Publications by authors named "Manabu Kubota"

Background: Pick's disease (PiD) is classified as frontotemporal lobar degeneration with pathological tau aggregates. Positron emission tomography (PET) with F-florzolotau provides high-contrast imaging of diverse tau fibrils. While our previous work demonstrated the detectability of three repeat (3R) tau pathology by F-florzolotau PET in an autopsy-confirmed PiD patient, its potential for quantitative assessment of 3R tau aggregates in living individuals remains unclear.

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Introduction: Late-life mood disorders (LLMDs) may represent prodromal manifestations of neurodegenerative dementia; however, the neuropathological basis of LLMDs, including depression and bipolar disorder, remains unclear. We aimed to investigate the involvement of Alzheimer's disease (AD) and non-AD tau pathologies in LLMD participants.

Methods: Fifty-two LLMD participants and 47 age- and sex-matched healthy controls (HCs) underwent tau and amyloid beta (Aβ) positron emission tomography (PET) imaging using F-florzolotau and C-Pittsburgh compound B.

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One of the challenges in diagnosing psychiatric disorders is that the results of biological and neuroscience research are not reflected in the diagnostic criteria. Thus, data-driven analyses incorporating biological and cross-disease perspectives, regardless of the diagnostic category, have recently been proposed. A data-driven clustering study based on subcortical volumes in 5604 subjects classified into four brain biotypes associated with cognitive/social functioning.

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The left posterior superior temporal gyrus (pSTG) is thought to be involved in the pathophysiology and core symptoms of schizophrenia, although its structural connectivity has not yet been systematically investigated. Here, we aimed to evaluate its white matter (WM) connectivity with Broca's area, the thalamus, and the right pSTG. Eighty-three patients with schizophrenia and 141 healthy controls underwent diffusion-weighted imaging and T1-weighted three-dimensional magnetic resonance imaging.

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Background: Social dysfunctions can affect the quality of life (QOL) of patients with schizophrenia. The autism-spectrum quotient (AQ) is a widely used measure of innate autistic traits. However, in patients with schizophrenia, the score may represent the severity of autism-like social dysfunctions as a consequence of symptoms.

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Background: The Frontal Assessment Battery (FAB) is widely used to assess executive dysfunction in patients with amnestic mild cognitive impairments due to Alzheimer's disease (aMCI-AD), but its neurobiological meaning is unclear. To elucidate this, we examined the relationship between the FAB score and three key imaging biomarkers: gray matter volume, amyloid-beta (Aβ) deposition, and glucose metabolism.

Methods: Twenty Aβ- and tau-positive aMCI-AD patients and age-matched controls underwent structural magnetic resonance imaging and positron emission tomography with [C]PiB and [F]FDG.

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Background: Although central disorders of hypersomnolence (CDH) and attention-deficit/hyperactivity disorder (ADHD) are frequently comorbid, they often remain underdiagnosed, leading to insufficient treatment and sociopsychological outcomes.

Case Presentation: Here, we present a case of a male in his late 20s with ADHD and autism spectrum disorder who exhibited symptoms suggestive of idiopathic hypersomnia (IH), a subtype of CDH. The patient experienced difficulty waking up and dropped out of university.

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Article Synopsis
  • This study investigates tau accumulation in the nucleus basalis of Meynert (nbM) in early-onset Alzheimer's disease (EOAD) compared to late-onset Alzheimer's disease (LOAD), using F-florzolotau PET imaging.
  • EOAD patients exhibited a higher overall tau burden in the nbM, but cognitive decline was more closely associated with nbM tau levels in LOAD patients.
  • The research highlights the differing pathological trajectories and relationships between tau in the nbM and neocortex, emphasizing the significance of age of onset in assessing Alzheimer's disease pathology and cognition.
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Phosphodiesterase 10 A (PDE10A), a pivotal element of the second messenger signaling downstream of the dopamine receptor stimulation, is conceived to be crucially involved in the mood instability of bipolar I disorder (BD-I) as a primary causal factor or in response to dysregulated dopaminergic tone. We aimed to determine whether striatal PDE10A availability is altered in patients with BD-I and assessed its relationship with the clinical characteristics of BD-I. This case-control study used positron emission tomography (PET) with 2-(2-(3-(4-(2-[F]fluoroethoxy)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([F]MNI-659), a radioligand that binds to PDE10A, to examine the alterations of the striatal PDE10A availability in the living brains of individuals with BD-I and their association with the clinical characteristics of BD-I.

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Tau positron emission tomography (PET) is a neuroimaging technique that visualizes tau deposition using PET tracers that selectively bind to tau aggregates. Studies have reported the diagnostic and prognostic value of tau PET in Alzheimer's disease and other tauopathies. However, the binding profiles of tau PET drugs vary widely across tauopathies; therefore, an accurate understanding of the disease-specific characteristics is essential for interpretation of tau PET findings.

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Cognitive dysfunction, especially memory impairment, is a typical clinical feature of long-term symptoms caused by repetitive mild traumatic brain injury (rmTBI). The current study aims to investigate the relationship between regional brain atrophy and cognitive impairments in retired athletes with a long history of rmTBI. Overall, 27 retired athletes with a history of rmTBI (18 boxers, 3 kickboxers, 2 wrestlers, and 4 others; rmTBI group) and 23 age/sex-matched healthy participants (control group) were enrolled.

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Frontotemporal dementia refers to a group of neurodegenerative disorders with diverse clinical and neuropathological features. neuropathological assessments of frontotemporal dementia at an individual level have hitherto not been successful. In this study, we aim to classify patients with frontotemporal dementia based on topologies of tau protein aggregates captured by PET with F-florzolotau (aka F-APN-1607 and F-PM-PBB3), which allows high-contrast imaging of diverse tau fibrils in Alzheimer's disease as well as in non-Alzheimer's disease tauopathies.

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Immune checkpoint molecules PD-1/PD-L1 cause T-cell exhaustion and contribute to disease progression in chronic infections of cattle. We established monoclonal antibodies (mAbs) that specifically inhibit the binding of bovine PD-1/PD-L1; however, conventional anti-PD-1 mAbs are not suitable as therapeutic agents because of their low binding affinity to antigen. In addition, their sensitivity for the detection of bovine PD-1 is low and their use for immunostaining PD-1 is limited.

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Purpose: The topological distribution of dopamine-related proteins is determined by gene transcription and subsequent regulations. Recent research strategies integrating positron emission tomography with a transcriptome atlas have opened new opportunities to understand the influence of regulation after transcription on protein distribution. Previous studies have reported that messenger (m)-RNA expression levels spatially correlate with the density maps of serotonin receptors but not with those of transporters.

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Article Synopsis
  • The study investigates the role of increased excitatory signals in autism, focusing on elevated levels of glutamate and its relation to astrocyte activation and dopamine signaling.
  • Using imaging techniques, researchers compared 18 adults with high-functioning autism to 20 typically developed individuals, finding significant increases in glutamate, glutamine, and myo-inositol levels in the autism group.
  • Results indicate a correlation between glutamine levels and dopamine receptor binding, suggesting that heightened excitation and astrocyte activity may contribute to autism's symptoms by disrupting normal inhibitory dopamine signaling.
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Individuals with autism spectrum disorder (ASD) often show limited empathy (poor recognition of others' emotions) and high alexithymia (poor recognition of own emotions and external thinking), which can negatively impact their social functioning. Previous experimental studies suggest that alterations in cognitive flexibility play key roles in the development of these characteristics in ASD. However, the underlying neural mechanisms that link cognitive flexibility and empathy/alexithymia are still largely unknown.

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Background: Central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission has been implicated in the etiology of depression. Most antidepressants ameliorate depressive symptoms by increasing 5-HT at synaptic clefts, but their effect on 5-HT receptors has yet to be clarified. 11C-WAY-100635 and 18F-MPPF are positron emission tomography (PET) radioligands for 5-HT1A receptors.

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Background: Electroconvulsive therapy (ECT) is one of the most effective treatments for depression and schizophrenia, particularly in urgent or treatment-resistant cases. After ECT, regional gray matter volume (GMV) increases have been repeatedly reported both in depression and schizophrenia. However, the interpretation of these findings remains entangled because GMV changes do not necessarily correlate with treatment effects and may be influenced by the intervention itself.

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Patients with progressive supranuclear palsy (PSP) frequently exhibit apathy but the neuropathological processes leading to this phenotype remain elusive. We aimed to examine the involvement of tau protein depositions, oxidative stress (OS), and neuronal loss in the apathetic manifestation of PSP. Twenty patients with PSP and twenty-three healthy controls were enrolled.

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Background And Hypothesis: Phosphodiesterase 10A (PDE10A) is a highly expressed enzyme in the basal ganglia, where cortical glutamatergic and midbrain dopaminergic inputs are integrated. Therapeutic PDE10A inhibition effects on schizophrenia have been reported previously, but the status of this molecule in the living patients with schizophrenia remains elusive. Therefore, this study aimed to investigate the central PDE10A status in patients with schizophrenia and examine its relationship with psychopathology, cognition, and corticostriatal glutamate levels.

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Objective: Previously, we reported that insulinoma-associated protein 1 (INSM1) immunohistochemistry (IHC) showed high sensitivity for neuroendocrine carcinoma of the uterine cervix and was an effective method for histopathological diagnosis, but that its specificity remained to be verified. Therefore, the aim was to verify the specificity of INSM1 IHC for a large number of non-neuroendocrine neoplasia (NEN) of the cervix.

Methods: RNA sequences were performed for cell lines of small cell carcinoma (TCYIK), squamous cell carcinoma (SiHa), and adenocarcinoma (HeLa).

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Background: Although gel immersion endoscopic resection (GIER) is a potential alternative to underwater endoscopic mucosal resection (UEMR) for superficial nonampullary duodenal epithelial tumors (SNADETs), comparisons between the two are currently insufficient.

Methods: 40 consecutive procedures performed in 35 patients were retrospectively reviewed; the primary outcome was procedure time, and the secondary outcomes were en bloc and R0 resection rates, tumor and specimen size, and adverse events.

Results: Lesions were divided into GIER (n = 22) and UEMR groups (n = 18).

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Treatments for acute cholecystitis include cholecystectomy and percutaneous drainage. However, some patients are at high risk for surgery, and prolonged drainage can decrease their quality of life. To determine the feasibility of percutaneous transhepatic gallbladder filling (PTGBF) with n-butyl-cyanoacrylate (NBCA) in a swine model.

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Introduction: Corticobasal degeneration (CBD) is the most common neuropathological substrate for clinically diagnosed corticobasal syndrome (CBS), while identifying CBD pathology in living individuals has been challenging. This study aimed to examine the capability of positron emission tomography (PET) to detect CBD-type tau depositions and neuropathological classification of CBS.

Methods: Sixteen CBS cases diagnosed by Cambridge's criteria and 12 cognitively healthy controls (HCs) underwent PET scans with C-PiB, C-PBB3, and F-FDG, along with T1-weighted magnetic resonance imaging.

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