Publications by authors named "Okazawa H"

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  • Mutations in certain genes are associated with frontotemporal lobar degeneration (FTLD), but whether these mutations lead to gain or loss of function is still debated.
  • Research using Drosophila flies showed that knocking down the TER94 gene, similar to the human gene VCP/p97, resulted in severe health issues like early death and changes in brain structure, which were not restored by a known mutant version of the gene.
  • The study implies that the issues caused by TER94 knockdown are due to loss-of-function effects, particularly affecting cell proliferation and leading to the loss of another protein, TBPH, from cell nuclei.
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  • Researchers developed a new PET tracer, [C]K-2, that allows for the visualization and measurement of AMPAR density in the brains of living human patients, which is important for understanding neurotransmission in psychiatric disorders.
  • The study involved 149 patients with various psychiatric disorders (like schizophrenia and bipolar disorder) and 70 healthy individuals, revealing correlations between AMPAR density and symptom severity.
  • The findings highlight unique patterns of AMPAR distribution across different psychiatric disorders, suggesting potential new approaches for diagnosing and treating these conditions based on biological mechanisms.
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PQBP3 is a protein binding to polyglutamine tract sequences that are expanded in a group of neurodegenerative diseases called polyglutamine diseases. The function of PQBP3 was revealed recently as an inhibitor protein of proteasome-dependent degradation of Lamin B1 that is shifted from nucleolus to peripheral region of nucleus to keep nuclear membrane stability. Here, we address whether PQBP3 is an intrinsically disordered protein (IDP) like other polyglutamine binding proteins including PQBP1, PQBP5 and VCP.

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Senescence of nondividing neurons remains an immature concept, with especially the regulatory molecular mechanisms of senescence-like phenotypes and the role of proteins associated with neurodegenerative diseases in triggering neuronal senescence remaining poorly explored. In this study, we reveal that the nucleolar polyglutamine binding protein 3 (PQBP3; also termed NOL7), which has been linked to polyQ neurodegenerative diseases, regulates senescence as a gatekeeper of cytoplasmic DNA leakage. PQBP3 directly binds PSME3 (proteasome activator complex subunit 3), a subunit of the 11S proteasome regulator complex, decreasing PSME3 interaction with Lamin B1 and thereby preventing Lamin B1 degradation and senescence.

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  • The study analyzed 5804 days of Super-Kamiokande data from 1996 to 2018 to detect variations in solar ^{8}B neutrino flux.
  • The researchers utilized a five-day interval measurement approach and employed maximum likelihood and Lomb-Scargle methods to find any periodic modulations.
  • They found a significant modulation related to Earth's elliptical orbit around the Sun, with measurements of eccentricity and perihelion shift aligning with astronomical data.
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The glymphatic system is considered to play a pivotal role in the clearance of disease-causing proteins in neurodegenerative diseases. This study employed MR diffusion tensor imaging (DTI) to evaluate glymphatic system function and its correlation with brain amyloid accumulation levels measured using [C]Pittsburgh compound-B (PiB) PET/MRI. Fifty-six patients with mild cognitive impairment and early Alzheimer's disease (AD: 70 ± 11 y) underwent [C]PiB PET/MRI to assess amyloid deposition and were compared with 27 age-matched cognitively normal volunteers (CN: 69 ± 10y).

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Childhood maltreatment is reportedly associated with atypical gray matter structures in the primary visual cortex (V1). This study explores the hypothesis that retinal structures, the sensory organs of vision, are associated with brain atypicality and child maltreatment and examines their interrelation. General ophthalmologic examinations, visual cognitive tasks, retinal imaging, and structural magnetic resonance imaging (MRI) were conducted in children and adolescents aged 9-18 years with maltreatment experiences (CM) and typically developing (TD) children.

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The mechanisms of neuronal cell death in neurodegenerative disease remain incompletely understood, although recent studies have made significant advances. Apoptosis was previously considered to be the only mechanism of neuronal cell death in neurodegenerative diseases. However, recent findings have challenged this dogma, identifying new subtypes of necrotic neuronal cell death.

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  • Understanding the early molecular pathologies of neurodegenerative diseases like spinocerebellar ataxia type 1 (SCA1) can lead to better treatments for these conditions.
  • This study focused on the earliest developmental changes in SCA1 by analyzing RNA-seq data from patient-derived stem cells transforming into Purkinje cells, which are crucial for motor control.
  • The findings highlighted the involvement of specific histone and immune response genes in early SCA1 pathology, particularly noting the role of ISG15 in the degradation of mutant ataxin-1 within Purkinje cells.
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  • Child maltreatment, especially neglect, significantly impacts brain development, increasing risks for psychiatric disorders.
  • A study comparing neglected children to typically developing peers revealed specific structural brain changes, such as larger anterior cingulate cortex and smaller angular gyrus volumes.
  • The findings suggest that these brain alterations are linked to behavioral issues like hyperactivity and depression, indicating that neglect can disrupt normal brain connectivity and lead to emotional difficulties.
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  • * A study compared brain structures of 11 abusive mothers with 40 control mothers, revealing reduced axial diffusivity and trends indicating potential issues in voluntary movement control among the abusive group.
  • * Findings suggest a link between childhood abuse experiences and neurobiological changes in mothers, with higher depressive symptoms correlating to lower brain fiber integrity, though these were not directly tied to parenting practices or empathy.
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Aim: Pain is reconstructed by brain activities and its subjectivity comes from an interplay of multiple factors. The current study aims to understand the contribution of genetic factors to the neural processing of pain. Focusing on the single-nucleotide polymorphism (SNP) of opioid receptor mu 1 (OPRM1) AG (rs1799971) and catechol-O-methyltransferase (COMT) valmet (rs4680), we investigated how the two pain genes affect pain processing.

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  • A survey in Japan assessed adverse reactions to radiopharmaceuticals in FY2022 by collecting responses from nuclear medicine institutions.
  • Out of 1,181 institutions, 1,004 participated, reporting a total of 911,977 administered radiopharmaceuticals.
  • Only 17 adverse reactions were noted, resulting in an incidence rate of 1.9 per 100,000 cases, and no defective products were reported.
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Background: Charcot-Marie-Tooth disease type 1A (CMT1A) is one of the most common hereditary peripheral neuropathies caused by duplication of 1.5 Mb genome region including PMP22 gene. We aimed to correct the duplication in human CMT1A patient-derived iPS cells (CMT1A-iPSCs) by genome editing and intended to analyze the effect on Schwann cells differentiated from CMT1A-iPSCs.

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The effect on survival of radiographic lymph node metastasis in uterine cervical cancer patients is more important than before, even though its prognostic value not been well investigated. The aim of our study is to evaluate the prognostic potential of F-fluorodeoxyglucose Positron Emission Tomography (F-FDG PET) compared with Computed Tomography (CT) in uterine cervical cancer patients with stage IIICr allocated by imaging. Fifty-five patients with biopsy-proven primary cervical cancer underwent definitive radiation therapy for stages IIB-IVB of The International Federation of Gynecology and Obstetrics (FIGO) 2018 classifications.

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Background And Objectives: Magnetic resonance imaging with arterial spin labeling (ASL) perfusion imaging is a noninvasive method for quantifying cerebral blood flow (CBF). We aimed to evaluate the clinical utility of ASL perfusion imaging to aid in the diagnosis of Creutzfeldt-Jakob disease (CJD).

Methods: This retrospective study enrolled 10 clinically diagnosed with probable sporadic CJD (sCJD) based on the National CJD Research & Surveillance Unit and EuroCJD criteria and 18 healthy controls (HCs).

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Introduction: This study aimed to examine the effect of newly developed scissors-attached micro-forceps in superficial temporal artery-to-middle cerebral artery (STA-MCA) anastomosis for moyamoya disease (MMD).

Materials And Methods: Of 179 consecutive STA-MCA anastomoses on 95 hemispheres of 71 MMD patients at the University of Fukui Hospital between 2009 and 2023, 49 anastomoses on 26 hemispheres of 21 patients were enrolled in this retrospective cohort clinical trial intraoperative indocyanine green video-angiography did not demonstrate bypass patency in three anastomoses in two patients who were excluded. Twenty-one anastomosis in 19 hemispheres of 16 patients were performed using the conventional micro-forceps (conventional group, CG), and 25 anastomoses in 22 hemispheres of 19 patients were performed using scissors-attached micro-forceps (scissors group, SG).

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Objective: Compared with radiation therapy using photon beams, particle therapies, especially those using carbons, show a high relative biological effectiveness and low oxygen enhancement ratio. Using cells cultured under normoxic conditions, our group reported a greater suppressive effect on cell growth by carbon beams than X-rays, and the subsequent therapeutic effect can be predicted by the cell uptake amount of 3'-deoxy-3'-[F]fluorothymidine (F-FLT) the day after treatment. On the other hand, a hypoxic environment forms locally around solid tumors, influencing the therapeutic effect of radiotherapy.

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Expansions of repeat DNA tracts cause >70 diseases, and ongoing expansions in brains exacerbate disease. During expansion mutations, single-stranded DNAs (ssDNAs) form slipped-DNAs. We find the ssDNA-binding complexes canonical replication protein A (RPA1, RPA2, and RPA3) and Alternative-RPA (RPA1, RPA3, and primate-specific RPA4) are upregulated in Huntington disease and spinocerebellar ataxia type 1 (SCA1) patient brains.

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Cord blood is an important donor source for allogeneic hematopoietic stem cell transplantation (allo-HSCT), with its unique composition and quality of hematopoietic cells. The proliferation site and potency of infused hematopoietic stem cells in humans may vary between stem cell sources. We investigated this possibility in a prospective, exploratory study to assess hematopoietic dynamics using the radiopharmaceutical 3'-deoxy-3'-F-fluorothymidine (F-FLT), a thymidine analog used in positron emission tomography imaging, before allo-HSCT and on days 50 and 180 after allo-HSCT.

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Prion-like protein propagation is considered a common pathogenic mechanism in neurodegenerative diseases. Here we investigate the in vivo propagation pattern and aggregation state of mutant α-synuclein by injecting adeno-associated viral (AAV)-α-synuclein-A53T-EGFP into the mouse olfactory cortex. Comparison of aggregation states in various brain regions at multiple time points after injection using western blot analyses shows that the monomeric state of the mutant/misfolded protein propagates to remote brain regions by 2 weeks and that the propagated proteins aggregate in situ after being incorporated into neurons.

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Introduction: Extramural vascular invasion in patients with rectal cancer is a poor prognostic factor associated with distant metastasis; thus, accurate preoperative diagnosis is important. However, the accurate detection of extramural vascular invasion using magnetic resonance imaging (MRI) is difficult, and an improved diagnostic modality is required. In addition, the factors involved in the formation of extramural venous invasion (EMVI) remain unclear.

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Introduction: Neuroimaging studies on attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have demonstrated differences in extensive brain structure, activity and network. However, there remains heterogeneity and inconsistency across these findings, presumably because of the diversity of the disorders themselves, small sample sizes, and site and parameter differences in MRI scanners, and their overall pathogenesis remains unclear. To address these gaps in the literature, we will apply the travelling-subject approach to correct site differences in MRI scanners and clarify brain structure and network characteristics of children with ADHD and ASD using large samples collected in a multi-centre collaboration.

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Coronavirus disease (COVID-19) vaccination is known to cause a diagnostic dilemma due to false-positive findings on [F]FDG PET in vaccine-associated hypermetabolic lymphadenopathy. We present two case reports of women with estrogen-receptor (ER)-positive cancer of the breast who were vaccinated for COVID-19 in the deltoid muscle. [F]FDG positron emission tomography (PET) demonstrated primary breast cancer and multiple axillary lymph nodes with increased [F]FDG uptake, diagnosed as vaccine-associated [F]FDG-avid lymph nodes.

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