National Hospital Organization Iou Hospital

Komatsu, Japan

National Hospital Organization Iou Hospital

Komatsu, Japan
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Morinaga A.,Kanazawa University | Morinaga A.,National Hospital Organization Iou Hospital | Ono K.,Kanazawa University | Takasaki J.,Kanazawa University | And 4 more authors.
Experimental Neurology | Year: 2011

The folding of amyloid β-protein (Aβ) into oligomeric, protofibrillar, and fibrillar assemblies is hypothesized to be the key pathogenic event in Alzheimer's disease (AD), with oligomeric assemblies thought to be the most neurotoxic. Inhibitors of oligomer formation, therefore, could be valuable therapeutics for patients with AD. Epidemiological studies have indicated that estrogen therapy reduces the risk of developing AD in women. Here, we examined the effects of estrogen (estrone (E1), estradiol (E2), and estriol (E3)) and related sexual steroids (androstenedione (AND) and testosterone (TES)) on the in vitro oligomer formation of Aβ(1-40) and Aβ(1-42) using a method of photo-induced cross-linking of unmodified proteins (PICUP) and electron microscopic studies. Estrogens (E1, E2, and E3) inhibited low-order Aβ oligomer formation, and among them, E3 had the strongest in vitro activity. Estrogen could be a potential therapeutic agent to prevent or delay AD progression, and further understanding of the fact that these very similar molecules have different anti-oligomeric effects would contribute to the development of new agents. © 2011 Elsevier Inc.


Ishida C.,National Hospital Organization Iou Hospital | Kobayashi K.,Awazu Neuropsychiatric Sanatorium | Kitamura T.,Ishikawa Prefectual Takamatsu Hospital | Ujike H.,Ujike Nishiguchi Clinic | And 2 more authors.
Neuropathology | Year: 2015

We report the autopsy results of a patient with familial dementia who was diagnosed as having frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) with an R406W mutation in the microtubule-associated protein tau (MAPT) gene. This patient showed Alzheimer's disease (AD)-like clinical manifestations from the age of 59, with reduced β-amyloid1-42 (Aβ42) and elevated total and phosphorylated tau levels in the cerebrospinal fluid. He did not present with any apparent parkinsonism throughout the disease course. His autopsy at age 73 showed atrophy and neurodegeneration in many brain regions, particularly in the antero-medial temporal cortex and hippocampus, followed by the frontal lobes, with abundant neurofibrillary tangles. In addition, a diffuse distribution of Aβ-positive senile plaques, including many neuritic plaques, was observed and classified as stage C according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. These results suggest that analyzing of the MAPT gene is essential for diagnosing familial dementia, even if amyloid markers such as Aβ42 in the cerebrospinal fluid and amyloid imaging are positive, or if neuropathological findings indicate a diagnosis of AD. © 2014 Japanese Society of Neuropathology.


Ishida C.,National Hospital Organization Iou Hospital | Komai K.,National Hospital Organization Iou Hospital | Yonezawa K.,Yonezawa Hospital | Sakajiri K.-I.,National Hospital Organization | And 3 more authors.
Neuropathology | Year: 2011

We report the case of a woman who developed limb clumsiness in her fifties and gait disturbance in her sixties. She was bedridden after bone fractures at age 75 and showed disorientation, slow eye movement, gaze palsy, ataxic speech, muscle atrophy and weakness, and areflexia with pathological reflex. She died of respiratory failure at age 85. This patient was diagnosed genetically as having spinocerebellar ataxia type 2 (SCA2), and the number of expanded CAG repeats was 41. At autopsy, the brain weighed 965g, and the brainstem, cerebellum, frontal convexity and spinal cord were atrophic. Neuronal loss and gliosis were severe in the pontine nucleus, inferior olivary nucleus, cerebellar cortex, gracile and cuneate nuclei and moderate in the substantia nigra, cerebellar dentate nucleus, anterior horns of the spinal cord and dorsal root ganglia. Axonal loss was observed in the middle and inferior cerebellar peduncles, pyramidal tract and posterior column of the spinal cord. Senile plaques and neurofibrillary tangles (NFTs) were diffusely found in the cerebrum (plaque stage C; NFT stage IV). Expanded polyglutamine-immunoreactive inclusions in the neuronal cytoplasm were widely distributed in the CNS, and neuronal intranuclear inclusions were observed in the pontine nucleus and cerebral cortex. This patient in this autopsy case is a late-onset and aged patient with SCA2, and this is the first report of SCA2 combined with Alzheimer's disease (AD) pathology. Neuropathological findings in this patient, except for AD pathology, were consistent with those of reported SCA2 cases. However, the olivo-ponto-cerebellar system of this patient was relatively preserved and the cerebellar dentate nucleus was more involved as compared with previously reported cases. These results suggest that age at onset or the number of CAG repeat expansions could correlate with the distribution pattern of SCA2 neurodegeneration. © 2010 Japanese Society of Neuropathology.


Ono K.,Kanazawa University | Takahashi R.,Kanazawa University | Ikeda T.,Kanazawa University | Ikeda T.,National Hospital Organization Iou Hospital | And 3 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2014

Amyloid β-protein (Aβ) aggregation is considered to be a critical step in the neurodegeneration of Alzheimer's disease (AD). In addition to Aβ, many proteins aggregate into the amyloid state, in which they form elongated fibers with spines comprising stranded β-sheets. However, the cross-seeding effects of other protein aggregates on Aβ aggregation pathways are not completely clear. To investigate the cross-seeding effects of exogenous and human non-CNS amyloidogenic proteins on Aβ aggregation pathways, we examined whether and how sonicated fibrils of casein, fibroin, sericin, actin, and islet amyloid polypeptide affected Aβ40 and Aβ42 aggregation pathways using the thioflavin T assay and electron microscopy. Interestingly, the fibrillar seeds of all amyloidogenic proteins functioned as seeds. The cross-seeding effect of actin was stronger but that of fibroin was weaker than that of other proteins. Furthermore, our nuclear magnetic resonance spectroscopic studies identified the binding sites of Aβ with the amyloidogenic proteins. Our results indicate that the amyloidogenic proteins, including those contained in foods and cosmetics, contribute to Aβ aggregation by binding to Aβ, suggesting their possible roles in the propagation of Aβ amyloidosis. © 2014 Elsevier B.V.


Takahashi K.,National Hospital Organization Iou Hospital | Takahashi K.,Kanazawa University | Tanaka K.,Kanazawa Medical University
Journal of Neuroimmunology | Year: 2012

Previous reports of multiple sclerosis (MS) with autoantibodies might include neuromyelitis optica (NMO). We investigated the frequency of autoreactive antibodies (AR) in both MS and NMO. Systemic lupus erythematosus (SLE)-associated autoantibodies such as anti-Sm antibodies, anti-single stranded DNA antibodies and lupus anticoagulants were only identified in MS, whereas SLE itself is more commonly associated with NMO. Moreover, when magnetic resonance imaging features between autoreactive antibody-positive (AR(+))MS and -negative (AR(-))MS were compared, AR(+)MS cases showed significantly fewer than 3 periventricular lesions compared to AR(-)MS cases. These results may indicate different pathogenetic mechanisms underlying AR(+)MS and AR(-)MS. © 2012 Elsevier B.V.


Takahashi R.,Kanazawa University | Ono K.,Kanazawa University | Takamura Y.,University of Toyama | Mizuguchi M.,University of Toyama | And 4 more authors.
Journal of Neurochemistry | Year: 2015

Lewy bodies, mainly composed of α-synuclein (αS), are pathological hallmarks of Parkinson's disease and dementia with Lewy bodies. Epidemiological studies showed that green tea consumption or habitual intake of phenolic compounds reduced Parkinson's disease risk. We previously reported that phenolic compounds inhibited αS fibrillation and destabilized preformed αS fibrils. Cumulative evidence suggests that low-order αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies. To develop disease modifying therapies for α-synucleinopathies, we examined effects of phenolic compounds (myricetin (Myr), curcumin, rosmarinic acid (RA), nordihydroguaiaretic acid, and ferulic acid) on αS oligomerization. Using methods such as photo-induced cross-linking of unmodified proteins, circular dichroism spectroscopy, the electron microscope, and the atomic force microscope, we showed that Myr and RA inhibited αS oligomerization and secondary structure conversion. The nuclear magnetic resonance analysis revealed that Myr directly bound to the N-terminal region of αS, whereas direct binding of RA to monomeric αS was not detected. Electrophysiological assays for long-term potentiation in mouse hippocampal slices revealed that Myr and RA ameliorated αS synaptic toxicity by inhibition of αS oligomerization. These results suggest that Myr and RA prevent the αS aggregation process, reducing the neurotoxicity of αS oligomers. © 2015 International Society for Neurochemistry.


Ono K.,Kanazawa University | Takasaki J.-I.,Kanazawa University | Takahashi R.,Kanazawa University | Ikeda T.,Kanazawa University | And 2 more authors.
Journal of Neuroscience Research | Year: 2013

The aggregation of β-amyloid protein (Aβ) and α-synuclein (αS) are hypothesized to be the key pathogenic event in Alzheimer's disease (AD) and Lewy body diseases (LBD), with oligomeric assemblies thought to be the most neurotoxic. Inhibitors of oligomer formation, therefore, could be valuable therapeutics for patients with AD and LBD. Here, we examined the effects of antiparkinsonian agents (dopamine, levodopa, trihexyphenidyl, selegiline, zonisamide, bromocriptine, peroxide, ropinirole, pramipexole, and entacapone) on the in vitro oligomer formation of Aβ40, Aβ42, and αS using a method of photo-induced cross-linking of unmodified proteins (PICUP), electron microscopy, and atomic force microscopy. The antiparkinsonian agents except for trihexyphenidyl inhibited both Aβ and αS oligomer formations, and, among them, dopamine, levodopa, pramipexole, and entacapone had the stronger in vitro activity. Circular dichroism and thioflavin T(S) assays showed that secondary structures of Aβ and αS assemblies inhibited by antiparkinsonian agents were statistical coil state and that their seeding activities had disappeared. The antiparkinsonian agents could be potential therapeutic agents to prevent or delay AD and LBD progression. © 2013 Wiley Periodicals, Inc.


PubMed | National Hospital Organization Iou Hospital
Type: Journal Article | Journal: Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry | Year: 2016

To evaluate the effectiveness of an electric toothbrush for oral care in patients with neuromuscular disability.In this randomized observer-blind crossover trial, 30 patients with neuromuscular disease performed either electric or manual toothbrushing each for 4 weeks. Plaque status (plaque control record), periodontal pocket depth, oral status (oral assessment guide), salivary bacterial count, and toothbrushing time were assessed after each period and compared between the two groups by Wilcoxon signed-rank test.Twenty-eight patients completed the study, including 18 communicative patients. Periodontal pockets were significantly shallower and toothbrushing time was significantly shorter with electric toothbrush use than with manual toothbrush use. No significant differences in oral status and salivary bacterial counts were noted between the approaches, but plaque status significantly improved after electric toothbrushing in communicative patients.Electric toothbrushing is beneficial for maintaining oral health in patients with neuromuscular disability and reducing the caregivers oral care burden.


PubMed | National Hospital Organization Iou Hospital and Kanazawa University
Type: | Journal: Journal of medical case reports | Year: 2015

Qing fei tang, which is used for various respiratory diseases, is useful for reducing relapse of aspiration pneumonia and bronchopneumonia in stroke, but the effect remains unknown in Parkinsons syndrome. We report two cases of Japanese patients with progressive supranuclear palsy and relapsing aspiration pneumonia and bronchopneumonia, which was successfully prevented by qing fei tang.Two Japanese men with progressive supranuclear palsy and receiving total enteral feeding (patient one (66-years-old) and patient two (76-years-old)) had experienced recurrent aspiration pneumonia and bronchopneumonia, which was unresponsive to conventional therapy. The respiratory infection developed twice at intervals of two months in patient one, and nine times at almost monthly intervals in patient two. Thereafter, they were given qing fei tang. After administration of qing fei tang, the respiratory infection reoccurred only once; after 5.5 months for patient one, and six months for patient two. Both of our patients clearly showed a reduced incidence of respiratory infection.Both of our patients clearly showed a reduced incidence of respiratory infection after the administration of qing fei tang. Qing fei tang could be useful for the prevention of recurrent aspiration pneumonia and bronchopneumonia in progressive supranuclear palsy.


PubMed | National Hospital Organization Iou Hospital
Type: Case Reports | Journal: Neuropathology : official journal of the Japanese Society of Neuropathology | Year: 2015

We report the autopsy results of a patient with familial dementia who was diagnosed as having frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) with an R406W mutation in the microtubule-associated protein tau (MAPT) gene. This patient showed Alzheimers disease (AD)-like clinical manifestations from the age of 59, with reduced -amyloid1-42 (A42 ) and elevated total and phosphorylated tau levels in the cerebrospinal fluid. He did not present with any apparent parkinsonism throughout the disease course. His autopsy at age 73 showed atrophy and neurodegeneration in many brain regions, particularly in the antero-medial temporal cortex and hippocampus, followed by the frontal lobes, with abundant neurofibrillary tangles. In addition, a diffuse distribution of A-positive senile plaques, including many neuritic plaques, was observed and classified as stage C according to the Consortium to Establish a Registry for Alzheimers Disease (CERAD) criteria. These results suggest that analyzing of the MAPT gene is essential for diagnosing familial dementia, even if amyloid markers such as A42 in the cerebrospinal fluid and amyloid imaging are positive, or if neuropathological findings indicate a diagnosis of AD.

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