Publications (74)170.79 Total impact
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Dataset: Clinical Section Decline of Vertical Gaze and Convergence with Aging
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ABSTRACT: Background: Disturbance of vertical eye movement and ocular convergence is often observed in elderly people, but little is known about its frequency. Objective: The purpose of this study was to investigate age-associated changes in vertical eye movement and convergence in healthy elderly people, using a digital video camera sys-tem. Methods: We analyzed vertical eye movements and convergence in 113 neurologically normal elderly sub-jects (mean age 70 years) in comparison with 20 healthy young controls (mean age 32 years). The range of verti-cal eye movement was analyzed quantitatively and con-vergence was analyzed qualitatively. Results: In the el-derly subjects, the angle of vertical gaze decreased with advancing age and it was significantly smaller than that of the younger subjects. The mean angle of upward gaze was significantly smaller than that of downward gaze for both young and elderly subjects. Upward gaze impair-ment became apparent in subjects in their 70s, and downward gaze impairment in subjects in their 60s. Dis-turbance in convergence also increased with advancing age, and was found in 40.7% of the elderly subjects. Con-clusion: These findings indicate that the mechanisms of age-related change are different for upward and down-ward vertical gaze. Digital video camera monitoring was useful for assessing and monitoring eye movements. -
Article: Comparative analysis of a complement fixation assay and enzyme immunoassay to determine the seroprevalence of measles and varicella in a survey of healthcare workers.
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ABSTRACT: Seroprevalence surveys of healthcare workers for vaccine-preventable diseases, including measles and varicella, are essential for disease prevention and infection control programmes. The purpose of this study was to compare the complement fixation (CF) assay and an enzyme immunoassay (EIA) to determine the prevalence of immunoglobulin G antibodies directed against measles and varicella viruses in healthcare workers. Antimeasles and antivaricella antibody titres were measured simultaneously in serum samples from healthcare workers employed at a Japanese university hospital, using the CF assay and an EIA. Serum samples were obtained from 898 healthcare workers. Seropositivity rates determined using the CF assay and EIA were 67.8% versus 94.0%, respectively, for measles, and 83.2% versus 97.6% for varicella. Compared with EIA, a nine- and 22-fold higher number of seronegative subjects was identified by the CF assay for measles and varicella, respectively. Differences between the CF assay and EIA in detecting seronegative or seropositive healthcare workers for measles and varicella suggest that undertaking a seroprevalence survey using an EIA, rather than a CF assay, would more accurately determine susceptibility to vaccine-preventable diseases, in healthcare settings.The Journal of international medical research 02/2013; 41(1):224-30. · 0.90 Impact Factor -
Article: Validation of a new mass screening tool for cognitive impairment: Cognitive Assessment for Dementia, iPad version.
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ABSTRACT: We have developed a new screening test for dementia that runs on an iPad and can be used for mass screening, known as the Cognitive Assessment for Dementia, iPad version (CADi). The CADi consists of items involving immediate recognition memory for three words, semantic memory, categorization of six objects, subtraction, backward repetition of digits, cube rotation, pyramid rotation, trail making A, trail making B, and delayed recognition memory for three words. The present study examined the reliability and validity of the CADi. CADi evaluations were conducted for patients with dementia, healthy subjects selected from a brain checkup system, and community-dwelling elderly people participating in health checkups. CADi scores were lower for dementia patients than for healthy elderly individuals and correlated significantly with Mini-Mental State Examination scores. Cronbach's alpha values for the CADi were acceptable (over 0.7), and test-retest reliability was confirmed via a significant correlation between scores separated by a one-year interval. These results suggest that the CADi is a useful tool for mass screening of dementia in Japanese populations.Clinical Interventions in Aging 01/2013; 8:353-60. · 2.08 Impact Factor -
Article: Efficacy of t2∗-weighted gradient-echo MRI in early diagnosis of cerebral venous thrombosis with unilateral thalamic lesion.
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ABSTRACT: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke with diverse etiologies and varied clinical presentations. Because of variability in clinical presentation and neuroimaging, CVT remains a diagnostic challenge. Recently, some studies have highlighted the value of T2∗-weighted gradient-echo MRI (T2∗WI) in the diagnosis of CVT. We report the case of a 79-year-old woman with CVT due to a hypercoagulable state associated with cancer. On the initial T2-weighted image (T2WI), there was a diffuse high-intensity lesion in the right thalamus, extending into the posterior limb of the internal capsule and midbrain. T2∗WI showed diminished signal and enlargement of the right basilar vein and the vein of Galen. Even though there is a wide range of differential diagnoses in unilateral thalamic lesions, and a single thalamus lesion is a rare entity of CVT, based on T2∗WI findings we could make an early diagnosis and perform treatment. Our case report suggests that T2∗WI could detect thrombosed veins and be a useful method of early diagnosis in CVT.Case reports in neurological medicine. 01/2013; 2013:964650. -
Article: Decreased functional connectivity by aging is associated with cognitive decline.
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ABSTRACT: Aging is related to cognitive decline, and it has been reported that aging disrupts some resting state brain networks. However, most studies have focused on the default mode network and ignored other resting state networks. In this study, we measured resting state activity using fMRI and explored whether cognitive decline with aging is related to disrupted resting state networks. Independent component analysis was used to evaluate functional connectivity. Notably, the connectivity within the salience network that consisted of the bilateral insula and the anterior cingulated cortex decreased with aging; the impairment of functional connectivity was correlated with measured decreases in individual cognitive abilities. Furthermore, certain internetwork connectivities (salience to auditory, default mode to visual, etc.) also decreased with aging. These results suggest that (1) aging affects not only the default mode network but also other networks, specifically the salience network; (2) aging affects internetwork connectivity; and (3) disruption of the salience network is related to cognitive decline in elderly people.Journal of Cognitive Neuroscience 07/2012; 24(11):2186-98. · 5.18 Impact Factor -
Article: The effect of ropinirole on apathy and depression after herpes encephalitis.
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ABSTRACT: We describe a 76-year-old man with herpes encephalitis whose symptom of severe apathy was improved by the dopamine D2/D3 receptor agonist ropinirole. Brain magnetic resonance imaging had shown lesions in the patient's right mesial temporal cortex, right insula, and bilateral medial frontal regions. During treatment with acyclovir, he had developed severe apathy and depression. On neuropsychological assessment, he scored 21/30 points on the Mini-Mental State Examination, 30/42 on the Starkstein Apathy Scale (cutoff score =16), and 59/80 on the Zung Self-Rating Depression Scale (cutoff score=40). We then started him on ropinirole 0.25 mg/day. Over the next 10 days, his apathy and depression gradually improved. On day 10 of treatment, follow-up testing showed that his Apathy Scale score had improved to 25 points. This case suggests that a low dose of a dopamine receptor agonist may be an effective treatment for patients who develop apathy and depression after encephalitis.Cognitive and behavioral neurology: official journal of the Society for Behavioral and Cognitive Neurology 05/2012; 25(2):98-102. · 1.09 Impact Factor -
Article: Reevaluation of the association of seven candidate genes with blood pressure and hypertension: a replication study and meta-analysis with a larger sample size.
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ABSTRACT: To obtain evidence for blood pressure (BP) trait association, we conducted an association study of selected candidate gene variants. In Japan, a total of 19,426 individuals underwent testing for genetic associations with systolic BP (SBP)/diastolic BP (DBP) and 9271 individuals (3460 cases and 5811 controls) underwent testing for genetic associations with dichotomous hypertension. Association with seven notable candidate genes was tested, namely, ACE, ADD1, ADRB2, AGT, CYP11B2, GNB3 and NOS3, followed by a joint meta-analysis involving previously reported multi-study populations, including >20,000 individuals (for SBP/DBP) and >17,000 individuals (for hypertension). BP trait associations at two loci (AGT rs699 and CYP11B2 rs1799998) were consistently replicated in the Japanese association study and joint meta-analysis involving the populations described above. Hypertension association reached genome-wide significance for the two variants, specifically, P=7.3 × 10(-10) for AGT rs699 and P=3.9 × 10(-8) for CYP11B2 rs1799998. In our study panels, the most significant association was found for CYP11B2 rs1799998 with all three BP traits: P=1.5 × 10(-5) for SBP, P=1.8 × 10(-5) for DBP and P=2.3 × 10(-5) for hypertension. A suggestive association with SBP (P=0.042), DBP (P=0.01) and hypertension (P=1.4 × 10(-5)) was also detected for ACE rs4340 (a proxy for ACE D/I polymorphism) in the joint meta-analysis. Our data provide evidence for true BP trait associations with two candidate gene variants. These variants were not identified in the previous genome-wide association studies, presumably because they did not reach a given threshold in the discovery stage. Thus, certain variants in genes with clinical and physiological relevance are likely to account for a portion of BP variance in the general population and are worth following up via a target gene approach.Hypertension Research 03/2012; 35(8):825-31. · 2.58 Impact Factor -
Article: Dysfunction of default-mode network in encephalopathy with a reversible corpus callosum lesion.
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ABSTRACT: Increasing attention has been paid recently to the study of spontaneous brain activity; moreover, particular attention has been paid to the concept of a default-mode network of brain function. Although the functional significance of the default-mode network remains a matter of debate, it has been suggested to be a candidate for the network subserving basic functions related to consciousness. We report the case of a 29-year-old man with encephalopathy and a reversible lesion of the entire corpus callosum. Despite resolution of corpus callosum lesion on magnetic resonance imaging (MRI) within 1 week, the patient persistently presented disturbance of consciousness. Resting-state functional MRI revealed that the posterior cingulate cortex/precuneus was functionally disconnected from other brain regions within the default-mode network. Our case report suggests that assessment of the functional connectivity in the resting-state default-mode network could be a useful marker of consciousness disturbance even in the presence of a reversible brain lesion.Journal of the neurological sciences 03/2012; 317(1-2):154-6. · 2.32 Impact Factor -
Article: Genome-wide association study of coronary artery disease in the Japanese.
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ABSTRACT: A new understanding of the genetic basis of coronary artery disease (CAD) has recently emerged from genome-wide association (GWA) studies of common single-nucleotide polymorphisms (SNPs), thus far performed mostly in European-descent populations. To identify novel susceptibility gene variants for CAD and confirm those previously identified mostly in populations of European descent, a multistage GWA study was performed in the Japanese. In the discovery phase, we first genotyped 806 cases and 1337 controls with 451 382 SNP markers and subsequently assessed 34 selected SNPs with direct genotyping (541 additional cases) and in silico comparison (964 healthy controls). In the replication phase, involving 3052 cases and 6335 controls, 12 SNPs were tested; CAD association was replicated and/or verified for 4 (of 12) SNPs from 3 loci: near BRAP and ALDH2 on 12q24 (P=1.6 × 10(-34)), HLA-DQB1 on 6p21 (P=4.7 × 10(-7)), and CDKN2A/B on 9p21 (P=6.1 × 10(-16)). On 12q24, we identified the strongest association signal with the strength of association substantially pronounced for a subgroup of myocardial infarction cases (P=1.4 × 10(-40)). On 6p21, an HLA allele, DQB1(*)0604, could show one of the most prominent association signals in an ∼8-Mb interval that encompasses the LTA gene, where an association with myocardial infarction had been reported in another Japanese study. CAD association was also identified at CDKN2A/B, as previously reported in different populations of European descent and Asians. Thus, three loci confirmed in the Japanese GWA study highlight the likely presence of risk alleles with two types of genetic effects - population specific and common - on susceptibility to CAD.European journal of human genetics: EJHG 03/2012; 20(3):333-40. · 3.56 Impact Factor -
Article: Elevated BAFF levels in the cerebrospinal fluid of patients with neuro-Behçet's disease: BAFF is correlated with progressive dementia and psychosis.
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ABSTRACT: Neuro-Behçet's disease (NBD) is a serious complication of Behçet's disease. Generally, NBD patients with a chronic course are refractory to immunosuppressive treatment, resulting in the deterioration of personality. In this study, levels of B cell-activating factor belonging to the TNF family (BAFF) were measured in the cerebrospinal fluid (CSF) from 18 patients with NBD, 27 patients with epidemic aseptic meningitis (AM), 24 patients with multiple sclerosis (MS) and 34 healthy controls. BAFF levels in patients with NBD were significantly elevated compared with healthy controls, but showed no statistically significant elevation compared with either of the disease controls. In contrast, CSF IL-6 levels were slightly elevated in patients with NBD and significantly elevated in patients with AM and MS compared with healthy controls. Patients with NBD were subdivided into two groups according to their clinical course (eight patients with a slowly progressive course presenting with psychosis and dementia and 10 patients with an acute course including aseptic meningitis, brainstem involvement and myelopathy). BAFF levels were significantly increased in those with a slowly progressive course compared with those with an acute course. CSF BAFF levels did not correlate with serum BAFF levels, CSF cell counts or CSF IL-6 levels in patients with NBD. These data suggested that BAFF was produced within the central nervous system and may be associated with the development of NBD, particularly with a progressive course.Scandinavian Journal of Immunology 02/2012; 75(6):633-40. · 2.23 Impact Factor -
Article: Cerebral embolism associated with left atrial myxoma that was treated with thrombolytic therapy.
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ABSTRACT: We present a case of cerebral embolism associated with a left atrial myxoma that was treated with intravenous thrombolytic therapy. A 79-year-old right-handed man with no history of neurological or psychiatric illnesses was referred to our hospital because of confusion. He had been self-supported in the activity of daily living and could enjoy gardening until just before his admission. He had aphasia, left conjugate deviation, right hemiparesis, and right pathological reflexes. His NIHSS score was 24. Cranial DWI showed hyperintense lesions in the left middle cerebral artery territory, and MRA revealed left middle cerebral artery occlusion. We started treatment with the recombinant tissue plasminogen activator alteplase intravenously 3 h after the onset. However, the therapy was ineffective, and the NIHSS score was 25 on the second day. A transthoracic echocardiogram and heart MRI showed a left atrial myxoma. However, surgery was contraindicated because of the patient's poor general condition. Although intravenous recombinant tissue plasminogen activator is a reasonable treatment for stroke patients, even with a cardiac myxoma, we cannot always expect good effects, especially if the emboli are parts of the tumor itself. In this case, we could not perform an endovascular mechanical embolectomy; however, we speculate that mechanical embolus retrieval in cerebral ischemia might be effective in such cases.Case Reports in Neurology 01/2012; 4(1):38-42. -
Article: Association of genetic variants influencing lipid levels with coronary artery disease in Japanese individuals.
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ABSTRACT: In Japanese populations, we performed a replication study of genetic loci previously identified in European-descent populations as being associated with lipid levels and risk of coronary artery disease (CAD). We genotyped 48 single nucleotide polymorphisms (SNPs) from 22 candidate loci that had previously been identified by genome-wide association (GWA) meta-analyses for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and/or triglycerides in Europeans. We selected 22 loci with 2 parallel tracks from 95 reported loci: 16 significant loci (p<1×10(-30) in Europeans) and 6 other loci including those with suggestive evidence of lipid associations in 1292 GWA-scanned Japanese samples. Genotyping was done in 4990 general population samples, and 1347 CAD cases and 1337 controls. For 9 SNPs, we further examined CAD associations in an additional panel of 3052 CAD cases and 6335 controls. Significant lipid associations (one-tailed p<0.05) were replicated for 18 of 22 loci in Japanese samples, with significant inter-ethnic heterogeneity at 4 loci-APOB, APOE-C1, CETP, and APOA5-and allelic heterogeneity. The strongest association was detected at APOE rs7412 for LDL-C (p = 1.3×10(-41)), CETP rs3764261 for HDL-C (p = 5.2×10(-24)), and APOA5 rs662799 for triglycerides (p = 5.8×10(-54)). CAD association was replicated and/or verified for 4 loci: SORT1 rs611917 (p = 1.7×10(-8)), APOA5 rs662799 (p = 0.0014), LDLR rs1433099 (p = 2.1×10(-7)), and APOE rs7412 (p = 6.1×10(-13)). Our results confirm that most of the tested lipid loci are associated with lipid traits in the Japanese, further indicating that in genetic susceptibility to lipid levels and CAD, the related metabolic pathways are largely common across the populations, while causal variants at individual loci can be population-specific.PLoS ONE 01/2012; 7(9):e46385. · 4.09 Impact Factor -
Article: Interaction between Emotion and Attention Systems.
Frontiers in Neuroscience 01/2012; 6:139. -
Article: Is dorsal anterior cingulate cortex activation in response to social exclusion due to expectancy violation? An fMRI study.
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ABSTRACT: People are typically quite sensitive about being accepted or excluded by others. Previous studies have suggested that the dorsal anterior cingulate cortex (dACC) is a key brain region involved in the detection of social exclusion. However, this region has also been shown to be sensitive to non-social expectancy violations. We often expect other people to follow an unwritten rule in which they include us as they would expect to be included, such that social exclusion likely involves some degree of expectancy violation. The present event-related functional magnetic resonance imaging (fMRI) study sought to separate the effects of expectancy violation from those of social exclusion, such that we employed an "overinclusion" condition in which a player was unexpectedly overincluded in the game by the other players. With this modification, we found that the dACC and right ventrolateral prefrontal cortex (rVLPFC) were activated by exclusion, relative to overinclusion. In addition, we identified a negative correlation between exclusion-evoked brain activity and self-rated social pain in the rVLPFC, but not in the dACC. These findings suggest that the rVLPFC is critical for regulating social pain, whereas the dACC plays an important role in the detection of exclusion. The neurobiological basis of social exclusion is different from that of mere expectancy violation.Frontiers in Evolutionary Neuroscience 01/2012; 4:11. -
Article: Contribution of cystatin C gene polymorphisms to cerebral white matter lesions.
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ABSTRACT: Vascular remodeling plays an important role in the development of arteriosclerosis and any of the resulting white matter lesions in the brain. An imbalance between cysteine proteases and the cysteine protease inhibitor cystatin C (CST3) may exacerbate vascular remodeling through degradation of extracellular matrix proteins. Therefore, we evaluated the association between functional polymorphisms in the CST3 gene and the development of cerebral white matter lesions. In a total of 2,676 participants, 3 CST3 genepolymorphisms were genotyped in 92 cases with severe deep white matter hyperintensity (DWMH), and 184 subjects were randomly selected age- and sex-matched controls without any signs of DWMH. The genetic effects of these polymorphisms on DWMH and plasma CST3 levels were examined. CST3 expression vectors were transfected into an astrocytoma cell line and the expression level of CST3 mRNA was analyzed by quantitative RT-PCR. Intracellular and secreted levels of CST3 in the cell culture were quantified by Western blot and ELISA, respectively. A significant association was found between one CST3 gene haplotype and DWMH (p = 0.002). This haplotype was also associated with lower plasma CST3 levels (p = 0.01). An in vitro transfection study revealed that the +148A allele, which is included in the risk haplotype, significantly reduced the secretion and increased the intracellular accumulation of CST3; however, it had no effect on the mRNA expression. Our study shows that polymorphisms in the CST3 gene are significantly associated with the likelihood of DWMH. Substitution of A for G at +148 of the CST3 gene decreased the extracellular availability of CST3 in vitro, which might result in the activation of protease activity.Cerebrovascular Diseases 11/2011; 32(5):489-96. · 2.72 Impact Factor -
Article: Gastroesophageal Reflux during Enteral Feeding in Stroke Patients: A 24-hour Esophageal pH-monitoring Study.
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ABSTRACT: BACKGROUND: Patients who are unable to eat or drink after stroke may receive percutaneous endoscopic gastrostomy (PEG) or nasogastric tube feeding. Although the most common serious complication is well known to be aspiration pneumonia, the role of gastroesophageal reflux (GER) has not been fully assessed. The aim of this study was to examine, by means of 24-hour esophageal pH monitoring, whether GER is related to aspiration pneumonia and whether the size and laterality of brain lesions influence GER. METHODS: Sixteen stroke patients were examined using a Degitrapper pH400 (Medtronic Japan Co., Tokyo, Japan) and Zinetics 24ME multiuse pH catheter (Medtronic). All patients had stroke lesions in the territory of the left or right middle cerebral artery that were confirmed by magnetic resonance imaging (MRI) and were receiving PEG or nasogastric feeding. Stroke volume was measured with MRIcron software. RESULTS: Nine patients (56%) were diagnosed with GER, and 10 (63%) developed aspiration pneumonia after enteral feeding. The rate of aspiration pneumonia was significantly higher in patients with GER (88.9%) than in those without GER (42.9%; P = .04). Patients with left hemispheric lesions had a significantly higher incidence of acid reflex than those with right lesions (116 ± 105 vs 13 ± 17; P = .04). There were no significant differences in total time of acid reflux or mean pH value between patients with left and right hemispheric lesions. The lesion volume had no significant effect on any of 3 indices of GER. CONCLUSIONS: GER is associated with aspiration pneumonia and occurs more often in patients with stroke lesions in the left hemisphere.Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 08/2011; -
Article: Association of cognitive dysfunction with hippocampal atrophy in elderly Japanese people with type 2 diabetes.
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ABSTRACT: This study aimed to examine the associations of cognitive function with hippocampal and whole brain atrophies, age, education, and diabetes-related parameters in patients with type 2 diabetes. Sixty-one patients over 65 years of age with type 2 diabetes and 53 age- and sex-matched non-diabetic controls were enrolled. Hippocampal and whole brain atrophies were assessed by quantifying hippocampal and brain volumes by brain magnetic resonance imaging. Cognitive function was evaluated by Mini-Mental State Examination (MMSE) and the Revised Hasegawa Dementia Scale (HDS-R). Compared with the non-diabetic group, patients with type 2 diabetes showed significant increases in hippocampal and whole brain atrophies. The MMSE and HDS-R scores in type 2 diabetic patients showed significant negative correlations with age and significant positive correlations with years of education. These scores were also significantly negatively correlated with hippocampal atrophy, but not whole brain atrophy. Hippocampal atrophy in diabetic patients did not, however, correlate with age, years of education, or diabetes-related parameters. We showed hippocampal and whole brain atrophies to be more frequent in elderly patients with type 2 diabetes than in non-diabetic controls. Their cognitive functions were significantly and negatively associated with hippocampal atrophy.Diabetes research and clinical practice 08/2011; 94(2):180-5. · 2.16 Impact Factor -
Article: Inter-individual discount factor differences in reward prediction are topographically associated with caudate activation.
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ABSTRACT: In general, humans tend to devalue a delayed reward. Such delay discounting is a theoretical and computational concept in which the discount factor influences the time scale of the trade-off between delay of reward and amount of reward. The discount factor relies on the individual's ability to evaluate the future reward. Using functional magnetic resonance imaging, we investigated brain mechanisms for reward valuation at different individual discount factors in a delayed reward choice task. In the task, participants were required to select small/immediate or large/delayed rewards to maximize the total reward over time. The discount factor for each participant individually was calculated from the behavioral data based on an exponential discounting model. The estimated value of a future reward increases as the expected delivery approaches, so the time course of these estimated values was computed based on each individual's discount factor; each was entered into the regression analysis as an explanatory (independent) variable. After the region of interest was narrowed anatomically to the caudate, a peak coordinate was detected in each individual. A correlation analysis revealed that the location of the peak along the dorsal-ventral axis in the right caudate was positively correlated with the discount factor. This implies that individuals who showed a larger discount factor had peak activations in a more dorsal part of the right caudate associated with future reward prediction. This evidence also suggests that a higher ability to delay reward prediction might be related to activation of the more dorsal caudate.Experimental Brain Research 06/2011; 212(4):593-601. · 2.39 Impact Factor -
Article: Cystatin C induces apoptosis and tyrosine hydroxylase gene expression through JNK-dependent pathway in neuronal cells.
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ABSTRACT: Cystatin C (CysC), an endogenous cysteine protease inhibitor, has been implicated in the apoptosis and differentiation processes of neuronal cells. In this study, we have investigated the pathway involved in the process. A human neuronal hybridoma cell line (A1 cell) was treated with CysC in both undifferentiated and retinoic acid (RA)-induced differentiated conditions, which decreased overall process length in both conditions. Also, CysC increased apoptotic cell number time-dependently, as revealed by TUNEL assay. Western blot analysis demonstrated that in differentiated A1 cells, CysC treatment decreased Bcl-2 and increased active caspase-9 protein level time-dependently. Immunocytochemistry results revealed that, CysC treatment significantly increased active form of Bax expressing cell number, which co-localized with mitochondria. Mitogen activated protein (MAP) kinase inhibition experiments showed that Bax mRNA induction and Bcl-2 mRNA inhibition by CysC treatment were c-Jun N-terminal kinase (JNK)-dependent. After RA-induced differentiation, choline acetyltransferase (ChAT) and neurofilament (NF) mRNA levels were increased in A1 cells. CysC treatment inhibited NF mRNA level in both undifferentiated and RA-differentiated, and increased TH mRNA in differentiated A1 neurons. Analysis of signal transduction pathway demonstrated that TH gene induction was also JNK-dependent. Thus, our results demonstrated the significance of JNK-dependent pathways on CysC-induced apoptosis and TH gene expression in neuronal cells, which might be an important target in the management of CysC dependent neurodegenerative processes.Neuroscience Letters 06/2011; 496(2):100-5. · 2.11 Impact Factor -
Article: Microbleeds are associated with subsequent hemorrhagic and ischemic stroke in healthy elderly individuals.
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ABSTRACT: Cerebral microbleeds (MBs) are frequently detected in patients with stroke, especially those who experience intracerebral hemorrhage. However, the clinical significance of MBs in subjects without cerebrovascular disease is still unclear. We performed a prospective study to determine whether the presence of MBs provides useful prognostic information in healthy elderly individuals. We tracked 2102 subjects (mean age, 62.1 years) over a mean interval of 3.6 years after they voluntarily participated in the brain checkup system at the Shimane Institute of Health Science. An initial assessment was performed to document the presence of MBs and silent ischemic brain lesions and to map the location of the MBs. During the follow-up period, we obtained information about stroke events that occurred in each subject. MBs were detected in 93 of the 2102 subjects (4.4%). Strokes occurred in 44 subjects (2.1%) during the follow-up period. They were significantly more common among subjects with MBs. Age and hypertension were independent risk factors for MBs. The presence of MBs was more strongly associated with a deep brain hemorrhage (hazard ratio, 50.2; 95% CI, 16.7 to 150.9) than ischemic stroke (hazard ratio, 4.48; 95% CI, 2.20 to 12.2). All hemorrhagic strokes occurred in deep brain regions, and they were associated with MBs located in the deep brain region. This longitudinal study demonstrated that the presence of MBs can be used to predict hemorrhagic and ischemic stroke, even in healthy elderly individuals.Stroke 05/2011; 42(7):1867-71. · 5.73 Impact Factor
Top co-authors
Top Journals
Institutions
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2002–2013
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Shimane University
- • Department of Laboratory Medicine
- • Faculty of Medicine
- • Department of Neurology
- • Department of Internal Medicine II
Matsue-shi, Shimane-ken, Japan
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2011–2012
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National Center for Global Health and Medicine in Japan
Tokyo, Tokyo-to, Japan
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