Publications by authors named "Nakashima Makoto"

Human T-cell leukemia virus type 1 (HTLV-1) broadly impacts host genes, affecting the infected cell population and inducing the development of a disease with a poor prognosis, adult T-cell leukemia-lymphoma (ATL). This study aimed to provide a comprehensive epigenomic characterization of the infected cell population and evaluated the transcriptome and chromatin structures of peripheral blood cells in HTLV-1-infected individuals using RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq). The infected cells showed significant changes in gene expression patterns from the polyclonal stage and before ATL onset while demonstrating similarities to tumor-forming ATL cells.

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  • The study investigates the effectiveness of testing cerebrospinal fluid (CSF) for anti-HTLV-1 antibodies in diagnosing HTLV-1-associated myelopathy (HAM), highlighting the diagnostic accuracy of various test kits.
  • It found that while CSF antibody levels were stable when refrigerated, they were affected by freeze-thaw cycles, leading to strong correlations in test results across different methods used on samples from 92 patients (69 with HAM, 23 carriers).
  • The results showed high diagnostic performance for HAM, with five test kits achieving 100% sensitivity and varying specificity, suggesting that these tests combined with clinical evaluation can improve HAM diagnosis.
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The dynamic change of redox conditions is a key factor in emission of elemental mercury (Hg) from riparian soils. The objective of this study was to elucidate the influences of redox conditions on Hg emission from riparian soils. Soil suspension experiments were conducted to measure Hg emission from five Hg-contaminated soil samples in two redox conditions (i.

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  • Epigenomes play a crucial role in correcting abnormal gene expressions in cancer, and targeting histone H3K27me3 is effective for new drug therapies, although the mechanisms are not fully understood.
  • Valemetostat, an EZH1-EZH2 dual inhibitor, has shown promise in clinical trials for aggressive lymphomas by reducing tumor size and providing long-lasting responses even in genetically diverse cancer cases.
  • However, resistance develops over time due to mutations that restore condensed chromatin states, leading to increased H3K27me3 expression and highlighting the need for innovative epigenetic therapies to overcome such challenges in cancer treatment.
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Introduction: The membranous septum (MS) length measured by cardiac computed tomography (CT) is useful for the prediction of permanent pacemaker implantation (PPMI) and new left bundle branch block (LBBB) after transcatheter aortic valve replacement. However, its predictive value for patients undergoing surgical aortic valve replacement (SAVR) is unknown.

Methods: A total of 2531 consecutive patients were registered in the institutional Society of Thoracic Surgeons database between July 2017 and June 2020.

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Classic Hodgkin lymphoma (cHL) is characterized by multinucleated cells called Reed-Sternberg (RS) cells and genetic complexity. Although CD30 also characterizes cHL cells, its biological roles are not fully understood. In this report, we examined the link between CD30 and these characteristics of cHL cells.

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  • * It is frequently found in cells infected by HTLV-1, a virus linked to cancer, and some ATL cases exhibit high levels of CD30 expression, although the connection between CD30 and the cancer's progression isn't fully understood.
  • * Recent studies highlight how CD30 is overexpressed through super-enhancers, its role in cancer development via a process called trogocytosis, and the success of targeted therapies against CD30 in treating specific lymphomas.
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Adult T-cell leukemia/lymphoma (ATL) develops via stepwise accumulation of gene mutations and chromosome aberrations. However, the molecular mechanisms underlying this tumorigenic process are poorly understood. We previously reported the presence of a biological link between the expression of CD30, which serves as a marker for ATL progression, and the actively proliferating fraction of human T-cell leukemia virus type 1 (HTLV-1)-infected cells that display polylobulation.

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Both natural viral infections and therapeutic interventions using viral vectors pose significant risks of malignant transformation. Monitoring for clonal expansion of infected cells is important for detecting cancer. Here we developed a novel method of tracking clonality via the detection of transgene integration sites.

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Purpose Of Review: We review the pathology, prevalence, diagnosis, hemodynamics, risk factors, prognosis, and treatment of leaflet thrombosis (LT), and suggest future directions in this field.

Recent Findings: The latest meta-analysis showed the prevalence of overall LT is 5.4% (clinical LT of 1.

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Objectives: The aim of this study was to clarify the dynamics of the mitral annulus throughout the cardiac cycle and its relevance to transcatheter mitral valve replacement (TMVR) sizing and case selection.

Background: Limited data are available regarding the relevance of mitral annular (MA) and neo-left ventricular outflow tract (LVOT) dynamics in the overall population presenting with significant mitral valve disease.

Methods: Patients attending a combined surgical-transcatheter heart valve clinic for severe symptomatic mitral valve disease were assessed using multiphase computed tomography.

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Conduction disturbances (CDs) after transcatheter artic replacement remain a clinical concern and relatively common complication. A recent meta-analysis showed both new-onset persistent left bundle branch block and new permanent pacemaker implantation were related to all-cause death with risk ratio 1.32 (95% confidence interval [CI] 1.

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Purpose: Although several reports have described the relationship between periodontal disease and cardiovascular disease, information about the association between periodontal disease and the progression of degenerative aortic stenosis (AS) is lacking. Therefore, we performed a retrospective, single-center, pilot study to provide insight into this potential association.

Methods: Data from 45 consecutive patients (19 men; median age, 83 years) with mild or moderate degenerative aortic stenosis were analyzed for a mean observation period of 3.

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Subclonal genetic heterogeneity and their diverse gene expression impose serious problems in understanding the behavior of cancers and contemplating therapeutic strategies. Here we develop and utilize a capture-based sequencing panel, which covers host hotspot genes and the full-length genome of human T-cell leukemia virus type-1 (HTLV-1), to investigate the clonal architecture of adult T-cell leukemia-lymphoma (ATL). For chronologically collected specimens from patients with ATL or pre-onset individuals, we integrate deep DNA sequencing and single-cell RNA sequencing to detect the somatic mutations and virus directly and characterize the transcriptional readouts in respective subclones.

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Background: The impact of balloon post-dilatation (BPD) on short- and long-term valve performance after Sapien 3 (S3) implantation is unknown. This study aimed to evaluate the impact of balloon post-dilatation (BPD) on short- and long-term valve performance after the implantation of S3.

Methods: A total of 846 patients implanted with S3 from the OCEAN-TAVI registry were included in this study.

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Background: Recent improvements in devices and medications may diminish the risk of adverse events following percutaneous coronary intervention (PCI) in women. However, complex calcified coronary lesions are increasingly being encountered in clinical practice, which remain challenging for contemporary PCI. Rotational atherectomy (RA) of severely calcified lesions is an option that facilitates the technical success of PCI.

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We previously indicated that Hodgkin lymphoma (HL) cells contain a small side population (SP) that differentiate into a large major population (MP) with giant Hodgkin and Reed-Sternberg (H and RS)-like cells. However, its molecular mechanisms are not fully understood. In this study, we found that intracellular reactive oxygen species (ROS) are low in the SP compared to the MP.

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  • * In a study of 575 patients not on hemodialysis, it was found that lower GFR was associated with higher peri-procedural stroke rates, particularly in patients with GFR levels below 60 ml/min, while device success rates remained consistent across GFR groups.
  • * Despite procedural improvements like low-contrast techniques, patients with renal insufficiency still face poor long-term outcomes, highlighting the need for ongoing research and optimized strategies for managing this population.
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Objectives: The aim of this study was to compare long-term all-cause mortality between direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) after transcatheter aortic valve replacement (TAVR).

Background: The optimal anticoagulant agent for patients with AF after TAVR has not been clarified.

Methods: OCEAN (Optimized Transcatheter Valvular Intervention) is a prospective, multicenter, observational cohort registry comprising 2,588 patients who underwent TAVR between October 2013 and May 2017.

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Background: The reliable diagnosis of human T-cell leukemia virus type 1 (HTLV-1) infection is important, particularly as it can be vertically transmitted by breast feeding mothers to their infants. However, current diagnosis in Japan requires a confirmatory western blot (WB) test after screening/primary testing for HTLV-1 antibodies, but this test often gives indeterminate results. Thus, this collaborative study evaluated the reliability of diagnostic assays for HTLV-1 infection, including a WB-based one, along with line immunoassay (LIA) as an alternative to WB for confirmatory testing.

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Approximately 10-20 million of Human T-cell leukemia virus type-1 (HTLV-1)-infected carriers have been previously reported, and approximately 5% of these carriers develop adult T-cell leukemia/lymphoma (ATL) with a characteristic poor prognosis. In Japan, Southern blotting has long been routinely performed for detection of clonally expanded ATL cells in vivo, and as a confirmatory diagnostic test for ATL. However, alternative methods to Southern blotting, such as sensitive, quantitative, and rapid analytical methods, are currently required in clinical practice.

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Patients with adult T-cell leukemia (ATL) exhibit a poor prognosis and overall survival rate when treated with standard chemotherapy, highlighting the continued requirement for the development of novel safe and effective therapies for human T-cell leukemia virus type 1 (HTLV-1)-related diseases. In this study, we demonstrated that MK-2048, a second-generation HIV-1 integrase (IN) inhibitor, potently and selectively kills HTLV-1-infected cells. Differential transcriptome profiling revealed significantly elevated levels of gene expression of the unfolded protein response (UPR) PKR-like ER kinase (PERK) signaling pathway in ATL cell lines following MK-2048 treatment.

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