A5021757506- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Genetic Neurodegenerative Diseases
- Myasthenia Gravis and Thymoma
- Nicotinic Acetylcholine Receptors Study
- Nanopore and Nanochannel Transport Studies
- Neuroscience and Neural Engineering
- Parkinson's Disease and Spinal Disorders
- Mitochondrial Function and Pathology
- Antifungal resistance and susceptibility
- Peripheral Neuropathies and Disorders
- Neuroscience and Neuropharmacology Research
- Ion Transport and Channel Regulation
- Parkinson's Disease Mechanisms and Treatments
- Advanced biosensing and bioanalysis techniques
- Electrostatics and Colloid Interactions
- RNA and protein synthesis mechanisms
- Electrochemical Analysis and Applications
- RNA Research and Splicing
- Chemical Synthesis and Analysis
- Muscle Physiology and Disorders
- Natural product bioactivities and synthesis
- Mental Health and Patient Involvement
- Railway Systems and Energy Efficiency
- Traditional and Medicinal Uses of Annonaceae
Osaka University
2015-2024
Kubota (Japan)
2008-2024
Toho University Ohashi Medical Center
2024
Toho University
2024
Tokyo Medical University
2024
Keio University
2024
Osaka Metropolitan University
2024
Nagoya University
2021
University of Chicago
2012-2020
Nara Institute of Science and Technology
2020
Despite a growing number of ion channel genes implicated in hereditary ataxia, it remains unclear how mutations lead to loss-of-function or death cerebellar neurons. Mutations the gene KCNMA1, encoding α-subunit BK have emerged as responsible for variety neurological phenotypes. We describe mutation (BKG354S) child with congenital and progressive ataxia cognitive impairment. The selectivity filter dramatically reduced single-channel conductance selectivity. BKG354S trafficked normally...
Background Early fast-acting treatment (EFT) is the aggressive use of therapies such as plasmapheresis, intravenous immunoglobulin and/or high-dose methylprednisolone (IVMP) from early phases treatment. EFT reportedly beneficial for achievement minimal manifestations (MM) or better status with ≤5 mg/day prednisolone (MM5mg), a practical therapeutic target myasthenia gravis (MG). Objective The current study aimed to clarify which specific regimen efficacious and patient characteristics that...
Efgartigimod, which has been well tolerated and efficacious in individuals with generalized myasthenia gravis (MG), is available Japan not only for the treatment of anti-acetylcholine receptor-positive (AChR+) but also anti-muscle-specific receptor tyrosine kinase (MuSK+) seronegative MG. We report details use efgartigimod MG clinical practice Japan.
Abstract Objective Eculizumab and ravulizumab are complement protein C5 inhibitors, showing efficacy tolerability for patients with anti‐acetylcholine receptor‐positive (AChR+) generalized myasthenia gravis (gMG) in phase 3 clinical trials subsequent analyses. The purpose of the present study was to evaluate significance eculizumab switching refractory AChR+ gMG real‐world experience. Methods Among database Japan MG registry survey 2021, we studied who received eculizumab. We also evaluated...
We have re-examined the utility of native chemical ligation at -Gln/Glu-Cys- [Glx-Cys] and -Asn/Asp-Cys- [Asx-Cys] sites. Using improved thioaryl catalyst 4-mercaptophenylacetic acid (MPAA), could be performed -Gln-Cys- Asn-Cys- sites without side reactions. After optimization, a -Glu-Cys- site also used as site, with minimal levels byproduct formation. However, -Asp-Cys- is not appropriate for use because formation significant amounts β-linked byproduct. The feasibility enabled convergent...
<h3>Objective:</h3> To identify other causative genes for Andersen–Tawil syndrome, which is characterized by a triad of periodic paralysis, cardiac arrhythmia, and dysmorphic features. syndrome caused in majority cases mutations <i>KCNJ2</i>, encodes the Kir2.1 subunit inwardly rectifying potassium channel. <h3>Methods:</h3> The proband exhibited episodic flaccid weakness characteristic TU-wave pattern, both suggestive but did not harbor <i>KCNJ2</i> mutations. We performed exome capture...
Parasitic plants form a specialized organ, haustorium, to invade host tissues and acquire water nutrients. To understand the molecular mechanism of haustorium development, we performed forward genetics screening isolate mutants exhibiting haustorial defects in model parasitic plant Phtheirospermum japonicum. We isolated two that show prolonged sometimes aberrant meristematic activity apex, resulting severe on invasion. Whole-genome sequencing revealed respectively have point mutations...
Significance Physical activities of our body and extremities are achieved by the propagation electrical signals called action potentials from brain, through nerves, to skeletal muscles. Voltage-gated sodium channel (Navs) play essential roles in generation such excitable cells. Although mammalian Nav function has been studied comprehensively, precise structural basis for gating mechanisms not fully clarified. In this study, we have used lanthanide-based resonance energy transfer obtain...
Abstract The primary purpose of the Japanese myasthenia gravis registry (JAMG‐R) has been to research and promote high‐quality medical care for MG patients in Japan. We reviewed findings surveys performed by JAMG‐R over an ~10‐y period. first goal favorable quality life (QOL) is a status minimal manifestations (MM) or better with oral prednisolone (PSL) dose 5 mg/d less (MM‐5 mg). E arly aggressive use nonoral f ast‐acting t reatment together low‐dose PSL (the “EFT strategy”) recommended...
<b>Background: </b> Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by CTG repeat expansion in the <i>DMPK</i> gene. Aberrant messenger RNA (mRNA) splicing of several genes has been reported to explain some symptoms DM1, but cause muscle wasting still unknown. By contrast, many forms muscular are abnormalities dystrophin–glycoprotein complex (DGC). α-Dystrobrevin key component DGC striated and plays important roles maturation signal transduction interacting with...
Abstract Myotonia manifests in several hereditary diseases, including hyperkalemic periodic paralysis (HyperPP), paramyotonia congenita (PMC), and potassium‐aggravated myotonia (PAM). These are allelic disorders originating from missense mutations the gene that codes skeletal muscle sodium channel, Nav1.4. Moreover, a severe form of PAM has been designated as permanens. A new mutation Nav1.4, Q1633E, was identified Japanese family presenting with phenotype. The proband suffered cyanotic...
Non-motor symptoms in myasthenia gravis (MG) are rarely confirmed. Although there some small cohort studies, a large-systemic survey has not yet been performed.
Abstract Ts1 toxin is a protein found in the venom of Brazilian scorpion Tityus serrulatus. binds to domain II voltage sensor voltage‐gated sodium channel Nav and modifies its dependence. In work reported here, we established an efficient total chemical synthesis using modern ligation methods demonstrated that it was fully active modifying dependence rat skeletal muscle rNav1.4 expressed oocytes. Total combined with click chemistry used label molecule fluorescent dyes Alexa‐Fluor 488 Bodipy....
Motions of circular and linear DNA molecules various lengths near a nanopore 100 or 200 nm diameter were experimentally observed investigated by fluorescence microscopy. The movement through nanopores, known as translocation, is mainly driven electric fields inside the pores. We found significant clogging nanopores molecules, particularly T4 (165.65 kbp). Here, probabilities events, depending on length shape-linear circular-were determined. Furthermore, two distinct motions observed: clog...
Abstract Background The role of patients in medical research is changing, as more emphasis being placed on patient involvement, and reported outcomes are increasingly contributing to clinical decision-making. Information communication technology provides new opportunities for actively become involved research. These trends particularly noticeable Europe the US, but less obvious Japan. aim this study was investigate practice active involvement Japan by utilizing a digital platform, analyze...
Many mutations in the skeletal-muscle sodium-channel gene SCN4A have been associated with myotonia and/or periodic paralysis, but so far all of these are located exons. We found a patient caused by deletion/insertion intron 21 SCN4A, which is an AT-AC type II intron. This rare class introns that, despite having boundaries, spliced major or U2-type spliceosome. The patient's skeletal muscle expressed aberrantly mRNA isoforms generated activation cryptic splice sites. In addition, genetic...
Abstract Ts3 is an alpha scorpion toxin from the venom of Brazilian Tityus serrulatus . binds to domain IV voltage sensor voltage‐gated sodium channels (Na v ) and slows down their fast inactivation. The covalent structure uncertain, folded protein molecule unknown. Herein, we report total chemical synthesis four candidate molecules results structure–activity studies that enabled us establish biologically active toxin. We also mirror image form molecule, use racemic crystallography determine...
To elucidate mutation spectrum and genotype-phenotype correlations in Japanese patients with OI, we conducted comprehensive genetic analyses using NGS, as this had not been analyzed comprehensively patient population. Most mutations were located on COL1A1 COL1A2. Glycine substitutions resulted the severe phenotype.Most cases of osteogenesis imperfecta (OI) are caused by or COL1A2, which encode α chains type I collagen. However, at least 16 other genes also cause OI. The OI has analyzed, it...