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Parkinson Disease: HELP
Articles from Tokyo
Based on 545 articles published since 2008

These are the 545 published articles about Parkinson Disease that originated from Tokyo during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10 · 11 · 12 · 13 · 14 · 15 · 16 · 17 · 18 · 19 · 20
401 Article Pale neurites, premature α-synuclein aggregates with centripetal extension from axon collaterals. 2012

Kanazawa, Toshiro / Adachi, Eijiro / Orimo, Satoshi / Nakamura, Ayako / Mizusawa, Hidehiro / Uchihara, Toshiki. ·Laboratory of Strucutural Neuropathology, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo, Japan. ·Brain Pathol · Pubmed #21672073.

ABSTRACT: Progressive aggregation of α-synuclein (αS) from pale bodies (PBs) and extension from Lewy neurites (LNs) are candidate mechanisms for Lewy body (LB) formation. To identify how aggregation of αS is related to its extension along neurites, 60-µm-thick brainstem sections of Parkinson disease (PD) patients were prepared for three-dimensional (3D) reconstruction of αS-positive neurites with neurofilament (NF) and thiazin red (TR), a fluorochrome with an affinity to solid aggregates. This demonstrated 3D layering of αS surrounded by NF with the aggregates probed by TR in the center, corresponding to the eosinophilic core of mature LBs. This eosinophilic/TR-positive profile, characteristically absent in PBs, premature counterpart of LBs, was similarly absent in some LNs. We would like to refer these premature LNs as "pale neurites" (PNs). Their premature nature was evidenced by 3D fluoroprofiling with quantum dots (QDs) and subsequent electron microscopic identification (3D-oriented immunoelectron microscopy) as loosely packed αS (QDs)-positive filaments. Quantification of LNs, frequently extended around branching axons, demonstrated that LNs are initiated at axon collaterals to extend centripetally into proximal segments. This branching-oriented extension of αS is related to its selective predisposition to systems with highly divergent axons, preferentially affected in PD, which may explain barely somatotopic manifestations of PD.

402 Article Cognitive status correlates with white matter alteration in Parkinson's disease. 2012

Hattori, Takaaki / Orimo, Satoshi / Aoki, Shigeki / Ito, Kenji / Abe, Osamu / Amano, Atsushi / Sato, Ryo / Sakai, Kasumi / Mizusawa, Hidehiro. ·Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. ·Hum Brain Mapp · Pubmed #21495116.

ABSTRACT: Patients with Parkinson's disease (PD) can develop mild cognitive impairment (PD-MCI), frequently progressing to dementia (PDD). Here, we aimed to elucidate the relationship between white matter alteration and cognitive status in PD and dementia with Lewy bodies (DLB) by using diffusion tensor imaging. We also compared the progression patterns of white and gray matter and the cerebral perfusion. We enrolled patients with PD cognitively normal (PD-CogNL, n = 32), PD-MCI (n = 28), PDD (n = 25), DLB (n = 29), and age- and sex-matched healthy control subjects (n = 40). Fractional anisotropy (FA) map of a patient group was compared with that of control subjects by using tract-based spatial statistics. For the patient cohort, intersubject voxel-wise correlation was performed between FA values and Mini-Mental Status Examination (MMSE) scores. We also evaluated the gray matter and the cerebral perfusion by conducting a voxel-based analysis. There were significantly decreased FA values in many major tracts in patients with PD-MCI, PDD, and DLB, but not in PD-CogNL, compared with control subjects. FA values in the certain white matter areas, particularly the bilateral parietal white matter, were significantly correlated with MMSE scores in patients with PD. Patients with PDD and DLB had diffuse gray matter atrophy. All patient groups had occipital and posterior parietal hypoperfusion when compared with control subjects. Our results suggest that white matter damage underlies cognitive impairment in PD, and cognitive impairment in PD progresses with functional alteration (hypoperfusion) followed by structural alterations in which white matter alteration precedes gray matter atrophy.

403 Article [Up to date on Parkinson's disease --therapy]. 2011

Hatano, Taku. ·Department of Neurology, Juntendo University School of Medicine. ·Rinsho Shinkeigaku · Pubmed #22277523.

ABSTRACT: -- No abstract --

404 Article [Neurodegenerative disorder as "mitochondrial dysfunction disease"]. 2011

Matsuda, Noriyuki / Tanaka, Keiji. ·Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science. ·Rinsho Shinkeigaku · Pubmed #22277451.

ABSTRACT: -- No abstract --

405 Article [The pathomechanisms of young-onset Parkinson's disease (PD), approach to the causes of PD form the mechanisms of insulin secretion system]. 2011

Hattori, Nobutaka / Eguchi, Hiroto / Imaizumi, Mika / Saiki, Shinji / Sato, Shigeto / Nagamatsu, Shinya. ·Department of Neurology, Juntendo University School of Medicine. ·Rinsho Shinkeigaku · Pubmed #22277450.

ABSTRACT: -- No abstract --

406 Article [Genetics of sporadic disease: insights from high-throughput sequencing --Parkinson disease]. 2011

Mitsui, Jun. ·Department of Neurology, The University of Tokyo. ·Rinsho Shinkeigaku · Pubmed #22277445.

ABSTRACT: To identify susceptibility genes that account for the heritability seen for complex traits, genome-wide association studies (GWAS) employing common single nucleotide polymorphisms (SNPs) have been conducted. The theoretical framework for GWAS is the 'common disease-common variant hypothesis'. Although GWAS have successfully revealed numerous susceptibility genes for common diseases, they generally account for only a small proportion of estimated heritability. In contrast, the prominent role of rare variants in neurodegenerative disease is best highlighted by the recent discovery of the glucocerebrosidase gene (GBA) as a robust genetic risk factor for Parkinson disease. Emerging new technology of next-generation sequencer will be a promising tool which enables an efficient search for remaining disease-relevant alleles.

407 Article [Assessment of cognitive and emotional functions in Parkinson's disease]. 2011

Kawamura, Mitsuru / Kobayakawa, Mutsutaka / Tsuruya, Natsuko. ·Department of Neurology, Showa University School of Medicine. ·Rinsho Shinkeigaku · Pubmed #22277393.

ABSTRACT: -- No abstract --

408 Article The odor stick identification test for Japanese differentiates Parkinson's disease from multiple system atrophy and progressive supra nuclear palsy. 2011

Suzuki, Masahiko / Hashimoto, Masaya / Yoshioka, Masayuki / Murakami, Maiko / Kawasaki, Keiichi / Urashima, Mitsuyoshi. ·Department of Neurology, Aoto Hospital, Jikei University School of Medicine, 6-41-2 Aoto Katsushika-ku, Tokyo 125-8506, Japan. suzukimd@jikei.ac.jp ·BMC Neurol · Pubmed #22192419.

ABSTRACT: BACKGROUND: Progressive supranuclear palsy (PSP) and parkinsonian variant of multiple system atrophy (MSA-P) are clinically difficult to differentiate from idiopathic Parkinson's disease (PD), particularly in the early stages of the disease. Previous reports indicated that the olfactory function is relatively intact or slightly reduced in patients with PSP and MSA-P, suggesting that the odor stick identification test for Japanese (OSIT-J), which is a short and simple noninvasive test that is potentially useful clinically for detecting early-stage PD in Japan, may be useful in the differential diagnosis of early-stage PD from MSA-P and PSP. There is no information on the sensitivity and specificity of OSIT-J in the diagnosis of parkinsonian syndromes such as PSP and MSA-P. METHODS: We assessed the olfactory function using the OSIT-J test in 94 Japanese patients with idiopathic PD, 15 with MSA-P, 7 with PSP, and 29 age-matched control subjects. RESULTS: The mean ± SD score of OSIT-J in patients with PD (4.4 ± 2.9) was significantly lower than in patients with MSA-P (8.7 ± 2.2, P < 0.0001), PSP (7.6 ± 2.2, P < 0.0057), and control subjects (10.5 ± 1.3, P < 0.0001). The area under the curve (AUC) of receiver operating characteristic (ROC) to discriminate PD from normal control using OSIT-J scores was 0.97 (95% confidence interval, 0.95-1.00), from MSA-P 0.87 (0.80-0.95), and from PSP 0.81 (0.66-0.96). CONCLUSION: The OSIT-J is a potentially useful clinical test not only for detection of olfactory deficit in PD but also for differentiating PD from MSA-P and PSP.

409 Article [Effects of the induction of anesthesia with propofol on hemodynamics in patients with Parkinson's disease]. 2011

Nakajima, Ryo / Kato, Jitsu / Iwasaki, Ken-ichi / Ogawa, Yojiro / Gokan, Dai / Ogawa, Setsuro. ·Division of Anesthesiology, Department of Anesthesiology, Nihon University School of Medicine, Tokyo 173-8610. ·Masui · Pubmed #22111351.

ABSTRACT: BACKGROUND: Patients with Parkinson's disease frequently suffer from impaired autonomic nervous function. To elucidate the effects of the induction of anesthesia with propofol on cardiovascular hemodynamics has become important, since the number of patients with Parkinson's disease undergoing deep brain stimulation under general anesthesia has increased recently. METHODS: Effects of induction with propofol in patients with Parkinson's disease on cardiovascular hemodynamics and autonomic nervous activity were compared with those of the control patients. Moreover, possible different effect on hemodynamics between the propofol alone and the combination of propofol and fentanyl for the induction were examined in patients with Parkinson's disease. RESULTS: Although heart rate or blood pressure was not different between patients with Parkinson's disease and the control patients before the induction, sympathetic vasomotor activity was lower in patients with Parkinson's disease than the control patients. The induction of anesthesia significantly decreased blood pressure in patients with Parkinson's disease. However the decreasing systolic blood pressure after the induction of anesthesia was more marked in patients with Parkinson's disease than the control patients. We did not find differences in the changes of blood pressure between the propofol alone and the combination of propofol and fentanyl in patients with Parkinson's disease. CONCLUSIONS: No abnormal responses to the induction of anesthesia with propofol were found in the patients with Parkinson's disease.

410 Article Camptocormia in Japanese patients with Parkinson's disease: a multicenter study. 2011

Seki, Morinobu / Takahashi, Kazushi / Koto, Atsuo / Mihara, Ban / Morita, Yoko / Isozumi, Kazuo / Ohta, Kouichi / Muramatsu, Kazuhiro / Gotoh, Jun / Yamaguchi, Keiji / Tomita, Yutaka / Sato, Hideki / Nihei, Yoshihiro / Iwasawa, Satoko / Suzuki, Norihiro / Anonymous2520706. ·Department of Neurology, Keio University School of Medicine, Tokyo, Japan. ·Mov Disord · Pubmed #21953897.

ABSTRACT: OBJECTIVE: The aim of this work was to investigate the prevalence of camptocormia and the clinical characteristics of patients with camptocormia in a large population of PD patients. BACKGROUND: Although camptocormia has been recognized as a prominent phenomenon in PD, the previous epidemiological reports were limited, especially in terms of sample size. METHODS: We evaluated 531 PD patients (disease duration: 7.0 ± 5.5 years, mean ± standard deviation). We examined their clinical features and the prevalence of camptocormia. RESULTS: Camptocormia was detected in 22 patients (4.1%) and found in patients who were older and had more severe motor symptoms and a higher levodopa (L-dopa) dose (P < 0.05), compared to the patients without camptocormia. Patients with camptocormia showed significantly higher frequencies of autonomic symptoms, such as constipation and urinary incontinence (P < 0.05). CONCLUSIONS: Camptocormia is uncommon in PD and is associated with disease severity, higher L-dopa dose and higher frequencies of autonomic symptoms.

411 Article Short-interval intracortical inhibition in Parkinson's disease using anterior-posterior directed currents. 2011

Hanajima, R / Terao, Y / Shirota, Y / Ohminami, S / Nakatani-Enomoto, S / Okabe, S / Matsumoto, H / Tsutsumi, R / Ugawa, Y. ·Department of Neurology, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. hanajima-tky@umin.ac.jp ·Exp Brain Res · Pubmed #21842190.

ABSTRACT: Reduced short-interval intracortical inhibition (SICI) is reported in Parkinson's disease (PD) and is considered to reflect abnormal GABAergic inhibitory system of the primary motor cortex in PD. We have recently shown, however, that SICI using anterior-posterior directed currents in the brain was normal in focal dystonia even though that using posterior-anterior currents was abnormal, indicating that the GABAergic system of the primary motor cortex is largely normal in dystonia. Here, we studied SICI in PD to clarify whether the GABAergic system is completely impaired in PD. We used paired-pulse transcranial magnetic stimulation to study SICI at interstimulus intervals of 3 and 4 ms with anterior-posterior or posterior-anterior directed currents in eight PD patients and ten healthy volunteers. The amount of SICI with posterior-anterior directed currents was reduced in PD patients compared with healthy volunteers; in contrast, SICI studied with anterior-posterior directed currents was normal in PD patients. These observations may be due to the difference in I-wave composition generated by the two directed currents and/or the difference in responsible inhibitory interneurons for the inhibition between the two current directions. We suggest that some or a part of inhibitory interneurons are not involved in PD. This discrepancy between SICI using posterior-anterior and anterior-posterior directed currents experiments may provide additional information about the circuits of the motor cortex.

412 Article Altered microstructure in corticospinal tract in idiopathic normal pressure hydrocephalus: comparison with Alzheimer disease and Parkinson disease with dementia. 2011

Hattori, T / Yuasa, T / Aoki, S / Sato, R / Sawaura, H / Mori, T / Mizusawa, H. ·Department of Neurology and Neurological Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. ·AJNR Am J Neuroradiol · Pubmed #21816921.

ABSTRACT: BACKGROUND AND PURPOSE: Previous neuropathologic studies in chronic hydrocephalus have suggested the presence of white matter damage, presumably from mechanical pressure due to ventricular enlargement and metabolic derangement. This study aimed to investigate the diffusional properties of the CST in patients with iNPH by using DTI and to determine whether this method could be used as a new diagnostic tool to differentiate patients with iNPH from those with AD and PDD and control subjects. MATERIALS AND METHODS: We enrolled 18 patients with iNPH, 11 patients with AD, 11 patients with PDD, and 19 healthy control subjects. Diffusion tensor metrics of the segmented CST, including FA values, axial eigenvalues, and radial eigenvalues, were evaluated by using tract-specific analysis. The anisotropy color-coding tractography of the CST was visually evaluated. The DTI findings were compared among groups. RESULTS: Tract-specific analysis of the CST showed that FA values and axial eigenvalues were significantly increased (P < .001), whereas radial eigenvalues were not significantly altered, in patients with iNPH compared with other subjects. The CST tractographic images in patients with iNPH was visually different from those in other subjects (P < .001). In discriminating patients with iNPH from other subjects, the CST FA values had a sensitivity of 94% and specificity of 80% at a cutoff value of 0.59. CONCLUSIONS: Our results suggest that patients with iNPH have altered microstructures in the CST. Quantitative and visual CST evaluation by using DTI may be useful for differentiating patients with iNPH from patients with AD or PDD or healthy subjects.

413 Article Relationship between slowing of the EEG and cognitive impairment in Parkinson disease. 2011

Morita, Akihiko / Kamei, Satoshi / Mizutani, Tomohiko. ·Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. ·J Clin Neurophysiol · Pubmed #21811128.

ABSTRACT: A previous study using the quantitative EEG technique confirmed that diffuse slowing of the EEG is present in Parkinson disease. The present study was the first to assess the relationship between cognitive impairment and quantitative EEG in Parkinson disease. A total of 100 patients with Parkinson disease with a mean Hoehn-Yahr stage of 2.68 were serially enrolled. Cognitive impairment was assessed using the Mini-Mental State Examination. Lack of ischemic lesions was confirmed in all the patients by MRI. Absolute power values were measured for four frequency bands from δ to β. The electrodes were divided among six locations as follows: frontal pole and frontal, central, parietal, temporal, and occipital locations. Spectral ratio was calculated as the sum of power values for the α- and β-waves divided by the sum of values for slow waves. The relationship between Mini-Mental State Examination score and spectral ratio was assessed by the Jonckheere-Terpstra trend test. At all electrode locations, spectral ratio significantly decreased with a decline in Mini-Mental State Examination score (frontal pole, P = 0.017; frontal, P = 0.028; central, P = 0.019; parietal, P = 0.004; temporal, P = 0.002; occipital, P = 0.006). The rate of patients with Parkinson disease with slowing of the EEG was more frequent with serious cognitive impairment.

414 Article [The development and validation of a new comprehensive self-completing questionnaire for symptoms in Parkinson's disease (MASAC-PD 31)]. 2011

Nogawa, Shigeru / Takahashi, Hirohide / Hattori, Nobutaka. ·Department of Internal Medicine, Tokyo Dental College Ichikawa General Hospital ·Rinsho Shinkeigaku · Pubmed #21706828.

ABSTRACT: BACKGROUND: Patients with Parkinson's disease (PD) suffer from various symptoms. In order to identify untreated symptoms within the limited time of a clinical interview, we developed a new self-completing questionnaire (MASAC-PD 31). The questionnaire consists of two parts (5 domains, 31 items); Part I intended at rating the motor symptoms and activities of daily living (ADL) during both "on" and "off" periods, and Part II aimed at screening and assessing mainly the non-motor symptoms, such as sleep-related difficulties, autonomic symptoms, cognition, mood and others. The purpose of this study was to evaluate the validity, reliability, and clinical usefulness of the questionnaire. SUBJECTS AND METHODS: Based on the number of valid answers in a pilot trial, MASAC-PD 31 was refined by improving the expression and layout. Of the initially enrolled 107 patients attending three hospitals, 102 patients were included in the final analysis. Correlations of the scores on the MASAC-PD 31 with other clinical scales were evaluated. A second trial consisting of 57 participants was conducted a month later to assess the test-retest reproducibility of the questionnaire. RESULTS: The average time needed to complete MASAC-PD 31 was 17 min (range: 3-90 min). Each of the domains in Part I showed high internal consistency (Cronbach's alpha: 0.663 for "on" motor) and strong correlations with preexisting indices (Spearman's correlation coefficient: 0.547, 0.544, and 0.571 for "on" motor against "on" UPDRS, PDQ-39, and Schwab & England ADL scale, respectively). The questions in the Part II domains also showed strong correlations with preexisting scales. Most of the items showed high reproducibility (weighted kappa coefficient) and consistency. CONCLUSION: This new comprehensive questionnaire was shown to be valid and reliable for assessing the motor disability in patients with PD. Moreover, it may be useful in clinical management for identifying clinically unrecognized symptoms, especially non-motor problems.

415 Article Unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve in Parkinson's disease. 2011

Orimo, S / Uchihara, T / Kanazawa, T / Itoh, Y / Wakabayashi, K / Kakita, A / Takahashi, H. ·Department of Neurology, Kanto Central Hospital, Tokyo, Japan. orimo@kanto-ctr-hsp.com ·Neuropathol Appl Neurobiol · Pubmed #21696416.

ABSTRACT: AIMS: We recently demonstrated accumulation of α-synuclein aggregates of the cardiac sympathetic nerve in Parkinson's disease (PD) and a possible relationship between degeneration of the cardiac sympathetic nerve and α-synuclein aggregates. The aim of this study is to determine whether there is a difference in the degenerative process between unmyelinated and myelinated axons of the cardiac nerve. METHODS: We immunohistochemically examined cardiac tissues from four pathologically verified PD patients, nine patients with incidental Lewy body disease (ILBD) and five control subjects, using antibodies against neurofilament, myelin basic protein (MBP) and α-synuclein. First, we counted the number of neurofilament-immunoreactive axons not surrounded by MBP (unmyelinated axons) and those surrounded by MBP (myelinated axons). Next, we counted the number of unmyelinated and myelinated axons with α-synuclein aggregates. RESULTS: (i) The percentage of unmyelinated axons in PD (77.5 ± 9.14%) was significantly lower compared to that in control subjects (92.2 ± 2.40%). (ii) The ratio of unmyelinated axons with α-synuclein aggregates to total axons with α-synuclein aggregates in ILBD ranged from 94.4 to 100 (98.2 ± 2.18%). Among axons with α-synuclein aggregates, unmyelinated axons were the overwhelming majority, comprising 98.2%. CONCLUSION: These findings suggest that in PD unmyelinated axons are more vulnerable to degeneration than myelinated axons of the cardiac nerve, because α-synuclein aggregates accumulate much more abundantly in unmyelinated axons.

416 Article Parkinson's disease-associated mutations in α-synuclein and UCH-L1 inhibit the unconventional secretion of UCH-L1. 2011

Konya, Chiho / Hatanaka, Yusuke / Fujiwara, Yuuki / Uchida, Kenko / Nagai, Yoshitaka / Wada, Keiji / Kabuta, Tomohiro. ·Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. ·Neurochem Int · Pubmed #21693148.

ABSTRACT: Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is an intracellular protein abundantly expressed in neurons, and a mutation in UCH-L1 has been identified in familial Parkinson's disease. UCH-L1 has been detected in human cerebrospinal fluid, raising the possibility that UCH-L1 is secreted from neurons. In the present study, we showed that a portion of UCH-L1 is secreted from cultured cells. The secretion of D30K UCH-L1, which lacks ubiquitin binding activity, was decreased compared with that of wild-type UCH-L1, while the secretion of C90S UCH-L1, which lacks hydrolase activity, was not. Treatment with Brefeldin A, an inhibitor of vesicle transport from the endoplasmic reticulum to the Golgi, did not block the secretion of UCH-L1, indicating that UCH-L1 is secreted by an unconventional pathway. The UCH-L1 sequence from Leu-32 to Leu-39 is similar to the unconventional secretory signal sequence of engrailed 2, and substitution of the leucines within this region (L32S/L32A/L34S/L34A/L39S/L39A) reduced the secretion of UCH-L1. We found that the Parkinson's disease-associated mutation I93M in UCH-L1 decreased the secretion of I93M UCH-L1. In addition, Parkinson's disease-linked α-synuclein mutants reduced the secretion of endogenous UCH-L1. Our results indicate that the hydrolase activity is not necessary for the unconventional secretion of UCH-L1, and suggest that the ubiquitin binding activity and the sequence between Leu-32 and Leu-39 are involved in the secretion. Moreover, the secretion of UCH-L1 could be involved in the pathology of Parkinson's disease.

417 Article A novel protein degradation system in young-onset Parkinson's disease: mitophagy is a therapeutic target as a quality control for damaged mitochondria. 2011

Hatano, Taku. ·Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan. ·Mov Disord · Pubmed #21671510.

ABSTRACT: -- No abstract --

418 Article LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: impairment of the kinase activity by Parkinson's disease-associated mutations. 2011

Ohta, Etsuro / Kawakami, Fumitaka / Kubo, Makoto / Obata, Fumiya. ·Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, Minami-ku, Sagamihara, Kanagawa, Japan. eohta@kitasato-u.ac.jp ·FEBS Lett · Pubmed #21658387.

ABSTRACT: LRRK2 is the causal molecule for autosomal-dominant familial Parkinson's disease, although its true function, including its physiological substrates, remains unknown. Here, using in vitro kinase assay with recombinant proteins, we demonstrated for the first time that LRRK2 directly phosphorylates Akt1, a central molecule involved in signal transduction for cell survival and prevention of apoptosis. Ser473, one of two amino acids essential for Akt1 activation, was the target site for LRRK2. A knockdown experiment using intact cells also demonstrated LRRK2-mediated phosphorylation of Akt1 (Ser473), suggesting that Akt1 is a convincing candidate for the physiological substrate of LRRK2. The disease-associated mutations, R1441C, G2019S, and I2020T, exhibited reduced interaction with, and phosphorylation of, Akt1, suggesting one possible mechanism for the neurodegeneration caused by LRRK2 mutations.

419 Article DJ-1 associates with synaptic membranes. 2011

Usami, Yukiko / Hatano, Taku / Imai, Satoshi / Kubo, Shin-ichiro / Sato, Shigeto / Saiki, Shinji / Fujioka, Yoichiro / Ohba, Yusuke / Sato, Fumiaki / Funayama, Manabu / Eguchi, Hiroto / Shiba, Kaori / Ariga, Hiroyoshi / Shen, Jie / Hattori, Nobutaka. ·Department of Neurology, Juntendo University School of Medicine, Japan. ·Neurobiol Dis · Pubmed #21645620.

ABSTRACT: Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons. Although many reports have suggested that genetic factors are implicated in the pathogenesis of PD, molecular mechanisms underlying selective dopaminergic neuronal degeneration remain unknown. DJ-1 is a causative gene for autosomal recessive form of PARK7-linked early-onset PD. A number of studies have demonstrated that exogenous DJ-1 localizes within mitochondria and the cytosol, and functions as a molecular chaperone, as a transcriptional regulator, and as a cell protective factor against oxidative stress. However, the precise subcellular localization and function of endogenous DJ-1 are not well known. The mechanisms by which mutations in DJ-1 contributes to neuronal degeneration also remain poorly understood. Here we show by immunocytochemistry that DJ-1 distributes to the cytosol and membranous structures in a punctate appearance in cultured cells and in primary neurons obtained from mouse brain. Interestingly, DJ-1 colocalizes with the Golgi apparatus proteins GM130 and the synaptic vesicle proteins such as synaptophysin and Rab3A. Förster resonance energy transfer analysis revealed that a small portion of DJ-1 interacts with synaptophysin in living cells. Although the wild-type DJ-1 protein directly associates with membranes without an intermediary protein, the pathogenic L166P mutation of DJ-1 exhibits less binding to synaptic vesicles. These results indicate that DJ-1 associates with membranous organelles including synaptic membranes to exhibit its normal function.

420 Article Small saccades restrict visual scanning area in Parkinson's disease. 2011

Matsumoto, Hideyuki / Terao, Yasuo / Furubayashi, Toshiaki / Yugeta, Akihiro / Fukuda, Hideki / Emoto, Masaki / Hanajima, Ritsuko / Ugawa, Yoshikazu. ·Department of Neurology, University of Tokyo, Tokyo, Japan. hideyukimatsumoto.jp@gmail.com ·Mov Disord · Pubmed #21449014.

ABSTRACT: The purpose of this study was to investigate abnormalities in visual scanning when Parkinson's disease patients view images of varying complexity. Eighteen nondemented Parkinson's disease patients and 18 normal subjects participated in the study. The ocular fixation position during viewing visual images was recorded using an eye-tracking device. The number of saccades, duration of fixation, amplitude of saccades, and scanned area in Parkinson's disease patients were compared with those in normal subjects. We also investigated whether the number of saccades, duration of fixation, or amplitude of saccades influenced the scanned area. While scanning images of varying complexity, Parkinson's disease patients made fewer saccades with smaller amplitude and longer fixation compared with normal subjects. As image complexity increased, the number of saccades and duration of fixation gradually approached those of normal subjects. Nevertheless, the scanned area in Parkinson's disease patients was consistently smaller than that in normal subjects. The scanned area significantly correlated with saccade amplitude in most images. Importantly, although Parkinson's disease patients cannot make frequent saccades when viewing simple figures, they can increase the saccade number and reduce their fixation duration when viewing more complex figures, making use of the abundant visual cues in such figures, suggesting the existence of ocular kinesie paradoxale. Nevertheless, both the saccade amplitude and the scanned area were consistently smaller than those of normal subjects for all levels of visual complexity. This indicates that small saccade amplitude is the main cause of impaired visual scanning in Parkinson's disease patients.

421 Article Posterior hypoperfusion in Parkinson's disease with and without dementia measured with arterial spin labeling MRI. 2011

Kamagata, Koji / Motoi, Yumiko / Hori, Masaaki / Suzuki, Michimasa / Nakanishi, Atsushi / Shimoji, Keigo / Kyougoku, Shinsuke / Kuwatsuru, Ryohei / Sasai, Keisuke / Abe, Osamu / Mizuno, Yoshikuni / Aoki, Shigeki / Hattori, Nobutaka. ·Department of Radiology, Juntendo University School of Medicine, Tokyo, Japan. kkamagat@juntendo.ac.jp ·J Magn Reson Imaging · Pubmed #21448943.

ABSTRACT: PURPOSE: To determine whether quantitative arterial spin labeling (ASL) can be used to evaluate regional cerebral blood flow in Parkinson's disease with dementia (PDD) and without dementia (PD). MATERIALS AND METHODS: Thirty-five PD patients, 11 PDD patients, and 35 normal controls were scanned by using a quantitative ASL method with a 3 Tesla MRI unit. Regional cerebral blood flow was compared in the posterior cortex using region-of-interest analysis. RESULTS: PD and PDD patients showed lower regional cerebral blood flow in the posterior cortex than normal controls (P = 0.002 and P = 0.001, respectively, analysis of variance with a Bonferroni post hoc test). CONCLUSION: This is the first study to detect hypoperfusion in the posterior cortex in PD and PDD patients using ASL perfusion MRI. Because ASL perfusion MRI is completely noninvasive and can, therefore, safely be used for repeated assessments, this method can be used to monitor treatment effects or disease progression in PD.

422 Article Initiation and inhibitory control of saccades with the progression of Parkinson's disease - changes in three major drives converging on the superior colliculus. 2011

Terao, Yasuo / Fukuda, Hideki / Yugeta, Akihiro / Hikosaka, Okihide / Nomura, Yoshiko / Segawa, Masaya / Hanajima, Ritsuko / Tsuji, Shoji / Ugawa, Yoshikazu. ·Department of Neurology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. yterao-tky@umin.ac.jp ·Neuropsychologia · Pubmed #21420990.

ABSTRACT: The cardinal pathophysiology of Parkinson's disease (PD) is considered to be the increase in the activities of basal ganglia (BG) output nuclei, which excessively inhibits the thalamus and superior colliculus (SC) and causes preferential impairment of internal over external movements. Here we recorded saccade performance in 66 patients with PD and 87 age-matched controls, and studied how the abnormality changed with disease progression. PD patients were impaired not only in memory guided saccades, but also in visually guided saccades, beginning in the relatively early stages of the disease. On the other hand, they were impaired in suppressing reflexive saccades (saccades to cue). All these changes deteriorated with disease progression. The frequency of reflexive saccades showed a negative correlation with the latency of visually guided saccades and Unified Parkinson's Disease Rating Scale motor subscores reflecting dopaminergic function. We suggest that three major drives converging on SC determine the saccade abnormalities in PD. The impairment in visually and memory guided saccades may be caused by the excessive inhibition of the SC due to the increased BG output and the decreased activity of the frontal cortex-BG circuit. The impaired suppression of reflexive saccades may be explained if the excessive inhibition of SC is "leaky." Changes in saccade parameters suggest that frontal cortex-BG circuit activity decreases with disease progression, whereas SC inhibition stays relatively mild in comparison throughout the course of the disease. Finally, SC disinhibition due to leaky suppression may represent functional compensation from neural structures outside BG, leading to hyper-reflexivity of saccades and milder clinical symptoms.

423 Article The impact in Japan of regulatory action on prescribing of dopamine receptor agonists: analysis of a claims database between 2005 and 2008. 2011

Ooba, Nobuhiro / Yamaguchi, Takuhiro / Kubota, Kiyoshi. ·Department of Pharmacoepidemiology, University of Tokyo, Graduate School of Medicine, Hongo 7-3-1, Tokyo, Japan. ·Drug Saf · Pubmed #21417505.

ABSTRACT: BACKGROUND: Use of the ergot-derived dopamine receptor agonists (cabergoline and pergolide) is associated with an increased risk of cardiac valvulopathy. Pergolide was withdrawn from the US market in 2007 because of the risk of valvular heart disease, while the European Medicines Agency (EMA) required a reduction in the maximum daily dosage of cabergoline and pergolide from 6 mg/day to 3 mg/day in 2008. In Japan, the package inserts of both drugs were revised in April 2007 to request that physicians conduct periodic ultrasonic cardiography (UCG) examinations for patients taking cabergoline or pergolide. Also, through face-to-face communication with medical representatives of drug companies, physicians were informed that use of cabergoline and pergolide has increased the risk of valvulopathy. However, cabergoline and pergolide have remained in wide use, even following the regulatory actions. OBJECTIVE: The objective of this study was to assess the impact of actions, including the package insert revision in April 2007, to encourage periodic UCG. METHODS: Data on monthly claims (January 2005-October 2008) covering 330 000 patients were obtained from a Japanese database vendor. We selected patients ≥40 years of age with Parkinson's disease. The impact of the regulatory action on the proportion of patients with Parkinson's disease prescribed cabergoline or pergolide was assessed by segmented regression analysis and by a statistical model of the rates of UCG examination in patients taking/not taking cabergoline or pergolide before and after the action. We also compared the use of cabergoline and pergolide before and after the action with that of other antiparkinson drugs. RESULTS: Of 574 patients with Parkinson's disease, the proportion of patients prescribed cabergoline or pergolide did not decrease but rather tended to increase after the action when analysed by segmented regression analysis (p = 0.13). Similarly, the proportion of the prevalent and incident users of cabergoline or pergolide did not change between two 19-month periods before and after the action. The adjusted rates of UCG examination per person-year before and after the action were both 0.02 in those not prescribed cabergoline or pergolide, but 0.02 before the action and 0.09 after the action in those taking either drug. The excess UCG examination rate of cabergoline or pergolide attributable to the action was 0.08 per person-year (95% CI 0.03, 0.11). While 1 of 49 (2%) patients taking cabergoline or pergolide had a UCG up to 19 months before the action, 9 of 36 (25%) patients taking cabergoline or pergolide had a UCG up to 19 months after the action. Annual sales from 2004 to 2008 were 195, 195, 170, 110 and 75 billion yen, respectively, and the number of valvulopathy events, including incompetence of aortic/mitral/tricuspid valves and cardiac valve disease, per annual sales from 2004 to 2008 were estimated at 0.23, 0.03, 0.08, 0.25 and 0.19 per billion yen, respectively. CONCLUSIONS: Following the actions in April 2007, no decrease in the use of cabergoline or pergolide occurred, although more patients administered the drug underwent a UCG. However, those undergoing a UCG represented one-quarter of the total number prescribed cabergoline or pergolide. To mitigate the risk, additional risk management tools such as patient registration may be needed to secure careful clinical examination (including UCG examination, if necessary) for cardiac function.

424 Article [Social cognitive impairment is an integral part of Parkinson disease]. 2011

Kawamura, Mitsuru. ·Department of Neurology, Showa University School of Medicine. ·Rinsho Shinkeigaku · Pubmed #21387692.

ABSTRACT: Parkinson disease (PD) is thought to be primarily a disorder of the motor system due to dysfunction of the nigrostriatal dopaminergic system. However, recent studies have revealed that social cognition tasks, such as facial expression recognition, decision-making, and mind-reading, are also impaired in PD. The studies also demonstrated that these impairments can occur due to dysfunctions of mesocorticolimbic dopaminergic system, particularly in the amygdala. Furthermore social cognitive impairments may develop in the early stage of PD. Therefore we have to understand PD as a not only movement but also cognitive disorder.

425 Article Adenosine A(2A) receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients. 2011

Mishina, Masahiro / Ishiwata, Kiichi / Naganawa, Mika / Kimura, Yuichi / Kitamura, Shin / Suzuki, Masahiko / Hashimoto, Masaya / Ishibashi, Kenji / Oda, Keiichi / Sakata, Muneyuki / Hamamoto, Makoto / Kobayashi, Shiro / Katayama, Yasuo / Ishii, Kenji. ·Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan. mishina@nms.ac.jp ·PLoS One · Pubmed #21386999.

ABSTRACT: Adenosine A(2A) receptors (A2ARs) are thought to interact negatively with the dopamine D(2) receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test). In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.

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