A5073781193- Coronary Interventions and Diagnostics
- Cardiomyopathy and Myosin Studies
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- Vascular Procedures and Complications
- Cardiovascular Function and Risk Factors
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- RNA Research and Splicing
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- Electrostatic Discharge in Electronics
- Pluripotent Stem Cells Research
- Aortic aneurysm repair treatments
- Eosinophilic Disorders and Syndromes
- Tissue Engineering and Regenerative Medicine
- Dialysis and Renal Disease Management
- SARS-CoV-2 and COVID-19 Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cardiac and Coronary Surgery Techniques
- Trypanosoma species research and implications
- Peripheral Artery Disease Management
- Cardiac Arrhythmias and Treatments
- Muscle Physiology and Disorders
- Video Analysis and Summarization
Osaka University
2020-2023
Sakurabashi Watanabe Hospital
2014-2023
Loss-of-function mutations in PKP2, which encodes plakophilin-2, cause arrhythmogenic cardiomyopathy (AC). Restoration of deficient molecules can serve as upstream therapy, thereby requiring a human model that recapitulates disease pathology and provides distinct readouts phenotypic analysis for proof concept gene replacement therapy. Here, we generated isogenic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with precisely adjusted expression plakophilin-2 from patient AC...
Abstract Desmoglein-2, encoded by DSG2, is one of the desmosome proteins that maintain structural integrity tissues, including heart. Genetic mutations in DSG2 cause arrhythmogenic cardiomyopathy, mainly an autosomal dominant manner. Here, we identified a homozygous stop-gain (c.C355T, p.R119X) led to complete desmoglein-2 deficiency patient with severe biventricular heart failure. Histological analysis revealed abnormal deposition proteins, disrupted intercalated disk structures myocardium....
Abstract Post-mitotic cardiomyocytes have been considered to be non-permissive precise targeted integration including homology-directed repair (HDR) after CRISPR/Cas9 genome editing. Here, we demonstrate that direct delivery of large amounts transgene encoding guide RNA (gRNA) and template DNA via intra-ventricular injection adeno-associated virus (AAV) promotes replacement in adult murine expressing Cas9. Neither systemic AAV nor adenovirus integration, suggesting high copy numbers...
To perform intravascular ultrasound (IVUS)-based real-time 3-dimensional wiring in chronic total occlusion percutaneous coronary intervention, we devised a tip detection method and developed AnteOwl WR (AO)-IVUS, which is an upgraded version of Navifocus (Navi)-IVUS with added pull back transducer system. We compared the procedural outcomes AO-IVUS-based using (n = 30) Navi-IVUS-based conventional 17) intervention. The success rate IVUS-guided was markedly improved AO-IVUS group Navi-IVUS...
Background: The Δ160E mutation in TNNT2 , which encodes troponin T, is a rare pathogenic variant identified patients with hypertrophic cardiomyopathy and associated poor prognosis. Thus, convenient human model recapitulating the pathological phenotype caused by required for therapeutic development. Methods: We heterozygous in-frame deletion (c.478_480del, p.Δ160E) patient familial showing progressive left ventricular systolic dysfunction, leading to advanced heart failure. To investigate...
Study investigators encountered a female Becker muscular dystrophy (BMD) carrier with advanced heart failure (HF) and identified stop-gain variant in procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) as potential second-hit variant. Isogenic induced pluripotent stem cells (iPSCs) dominant expression of WT-DMD, Δ45-48-DMD, or Δ45-48-DMD corrected PLOD3 were established. Microforce testing using 3-dimensional self-organized tissue rings (SOTRs) generated from iPSC-derived...
The MYH7 R453 variant has been identified in inherited hypertrophic cardiomyopathy (HCM) and is associated with sudden death a poor prognosis. detailed clinical course of HCM the variant, from preserved to reduced left ventricular ejection fraction, not reported. We R453C R453H variants three patients who progressively developed advanced heart failure requiring circulatory support summarized echocardiographic parameters these over years. Because rapid disease progression, we consider genetic...
Although an increased risk of myocarditis has been observed after vaccination with mRNA encoding severe acute respiratory syndrome coronavirus 2 spike protein, its underlying mechanism not elucidated. This study investigated the direct effects receptor-binding domain (S-RBD) on human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs). Immunostaining experiments using ACE2 wild-type (WT) and knockout (KO) iPSC-CMs treated purified S-RBD demonstrated that was bound to...
Kinetic analysis of intracellular calcium (Ca2+) in cardiomyocytes is commonly used to determine the pathogenicity genetic mutations identified patients with dilated cardiomyopathy (DCM). Conventional methods for measuring Ca2+ kinetics target whole-well cultured and therefore lack information concerning individual cells. Results are also affected by heterogeneity cell populations. Here, we developed an analytical method using CRISPR/Cas9 genome editing combined high-content image (HCIA)...
Introduction: Assessment of left ventricular (LV) dyssynchrony by echocardiography has only a limited ability to predict response cardiac resynchronizing therapy (CRT) because high variability the measurement.Tissue mitral annular displacement (TMAD) is rapid and robust method for assessment longitudinal deformity. We previously reported that TMAD predicts good responders CRT among patients with severe heart failure (AHA scientific meeting 2012). In present study, we investigated whether...
Objective:Rare disease Background:Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), are associated with pulmonary hypertension (PH) and malignant lymphomas.Although the underlying mechanisms have not been completely clarified, it has suggested that Janus kinase 2 (JAK2) mutation, which is frequently identified in PV, can be involved development and/or progression of these distinct diseases patients MPNs.However, no reports described coexistence PH lymphoma MPNs. Case...
目的: 慢性透析患者において著明な低血圧症や透析中の血圧降下の為, 透析療法に苦慮する場合がある. このような透析困難症例に対し, 高Na透析, 重曹透析などの透析液組成を変更して, 無症候透析を試みた.対象および方法: 対象は69歳女性で透析歴36か月, 原疾患は慢性糸球体腎炎である. 通常の透析方法では, 低血圧ショック等の頻発する透析困難な症例である. 透析方法は以下に述べる3種方法を行なった. 1) Na150-acetate透析; Na150mEq/l, acetate37mEq/lによる透析液を用いた. 2) Na150-bicarbonate併用透析; HCO3-30mEq/lによる透析液を用いた. この液中にはacetate8mEq/lを含む. 3) Na160-bicarbonate併用透析; Na160mEq/l, この液中にはacetate7.5mEq/lを含む. 1), 2), の透析液によって, それぞれ4週間継続施行した. 高Naによる体重増加を防止する目的で, 透析終了1時間前にそれぞれの方法についてNa濃度を, 約130mEq/lまで下降させた....