المؤلفون: Risa Konishi, Yuki Ichimura, Ryota Tanaka, Hanako Miyahara, Mari Okune, Masahide Miyamoto, Monami Hara, Atsushi Iwabuchi, Hidetoshi Takada, Yasuo Nakagishi, Mao Mizuta, Shuya Kaneko, Masaki Shimizu, Tomohiro Morio, Ichizo Nishino, Toshifumi Nomura, Naoko Okiyama

المصدر: Immunological Medicine, Vol 47, Iss 2, Pp 100-105 (2024)

مصطلحات موضوعية: Dermatomyositis, nuclear matrix protein 2, interleukin-8, cytokine, Immunologic diseases. Allergy, RC581-607

الوصف: AbstractAnti-nuclear matrix protein 2 (NXP2) antibody-positive dermatomyositis (DM) is characterized by extensive and severe myositis. In this study, we evaluated which cytokines/chemokines involved with the activity of the myositis. We performed quantitative immunoassays using the MILLIPLEX® Multiplex Assays Using Luminex to evaluate serum levels of interferon-γ, interleukin (IL)-1β, IL-6, IL-8, IL-12p40, and tumor necrosis factor-α in samples collected over time from a 9-year-old female with anti-NXP2 antibody-positive DM. In our case, the serum level of IL-8 was elevated when the myositis worsened, and decreased in accordance with the improvement of myositis, suggesting that the serum IL-8 levels were correlated with the myositis activity. Serum levels of IL-8 in samples from five patients with anti-NXP2 antibody-positive DM and five patients with anti-transcriptional intermediary factor 1γ (TIF1γ) antibody-positive DM without both interstitial lung disease (ILD) and malignancy before starting treatments, along with five healthy controls, were also evaluate by an enzyme-linked immunosorbent assay. Serum IL-8 levels were significantly elevated in anti-NXP2 or anti-TIF1γ antibody-positive DM patients with myositis but not ILD, than healthy controls. It was suggested that serum levels of IL-8 correlate with the activity of myositis in DM including anti-NXP2 antibody-positive DM.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2578-5826Test

الوصول الحر: https://doaj.org/article/2b1791d436b1447aa8520e6fcdc13476Test

المؤلفون: Koji Fukushima, Takeshi Yoshida, Hiroki Yamazaki, Naoko Takamatsu, Takashi Nagai, Yusuke Osaki, Masafumi Harada, Ichizo Nishino, Naoko Okiyama, Kazuma Sugie, Yuishin Izumi

المصدر: Internal Medicine. 2024, 63(12):1813-1817

المؤلفون: Hiroaki Ohara, Motoyasu Hosokawa, Tomonari Awaya, Atsuko Hagiwara, Ryo Kurosawa, Yukiya Sako, Megumu Ogawa, Masashi Ogasawara, Satoru Noguchi, Yuichi Goto, Ryosuke Takahashi, Ichizo Nishino, Masatoshi Hagiwara

المصدر: Molecular Therapy: Nucleic Acids, Vol 33, Iss , Pp 404-412 (2023)

مصطلحات موضوعية: MT: Oligonucleotides: Therapies and Applications, branchpoint, muscular dystrophy, exon-skipping therapy, splicing regulatory elements, antisense oligonucleotide, Therapeutics. Pharmacology, RM1-950

الوصف: Fukutin (FKTN) c.647+2084G>T creates a pseudo-exon with a premature stop codon, which causes Fukuyama congenital muscular dystrophy (FCMD). We aimed to ameliorate aberrant splicing of FKTN caused by this variant. We screened compounds focusing on splicing regulation using the c.647+2084G>T splicing reporter and discovered that the branchpoint, which is essential for splicing reactions, could be a potential therapeutic target. To confirm the effectiveness of branchpoints as targets for exon skipping, we designed branchpoint-targeted antisense oligonucleotides (BP-AONs). This restored normal FKTN mRNA and protein production in FCMD patient myotubes. We identified a functional BP by detecting splicing intermediates and creating BP mutations in the FKTN reporter gene; this BP was non-redundant and sufficiently blocked by BP-AONs. Next, a BP-AON was designed for a different FCMD-causing variant, which induces pathogenic exon trapping by a common SINE-VNTR-Alu-type retrotransposon. Notably, this BP-AON also restored normal FKTN mRNA and protein production in FCMD patient myotubes. Our findings suggest that BPs could be potential targets in exon-skipping therapeutic strategies for genetic disorders.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2162253123001828Test; https://doaj.org/toc/2162-2531Test

الوصول الحر: https://doaj.org/article/1c5129f55e474d49b6d07d5fc97c7b1dTest

المؤلفون: Madoka Mori-Yoshimura, Naoki Suzuki, Masahisa Katsuno, Masanori P. Takahashi, Satoshi Yamashita, Yasushi Oya, Atsushi Hashizume, Shinichiro Yamada, Masayuki Nakamori, Rumiko Izumi, Masaaki Kato, Hitoshi Warita, Maki Tateyama, Hiroshi Kuroda, Ryuta Asada, Takuhiro Yamaguchi, Ichizo Nishino, Masashi Aoki

المصدر: Orphanet Journal of Rare Diseases, Vol 18, Iss 1, Pp 1-10 (2023)

مصطلحات موضوعية: GNE myopathy, Aceneuramic acid, Efficacy confirmation study, Ultra-orphan disease, Medicine

الوصف: Abstract Background A rare muscle disease, GNE myopathy is caused by mutations in the GNE gene involved in sialic acid biosynthesis. Our recent phase II/III study has indicated that oral administration of aceneuramic acid to patients slows disease progression. Methods We conducted a phase III, randomized, placebo-controlled, double-blind, parallel-group, multicenter study. Participants were assigned to receive an extended-release formulation of aceneuramic acid (SA-ER) or placebo. Changes in muscle strength and function over 48 weeks were compared between treatment groups using change in the upper extremity composite (UEC) score from baseline to Week 48 as the primary endpoint and the investigator-assessed efficacy rate as the key secondary endpoint. For safety, adverse events, vital signs, body weight, electrocardiogram, and clinical laboratory results were monitored. Results A total of 14 patients were enrolled and given SA-ER (n = 10) or placebo (n = 4) tablets orally. Decrease in least square mean (LSM) change in UEC score at Week 48 with SA-ER (− 0.115 kg) was numerically smaller as compared with placebo (− 2.625 kg), with LSM difference (95% confidence interval) of 2.510 (− 1.720 to 6.740) kg. In addition, efficacy was higher with SA-ER as compared with placebo. No clinically significant adverse events or other safety concerns were observed. Conclusions The present study reproducibly showed a trend towards slowing of loss of muscle strength and function with orally administered SA-ER, indicating supplementation with sialic acid might be a promising replacement therapy for GNE myopathy. Trial registration number: ClinicalTrials.gov (NCT04671472).

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1750-1172Test

الوصول الحر: https://doaj.org/article/6628f652b5c34969bbb20872f77b28faTest

المؤلفون: Atsushi Niwa, Hidekazu Tomimoto, Hirofumi Matsuyama, Ichizo Nishino, Koichi Miyashita, Narihiro Minami, Soshi Shibata, Yosuke Kawana, Yuichiro Ii

المصدر: Internal Medicine. 2023, 62(20):3027

المؤلفون: Daisuke Yamamoto, Fuyuki Kametani, Hiroki Takeuchi, Ichizo Nishino, Kazuna Ikeda, Keiko Usui, Masahide Yazaki, Nagaaki Katoh, Nobuyuki Oka, Shin Hisahara

المصدر: Internal Medicine. 2023, 62(15):2261

المؤلفون: Jantima Tanboon, Merrilee Needham, Tahseen Mozaffar, Werner Stenzel, Ichizo Nishino

المصدر: Frontiers in Neurology, Vol 14 (2023)

مصطلحات موضوعية: myositis, dermatomyositis, inclusion body myositis, immune mediated necrotizing myopathy, antisynthetase syndrome, imaging, Neurology. Diseases of the nervous system, RC346-429

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fneur.2023.1259275/fullTest; https://doaj.org/toc/1664-2295Test

الوصول الحر: https://doaj.org/article/b802cf0b91df42c7b6619ae2b4d4336bTest

المؤلفون: Asami Munekane, Hirotake Nishimura, Ichizo Nishino, Mariko Okubo, Taiji Nagai, Yoshihide Sunada, Yutaka Ohsawa

المصدر: Internal Medicine. 2023, 62(9):1345

المؤلفون: Wakako Yoshioka, Aritoshi Iida, Kyuto Sonehara, Kazuki Yamamoto, Yasushi Oya, Madoka Mori-Yoshimura, Takashi Kurashige, Mariko Okubo, Megumu Ogawa, Fumihiko Matsuda, Koichiro Higasa, Shinichiro Hayashi, Harumasa Nakamura, Masakazu Sekijima, Yukinori Okada, Satoru Noguchi, Ichizo Nishino

المصدر: Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract GNE myopathy is a distal myopathy caused by biallelic variants in GNE, which encodes a protein involved in sialic acid biosynthesis. Compound heterozygosity of the second most frequent variant among Japanese GNE myopathy patients, GNE c.620A>T encoding p.D207V, occurs in the expected number of patients; however, homozygotes for this variant are rare; three patients identified while 238 homozygotes are estimated to exist in Japan. The aim of this study was to elucidate the pathomechanism caused by c.620A>T. Identity-by-descent mapping indicated two distinct c.620A>T haplotypes, which were not correlated with age onset or development of myopathy. Patients homozygous for c.620A>T had mildly decreased sialylation, and no additional pathogenic variants in GNE or abnormalities in transcript structure or expression of other genes related to sialic acid biosynthesis in skeletal muscle. Structural modeling of full-length GNE dimers revealed that the variant amino acid localized close to the monomer interface, but far from catalytic sites, suggesting functions in enzymatic product transfer between the epimerase and kinase domains on GNE oligomerization. In conclusion, homozygotes for c.620A>T rarely develop myopathy, while symptoms occur in compound heterozygotes, probably because of mildly decreased sialylation, due to partial defects in oligomerization and product trafficking by the mutated GNE protein.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/4f9dabf851b449cc98ef9808181bb5acTest

المؤلفون: Masashi Ogasawara, Nobuyuki Eura, Aritoshi Iida, Theerawat Kumutpongpanich, Narihiro Minami, Ikuya Nonaka, Shinichiro Hayashi, Satoru Noguchi, Ichizo Nishino

المصدر: Acta Neuropathologica Communications, Vol 10, Iss 1, Pp 1-7 (2022)

مصطلحات موضوعية: Oculopharyngodistal myopathy, LRP12, GIPC1, NOTCH2NLC, CGG repeat expansion, Oculopharyngeal muscular dystrophy, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Oculopharyngodistal myopathy (OPDM) and oculopharyngeal muscular dystrophy (OPMD) are similar and even believed to be indistinguishable in terms of their myopathological features. To address the diagnostic gap, we evaluated the muscle biopsy samples for p62 expression by immunohistochemistry and compared the occurrence and the frequency of intranuclear inclusions among the individuals with OPDM (harboring CGG repeat expansion in LRP12 (n = 19), GIPC1 (n = 6), or NOTCH2NLC (n = 7)), OPMD (n = 15), and other rimmed vacuolar myopathies. We found that myonuclei with p62-positive intra-nuclear inclusions (myo-INIs) were significantly more frequent in OPMD (11.9 ± 1.1%, range 5.9–18.6%) than in OPDM and other rimmed vacuolar myopathies (RVMs) (0.9–1.5% on average, range 0.0–2.8%, p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2051-5960Test

الوصول الحر: https://doaj.org/article/bf430c0312ca4de89b480b931a09d9f1Test