PubMed Health⌕ Search

Biomedical subjects

Saburo Sakoda

Publications and source records attributed to Saburo Sakoda.

At least 19 recordsLinked to original sources
PubMed2006

Frontal regions involved in learning of motor skill--A functional NIRS study.

To investigate cerebral mechanisms underlying learning of motor skill, we assessed serial changes of cortical activation patterns during a pursuit rotor (PR) task in 18 right-handed, healthy subjects using a functional near-infrared spectroscopy (fNIRS) system. Subjects performed the task with the right hand for 30 s alternated with 30-s rest for 8 repetitions (cycle1 to 8). Gains in motor skill were evaluated by time for keeping the stylus on the target (max 30 s), surface EMG patterns and trajectories of the arm. Performance improved with repetitions of the task cycles (12.9/17.1/19.3/20.0/21.1/22.2/23.6/23.9 s on average) and reached plateau at the 7th cycle. Reciprocal EMG patterns and steady trajectories were associated with acquisition of the motor skill. Task-related increases of oxygenated hemoglobin (oxyHb) were observed in the channels covering the sensorimotor cortex (SMC), premotor and prefrontal regions. There were also task-related decreases of deoxygenated hemoglobin (deoxyHb) in these areas although the changes were smaller compared with those of oxyHb. The center of task-related increases of oxyHb was initially located in the presupplementary motor area (preSMA) and shifted caudally to the supplementary motor area (SMA) with cycle repetitions. The ratios of oxyHb changes in preSMA to SMA significantly decreased with task repetitions. DeoxyHb changes confirmed the activation patterns. These data suggest that preSMA plays an important role in the early phase of motor learning while the SMA might be more involved in the late learning phase of the motor skill.

Adult↗
PubMed2006

Plexin-A1 and its interaction with DAP12 in immune responses and bone homeostasis.

Semaphorins and their receptors have diverse functions in axon guidance, organogenesis, vascularization and/or angiogenesis, oncogenesis and regulation of immune responses. The primary receptors for semaphorins are members of the plexin family. In particular, plexin-A1, together with ligand-binding neuropilins, transduces repulsive axon guidance signals for soluble class III semaphorins, whereas plexin-A1 has multiple functions in chick cardiogenesis as a receptor for the transmembrane semaphorin, Sema6D, independent of neuropilins. Additionally, plexin-A1 has been implicated in dendritic cell function in the immune system. However, the role of plexin-A1 in vivo, and the mechanisms underlying its pleiotropic functions, remain unclear. Here, we generated plexin-A1-deficient (plexin-A1(-/-)) mice and identified its important roles, not only in immune responses, but also in bone homeostasis. Furthermore, we show that plexin-A1 associates with the triggering receptor expressed on myeloid cells-2 (Trem-2), linking semaphorin-signalling to the immuno-receptor tyrosine-based activation motif (ITAM)-bearing adaptor protein, DAP12. These findings reveal an unexpected role for plexin-A1 and present a novel signalling mechanism for exerting the pleiotropic functions of semaphorins.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Inverse correlation between the formation of mitochondria-derived vacuoles and Lewy-body-like hyaline inclusions in G93A superoxide-dismutase-transgenic mice.

In G93A mice, the most popular model of amyotrophic lateral sclerosis (ALS), neuronal Lewy-body-like hyaline inclusions (LBHIs) and mitochondria-derived vacuoles are observed in addition to motor neuron loss. Although LBHIs are thought to be toxic, the significance of the mitochondria-derived vacuoles has not been fully investigated. In this study, the relationship between the formation of these vacuoles and LBHIs was clarified statistically in the lumbar segment from two phyletic lines of G93A mice (G1L, G1H), using immunohistochemical methods. Furthermore, the distributions of vacuoles and LBHIs were examined in the pons including the facial nucleus, where pathological changes occur in ALS patients and G93A mice. Numerous vacuoles 2-3 microm in diameter were detected in the neuropil of the lumbar segment from G1L mice euthanatized approximately 3.5 months prior to the onset of the disease. Most of the vacuoles disappeared, but some became larger as the disease progressed. The number of vacuoles with a diameter exceeding 5 microm began to decrease after disease onset, while that of intra-neuritic LBHIs increased rapidly. There was a strong inverse correlation between the numbers of vacuoles and LBHIs in symptomatic mice (P<0.01; G1L, r=-0.91; G1H, r=-0.93). In the facial nucleus of G1L mice, where the number of motor neurons was significantly reduced, only a few LBHIs were detected along with prominent vacuole formation. In contrast, significantly more LBHIs with little vacuole formation were evident around the facial nucleus in G1L mice. Furthermore, the SOD1 immunoreactivity in vacuoles initially increased and then decreased after disease onset. Taken together, the present findings suggest that the mitochondria-derived vacuoles might prevent the formation of LBHIs by sequestering mutated SOD1 from the cytoplasm.

Amyotrophic Lateral Sclerosis↗
PubMed2006

Magnetic resonance spectroscopic study of Alzheimer's disease and frontotemporal dementia/Pick complex.

Disease-specific metabolic changes in Alzheimer's disease and frontotemporal dementia/Pick complex were examined by proton magnetic resonance spectroscopy at 3.0 T. Spectra were acquired from posterior and anterior cingulate cortices and the parieto-occipital and frontal white matter. This study included eight Alzheimer's disease patients, 10 frontotemporal dementia/Pick complex patients and 14 healthy volunteers. N-acetylaspartate/creatine+phosphocreatine ratio was reduced in the posterior cingulate cortex in the Alzheimer's disease and frontotemporal dementia/Pick complex patients. The Alzheimer's disease patients, however, showed a posterior dominant decrease, whereas the frontotemporal dementia/Pick complex patients showed a frontal predominant decrease. These different distributions of metabolic changes may represent the underlying pathological processes in each disease. Our standardized protocol of proton magnetic resonance spectroscopy measurement may be helpful in differentiating these dementia subtypes.

Aged↗
PubMed2006

Class Ic antiarrhythmics block human skeletal muscle Na channel during myotonia-like stimulation.

Flecainide, a class Ic antiarrhythmic drug, has been anecdotally reported to improve myotonia, but little is known about its kinetics on human skeletal muscle sodium channels applicable in vivo. Here we explored the anti-myotonic action of flecainide for human skeletal muscle sodium channels heterologously expressed in cultured cells. Flecainide blocked sodium channels in a highly state-dependent manner with 20-fold difference in IC(50) between use-dependent and tonic blocks. When pulses of brief depolarization simulating myotonia were applied from a holding potential of -90 mV, flecainide at therapeutic concentrations significantly blocked sodium currents. Flecainide slowed the time course of recovery but most channels recovered from block within 10-20 s. In contrast to mexiletine, flecainide did not markedly block sodium current during prolonged depolarization, suggesting an open-channel blocking action. Considering the slow recovery from block and the specific action against repetitive depolarization, flecainide may represent a potent therapeutic agent for myotonia.

Anti-Arrhythmia Agents↗
PubMed2006

The "cross" signs in patients with multiple system atrophy: a quantitative study.

Patients with multiple system atrophy (MSA) may show the "cross" sign in the pontine base that has been considered as an expression of the degeneration of pontine neurons and transverse pontocerebellar fibers. However, correlations between pontine base atrophy and existence of "cross" sign have not been fully investigated. The authors studied 68 patients with MSA (47 MSA-C [predominantly cerebellar ataxia], 21 MSA-P [predominantly parkinsonism], mean [+/-SD ] 58.7 +/- 10.9 years). T1-weighted (T1W) sagittal and axial images and T2-weighted (T2W) axial images were obtained for all patients and controls. To measure the areas of pontine basis and cerebellar vermis, the authors used midsagittal T1W images and analyzed a bit map transformed on a computer. They classified atrophy in the pontine base into 3 grades. There is significant correlation between atrophies of pontine base and existence of the cross sign. All patients with a smaller area of pontine base 2 standard deviations below those of normal controls had the cross sign. This supports that existence of the cross sign depends only on the extent of pontine base atrophies.

Adult↗
PubMed2005

Loss of dopaminergic neurons by the induction of inducible nitric oxide synthase and cyclooxygenase-2 via CD 40: relevance to Parkinson's disease.

A glial reaction associated with up-regulation of inflammatory molecules has been suggested to play an important role in dopaminergic neuron loss in Parkinson's disease (PD). Among inflammatory molecules, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) have been focused upon as key factors in the pathogenesis. However, the mechanism of how these molecules are induced in PD brains is not clearly understood. We focused on CD 40, which is expressed on neural cells and could be implicated in the neuroinflammation by inducing inflammatory molecules. We showed that both iNOS and COX-2 were up-regulated in microglia and astrocytes by CD 40 stimulation in association with a low dose of interferon-gamma (IFN-gamma) in vitro. Selective loss of dopaminergic neurons was induced by costimulation with CD 40 and IFN-gamma in mesencephalic cultures, which was protected by selective inhibitors of iNOS and/or COX-2. We also found in CD 40-stimulated astrocytes an increase of a low-affinity IgE receptor CD 23, which is known to induce iNOS expression. Together these data suggest that up-regulated iNOS and COX-2 via the CD 40 pathway may lead to dopaminergic neuron loss and may participate in the neuroinflammaory pathway of PD.

Animals↗
PubMed2005

Vitamin K2 ameliorates experimental autoimmune encephalomyelitis in Lewis rats.

Vitamin K2 (VK2), which has been in wide use for the management of hypoprothrombinemia and osteoporosis in Japan, was tested for its efficacy on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). The severity of EAE was significantly ameliorated by the prophylactic administration of VK2, though it was not effective when given after the onset. Inflammatory cellular infiltration and the expression of both MHC class II and inducible nitric oxide synthase (iNOS) were reduced in the spinal cords of VK2-treated rats with EAE. The inhibitory effect of VK2 on the iNOS expression in glial cells was also observed in vitro. Considering the long use of VK2 without noticeable untoward effects, it may be applicable to the patients with MS.

Animals↗
PubMed2005

Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a debilitating multisystemic disorder caused by a CTG repeat expansion in the DMPK gene. Aberrant splicing of several genes has been reported to contribute to some symptoms of DM1, but the cause of muscle weakness in DM1 and elevated Ca2+ concentrations in cultured DM muscle cells is unknown. Here, we investigated the alternative splicing of mRNAs of two major proteins of the sarcoplasmic reticulum, the ryanodine receptor 1 (RyR1) and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) 1 or 2. The fetal variants, ASI(-) of RyR1 which lacks residue 3481-3485, and SERCA1b which differs at the C-terminal were significantly increased in skeletal muscles from DM1 patients and the transgenic mouse model of DM1 (HSA(LR)). In addition, a novel variant of SERCA2 was significantly decreased in DM1 patients. The total amount of mRNA for RyR1, SERCA1 and SERCA2 in DM1 and the expression levels of their proteins in HSA(LR) mice were not significantly different. However, heterologous expression of ASI(-) in cultured cells showed decreased affinity for [3H]ryanodine but similar Ca2+ dependency, and decreased channel activity in single-channel recording when compared with wild-type (WT) RyR1. In support of this, RyR1-knockout myotubes expressing ASI(-) exhibited a decreased incidence of Ca2+ oscillations during caffeine exposure compared with that observed for myotubes expressing WT-RyR1. We suggest that aberrant splicing of RyR1 and SERCA1 mRNAs might contribute to impaired Ca2+ homeostasis in DM1 muscle.

Alternative Splicing↗
PubMed2005

Ssdp1 regulates head morphogenesis of mouse embryos by activating the Lim1-Ldb1 complex.

The transcriptional activity of LIM-homeodomain (LIM-HD) proteins is regulated by their interactions with various factors that bind to the LIM domain. We show that reduced expression of single-stranded DNA-binding protein 1 (Ssdp1), which encodes a co-factor of LIM domain interacting protein 1 (Ldb1), in the mouse mutant headshrinker (hsk) disrupts anterior head development by partially mimicking Lim1 mutants. Although the anterior visceral endoderm and the anterior definitive endoderm, which together comprise the head organizer, were able to form normally in Ssdp1(hsk/hsk) mutants, development of the prechordal plate was compromised. Head development is partially initiated in Ssdp1(hsk/hsk) mutants, but neuroectoderm tissue anterior to the midbrain-hindbrain boundary is lost, without a concomitant increase in apoptosis. Cell proliferation is globally reduced in Ssdp1(hsk/hsk) mutants, and approximately half also exhibit smaller body size, similar to the phenotype observed in Lim1 and Ldb1 mutants. We also show that Ssdp1 contains an activation domain and is able to enhance transcriptional activation through a Lim1-Ldb1 complex in transfected cells, and that Ssdp1 interacts genetically with Lim1 and Ldb1 in both head development and body growth. These results suggest that Ssdp1 regulates the development of late head organizer tissues and body growth by functioning as an essential activator component of a Lim1 complex through interaction with Ldb1.

Animals↗
PubMed2005

Determination of transverse relaxation rate for estimating iron deposits in central nervous system.

To determine the amount of iron deposits in the basal ganglia, we examined 13 healthy volunteers with a 1.5 T MRI system using three transverse relaxation rates measured with two sequences. The transverse relaxation rates comprise the reversible contribution (R2') and irreversible contribution (R2) to a phase-reversal 180 degrees -pulse sequence. The transverse relaxation rates with the estimated iron indicated that both R2 and R2' had a robust relationship with brain iron level as determined from published post mortem data. This was the case only when the analyses are limited to the subcortical gray matter regions, however. R2' was affected by macroscopic magnetic field inhomogeneity arising from the skull bases, so that it was less robust for estimating the amount of iron deposits in the basal ganglia.

Adult↗
PubMed2005

[A hypnotic drug for sleep disturbances in patients with Parkinson's disease].

Patients with Parkinson's disease have been known to have sleep disturbances of various types. Zolpidem tartrate, an imidazopyrimidine short-acting hypnotic drug used treat insominia and several patients with PD have described a significant improvement of parkinsonian symptoms after administration of zolpidem tartrate. We tried to evaluate effect of zolpidem tartrate for sleep disturbances in patients with PD by a Japanese version of Chaudhuri's Parkinson's disease Sleep Scale (PDSS) and Unified Parkinson's disease rating Scale (UPDRS) motor scale. Twelve patients with PD (mean age 67.4 years old, range 40-77 years old) were evaluated by PDSS and UPDRS before and two weeks after prescribed zolpidem tartrate 5 mg per day. Patients showed improvement in items relating overall sleep disturbances, sleep refreshment and morning stiffness. Disabilities remained unchanged before and two weeks after prescribing zolipdem tartrate. Zolpidem tartrate may be useful for sleep disturbances in patients with PD and for improving their quality of daily livings.

Adult↗
PubMed2004

Accumulation of protein-bound 4-hydroxy-2-hexenal in spinal cords from patients with sporadic amyotrophic lateral sclerosis.

4-Hydroxy-2-hexenal (HHE) is a toxic, reactive aldehydic intermediate formed by nonenzymatic peroxidation of n-3 polyunsaturated fatty acids. The aim of this study was to determine the implication for HHE in the pathomechanism of amyotrophic lateral sclerosis (ALS) by immunohistochemical and enzyme-linked immunosorbent assay (ELISA) techniques using a mouse monoclonal IgG(1) antibody mAbHHE53 specific for protein-bound HHE. Immunohistochemical analysis on formalin-fixed, paraffin-embedded sections and frozen sections of spinal cords obtained at autopsy from 10 sporadic ALS patients and 10 age-matched control subjects demonstrated that protein-bound HHE immunoreactivity was seen and was prominent in the entire gray matter in the ALS cases and localized in the neurons, reactive astrocytes, microglial cells, and the surrounding neuropil, while the immunoreactivity was obscure or undetectable in the control cases. No significant protein-bound HHE immunoreactivity was seen in sections processed with omission of mAbHHE53 or in sections incubated with the antibody with an excess of the respective antigen. Competitive ELISA analysis on trypsin-digested protein extracts of fresh-frozen spinal cord samples disclosed a significant increase in protein-bound HHE level in the ALS cases compared with the control cases. Our results indicate that enhanced HHE formation occurs in the entire gray matter of sporadic ALS spinal cords and suggest that the selective vulnerability of motor neurons to HHE mediates the pathomechanism of this disease.

Aged↗
PubMed2004

Critical roles of CXC chemokine ligand 16/scavenger receptor that binds phosphatidylserine and oxidized lipoprotein in the pathogenesis of both acute and adoptive transfer experimental autoimmune encephalomyelitis.

The scavenger receptor that binds phosphatidylserine and oxidized lipoprotein (SR-PSOX)/CXCL16 is a chemokine expressed on macrophages and dendritic cells, while its receptor expresses on T and NK T cells. We investigated the role of SR-PSOX/CXCL16 on acute and adoptive experimental autoimmune encephalomyelitis (EAE), which is Th1-polarized T cell-mediated autoimmune disease of the CNS. Administration of mAb against SR-PSOX/CXCL16 around the primary immunization decreased disease incidence of acute EAE with associated reduced infiltration of mononuclear cells into the CNS. Its administration was also shown to inhibit elevation of serum IFN-gamma level at primary immune response, as well as subsequent generation of Ag-specific T cells. In adoptive transfer EAE, treatment of recipient mice with anti-SR-PSOX/CXCL16 mAb also induced not only decreased clinical disease incidence, but also diminished traffic of mononuclear cells into the CNS. In addition, histopathological analyses showed that clinical development of EAE correlates well with expression of SR-PSOX/CXCL16 in the CNS. All the results show that SR-PSOX/CXCL16 plays important roles in EAE by supporting generation of Ag-specific T cells, as well as recruitment of inflammatory mononuclear cells into the CNS.

Acute Disease↗