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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 DRS1 (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.

Objective We compared brain perfusion image using 3D-SSP analysis of 123I-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.

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. 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. There were significant reductions in FA values in the bilateral frontal ROIs possibly representing anterior cingulate bundles. 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.

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)≤2 or (2) CA≥3. We performed three-dimensional stereotactic surface projection and volume of interest analysis using 123I-IMP scintigraphy. Results Hypoperfusions of the bilateral posterior cingulate, rostrodorsal prefrontal, and left frontopolar cortices were shown in CA≤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.

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 ≥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.

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.

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).

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.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.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.

Objective – To compare brain perfusion image using three-dimensional stereotactic surface projection (3D-SSP) analysis of N-isopropyl-p-123I iodoamphetamine (123I-IMP) single photon emission computed tomography (SPECT) between patients with Parkinson's disease with 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.

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 < 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.

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-free 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.

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 123I-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.

Ni(mnt) 2 salts of 1′, 1′′′-diisopropyl-1,1′′-biferrocene ( 1 ) and 1′,l′′′-dibenzyl-1 ,1′′-biferrocene ( 2 ) have been prepared. Both complexes show segregated-stack crystal structure, consisting of a mixed-valent biferrocenium monocation and a Ni(mnt) 2 monoanion. The D-A ratio is 1:1 in both compounds. The trapped-valence state is demonstrated for 2 at room temperature.

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.

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.

Toyota has developed a new parallel hybrid power train system. This hybrid system achieved 50% reduction of CO2 emission in the 10–15 mode. The transaxle of this hybrid power train system contains a generator and a motor. It works as a continuously variable transmission by controlling the generator and the motor. The load for this transaxle and behavior of the power train under this hybrid system were analyzed by a simulation and an experiment. We designed the transaxle using the results.

喉頭横隔膜症とは, 喉頭に先天性または後天性の膜様組織が形成される疾患である. 今回われわれは術前に特記すべき上気道症状を呈さず, 気管挿管時に偶然発見された喉頭横隔膜症を経験したので報告する. 患者は60歳, 男性. 慢性副鼻腔炎に対し全身麻酔下での両側上顎洞篩骨洞根本術が予定された. 気管チューブ挿入時, 声門下に抵抗があったためラリンジアルマスク挿入下に気管支鏡検査を施行したところ, 喉頭に膜様物が確認された. 患者は1997年に他院にて直腸癌の手術を施行されており, このときの麻酔記録上特記事項はなかったことから後天性の喉頭横隔膜症が疑われた. 同疾患は無症状の患者がいるため, 気管挿管時には注意が必要である.

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.

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.

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.

Autosomal recessively inherited, loss of function mutations in PTEN‐induced kinase 1 (PINK1) typically lead to early onset Parkinson disease (EOPD).1 The PINK1 protein is expressed ubiquitously throughout the human brain.2 Impaired mitochondrial function and morphology have been described in both human PINK1 mutant patient tissue and different PINK1‐deficient in vitro or in vivo model systems.3 PINK1 has also been implicated in oxidative stress defense, mitophagy, and the regulation of mitochondrial calcium homeostasis.3 However, the precise mechanisms leading to neuronal cell death remain unclear. Pink1 knockout mice do not develop loss of dopamine (DA) neurons in the substantia nigra and can therefore only be of limited use in investigating the mechanisms leading to neuronal cell death in human Parkinson disease (PD).6 Zebrafish are increasingly being used to model neurodegenerative diseases.7 As vertebrates, they are closer to humans than other genetically tractable model organisms such as Drosophila or Caenorhabditis elegans. Zebrafish embryos develop externally, are transparent, and have a well‐characterized DA nervous system.8 To date, investigations of the functional consequences of PD gene dysfunction in zebrafish have relied on the injection of morpholino antisense oligonucleotides (MOs).7 A major limitation of this approach is that MOs injected into the fertilized egg lose their effect within 3 to 5 days postfertilization, thus precluding investigation of the morphological, biochemical, or behavioral effects of gene dysfunction at larval and adult stages. In addition, morpholinos are frequently associated with nonspecific, off‐target effects.9 Previous studies using the MO strategy to investigate the effects of PINK1 deficiency in zebrafish have led to conflicting results.10 Using the targeting induced local lesions in genomes (TILLING) approach, we have now established a stable line carrying a premature stop mutation in the kinase‐encoding domain of pink1 (Y431*), the zebrafish orthologue of human PINK1. We provide confirmation that this mutation leads to inactivation of PINK1 catalytic activity and decreased mRNA stability. We further demonstrate that PINK1 deficiency in Danio rerio results in highly specific abnormalities in early development, which closely match the biochemical and morphological manifestations of the human disease, with persisting loss of dopaminergic neurons in adulthood and also persisting mitochondrial impairment. Genome‐wide gene expression studies identified upregulation of TigarB, the zebrafish homologue of the TP53‐induced glycolysis and apoptosis regulator (TIGAR).13 Remarkably, TigarB knockdown resulted in normalization of mitochondrial function and complete rescue of ascending dopaminergic neurons. Modulation of TIGAR‐related mechanisms may therefore be a promising novel strategy to develop disease‐modifying therapy for PINK1‐related PD.

The effects of uniaxial strain and hydrostatic pressure on Y0.98Ca0.02Ba2Cu4O8 [called Y0.98(Ca0.02)-124] are investigated via AC magnetic measurements under stress corresponding to a pressure of (at most) 20 GPa. Hydrostatic contraction results in the largest enhancement of the superconducting transition temperature (Tc), whose maximum is 99 K, which is slightly lower than the maximum Tc achieved in YBa2Cu4O8 (called Y-124). The Meissner signal disappears at a hydrostatic pressure of approximately 15 GPa. This pressure region representing the Meissner signal is reduced by the out-of-plane contraction (along the c-axis), whereas it is increased by the in-plane contraction (along the c-plane). In the case of Y-124, both uniaxial contractions result in the disappearance of the Meissner signal at approximately 10 GPa prior to reaching the overdoped region. However, by doping Ca into the Y-site, we could investigate uniaxial strain effects characteristic of the so-called 124 structure without causing the stre...

Prognostic examinations and therapeutic strategy for peripheral facial nerve palsy are still obscure. We investigated the utility of examinations and the effects of treatment in these patients retrospectively.A total of 301 patients with peripheral facial nerve palsy were classified into three groups: Group A, cured within two months (n = 208), Group B, cured within six months (n = 34), Group C, uncured (n = 59). Patient's characteristics, electrophysiological examinations and treatment methods were compared between the groups.The mean age of patients was higher in Group C than in Group A, and the lowest palsy score was higher in Group A than in another groups (P0.05). Sensitivity and specificity for prognostic diagnosis were higher in electroneurography rather than blink reflex and Yanagihara grading system. Cervical sympathetic nerve block and hyperbaric oxygen therapy did not affect patients' prognosis. There were not significant difference on prognosis between over 120 mg x day(-1) and 60 mg x day(-1) of prednisolone.Lower palsy score and higher age were risks of bad prognosis and electroneurography is useful for prognostic evaluation of peripheral facial nerve palsy. Therapeutic effects of sympathetic nerve block and hyperbaric oxygen were not entirely clarified. Administration dose of prednisolone was thought to be sufficient with 60 mg x day(-1).

The nonlinear and linear magnetic responses to an ac magnetic field H are useful for the study of the magnetic dynamics of both magnetic domains and their constituent spins. In particular, the third-harmonic magnetic response M3ω reflects the dynamics of magnetic domains. Furthermore, by considering the ac magnetic response as a function of H, we can evaluate the degree of magnetic nonlinearity, which is closely related to M3ω. In this study, a series of approaches was used to examine the itinerant magnet MnP, in which both ferromagnetic and helical phases are present. On the basis of this investigation, we systematize the diagnostic approach to evaluating nonlinearity in magnetic responses.

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 α-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 of PD.

Recent findings suggest that a defect in the ubiquitin-proteasome system plays an important role in the pathogenesis of Parkinson'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.

Parkinson'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.

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 alpha-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.

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.

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 >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.

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.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.Attention should be paid to this syndrome when unexplained brain infarctions occur in patients with pleural mesothelioma.

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., Author Summary Parkinson’s disease (PD) is a neurodegenerative disease characterized by intraneuronal accumulation of alpha-synuclein (α-syn) called Lewy bodies and Lewy neurites. Recent genetic studies have revealed that mutations in glucocerebrosidase (GBA), a causative gene of Gaucher disease (GD), are a strong risk for PD. However, its pathological mechanisms leading to PD remain largely unknown. Here, we generated GBA nonsense mutant (GBA -/-) medaka which survive long enough for pathological analysis of disease progression. These mutant medaka display not only the phenotypes resembling human neuronopathic GD but also axonal accumulation of α-syn accompanied by impairment of the autophagy-lysosome pathway. Furthermore, the present study demonstrates this α-syn accumulation has negligible contribution to the pathogenesis of neuronopathic GD in medaka. GBA -/- medaka represent a valuable model for exploring the pathological mechanisms of PD with GBA mutations as well as neuronopathic GD, and our findings have important implications for the association of GBA mutations with PD.

We examined patients with and without auditory hallucinations, using n-isopropyl-p-[123I]iodoamphetamine 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.

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-1231 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 > or = 10 were included in the EDS group, and patients with an Epworth Sleepiness Scale score < or = 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.

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.

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.

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".

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.

The objective was to compare brain perfusion image using 3-dimensional stereotactic surface projection analysis of N-isopropyl-p-123I 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-123I 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.

In recent years, the demand for making a car comfortable is increasing and as a factor which governs the comfort of a car, improvement in the driving-stability is attempted. Although body rigidity, tire characteristic, aerodynamics, etc. are raised as factors affecting the design results, it is known experientially that the influence of a suspension is especially great. Therefore, the design of a suspension system becomes important for making a comfortable car. Generally, the design processes of a complicated system can be finished through three major stages, the concept design, the basic design, and the detailed design. For example, at the stage of detailed design, the design engineers have the CAD data for the manufacture, and at the same time they can develop very accurate computer simulation model from the CAD data to help them to make decision for special design factors. The basic concept of every CAE tool is to generate the analytical model by a series of discrete elements set instead of the physical parts. As a result, it becomes very difficult for the engineers to find the physical mechanism of the complicated behavior of their design from the results of numerical analysis. For the concept design processes, it is very important for the design engineers to understand the basic principle of their basic design plans and to compare with the different concepts to know which one has the highest potential to achieve the design aims. However the engineers have to accomplish these processes by only their experience. In this study, the authors proposed a new method to identify the important information which links to the basic principle of the physical behavior by using CAE technology. This method can help the engineers to grasp the basic physical characteristic that governs the first-order behavior.

Charge-transfer salts of branched-alkyl biferrocenes, (1',1' ''-R2-1,1' '-biferrocene)[Ni(mnt)2] (1a, R = isopropyl; 2a, R = dineopentyl) and (1',1' ''-R2-1,1' '-biferrocene)2[Co(mnt)2]2 (1b, R = isopropyl; 2b, R = dineopentyl), were prepared. Their valence states were investigated using X-ray crystallography and Mössbauer spectroscopy. Complexes 1a and 1b show segregated-stack crystal structures that contain columns of acceptors, whereas structures of 2a and 2b, which contain bulky donors, are rather discrete. All of the complexes contain mixed-valent biferrocenium monocations. A two-step valence transition was found in complex 1a. The crystal contains two crystallographically independent cations: one undergoes valence localization below room temperature; the other undergoes valence localization below ca. 130 K. The former transition is derived from asymmetry of the crystal environment around the cation, whereas the latter one is caused by symmetry lowering coupled with a spin-Peierls transition (T(C) = 133.2 K) associated with the dimerization of the acceptors. This compound was found to exhibit a dielectric response based on valence tautomerization. Other complexes (1b, 2a, and 2b) show a valence-trapped state. In all complexes, charge localization was found to occur through local electrostatic interactions between the donor's cationic moiety and the acceptor's electronegative moieties.

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.

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-123I 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 11 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. © 2005 Movement Disorder Society

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/M: 1.668+/-0.325, late H/M: 1.500+/-0.402) was less than that in multiple system atrophy (early H/M: 2.395+/-0.186, late H/M: 2.530+/-0.391) and controls (early H/M: 2.635+/-0.508, late H/M: 2.575+/-0.635) (early: P0.0001, late: P0.0001). 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+/-0.78) and Parkinson's disease (early S/M: 0.470+/-0.710) was decreased compared to that in controls (early S/M: 0.560+/-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.

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 123 I-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 123 I-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 123 I-IMP SPECT between the two diseases.

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.