cleaved from amyloid precursor protein (APP). Among the AβAPs, APP669-711 appeared to be a good reference for deciphering pathological change of Aβ1-42. We evaluated the performance of the ratio of APP669-711 to Aβ1-42 (APP669-711/Aβ1-42) as a biomarker. APP669-711/Aβ1-42 significantly increased in the PiB+ groups. The sensitivity and specificity to discriminate PiB+ individuals from PiB− individuals were 0.925 and 0.955, respectively. Our plasma biomarker precisely surrogates cerebral amyloid deposition.

著者

Daniel J. CAPON Naoki KANEKO Takayuki YOSHIMORI Takashi SHIMADA Florian M. WURM Peter K. HWANG Xiaohe TONG Staci A. ADAMS Graham SIMMONS Taka-Aki SATO Koichi TANAKA

出版者

The Japan Academy

雑誌

Proceedings of the Japan Academy, Series B (ISSN:03862208)

巻号頁・発行日

vol.87, no.9, pp.603-616, 2011-11-11 (Released:2011-11-11)

参考文献数

27

被引用文献数

7 7

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There is a significant need for antibodies that can bind targets with greater affinity. Here we describe a novel strategy employing chemical semisynthesis to produce symmetroadhesins: antibody-like molecules having nonprotein hinge regions that are more flexible and extendible and are capable of two-handed binding. Native chemical ligation was carried out under mild, non-denaturing conditions to join a ligand binding domain (Aβ peptide) to an IgG1 Fc dimer via discrete oxyethylene oligomers of various lengths. Two-handed Aβ–Fc fusion proteins were obtained in quantitative yield and shown by surface plasmon resonance to bind an anti-Aβ antibody with a KD at least two orders of magnitude greater than the cognate Aβ peptide. MALDI-TOF MS analysis confirmed the protein/nonprotein/protein structure of the two-handed molecules, demonstrating its power to characterize complex protein-nonprotein hybrids by virtue of desorption/ionization mediated by peptide sequences contained therein. We anticipate many applications for symmetroadhesins that combine the target specificity of antibodies with the novel physical, chemical and biological properties of nonprotein hinges.(Contributed by Koichi TANAKA, M.J.A.)

著者

Koichi TANAKA

出版者

The Association of Japanese Geographers

雑誌

地理学評論 (ISSN:13479555)

巻号頁・発行日

vol.81, no.5, pp.292-302, 2008-05-31 (Released:2010-03-12)

参考文献数

67

被引用文献数

2 3

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The purpose of this paper is to review the achievements and issues in transportation geography in Japan since 1990, focusing on modern transportation. Although the number of studies in transportation geography has decreased, the studies that have been conducted can be classified into four types, namely, studies on (1) transportation enterprises, (2) the effects of transportation developments on given areas, (3) nodal structures, and (4) airports and harbors and their hinterland. Most of the studies focus on the former two themes, while some papers have been presented on the latter two themes in the 2000s. Finally, the author points out the issues that need to be addressed —in the study of transportation geography— against the backdrop of the trend of deregulation and globalization. It is necessary to examine the significance of deregulation in a region by considering the transportation in and orientation of the city as well as its public transportation. Meanwhile, the transportation geographers in Japan should conduct studies on air liberalization and the hub airport competition in Asia.