Curriculum Vitaes

Hijikata Takao

  (土方 貴雄)

Profile Information

Affiliation
Professor, Faculty of Pharmacy Department of Pharmaceutical Sciences, Musashino University
Degree
博士(東京大学)

J-GLOBAL ID
200901077554312390
researchmap Member ID
5000034967

Research History

 11

Papers

 30
  • Tetsuyuki Takahashi, Yuri Ando, Hirona Ichikawa, Koichi Tsuneyama, Takao Hijikata
    The FEBS Journal, in press, Apr, 2023  Peer-reviewed
  • Tetsuyuki Takahashi, Hirona Ichikawa, Yukiko Okayama, Manami Seki, Takao Hijikata
    Non-Coding RNA, 8(4) 57-57, Jul 28, 2022  
    Virus-encoded microRNAs (miRNAs) target viral and host mRNAs to repress protein production from viral and host genes, and regulate viral persistence, cell transformation, and evasion of the immune system. The present study demonstrated that simian virus 40 (SV40)-encoded miRNA miR-S1 targets a cellular miRNA miR-1266 to derepress their respective target proteins, namely, T antigens (Tags) and telomerase reverse transcriptase (TERT). An in silico search for cellular miRNAs to interact with viral miR-S1 yielded nine potential miRNAs, five of which, including miR-1266, were found to interact with miR-S1 in dual-luciferase tests employing reporter plasmids containing the miRNA sequences with miR-S1. Intracellular bindings of miR-1266 to miR-S1 were also verified by the pull-down assay. These miRNAs were recruited into the Ago2-associated RNA-induced silencing complex. Intracellular coexpression of miR-S1 with miR-1266 abrogated the downregulation of TERT and decrease in telomerase activity induced by miR-1266. These effects of miR-S1 were also observed in miR-1266-expressing A549 cells infected with SV40. Moreover, the infected cells contained more Tag, replicated more viral DNA, and released more viral particles than control A549 cells infected with SV40, indicating that miR-S1-induced Tag downregulation was antagonized by miR-1266. Collectively, the present results revealed an interplay of viral and cellular miRNAs to sequester each other from their respective targets. This is a novel mechanism for viruses to manipulate the expression of viral and cellular proteins, contributing to not only viral lytic and latent replication but also cell transformation observed in viral infectious diseases including oncogenesis.
  • Misa Tokorodani, Hirona Ichikawa, Katsutoshi Yuasa, Tetsuyuki Takahashi, Takao Hijikata
    Biological and Pharmaceutical Bulletin, 43(11) 1715-1728, Nov 1, 2020  
  • Tetsuyuki Takahashi, Hirona Ichikawa, Yuuki Morimoto, Koichi Tsuneyama, Takao Hijikata
    Biochemical and Biophysical Research Communication, 516 388-396, 2019  Peer-reviewed
  • Tetsuyuki Takahashi, Ulrich Deuschle, Shu Taira, Takeshi Nishida, Makoto Fujimoto, Takao Hijikata, Koichi Tsuneyama
    Hepatology International, 12(3) 254-261, May, 2018  Peer-reviewed
    Background and aims: Tsumura-Suzuki obese diabetic (TSOD) is a good model of metabolic syndrome showing typical lesions found in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and develops spontaneous hepatic tumors with a high frequency. Majority of the developing tumors overexpress glutamine synthetase (GS), which is used as a marker of hepatocellular carcinoma (HCC). The aim of this study is to assess the status of expression of metabolism-related genes and the level of bile acids in the TSOD mice-derived tumors and to determine the association with metabolic dysregulation between human HCC and TSOD mice-derived tumors. Methods: GS-positive hepatic tumors or adjacent normal tissues from 71-week-old male TSOD mice were subjected to immunohistochemical staining, quantitative RT-PCR (qRT-PCR), quantitation of cholic acid and taurocholic acid. Results: We found that downregulation of the rate-limiting enzyme for betaine synthesis (BADH), at both mRNA and protein levels in GS-positive TSOD mice-derived tumors. Furthermore, the bile acid receptor FXR and the bile acid excretion pump BSEP (Abcb11) were found to be downregulated, whereas BAAT and Akr1c14, involved in primary bile acid synthesis and bile acid conjugation, were found to be upregulated at mRNA level in GS-positive TSOD mice-derived tumors. BAAT and Akr1c14 were also overexpressed at protein levels. Total cholic acid was found to be increased in GS-positive TSOD mice-derived tumors. Conclusion: Our results strongly support the significance of TSOD mice as a model of spontaneously developing HCC.

Misc.

 40
  • 青木 寧々, 青木 夏美, 木田 ほのか, 上原 久典, 高橋 徹行, 土方 貴雄
    日本薬学会年会要旨集, 138年会(4) 198-198, Mar, 2018  
  • 高橋徹行, 高橋徹行, 上原久典, 常山幸一, 土方貴雄
    日本薬学会年会要旨集(CD-ROM), 136th(4) ROMBUNNO.27AB‐PM260-202, Mar, 2016  
  • 依藤宏, 佐藤真人, 土方貴雄, 多鹿友喜, 高橋麻衣子, 村上徹
    厚生労働省精神・神経疾患研究委託費による研究報告集 平成21年度 (2年度班・初年度班), 2010  
  • Tohru Murakami, Takao Hijikata, Hiroshi Yorifuji
    Anatomical science international, 83(2) 68-76-76, Jun, 2008  
    The Japanese population is rapidly aging, thereby causing excess demand for facilities for elderly invalids. It is imperative that social measures and scientific studies be carried out to enable better care of bedridden elderly people. The purpose of the present study was to review the histological changes that occur in disuse atrophy of skeletal muscles, the primary pathophysiology of bedridden invalids, with the object of developing a staging standard to be used by researchers and clinicians. Rat hindlimb suspension was used as an experimental model. Atrophy of the soleus muscle was evaluated qualitatively and quantitatively on immunofluorescence microscopy. The myofibrils decreased significantly in the first 2-3 weeks of disuse atrophy. The earliest morphological change was fan-shaped multistep forking of sarcomeres, which appeared by the first week. This type of muscular lesion, designated here as 'sarcomeric disarray', was first described in the present study. Central-core lesions appeared mainly in slow muscle fibers by the second week. These lesions disappeared by the fourth or fifth week. Nerves remained intact and no inflammation or regeneration occurred up to the fifth week. Methods and criteria were compiled for staging of disuse atrophy based on the present results and a diagnosis kit designed for studies on disuse atrophy of skeletal muscles.
  • Takao Hijikata, Akio Nakamura, Keitaro Isokawa, Michihiro Imamura, Katsutoshi Yuasa, Ryoki Ishikawa, Kazuhiro Kohama, Shinichi Takeda, Hiroshi Yorifuji
    JOURNAL OF CELL SCIENCE, 121(12) 2062-2074, Jun, 2008  
    In skeletal muscles, the sarcolemma is possibly stabilized and protected against contraction-imposed stress by intermediate filaments (IFs) tethered to costameric sarcolemma. Although there is emerging evidence that plectin links IFs to costameres through dystrophin-glycoprotein complexes (DGC), the molecular organization from plectin to costameres still remains unclear. Here, we show that plectin 1, a plectin isoform expressed in skeletal muscle, can interact with beta-synemin, actin and a DGC component, alpha-dystrobrevin, in vitro. Ultrastructurally, beta-synemin molecules appear to be incorporated into costameric dense plaques, where they seem to serve as actin-associated proteins rather than IF proteins. In fact, they can bind actin and alpha-dystrobrevin in vitro. Moreover, in vivo immunoprecipitation analyses demonstrated that alpha-synemin-and plectin-immune complexes from lysates of muscle light microsomes contained alpha-dystrobrevin, dystrophin, nonmuscle actin, metavinculin, plectin and beta-synemin. These findings suggest a model in which plectin 1 interacts with DGC and integrin complexes directly, or indirectly through nonmuscle actin and beta-synemin within costameres. The DGC and integrin complexes would cooperate to stabilize and fortify the sarcolemma by linking the basement membrane to IFs through plectin 1, beta-synemin and actin. Besides, the two complexes, together with plectin and IFs, might have their own functions as platforms for distinct signal transduction.
  • Katsutoshi Yuasa, Takao Hijikata
    JOURNAL OF GENE MEDICINE, 10(4) 477-477, Apr, 2008  
  • Katsutoshi Yuasa, Akinori Nakamura, Takao Hijikata, Shinichi Takeda
    BMC MUSCULOSKELETAL DISORDERS, 9(1), Jan, 2008  
    Background: Skeletal muscles are composed of heterogeneous collections of muscle fiber types, the arrangement of which contributes to a variety of functional capabilities in many muscle types. Furthermore, skeletal muscles can adapt individual myofibers under various circumstances, such as disease and exercise, by changing fiber types. This study was performed to examine the influence of dystrophin deficiency on fiber type composition of skeletal muscles in canine X-linked muscular dystrophy in Japan (CXMD(J)), a large animal model for Duchenne muscular dystrophy. Methods: We used tibialis cranialis (TC) muscles and diaphragms of normal dogs and those with CXMDJ at various ages from 1 month to 3 years old. For classification of fiber types, muscle sections were immunostained with antibodies against fast, slow, or developmental myosin heavy chain (MHC), and the number and size of these fibers were analyzed. In addition, MHC isoforms were detected by gel electrophoresis. Results: In comparison with TC muscles of CXMDJ, the number of fibers expressing slow MHC increased markedly and the number of fibers expressing fast MHC decreased with growth in the affected diaphragm. In populations of muscle fibers expressing fast and/or slow MHC(s) but not developmental MHC of CXMDJ muscles, slow MHC fibers were predominant in number and showed selective enlargement. Especially, in CXMDJ diaphragms, the proportions of slow MHC fibers were significantly larger in populations of myofibers with non-expression of developmental MHC. Analyses of MHC isoforms also indicated a marked increase of type I and decrease of type IIA isoforms in the affected diaphragm at ages over 6 months. In addition, expression of developmental (embryonic and/or neonatal) MHC decreased in the CXMDJ diaphragm in adults, in contrast to continuous high-level expression in affected TC muscle. Conclusion: The CXMDJ diaphragm showed marked changes in fiber type composition unlike TC muscles, suggesting that the affected diaphragm may be effectively adapted toward dystrophic stress by switching to predominantly slow fibers. Furthermore, the MHC expression profile in the CXMDJ diaphragm was markedly different from that in mdx mice, indicating that the dystrophic dog is a more appropriate model than a murine one, to investigate the mechanisms of respiratory failure in DMD.
  • K. Yuasa, M. Yoshimura, N. Urasawa, S. Ohshima, J. M. Howell, A. Nakamura, T. Hijikata, Y. Miyagoe-Suzuki, S. Takeda
    GENE THERAPY, 14(17) 1249-1260, Sep, 2007  
    Using murine models, we have previously demonstrated that recombinant adeno-associated virus (rAAV)-mediated microdystrophin gene transfer is a promising approach to treatment of Duchenne muscular dystrophy (DMD). To examine further therapeutic effects and the safety issue of rAAV-mediated microdystrophin gene transfer using larger animal models, such as dystrophic dog models, we first investigated transduction efficiency of rAAV in wild-type canine muscle cells, and found that rAAV2 encoding beta-galactosidase effectively transduces canine primary myotubes in vitro. Subsequent rAAV2 transfer into skeletal muscles of normal dogs, however, resulted in low and transient expression of b-galactosidase together with intense cellular infiltrations in vivo, where cellular and humoral immune responses were remarkably activated. In contrast, rAAV2 expressing no transgene elicited no cellular infiltrations. Co-administration of immuno-suppressants, cyclosporine and mycophenolate mofetil could partially improve rAAV2 transduction. Collectively, these results suggest that immune responses against the transgene product caused cellular infiltration and eliminated transduced myofibers in dogs. Furthermore, in vitro interferon-g release assay showed that canine splenocytes respond to immunogens or mitogens more susceptibly than murine ones. Our results emphasize the importance to scrutinize the immune responses to AAV vectors in larger animal models before applying rAAV-mediated gene therapy to DMD patients.
  • K Yuasa, M Yoshimura, A Nishiyama, M Ikemoto, S Ohshima, Y Miyagoe-Suzuki, JM Howell, T Hijikata, S Takeda
    JOURNAL OF GENE MEDICINE, 8(3) 390-390, Mar, 2006  
  • T Murakami, T Hijikata, M Matsukawa, H Ishikawa, H Yorifuji
    DEVELOPMENTAL DYNAMICS, 235(2) 506-514, Feb, 2006  
    Here, we present the first report of the molecular cloning of zebrafish protocadherin 10 (Pcdh10, OL-protocadherin) and describe its functional analyses in the development of segmental plate. Epitope-tagged Pcdh10 expressed in embryos was localized on cell peripheries of adjacent cells. In situ hybridization showed that pcdh10 was expressed in the paraxial mesoderm (PAM) and developing somites, and in the pineal body, the diencephalon, and the vicinity of otocysts. Expression in PAM increased in the last few presumptive somites, reached the maximum level in the latest segmenting somites, and decreased thereafter during somite maturation. These expression patterns suggested that Pcdh10 is involved in development of PAM and somites. This was confirmed by morpholino knockdown and dominant-negative inhibition of Pcdh10 in embryos, which disturbed movements of PAM cells and somite segmentation. Comparative studies showed that pcdh10 expression lasted up to approximately three times longer in maturing somites than that of paraxial protocadherin (pcdh8). They also indicated that the adaxial cells expressed pcdh8 but not pcdh10. We propose that Pcdh10 is involved in the morphogenic movements of PAM cells and somite segmentation and that differential adhesion of Pcdh8 and Pcdh10 plays a role in the morphogenic machinery of somites and adaxial cells.
  • 村上徹, 土方貴雄, 久保田文隆, 依藤宏
    解剖学雑誌, 81(Supplement), 2006  
  • Murakami Tohru, Hijikata T, Matsukawa M, Yorifuji H
    Anatomical Science International, 79(Supplement) 246, 2004  
  • Yorifuji H, Hijikata T, Murakami T
    Anatomical Science International, 79(Supplement) 245, 2004  
  • Hijikata T, Yorifuji H
    Anatomical Science International, 79(Supplement) 97, 2004  
  • T Hijikata, T Murakami, H Ishikawa, H Yorifuji
    HISTOCHEMISTRY AND CELL BIOLOGY, 119(2) 109-123, Feb, 2003  
    Plectin is a versatile cytoskeletal linker protein that preferentially localizes at interfaces between intermediate filaments and the plasma membrane in muscle, epithelia] cells, and other tissues. Its deficiency causes muscular dystrophy with epidermolysis bullosa simplex. To better understand the functional roles of plectin beneath the sarcolemma of skeletal muscles and to gain some insights into the underlying mechanism of plectin-deficient muscular dystrophy, we studied in vivo structural and molecular relationships of plectin to subsarcolemmal cytoskeletal components, such as desmin, dystrophin, and vinculin, in rat skeletal muscles. Immunogold electron microscopy revealed that plectin fine threads tethered desmin intermediate filaments onto subsarcolemmal dense plaques overlying Z-lines and I-bands. These dense plaques were found to contain dystrophin and vinculin, and thus may be the structural basis of costameres. The in vivo association of plectin with desmin, (meta-)vinculin, dystrophin, and actin was demonstrated by immunoprecipitation experiments. Treatment of plectin immunoprecipitates with gelsolin reduced actin, dystrophin, and (meta-)vinculin but not desmin, implicating that subsarcolemmal actin could partly mediate the interaction between plectin and dystrophin or (meta-)vinculin. Altogether, our data suggest that plectin, along with desmin intermediate filaments, might serve a vital structural role in the stabilization of the subsarcolemmal cytoskeleton.
  • 土方貴雄, 村上徹, 依藤宏
    解剖学雑誌, 78(Supplement), 2003  
  • 村上徹, 土方貴雄, 石川春律, 依藤宏
    解剖学雑誌, 78(Supplement), 2003  
  • H Tanaka, T Hijikata, T Murakami, N Fujimaki, H Ishikawa
    CELL STRUCTURE AND FUNCTION, 26(2) 61-70, Apr, 2001  
    Plectin is a versatile linker protein which is associated with various types of cytoskeletal components and/or filaments including intermediate filaments. To better understand the functional roles of plectin in smooth muscle cells, we examined the distribution of plectin and other related proteins in rat colon smooth muscles by confocal laser and electron microscopy. The sarcolemma of smooth muscle cells exhibits two ultrastructurally distinct domains, domains associated with dense plaques and caveola-rich domains. Staining with anti-plectin and anti-desmin antibodies showed that plectin was localized along the sarcolemma in an intermittent manner and desmin was distributed in the sarcoplasm and intermittently at the cell periphery where it was codistributed with desmin. Plectin exhibited complementary and non-overlapping distribution to caveolin-1 and dystrophin, components of caveola domains, whereas plectin was codistributed with vinculin, talin and integrin beta1, components of dense plaques. Plectin was also codistributed with beta2-chain laminin but not with beta1-chain laminin, Electron microscopic observations on the sarcolemma revealed close association of intermediate filaments with dense plaques. Correlated confocal and electron microscopy clearly demonstrated that anti-plectin fluorescence corresponded to dense plaques but not to caveola domains in electron microscopic images. These findings indicate that plectin is confined to dense plaques to which desmin intermediate filaments may be anchored in rat colon smooth muscle cells.
  • 田中秀幸, 土方貴雄, 村上徹, 藤巻昇, 石川春律
    解剖学雑誌, 75(5), 2000  
  • 田中秀幸, 土方貴雄, 村上徹, 藤巻昇, 石川春律
    解剖学雑誌, 75(1), 2000  
  • K Ojima, ZX Lin, ZQ Zhang, T Hijikata, S Holtzer, S Labeit, HL Sweeney, H Holtzer
    JOURNAL OF CELL SCIENCE, 112(22) 4101-4112, Nov, 1999  
    While over a dozen I-Z-I proteins are expressed in postmitotic myoblasts and myotubes it is unclear how, when, or where these first assemble into transitory I-Z-I bodies (thin filament/Z-band precursors) and, a short time later, into definitive I-Z-I bands. By double-staining the growth tips of transfected myotubes expressing (a) MYC-tagged s-alpha-actinins (MYC/s-alpha-actinins) or (b) green fluorescent protein-tagged titin cap (GFP/T-cap) with antibodies against MYC and I-Z-I band proteins, we found that the de novo assembly of I-Z-I bodies and their maturation into I-Z-I bands involved relatively concurrent, cooperative binding and reconfiguration of, at a minimum, 5 integral Z-band molecules. These included s-alpha-actinin, nebulin, titin, T-cap and alpha-actin, Resolution of the similar to 1.0 mu m polarized alpha-actin/nebulin/tropomyosin/troponin thin filament complexes occurred subsequent to the maturation of Z-bands into a dense tetragonal configuration. Of particular interest is finding that mutant MYC/s-alpha-actinin peptides (a) lacking spectrin-like repeats 1-4, or consisting of spectrin-like repeats 1-4 only, as well as (b) mutants/fragments lacking titin or alpha-actin binding sites, were promptly and exclusively incorporated into de novo assembling I-Z-I bodies and definitive I-Z-I bands as was exogenous full length MYC/s-alpha-actinin or GFP/T-cap.
  • T Hijikata, T Murakami, M Imamura, N Fujimaki, H Ishikawa
    JOURNAL OF CELL SCIENCE, 112(6) 867-876, Mar, 1999  
    Plectin is a versatile linker protein which is associated with various types of cytoskeletal components and/or filaments including intermediate filaments, and its deficiency causes the disruption of myofibrils, or muscular dystrophy. To better understand the functional role of plectin in skeletal muscle fibers, we have examined the topological and structural relationships of plectin to intermediate filaments and Z-discs in rat diaphragm muscles by confocal and immunoelectron microscopy. Immunofluorescence analysis revealed that plectin was colocalized with desmin at the periphery of Z-discs. This plectin localization around Z-discs was constantly maintained irrespective of the contracted or extended state of the muscle fibers, suggesting either direct or indirect association of plectin with Z-discs. Immunogold labeling in skinned muscle fibers clearly demonstrated that plectin-labeled fine threads linked desmin intermediate filaments to Z-discs and connected intermediate filaments to each other. These results indicate that through plectin threads desmin intermediate filaments form lateral linkages among adjacent Z-discs, preventing individual myofibrils from disruptive contraction and ensuring effective force generation.
  • 村上 徹, 萩原 治夫, 土方 貴雄, 藤巻 昇, 石川 春律
    解剖学雑誌, 74(1) 147-147, Feb, 1999  
  • 石川春律, 土方貴雄, 藤巻昇, 村上徹, 田中秀幸
    筋ジストロフィーの分子病態学的基礎研究 平成8-10年度 総括研究報告書, 1999  
  • T Hijikata, N Fujimaki, H Osawa, H Ishikawa
    BIOLOGY OF THE CELL, 90(9) 629-639, Dec, 1998  
    It has been biochemically shown that dystrophin and alpha- and beta-dystroglycan form an oligomeric complex which links laminin, a component of the basement membrane, to components of the subsarcolemmal cytoskeleton in skeletal muscle fibers. In the present study the dystrophin-glycoprotein complex and its structural relationships to laminin and subsarcolemmal cytoskeleton were ultrastructurally examined in crude surface membranes prepared from rat skeletal muscles. Sarcolemmal vesicles within crude surface membranes were identified and characterized by fine protrusions on their outer surface and electron-dense materials or patches associated with the inner surface. These two components were seen to be in register with each other across the sarcolemma. The fine protrusions were immunolabeled by anti-alpha-dystroglycan and reassociated with exogenous laminin. Immunolabeling in combination with laminin reassociation demonstrated that the electron-dense materials contained dystrophin at laminin-binding domains of the membrane. In addition, they were often associated with very fine filaments. These results provide morphological evidence for the biochemically proposed model of molecular array of dystrophin complex from the basement membrane to the subsarcolemmal cytoskeleton. ((C) Elsevier, Paris).
  • Z Lin, T Hijikata, Z Zhang, J Choi, S Holtzer, HL Sweeney, H Holtzer
    DEVELOPMENTAL BIOLOGY, 199(2) 291-308, Jul, 1998  
    To explore the roles of specific domains of sarcomeric a-actinin (s-alpha-aetinin) in the assembly and maintenance of striated myofibrils, myogenic cultures were transfected with four MYC-tagged s-alpha-actinin peptides. They were: (1) full-length sarcomeric alpha-actinin, (2) an N-terminal deletion that removed the actin-binding site only (MYC/A(-)), (3) a peptide that consisted of the actin-binding site only (MYC/A(+)), and (4) an N-terminal deletion that removed the EF-hands and titin-binding domains (MYC/EFT-). While cytotoxic in replicating myogenic cells, as they were in PtK2 cells, the four MYC peptides were not cytotoxic in postmitotic myotubes. In myotubes each of the four different MYC peptides were promptly and selectively incorporated into normal Z bands. The incorporation of MYC/A(-), MYC/A(+), and MYC/EFT- into Z bands suggests that (a) the actin-binding site, (b) the spectrin-repeats believed to be responsible for anti-parallel dimerization, and (c) the C-terminal EF-hands and titin-binding domains are each dispensable for targeting s-alpha-actinin/MYC peptides into Z bands. These findings could not have been predicted from the behavior of alpha-actinin (a) in binding assays in cell-free systems or (b) when expressed in transfected nonmuscle cells. (C) 1998 Academic Press.
  • H Holtzer, T Hijikata, ZX Lin, ZQ Zhang, S Holtzer, F Protasi, C FranziniArmstrong, HL Sweeney
    CELL STRUCTURE AND FUNCTION, 22(1) 83-93, Feb, 1997  
  • T Hijikata, H Ishikawa
    ACTA ANATOMICA, 159(2-3) 99-107, 1997  
    In the skeletal muscle fiber organization of many vertebrate muscles, serial arrangements or linkages of muscle fibers along the muscle or fascicle are commonly found. These serially linked muscle fibers employ distinct junctional morphologies from muscle to muscle. Notable are the end-to-end linkages of muscle fibers through tendinous intersections (TIs), where many fibers end onto a continuous connective tissue plate with folded terminations similar to myotendinous junctions. Besides this end-to-end linkage, overlapping linkages or arrangements occur among nonspanning fibers terminating intrafascicularly. These nonspanning fibers bear tapering terminations with direct cell-cell (myomuscular) junctions or without any specialized junctions. Despite their overlapping linkages or tapering profiles, nonspanning fibers maintain a uniform sarcomere length along the linked fibers, suggesting that the overlapping-linked nonspanning fibers are equivalent to the end-to-end linked fibers in their mechanical capacity. However, the junctional compliance could differ in their extracellular elastic components and their organization at junctional sites, e.g., direct mechanical (myomuscular) junctions vs, indirect linkages through connective tissue. Increasing evidence suggests that the elastic components, including muscle fibers as well as connective tissues, are more critical than previously thought for the mode and/or the efficiency of tension transmission among serially arranged fibers and thus for the mechanical properties of the muscle.
  • T Hijikata, ZX Lin, S Holtzer, J Choi, HL Sweeney, H Holtzer
    CELL MOTILITY AND THE CYTOSKELETON, 38(1) 54-74, 1997  
    To understand the multiple roles of alpha-actinin in the assembly of (1) Z bands in muscle, and (2) a variety of cytoskeletal structures in non-muscle cells, 4 sarcomeric alpha-actinin derived cDNAs tagged with a MYC epitope were constructed. The constructs were: (1) full-length (FL/MYC); (2) minus EF-hands (-EF/MYC); (3) actin-binding site ((+)A/MYC); and (4) minus actin-binding site ((-)A/MYC). These four cDNAs were individually transfected into PtK2 cells. The exogenous sarcomeric alpha-actinin (s-alpha-actinin/MYC) was followed with labeled anti-MYC, the endogenous non-sarcomeric alpha-actinin (non-s-alpha-actinin) with labeled anti-non-s-alpha-actinin. The salient findings were: (1) the selective intracellular localizations of each expressed MYC-tagged peptide differed one from the other; (2) their respective localizations in the 10-24-h post-transfection (p.t.) period differed from their localizations in the 48-72-h p.t. period; (3) each MYC-positive peptide was cytotoxic, but each in a distinctive way; and (4) while the selective targeting of FL/MYC to dense bodies, adhesion plaques, adherens junctions, and ruffled membranes was consistent with binding studies in cell-free systems, the incorporation of the mutated peptides, particularly (+)A/MYC and -A/MYC was not. Changes in localization over time and the distinctive cytopathologies probably reflect domain-specific targeting. They also suggest unexpected cooperative involvement of multiple domains of alpha-actinin with specific receptors in distal cytoskeletal structures. To date, such qualitative in vivo interactions have not been described either in in vitro binding studies, or in short-term experiments involving localization and/or fate of microinjected labeled molecules into living cells. (C) 1997 Wiley-Liss, Inc.
  • KR YU, T HIJIKATA, ZX LIN, HL SWEENEY, SW ENGLANDER, H HOLTZER
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 91(7) 2497-2501, Mar, 1994  
    The earliest expression of truncated desmin in transfected PtK2 cells results in the formation of dispersed microprecipitates containing not only the truncated desmin, but also endogenous vimentin and cytokeratin proteins. Desmin microprecipitates without vimentin or vimentin microprecipitates without desmin are not observed. The microprecipitates involving cytokeratin invariably are also positive for desmin and vimentin. Over time, the precipitates enlarge into 1- to 2-mum spheroids and then fuse into amorphous chimeric juxtanuclear masses that can occupy >30% of the cell volume. Concurrently, first the vimentin and then the cytokeratin networks are resorbed. The chimeric precipitates are not recognized or marked for degradation by the lysosomal system. Ultimately the cell nucleus fragments and the cell dies. Similar protein complexes appear in many human and animal pathologies, suggesting that a similar protein-precipitation sequence initiated by the introduction of a mutationally or environmentally altered protein molecule is at work.
  • H WAKISAKA, T HIJIKATA, T YOHRO
    BIOMEDICAL RESEARCH-TOKYO, 14(5) 353-361, Oct, 1993  
    A procedure for classifying histochemically stained skeletal muscle fibers using a personal computer was established. Frozen sections of rat rectus abdominis muscle were stained for myosin ATPase with preincubation at low and high pH, and for a mitochondrial enzyme, NADH tetrazolium reductase. Light microscopic images of the sections were converted through a video camera into computerized images which were then analyzed with digital image-processing software in a personal computer to recognize individual muscle fibers and to categorize them into slow-twitch, oxidative type; fast-twitch, oxidative-glycolytic type; and fast-twitch, glycolytic type. This procedure yielded not only number of fibers but also cross-sectional area of fibers for each fiber type. Video copies of the identical fields were used for the visual assessment of fiber types to compare the results with those obtained by the computer. The discrepancy between the computer-aided procedure and the conventional visual assessment on video copies was less than 10 percent, except for 30 percent in 'intermediate' fibers in sections stained for the mitochondrial enzyme. The present procedure, employing a relatively small-sized multi-purpose personal computer system, proved to be effective and reliable in the analysis of local fiber-type composition.
  • T HIJIKATA, H WAKISAKA, S NIIDA
    ANATOMICAL RECORD, 236(4) 602-610, Aug, 1993  
    Using digital image analysis and several anatomical methods, morphometric analysis of nonspanning fibers which had tapering profiles at their intrafascicular termination sites and represented overlapping arrangements within the fiber fascicles was performed in the rat rectus abdominis. Special emphasis was focused on dimensional relationships occurring between overlapping portions and tapering segments and sarcomere lengths in non- and overlapping portions. Nonspanning fibers were found to overlap each other for more than 40% of their length. In length, their overlapping portions generally corresponded to their tapering segments, which were also greater than 40% of the fiber length. In addition, despite the presence of overlapping linkages, nonspanning fibers maintained a fairly uniform length irrespective of their overlapping and non-overlapping portions. Overlapping linkages in fibers without tapering profiles have a larger cross-sectional area in the overlapping portion than in the non-overlapping one, resulting in a phenomenon which will cause different sarcomere lengths between the two portions during fiber stretching. The present results suggest that tapering profiles in the overlapping portion ensure uniform sarcomere lengths within nonspanning fibers, thereby providing mechanical stability in each fiber. (C) 1993 Wiley-Liss, Inc.
  • T HIJIKATA, H WAKISAKA, T YOHRO
    ANATOMICAL RECORD, 234(4) 500-512, Dec, 1992  
    The rectus abdominis muscle is architecturally compartmentalized by tendinous intersections and is supplied by multiple thoracic nerves. In this study, the rectus abdominis of the rat has been qualitatively and quantitatively examined with regard to muscle dimensions, fiber organization, fiber-type composition, and innervation. The muscle exhibits architectural heterogeneity and different patterns of innervation among its thoracic, epigastric, and hypogastric parts. The epigastric part, adherent to the rectus sheath via tendinous intersections, represents relatively simple design. It is formed by serially arranged compartments with shorter fibers, compared with the other parts. These compartments are segmentally supplied by thoracic nerves. The hypogastric part is more complex, forms an interdigitation of muscular slips, and has segmental distribution of thoracic nerves in mediolateral direction. The thoracic part much differs from the other parts. It has smaller cross-sectional areas, compartments composed of abundant nonspanning fibers with intrafascicular termination, and non-segmental distribution of thoracic nerves. In addition to these craniocaudal specializations among the three parts, the muscle exhibits mediolateral differences in fiber-type composition. Slow-twitch oxidative fibers are more densely distributed in the medial half region than the lateral, whereas fast-twitch glycolytic fibers follow an inverse pattern. The mediolateral differences in fiber-type composition as well as the craniocaudal specializations in architectural design and innervation imply regionally differentiated recruitments of the muscle in various behaviors.
  • T HIJIKATA, T SAKAI
    CELL AND TISSUE RESEARCH, 266(1) 11-22, Oct, 1991  
    The ultrastructure of the basement membrane of the rat proximal tubule was observed by transmission electron microscopy after the use of a cold dehydration technique. The basement membrane of the P1 segment is thick and possesses several structural specializations that are rare in other basement membranes; these include intraepithelial ridges, dense bars, and basement membrane vesicles. The intraepithelial ridges are found in the intercellular spaces between interdigitating processes of the proximal tubule cells. The ridges and the interdigitating processes run circumferentially around the tubule. The dense bars are frequently found in the intraepithelial ridges. They are especially prominent on the concave side of the tubular bends and to a lesser extent near sites where intracellular actin filaments anchor onto the basal cell membranes. The basement membrane vesicles are bounded by unit membranes; they are variable in both their electron density and their size. They are usually found in association with dense bars, and the grade of their accumulation is positively correlated with the development of the dense bars. These three specializations have no topographical relationship with the interstitial structures, such as fibroblasts and collagen fibrils. The specializations are best developed on the concave side of tubular bends where the circumferential stresses caused by the intraluminal hydraulic pressure are presumably the largest; we therefore propose that they are an adaptation to, or a manifestation of, the increased wall stress in the proximal tubule.
  • T SAKAI, T HIJIKATA
    CELLULAR AND MOLECULAR BIOLOGY OF THE KIDNEY, 95 34-47, 1991  
  • T. Hijikata, T. Sakai, T. Yohro
    Acta Anatomica Nipponica, 65(4) 159-175, 1990  
  • N NISHIYAMA, CH WANG, T HIJIKATA, H SAITO
    CHEMICAL & PHARMACEUTICAL BULLETIN, 36(8) 3176-3179, Aug, 1988  
  • SC LIN, T HIJIKATA, H SAITO, S KAMEI, J SHIGA, C WANG
    EXPERIMENTAL ANIMALS, 36(1) 57-63, Jan, 1987  
  • T HIJIKATA, H SAITO, T YOHRO
    PROSTATE, 8(3) 277-291, 1986  

Books and Other Publications

 5
  • 福永哲夫, 者, 土方貴雄 (Role: Joint author)
    朝倉書店, Nov, 2002
    骨格筋の解剖、生理、運動などを詳細に解説した事典。 担当執筆部分1.1骨格筋の解剖学的基礎 骨格筋の肉眼解剖、組織構築、分子構築を解剖学的観点から詳細に解説した。(全505ページ)
  • 著者:Kawakami Y, Kumagai K, Huijing PA, Hijikata T, Fukunaga T (Role: Joint author)
    John Wiley & Sons, LTD., Oct, 2000
    骨格筋の運動や力学的特性に関するシンポジウムのプロシーディング。19. The length-force characteristics of human gastrocnemius and soleus muscles in vivo. .ヒトの腓腹筋とヒラメ筋の筋線維構築を解剖学的に明らかにし、さらに超音波画像によりこれら筋の筋線維の動きや力の特性を明らかにした。これら結果にもとづき、筋線維構築と筋線維の運動ならびに力の特性を比較検討した総説的論文。(筋線維構築の解析箇所で貢献している).(全554ページ)
  • 板倉 照好編集, 著者, 石川春律, 村上徹, 土方貴雄 (Role: Joint author)
    羊土社, Jun, 1998
    細胞接着装置と細胞外マトリックスを介した細胞内情報伝達機構および生体内での機能発現調節についての解説書。また細胞接着の異常による疾患についても言及している。 分担執筆部分:デスモゾームの分子構築に関しての部分。(全126ページ)
  • 訳者 土方貴雄コメディカルサポート研究会 (Role: Joint author)
    医学書院, May, 1998
    コメディカルの学生のための解剖生理学の教科書。図説も豊富で生理的機能についても学生に分かりやすく解説している。 担当訳部分第5章 骨格系 .第6章 骨格筋系 .第19章 生殖器系(全505ページ)
  • 監修 佐藤達夫, 著者, 土方貴雄 (Role: Joint author)
    サイエンス・コミュニケーション・インターナショナル, Apr, 1995
    医学生および専門家のための末梢神経の解剖学的な解説書。先端研究の事例をあげ神経分岐パターンやその意義を解説している。 分担執筆部分:II腹直筋の支配神経。腹直筋の支配神経が局所的に異質であることを系統解剖学的に解説した。また、腹直筋の支配神経の運動制御についても言及している。(全285ページ)

Research Projects

 10

Social Activities

 1

教育内容・方法の工夫

 2
  • Subject
    シュミレーション実験的授業の実施
    Date(From)
    1998/04
    Date(To)
    2004/03
    Summary
    解剖の講義はノミナおよび知識の羅列になりがちであるが、このような状況を打破するために、シュミレーション実験を行うようにして授業をすすめている。例えば、末梢神経と骨格筋との間にみられる法則性を提起し、この法則性が実際にあてはまるかどうかを解剖図譜などを用いて個々の事例で学生自身に検証してもらう。こういったシュミレーション実験的な授業の後には必ず学生から質問が出され、非常に好評であるという感触を得ている。
  • Subject
    パワーポイントと空欄のあるプリントを用いた授業の実施
    Date(From)
    2005/04
    Date(To)
    2005/04
    Summary
    授業形式としては、学生にパワーポイントのスライドに対応する書き込み空欄のあるプリントを渡し、スライドでの説明に則して空欄に書き込みをさせる形で授業を進めた。授業中は、説明を理解する時間と書き込む時間を細かくわけ、理解した後に書き込みをさせインプットを確実なものにするよう努めた。

教育上の能力に関する大学等の評価

 1
  • Subject
    授業評価
    Date(From)
    1998/04
    Date(To)
    2004/03
    Summary
    古典的肉眼解剖学、比較解剖学、および系統発生から現代の分子生物学までの広範囲の研究実績ならびに背景から、人体構造のもつ意味並びに構造の進化を説明していくことで、学生から好評を得ている。このことは教育者として高く評価できる。また、本学部学生だけでなくその訳書や看護学生の解剖実習見学を通じてコメディカルの学生への教育にも携わっており社会的貢献度の高い教員といえる。

その他(教育上の能力)

 3
  • Subject
    コメディカル学生への解剖実習指導
    Date(From)
    1995/04
    Date(To)
    2000/03
    Summary
    毎年秋に看護学の学生の解剖実習見学があるが、その講師として人体解剖実習を指導した。
  • Subject
    大学院学生への実験と論文作成の指導
    Date(From)
    1995/04
    Date(To)
    2000/03
    Summary
    大学院学生の研究では、はじめに実験を一緒に行うことで基本的実験手技を修得させる。その後、実験プロトコールをチェックしながら実験の展開を具体的に指導した。最終的にはデータを論文の中でどのようにまとめていくかについての指導も行った。また、抗体の提供という形で博士論文研究にも貢献した。
  • Subject
    厚生労働省助成金
    Date(From)
    2006
    Summary
    筋ジストロフィー及びその関連する疾患の病態生理の解明と治療薬物の開発に関する研究 助成金 1,000,000円 共同研究者:清水輝夫

資格・免許

 1
  • Subject
    薬剤師
    Date
    2002/07/31
    Summary
    第371016号