Publications by authors named "Yuko Ishii"

Strategies for gene and nucleic acid delivery to skeletal muscles have been extensively explored to treat Duchenne muscular dystrophy (DMD) and other neuromuscular diseases. Of these, effective intravascular delivery of naked plasmid DNA (pDNA) and nucleic acids into muscles is an attractive approach, given the high capillary density in close contact with myofibers. We developed lipid-based nanobubbles (NBs) using polyethylene-glycol-modified liposomes and an echo-contrast gas and found that these NBs could improve tissue permeability by ultrasound (US)-induced cavitation.

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BCR/ABL1 causes dysregulated cell proliferation and is responsible for chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL). In addition to the deregulatory effects of its kinase activity on cell proliferation, BCR/ABL1 induces genomic instability by downregulating BRCA1. PARP inhibitors (PARPi) effectively induce cell death in BRCA-defective cells.

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Introduction: The long-term use of topical corticosteroids (TCS) is associated with side effects such as skin atrophy and barrier deterioration. Moisturizers, such as mucopolysaccharide polysulfate (MPS), have been reported to prevent relapses in atopic dermatitis (AD) when used in combination with TCS. However, the mechanisms underlying the positive effects of MPS in combination with TCS in AD are poorly understood.

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We previously found increases in uncoupling protein (Ucp)-1 transcription in brown adipose tissue (BAT) of mice following a single oral dose of flavan 3-ol (FL)s, a fraction of catechins and procyanidins. It was confirmed that these changes were totally reduced by co-treatment of adrenaline blockers. According to these previous results, FLs possibly activate sympathetic nervous system (SNS).

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Article Synopsis
  • - Gemcitabine and Docetaxel (GEM/DTX) are common chemotherapy drugs used for soft tissue sarcomas but their effectiveness against malignant rhabdoid tumors (MRTs) is not well-studied.
  • - In a small study, GEM/DTX was used as salvage therapy for relapsed MRTs, showing partial responses in 3 out of 4 patients, including two with malignant rhabdoid tumors of the kidney.
  • - While GEM/DTX shows potential for treating resistant MRTs, there are specific side effects that require careful monitoring, such as localized edema and pleural effusion.
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 mutations occur in approximately 13% of intrahepatic cholangiocarcinomas (IHCCs). The oral, targeted, mutant IDH1 (mIDH1) inhibitor ivosidenib (AG-120) suppresses production of the oncometabolite D-2-hydroxyglutarate, promoting disease stabilization and improved progression-free survival (PFS) in m IHCC. Harnessing matched baseline and on-treatment biopsies, we investigate the potential mechanisms underlying ivosidenib's efficacy.

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  • - Neuroblastoma (NB) is a serious tumor linked to neural crest cells, with MYCN gene amplification and certain chromosome alterations generally indicating a worse prognosis for patients.
  • - This study utilized digital droplet PCR to effectively detect MYCN amplification and chromosome 11q copy number alterations (CNA) in NB samples, comparing results with more traditional SNP chip arrays to ensure accuracy.
  • - Digital droplet PCR provides a faster and practical alternative to methods like FISH and Southern blotting for identifying CNAs in neuroblastoma, which can aid in timely risk assessment after diagnosis.
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Given the role of Ca3.2 isoform among T-type Ca channels (T-channels) in somatic and visceral nociceptive processing, we analyzed the contribution of Ca3.2 to butyrate-induced colonic pain and nociceptor hypersensitivity in mice, to evaluate whether Ca3.

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Purpose: Patients with advanced renal cell carcinoma with sarcomatoid features (sRCC) have poor prognoses and suboptimal outcomes with targeted therapy. This analysis of the phase III CheckMate 214 trial analyzed the efficacy of nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib in patients with sRCC.

Patients And Methods: Patients with sRCC were identified via independent central pathology review of archival tumor tissue or histologic classification per local pathology report.

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Hereditary myopathy with early respiratory failure (HMERF) with heterozygous mutations in the titin gene (TTN) is characterized by respiratory failure developing from the early phase of limb weakness or gait disturbance. Here, we describe a characteristic distribution of muscle involvement in three members of a HMERF family with a TTN mutation. Despite the differences in severity exhibited among the father, daughter and son, the systemic imaging studies showed a similar pattern among these individuals.

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  • The study shows that neurons from mouse embryos can survive in adult brains and connect to the spinal cord, hinting at cell transplantation as a potential method to repair the corticospinal tract (CST).
  • Researchers discovered that grafted cells in the adult brain expressed a protein called CTIP2, which is related to axon growth in the CST.
  • By isolating L1CAM+ cells, they found these cells were more effective in generating axons compared to other cells, suggesting that sorting these specific cells could enhance efforts to reconstruct the CST.
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  • The study explored levels of prostaglandin D2 synthase (PGDS) in patients with sleep and neurological disorders, focusing on its potential role in sleep regulation.
  • Among 63 patients analyzed, those with Parkinson's disease (both with and without excessive daytime sleepiness) and Alzheimer's disease showed higher levels of lipocalin-type PGDS (L-PGDS) compared to healthy controls.
  • However, levels of L-PGDS and hematopoietic PGDS (H-PGDS) did not correlate with sleepiness scores, suggesting further research is needed to determine the significance of increased L-PGDS in these conditions.
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Background: Although several therapeutic options for patients with renal cell carcinoma (RCC) have been approved over recent years, including immune checkpoint inhibitors, considerable need remains for molecular biomarkers to assess disease prognosis. The higher pharmacokinetic (PK) clearance of checkpoint inhibitors, such as the anti-programmed death-1 (PD-1) therapies nivolumab and pembrolizumab, has been shown to be associated with poor overall survival (OS) across several tumor types. However, determination of PK clearance requires the collection and analysis of post-treatment serum samples, limiting its utility as a prognostic biomarker.

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This cohort study examines whether alterations are associated with response to immune checkpoint inhibitor treatment in patients with metastatic clear cell renal cell carcinoma.

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Background: We investigated serum insulin-like growth factor (IGF)-1 levels in patients with neurodegenerative diseases and correlated these levels with clinical parameters.

Methods: One hundred and fifty-six patients with neurodegenerative diseases were included in this study, and serum IGF-1 levels were determined.

Results: Serum IGF-1 levels (mean ± standard error) were not significantly different among the patients with different neurodegenerative diseases: Parkinson's disease (PD; n = 73), 112.

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Purpose: Immune-related RECIST (irRECIST) were designed to capture atypical responses seen with immunotherapy. We hypothesized that, in patients with metastatic clear cell renal cell carcinoma (mccRCC), candidate biomarkers for nivolumab response would show improved association with clinical endpoints capturing atypical responders (irRECIST) compared with standard clinical endpoints (RECISTv1.1).

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Williams-Beuren syndrome (WBS) is a multisystemic neurodevelopmental disorder caused by a hemizygous deletion on chromosome 7q11.23. Though at present there is a limited number of reports on WBS patients with tumors, most cases are related to blood cancer in children with WBS.

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The TOM1/TOM3 genes from Arabidopsis are involved in the replication of tobamoviruses. Tomato homologs of these genes, LeTH1, LeTH2 and LeTH3, are known. In this study, we examined transgenic tomato lines where inverted repeats of either LeTH1, LeTH2 or LeTH3 were introduced by Agrobacterium.

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Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration, caused by nonsense or frameshift mutations in the dystrophin (DMD) gene. Antisense oligonucleotides can be used to induce specific exon skipping; recently, a phosphorodiamidate morpholino oligomer (PMO) has been approved for clinical use in DMD. However, an efficient PMO delivery strategy is required to improve the therapeutic efficacy in DMD patients.

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Diagnosing sepsis can be very difficult and without prompt treatment, sepsis frequently results in death. No definitive biomarker for diagnosing sepsis currently exists, although the use of various biomarkers, includ- ing procalcitonin (PCT), as diagnostic indicators has been considered valuable. The biomarker presepsin (P- SEP) has gained attention as a diagnostic tool for sepsis since health insurance coverage approval in Japan in 2014.

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Background: In hereditary myopathy with early respiratory failure (HMERF), cytoplasmic bodies (CBs) are often localised in subsarcolemmal regions, with necklace-like alignment (necklace CBs), in muscle fibres although their sensitivity and specificity are unknown.

Objective: To elucidate the diagnostic value of the necklace CBs in the pathological diagnosis of HMERF among myofibrillar myopathies (MFMs).

Methods: We sequenced the exon 343 of TTN gene (based on ENST00000589042), which encodes the fibronectin-3 (FN3) 119 domain of the A-band and is a mutational hot spot for HMERF, in genomic DNA from 187 patients from 175 unrelated families who were pathologically diagnosed as MFM.

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Objective: The aim of this study was to evaluate the relationship between fatty liver disease (FLD) and cerebrovascular disease.

Methods: We conducted a cross-sectional study of 76 consecutive healthy subjects who participated in a two-day hospitalized health checkup program. The maximal intima-media thickness (IMT) of the common carotid artery and bifurcation of the carotid artery as well as the plaque score (PS) were evaluated on carotid artery ultrasonography.

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Duchenne muscular dystrophy (DMD) is a genetic disorder that is caused by mutations in the DMD gene that lead to an absence of functional protein. The mdx dystrophic mouse contains a nonsense mutation in exon 23 of the dystrophin gene; a phosphorodiamidate morpholino oligomer (PMO) designed to skip this mutated exon in the mRNA induces dystrophin expression. However, an efficient PMO delivery method is needed to improve treatment strategies for DMD.

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Purpose: To apply the acceleration time (AcT) ratio as an additional marker for diagnosing internal carotid artery (ICA) stenosis.

Methods: Carotid artery sonography was performed in 140 patients, and the AcT ratio was calculated as the AcT of the ICA divided by the AcT of the ipsilateral common carotid artery, and compared with diameter stenosis.

Results: There was a significant correlation between diameter stenosis and the AcT ratio.

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