Yukiko K Hayashi

Publications (218) View all

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  Available from: Ichizo Nishino

  Article: Positive association between STAT4 polymorphisms and polymyositis/dermatomyositis in a Japanese population.

  Tomoko Sugiura, Yasushi Kawaguchi, Kanako Goto, Yukiko Hayashi, Rie Tsuburaya, Takefumi Furuya, Takahisa Gono, Ichizo Nishino, Hisashi Yamanaka
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  ABSTRACT: To investigate associations between signal transducer and activator of transcription 4 (STAT4), one of the most commonly acknowledged genes for the risk of multiple autoimmune diseases, with susceptibility to adult-onset polymyositis/dermatomyositis among Japanese individuals. A single nucleotide polymorphism of STAT4, rs7574865, was genotyped using TaqMan assay in 1143 Japanese individuals. The first set comprised 138 polymyositis/dermatomyositis patients and 289 controls and the second set comprised 322 patients and 394 controls. 460 patients (273 polymyositis and 187 dermatomyositis patients) and 683 controls were genotyped. rs7574865T conferred a risk of polymyositis/dermatomyositis with an OR of 1.37 (95% CI 1.16 to 1.64; p=4x10(-4); p(corr)=0.0012). Both polymyositis and dermatomyositis exhibited high associations with the rs7574865T allele (polymyositis: OR=1.36, 95% CI 1.11 to 1.67; p=0.0039; p(corr)=0.012; dermatomyositis: OR=1.40, 95% CI 1.10 to 1.78; p=0.0054; p(corr)=0.016). The association between this STAT4 polymorphism and interstitial lung disease (ILD) was also investigated in the first set of polymyositis/dermatomyositis patients (n=138); those with ILD (n=79) bore rs7574865T more frequently compared with controls (OR 1.59, 95% CI 1.10 to 2.28; p=0.013; p(corr)=0.039). This is the first study to show a positive association between a STAT4 polymorphism and polymyositis/dermatomyositis, suggesting that polymyositis/dermatomyositis shares a gene commonly associated with the risk of other autoimmune diseases.
  Annals of the rheumatic diseases 03/2012; 71(10):1646-50. · 8.11 Impact Factor
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  Article: Characterization of the Asian myopathy patients with VCP mutations.

  Z Shi, Y K Hayashi, S Mitsuhashi, K Goto, D Kaneda, Y-C Choi, C Toyoda, S Hieda, T Kamiyama, H Sato, M Wada, S Noguchi, I Nonaka, I Nishino
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  ABSTRACT: Mutations in the valosin-containing protein (VCP) gene are known to cause inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD) and familial amyotrophic lateral sclerosis (ALS). Despite an increasing number of clinical reports, only one Asian family with IBMPFD has been described. To characterize patients with VCP mutations, we screened a total of 152 unrelated Asian families who were suspected to have rimmed vacuolar myopathy. We identified VCP mutations in seven patients from six unrelated Asian families. Five different missense mutations were found, including a novel p.Ala439Pro substitution. All patients had adult-onset progressive muscle wasting with variable involvement of axial, proximal, and distal muscles. Two of seven patients were suggested to have mild brain involvement including cerebellar ataxia, and only one showed radiological findings indicating a change in bone. Findings from skeletal muscle indicated mixed neurogenic and myogenic changes, fibers with rimmed vacuoles, and the presence of cytoplasmic and nuclear inclusions. These inclusions were immunopositive for VCP, ubiquitin, transactivation response DNA-binding protein 43, and also histone deacetylase 6 (HDAC6), of which function is regulated by VCP. Evidence of early nuclear and mitochondrial damage was also characteristic.   Valosin-containing protein mutations are not rare in Asian patients, and gene analysis should be considered for patients with adult-onset rimmed vacuolar myopathy with neurogenic changes. A wide variety of central and peripheral nervous system symptoms coupled with rare bone abnormalities may complicate diagnosis.
  European Journal of Neurology 03/2012; 19(3):501-9. · 3.69 Impact Factor
• Article: The C2A domain in dysferlin is important for association with MG53 (TRIM72).

  Chie Matsuda, Katsuya Miyake, Kimihiko Kameyama, Etsuko Keduka, Hiroshi Takeshima, Toru Imamura, Nobukazu Araki, Ichizo Nishino, Yukiko Hayashi
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  ABSTRACT: In skeletal muscle, Mitsugumin 53 (MG53), also known as muscle-specific tripartite motif 72, reportedly interacts with dysferlin to regulate membrane repair. To better understand the interactions between dysferlin and MG53, we conducted immunoprecipitation (IP) and pull-down assays. Based on IP assays, the C2A domain in dysferlin associated with MG53. MG53 reportedly exists as a monomer, a homodimer, or an oligomer, depending on the redox state. Based on pull-down assays, wild-type dysferlin associated with MG53 dimers in a Ca2+-dependent manner, but MG53 oligomers associated with both wild-type and C2A-mutant dysferlin in a Ca2+-independent manner. In pull-down assays, a pathogenic missense mutation in the C2A domain (W52R-C2A) inhibited the association between dysferlin and MG53 dimers, but another missense mutation (V67D-C2A) altered the calcium sensitivity of the association between the C2A domain and MG53 dimers. In contrast to the multimers, the MG53 monomers did not interact with wild-type or C2A mutant dysferlin in pull-down assays. These results indicated that the C2A domain in dysferlin is important for the Ca2+-dependent association with MG53 dimers and that dysferlin may associate with MG53 dimers in response to the influx of Ca2+ that occurs during membrane injury. To examine the biological role of the association between dysferlin and MG53, we co-expressed EGFP-dysferlin with RFP-tagged wild-type MG53 or RFP-tagged mutant MG53 (RFP-C242A-MG53) in mouse skeletal muscle, and observed molecular behavior during sarcolemmal repair; it has been reported that the C242A-MG53 mutant forms dimers, but not oligomers. In response to membrane wounding, dysferlin accumulated at the injury site within 1 second; this dysferlin accumulation was followed by the accumulation of wild-type MG53. However, accumulation of RFP-C242A MG53 at the wounded site was impaired relative to that of RFP-wild-type MG53. Co-transfection of RFP-C242A MG53 inhibited the recruitment of dysferlin to the sarcolemmal injury site. We also examined the molecular behavior of GFP-wild-type MG53 during sarcolemmal repair in dysferlin-deficient mice which show progressive muscular dystrophy, and found that GFP-MG53 accumulated at the wound similar to wild-type mice. Our data indicate that the coordination between dysferlin and MG53 plays an important role in efficient sarcolemmal repair.
  PLoS currents. 01/2012; 4:e5035add8caff4.
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  Chapter: Inflammatory changes in infantile-onset LMNA-associated myopathy

  H. Komaki, Y. K. Hayashi, R. Tsuburaya, K. Sugie, M. Kato, T. Nagai, G. Imataka, S. Suzuki, S. Saitoh, N. Asahina, K. Honke, Y. Higuchi, H. Sakuma, Y. Saito, E. Nakagawa, K. Sugai, M. Sasaki, I. Nonaka, I. Nishino
  01/2011: pages 563-8; , ISBN: 1873-2364 (Electronic)
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  Available from: Ichizo Nishino

  Article: Lobulated fibers in a patient with 46-year history of limb-girdle muscle weakness

  R. Tsuburaya, T. Suzuki, K. Saiki, I. Nonaka, H. Sugita, Y. K. Hayashi, I. Nishino
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  ABSTRACT: Tsuburaya, Rie
  Neuropathology : official journal of the Japanese Society of Neuropathology. 01/2011; 31:455-7.