Hiroyuki Matsumoto

Sapporo Medical University, Sapporo, Hokkaidō, Japan

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Publications (43)106.01 Total impact

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    ABSTRACT: Neural precursor cells (NPCs) differentiate into neurons, astrocytes, and oligodendrocytes in response to intrinsic and extrinsic changes. Notch signals maintain undifferentiated NPCs, but the mechanisms underlying the neuronal differentiation are largely unknown. We show that SIRT1, an NAD(+)-dependent histone deacetylase, modulates neuronal differentiation. SIRT1 was found in the cytoplasm of embryonic and adult NPCs and was transiently localized in the nucleus in response to differentiation stimulus. SIRT1 started to translocate into the nucleus within 10 min after the transfer of NPCs into differentiation conditions, stayed in the nucleus, and then gradually retranslocated to the cytoplasm after several hours. The number of neurospheres that generated Tuj1(+) neurons was significantly decreased by pharmacological inhibitors of SIRT1, dominant-negative SIRT1 and SIRT1-siRNA, whereas overexpression of SIRT1, but not that of cytoplasm-localized mutant SIRT1, enhanced neuronal differentiation and decreased Hes1 expression. Expression of SIRT1-siRNA impaired neuronal differentiation and migration of NPCs into the cortical plate in the embryonic brain. Nuclear receptor corepressor (N-CoR), which has been reported to bind SIRT1, promoted neuronal differentiation and synergistically increased the number of Tuj1(+) neurons with SIRT1, and both bound the Hes1 promoter region in differentiating NPCs. Hes1 transactivation by Notch1 was inhibited by SIRT1 and/or N-CoR. Our study indicated that SIRT1 is a player of repressing Notch1-Hes1 signaling pathway, and its transient translocation into the nucleus may have a role in the differentiation of NPCs.
    Proceedings of the National Academy of Sciences 11/2008; 105(40):15599-604. DOI:10.1073/pnas.0800612105 · 9.67 Impact Factor
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    ABSTRACT: Sphinganine, a biosynthetic precursor of ceramide, was non-enzymatically acetylated with acetyl coenzyme A at the C-2-amino residue to produce C2-H2-ceramide (N-acetyl sphinganine) in an organic solvent and in an aqueous solution with a high yield, where as sphingenine was only acetylated slightly. The structure of the N-acetyl sphinganine was identified with mass spectrum, and with chromatography using an authentic N-acetylated substance. Furthermore, the C2-H2-ceramide was examined for enzymatic desaturation to determine whether C2-ceramide, a cell-permeable ceramide responsible for apoptosis of cells, was produced, revealing an inferior substrate for H2-ceramide desaturase of horse brain microsomes.
    International Union of Biochemistry and Molecular Biology Life 01/2008; 42(5):1071 - 1080. DOI:10.1080/15216549700203531 · 3.14 Impact Factor
  • Neuroscience Research 12/2007; 58:S32. DOI:10.1016/j.neures.2007.06.183 · 1.94 Impact Factor
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    ABSTRACT: Superior saggital sinus thrombosis (SSST), which has a strong causal link with antiphospholipid syndrome, rarely occurs in patients with systemic lupus erythematosus (SLE). We describe a 34-year-old woman with SLE whose clinical problem was mild headache. Her serology indicated negative antiphospholipid, anticardiolipin antibodies and lupus anticoagulants. However, marked dilatation of the entire saggital sinus with scattered thrombi was observed in enhanced-, surface- and three-dimensional reconstructed CTs (3D-CTs) without abnormal intra-axial signal in brain MRI. The enhanced-, surface- and 3D-CTs are useful to detect silent dural sinus dilatation with scattered thrombi in a patient with SLE without any symptoms of SSST.
    Clinical Rheumatology 12/2006; 25(6):911-3. DOI:10.1007/s10067-005-0094-0 · 1.70 Impact Factor
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    ABSTRACT: Interferons (IFNs)-inducible myxovirus resistance protein A (MxA) has recently been used as an indirect marker of neutralizing antibody against IFN in patients with multiple sclerosis (MS). On the other hand, MxA inhibits the replication of viruses by means of modifying cellular function, including apoptotic pathway. Our objective is to investigate the genetic and pathological role of MxA in patients with MS. We examined SNPs of MxA promoter region in 67 patients with MS. Moreover, to elucidate the functional roles of SNPs, we conducted Luciferase assay with pGL3-basic vector including patient-derived or artificially mutated MxA promoter region. A significantly higher frequency of the haplotype with -88T and -123A, which correlates with over-expression of MxA, was observed in MS. Moreover, we elucidated novel findings showing that nt -88 played a leading part with type I IFNs and that nt -123 played the same role independently without type I IFNs, respectively. SNPs on MxA promoter region may play an important role in the pathophysiology of MS and provide a novel strategy for the therapeutic resolutions of MS.
    Journal of the Neurological Sciences 12/2006; 249(2):153-7. DOI:10.1016/j.jns.2006.06.012 · 2.47 Impact Factor
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    ABSTRACT: We examined the usefulness of non-invasive positive pressure ventilation (NPPV) in the management of nocturnal laryngeal stridor associated with vocal cord dysfunction in five cases of multiple system atrophy (MSA). First, the patients were investigated during sleep induced by a minimal dose of propofol. Laryngoscopy showed paradoxical vocal cord movement resulting in inspiratory stridor. Electromyographic (EMG) study revealed synchronized bursts in the thyroarytenoid muscles and diaphragm in every inspiratory phase whenever the stridor emerged. NPPV was initiated after paradoxical movement was recognized with laryngoscopy. The NPPV mask was equipped with an additional channel for laryngoscopic monitoring. The optimal pressure for treatment was determined according to laryngoscopic and EMG findings. Next, NPPV was applied to natural sleep using the conditions determined in propofol-induced sleep. In all cases, NPPV eliminated nocturnal stridor and oxygen desaturation during natural sleep. Laryngoscopic observation during induced sleep is recommended as a useful procedure to titrate the optimal pressure for NPPV therapy. Since central hypoventilation progresses in the course of MSA, the choice of NPPV rather than continuous positive airway pressure should be encouraged to treat laryngeal contraction disorder associated with MSA.
    Journal of the Neurological Sciences 09/2006; 247(1):53-8. DOI:10.1016/j.jns.2006.03.008 · 2.47 Impact Factor
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    ABSTRACT: We evaluated the specific IgG antibodies against heat shock proteins (HSPs) in cerebrospinal fluids (CSF) from patients with multiple sclerosis (MS). ELISA was employed to examine IgG antibodies against ten HSPs (HSP27, alphaA and alphaB crystallins, HSP60, CCT, Mycobacterium bovis HSP65, Escherichia coli GroEL, HSP70, HSC70 and HSP90) in CSF from 30 patients with MS, and 25 patients with motor neuron diseases (MND). Significantly higher antibody titers against HSP70 and HSC70 proteins were found in CSF obtained from patients with MS as compared with MND independent of CSF total protein, IgG concentrations and IgG indices, respectively. The antibody titers against HSP70 were indicated to be significantly higher in the progressive cases than in cases of remission. The results suggest that IgG antibodies against specific types of HSPs especially HSP70 family proteins (HSP70 and HSC70) in CSF may play an important role in the pathophysiology of MS through the modification of immune response and cytoprotective functions of molecular chaperons.
    Journal of the Neurological Sciences 03/2006; 241(1-2):39-43. DOI:10.1016/j.jns.2005.10.009 · 2.47 Impact Factor
  • Tomihiro Imai · Hiroyuki Matsumoto
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    ABSTRACT: A 49-year-old woman with amyotrophic sequelae of poliomyelitis experienced progressive left upper limb weakness and breathing discomfort while walking that had developed over one year prior to presentation. She had flaccid quadriplegia which was more marked in the left upper limb, with the C4- and C5-innervated muscles being most severely affected. Chest radiographs double exposed at maximal inspiration and expiration revealed poor respiratory movements in the left hemidiaphragm. Phrenic nerve conduction study demonstrated conspicuous diaphragmatic paralysis on the left side. The electrophysiological study supports radiological findings and provides useful evidence for insidious phrenic nerve involvement in postpolio syndrome.
    Internal Medicine 02/2006; 45(8):563-4. DOI:10.2169/internalmedicine.45.1657 · 0.90 Impact Factor
  • Tomihiro Imai · Hiroo Yuasa · Yasuo Kato · Hiroyuki Matsumoto
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    ABSTRACT: We elucidated the possible relationship between age and conduction parameters of phrenic nerve in subjects above the sixth decade, comparing with the data from middle-age controls. Diaphragmatic action potentials (DAPs) were recorded on bilateral hemithoraces of 41 volunteers aged 60-101 years (old group) and 25 volunteers aged 35-55 years (middle-age group). Statistical analyses were performed to assess the effects of aging on latency, latency corrected by size (Lat/Dist), amplitude, and the right-left difference of these DAP parameters. In all 61 subjects, age showed a significant quadratic correlation with latency and with Lat/Dist, and a linear correlation with amplitude. The right-left differences ranged from 0.0 to 14.5% for latency and from 6.5 to 112.4% for amplitude in the elderly. The normal ranges of DAP parameters should be determined according to age. The left-right difference may be a useful reference in diagnosing unilateral phrenic nerve lesion. The precise normal ranges of phrenic nerve conduction parameters presented will encourage investigations of neuropathies in subjects aged above 60.
    Clinical Neurophysiology 12/2005; 116(11):2560-4. DOI:10.1016/j.clinph.2005.08.003 · 3.10 Impact Factor
  • Shin Hisahara · Susumu Chiba · Hiroyuki Matsumoto · Yoshiyuki Horio
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    ABSTRACT: Sir2 (silent information regulator 2) is an NAD-dependent deacetylase that is broadly conserved from bacteria to humans. It catalyzes a unique deacetylation reaction using NAD, and specific inhibitors and activators of its activity have been discovered. In yeast, Sir2 deacetylates histones and participates in transcription silencing and the suppression of recombination. Sir2 is also implicated in the regulation of aging, because its increased expression extends the lifespan of yeast and nematodes. Mammalian SIRT1 (Sir2alpha) is a member of the Sir2 family. Recently, SIRT1 was shown to interact with various transcription factors such as p53, forkhead transcription factor (FOXO) family proteins, and MyoD, and to participate in stress tolerance, differentiation, and development.
    Journal of Pharmacological Sciences 08/2005; 98(3):200-4. DOI:10.1254/jphs.FMJ05001X2 · 2.36 Impact Factor
  • Tomihiro Imai · Emiko Tsuda · Mikiya Suzuki · Takayoshi Hozuki · Hiroyuki Matsumoto
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    ABSTRACT: We conducted spinal MR imaging on a 35-year-old man with Lhermitte's sign that had manifested over the previous 4 years. He had consumed more than 500 ml of whisky daily for at least 10 years. However, he did not show any evidence of severe liver disease with hepato-systemic blood shunting. Neurologic examination revealed markedly depressed sense of vibration in the feet and mild spasticity in the lower limbs, together with Lhermitte's sign. MR imaging revealed abnormal signal intensity in the posterior column spanning the whole length of the upper cervical cord, which is consistent with Lhermitte's sign.
    Internal Medicine 03/2005; 44(2):153-4. DOI:10.2169/internalmedicine.44.153 · 0.90 Impact Factor
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    ABSTRACT: We examined antibodies against 10 heat shock proteins (HSPs) in cerebrospinal fluids (CSF) and sera from patients with Guillain-Barré syndrome (GBS). Significantly higher IgG antibody titers against HSP27, HSP60, HSP70 and HSP90 family, including mycobacterial HSP65 and Escherichia coli GroEL, were found in CSF from GBS patients as compared with motor neuron disease. Serum IgG antibodies against each HSP showed no difference between GBS patients and normal controls. GBS seems to be induced by reactive autoimmune responses frequently triggered by infections. The CSF antibodies against HSPs may modify the immune responses and/or cell-protective functions of HSPs in the pathophysiology of GBS.
    Journal of Neuroimmunology 12/2004; 156(1-2):204-9. DOI:10.1016/j.jneuroim.2004.07.017 · 2.47 Impact Factor
  • Tomihiro Imai · Takuro Wada · Hiroyuki Matsumoto
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    ABSTRACT: The aim of this study is to elucidate the significance of electrophysiological data of the palmar cutaneous branch of the median nerve (PCBm) in the diagnosis entrapment of the PCBm concomitant with carpal tunnel syndrome (CTS). Clinical and electrophysiological studies were conducted for abnormal sensation of the thenar eminence in eight CTS patients. Sensory nerve action potentials (SNAPs) of the PCBm were recorded from bipolar surface electrodes over the forearm using an orthodromic method. The preoperative SNAP evaluation was compared with the operative findings. The eight patients were divided into two groups based on the characteristics of SNAPs of the PCBm; five patients had normal SNAPs of the PCBm and three patients had delayed or absent SNAPs. Open surgery confirmed entrapment of the PCBm in one patient in the first group and all patients in the latter group. Although clinical symptoms were not always reliable to diagnose entrapment of the PCBm in CTS, electrophysiological study of the PCBm was highly sensitive (75%) and entirely specific (100%) to demonstrate the entrapment of the PCBm preoperatively.
    Clinical Neurophysiology 12/2004; 115(11):2514-7. DOI:10.1016/j.clinph.2004.05.015 · 3.10 Impact Factor
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    ABSTRACT: We report a 42-year-old woman of non-herpetic acute limbic encephalitis (NHALE) whose CT perfusion (CTP) images revealed abnormalities of the limbic system at the early stage. The patient had high fever, convulsion and memory disturbance soon after having caught a common cold, and was admitted to a hospital where she developed progressive disturbance of consciousness. She was then transferred to our hospital 7 days after the initial manifestations. Although enhanced CT images of the brain failed to find any lesion, CTP images revealed a focal increase in the cerebral blood flow and shortening of mean transit time in the bilateral hippocampi and amygdalae. MRI of the subsequent day showed high signal intensity lesions on diffusion, T2-weighted and FLAIR images at the same area. Her consciousness improved by intravenous administration of high-dose methylprednisolone together with other combination therapies. Her CTP images apparently improved by 5 weeks after the onset, but she was left with mild memory disturbance, amenorrhea secondary to hypothalamic failure, hyperosmia, and hypogeusia. In conclusion, CTP is sensitive enough to detect the lesions of the limbic system even in the early stage of NHALE.
    Rinsho shinkeigaku = Clinical neurology 09/2004; 44(8):537-40.
  • Tomihiro Imai · Hirohiko Shizukawa · Hitoshi Imaizumi · Hiroyuki Matsumoto
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    ABSTRACT: The aims of this study were to prove the presence of transient phrenic nerve palsy in children after cardiac surgery by successive recordings of diaphragmatic action potentials (DAPs), and to decide the indication of diaphragmatic plication in infants with postoperative phrenic nerve palsy. The DAPs were recorded from 11 infants (age 0-54 months) under artificial ventilation after cardiac surgery. The successive DAP recordings were performed within 3-4 days (0W), 1 week (1W) and 2 weeks (2W) after operation to make a final decision for diaphragmatic plication to wean artificial ventilation. The patients were divided into 3 groups according to the DAP changes in successive recordings, namely, patients with normal DAPs at 0W, patients with transient depression of DAPs at 0W followed by recovery to normal DAPs by 1W and/or 2W, and patients with persistent depression of DAPs of the affected side necessitating plication of hemidiaphragm. In infants with phrenic nerve palsy after cardiothoracic surgery, persistently abnormal DAPs in repeated electrophysiologic examinations for at least 2 weeks after surgery are a useful guidance to support clinical and radiological evidence for an indication of diaphragmatic plication.
    Clinical Neurophysiology 07/2004; 115(6):1469-72. DOI:10.1016/j.clinph.2004.01.007 · 3.10 Impact Factor
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    ABSTRACT: Heat shock protein 40 (Hsp40) family proteins are known to bind to Hsp70 through their J-domain and regulate the function of Hsp70 by stimulating its adenosine triphosphatase activity. In the endoplasmic reticulum (ER), there are 5 Hsp40 family proteins known so far, 3 of which were recently identified. In this report, one of the novel Hsp40 cochaperones, ERdj3, was characterized in terms of its subcellular localization, stress response, and stress tolerance of cells. By using ERdj3-specific polyclonal antibody, endogenous ERdj3 protein was shown to reside in the ER as gene transfer-mediated exogenous ERdj3. Analysis of the expression level of endogenous ERdj3 protein revealed its moderate induction in response to various ER stressors, indicating its possible action as a stress protein in the ER. Subsequently, we analyzed whether this molecule was involved in ER stress tolerance of cells, as was the case with the ER-resident Hsp70 family protein BiP. Although overexpression of ERdj3 by gene transfection could not strengthen ER stress tolerance of neuroblastoma cells, reduction of ERdj3 expression by small interfering ribonucleic acid decreased the tolerance of cells, indicating that ERdj3 might have just a marginal role in the ER stress resistance of neuroblastoma cells. In contrast, overexpression of ERdj3 notably suppressed vero toxin-induced cell death. These data suggest that ERdj3 might have diverse roles in the ER, including that of the molecular cochaperone of BiP and an as yet unknown protective action against vero toxin.
    Cell Stress and Chaperones 02/2004; 9(3):253-64. DOI:10.1379/CSC-52.1 · 3.16 Impact Factor
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    ABSTRACT: A case report is presented. To report a case of synovial chondromatosis of a cervical facet joint and describe the appearance with magnetic resonance imaging and computed tomography myelography. Synovial chondromatosis is an uncommon disorder characterized by the presence of multiple cartilaginous or osteocartilaginous nodules in the synovium of a joint space. Synovial chondromatosis in the cervical facet joint is rare. A 52-year-old woman experienced the sudden onset of severe pain in the dorsal shoulder girdle and in the ulnar side of her right arm and forearm. This refractory pain only responded to an epidural nerve root block. Neurologic examination showed right nerve root signs that ranged from the C7 to Th1 segments of the spinal cord. Radiologic and electrophysiological examinations were carried out. A mass was found in the right facet joint between C7 and Th1 with magnetic resonance imaging and computed tomography myelography. These investigations clearly indicated the location, size, and extent of the lesion accompanying the irregularity of the joint and osteolytic change. Somatosensory-evoked potentials with right ulnar nerve stimulation indicated a significant conduction block in the lower right cervical nerve roots. After surgical removal of this lesion, the neurologic symptoms markedly improved. The histopathology diagnosed synovial chondromatosis. Synovial chondromatosis should be included in the differential diagnosis of radiculopathies of unknown etiology.
    Spine 11/2003; 28(19):E396-400. DOI:10.1097/01.BRS.0000085161.79758.23 · 2.30 Impact Factor
  • Tomihiro Imai · Masaki Saitoh · Hiroyuki Matsumoto
    Neurology 09/2003; 61(3):416. DOI:10.1212/WNL.61.3.416 · 8.29 Impact Factor
  • Nihon Naika Gakkai Zasshi 05/2003; 92(4):668-70.
  • Tomihiro Imai · Hiroyuki Matsumoto
    Journal of the Japan Epilepsy Society 01/2002; 20(3):159-166. DOI:10.3805/jjes.20.159

Publication Stats

476 Citations
106.01 Total Impact Points


  • 1990–2008
    • Sapporo Medical University
      • • Division of Neurology
      • • School of Medicine
      Sapporo, Hokkaidō, Japan
  • 1998
    • Hokkaido University
      • Department of Neurology
      Sapporo, Hokkaidō, Japan