担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Neurodegenerative disorders are characterized by the progressive loss of neuronal structure or function, resulting in memory loss and movement disorders. Although the detailed pathogenic mechanism has not been elucidated, it is thought to be related to the loss of mitochondrial function in the process of aging. Animal models that mimic the pathology of a disease are essential for understanding human diseases. In recent years, small fish have become ideal vertebrate models for human disease due to their high genetic and histological homology to humans, ease of in vivo imaging, and ease of genetic manipulation. In this review, we first outline the impact of mitochondrial dysfunction on the progression of neurodegenerative diseases. Then, we highlight the advantages of small fish as model organisms, and present examples of previous studies regarding mitochondria-related neuronal disorders. Lastly, we discuss the applicability of the turquoise killifish, a unique model for aging research, as a model for neurodegenerative diseases. Small fish models are expected to advance our understanding of the mitochondrial function in vivo, the pathogenesis of neurodegenerative diseases, and be important tools for developing therapies to treat diseases.

DOI： 10.3390/ijms24087079

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The cerebellum is organized into functional regions each dedicated to process different motor or sensory inputs for controlling different locomotor behaviors. This functional regionalization is prominent in the evolutionary conserved single-cell layered Purkinje cell (PC) population. Fragmented gene expression domains suggest a genetic organization of PC layer regionalization during cerebellum development. However, the establishment of such functionally specific domains during PC differentiation remained elusive. METHODS AND RESULTS: We show the progressive emergence of functional regionalization of PCs from broad responses to spatially restricted regions in zebrafish by means of in vivo Ca2+-imaging during stereotypic locomotive behavior. Moreover, we reveal that formation of new dendritic spines during cerebellar development using in vivo imaging parallels the time course of functional domain development. Pharmacological as well as cell-type specific optogenetic inhibition of PC neuronal activity results in reduced PC dendritic spine density and an altered stagnant pattern of functional domain formation in the PC layer. DISCUSSION: Hence, our study suggests that functional regionalization of the PC layer is driven by physiological activity of maturing PCs themselves.

DOI： 10.3389/fnmol.2023.1166900

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

The African turquoise killifish Nothobranchius furzeri (N. furzeri) is a useful model organism for studying aging, age-related diseases, and embryonic diapause. CRISPR/Cas9-mediated gene knockout and Tol2 transposon-mediated transgenesis in N. furzeri have been reported previously. However, these methods take time to generate knockout and transgenic fish. In addition, knock-in technology that inserts large DNA fragments as fluorescent reporter constructs into the target gene in N. furzeri has not yet been established. Here, we show that triple-target CRISPR-mediated single gene disruption efficiently produces whole-body biallelic knockout and enables the examination of gene function in the F0 generation. In addition, we developed a method for creating the knock-in reporter N. furzeri without crossing by optimizing the CRISPR/Cas9 system. These methods drastically reduce the duration of experiments, and we think that these advances will accelerate aging and developmental studies using N. furzeri.

DOI： 10.1038/s41598-022-15972-3

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その他リンク： https://www.nature.com/articles/s41598-022-15972-3

担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.4103/1673-5374.335816

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

Glutamate acts as the main excitatory neurotransmitter in the brain and plays a vital role in physiological and pathological neuronal functions. In mammals, glutamate can cause detrimental excitotoxic effects under anoxic conditions. In contrast, Trachemys scripta, a freshwater turtle, is one of the most anoxia-tolerant animals, being able to survive up to months without oxygen. Therefore, turtles have been investigated to assess the molecular mechanisms of neuroprotective strategies used by them in anoxic conditions, such as maintaining low levels of glutamate, increasing adenosine and GABA, upregulating heat shock proteins, and downregulating K_ATP channels. These mechanisms of anoxia tolerance of the turtle brain may be applied to finding therapeutics for human glutamatergic neurological disorders such as brain injury or cerebral stroke due to ischemia. Despite the importance of glutamate as a neurotransmitter and of the turtle as an ideal research model, the glutamatergic circuits in the turtle brain remain less described whereas they have been well studied in mammalian and avian brains. In reptiles, particularly in the turtle brain, glutamatergic neurons have been identified by examining the expression of vesicular glutamate transporters (VGLUTs). In certain areas of the brain, some ionotropic glutamate receptors (GluRs) have been immunohistochemically studied, implying that there are glutamatergic target areas. Based on the expression patterns of these glutamate-related molecules and fiber connection data of the turtle brain that is available in the literature, many candidate glutamatergic circuits could be clarified, such as the olfactory circuit, hippocampal–septal pathway, corticostriatal pathway, visual pathway, auditory pathway, and granule cell–Purkinje cell pathway. This review summarizes the probable glutamatergic pathways and the distribution of glutamatergic neurons in the pallium of the turtle brain and compares them with those of avian and mammalian brains. The integrated knowledge of glutamatergic pathways serves as the fundamental basis for further functional studies in the turtle brain, which would provide insights on physiological and pathological mechanisms of glutamate regulation as well as neural circuits in different species.

DOI： 10.3389/fnana.2022.937504

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

Animal models have been used to model human diseases, and among them, small fishes have been highlighted for their usefulness in various ways, such as the low cost of maintenance, ease of genetic modification, small size for easy handling, and strength in imaging studies due to their relative transparency. Recently, the use of turquoise killifish, Nothobranchius furzeri, which is known to exhibit various aging phenotypes in a short period, has attracted attention in research on aging and age-related diseases. However, when using animal models, it is important to keep their genetic background and interspecies differences in mind for translating them into human diseases. In this article, we obtained the gene symbols of protein-coding genes of turquoise killifish, medaka, zebrafish, and humans from NCBI datasets and extracted common shared genes among four species to explore the potential of interspecies translational research and to apply small fish models for human age-related disorders. Common shared protein-coding genes were analyzed with the Reactome Pathway Database to determine the coverage of these genes in each pathway in humans. We applied common shared genes to the Orphanet database to establish a list of human diseases that contain common shared genes among the four species. As examples, the senescence-related pathways and some pathways of human age-related diseases, such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, nonalcoholic fatty liver disease, progeria, hepatocellular carcinoma, and renal cell carcinoma, were extracted from the curated pathway and disease list to discuss the further utility of fish models for human age-related disorders.

DOI： 10.3389/fgene.2022.928597

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two debilitating neurodevelopmental disorders. The former is associated with social impairments whereas the latter is associated with inattentiveness, hyperactivity, and impulsivity. There is recent evidence that both disorders are somehow related and that genes may play a large role in these disorders. Despite mounting human and animal research, the neurological pathways underlying ASD and ADHD are still not well understood. Scientists investigate neurodevelopmental disorders by using animal models that have high similarities in genetics and behaviours with humans. Mice have been utilized in neuroscience research as an excellent animal model for a long time; however, the zebrafish has attracted much attention recently, with an increasingly large number of studies using this model. In this review, we first discuss ASD and ADHD aetiology from a general point of view to their characteristics and treatments. We also compare mice and zebrafish for their similarities and discuss their advantages and limitations in neuroscience. Finally, we summarize the most recent and existing research on zebrafish and mouse models of ASD and ADHD. We believe that this review will serve as a unique document providing interesting information to date about these models, thus facilitating research on ASD and ADHD.

DOI： 10.3390/ijms23147550

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Parkinson's disease is a neurodegenerative disorder that causes motor and nonmotor symptoms due to the loss of dopaminergic nerves and is characterized by the presence of Lewy bodies, which are mainly composed of α-synuclein. Glucosylceramidase beta (GBA), which is a causative gene of autosomal recessive Gaucher disease, is also known to be a risk gene for Parkinson's disease. In this study, we tried to detect synergistic effects of α-synuclein accumulation and gba depletion on dopaminergic neurodegeneration in zebrafish. METHODS: We generated a transgenic line of zebrafish overexpressing the A53T α-synuclein and gba mutant fish, and analyzed pathologies of α-synuclein aggregation and neurodegeneration. RESULTS: Zebrafish overexpressing the A53T α-synuclein did not exhibit α-synuclein aggregate formation. After the loss of gba function in this mutant α-synuclein transgenic line, we observed the marked presence of α-synuclein aggregates. Loss of gba function in zebrafish resulted in dopaminergic and noradrenergic neurodegeneration but this level of neurodegeneration was not exacerbated by overexpression of mutant α-synuclein. CONCLUSIONS: These results indicate that loss of gba function was sufficient to generate a neurodegenerative phenotype in zebrafish regardless of the expression of α-synuclein.

DOI： 10.1097/WNR.0000000000001788

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担当区分：最終著者,　責任著者   掲載種別：研究論文（学術雑誌）  

The presence of ectopic DNA in the cytoplasm induces inflammation and cell death. It has been widely reported that leakage of nuclear DNA into the cytoplasm can mainly be sensed by cyclic GMP-AMP synthase (cGAS). We recently reported that mitochondria-derived cytoplasmic double-stranded DNA (dsDNA) that has escaped lysosomal degradation induces significant cytotoxicity in cultured cells and in vivo. Cytoplasmic mitochondrial DNA is assumed to be involved in various diseases and disorders, and more and more papers have been published confirming this. On the other hand, the current method for evaluating mitochondrial DNA in the cytoplasm may not be quantitative. Here, we introduce in detail a method to evaluate ectopic mitochondrial DNA in cells. This method is useful in basic research as well as in the study of aging, Parkinson’s disease, Alzheimer’s disease, heart failure, autoimmune diseases, cancer, and other conditions.

DOI： 10.3390/cimb44030080

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

In recent years, small fishes such as zebrafish and medaka have been widely recognized as model animals. They have high homology in genetics and tissue structure with humans and unique features that mammalian model animals do not have, such as transparency of embryos and larvae, a small body size and ease of experiments, including genetic manipulation. Zebrafish and medaka have been used extensively in the field of neurology, especially to unveil the mechanisms of neurodegenerative diseases such as Parkinson's and Alzheimer's disease, and recently, these fishes have also been utilized to understand neurodevelopmental disorders such as autism spectrum disorder. The turquoise killifish has emerged as a new and unique model animal, especially for ageing research due to its unique life cycle, and this fish also seems to be useful for age-related neurological diseases. These small fishes are excellent animal models for the analysis of human neurological disorders and are expected to play increasing roles in this field. Here, we introduce various applications of these model fishes to improve our understanding of human neurological disorders.

DOI： 10.3390/ijms23031399

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

<title>Abstract</title>Mitochondrial dysfunction and lysosomal dysfunction have been implicated in Parkinson’s disease (PD), but the links between these dysfunctions in PD pathogenesis are still largely unknown. Here we report that cytosolic dsDNA of mitochondrial origin escaping from lysosomal degradation was shown to induce cytotoxicity in cultured cells and PD phenotypes in vivo. The depletion of PINK1, GBA and/or ATP13A2 causes increases in cytosolic dsDNA of mitochondrial origin and induces type I interferon (IFN) responses and cell death in cultured cell lines. These phenotypes are rescued by the overexpression of DNase II, a lysosomal DNase that degrades discarded mitochondrial DNA, or the depletion of IFI16, which acts as a sensor for cytosolic dsDNA of mitochondrial origin. Reducing the abundance of cytosolic dsDNA by overexpressing human DNase II ameliorates movement disorders and dopaminergic cell loss in gba mutant PD model zebrafish. Furthermore, IFI16 and cytosolic dsDNA puncta of mitochondrial origin accumulate in the brain of patients with PD. These results support a common causative role for the cytosolic leakage of mitochondrial DNA in PD pathogenesis.

DOI： 10.1038/s41467-021-23452-x

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その他リンク： http://www.nature.com/articles/s41467-021-23452-x

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder. However, due to its rarity and difficult histological investigation, its pathophysiology has not been characterized. AIM: Therefore, in this study, we aimed to determine the role of esophageal high-resolution manometry (HRM) in CIPO and the histological and clinical characteristics of the disease. METHODS: Patients with CIPO were analyzed for clinical characteristics; histological findings; and clinical courses after therapeutic intervention. In addition, HRM was performed to determine the esophageal involvement. RESULTS: Eleven patients were diagnosed with CIPO, and five required the long period of parenteral nutrition showing impaired esophageal motility including achalasia and absent contractility diagnosed with HRM. The four of these five cases showed acute onset of the CIPO following the triggering events of pregnancy, appendicitis, and surgery. In contrast, other six patients with normal or Jackhammer esophagus on HRM had moderate severity of CIPO with gradual onset. The histological analyses revealed that the loss of the intestinal neural ganglion cells and layers by inflammation, destruction, and atrophy are related to the severity of the clinical course of the disease and esophageal HRM findings of achalasia and absent contractility. CONCLUSIONS: HRM may be useful to diagnose the severity of the clinical course and to determine the therapeutic options for CIPO.

DOI： 10.1007/s10620-020-06701-9

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

ATP13A2 is the autosomal recessive causative gene for juvenile-onset Parkinson's disease (PARK9, Parkinson's disease 9), also known as Kufor-Rakeb syndrome. The disease is characterized by levodopa-responsive Parkinsonism, supranuclear gaze palsy, spasticity, and dementia. Previously, we have reported that Atp13a2 deficient medaka fish showed dopaminergic neurodegeneration and lysosomal dysfunction, indicating that lysosome-autophagy impairment might be one of the key pathogeneses of Parkinson's disease. Here, we established Atp13a2 deficient zebrafish using CRISPR/Cas9 gene editing. We found that the number of TH + neurons in the posterior tuberculum and the locus coeruleus significantly reduced (dopaminergic neurons, 64 % at 4 months and 37 % at 12 months, p < 0.001 and p < 0.05, respectively; norepinephrine neurons, 52 % at 4 months and 40 % at 12 months, p < 0.001 and p < 0.05, respectively) in Atp13a2 deficient zebrafish, proving the degeneration of dopaminergic neurons. In addition, we found the reduction (60 %, p < 0.05) of cathepsin D protein expression in Atp13a2 deficient zebrafish using immunoblot. Transmission electron microscopy analysis using middle diencephalon samples from Atp13a2 deficient zebrafish showed lysosome-like bodies with vesicle accumulation and fingerprint-like structures, suggesting lysosomal dysfunction. Furthermore, a significant reduction (p < 0.001) in protein expression annotated with vesicle fusion with Golgi apparatus in Atp13a2 deficient zebrafish by liquid-chromatography tandem mass spectrometry suggested intracellular trafficking impairment. Therefore, we concluded that Atp13a2 deficient zebrafish exhibited degeneration of dopaminergic neurons, lysosomal dysfunction and the possibility of intracellular trafficking impairment, which would be the key pathogenic mechanism underlying Parkinson's disease.

DOI： 10.1016/j.ibror.2020.05.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study aimed to determine whether enteric neurons are involved in multiple system atrophy (MSA). Four-μm-thick slices of small intestine were prepared from 10%-formalin-fixed and paraffin-embedded materials obtained from autopsied cases. Enteric neurons were stained using an anti-peripherin antibody. Immunostaining of phosphorylated α-synuclein was also performed. Areas of the cytoplasm and nucleus that showed nucleoli were measured using computer software. Both areas of myenteric neurons were significantly smaller in MSA cases (n = 3) than in control subjects (n = 3) (P < 0.0001); however, no deposits of phosphorylated α-synuclein were observed. These findings suggest that myenteric neurons in MSA are affected independent of α-synuclein accumulation.

DOI： 10.1016/j.autneu.2019.102583

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担当区分：筆頭著者,　責任著者   記述言語：英語  

DOI： 10.1016/j.celrep.2019.01.015

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Parkinson's disease is a neurodegenerative disorder that involves movement discloses, degeneration of dopaminergic neurons, and presence of cytoplasmic inclusion bodies. Various animal models have been developed and small fish including zebrafish and medaka fish have recently been employed as a new model for Parkinson disease. In this review, we summarize fish models of Parkinson's disease mainly using our own findings and explain two major hypotheses of PD: lysosome dysfunction theory and mitochondrial dysfunction theory. Finally, we discuss the potential for future application of small fish model.

DOI： 10.1007/s00702-017-1772-1

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER WIEN  

A modified method of cerebrospinal fluid injection was developed for the efficient and reliable administration of substances to the zebrafish central nervous system. The accuracy of this modified method was evaluated using Alexa Fluor dye injection. A high survival ratio was achieved due to the simplicity of the procedure and ice-tricaine combined anaesthesia. To validate this new method, we injected ammonium chloride, which successfully blocked lysosome function resulting in elevated LC3-II and the accumulation of ubiquitinated proteins. Injection of human α-synuclein fibrils initiated a prion-like propagation of α-synuclein pathology in zebrafish. This method can be used to investigate the effects of various substances and the propagation of α-synuclein in the central nervous system.

DOI： 10.1007/s00702-017-1787-7

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担当区分：筆頭著者,　最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Small teleost fish including zebrafish and medaka have been used as animal models in basic science research due to the relative ease of handling and transparency during embryogenesis. Current advances in genetic engineering and progress in disease genetics allowed utilization of these fish to study neurological diseases and psychiatric disorders. This review summarizes the advantages and disadvantages of using fish for neuropsychiatric research using primarily our own studies as examples. We discuss how fish belong to a class of vertebrates, are feasible for imaging, and include diverse species with multiple research possibilities yet to be discovered.

DOI： 10.1016/j.neures.2017.02.004

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担当区分：筆頭著者,　最終著者,　責任著者   記述言語：英語   出版者・発行元：WILEY  

Small teleost fish including zebrafish and medaka have been used as animal models for research because of their small body size, vast amounts of eggs produced, their rapid development, low husbandry costs, and transparency during embryogenesis. Although the body size and appearance seem different, fish and mammals including human still possess anatomical and functional similarities in their brains. This review summarizes the similarities of brain structures and functions between teleost fish and mammalian brains, focusing on the dopamine system, functional regionalization of the cerebellum, and presence of the nucleus ruber.

DOI： 10.1111/dgd.12357

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JOURNAL OF VISUALIZED EXPERIMENTS  

The nervous system has the remarkable ability to adapt and respond to various stimuli. This neural adjustment is largely achieved through plasticity at the synaptic level. The Active Zone (AZ) is the region at the presynaptic membrane that mediates neurotransmitter release and is composed of a dense collection of scaffold proteins. AZs of Drosophila melanogaster (Drosophila) photoreceptors undergo molecular remodeling after prolonged exposure to natural ambient light. Thus the level of neuronal activity can rearrange the molecular composition of the AZ and contribute to the regulation of the functional output. Starting from the light exposure set-up preparation to the immunohistochemistry, this protocol details how to quantify the number, the spatial distribution, and the delocalization level of synaptic molecules at AZs in Drosophila photoreceptors. Using image analysis software, clusters of the GFP-fused AZ component Bruchpilot were identified for each R8 photoreceptor (R8) axon terminal. Detected Bruchpilot spots were automatically assigned to individual R8 axons. To calculate the distribution of spot frequency along the axon, we implemented a customized software plugin. Each axon's start-point and end-point were manually defined and the position of each Bruchpilot spot was projected onto the connecting line between start and end-point. Besides the number of Bruchpilot clusters, we also quantified the delocalization level of Bruchpilot-GFP within the clusters. These measurements reflect in detail the spatially resolved synaptic dynamics in a single neuron under different environmental conditions to stimuli.

DOI： 10.3791/55176

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

In recent years, considerable effort has been devoted to the development of a fish model for Parkinson's disease (PD) to examine the pathological mechanisms of neurodegeneration. To effectively evaluate PD pathology, the ability to accurately and reliably count dopaminergic neurons is important. However, there is currently no such standardized method. Due to the relatively small number of dopaminergic neurons in fish, stereological estimation would not be suitable. In addition, serial sectioning requires proficiency to not lose any sections, and it permits double counting due to the large size of some of the dopaminergic neurons. In this study, we report an optimized protocol for staining dopaminergic neurons in zebrafish and provide a reliable counting method. Finally, using our optimized protocol, we confirmed that administration of 6-hydroxydopamine (a neurotoxin) or the deletion of the PINK1 gene (one of the causative genes of familiar PD) in zebrafish caused significant reduction in the number of dopaminergic and noradrenergic neurons. In summary, this method will serve as an important tool for the appropriate evaluation and establishment of fish PD models.

DOI： 10.1371/journal.pone.0184363

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担当区分：筆頭著者   記述言語：英語  

BACKGROUND: Members of the junctional adhesion molecule (JAM) family function as cell adhesion molecules and cell surface receptors. The zebrafish genome contains six different jam genes, and jam-b and jam-c were shown to be essential for myoblast fusion during skeletal muscle development. However, little is known about jam-b2 expression and function. RESULTS: We isolated the cDNA of zebrafish jam-b2. jam-b2 is expressed specifically in extraocular muscles (EOMs), jaw muscles, and pectoral fins in zebrafish larvae, but not in trunk muscles. The identified jam-b2 expression pattern is supported by the analysis of a zebrafish Gal4-enhancer trap line, in which the coding sequence of the transcriptional activator KalTA4 together with a Gal4-dependent UAS-mCherry expression cassette was inserted into the jam-b2 locus. Intercrosses with an UAS:EGFP strain proves the possibility for targeting transgene expression to EOMs, jaw muscles and fins. Finally, we characterized the concerted contraction pattern of EOMs in larvae performing an optokinetic response. CONCLUSIONS: The expression pattern of jam-b2 suggests that it may contribute different properties to EOMs, jaw muscles, and pectoral fins. The jam-b2:KalTA4-UAS-mCherry transgenic strain serves a dual role as both a reporter for these muscles and as a valuable genetic tool for targeting transgene expression to EOMs.

DOI： 10.1002/dvdy.24347

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：4  

Homozygous mutations in the glucocerebrosidase (GBA) gene result in Gaucher disease (GD), the most common lysosomal storage disease. Recent genetic studies have revealed that GBA mutations confer a strong risk for sporadic Parkinson's disease (PD). To investigate how GBA mutations cause PD, we generated GBA nonsense mutant (GBA-/-) medaka that are completely deficient in glucocerebrosidase (GCase) activity. In contrast to the perinatal death in humans and mice lacking GCase activity, GBA-/- medaka survived for months, enabling analysis of the pathological progression. GBA-/- medaka displayed the pathological phenotypes resembling human neuronopathic GD including infiltration of Gaucher cell-like cells into the brains, progressive neuronal loss, and microgliosis. Detailed pathological findings represented lysosomal abnormalities in neurons and alpha-synuclein (α-syn) accumulation in axonal swellings containing autophagosomes. Unexpectedly, disruption of α-syn did not improve the life span, formation of axonal swellings, neuronal loss, or neuroinflammation in GBA-/- medaka. Taken together, the present study revealed GBA-/- medaka as a novel neuronopathic GD model, the pahological mechanisms of α-syn accumulation caused by GCase deficiency, and the minimal contribution of α-syn to the pathogenesis of neuronopathic GD.

DOI： 10.1371/journal.pgen.1005065

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

The red nucleus is located in the rostral midbrain of the vertebrate brain and controls motor coordination during locomotion. It receives input from the cerebellum and sends its output to the spinal cord. The presence of the red nucleus is well established in tetrapods, and its existence has also been suggested in teleosts but its presence and position has still been under discussion. By using wheat germ agglutinin (WGA) as a genetically encoded anterograde tracer, we recently identified contralateral projections from the cerebellum to a putative red nucleus in the zebrafish midbrain tegmentum. In this report we further revealed red nucleus derived from this contralateral afferent from the cerebellum using WGA and contralateral projections to the hindbrain-spinal cord junction site using DiI-mediated retrograde tracing. Thus the structure that we have identified by anterograde and retrograde tracing fulfills the anatomical demands for the red nucleus: the location in the midbrain tegmentum, contralateral afferent from the cerebellum (cerebello-ruber projection) and contralateral efferent to the spinal cord (rubro-spinal projection).

DOI： 10.4161/19420889.2014.994383

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：32  

There has been accumulating evidence for a regionalized organization of the cerebellum, which was mostly deduced from anatomical mapping of axonal projections of cerebellar afferents. A likewise regionalization of the cerebellar output has been suggested from lesion studies and dye-tracer experiments, but its physiological targets as well as the functional relevance of such an output regionalization are less clear. Ideally, such functional regionalization should be proven noninvasively in vivo. We here provide evidence for such a regionalization of the output from the cerebellar cortex by genetically encoded transneuronal mapping of efferent circuits of zebrafish Purkinje neurons. These identified circuits correspond to distinct regionalized Purkinje cell activity patterns in freely behaving zebrafish larvae during the performance of cerebellar-dependent behaviors. Furthermore, optogenetic interrogation of selected Purkinje cell regions during animal behavior confirms the functional regionalization of Purkinje cell efferents and reveals their contribution to behavior control as well as their function in controlling lateralized behavioral output. Our findings reveal how brain compartments serve to fulfill a multitude of functions by dedicating specialized efferent circuits to distinct behavioral tasks.

DOI： 10.1073/pnas.1403105111

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：2  

Teleost fish have recently been employed as a model for human neurodegenerative diseases. We used toxin exposure and genetic engineering to develop models of Parkinson's disease (PD) in the teleost fish, medaka. Among the toxins examined, 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), proteasome inhibitors, lysosome inhibitors, and tunicamycin all induced important features of PD in medaka. Specifically, these agents induced dopaminergic cell loss and reduced spontaneous movement, and the latter three toxins produced inclusion bodies that were ubiquitously distributed in the medaka brain. Despite the extensive distribution of these inclusion bodies, the middle diencephalic dopaminergic neurons were particularly susceptible to the effect of the toxins, suggesting that this cluster of dopaminergic neurons is analogous to the human substantia nigra. We have also created a variety of different genetic models using the Targeting Induced Local Lesions in Genomes (TILLING) method, and found that neither PTEN-induced putative kinase 1 (PINK1) mutants nor Parkin mutants disclosed significant dopaminergic cell loss. Surprisingly however, PINK1 and Parkin double mutants exhibited selective dopamine cell loss, as well as aggregation and deficit of mitochondrial activity. Another mutant, the ATP13A2 mutant, also expressed a PD phenotype, exhibiting marked cathepsin D reduction and fingerprint-like structures that are generally found in lysosome storage diseases. Taken together, these data indicate that medaka fish can serve as a new animal model for PD. In this review, we summarize our data and discuss the potential for future application of this animal model.

DOI： 10.3233/JPD-130289

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記述言語：英語   出版者・発行元：6  

OBJECTIVE: Loss of function mutations in PINK1 typically lead to early onset Parkinson disease (PD). Zebrafish (Danio rerio) are emerging as a powerful new vertebrate model to study neurodegenerative diseases. We used a pink1 mutant (pink(-/-) ) zebrafish line with a premature stop mutation (Y431*) in the PINK1 kinase domain to identify molecular mechanisms leading to mitochondrial dysfunction and loss of dopaminergic neurons in PINK1 deficiency. METHODS: The effect of PINK1 deficiency on the number of dopaminergic neurons, mitochondrial function, and morphology was assessed in both zebrafish embryos and adults. Genome-wide gene expression studies were undertaken to identify novel pathogenic mechanisms. Functional experiments were carried out to further investigate the effect of PINK1 deficiency on early neurodevelopmental mechanisms and microglial activation. RESULTS: PINK1 deficiency results in loss of dopaminergic neurons as well as early impairment of mitochondrial function and morphology in Danio rerio. Expression of TigarB, the zebrafish orthologue of the human, TP53-induced glycolysis and apoptosis regulator TIGAR, was markedly increased in pink(-/-) larvae. Antisense-mediated inactivation of TigarB gave rise to complete normalization of mitochondrial function, with resulting rescue of dopaminergic neurons in pink(-/-) larvae. There was also marked microglial activation in pink(-/-) larvae, but depletion of microglia failed to rescue the dopaminergic neuron loss, arguing against microglial activation being a key factor in the pathogenesis. INTERPRETATION: Pink1(-/-) zebrafish are the first vertebrate model of PINK1 deficiency with loss of dopaminergic neurons. Our study also identifies TIGAR as a promising novel target for disease-modifying therapy in PINK1-related PD.

DOI： 10.1002/ana.23999

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：12  

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by selective dopaminergic cell loss in the substantia nigra, but its pathogenesis remains unclear. The recessively inherited familial PD genes PARK2 and PARK6 have been attributed to mutations in the Parkin and PTEN-induced kinase 1 (PINK1) genes, respectively. Recent reports suggest that PINK1 works upstream of Parkin in the same pathway to regulate mitochondrial dynamics and/or conduct autophagic clearance of damaged mitochondria. This phenomenon is preserved from Drosophila to human cell lines but has not been demonstrated in a vertebrate animal model in vivo. Here, we developed a medaka fish (Oryzias latipes) model that is deficient in Pink1 and Parkin. We found that despite the lack of a conspicuous phenotype in single mutants for Pink1 or Parkin, medaka that are deficient in both genes developed phenotypes similar to that of human PD: late-onset locomotor dysfunction, a decrease in dopamine levels and a selective degeneration of dopaminergic neurons. Further analysis also revealed defects in mitochondrial enzymatic activity as well as cell death. Consistently, PINK1 and Parkin double-deficient MEF showed a further decrease in mitochondrial membrane potential and mitochondrial complex I activity as well as apoptosis compared with single-deficient MEF. Interestingly, these mitochondrial abnormalities in Parkin-deficient MEF were compensated by exogenous PINK1, but not by disease-related mutants. These results suggest that PINK1 and Parkin work in a complementary way to protect dopaminergic neurons by maintaining mitochondrial function in vertebrates.

DOI： 10.1093/hmg/ddt095

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：9  

Kufor-Rakeb syndrome (KRS) was originally described as an autosomal recessive form of early-onset parkinsonism with pyramidal degeneration and dementia. ATP13A2 was identified as the causative gene in KRS. ATP13A2 encodes the ATP13A2 protein, which is a lysosomal type5 P-type ATPase, and ATP13A2 mutations are linked to autosomal recessive familial parkinsonism. Here, we report that normal ATP13A2 localizes in the lysosome, whereas disease-associated variants remain in the endoplasmic reticulum. Cathepsin D activity was decreased in ATP13A2-knockdown cells that displayed lysosome-like bodies characterized by fingerprint-like structures. Furthermore, an atp13a2 mutation in medaka fish resulted in dopaminergic neuronal death, decreased cathepsin D activity, and fingerprint-like structures in the brain. Based on these results, lysosome abnormality is very likely to be the primary cause of KRS/PARK9.

DOI： 10.1016/j.febslet.2013.02.046

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：3  

The teleost fish has been widely used in creating neurodegenerative models. Here we describe the teleost medaka fish Parkinson's disease (PD) models we developed using toxin treatment and genetic engineering. 1-Methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), proteasome inhibitors, lysosome inhibitors and tunicamycin treatment in our model fish replicated some salient features of PD: selective dopamine cell loss and reduced spontaneous movement with the last three toxins producing inclusion bodies ubiquitously in the brain. Despite the ubiquitous distribution of the inclusion bodies, the middle diencephalic dopaminergic neurons were particularly vulnerable to these toxins, supporting the idea that this dopamine cluster is similar to the human substantia nigra. PTEN-induced putative kinase 1 (PINK1) homozygous mutants also showed reduced spontaneous swimming movements. These data indicate that medaka fish can serve as a new model animal of PD. In this review we summarize our previous data and discuss future prospects.

DOI： 10.5607/en.2012.21.3.94

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Perturbations in protein folding and degradation are key pathological mechanisms in neurodegenerative diseases, including Parkinson's disease (PD). Recent evidence suggests that mishandling of proteins may play an important role in the pathogenesis of PD. We have utilized medaka fish to monitor the effects of injecting neurotoxins into the CSF space. In this study, ammonium chloride, tunicamycin, and lactacystin were tested for their ability to disturb lysosomal proteolysis, N-glycosylation in the endoplasmic reticulum, and proteasomal degradation, respectively. All of the substances tested induced selective loss of dopaminergic neurons, movement disorders and inclusion bodies. Among them, the features of the inclusion bodies that developed after ammonium chloride injection mimicked those of PD: co-localization of ubiquitin and phosphorylated alpha-synuclein, as well as the presence of LC3 protein in the inclusion bodies. Our study demonstrated that medaka fish are useful for examining the effects of environmental toxins and lysosome inhibition, and lysosome inhibitors may be factors in the development

DOI： 10.1111/j.1471-4159.2010.07012.x

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL PUBLISHING, INC  

P&gt;Recent findings suggest that a defect in the ubiquitin-proteasome system plays an important role in the pathogenesis of Parkinson&apos;s disease (PD). A previous report (McNaught et al. 2004) demonstrated that rats systemically injected with proteasome inhibitors exhibited PD-like clinical symptoms and pathology. However, because these findings have not been consistently replicated, this model is not commonly used to study PD. We used medaka fish to test the effect of systemic administration of proteasome inhibitors because of the high level of accessibility of the cerebrospinal fluid in fish. We injected lactacystin or epoxomicin into the CSF of medaka. With proteasome inhibition in the medaka brain, selective dopaminergic and noradrenergic cell loss was observed. Furthermore, treated fish exhibited reduced spontaneous movement. Treatment with proteasome inhibitors also induced the formation of inclusion bodies resembling Lewy bodies, which are characteristic of PD. Treatment with 6-OHDA also induced dopaminergic cell loss but did not produce inclusion bodies. These findings in medaka are consistent with previous results reporting that non-selective proteasome inhibition replicates the cardinal features of PD: locomotor dysfunction, selective dopaminergic cell loss, and inclusion body formation.

DOI： 10.1111/j.1471-4159.2010.06918.x

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Parkinson&apos;s disease is a neurodegenerative disease associated with the degeneration of dopaminergic neurons in the substantia nigra. The PTEN-induced kinase 1 gene (PINK1) is responsible for recessive inherited familial Parkinson&apos;s disease (PARK6). Neither the function of PINK1 nor its role in the prevention of Parkinson&apos;s disease is fully understood. Gene disruption of PINK1 causes remarkably different phenotypes in animal models such as Drosophila melanogaster, zebrafish, and mouse, none of which recapitulate Parkinson&apos;s-disease-like symptoms. We established PINK1-gene-disrupted medaka fish. These mutant fish grew normally at first, then developed significant decrease in the frequency of spontaneous swimming movements in the late-adult stage. Although the mutants did not show any dopaminergic cell loss, the amount of 3,4-dihydroxyphenylacetic acid, a major metabolite of dopamine. decreased. Thus, PINK1 contributes to the maintenance of dopamine metabolism, even before the selective death of dopaminergic neurons. Our animal model is therefore a valuable tool to detect pathogenesis in Parkinson&apos;s patients in the early stages. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2009.10.010

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担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Parkinson&apos;s disease (PD) is the second most common neurodegenerative disease associated with the degeneration of dopaminergic neurons in the substantia nigra. To create a new model of PD, we used medaka (Oryzias latipes). a small teleost that has been used in genetics and environmental biology. We identified tyrosine hydroxylase (TH) immunopositive dopaminergic and noradrenergic fibers and neurons in the medaka brain. Following establishment of a method for counting the number of dopaminergic neurons and an assay for the evaluation of the medaka behavior. we exposed medaka to 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP). The treatment of medaka at the larval stage, but not at adult stage. decreased the number of dopaminergic cells in the diencephalon and reduced spontaneous movement, which is reminiscent of human PD patients and other MPTP-induced animal PD models. Among TH(+) neurons in the medaka brain, only a specific cluster in the paraventricular area of the middle diencephalon was vulnerable to MPTP toxicity. Detailed examinations of medaka transiently exposed to MPTP at the larval stage revealed that the number of dopaminergic cells was not fully recovered at their adult stage Moreover. the amounts of dopamine persistently decreased in the brain of these MPTP-treated fish MPTP-treated medaka is valuable for modeling human PD. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

DOI： 10.1016/j.neures.2009.07.010

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：DR DIETRICH STEINKOPFF VERLAG  

Objectives The pathophysiology of depression and anxiety in Parkinson's disease remains obscure. We aimed to compare the fractional anisotropy (FA) values of Parkinson's disease (PD) patients with and without depression to investigate the nature of depression in PD. Methods Twenty-eight patients were divided into two groups: those with depression and those without. Diagnosis of depression was made using the DSM-IV criteria. Patients in the two groups were matched for Hoehn Yahr stage. Results There were significant reductions in FA values in the bilateral frontal ROIs possibly representing anterior cingulate bundles. Conclusions The anterior cingulate bundles play an important role in depression in PD, and some aspects of depression in PD have pathological processes in common with de novo depression.

DOI： 10.1007/s00415-006-0236-6

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Objective - Dementia occurs frequently in patients with Parkinson's disease (PD). However, the nature of the dementing process remains controversial. We evaluated various cognitive functions in patients with PD, compared fractional anisotropy (FA) values between PD patients with and without dementia.
Methods - Thirty-seven consecutive patients with Hoehn-Yahr stage III or IV PD participated in this study. Patients were divided into two groups: (i) PD with dementia group (PDD) and (ii) PD without dementia group (PDND). There were 11 PDD and 26 PDND cases. Ten controls were also studied.
Results - The PDD group showed significant FA reduction in the bilateral posterior cingulate bundles compared with PDND. FA values in the left posterior cingulate bundle showed significant correlations with many cognitive parameters.
Interpretation - Our results showed that the posterior cingulate areas play some important roles in the dementing process in PDD. However, as the pathological processes responsible for dementia in PD patients may be multifaceted, further studies are necessary.

DOI： 10.1111/j.1600-0404.2007.00838.x

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Introduction - It is generally assumed that executive dysfunctions in Parkinson's disease (PD) are caused by degeneration of the basal ganglia or frontal cortex or both. However, there have been few studies investigating the relationship between executive dysfunctions and cerebral pathological change. The objective of this study was to evaluate various cognitive functions in non-demented patients with PD, and to compare the fractional anisotropy (FA) values of PD patients with and without executive dysfunction. Materials and Methods - Twenty-one consecutive non-demented patients with PD were enrolled in this study. Patients were divided into two groups on the basis of their Wisconsin Card Sorting Test score. Results - There was significant FA reduction in the left parietal white matter in the group in which the number of categories achieved was : 2 relative to the group that achieved &gt; 2. Conclusion - Accumulating evidence suggests that conventional 'frontal' tasks correlate with both frontal lobe and parietal lobe function, and we suggest that pathological changes in the left parietal lobe may cause, in part, disturbances in executive tasks in PD.

DOI： 10.1111/j.1600-0404.2006.00795.x

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background: Thrombosis involving a brain infarction frequently occurs in patients with a malignant tumor. Although nearly all types of tumor have been reported in association with a hypercoagulable state, pleural mesothelioma-associated Trousseau syndrome is extremely rare.
Summary: A 69-year-old female was admitted to our hospital with cough, sputum, and breathing difficulties. She was diagnosed as having a mesothelioma from a percutaneous pleural biopsy. Although there were no risk factors for atherosclerosis, brain infarctions showed frequent relapses, even under anticoagulant therapy, and there was a marked hypercoagulable state.
Conclusion: Attention should be paid to this syndrome when unexplained brain infarctions occur in patients with pleural mesothelioma.

DOI： 10.1097/01.nrl.0000253113.53846.ec

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Background: Nature of the dementing process in Parkinson's disease, and particularly its relationship with Alzheimer's disease, diffuse Lewy body disease or frontal dementia remains controversial.
Objective: We hypothesize that origins of dementia in Parkinson's disease are heterogeneous, so we compared cortical regional cerebral blood flow (rCBF) between Parkinson's disease patients with and without dementia.
Patients: Forty consecutive patients with Hoehn-Yahr stage III or IV Parkinson's disease were used (13 patients had dementia (PDD group), and 27 patients had no dementia (PDND group)).
Results: There were significant rCBF reductions in the left parietal association cortex and left frontal association cortex in PDD. Multiple logistic regression analysis demonstrated that only rCBF of the left frontal association cortex was significant. PDD patients were divided into three groups according to rCBF patterns: frontal hypoperfusion group, Alzheimer's disease-like group, and diffuse Lewy body disease-like group.
Conclusions: Controversial study results involving PDD patients may be mainly due to heterogeneity in dementing processes in Parkinson's disease. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.parkreldis.2006.10.005

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective We compared brain perfusion image using 3D-SSP analysis of I-123-IMP SPECT between Parkinson's disease patients with auditory verbal hallucination and those without auditory hallucination.
Methods Eighty-three cases with Parkinson's disease were studied. In 6 of these patients, auditory hallucination was noted. Among them, four cases had verbal hallucination and two other cases had elementary hallucination. Auditory hallucination was not found in the other 77 cases.
Results Right thalamic perfusion was significantly increased in the verbal hallucination group compared to the group that lacked auditory hallucination.
Conclusion In Parkinson's disease, the right thalamic hyperactive state may be related to verbal hallucination.

DOI： 10.2169/internalmedicine.46.0191

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Objective: Auditory P300 has been reported to be abnormal in demented patients with Parkinson's disease. However, it is still controversial which factors in Parkinson's disease influence P300 parameters. Methods: Forty patients with Parkinson's disease were included. Patients were divided into two groups: patients with dementia (PDD) and without dementia (PDND). An `odd-ball' paradigm was used for auditory event-related potentials. Results: P300 latency was markedly delayed in PDD patients. Age and DRSI (attention) were the most important factors influencing P300 latency. Conclusions: Although there have been reports of P300 in the past, its abnormalities reflect the deficit of attention in Parkinson's disease. (C) 2007 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.parkreldis.2006.12.012

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：NEUROL SOC INDIA  

DOI： 10.4103/0028-3886.28136

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

We examined patients with and without auditory hallucinations, using n-isopropyl-p-[I-123] iodoamphetarnine single photon emission computed tomographic imaging. We assessed verbal hallucinations in the present study: patients with nonverbal auditory hallucinations were excluded. A total of 11 patients with verbal and visual hallucinations and 17 patients with visual hallucinations only were enrolled. Patients with both verbal and visual hallucinations revealed significant hypoperfusion in the bilateral prefrontal cortex and right superior temporal gyrus compared to patients with visual hallucinations only. There were no significant hyperperfusion in patients with verbal plus visual hallucinations. These results may support the release hallucination theory in verbal hallucinations of Parkinson's disease, although another explanations may be more appropriate and further studies are required. (C) 2006 Movement Disorder Society.

DOI： 10.1002/mds.21147

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

Little is known about the developing mechanisms of visual hallucinations in Parkinson's disease. This study aimed to investigate perfusion changes in parkinsonian patients with visual hallucinations using n-isopropyl-p-[I-123]iodoamphetamine ([I-123]IMP) single photon emission computed tomography imaging. A total of 70 consecutive patients, including 31 patients with visual hallucinations, and 39 patients without hallucinations, participated in this study. Patients with severe cognitive impairment (Mini-Mental State Examination score &lt; 20), nonvisual hallucinations, or confusion were excluded. We compared brain perfusion changes between the two groups. We found that hallucinatory patients had significant perfusion reductions in the bilateral inferior parietal lobule, inferior temporal gyrus, precuneus gyrus, and occipital cortex compared to nonhallucinatory patients. These results suggested that hypoperfusion of the visual pathway was closely related to visual hallucinations in Parkinson's disease. (C) 2006 Movement Disorder Society.

DOI： 10.1002/mds.21140

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

Depression is common in individuals with Parkinson's disease. However, the pathophysiology of depression in Parkinson's disease remains obscure. Here we compared brain perfusion images of Parkinson's disease patients with and without depression to investigate correlations between depression and brain perfusion images in Parkinson's disease. We divided 40 consecutive patients with Parkinson's disease into two groups: patients with minor depression (n = 22) and patients without depression (n = 18). We then compared brain perfusion images between the two groups. As a result, hypoperfusion of the left superior and inferior frontal gyrus was demonstrated in depressed patients. These results were partially in agreement with previous studies on de novo and parkinsonian major depression. We could not conclude on whether pathophysiological mechanisms differed between de novo depression and depression with Parkinson's disease, and between major and minor depressions. (C) 2006 Movement Disorder Society.

DOI： 10.1002/mds.20923

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ACADEMY SLEEP MEDICINE  

Study Objectives: The underlying pathologic mechanism of excessive daytime sleepiness (EDS) in Parkinson disease and the relative contributions of brain function to this process are poorly understood. We compared brain perfusion images between patients with Parkinson disease and EDS and those without EDS using n-isopropyl-p-123I iodoamphetamine single photon emission computed tomography. Design: Clinical study. Setting: Sumitomo Hospital. Patients: Thirteen patients with Parkinson disease with EDS (EDS group) and 27 patients with Parkinson disease without EDS (no-EDS group) were studied. Whether or not each case had EDS was determined according to the response to the Epworth Sleepiness Scale: patients with an Epworth Sleepiness Scale score &gt;= 10 were included in the EDS group, and patients with an Epworth Sleepiness Scale score :5 9 were included in the no-EDS group. Measurements and Results: There were significant hypoperfusions in the left parietal and temporal association cortex in the EDS group, In the multivariable logistic regression model, attention and decreased regional cerebral blood flow of the left parietal association cortex and right caudate and increased regional cerebral blood flow of the right thalamus were the independent and significant factors. Conclusions: The cortical hypofunction relative to hyperfunction of the brain stem may relate to EDS in Parkinson disease. This is the first imaging study about EDS in Parkinson disease, and further studies are required.

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS INC  

The objective was to compare brain perfusion image using 3-dimensional stereotactic surface projection analysis of N-isopropyl-p-I-123 iodoamphetamine single photon emission computed tomography between Parkinson's disease patients with a high frontal assessment battery score and those with a low frontal assessment battery score. Thirty nondemented patients with Parkinson's disease were studied. Patients were divided into 2 groups: a high-scoring group whose frontal assessment battery score was 12 or more and a low-scoring group whose frontal assessment battery score was 11 or less. The high-scoring group included 21 patients, and the low-scoring group included 9 patients. They underwent N-isopropyl-p-I-123 iodoamphetamine single photon emission computed tomography, and we analyzed the data by the 3-dimensional stereotactic surface projection method. Results showed that left inferior parietal lobule and left supramarginal gyrus perfusion of the low-scoring group were significantly decreased compared with the high-scoring group. It is concluded that-patients with Parkinson's disease may have frontal lobe dysfunction, but the decreased frontal assessment battery score may be caused not by progressed frontal lobe dysfunction but by parietal lobe dysfunction added to their preexisting frontal lobe impairment.

DOI： 10.1177/0891988705284714

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NEUROL SOC INDIA  

We described a 69-year-old woman with neurological manifestations due to mixed connective tissue disease (MCTD). The patient demonstrated subacute cognitive decline, seizure and gait disturbance with no connective tissue manifestation. She had been diagnosed with dementia at another hospital, later in our hospital, serological examinations disclosed high titers of anti-RNP antibody. Cognitive dysfunction in this patient was dramatically ameliorated by steroid therapy. Three months later, she developed edema of the hands, synovitis and acrosclerosis. The patient was finally diagnosed as having MCTD. We emphasized MCTD as a rare cause of "treatable dementia".

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background: Peripheral neuropathy with adult T-cell leukemia/ lymphoma (ATLL) has seldom been reported.
Review Summary: A 69-year-old woman with smoldering-type ATLL presented with pain and muscle weakness of the bilateral upper and lower limbs and gait disturbance. Anti-human T lymphotropic virus type I antibody was positive in the serum but negative in the cerebrospinal fluid. Magnetic resonance imaging (MRI) showed no abnormal signals in the spinal cord or brain. Nerve conduction Studies disclosed severe peripheral neuropathy. Sural nerve biopsy disclosed both axonal degeneration and demyelinated fibers, and marked perivascular inflammatory infiltrates mainly consisting of T lymphocytes without malignant changes were seen. Steroid therapy was markedly effective, and the patient became able to walk without assistance.
Conclusions: This is the first reported case of ATLL and peripheral neuropathy in which a nerve biopsy was performed. In our patient, the marked perivascular inflammatory infiltrates mainly consisting of T lymphocytes suggested either immune-mediated vasculitis or tumor invasion. Further studies are needed.

DOI： 10.1097/01.nrl.0000202598.81422.36

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE PUBLICATIONS INC  

Pathophysiology of hallucinations in Parkinson's disease is poorly understood. This study investigated relationships between visual hallucinations and visual acuity. Twenty-six consecutive patients with Parkinson's disease participated in this study. Patients were divided into two groups: patients with visual hallucinations (VH group) and those without visual hallucinations (no-VH group). Unaided and corrected eyesight was evaluated in all patients, and if frequent use of prescription glasses or contact lenses was involved, eyesight using these lenses was also measured as the patient's own best eyesight. If a patient did not use prescription glasses or contact lenses, the patient's own best eyesight was defined as the unaided eyesight. Multivariate regression analysis demonstrated that agonist use and best eyesight were different after the backward elimination method. Visual hallucinations were closely related not to uncorrected eyesight or unaided eyesight but to the patient's best eyesight. It is suggested that impaired visual acuity is a risk factor for visual hallucinations.

DOI： 10.1177/0891988705284739

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Background: Few imaging studies investigated frontal dysfunctions in Parkinson's disease.
Objectives: We investigated relationships between Wisconsin Card Sorting Test (WCST) and brain perfusion in patients with non-demented Parkinson's disease.
Methods: Patients were divided into two groups according to WCST score: (1) CA (number of category achieved) &lt;= 2 or (2) CA &gt;= 3. We performed three-dimensional stereotactic surface projection and volume of interest analysis using I-123-IMp scintigraphy.
Results: Hypoperfusions of the bilateral posterior cingulate, rostrodorsal prefrontal, and left frontopolar cortices were shown in CA &lt;= 2 group, with the left cingulate and right rostrodorsal prefrontal cortices showing prominent hypoperfusion. CA and PE (perseverative errors) scores significantly correlated with perfusion of the left posterior cingulate cortex. PE score also correlated with perfusion of the right rostrodorsal prefrontal cortex.
Conclusion: Data indicated participations of various regions in task achievement. Careful interpretation of WCST scores is required. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.parkreldis.2005.12.006

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：American Psychiatric Publishing Inc.  

DOI： 10.1176/jnp.18.1.130

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

DOI： 10.1016/j.parkreldis.2006.05.020

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Background: Although excessive daytime sleepiness (EDS) in Parkinson's disease (PD) has received a great deal of attention, the underlying pathological mechanism of its development and the relative contributions of brain function to this process are poorly understood.
Objective: To compare the fractional anisotropy (FA) values of PD patients with EDS and those without EDS, and to investigate the mechanism of EDS in this disease.
Methods: Eleven patients with PD with EDS, 26 patients with PD without EDS and 10 controls participated in this study. Patients with an ESS (Epworth Sleepiness Scale) score &gt;= 10 were defined as having EDS. The FA values of 5 regions of interest (ROI) including the fornix were compared between the three groups.
Results: There were significant reductions in FA values of the fornix fiber in patients with EDS. ESS scores had significant correlation with FA values of the fornix.
Conclusions: Our study is the first to find the fornix fiber degeneration in PD patients with EDS. These results indicate that fornix dysfunction may have some correlations with EDS in PD. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.parkreldis.2006.01.007

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Objectives: To compare MIBG (metaiodobenzylguanidine) uptake between Parkinson's disease patients with and without autonomic symptoms to investigate meanings of MIBG scintigraphy and correlations between autonomic symptoms and MIBG uptake.
Methods: Forty consecutive patients with Hoehn-Yahr III or IV Parkinson's disease and 12 controls were enrolled. We compared cardiac MIBG uptake between patients with and without orthostatic hypotension. Similar comparisons were performed for constipation and bladder dysfunction.
Results: MIBG uptake did not significantly correlate with age, disease duration, Hoehn-Yahr stage, Unified Parkinson's Disease Rating Scale (UPDRS) motor score or levodopa equivalent daily doses. There were no significant correlations between orthostatic hypotension/constipation and cardiac MIBG uptake. Only bladder symptoms significantly correlated with MIBG uptake.
Conclusion: Meanings of MIBG uptake abnormalities in Parkinson's disease and relationship between MIBG uptake and clinical parameters remain to be resolved in future studies. (c) 2006 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.parkreldis.2005.12.008

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-LISS  

Gait disturbance is a cardinal symptom in patients with Parkinson's disease. Among the gait disturbances, freezing of gait is a unique and troublesome symptom, but its mechanism is unclear. We compared brain perfusion images using three-dimensional stereotactic surface projection analysis of N-isopropyl-p-(123)] iodoamphetamine single photon emission computed tomography between Parkinson's disease patients with freezing of gait and those without. Twenty-four cases (freezing of gait group) with Parkinson's disease with freezing of gait, and 31 Hoehn and Yahr stage-matched cases (no freezing of gait group) with Parkinson's disease without freezing of gait were studied. Bilateral Brodmann area I I perfusion of the freezing of gait group decreased significantly compared to that of the no freezing of gait group. The Brodmann area 11 may play important roles in gait, and impairment in this region may have a close relationship with freezing of gait in Parkinson's disease. (c) 2005 Movement Disorder Society.

DOI： 10.1002/mds.20520

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Background Intellectual deterioration occurs in 10-40% of patients with Parkinson's disease. However, there are many conflicting studies on its relation with brain perfusion and the nature of this dementing process remains controversial.
Objective To compare cortical perfusion by SPECT using I-123-IMP between Parkinson's disease patients with dementia and those without dementia and to investigate the correlation between dementia in Parkinson's disease and brain perfusion in various areas.
Methods Fifty-two cases of Parkinson's disease and 10 control cases were studied. The Parkinson's disease with dementia group included 30 cases and the Parkinson's disease without dementia group included 22 cases. Results By multiple logistic regression method, we demonstrated significant hypoperfusion in the occipital cortex in Parkinson's disease with dementia.
Conclusions The cause of dementia in Parkinson's disease may vary. We demonstrated that occipital hypoperfusion was closely correlated to dementia in Parkinson's disease compared to frontal, parietal and temporal perfusion.

DOI： 10.2169/internalmedicine.44.1046

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

A 27-year-old woman was admitted to our hospital with tetraparesis, dysesthesia and hypoesthesia of all regions below the breasts, urinary disturbance, and difficulty in breathing. Since age 21 idiopathic thrombocytopenic purpura (ITP) was diagnosed and steroid therapy was continued. At age 26, she had splenectomy for her ITP. On admission, steroid pulse therapy was administered with a tentative diagnosis of transverse myelitis. Symptoms gradually ameliorated. At age 29, she gradually lost her left vision, and multiple sclerosis was diagnosed and steroid therapy was administered, and her left vision gradually ameliorated. There are several reports describing other autoimmune disorders that arise after splenectomy. Since the spleen acts as a major pool of type 2 helper T cells, it is plausible that peripheral type 1 helper T cell activity may increase after splenectomy, promoting the development of autoimmune disorders. We considered there would be a close relation between splenectomy for ITP and multiple sclerosis in this case.

DOI： 10.2169/internalmedicine.44.747

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BLACKWELL PUBLISHING  

Objective - To compare brain perfusion image using three-dimensional stereotactic surface projection (3D-SSP) analysis of N-isopropyl-p-I-123 iodoamphetamine (I-123-IMp) single photon emission computed With tomography (SPECT) between patients with Parkinson's disease orthostatic hypotension and those without orthostatic hypotension. Materials and methods -Fifteen patients with Parkinson's disease and orthostatic hypotension and 13 patients with Parkinson's disease without orthostatic hypotension were studied. We compared brain perfusion image between the two groups by 3D-SSP. Results-Bilateral anterior cingulate gyrus perfusion of the patients with orthostatic hypotension was significantly decreased compared to that of the patients without orthostatic hypotension. Conclusions - The disorder of anterior cingulate gyrus may participate in the autonomic failure in Parkinson's disease.

DOI： 10.1111/j.1600-0404.2005.00427.x

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Background: The patterns of regional cerebral blood flow in Parkinson's disease and multiple system atrophy remain inconsistent.
Objectives: To compare brain perfusion images of I-123-IMP SPECT between Parkinson's disease, multiple system atrophy with predominant parkinsonian features (MSA-P) and controls.
Methods: Eighty-two patients with Parkinson's disease, 10 patients with MSA-P and 14 controls were studied. We performed 3D-SSP and volume of interest analysis using I-123-IMP scintigraphy.
Results: Occipital perfusion of MSA-P increased compared to that of Parkinson's disease and perfusion in the cerebellum and primary sensorimotor cortex of Parkinson's disease increased compared to that of MSA-P. Perfusion in the putamen of MSA-P decreased compared to that of Parkinson's disease.
Conclusion: Our study demonstrated perfusion differences in I-123-IMP SPECT between the two diseases. &COPY; 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.parkreldis.2005.01.001

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPANESE SOCIETY NUCLEAR MEDICINE  

Background: Decreased cardiac metaiodobenzylguanidine (MIBG) uptake was reported in Parkinson's disease and this contributes to the differential diagnosis between Parkinson's disease and other forms of parkinsonism such as multiple system atrophy. However, decreased MIBG uptake of the thyroid has not been demonstrated. Objective: To compare MIBG uptake of the thyroid among Parkinson's disease, multiple system atrophy and controls. Methods: Twenty-six patients with Parkinson's disease, 11 patients with multiple system atrophy and 14 controls were examined in this study. Planar images were taken 15 minutes (early images) and 3 hours (late images) after intravenous injection of 111 MBq 123 I-MIBG. Results: MIBG uptake of the thyroid on early images decreased significantly in Parkinson's disease compared to controls (p &lt; 0.0001) and multiple system atrophy (p = 0.018). MIBG uptake of the thyroid on early images decreased significantly also in multiple system atrophy compared to controls (p = 0.027). On late images, thyroid uptake differed significantly only between Parkinson's disease and controls (p = 0.010). Conclusions: Our study is the first to demonstrate decreased MIBG uptake of the thyroid in Parkinson's disease. Sympathetic nervous denervation of Parkinson's disease occurred not only in the heart but also in the thyroid.

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.44.507

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

We compared MIBG uptake at various parts of the body in controls and patients with Parkinson's disease and multiple system atrophy. In the heart, MIBG uptake in Parkinson's disease (early H/N4: 1.668 0.325, late HIM: 1.500 &PLUSMN; 0.402) was less than that in multiple system atrophy (early H/M: 2.395 &PLUSMN; 0.186, late H/M: 2.530 &PLUSMN; 0.391) and controls (early H/M: 2.635 &PLUSMN; 0.508, late H/M: 2.575 &PLUSMN; 0.635) (early: P &LT; 0.0001, late: P &LT; 0.0001). There were no significant differences in uptake by the lung, thyroid, or liver in the three groups. Only on early images, uptake in the shoulder in multiple system atrophy (early S/M: 0.473 &PLUSMN; 0.78) and Parkinson's disease (early S/M: 0.470 &PLUSMN; 0.710) was decreased compared to that in controls (early SIM: 0.560 &PLUSMN; 0.118) (P = 0.0252). MIBG is reported to be taken up in the terminal part of sympathetic nerves and demonstrates sympathetic nerve activity, especially on late images. The cause of differences between the heart and other parts of the body remains unknown. We consider the following possibilities: (a) differences in the sympathetic nervous system between Parkinson's disease and multiple system atrophy are more subtle in organs other than the heart; (b) the cause of MIBG uptake reduction by the heart in Parkinson's disease involves factors in addition to sympathetic nervous system damage; and (c) MIBG uptake by organs other than the heart involves not only the sympathetic nervous system but also non-neuronal components. In conclusion, MIBG uptake by organs other than the heart cannot differentiate Parkinson's disease from multiple system atrophy at present. &COPY; 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.autneu.2005.03.003

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担当区分：筆頭著者,　責任著者   記述言語：英語   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Objective: The pathophysiology of hallucinations in Parkinson disease is poorly understood. This study investigated the relation between visual hallucination and visual evoked potentials (VEPs) in Parkinson disease.
Methods: Nineteen patients with Parkinson disease were studied. The authors divided patients into 2 groups: patients with visual hallucinations (VH group) and those without visual hallucinations (no-VH group). VEPs using a checkerboard stimulus were recorded under a drug-five state.
Results: On multivariate regression analysis, only the average P100 latency was selected and remained significant after the backward elimination method.
Conclusion: The authors demonstrated a close association between visual hallucinations and elongated VEP latency in Parkinson disease. VEPs may become one of the predictors for visual hallucination.

DOI： 10.1097/01.wnf.0000157066.50948.65

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

POEMS syndrome is a syndrome that presents with polyneuropathy, organomegaly, endocrinopathy, M-proteins and skin changes. Elevated vascular endothelial growth factor (VEGF) has recently been reported in POEMS syndrome. We report a case of POEMS syndrome with high VEGF titers. Steroid, plasmapheresis and intravenous gamma-globulin had little effect. Various immunosuppressive agents were discontinued due to side effects. Although administration of aspirin did not decrease VEGF, ticlopidine decreased VEGF significantly. This case suggests that ticlopidine is a candidate for supportive therapy in POEMS syndrome and we should measure VEGF before and after the administration of ticlopidine in other cases.

DOI： 10.2169/internalmedicine.43.1082

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担当区分：筆頭著者,　責任著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report two cases of Parkinson's disease in which visual hallucinations disappeared after cataract surgery. Patient 1 was a 72-year-old woman with Parkinson's disease, visual hallucinations and musical hallucinations. Patient 2 was a 77-year-old woman with Parkinson's disease and visual hallucinations. Both patients had severe bilateral cataracts. Though it was difficult to control their visual hallucinations with medication only, cataract surgery made them disappeared quickly. The visual hallucinations of Parkinson's disease are similar to those of Charles Bonnet syndrome. For example, both hallucinations often happen in dim light, at night and when patients are awake with eyes open. Though there have been many reports describing visual hallucinations in Parkinson's disease, there have been few reports discussing the relation between these hallucinations and impaired visual acuity. Similar to the hallucinations of Charles Bonnet syndrome, impaired visual acuity should be related to the visual hallucinations of Parkinson's disease. When Parkinson's disease, visual hallucinations and severe cataract coexist, visual hallucinations may disappear after cataract surgery.

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記述言語：日本語   出版者・発行元：(株)ニュー・サイエンス社  

αシヌクレインは特にパーキンソン病の病態を考える上で重要な分子である。αシヌクレインが病原性を獲得する上で、何らかの翻訳後修飾が関与している可能性がある。ここではリン酸化にしぼって、その意義、そして今後の課題を概説する。(著者抄録)

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

パーキンソン病(PD)の病態を明らかにし、その治療方法を検索するにあたって、ヒト患者さんの臨床所見、病理所見、画像所見などが重要であることはいうまでもない。それに加えて病態をより深く解析し理解するために、in vitro、培養細胞、さまざまなモデル動物も重要な役割を果たしている。著者らは小型魚類を利用してPDの病態解明に取り組んでいる。本稿では、毒物への曝露、遺伝子改変を用いたさまざまな小型魚類モデルを紹介し、その有用性について議論する。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00060&link_issn=&doc_id=20170808020011&doc_link_id=%2Faa7ayuma%2F2017%2F026206%2F012%2F0635-0640%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa7ayuma%2F2017%2F026206%2F012%2F0635-0640%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公財)パブリックヘルスリサーチセンター  

DOI： 10.5058/stresskagakukenkyu.31.88

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記述言語：日本語   出版者・発行元：(株)クバプロ  

2006年頃に小型魚類を神経精神疾患モデルとして利用し始めた。日本ではゼブラフィッシュに加えてメダカを用いている研究者も多い。小型魚類は小型でありながらも脊椎動物であり、特にその稚魚は透明で、中枢神経系を含めた内部構造の観察が容易である。また、多種多様であるなどの利点がある。小型魚類を用いた神経精神疾患研究について、どのような利点や欠点があるか述べた。

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記述言語：日本語   出版者・発行元：(公財)金原一郎記念医学医療振興財団  

DOI： 10.11477/mf.2425200581

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00731&link_issn=&doc_id=20170206050019&doc_link_id=10.11477%2Fmf.2425200581&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.2425200581&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J05233&link_issn=&doc_id=20160308180001&doc_link_id=%2Fai1parkd%2F2016%2F000901%2F001%2F0005-0013%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai1parkd%2F2016%2F000901%2F001%2F0005-0013%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公財)上原記念生命科学財団  

シナプス後膜に存在するAMPA型グルタミン酸受容体(AMPA-R)を特異的に可視化することにより、シナプスの可塑的かつ動的な変化について検討した。シナプスの可塑的な変化を半定量的に可視化するために、Postsynaptic densityprotein 95(PSD95)とAMPA-Rの間接的な相互作用を利用した。ラット神経初代培養細胞において、様々な切断部位によるsplit VenusをGluA1およびPSD95に付加し、Venus再構築シグナルを経時的に比較した。ある特定のVenus切断断片を利用する場合でのみ、chemical LTP(Long-term potentiation)やchemical LTD(Long-term depression)を鋭敏に反映することが可能であった。このVenus再構築は、GluA1のCTDあるいはPSD95のPDZドメインを欠損させた場合、著明に阻害された。TARP γ-8のdelta4変異体では、複合体形成が阻害されるが、この場合もVenus再構築のシグナルは減少した。

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(公社)日本生化学会  

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記述言語：日本語   出版者・発行元：(株)北隆館  

パーキンソン病は黒質ドパミン神経の変性などを来す神経変性疾患であり、未だ原因不明である。様々な動物モデルが作製され、その病態の理解に貢献している。著者らは小型魚類の可視性と小型のサイズに注目し、パーキンソン病の小型魚類モデルを多数作製してきた。ここではそれらの概要を紹介し、病態の解明や治療薬の開発に向けた今後を展望する。(著者抄録)

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記述言語：英語  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：Movement Disorder Society of Japan (MDSJ)  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：東京生化学研究会  

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記述言語：日本語   出版者・発行元：順天堂医学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：順天堂医学会  

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：(株)ニュー・サイエンス社  

小型魚類のメダカとゼブラフィッシュは古くから発生や生殖の研究などに利用されてきたモデル動物である。遺伝情報が整備され、また遺伝子改変がいくつかの方法で可能ないま、これら小型魚類の遺伝子改変を疾患モデルにも応用しようとする試みがなされている。果たして既存のモデル動物ではなしえない疾患の病態解明や治療に魚類はたどりつけるのだろうか。本解説では筆者がパーキンソン病モデルとして利用しているメダカを中心に現状を概説する。(著者抄録)

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-LISS  

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記述言語：英語   出版者・発行元：日本神経化学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2010.07.080

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：WILEY-LISS  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)金芳堂  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J04871&link_issn=&doc_id=20090416340013&doc_link_id=10.11477%2Fmf.1416100469&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1416100469&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：4  

Parkinson's disease (PD) is the second most common neurodegenerative disease. It is associated with the degeneration of dopaminergic neurons in the substantia nigra pars compacta and other areas of the brain. The pathology of PD is characterized by the accumulation of a cytoplasmic fibrillar structure, wherein α-synuclein is the major component. Most occurrences of PD were believed to be sporadic and associated with aging and environmental stress. However, there is now strong evidence for genetic inheritance in a small number of families. Although the pathological mechanisms of PD are still largely unknown, we present the major hypotheses and discuss the future directions of studies in this area.

Scopus

PubMed

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2009.09.557

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：共立出版(株)  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER IRELAND LTD  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)羊土社  

家族性(遺伝性)パーキンソン病(PD)では次々と原因遺伝子が同定されているが、本稿ではPINK1,DJ-1,LRRK2について概説する。PINK1,DJ-1はミトコンドリア機能に関与し、アポトーシスや各種ストレスに保護的に機能をもつ。変異体ではその生理的機能が失われ、ミトコンドリア機能喪失に伴うPD発症が考えられる。LRRK2の疾患関連の変異体ではキナーゼ活性の上昇や細胞毒性が観察されgain of functionによる発症が考えられる。PINK1,DJ-1はミトコンドリア機能障害仮説を支持するという点で、LRRK2変異は家族性および孤発性PDにおいて頻度が高いという点で特に興味深く、今後の研究が待たれる。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一財)住友病院  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

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記述言語：日本語   出版者・発行元：(一財)住友病院  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

症例は55歳男性。51歳時に浸潤性胸腺腫と診断されたが、既に左肺、心膜に浸潤しており手術において完全切除は困難であった。2004年8月頃から全身倦怠感、発汗過多、筋肉のこわばりが出現し徐々に悪化。症状に日内変動はなく睡眠時にも持続した。当科紹介され10月入院、入院時undulating muscle movementがあり、全身の筋肉にこわばりを認めた。明らかな末梢神経障害は認めなかった。Anti-AChR antibody:200nmol/Lと高値(Anti-VGKC antibodyは未測定)。反復刺激試験で眼輪筋にてwaningを認めた。表面筋電図でGastrocnemius muscleやDorsal interosseous muscleにmyokymiaを認めた。Isaacs' syndromeと考え血漿交換療法を行ったところ徐々に症状は軽減した。Isaacs' syndromeは稀な症候群であり考察も加えて報告する。(著者抄録)

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記述言語：日本語   出版者・発行元：(一財)住友病院  

パーキンソン病では運動症状だけでなく自律神経症状、精神症状などが多種多様に高頻度で出現する。なかでも精神症状は特異であり、様々な症状について自験例および文献をもとにして述べた。精神症状に関してはしばしば薬物との関連が強調されるが、実際には他の要因の関与のほうが大きいことが少くない。精神症状が問題となる場合には、個々の症例においてリスク要因を検討し、是正できるものを是正していく必要がある。また発症機序は何れも未だ不明であり今後の研究が必要である。(著者抄録)

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記述言語：日本語   出版者・発行元：(一財)住友病院  

35歳男性、虚血によって視神経障害を起こし後に脳梗塞を発症した1例を提示する。突然、右優位の両眼の羞明、吐気、右眼痛、右後頭部痛を発症。MRIT2強調像、拡散強調像では病変は描出できなかったがSTIR法では右の視神経病変が描出された。STIR法は眼窩の脂肪を抑制し化学シフトを減少させることで視神経病変が描出となる。STIR法は視神経炎、多発性硬化症などで有用であるとの報告が相次いでいるが、梗塞や虚血による視神経障害についての報告は少ない。STIR法は虚血性病変にも有用である可能性があり今後の検討が待たれる。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(株)南江堂  

65歳男.糖尿病,高血圧で通院中であった.起床時より突然両下肢が動かないことに気がつき,入院した.高血圧以外には異常を認めず,心房細動を含め不整脈は認めなかった.上肢の筋力は正常であったが,下肢は両下肢とも弛緩性の麻痺が存在した.Babinski反射は両側陽性であった.下肢の振動覚は中等度低下した.軽度の貧血と慢性腎不全を認めた.頭部MRIでは右の内包後脚および左の中心前回および中心後回に多発性の新鮮な梗塞を認めた.頭部精査で右の内包後脚および左の中心前回と中心後回に多発性の新鮮な梗塞を認めた.これが原因と考え,aspirinおよび補液による治療を継続した.徐々に軽快し退院した

J-GLOBAL

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2006&ichushi_jid=J00974&link_issn=&doc_id=20060111120035&doc_link_id=10.15106%2FJ00974.2006127547&url=https%3A%2F%2Fdoi.org%2F10.15106%2FJ00974.2006127547&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)南江堂  

76歳女.1ヵ月前に出現した首下がりが徐々に増悪した.頸部背屈力の低下を認めたが,他に異常所見はなかった.頸部MRIでは頸椎性変化をC4〜C6レベルに認め,表面筋電図では僧帽筋の活動増加を認めたが,胸鎖乳突筋の活動は正常であった.針筋電図では頭板状筋に線維自発電位と陽性鋭波を強く認めた.1年間の経過観察を行ったところ他の筋に症状が出ることはなく,首下がりは頸椎症によるものと診断した

CiNii Article

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2005&ichushi_jid=J00974&link_issn=&doc_id=20051025020033&doc_link_id=issn%3D0022-1961%26volume%3D96%26issue%3D5%26spage%3D975&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D96%26issue%3D5%26spage%3D975&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)南江堂  

46歳女.咳,後頸部痛,両上肢のふるえが出現し,自然経過で約2週間で消失した.咳が再度出現し,後頸部痛悪化し,両上肢のふるえも再度出現した.頸部MRIでC6/7椎体レベルに椎間板ヘルニアを認めた.脳波,視覚誘発電位,聴性誘発反応,末梢神経伝導速度,感覚誘発電位には異常を認めなかった.diazepam,loxoprofenを適宜使用し疼痛に対処したが,軽度の効果をみるのみであった.ミオクローヌスはdiazepam処方後もしばらく変化はなかったが,咳が軽快してくるとともにミオクローヌスも軽減し,咳とともに消失した.その後も後頸部痛は軽快するものの残存し続けた

CiNii Article

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2005&ichushi_jid=J00974&link_issn=&doc_id=20050928110035&doc_link_id=issn%3D0022-1961%26volume%3D96%26issue%3D4%26spage%3D792&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D96%26issue%3D4%26spage%3D792&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)南江堂  

56歳男性.患者は四肢のしびれ,両下肢の筋力低下を主訴に近医を受診,頸髄MRIにてC4〜C5レベルのT2高信号域を指摘され,著者らの施設へ入院となった.入院時,一般理学所見,皮膚所見,神経学的所見に異常はみられず,両下肢の筋力低下および筋萎縮を認めた.全血・生化学・甲状腺機能に異常はなく,抗カルジオリピン抗体と抗RNP抗体は血清で陽性であったが,髄液中では陰性であった.再発性髄膜炎と診断し,ステロイドパルス療法を行ったところ,症状および画像所見の軽快がみられた.症状軽快時の血清中の抗カルジオリピン抗体,抗RNP抗体は変化なく陽性で,更に髄液では抗カルジオリピン抗体が陽性化した

CiNii Article

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2005&ichushi_jid=J00974&link_issn=&doc_id=20050823170038&doc_link_id=issn%3D0022-1961%26volume%3D96%26issue%3D3%26spage%3D593&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D96%26issue%3D3%26spage%3D593&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(株)南江堂  

61歳男.約5年前から高血圧と気管支喘息で降圧薬を内服中,右方視時に複視を認め,脳梗塞の疑いで入院となった.入院後は複視,眼球運動障害共に消失し,血管炎を考慮し各種検査及び全身検索を行っていた.入院4日後,18時10分に食事中のところを確認されていたが,18時30分に腹臥位で心肺停止状態で発見され,蘇生処置を行うも効果なく死亡が確認された.遺族の了承と同意を得て病理解剖を行った結果,肉眼所見では急性大動脈解離を認め,死因と考えられた.顕微鏡学的所見では大動脈に巨細胞を含む炎症細胞浸潤がみられ,巨細胞動脈炎と診断した.炎症細胞浸潤は頭蓋内の左内頸動脈にもみられた

CiNii Article

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2005&ichushi_jid=J00974&link_issn=&doc_id=20050725470033&doc_link_id=issn%3D0022-1961%26volume%3D96%26issue%3D2%26spage%3D383&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D96%26issue%3D2%26spage%3D383&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：(一財)住友病院  

59歳男性.患者は両大腿前面の強い疼痛を伴うしびれ感が次第に両下肢全体に拡大し,更に両前腕にも軽いしびれ感が出現,受診となった.電気生理学的検査では両側正中神経の終末潜時の遅延,両側脛骨神経のF波潜時の遅延,下肢体性感覚誘導電位で両側P40潜時の遅延を認め,画像検査が予定されていたが,臍下より両下肢へのしびれが強くなり歩行障害,膀胱直腸障害,右腰部痛を認め緊急入院となった.入院時,痙性歩行をはじめ片足立ちは両側不可能で,深部腱反射は右下肢で亢進,腹壁反応は消失,両側性にBabinski徴候,右下肢の振動覚低下,左下肢の温痛覚低下,排尿障害,便秘を認めた.胸髄MRIでは第11〜12胸椎レベルで両側の黄色靱帯が肥厚して低信号を呈し,正中型の椎間板ヘルニアを伴う著しい脊柱管の狭小化を認め,T2強調で髄内の高信号変化が確認された.一方,CTでは黄色靱帯の骨化を認め,黄色靱帯骨化症と診断し,手術適応と考え,以後,整形外科へ転科となった

J-GLOBAL

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記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

著者らの施設において1991〜2004年までに診療が開始された重症筋無力症症例について,その病型分類と眼輪筋における反復刺激試験を,追跡可能な範囲で検討した.1)分類はMGFA(Myasthenia Garvis Foundation of America)のclassificationにより,I型20例,II型24例が存在した.2)I型の眼輪筋の反復刺激試験(1例施行せず)でwaningを認めた群(12例)では,認めない群(7例)に比し,年齢・抗アセチルコリン受容体抗体価が有意に高かったが,眼輪筋におけるwaningの有無では治療後の経過に有意差を認めなかった.3)I型においては,眼輪筋にwaningを認める群と認めない群は異なるsubtypeの可能性があり,waningを認める群はより全身型に近いと考えられた

J-GLOBAL

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記述言語：日本語   出版者・発行元：認知神経科学会  

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記述言語：日本語   出版者・発行元：(一財)住友病院  

22歳女性.患者は週に2〜3回の軽い左上下肢のけいれん発作があり,過換気症候群と言われていた.そのため大学入学後は大学の保健センターでバルプロ酸を処方されていたが,効果は少なかった.今回,卒業後の就職に際し紹介受診となった.所見では,顔面を含まない非常に軽度で本人も意識しない程度の左不全片麻痺を認めたものの,他の諸検査に異常は認めなかった.しかし,頭部MRIで右前頭葉にclosed lip typeの脳裂が認められ,脳裂に沿って厚みを持った異所性灰白質が側脳室に突出,透明中隔欠損を伴っていた.更に脳波では右頭頂葉中心に間欠的な鋭波と徐波を認めた.治療として,バルプロ酸とカルバマゼピンを投与した結果,発作は完全に消失した

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

78歳男性.患者は53歳時に胃癌で胃全摘術を受けていた.73歳時よりの両下肢遠位の感覚鈍麻が進行し,76歳時より杖歩行,近医で総合ビタミン剤点滴を行っていた.今回,歩行障害の進行で入院となった.所見では両下肢にpitting edemaと四肢の軽度筋力低下,腱反射の消失が認められ,歩行はataxicで,Romberg sign陽性であった.一方,血液検査では正球性正色素性貧血とビタミンB1の欠乏を認め,神経伝導検査では下肢の運動神経でtibial nerve,peroneal nerveの軸索障害がみられ,感覚神経ではsural nerveの活動電位が誘発されなかった.更にTibial nerve刺激による体性感覚誘発電位は,左右とも著明な潜時延長を認めた.以上より,ビタミンB1欠乏によるポリニューロパチーと診断し,ビタミンB1を含む総合的なビタミン補給を行なった.その結果,歩行障害は軽快傾向となったが,ある朝に心肺停止状態で発見され,蘇生処置を行うも死亡となった.剖検で,死亡原因は無症候性心筋梗塞による心破裂と判明した

J-GLOBAL

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記述言語：日本語   出版者・発行元：南江堂  

CiNii Article

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記述言語：日本語   出版者・発行元：(株)南江堂  

69歳男.左肩疼痛,左握力低下,左眼裂狭小,尿閉が出現した.浮腫はなく,神経学的には高次脳機能に異常を認めなかった.検査所見ではWBCの上昇,凝固系の亢進,TG,LDH,GGT,CKおよびCRP,C3c,CH50の上昇を認めた.頭部MRIで異常所見はなく,頸部MRIの矢状断で第4〜5頸椎レベルの頸髄にT2強調像高信号を認めた.横断面では頸髄の左側半分の前方に限局する高信号を認め,梗塞は灰白質に限局していると考えた.脊髄梗塞と診断し,尿閉に対しては尿道バルーンカテーテルを挿入すると共に,十分な補液とalprostadil 10μgを点滴し,aspirin 100mg内服を開始した.その結果,2週間後に左肩の疼痛は消失し,以後排尿,握力,瞳孔径も改善し,眼裂狭小は軽度残存するのみとなった

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2005&ichushi_jid=J00974&link_issn=&doc_id=20050708390032&doc_link_id=issn%3D0022-1961%26volume%3D96%26issue%3D1%26spage%3D169&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0022-1961%26volume%3D96%26issue%3D1%26spage%3D169&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：(一財)住友病院  

59歳男性.患者は両大腿前面の強い疼痛を伴うしびれ感が次第に両下肢全体に拡大し,更に両前腕にも軽いしびれ感が出現,受診となった.電気生理学的検査では両側正中神経の終末潜時の遅延,両側脛骨神経のF波潜時の遅延,下肢体性感覚誘導電位で両側P40潜時の遅延を認め,画像検査が予定されていたが,臍下より両下肢へのしびれが強くなり歩行障害,膀胱直腸障害,右腰部痛を認め緊急入院となった.入院時,痙性歩行をはじめ片足立ちは両側不可能で,深部腱反射は右下肢で亢進,腹壁反応は消失,両側性にBabinski徴候,右下肢の振動覚低下,左下肢の温痛覚低下,排尿障害,便秘を認めた.胸髄MRIでは第11〜12胸椎レベルで両側の黄色靱帯が肥厚して低信号を呈し,正中型の椎間板ヘルニアを伴う著しい脊柱管の狭小化を認め,T2強調で髄内の高信号変化が確認された.一方,CTでは黄色靱帯の骨化を認め,黄色靱帯骨化症と診断し,手術適応と考え,以後,整形外科へ転科となった

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記述言語：日本語   出版者・発行元：(株)医学書院  

首下がりを伴ったパーキンソン病患者3例に対しmuscle afferent block(MAB)を施行した.改善維持例1例,一時改善例1例,不変例1例であった.症例1(61歳女).第10回目終了時にはほぼ正面視が可能なまでに回復し,表面筋電図上でも安静時収縮活動は消失した.首下がりの改善は3ヵ月以上認めた.症例2(62歳女).表面筋電図で胸鎖乳突筋(SCM)の収縮活動を認め,同部位を中心にMAB療法を施行した.MABにより,施行後約12〜24時間の効果を認め,この間,表面筋電図上の安静収縮も消失した.正面視も可能であったが,その後,再度首下がりが出現した.計8回施行したが,終了後約1週間で入院時の状態となった.症例3(81歳女).両側SCMおよび両側肩甲挙筋に計8回のMABを施行するも,首下がりの改善および表面筋電図上の変化は認めなかった

DOI： 10.11477/mf.1552100117

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2005&ichushi_jid=J00780&link_issn=&doc_id=20050616060009&doc_link_id=10.11477%2Fmf.1552100117&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1552100117&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

67歳女.Parkinson病に対しlevodopa-benzerasideを内服中であったが,薬効持続時間の短縮と著明なwearing offを認めたため受診した.Levodopa単剤,levodopa-benzeraside,及びzonisamideは効果なく,pramipexoleでは紫斑が出現した.血液検査で白血球減少を認めたためpramipexole投与を中止し,以後白血球数は回復した

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記述言語：日本語   出版者・発行元：(有)科学評論社  

61歳女.54歳時にParkinson病(PD)と診断され,wearing offの加療目的で来院した.幻覚や睡眠障害はみられず,これまでの内服薬剤はL-dopa-carbidopa合剤500mg,selegiline 5mg,pergolide 750mgであった.Pergolideからの切り替えのためcabergolineを漸増投与中,主治医との会話中に突然睡眠に陥った.Sleep attackはその後も3回目撃され,pergolideの中止によって発作頻度は減少した.睡眠の持続時間は30分から2時間程度であった.1回目のsleep attack中,急速な眼球運動がみられたが,2,3回目の発作時にはみられなかった.また,3回とも,四肢の筋緊張はごく軽度低下しているのみであった

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

38歳男性.患者は痛覚鈍麻,判断力低下を主訴に,髄液検査で血清梅毒反応陽性を指摘され,著者らの施設へ入院となった.入院時,全身の温痛覚鈍麻を認め,髄液検査では細胞数128/3個,TPHA 5120倍以上であった.経過中,被害妄想や自殺を図るなどの統合失調症症状が出現した.以上より,神経梅毒と診断し,大量ペニシリン療法を開始したところ,臨床症状,髄液所見は軽快したが,123I-IMPを用いた脳血流SPECTでは大脳全体の脳血流は以前よりも悪化がみられた.本症例は妻の血清梅毒陽性が以前に判明しているにもかかわらず,妻から本人に告知がなされず,また本人も不特定多数の異性との性交渉の経験があり,どちらが最初に梅毒に感染したのかは不明であった

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

フルボキサミンにて軽快した高齢女性(81歳)の口腔内セネストパチー症例を報告した.患者には特に精神科疾患の家族歴や既往歴,現病は認めなかった.口がねばる,口の中からどろどろした流動物が出てくるという訴えを示すようになった.歯科,耳鼻咽喉科,内科にて精査したが異常はなく,口腔セネストパチーと診断され,スルピリドを処方したが,効果を得られず中止した.その後,フルボキサミン25mgを使用したところ,症状は完全には消失しないものの苦痛であることはなくなった

CiNii Article

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2004&ichushi_jid=J02464&link_issn=&doc_id=20041001010009&doc_link_id=%2Faj2rsizd%2F2004%2F001509%2F010%2F1065-1069%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faj2rsizd%2F2004%2F001509%2F010%2F1065-1069%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(有)科学評論社  

72歳女性.患者はParkinson病に対するrisperidone,L-dopa carbidopa合剤,bromocriptine投与中に,幻視,動作緩慢が出現し入院となった.入院後,risperidoneおよびbromocriptineを中止し,L-dopa carbidopa合剤を200mgから400mgに増量したところ,突然著明な頸部後屈が出現した.後頸部筋群の過緊張を認め,表面筋電図では左右板状筋の持続性活動亢進が確認された.以上より,retrocollisによる頸部後屈と考え,cabergolineを少量から漸増投与し1mgとしたところ,頸部後屈は消失し,以後出現することがなかった

J-GLOBAL

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：(株)アークメディア  

L-dopa増量に伴いパニック発作を引き起こしたパーキンソン病の2症例を報告した.症例1(72歳女性)では増量に伴い,on相とoff相におけるL-dopa血中濃度の差が大きくなり,off相の時に発作が起きたことが血中濃度測定により判明した.一方,症例2(71歳女性)ではジスキネジアを伴うことやL-dopaの内服時間との関連より,L-dopaの増量によりon相におけるL-dopa血中濃度がさらに増加しon相に発作が起きたと考えられた.両症例ともL-dopaを減量することによりパニック発作は速やかに消失した.パーキンソン病に伴って起こるパニック発作では日内変動との相関を把握することが重要であるが,それが困難な場合には血中濃度の測定やL-dopa増量・減量が役立つと示唆された

CiNii Article

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2004&ichushi_jid=J01552&link_issn=&doc_id=20040812070011&doc_link_id=%2Fao1clphd%2F2004%2F003308%2F011%2F1055-1059%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fao1clphd%2F2004%2F003308%2F011%2F1055-1059%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一財)住友病院  

70歳女性.患者は60歳時にパーキンソン病と診断され,62歳時よりL-dopa製剤やdopamine agonist投与にて経過中であったが,嚥下障害,誤嚥性肺炎,体重減少が出現し,著者らの施設へ入院となった.入院時,著明な嚥下障害による摂食不良,両手足・下顎の安静時振戦,四肢の著明な筋萎縮を認め,肺炎軽快後の安静時基礎代謝では亢進がみられた.体重減少および振戦の緩和目的でβblocker 20mg/日を計7日間投与したところ,振戦およびパーキンソニズムに変化はみられなかったが,基礎代謝量の減少および体重の増加が得られた

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

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記述言語：日本語   出版者・発行元：(一財)住友病院  

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記述言語：日本語   出版者・発行元：(一財)住友病院  

70歳女性.患者は60歳時にパーキンソン病と診断され,62歳時よりL-dopa製剤やdopamine agonist投与にて経過中であったが,嚥下障害,誤嚥性肺炎,体重減少が出現し,著者らの施設へ入院となった.入院時,著明な嚥下障害による摂食不良,両手足・下顎の安静時振戦,四肢の著明な筋萎縮を認め,肺炎軽快後の安静時基礎代謝では亢進がみられた.体重減少および振戦の緩和目的でβblocker 20mg/日を計7日間投与したところ,振戦およびパーキンソニズムに変化はみられなかったが,基礎代謝量の減少および体重の増加が得られた

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記述言語：日本語   出版者・発行元：(有)科学評論社  

症例1は74歳女で,小字症が出現し,ほどなく両手の振戦も出現した.Parkinson病と診断された.急に首下がりが出現し,顔貌は無欲様,両側胸鎖乳突筋の筋緊張の亢進が存在した.また,自律神経症候として便秘と起立性低血圧が存在した.Yahr IV度のParkinson病と診断した.Cabergoline 4mgで固定し,L-dopa carbidopa合剤を徐々に増量し首下がりがほぼ消失した.症例2は62歳女で,Parkinson病と診断された.pergolideを中心に使用され,徐々に首下がりが出現した.Cabergolineを3mgから徐々に減量し中止した結果,首下がりは消失した.症例3は63歳女で,Parkinson病と診断された.pergolideを使用され急に首下がりが出現した.Cabergolineを4mgから徐々に減量し中止した結果,首下がりは消失した

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記述言語：日本語   出版者・発行元：(一財)住友病院  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

81歳女性.患者は79歳時に首下がりを指摘され,しばらくしてから動作緩慢,書字の際の右手振戦が出現した.80歳時に近医でパーキンソン病と診断のもとL-dopa製剤,cebergoline投与を受けるも無効で,起立性低血圧による立ちくらみが著明となり,著者らの施設へ入院となった.入院時,首下がりが著明で,頭部MRIでは両側被殻外側に線状の高信号域を認めた.123I-MIBGによる心筋シンチグラフィーではH/M比が初期像で2.94,3時間後で2.92,洗い出し率5.2%で,表面筋電図にて両側胸鎖乳突筋の活動亢進を認めたが,針筋電図で後頸部筋群は保たれていた.以上より,多系統萎縮症と診断し,立ちくらみはdroxidopa投与にて改善した.また,首下がりはantecollisによるものと判断し,cabergolineを中止したところ,改善がみられた

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記述言語：日本語   出版者・発行元：(有)科学評論社  

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

パーキンソン病における首下がり10症例(自検例3例,文献例7例)について検討した.その結果,性別は男性2例,女性8例で,発症年齢は平均65.4歳であった.パーキンソン病の発症から首下がりの発症までに要する年数は平均5.6年で,首下がりの原因はantecollisが8例,isolated neck extensor myopathyが2例であった.antecollis症例では,dopamine agonistが首下がりを悪化させ,L-dopa製剤が首下がりを改善させる傾向を認めた.isolated neck extensor myopathy症例は,いずれも装具を使用中であった

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

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記述言語：日本語   出版者・発行元：(一財)住友病院  

57歳女性.患者は頭痛,発熱,意識障害を主訴とした.入院時,項部硬直や四肢の深部腱反射亢進などを認めたが,胃液,髄液の塗抹検査,PCR,培養は陰性であった.経過中,昏睡状態となり,強直間代性けいれんが出現し,髄液検査で総ADA活性,ADA-2/総ADA比(%ADA-2)の上昇を認めた.以上より,結核性髄膜炎を強く疑い,INH,RFP,EB,PZAによる抗結核剤投与を開始したところ,臨床症状の改善とともに総ADA活性,%ADA-2の正常化がみられた

J-GLOBAL

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記述言語：日本語   出版者・発行元：(有)科学評論社  

74歳女.1995年に小字症,両手の振戦からParkinson病(PD)と診断され,L-dopa carbidopa合剤を中心に加療された.2001年からcabergolineを追加し,2003年1月にcabergolineを3mgから4mgに増量したところ,3月末に急に首下がりが出現し,9月から幻視や首下がり,動作緩慢,歩行障害が悪化し,wearing offを著明に認めるようになった.病歴検査所見からYahrIV度のPDと診断した.Parkinson症状は首下がりを含めwearing offと考えられる日内変動を認めた.胸鎖乳突筋の筋緊張の亢進を認めること,後頸部筋群の運動単位が保たれており筋力低下を認めないことより,antecollisに伴う首下がりと考えらえた.OffはL-dopa製剤内服後2時間程度で出現しており,首下がりも同様にoffの時間帯にあわせて悪化していた.Cabergolineを4mgで固定したまま,L-dopa carbidopa合剤を徐々に増量し,L-dopaにて500mgを分五とし内服開始し,首下がりはほぼ消失した.その後,cabergolineを徐々に減量し1mgとしたが首下がりは出現しなかった

J-GLOBAL

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記述言語：日本語   出版者・発行元：社団法人日本リハビリテーション医学会  

CiNii Article

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：(公社)日本リハビリテーション医学会  

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記述言語：日本語   出版者・発行元：4  

PubMed

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記述言語：日本語   出版者・発行元：(株)医学書院  

症例1:72歳女.音楽性幻聴,振戦,歩行障害が出現しパーキンソン病の診断で薬物投与され症状は軽快した.しかし,その後は悪化しては薬物調節にて軽快するということを繰り返しており,幻視も出現してきた.症例2:77歳女.すりあし歩行,前傾姿勢,四肢の振戦が出現しパーキンソン病と診断された.薬物調節により経過良好であったが,幻視が出現しパーキンソン症状も悪化した.2症例とも薬剤の調節では幻視を消失させることが困難であった.両例とも重度の白内障を両眼に認めたため白内障手術を両眼ともに行ったところ,術直後より幻視は完全に消失した.パーキンソン病やCharles Bonnet症候群の幻視が,良好な視機能を持っている場合や,明るい所,閉眼時や明りのない暗闇では起こりにくく,開眼時の薄明りのもとで起こりやすいことを支持する結果となった.パーキンソン病においても幻視の出現に末梢性の視機能障害が関与している例があり,白内障合併症例では白内障手術が幻視の治療の一つの選択肢であると考えられた

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2004&ichushi_jid=J01231&link_issn=&doc_id=20040615360010&doc_link_id=10.11477%2Fmf.1406100274&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1406100274&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：医学書院  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一財)住友病院  

66歳男.右側の歯及び歯肉痛を自覚した.頭部MRIなどから脳梗塞と診断された.疼痛部位が口腔内及び右側顔面部にまで拡大した.薬物療法による疼痛の改善が乏しいため,精査及び加療目的で入院した.神経学的には,口腔内を中心とする右側顔面の疼痛及び冷覚過敏が認められた.頭部MRIで右橋被蓋部背外側から右中小脳脚にかけてT2強調像及びFLAIR像で高信号病変が認められた.右側星状神経節ブロックと併行して,ノリトリプチリンを開始した.血液検査などで副作用がないことを確認しながら徐々に増量した.当初の疼痛を10とすると,最終的な疼痛が6〜7程度にまで改善した

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

77歳女.10年前より糖尿病を指摘され,インスリンを導入された.左顔面神経麻痺と診断され,ステロイドの点滴治療を受け,1週間で症状は消失した.原因不明のブドウ膜炎と診断され,ステロイドの点滴を受け軽快した.胸部レントゲンで両側肺門リンパ節の腫脹(BHL)が疑われ,胸部CTを施行されたが,BHLは認められなかった.左眼部の違和感が出現し,左方視で複視が出現した.左顔半分が動きにくくなり,食事をすると左の口から物がこぼれる,左目が閉じにくくなる等の症状が出現した.ブドウ膜炎と診断され,更に眼球運動障害が認められた.胸部CTで両側肺門及び縦隔リンパ節の腫脹を認め,経気管支肺生検でサルコイド結節が認められた.神経サルコイドーシスと診断し,ステロイド治療を開始した.ステロイド開始直後に右外転神経麻痺を呈したが,ステロイドパルス療法により改善した.左顔面神経麻痺及び左外転神経麻痺は変化を認めなかった

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一財)住友病院  

77歳女.10年前より糖尿病を指摘され,インスリンを導入された.左顔面神経麻痺と診断され,ステロイドの点滴治療を受け,1週間で症状は消失した.原因不明のブドウ膜炎と診断され,ステロイドの点滴を受け軽快した.胸部レントゲンで両側肺門リンパ節の腫脹(BHL)が疑われ,胸部CTを施行されたが,BHLは認められなかった.左眼部の違和感が出現し,左方視で複視が出現した.左顔半分が動きにくくなり,食事をすると左の口から物がこぼれる,左目が閉じにくくなる等の症状が出現した.ブドウ膜炎と診断され,更に眼球運動障害が認められた.胸部CTで両側肺門及び縦隔リンパ節の腫脹を認め,経気管支肺生検でサルコイド結節が認められた.神経サルコイドーシスと診断し,ステロイド治療を開始した.ステロイド開始直後に右外転神経麻痺を呈したが,ステロイドパルス療法により改善した.左顔面神経麻痺及び左外転神経麻痺は変化を認めなかった

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記述言語：日本語   出版者・発行元：(一財)住友病院  

66歳男.右側の歯及び歯肉痛を自覚した.頭部MRIなどから脳梗塞と診断された.疼痛部位が口腔内及び右側顔面部にまで拡大した.薬物療法による疼痛の改善が乏しいため,精査及び加療目的で入院した.神経学的には,口腔内を中心とする右側顔面の疼痛及び冷覚過敏が認められた.頭部MRIで右橋被蓋部背外側から右中小脳脚にかけてT2強調像及びFLAIR像で高信号病変が認められた.右側星状神経節ブロックと併行して,ノリトリプチリンを開始した.血液検査などで副作用がないことを確認しながら徐々に増量した.当初の疼痛を10とすると,最終的な疼痛が6〜7程度にまで改善した

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記述言語：日本語   出版者・発行元：(一財)住友病院  

70歳女.10年ほど前より,被害妄想や感情の平板化或いは徘徊などの症状が出現した.精神分裂病との診断のもと抗精神病薬を処方されていた.昏睡状態及び40℃の高熱により搬送入院した.昏睡状態,高熱及び著明な高血清クレアチンキナーゼ(CK)血症を認め,向精神薬服用中であることから悪性症候群と診断された.ダントロレンやブロモクリプチンの投与及び大量輸液を行ったところ,全身状態の改善及び血清CK値の減少が認められた.しかし,昏睡状態が遷延していたため頭部MRIを施行し,両側小脳・後頭葉,左視床など広範囲にT2強調像及び拡散強調像にて高信号に描出される病変が認められた.その後,意識レベルは徐々に改善し,筋緊張も派常化したが,徐々に精神運動興奮状態が悪化した.悪性症候群のリスクは高いと思われたがハロペリドールを少量より開始,増量した.投与後より,精神運動興奮状態は改善し,それに伴い全身状態も改善した

J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

65歳男.糖尿病,高血圧で通院中であった.起床時より突然両下肢が動かないことに気がつき,入院した.高血圧以外には異常を認めず,心房細動を含め不整脈は認めなかった.上肢の筋力は正常であったが,下肢は両下肢とも弛緩性の麻痺が存在した.Babinski反射は両側陽性であった.下肢の振動覚は中等度低下した.軽度の貧血と慢性腎不全を認めた.頭部MRIでは右の内包後脚および左の中心前回および中心後回に多発性の新鮮な梗塞を認めた.頭部精査で右の内包後脚および左の中心前回と中心後回に多発性の新鮮な梗塞を認めた.これが原因と考え,aspirinおよび補液による治療を継続した.徐々に軽快し退院した

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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