PubMed Health⌕ Search

Biomedical subjects

Takao Mitsui

Publications and source records attributed to Takao Mitsui.

At least 19 recordsLinked to original sources
PubMed2006

Parkin affects mitochondrial function and apoptosis in neuronal and myogenic cells.

We investigated the effect of parkin on mitochondrial function and apoptosis in SH-SY5Y, L6, RD, and COS-1 cells. Wild-type parkin attenuated reactive oxygen species (ROS) production in SH-SY5Y cells and mutant parkin enhanced ROS production in SH-SY5Y and L6 cells. Reactive oxygen intermediates, that were detected in mitochondria, were decreased in cells with overexpression of parkin. Parkin prevented apoptosis and enhanced mitochondrial membrane potentials in SH-SY5Y and L6 cells not in COS-1 cells. Expressions and enzymatic activities of mitochondrial respiratory chain complexes were not uniformly enhanced but those of complex 1 were selectively enhanced. The present results suggest the cell-selective function of parkin, i.e., parkin possesses anti-apoptotic and anti-oxidant function in neuronal or myogenic cells but not in kidney cells.

Animals↗
PubMed2006

Parkin enhances mitochondrial biogenesis in proliferating cells.

We describe a novel function of parkin, a RING protein, which is elaborately involved in mitochondrial biogenesis. Parkin was located within the mitochondrial organelle of proliferating cells. Anti-proliferative treatments released parkin from mitochondria to cytosol. Results of pharmacological treatments indicate that parkin was released from mitochondria when permeability transition pore was opened. The extra-mitochondrial localization was also observed in differentiated cells. In proliferating cells, transcription and replication of mitochondrial DNA was enhanced by parkin overexpression and attenuated by parkin suppression with siRNA. Parkin was associated with mitochondrial transcription factor A (TFAM) and enhanced TFAM-mediated mitochondrial transcription. These results indicate that parkin is involved in the regulation of mitochondrial transcription/replication other than the ubiquitin-mediated protein degradation system in proliferating cells.

Animals↗
PubMed2005

Delayed motor and sensory neuropathy in a patient with brainstem encephalitis.

Bickerstaff's brainstem encephalitis (BBE), Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) are thought to be closely related and to form a continuous spectrum. However, chronic polyneuropathy in BBE has not been reported. We report the temporal profile of anti-ganglioside antibody titer in a case of BBE-like brainstem encephalitis complicated with chronic polyneuropathy. A 71-year-old Japanese woman presented with drowsiness and cerebellar ataxia in addition to mild weakness in distal limb muscles. Anti-GalNAc-GD1a IgG and anti-GalNAc-GM1b IgG antibodies were positive in her serum. Brain magnetic resonance imaging revealed high-intensity signals in the midbrain, pons, and middle cerebellar peduncles on T2-weighted images. Central nervous system manifestations improved after immunomodulating therapy that included prednisolone, plasmapheresis and intravenous immunoglobulin. Nevertheless, the distal muscle weakness was exacerbated when the anti-GalNAc-GD1a IgG titer was elevated. Nerve conduction study indicated motor and sensory neuropathy which was developed motor dominant axonal damage. These findings suggest that anti-ganglioside antibodies, including anti-GalNAc-GD1a IgG, may be involved in a common autoimmune mechanism in BBE-like brainstem encephalitis and chronic motor dominant axonal neuropathy. However, the fact that the latter manifestation exacerbated after the improvement of former one possibly indicates different thresholds of neurologic symptoms mediated by anti-ganglioside antibodies in the present patient.

Aged↗
PubMed2005

Involvement of mitochondria in myasthenia gravis complicated with dermatomyositis and rheumatoid arthritis: a case report.

We report a 57-year-old male with myasthenia gravis complicated with dermatomyositis and rheumatoid arthritis without evidence of thymoma. He showed prominent muscle wasting and weakness in the four extremities and trunk in addition to swallowing disturbance. He showed intolerance to exercise on a bicycle ergometer, and muscle biopsy specimens demonstrated ragged-red fibers. An anti-acetylcholine receptor (AChR) antibody was detected in his serum but no anti-mitochondrial M2 component antibody was found. In contrast, results of immunohistochemical study indicated that his serum sample reacted to muscle mitochondria as well as AChR. These results indicate the presence of an unidentified anti-mitochondrial antibody that may be involved in the development of mitochondrial dysfunction in skeletal muscle of the present patient.

Arthritis, Rheumatoid↗
PubMed2005

Central motor conduction in cervical dystonia with cervical spondylotic myelopathy.

OBJECTIVES: It has been known that cervical dystonia develops secondarily to spinal cord injuries as secondary dystonia. However, little is known about the pathophysiological mechanism. PATIENTS AND METHODS: We examined motor and sensory conduction in six patients with symptomatic cervical dystonia by transcranial magnetic stimulation (TMS). All of the patients exhibited unilateral head rotation. They had symptoms corresponding to cervical myelopathy and felt discomfort in the neck, shoulders or arms before involuntary movement occurred. RESULTS: Although the overall central motor conduction time (CMCT) was not different from that of normal controls, contralateral CMCT was significantly delayed compared to ipsilateral CMCT (p<0.05). The results of somatosensory evoked potential study demonstrated that contralateral central conduction time (CCT) was not significantly different from ipsilateral CCT. CONCLUSION: These findings indicate that there is a selective interference with the contralateral corticospinal tract in patients with symptomatic cervical dystonia.

Adult↗
PubMed2005

Vascular smooth muscle cell proliferation is dependent upon upregulation of mitochondrial transcription factor A (mtTFA) expression in injured rat carotid artery.

Consistent with the physiological response to increased energy demand in proliferating cells, the number of mitochondria is upregulated in synthetic states of vascular smooth muscle cells (VSMC) in atherosclerotic lesion. We hypothesized that mitochondrial transcription factor A (mtTFA), a prerequisite factor for the transcription and replication of mtDNA, may be upregulated in VSMC of injured rat carotid artery, and that inhibition of its expression can attenuate the intimal thickening. Changes of intimal thickening and mtTFA expression by a treatment with antisense oligodeoxynucleotides (ODN) for mtTFA were investigated in balloon-injured rat carotid artery model. The expression of mtTFA was upregulated as early as 3 h up to 7 days after balloon injury. Delivery of ansisense ODN for mtTFA from adventitia side to injured arterial wall caused a significant decrease in intima-to-media (I/M) ratio. Furthermore, the increase in immunoreactivity and mRNA expression of mtTFA in injured artery as well as the number of mitochondria in intimal VSMC was abrogated by antisense ODN treatment. These data demonstrate that expression of mtTFA is upregulated in intimal VSMC of injured rat carotid artery, and that suppression of mtTFA expression by antisense ODN can attenuate intimal thickening after balloon injury.

Animals↗
PubMed2004

Guillain-Barré syndrome and hemophagocytic lymphohistiocytosis in a patient with severe chronic active Epstein-Barr virus infection syndrome.

Epstein-Barr virus (EBV) infection causes a wide range of neurologic and hematologic manifestations. We report a 72-year-old Japanese male patient with severe chronic active EBV infection syndrome (SCAEBV) who presented with Guillain-Barré syndrome (GBS) and developed hemophagocytic lymphohistiocytosis (HLH) several months after the onset of GBS. He showed acute onset of distal muscle weakness, ophthalmoplegia and bulbar palsy. Results of nerve conduction study revealed acute motor-sensory axonal neuropathy (AMSAN). His serum was positive for anti-LM1 IgG and anti-GM1b IgM. Titers of antibodies to EBV-related antigens indicated chronic reactivated EBV infection. Treatment with IVIg resolved the acute ophthalmoplegia, but there was no notable improvement in the AMSAN and bulbar palsy despite repeated. Finally, he developed refractory HLH resulting in a fatal outcome. In the present patient, it seems that SCAEBV was associated with the development of GBS and fatal HLH via parainfectious autoimmunity and direct infectious immune mechanisms, respectively.

Aged↗
PubMed2004

Isolated cranial neuropathy associated with anti-glycolipid antibodies.

We describe seven patients with isolated cranial neuropathy in whom serum anti-glycolipid antibodies were detected. Trigeminal sensory neuropathy was found in four patients, who had exhibited symptoms for 2 months to 4 years. The other three patients showed facial nerve palsy with or without ophthalmoparesis. Temporal profile analysis of anti-glycolipid antibodies revealed that titers of anti-glycolipid IgM antibodies against GM2 and LM1 gradually decreased in patients having chronic trigeminal sensory neuropathy. In patients with acute trigeminal sensory neuropathy, elevation of anti-LM1 antibody titers continued over 12 months although anti-GalNAc-GD1a antibody disappeared. On the other hand, titers of anti-glycolipid antibodies rapidly decreased in patients with acute facial nerve palsy with or without ophthalmoparesis. We conclude that anti-glycolipid antibodies may play an important role in the development of isolated cranial neuropathy in some patients.

Action Potentials↗
PubMed2004

Neuro-Behçet's disease with chorea after remission of intestinal Behçet's disease.

Neuro-Behçet's disease shows various neuropsychiatric symptoms, but chorea has rarely been reported. We report a case of neuro-Behçet's disease in a 67-year-old woman with depression and chorea that occurred 22 years after the onset of intestinal Behçet's disease. Brain magnetic resonance imaging (MRI) using a fluid-attenuated inversion-recovery (FLAIR) sequence demonstrated lesions more clearly than did T2-weighted MRI. Some of the lesions appeared as small ring-like foci, i.e. low-intensity spots rimmed with remarkable hyperintense signals, in the periventricular white matter and basal ganglia. A review of the literature revealed that the onset of chorea in cases of Behçet's disease varied from the time of onset of Behçet's disease to 31 years after onset of the disease. Psychiatric manifestations have often been associated with neuro-Behçet's disease. In the present patient, treatment with prednisolone resolved the chorea, suggesting that the chorea was caused by an autoimmune mechanism. It seems likely that the long-term development of vasculitis in patients with Behçet's disease results in the formation of these particular brain lesions on FLAIR MR images. Chorea should be taken into consideration as one of the manifestations of Behçet's disease, even many years after remission of the disease.

Aged↗
PubMed2004

Oxidative stress-associated mitochondrial dysfunction in corticosteroid-treated muscle cells.

We analyzed the effects of corticosteroid on mitochondrial membrane potentials (DeltaPsi(m)), generation of reactive oxygen species (ROS), and apoptosis in a human rhabdomyosarcoma cell line, RD, and a dopaminergic neuroblastoma cell line, SH-SY5Y. The cell lines were cultured in the presence or absence of dexamethasone and superoxide dismutase (SOD) for up to 1 week. Dexamethasone treatment increased DeltaPsi(m), ROS generation, and apoptosis in proliferating RD cells. Treatment with SOD attenuated ROS generation and apoptosis, but not DeltaPsi(m). The increase in DeltaPsi(m) seemed to be the primary effect of dexamethasone on proliferating RD cells, which is probably mediated by mitochondrial transcription. In differentiated RD cells, but not differentiated SH-SY5Y cells, dexamethasone treatment showed a delayed effect of interfering with the DeltaPsi(m) and increasing ROS generation and apoptosis. Since these changes disappeared in the presence of SOD, dexamethasone primarily induced ROS generation, resulting in apoptosis. We speculate that this mechanism provides the basis of a pathophysiological model of corticosteroid myopathy.

Apoptosis↗
PubMed2003

Deletion of vitamin D receptor gene in mice results in abnormal skeletal muscle development with deregulated expression of myoregulatory transcription factors.

Although rachitic/osteomalacic myopathy caused by impaired vitamin D actions has long been described, the molecular pathogenesis remains elusive. To determine physiological roles of vitamin D actions through vitamin D receptor (VDR) in skeletal muscle development, we examined skeletal muscle in VDR gene deleted (VDR -/-) mice, an animal model of vitamin D-dependent rickets type II, for morphological changes and expression of myoregulatory transcription factors and myosin heavy chain isoforms. We found that each muscle fiber was small and variable in size in hindlimb skeletal muscle from VDR -/- mice, although overall myocyte differentiation occurred normally. These abnormalities were independent of secondary metabolic changes such as hypocalcemia and hypophosphatemia, and were accompanied by aberrantly high and persistent expression of myf5, myogenin, E2A, and early myosin heavy chain isoforms, which are normally down-regulated at earlier stages. Moreover, treatment of VDR-positive myoblastic cells with 1,25(OH)2D3 in vitro caused down-regulation of these factors. These results suggest that VDR plays a physiological role in skeletal muscle development, participating in temporally strict down-regulation of myoregulatory transcription factors. The present study can form a molecular basis of VDR actions on muscle and should help further establish the physiological roles of VDR in muscle development as well as pharmacological effects of vitamin D on muscle functions.

Animals↗
PubMed2003

Dissociation between titer of anti-ganglioside antibody and severity of symptoms in a case of Guillain-Barré syndrome with treatment-related fluctuation.

Since plasma exchange (PE) and intravenous immunoglobulin (i.v.Ig) have been widely used in treatment for Guillain-Barré syndrome (GBS), early relapse and treatment-related fluctuation have been a potential problem, but little is known about the mechanism of relapse and fluctuation. We describe a patient who had GBS with treatment-related fluctuation. A 37-year-old Japanese man exhibited acute distal-dominant weakness in upper limbs after upper respiratory infection. His cranial nerve system was normal and muscle weakness was limited to upper limbs. Anti-GT1a IgG was strongly positive and anti-GQ1b IgG was also detected in his serum. Muscle weakness responded well to double-filtration plasmapheresis (DFPP) followed by i.v.Ig, but relapsed 45 days after the initial treatment. Although repeated treatments were effective, the patient showed additional minor deterioration twice. Motor nerve conduction velocities (MCVs) corresponded to the muscle weakness, but elevated level of cerebrospinal fluid (CSF) protein remained and anti-ganglioside antibody titers steadily decreased throughout the clinical course. These findings indicate that the clinical fluctuation was not due to changes in the production of anti-ganglioside antibodies but presumably to the transient beneficial effects of DFPP/i.v.Ig and the outlasting inflammatory response in peripheral nerves.

Adult↗
PubMed2003

Glucocorticoid excess induces superoxide production in vascular endothelial cells and elicits vascular endothelial dysfunction.

Glucocorticoid (GC) excess often elicits serious adverse effects on the vascular system, such as hypertension and atherosclerosis, and effective prophylaxis for these complications is limited. We sought to reveal the mechanism underlying GC-induced vascular complications. Responses in forearm blood flow to reactive hyperemia in 20 GC-treated patients were significantly decreased to 43+/-8.9% (mean+/-SEM) from the values obtained before GC therapy (130+/-14%). An administration of vitamin C almost normalized blood flow responses. In human umbilical vein endothelial cells (HUVECs), production of hydrogen peroxide was increased up to 166.5+/-3.3% of control values by 10(-7) mol/L dexamethasone (DEX) treatment (P<0.01). Concomitant with DEX-induced hydrogen peroxide production, intracellular amounts of peroxynitrite significantly increased and those of nitric oxide (NO) decreased, respectively (P<0.01). Immunoblotting analysis using anti-nitrotyrosine antibody showed that peroxynitrite formation was increased in DEX-treated HUVECs. Using inhibitors against metabolic pathways for generation of reactive oxygen species (ROS), we identified that the major production sources of ROS by DEX treatment were mitochondrial electron transport chain, NAD(P)H oxidase, and xanthine oxidase. These findings suggest that GC excess causes overproduction of ROS and thereby perturbs NO availability in the vascular endothelium, leading to vascular complications in patients with GC excess.

Adolescent↗
PubMed2003

Overexpressions of myoglobin and antioxidant enzymes in ragged-red fibers of skeletal muscle from patients with mitochondrial encephalomyopathy.

To determine the relationship between myoglobin (Mb) and the defense system against reactive oxygen species in various myopathies, we performed immunohistochemical analyses of Mb and various antioxidant enzymes, including manganese superoxide dismutase (Mn-SOD), copper zinc SOD (CuZn-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Biopsied muscle specimens were obtained from patients with chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome (KSS), Duchenne muscular dystrophy (DMD), and polymyositis (PM). In patients with CPEO/KSS, stainings of Mb, SOD, CAT, and GSH-Px in nonatrophic ragged-red fibers (RRFs) were more intense than those in non-RRFs. These pronounced stainings corresponded to ragged-red lesions. The staining intensities of these antioxidant enzymes were significantly correlated with that of Mb (P < 0.001). Atrophic RRFs in specimens from patients with CPEO/KSS showed intense stainings of these antioxidant enzymes but not intense staining of Mb. In specimens from patients with DMD/PM, the antioxidant enzymes but not Mb were overexpressed in degenerative fibers. These results suggest that oxidative stress is associated with Mb expression specifically in mitochondrial diseases. The antioxidant enzymes seem to be upregulated to protect against muscle damage in nonatrophic RRFs. However, the Mb-mediated oxidative damage may become more extensive and result in further mitochondrial dysfunction and progressive atrophy of RRF with impaired upregulation of Mb.

Adult↗