Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Jun-ichi Kira Last modified date:2019.07.03

Professor / Department of Neurology, Neurological Institute, Graduate school of Medical Sciences / Department of Clinical Medicine / Faculty of Medical Sciences

1. Koji Shinoda, Takuya Matsushita, yuri nakamura, Katsuhisa Masaki, Ryo Yamasaki, Jun-Ichi Kira, HLA genotype and cortical lesions
Response to the letter from Spencer et al., Multiple Sclerosis Journal, 10.1177/1352458517734072, 24, 6, 819-820, 2018.05.
2. mitsuru watanabe, Wataru Shiraishi, Ryo Yamasaki, Noriko Isobe, Motohiro Sawatsubashi, Ryuji Yasumatsu, Takashi Nakagawa, Jun-Ichi Kira, Oral phase dysphagia in facial onset sensory and motor neuronopathy, Brain and Behavior, 10.1002/brb3.999, 8, 6, 2018.06, Introduction: Facial onset motor and sensory neuronopathy (FOSMN) is a rare disease whose cardinal features are initial asymmetrical facial sensory deficits followed by bulbar symptoms and spreading of sensory and motor deficits from face to scalp, neck, upper trunk, and upper extremities in a rostral–caudal direction. Although bulbar involvement is frequently observed in FOSMN, dysphagia in these patients has not been fully described. In this study, we aimed to characterize dysphagia as a prognostic factor in FOSMN by investigating our institutional case series. Methods: We retrospectively reviewed the medical records, including swallowing function tests, of six patients with FOSMN (three men and three women) who were thoroughly examined at Kyushu University Hospital between 1 January 2005 and 30 November 2017. Results: Average age at onset was 58.5 years; average disease duration was 5.7 years. All patients developed bulbar dysfunction and dysphagia (at an average of 1.8 and 2.6 years from onset, respectively), resulting in choking episodes in three patients, percutaneous endoscopic gastrostomy placement in three, and recurrent aspiration pneumonia in one. Four of five patients evaluated with videofluoroscopic swallowing studies had poor oral retention, leading to bolus flowing into the pharynx before swallowing; the fifth patient showed poor lingual transfer. Fiberoptic endoscopic evaluation of swallowing revealed leakage of blue-dyed water from the mouth to the pharynx in three patients because of poor oral retention, but only mild pharyngeal phase dysphagia in all four cases evaluated. Conclusions: Oral phase dysphagia predominates in the early stage of FOSMN..
3. Tomoyasu Marui, Youta Torii, Shuji Iritani, Hirotaka Sekiguchi, Chikako Habuchi, Hiroshige Fujishiro, Kenichi Oshima, Kazuhiro Niizato, Shotaro Hayashida, Katsuhisa Masaki, Jun-Ichi Kira, Norio Ozaki, The neuropathological study of myelin oligodendrocyte glycoprotein in the temporal lobe of schizophrenia patients, Acta Neuropsychiatrica, 10.1017/neu.2018.6, 30, 4, 232-240, 2018.08, Objective Recent studies based on the neuroimaging analysis, genomic analysis and transcriptome analysis of the postmortem brain suggest that the pathogenesis of schizophrenia is related to myelin-oligodendrocyte abnormalities. However, no serious neuropathological investigation of this protein in the schizophrenic brain has yet been performed. In this study, to confirm the change in neuropathological findings due to the pathogenesis of this disease, we observed the expression of myelin-oligodendrocyte directly in the brain tissue of schizophrenia patients.Methods Myelin oligodendrocyte glycoprotein (MOG) was evaluated in the cortex of the superior temporal gyrus (STG) and the hippocampus in 10 schizophrenic and nine age- And sex-matched normal control postmortem brains.Results The expression of MOG was significantly lower in the middle layer of the neocortex of the STG and stratum lucidum of CA3 in the hippocampus in the long-term schizophrenic brains (patients with ≥30 years of illness duration) than in the age-matched controls. Furthermore, the thickness of MOG-positive fibre-like structures was significantly lower in both regions of the long-term schizophrenic brains than in the age-matched controls.Conclusion These findings suggest that a long duration of illness has a marked effect on the expression of MOG in these regions, and that myelin-oligodendrocyte abnormalities in these regions may be related to the progressive pathophysiology of schizophrenia..
4. Norihisa Maeda, Hiroyuki Honda, Satoshi Suzuki, Naoki Fujii, Jun-Ichi Kira, Toru Iwaki, Mitochondrial dysfunction and altered ribostasis in hippocampal neurons with cytoplasmic inclusions of multiple system atrophy, Neuropathology, 10.1111/neup.12482, 38, 4, 361-371, 2018.08, Multiple system atrophy (MSA) is a sporadic adult-onset neurodegenerative disease. It has recently been shown that patients with MSA accompanied by cognitive decline display numerous neuronal cytoplasmic inclusions (NCIs) in the limbic neurons. We examined potential mechanisms underlying the formation of these NCIs by determining of mitochondrial function and statuses of RNA processing by analyzing 12 pathologically confirmed cases of MSA. Among them, four had cognitive impairment Semiquantitative evaluation using immunohistochemistry analyses revealed a significantly greater NCI burden in the hippocampal cornu ammonis 1 (CA1) subfield, subiculum, and amygdala in the cases with cognitive impairments compared with those without cognitive impairment. Immunofluorescent staining revealed that limbic neurons with NCIs often accelerated production of reactive oxygen species (ROS) and degraded mitochondrial quality control. Immunofluorescent staining also revealed that neurons with these NCIs translocated heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) from the nucleus and aggregated abnormally at the perinuclear rim. Since the NCIs in the hippocampal neurons of MSA with cognitive impairments were more numerous, the neuronal mitochondrial dysfunction and altered ribostasis observed in NCI formation may be involved in the hippocampal degeneration of MSA..
5. Koji Tanaka, Shoji Matsumoto, Takeshi Yamada, Daisuke Kondo, Hideo Chihara, Motohisa Koga, Taketo Hatano, Tomoya Miyagi, Ryo Yamasaki, Jun-Ichi Kira, Elevated end-diastolic ratio of the common carotid artery due to cerebral arteriovenous malformation
Two case reports, Radiology Case Reports, 10.1016/j.radcr.2018.06.007, 13, 4, 917-920, 2018.08, An elevated end-diastolic (ED) ratio of the common carotid artery (CCA) is an indicator of occlusive lesions of the distal portion of the internal carotid artery. We report 2 cases of cerebral arteriovenous malformation (AVM) showing an elevated ED ratio of the CCA, which decreased after surgery. Case 1 was a 28-year-old man with chronic recurrent headache with aura, and case 2 was a 29-year-old woman with sudden-onset headache and intracerebral hemorrhage without neurologic abnormality. In both cases, digital subtraction angiography revealed a Spetzler-Martin Grade IV AVM, which was mainly fed by branches of the left middle cerebral artery with venous drainage into superficial and deep cerebral veins. Preoperative carotid ultrasonography showed an elevated CCA ED ratio (1.38 in case 1 and 1.47 in case 2; left > right) without atherosclerotic lesions. Patients’ AVMs were successfully resected. In both cases, the ED ratio was decreased after surgery (to 1.05 in case 1 and 1.20 in case 2). A decrease in vascular resistance on 1 side caused by cerebral AVM can result in an increase in the CCA ED ratio comparable to that of carotid axis occlusion..
6. Atsushi Fujita, hiroo yamaguchi, Ryo Yamasaki, Yiwen Cui, Yuta Matsuoka, Ken-Ichi Yamada, Jun-Ichi Kira, Connexin 30 deficiency attenuates A2 astrocyte responses and induces severe neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride Parkinson's disease animal model, Journal of Neuroinflammation, 10.1186/s12974-018-1251-0, 15, 1, 2018.08, Background: The first pathology observed in Parkinson's disease (PD) is 'dying back' of striatal dopaminergic (DA) terminals. Connexin (Cx)30, an astrocytic gap junction protein, is upregulated in the striatum in PD, but its roles in neurodegeneration remain elusive. We investigated Cx30 function in an acute PD model by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to wild-type (WT) and Cx30 knockout (KO) mice. Methods: On days 1 and 7 after MPTP administration, we evaluated changes in astrocytic Cx30, Cx43, glial fibrillary acidic protein, and ionised calcium-binding adapter molecule 1 expression by immunostaining and biochemical analysis. Loss of DA neurons was evaluated by tyrosine hydroxylase immunostaining. Gene expression was analysed using A1, A2, pan-reactive astrocyte microarray gene sets, and M1, M2, and M1/M2 mixed microglial microarray gene sets. Real-time PCR and in situ hybridisation were performed to evaluate glial cell-derived neurotrophic factor (Gdnf) and S100a10 expression. Striatal GDNF protein levels were determined by enzyme-linked immunosorbent assay. Results: MPTP treatment induced upregulation of Cx30 and Cx43 levels in the striatum of WT and KO mice. DA neuron loss was accelerated in Cx30 KO compared with WT mice after MPTP administration, despite no change in the striatal concentration of methyl-4-phenylpyridinium+. Astrogliosis in the striatum of Cx30 KO mice was attenuated by MPTP, whereas microglial activation was unaffected. Microarrays of the striatum showed reduced expression of pan-reactive and A2 astrocyte genes after MPTP treatment in Cx30 KO compared with WT mice, while M1, M2, and M1/M2 mixed microglial gene expression did not change. MPTP reduced the number of striatal astrocytes co-expressing Gdnf mRNA and S100β protein or S100a10 mRNA and S100β protein and also reduced the level of GDNF in the striatum of Cx30 KO compared with WT mice. Conclusions: These findings indicate that Cx30 plays critical roles in astrocyte neuroprotection in an MPTP PD model..
7. Takayuki Fujii, Ryo Yamasaki, Kyoko Iinuma, Daisuke Tsuchimoto, Yoshinori Hayashi, Ban yu Saitoh, Takuya Matsushita, Mizuho A. Kido, Shinichi Aishima, Hiroshi Nakanishi, Yusaku Nakabeppu, Jun ichi Kira, A Novel Autoantibody against Plexin D1 in Patients with Neuropathic Pain, Annals of Neurology, 10.1002/ana.25279, 84, 2, 208-224, 2018.08, Objective: To identify novel autoantibodies for neuropathic pain (NeP). Methods: We screened autoantibodies that selectively bind to mouse unmyelinated C-fiber type dorsal root ganglion (DRG) neurons using tissue-based indirect immunofluorescence assays (IFA) with sera from 110 NeP patients with various inflammatory and allergic neurologic diseases or other neuropathies, and 50 controls without NeP including 20 healthy subjects and 30 patients with neurodegenerative diseases or systemic inflammatory diseases. IgG purified from IFA-positive patients' sera was subjected to Western blotting (WB) and immunoprecipitation (IP) using mouse DRG lysates. Immunoprecipitates were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify target autoantigens. Results: Antiunmyelinated C-fiber type DRG neuron antibodies were more frequent in patients with NeP than non-NeP subjects (10% vs 0%; p < 0.05). These autoantibodies were all from the IgG2 subclass and colocalized mostly with isolectin B4- and P2X3-positive pain-conducting small neurons but not with S100β-positive myelinated neurons. WB revealed a common immunoreactive band (approximately 220kDa). IP and LC-MS/MS studies identified plexin D1 as a target autoantigen. Immunoadsorption tests with recombinant human plexin D1 in IFA revealed that all 11 anti–small DRG neuron antibody-positive patients had anti–plexin D1 antibodies. Application of anti–plexin D1 antibody-positive patient sera to cultured DRG neurons increased membrane permeability, leading to cellular swelling. NeP patients with anti–plexin D1 antibodies commonly developed burning pain and current perception threshold abnormalities for C-fibers. Main comorbidities were atopy and collagen-vascular disease. Immunotherapies ameliorated NeP in 7 treated cases. Interpretation: Anti–plexin D1 antibodies are a novel biomarker for immunotherapy-responsive NeP..
8. yuri nakamura, Laura Gaetano, Takuya Matsushita, Altermatt Anna, Till Sprenger, Ernst Wilhelm Radue, Jens Wuerfel, Lorena Bauer, Michael Amann, Koji Shinoda, Noriko Isobe, Ryo Yamasaki, Takahiko Saida, Ludwig Kappos, Jun-Ichi Kira, A comparison of brain magnetic resonance imaging lesions in multiple sclerosis by race with reference to disability progression, Journal of Neuroinflammation, 10.1186/s12974-018-1295-1, 15, 1, 2018.09, Background: We compared the magnetic resonance imaging (MRI) features between Japanese and Caucasian patients with multiple sclerosis (MS), and identified the relationships between MRI features and disability. Methods: From the baseline data of phase II fingolimod trials, 95 Japanese and 246 Caucasian relapsing-remitting MS patients were enrolled. The number, volume, and distribution of brain MRI lesions were evaluated using T2-weighted (T2W) images. Cross-sectional total normalized brain volume (NBV), normalized cortical gray matter volume, normalized deep gray matter volume (NDGMV), normalized white matter volume (NWMV), and normalized thalamic volume were measured. Results: Japanese patients had significantly lower Expanded Disability Status Scale (EDSS) scores than Caucasian patients (mean 2.0 vs. 2.3, p = 0.008), despite a similar disease duration. Japanese patients showed a trend towards fewer T2W-lesions (median 50 vs. 65, p = 0.08) and significantly lower frequencies of cerebellar and parietal lobe lesions (p = 0.02 for both) than Caucasian patients. There were no differences in T2W-lesion volume between races, whereas Japanese patients had a significantly larger T2W-lesion volume per lesion compared with Caucasian patients (median 140 mm3 vs. 85 mm3, p < 0.0001). T2W-lesion volumes were positively correlated with EDSS scores in Japanese patients (p < 0.0001). In both races, NBV, normalized cortical gray matter volume, NDGMV, and thalamic volume were negatively correlated with disease duration and EDSS scores (p < 0.01 for all). NWMV was negatively correlated with disease duration and EDSS scores only in Caucasian patients (p = 0.03 and p = 0.004, respectively). NBV, NDGMV, NWMV, and thalamic volume were consistently smaller in Japanese compared with Caucasian patients throughout the entire examined disease duration (p = 0.046, p = 0.01, p = 0.005, and p = 0.04, respectively). Japanese patients had a significantly faster reduction in NDGMV (p = 0.001), particularly for thalamic volume (p = 0.001), with disease duration compared with Caucasian patients. Conclusions: Gray matter atrophy is a common denominator for disability in Japanese and Caucasian patients. Additional contributory factors for disability include T2W-lesion volume in Japanese patients and white matter atrophy in Caucasian patients. Less frequent parietal and cerebellar involvement with fewer T2W-lesions may underlie milder disability in Japanese patients..
9. Yosikazu Kikuchi, Toshiro Umezaki, Taira Uehara, hiroo yamaguchi, Koji Yamashita, Hiwatashi Akio, Motohiro Sawatsubashi, Kazuo Adachi, Yumi Yamaguchi, Daisuke Murakami, Jun-Ichi Kira, Takashi Nakagawa, A case of multiple system atrophy-parkinsonian type with stuttering- and palilalia-like dysfluencies and putaminal atrophy, Journal of Fluency Disorders, 10.1016/j.jfludis.2017.11.002, 57, 51-58, 2018.09, Both developmental and acquired stuttering are related to the function of the basal ganglia-thalamocortical loop, which includes the putamen. Here, we present a case of stuttering- and palilalia-like dysfluencies that manifested as an early symptom of multiple system atrophy-parkinsonian type (MSA-P) and bilateral atrophy of the putamen. The patient was a 72-year-old man with no history of developmental stuttering who presented with a stutter for consultation with our otorhinolaryngology department. The patient was diagnosed with MSA-P based on parkinsonism, autonomic dysfunction, and bilateral putaminal atrophy revealed by T2-weighted magnetic resonance imaging. Treatment with levodopa improved both the motor functional deficits related to MSA-P and stuttering-like dysfluencies while reading; however, the palilalia-like dysfluencies were much less responsive to levodopa therapy. The patient died of aspiration pneumonia two years after his first consultation at our hospital. In conclusion, adult-onset stuttering- and palilalia-like dysfluencies warrant careful examination of the basal ganglia-thalamocortical loop, and especially the putamen, using neuroimaging techniques. Acquired stuttering may be related to deficits in dopaminergic function..
10. Yuko Kobayakawa, Katsuhisa Masaki, Ryo Yamasaki, Wataru Shiraishi, Shotaro Hayashida, Shintaro Hayashi, Koichi Okamoto, Takuya Matsushita, Jun-Ichi Kira, Downregulation of neuronal and dendritic Connexin36-made electrical synapses without glutamatergic axon terminals in spinal anterior horn cells from the early stage of amyotrophic lateral sclerosis, Frontiers in Neuroscience, 10.3389/fnins.2018.00894, 12, NOV, 2018.11, Connexin36 (Cx36) forms gap junctions between neurons, which are called electrical synapses, enabling adjacent neurons to communicate directly. The participation of chemical synapses in neurodegeneration in amyotrophic lateral sclerosis (ALS) has long been indicated, but it remains unclear whether electrical synapses are involved in the pathogenesis of ALS. We performed extensive immunopathological analyses using mutant superoxide dismutase 1 (SOD1G93A) transgenic mice and their littermates to investigate whether Cx36-made electrical synapses are affected in motor neuron diseases. We found that in the lamina IX of the lumbar spinal cord from wild type mice, about half of the Cx36 puncta existed independently of chemical synapse markers, while the rest coexisted with chemical synapse markers, such as vesicular glutamate transporter 1 (VGLUT1), which is a glutamatergic axon terminal marker, and/or glutamate decarboxylase 65 (GAD65), which is a GABAergic axon terminal marker. Cx36 single or Cx36/GAD65 double positive puncta, but not VGLUT1-containing puncta, were preferentially decreased on neuronal and dendritic surfaces of the anterior horn cells in the early stage of SOD1G93A ALS mice. Moreover, in five human autopsied sporadic ALS cases with bulbar or upper limb onset, Cx36 immunoreactivity was diminished in the proximal dendrites and neuropils of well-preserved large motor neurons in the lumbar anterior horns. These findings suggest that downregulation of neuronal and dendritic Cx36 in the spinal anterior horns commonly occurs from the early stage of hereditary and sporadic ALS. Cx36-made electrical synapses without glutamatergic signaling appear to be more vulnerable than other chemical synapses and electrical synapses with glutamatergic signaling in the early stage of motor neuron degeneration, suggesting involvement of Cx36-made electrical synapses in the pathogenesis of human ALS..
11. Mei Fang, Ryo Yamasaki, Guangrui Li, Katsuhisa Masaki, Hiroo Yamaguchi, Atsushi Fujita, Noriko Isobe, Jun-Ichi Kira, Connexin 30 deficiency attenuates chronic but not acute phases of experimental autoimmune encephalomyelitis through induction of neuroprotective microglia, Frontiers in Immunology, 10.3389/fimmu.2018.02588, 9, NOV, 2018.11, Glial connexins (Cxs) form gap junction channels through which a pan-glial network plays key roles in maintaining homeostasis of the central nervous system (CNS). In multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), expression of astrocytic Cx43 is lost in acute lesions but upregulated in chronic plaques, while astrocytic Cx30 is very low in normal white matter and changes in its expression have not been convincingly shown. In Cx30 or Cx43 single knockout (KO) mice and even in Cx30/Cx43 double KO mice, acute EAE is unaltered. However, the effects of Cx30/Cx43 deficiency on chronic EAE remains to be elucidated. We aimed to clarify the roles of Cx30 in chronic neuroinflammation by studying EAE induced by myelin oligodendrocyte glycoprotein peptide 35-55 in Cx30 KO mice. We found that Cx30 deficiency improved the clinical symptoms and demyelination of chronic but not acute EAE without influencing CD3+ T cell infiltration. Furthermore, increased ramified microglia in the naïve state and induced earlier and stronger microglial activation in the acute and chronic phases of EAE was observed. These activated microglia had an anti-inflammatory phenotype, as shown by the upregulation of arginase-1 and brain-derived neurotrophic factor and the downregulation of nitric oxide synthase 2. In the naïve state, Cx30 deficiency induced modest enlargement of astrocytic processes in the spinal cord gray matter and a partial reduction of Cx43 expression in the spinal cord white matter. These astrocytes in Cx30 KO mice showed earlier and stronger activation during the acute phase of EAE, with upregulated A2 astrocyte markers and a significant decrease in Cx43 in the chronic phases. Spinal cord neurons and axons were more preserved in Cx30 KO mice than in littermates in the chronic phase of EAE. These findings suggest that Cx30 deficiency increased ramified microglia in the CNS in the naïve state and improved chronic EAE through redirecting microglia toward an anti-inflammatory phenotype, suggesting a hitherto unknown critical role of astrocytic Cx30 in regulating microglial number and functional state..
12. Yu Hashimoto, Hidenori Ogata, Ryo Yamasaki, Takakazu Sasaguri, Senri Ko, kenichiro yamashita, Zhang Xu, Takuya Matsushita, Takahisa Tateishi, Shin'Ichi Akiyama, Shoichi Maruyama, Akifumi Yamamoto, Jun-Ichi Kira, Chronic inflammatory demyelinating polyneuropathy with concurrent membranous nephropathy
An anti-paranode and podocyte protein antibody study and literature survey, Frontiers in Neurology, 10.3389/fneur.2018.00997, 9, NOV, 2018.11, Background: Several case reports have described the concurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN). The presence of autoantibodies against podocyte antigens phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A) in MN suggests an autoimmune mechanism. Some CIDP patients also harbor autoantibodies against paranodal proteins such as neurofascin 155 (NF155) and contactin-1 (CNTN1). We investigated the relationship between CIDP and MN by assaying autoantibodies against paranodal and podocyte antigens in a CIDP patient with MN, and by a literature survey on the clinical features of CIDP with MN. Methods: Anti-CNTN1 and NF155 antibodies were measured by flow cytometry using HEK293 cell lines stably expressing human CNTN1 or NF155. Binding capacity of antibodies was validated by immunostaining mouse teased sciatic nerve fibers. Anti-PLA2R antibodies were measured by enzyme-linked sorbent assay and anti-THSD7A antibodies by indirect immunofluorescence assay. Clinical features between 14 CIDP with MN cases including two with anti-CNTN1 antibodies and 20 anti-CNTN1 antibody-positive CIDP cases were compared. Results: A patient whose ages was in the late 70 s complained of progressive weakness and superficial and deep sensory impairment in four extremities over 6 months. Nerve conduction studies showed prominent demyelination patterns. The patient presented with nephrotic syndrome. Renal biopsy disclosed basement membrane thickening with local subepithelial projections and glomerular deposits of IgG4, compatible with MN. Autoantibody assays revealed the presence of IgG4 and IgG1 anti-CNTN1 antibodies, but an absence of anti-NF155, anti-PLA2R, and anti-THSD7A antibodies. The patient's serum stained paranodes of teased sciatic nerves. CIDP with MN and anti-CNTN1 antibody-positive CIDP commonly showed male preponderance, relatively higher age of onset, acute to subacute onset in 35-50% of cases, distal dominant sensorimotor neuropathy, proprioceptive impairment leading to sensory ataxia, and very high cerebrospinal fluid protein levels. However, 11 of 13 CIDP patients with MN had a favorable response to mono- or combined immunotherapies whereas anti-CNTN1 antibody-positive CIDP was frequently refractory to corticosteroids and intravenous immunoglobulin administration. Conclusion: CIDP with MN and anti-CNTN1 antibody-positive CIDP show considerable overlap but are not identical. CIDP with MN is probably heterogeneous and some cases harbor anti-CNTN1 antibodies..
13. Guangrui Li, Ryo Yamasaki, Mei Fang, Katsuhisa Masaki, Hirofumi Ochi, Takuya Matsushita, Jun-Ichi Kira, Novel disease-modifying anti-rheumatic drug iguratimod suppresses chronic experimental autoimmune encephalomyelitis by down-regulating activation of macrophages/microglia through an NF-κB pathway, Scientific reports, 10.1038/s41598-018-20390-5, 8, 1, 2018.12, We aimed to elucidate the effects of iguratimod, a widely used anti-rheumatic drug with no severe side effects, on chronic experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Iguratimod was orally administered to mice immunised with myelin oligodendrocyte glycoprotein peptide 35-55. Preventive administration of iguratimod from the time of immunisation was found to markedly reduce the clinical severity of acute and chronic EAE. Pathologically, iguratimod treatment significantly reduced demyelination and infiltration of CD3 + T, F4/80 + , and CD169 + cells into the spinal cord, and suppressed macrophage/microglia activation in the parenchyma at the acute and chronic stages compared with vehicle treatment. Therapeutic administration of iguratimod after the onset of clinical symptoms significantly ameliorated the clinical severity of chronic EAE and reduced demyelination, T helper (Th)1/Th17 cell infiltration, macrophage/microglia activation, and nuclear factor (NF)-κB p65 and cyclooxygenase-2 expression in the spinal cord. In vitro, iguratimod treatment inhibited nuclear translocation of NF-κB p65 and down-regulated pro-inflammatory responses in macrophages and microglia. Our results suggest that iguratimod ameliorates acute and chronic EAE by suppressing inflammatory cell infiltration and immune cell activation, partly through inhibition of NF-κB p65, supporting the therapeutic potential of this drug for not only acute, but also chronic MS..
14. Naomi Mezaki, Takeshi Miura, Kotaro Ogaki, Makoto Eriguchi, Yuri Mizuno, Kenichi Komatsu, Hiroki Yamazaki, Natsuki Suetsugi, Sumihiro Kawajiri, Ryo Yamasaki, Takanobu Ishiguro, Takuya Konno, Hiroaki Nozaki, Kensaku Kasuga, Yasuyuki Okuma, Jun-Ichi Kira, Hideo Hara, Osamu Onodera, Takeshi Ikeuchi, Duplication and deletion upstream of LMNB1 in autosomal dominant adult-onset leukodystrophy, Neurology: Genetics, 10.1212/NXG.0000000000000292, 4, 6, 2018.12, Objective To characterize the genetic and clinical features of patients with autosomal dominant adult-onset demyelinating leukodystrophy (ADLD) carrying duplication and deletion upstream of lamin B1 (LMNB1). Methods Ninety-three patients with adult-onset leukoencephalopathy of unknown etiology were genetically analyzed for copy numbers of LMNB1 and its upstream genes. We examined LMNB1 expression by reverse transcription-qPCR using total RNA extracted from peripheral leukocytes. Clinical and MRI features of the patients with ADLD were retrospectively analyzed. Results We identified 4 patients from 3 families with LMNB1 duplication. The duplicated genomic regions were different from those previously reported. The mRNA expression level of LMNB1 in patients with duplication was significantly increased. The clinical features of our patients with LMNB1 duplication were similar to those reported previously, except for the high frequency of cognitive impairment in our patients. We found 2 patients from 1 family carrying a 249-kb genomic deletion upstream of LMNB1. Patients with the deletion exhibited relatively earlier onset, more prominent cognitive impairment, and fewer autonomic symptoms than patients with duplication. The presence of cerebellar symptoms and lesions may be characteristic in our patients with the deletion compared with the previously reported family with the deletion. Magnetic resonance images of patients with the deletion exhibited a widespread distribution of white matter lesions including the anterior temporal region. Conclusions We identified 4 Japanese families with ADLD carrying duplication or deletion upstream of LMNB1. There are differences in clinical and MRI features between the patients with the duplication and those with the deletion upstream of LMNB1..
15. Masaaki Niino, Toshiyuki Fukazawa, Jun-Ichi Kira, Tatsusada Okuno, Masahiro Mori, Nobuo Sanjo, Takashi Ohashi, Hikoaki Fukaura, Juichi Fujimori, Yuko Shimizu, Nobuhiro Mifune, Yusei Miyazaki, Eri Takahashi, Seiji Kikuchi, Dawn Langdon, Ralph H.B. Benedict, Makoto Matsui, Cognition with magnetic resonance imaging findings and social activities in patients with multiple sclerosis in a Japanese cohort, Clinical and Experimental Neuroimmunology, 10.1111/cen3.12484, 10, 1, 41-48, 2019.02, Objective: We investigated the association of magnetic resonance imaging (MRI) findings and social activities with cognition in Japanese patients with multiple sclerosis (MS). Methods: Cognition was evaluated by the Brief International Cognitive Assessment for MS (BICAMS), using previously published data for 156 Japanese patients with MS. The BICAMS results were analyzed with available MRI data, focusing on hyperintense lesions on T2/fluid-attenuated inversion recovery images. Logistic regression analysis was used to assess associations between the BICAMS scores and social activities (i.e. “student,” “employed full time,” “employed part time,” “homemaker” and “unemployed because of MS”). The independent variables were the BICAMS scores, and the Expanded Disability Status Scale, sex, age at examination, education and disease duration. The dependent variable was the “social activity.”. Results: Analysis of variance showed that patients with MS and more cerebral lesions on MRI had lower scores in all three domains of the BICAMS (the Symbol Digit Modalities Test, the second edition of the California Verbal Learning Test and the revised Brief Visuospatial Memory Test). Scores of all three domains were also significantly lower in patients with cerebellar lesions. Regarding social activities, patients who were unemployed because of MS had lower BICAMS scores compared with employed patients. However, the BICAMS domain scores did not independently affect the other social activities. Conclusions: Higher numbers of cerebral lesions and the presence of cerebellar lesions evaluated by MRI affect cognitive function based on the BICAMS. Cognitive function might affect social activities in patients with MS..
16. Takayuki Fujii, Ryo Yamasaki, Jun-Ichi Kira, Anti-plexin D1 antibodies are a novel biomarker for immune-mediated neuropathic pain, Clinical and Experimental Neuroimmunology, 10.1111/cen3.12488, 10, 1, 7-8, 2019.02.
17. Noriko Isobe, Toshikazu Baba, Yuri Nakamura, Koji Shinoda, mitsuru watanabe, Takuya Matsushita, Jun-Ichi Kira, Case of central nervous system inflammatory disease in late pregnancy, Clinical and Experimental Neuroimmunology, 10.1111/cen3.12503, 10, S1, 54-58, 2019.03, Background: During pregnancy, dynamic changes occur not only in coagulation, but also in immune responses. We report a case of a patient who developed an inflammatory disease in the central nervous system during late pregnancy and was challenging to diagnose. Case presentation: A 27-year-old woman experienced dysarthria during pregnancy at approximately 33 gestational weeks. From the 38th week of pregnancy, she developed general fatigue, clumsiness of the left hand and numbness of the right side of the body. After delivery of her child at 41 weeks’ gestation, she was moved to the neurology ward for further investigation. She showed limb ataxia of the left extremities and sensory disturbance on the right side of the body, including the face. Magnetic resonance imaging detected multiple gadolinium-enhanced lesions at the brainstem and cerebrum. High-dose intravenous methylprednisolone pulse therapy was effective, but her symptoms still remained, including palatal myoclonus. Diagnosing this patient was challenging, but clinically isolated syndrome or multiple sclerosis and neuro-Behҫet's disease were the main candidates. Conclusions: We present a case of a pregnant woman who developed brain inflammatory lesions with unknown etiology. Longitudinal follow up is mandatory for diagnosis with careful tapering of oral prednisolone..
18. Yiwen Cui, Katsuhisa Masaki, Xu Zhang, Ryo Yamasaki, Takayuki Fujii, Hidenori Ogata, Shotaro Hayashida, Hiroo Yamaguchi, Fuminori Hyodo, Hinako Eto, Sachiko Koyama, Kyoko Iinuma, Tomomi Yonekawa, Takuya Matsushita, Mari Yoshida, Kazunori Yamada, Mitsuhiro Kawano, Marie Malissen, Bernard Malissen, Jun-Ichi Kira, A novel model for treatment of hypertrophic pachymeningitis, Annals of Clinical and Translational Neurology, 10.1002/acn3.715, 6, 3, 431-444, 2019.03, Objective: Immunoglobulin (Ig)G4-related disease is a major cause of hypertrophic pachymeningitis (HP), presenting as a progressive thickening of the dura mater. HP lacks an animal model to determine its underlying mechanisms. We developed a suitable animal model for the treatment of HP. Methods: We longitudinally evaluated dura in mice with a mutation (Y136F) in the linker for activation of T cells (LAT), which induced type 2 T helper (Th2) cell proliferation and IgG1 (IgG4 human equivalent) overexpression. Mice were therapeutically administered daily oral irbesartan from 3 to 6 weeks of age. Human IgG4-related, anti-neutrophil cytoplasmic antibody-related, and idiopathic HP dura were also immunohistochemically examined. Results: LATY136F mice showing dural gadolinium enhancement on magnetic resonance imaging had massive infiltration of B220+ B cells, IgG1+ cells, CD138+ plasma cells, CD3+ T cells, F4/80+ macrophages, and polymorphonuclear leukocytes in the dura at 3 weeks of age, followed by marked fibrotic thickening. In dural lesions, transforming growth factor (TGF)-β1 was produced preferentially in B cells and macrophages while TGF-β receptor I (TGF-βRI) was markedly upregulated on fibroblasts. Quantitative western blotting revealed significant upregulation of TGF-β1, TGF-βRI, and phosphorylated SMAD2/SMAD3 in dura of LATY136F mice aged 13 weeks. A similar upregulation of TGF-βRI, SMAD2/SMAD3, and phosphorylated SMAD2/SMAD3 was present in autopsied dura of all three types of human HP. Irbesartan abolished dural inflammatory cell infiltration and fibrotic thickening in all treated LATY136F mice with reduced TGF-β1 and nonphosphorylated and phosphorylated SMAD2/SMAD3. Interpretation: TGF-β1/SMAD2/SMAD3 pathway is critical in HP and is a potential novel therapeutic target..
19. Takayuki Fujii, Kei ichiro Takase, Hiroyuki Honda, Nobutoshi Kawamura, Ryo Yamasaki, Michiyo Urata, Takeshi Uchiumi, Toru Iwaki, Jun-Ichi Kira, Toxic myopathy with multiple deletions in mitochondrial DNA associated with long-term use of oral anti-viral drugs for hepatitis B
A case study, Neuropathology, 10.1111/neup.12548, 39, 2, 162-167, 2019.04, Oral nucleoside analogs (NAs) reduce hepatitis B virus (HBV) replication by inhibiting HBV DNA polymerase. However, NAs can also affect human mitochondrial DNA (mtDNA) polymerase, which can lead to mtDNA depletion (quantitative abnormality). Indeed, several mitochondrial myopathy cases have been reported in which a reduced mtDNA copy number was induced by oral NAs for hepatitis B. Herein, we report a case of toxic myopathy with multiple mtDNA deletions (qualitative abnormality) associated with long-term use of NAs for hepatitis B. A 68-year-old woman, who underwent long-term treatment with lamivudine and adefovir for chronic hepatitis B, developed proximal muscle weakness in the four extremities. Neurological examination showed mild proximal muscle weakness and atrophy in the four extremities. Upon admission to our hospital, her blood lactate/pyruvate ratio during an aerobic exercise test was elevated. Myogenic patterns were observed in lower limb muscles on electromyographic examination. Muscle magnetic resonance imaging revealed diffuse atrophy of proximal muscles in the four extremities with no signal changes. A biopsy from the biceps brachii muscle showed an abnormally large variation in fiber size, scattered muscle fibers with decreased cytochrome c oxidase activity, and ragged-red fibers. Analysis of mtDNA from skeletal muscle revealed no decrease in copy number but increased incidence of multiple deletions, including a deletion of 4977 base pairs (known as the common deletion) reflecting oxidative stress-induced mtDNA damage. This case study indicates that long-term oral antiviral therapy for hepatitis B can induce chronic oxidative damage to mtDNA resulting in qualitative mtDNA abnormalities and toxic myopathy..
20. Jun-Ichi Kira, Noriko Isobe, Helicobacter pylori infection and demyelinating disease of the central nervous system, Journal of Neuroimmunology, 10.1016/j.jneuroim.2018.06.017, 329, 14-19, 2019.04, Helicobacter pylori (H. pylori) colonize >50% of the entire human population. Generally, H. pylori infect the human stomach in infancy when parietal cells secreting gastric acids, which reduce the survival of H. pylori, are not well matured. Once acquired, the bacterium persists for life. Thus, H. pylori infection reflects sanitary conditions during childhood. >10 studies performed in various Eastern and Western countries as well as two meta-analyses collectively indicated the H. pylori infection rate is significantly lower in patients with multiple sclerosis (MS) than in healthy controls. Thus, the bacterium might be a protective factor for MS, especially in low prevalence countries and younger generations that grew up in the low prevalence era. The protective effects of H. pylori might be explained by the hygiene hypothesis—encountering generic infection early in life facilitates development of the immunoregulatory system, which suppresses overactivity of autoimmune T cells later in life. However, no influence of common childhood infections on MS risk was reported by large MS cohort studies. Direct attenuation of autoreactive Th1 and Th17 cells by H. pylori infection was found in experimental autoimmune encephalomyelitis, an animal model of MS. These observations may underscore the direct protective effects of H. pylori on MS rather than generic infection in childhood. By contrast, several studies reported that H. pylori infection rates are significantly higher in anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) than in healthy controls. H. pylori strongly activate Th17 cells via the induction of IL-23, resulting in neutrophil mobilization and activation. H. pylori neutrophil-activating protein (NAP) is a major proinflammatory protein responsible for the pathology of H. pylori-related gastric inflammatory diseases. Anti-H. pylori-NAP antibody levels were positively correlated with final EDSS scores and myeloperoxidase levels in anti-AQP4 antibody-positive NMOSD patients. Given that spinal cord lesions of NMOSD are heavily infiltrated with myeloperoxidase-positive neutrophils, H. pylori-NAP, which can be absorbed and presented to the host immune system, may exacerbate NMOSD. Thus, H. pylori infection and its proinflammatory proteins, such as NAP, may contribute to the pathology of anti-AQP4 antibody-related neural damage, by activating neutrophils. It is interesting that two representative demyelinating diseases of the central nervous system are differentially modulated by chronic H. pylori infection. The direct effects of H. pylori infection on MS and NMOSD warrant future studies..
21. Toshikazu Baba, Koji Shinoda, mitsuru watanabe, Shoko Sadashima, Dai Matsuse, Noriko Isobe, Ryo Yamasaki, Kimihiko Kaneko, Toshiyuki Takahashi, Toru Iwaki, Jun-Ichi Kira, MOG antibody disease manifesting as progressive cognitive deterioration and behavioral changes with primary central nervous system vasculitis, Multiple Sclerosis and Related Disorders, 10.1016/j.msard.2019.01.053, 30, 48-50, 2019.05, We report a 60-year-old male with anti-myelin oligodendrocyte glycoprotein (MOG) antibody who developed progressive cognitive deterioration and behavioral changes, with no other focal signs, over 9 months. MRI showed numerous T2-hyperintense lesions with partial contrast enhancement in white and grey matter of cerebrum, cerebellum and spinal cord. A brain biopsy revealed perivascular inflammatory cell infiltration, disturbed vascular continuity and no demyelination, indicative of a lymphocytic pattern of primary CNS vasculitis (PCNSV). Contrast enhancement disappeared after immunotherapy; however, cognitive impairment was not improved. Neurologists should note that MOG antibody disease can present as immunotherapy-resistant progressive cognitive impairment with PCNSV-like histopathology..
22. Xu Zhang, Takayuki Fujii, Hidenori Ogata, Ryo Yamasaki, Katsuhisa Masaki, Yiwen Cui, Takuya Matsushita, Noriko Isobe, Jun-Ichi Kira, Cerebrospinal fluid cytokine/chemokine/growth factor profiles in idiopathic hypertrophic pachymeningitis, Journal of Neuroimmunology, 10.1016/j.jneuroim.2019.01.010, 330, 38-43, 2019.05, Hypertrophic pachymeningitis (HP) is a rare neurologic disease causing inflammatory fibrous thickening of the brain and spinal dura mater. We investigated the cerebrospinal fluid cytokine profile of HP by measuring 28 cytokines/chemokines/growth factors with a multiplexed fluorescent immunoassay in 8 patients with HP (6 idiopathic, 1 IgG4-related, 1 anti-neutrophil cytoplasmic antibody-related), and 11 with other non-inflammatory neurologic diseases (OND). Interleukin (IL)-4, IL-5, IL-9, IL-10, TNF-α, and CXCL8/IL-8 levels were significantly higher in idiopathic HP (IHP) than OND. Cluster analyses disclosed two major clusters: one mainly consisted of IHP and the other of OND, suggesting a unique cytokine profile in IHP..
23. Masakazu Kawajiri, Junpei Koge, Tetsuya Hashimoto, Takeshi Yamada, Noriko Isobe, Jun-Ichi Kira, Recurrent rhombencephalomyelitis associated with allergen immunotherapy by mite antigen sublingual tablets, eNeurologicalSci, 10.1016/j.ensci.2019.100190, 15, 2019.06.
24. Ban yu Saitoh, Ryo Yamasaki, Hiwatashi Akio, Takuya Matsushita, Shintaro Hayashi, Yoshihiro Mitsunaga, Yasuhiro Maeda, Noriko Isobe, Kunihiro Yoshida, Shu ichi Ikeda, Jun-Ichi Kira, Discriminative clinical and neuroimaging features of motor-predominant hereditary diffuse leukoencephalopathy with axonal spheroids and primary progressive multiple sclerosis
A preliminary cross-sectional study, Multiple Sclerosis and Related Disorders, 10.1016/j.msard.2019.03.008, 31, 22-31, 2019.06, Background: Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) is a rare autosomal-dominant white matter disease, typically characterized by juvenile cognitive decline and frontoparietal white matter lesions. A portion of HDLS patients exhibit preferential motor dysfunctions as their initial symptoms, mimicking multiple sclerosis (MS). However, there is no study comparing this phenotype of HDLS and primary progressive multiple sclerosis (PPMS), which greatly resemble each other. This is the first preliminary study to clarify the clinical and neuroimaging features of motor-predominant HDLS, and compare it with PPMS, using cases whose colony stimulating factor 1 receptor (CSF1R) were sequenced. Methods: Clinical and radiological data from Japanese patients at the Department of Neurology, Kyushu University Hospital, Fukuoka, Japan, were evaluated retrospectively and cross-sectionally. Twenty-nine brain and 18 spinal cord magnetic resonance imaging (MRI) scans from four motor-predominant HDLS patients with CSF1R mutations and 15 PPMS patients without CSF1R mutations, were evaluated using an HDLS MRI scoring system. Results: Two patients with HDLS were initially diagnosed with MS and received immunotherapy. Clinically, motor-predominant HDLS and PPMS patients resembled each other in onset age and disability. However, motor-predominant HDLS patients had a significantly higher frequency of frontal release signs, lower positivity rates of oligoclonal IgG bands (OCB), and lower IgG index values. Total HDLS MRI scores, total white matter lesions (WMLs), and brain atrophy were similar between the diseases. However, motor-predominant HDLS patients had more marked atrophy of the corpus callosum (CC) body, more WMLs in the deep and subcortical regions of the frontoparietal lobes, fewer WMLs in the occipitotemporal periventricular regions, and more restricted diffusivity lesions on MRI than PPMS patients. There was a stronger association between disease duration and CC index in HDLS, suggesting more rapid progression compared with PPMS. Conclusions: Motor-predominant HDLS has characteristic frequent frontal release signs, normal findings for OCB and the IgG index, severe CC body atrophy, abundant deep and subcortical WMLs in the frontoparietal lobes, subtle occipitotemporal lobe periventricular WMLs, and more restricted diffusivity lesions on MRI. Although the present study was limited by the small number of HDLS cases, we propose that immunotherapy should be avoided in such cases..
25. Higuchi Y, Hashiguchi A, Shiraishi W, Jun-ichi Kira, Mutations in MME cause an autosomal recessive Charcot-Marie-Tooth disease type 2., Ann Neurol (in press), Ann Neurol (in press), 2016.08.
26. Saigoh K, Yoshimura S, Jun-ichi Kira, Chondroitin sulfate beta-1, 4-N-acetylgalactosaminyl transferase-1 (chGN-1) polymorphism: association with progression of multiple sclerosis., Neurochem Res (in press), Neurochem Res (in press), 2016.03.
27. Saida T, Makioka H, Jun-ichi Kira, Safety and efficiency response to interferon beta-la therapy in Japanese patients with multiple sclerosis: interium results of a postmarketing surveillance study., Clin Exp Neuroimmunol (in press) , Clin Exp Neuroimmunol (in press) , 2016.03.
28. Shinoda K, Sun X, Jun-ichi Kira, Requirement of CD30 expression on CD4 T cells in the pathogenesis of experimental autoimmune encephalomyelitis., J Neuroimmunol (in press) , J Neuroimmunol (in press) , 2016.03.
29. Ryo Yamasaki, Hiroyuki Murai, Takuya Matsushita, Jun-ichi Kira, Efficacy of intravenous methylprednisolone pulse therapy in patients with multiple sclerosis and neuromyelitis optica., Mult Scler (in press) , Mult Scler (in press) , 2016.03.
30. Tanaka K, Hiroyuki Murai, Jun-ichi Kira, Pure dysarthia and dysarthria-dacial paresis syndrome due to internal capsule and/or corona radiata infraction., BMC Neurology 15:184-188, 2015., BMC Neurology 15:184-188, 2015., 2015.12.
31. Chatani Y, Hayashi YK, Jun-ichi Kira, Neuromagnetic evidence for hippocampal modulation of auditory processing., Neuroimage 124(Pt A):256-266, 2016., Neuroimage 124(Pt A):256-266, 2016., 2016.01.
32. Uruha H, Hayashi YK, Jun-ichi Kira, Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure., J Neurol Neurosurg Psychiatry 86: 483-489, 2015., J Neurol Neurosurg Psychiatry 86: 483-489, 2015., 2015.04.
33. Yaldizli O, Penner I, yonekawa T, Jun-ichi Kira, The association between olfactory bulb atrophy, cognitive dysfunction, physical disability and depression in multiple sclerosis., Eur J Neurol (in press)., Eur J Neurol (in press)., 2015.10.
34. Nishi H, Nakahara I, Jun-ichi Kira, Platelet reactivity and hemorrhage risk in neurointerventional procedure under dual antiplatelet therapy., J Neurointervention Surg (in press)., J Neurointervention Surg (in press)., 2015.10.
35. Ogata H, Ryo Yamasaki, Takuya Matsushita, Hiroyuki Murai, Jun-ichi Kira, Characterization of IgG4 anti-neurofascin 155 antibody-positive neuropathy., Ann Clin Transl Neurol 2: 960-971, 2015., Ann Clin Transl Neurol 2: 960-971, 2015., 2015.10.
36. Sato S, Yamamoto K, Takuya Matsushita, Masaki Katsuhisa, Jun-ichi Kira, Copy number variations in multiple sclerosis and neuromyelitis optica., Ann Neurol 78: 762-774, 2015., Ann Neurol 78: 762-774, 2015., 2015.07.
37. Shimizu Y, Makioka H, Jun-ichi Kira, Outcomes of pregnancy during interferon beta-1a therapy in Japanese patients with multiple sclerosis: interim results of a postmarketing surveillance study., Clin Exp Neuroimmunol 6: 402-408, 2015., Clin Exp Neuroimmunol 6: 402-408, 2015., 2015.10.
38. Ramanathan S, Sato S, Takuya Matsushita, Masaki Katsuhisa, Jun-ichi Kira, Antibodies to myelin oligodendrocyte glycoprotein are uncommon in Japanese opticospinal multiple sclerosis., Mult Scler (in press)., Mult Scler (in press)., 2015.07.
39. Song ZY, Ryo Yamasaki, Hiroyuki Murai, Jun-ichi Kira, Peripheral blood T cell dynamics predict relapse in multiple sclerosis patients on fingolimod., PLoS ONE (in press) 2015 Apr 28;10(4):e0124923. doi: 10.1371., PLoS ONE (in press) 2015 Apr 28;10(4):e0124923. doi: 10.1371., 2015.07.
40. Tanaka K, Yamada T, Hiroyuki Murai, Jun-ichi Kira, Pre-admission CHADS2, CHA2DS2-VASc, and R2CHADS2 scores on severity and functional outcome in acute ischemic stroke with atrial fibrillation., J Stroke Cerebrovasc Dis 24: 1629-1635, 2015., J Stroke Cerebrovasc Dis 24: 1629-1635, 2015., 2015.07.
41. Tanaka M, Kinoshita M, Tanaka K, Jun-ichi Kira, Body weight based natalizumab treatment in adult patients with multiple sclerosis., J Neurol 262:781-782, 2015, J Neurol 262:781-782, 2015., 2015.03.
42. Niino M, Sato S, Fukazawa T, Jun-ichi Kira, Decreased serum vitamin D levels in Japanese patients with multiple sclerosis., J Neuroimmunol 279:40-45, 2015., J Neuroimmunol 279:40-45, 2015., 2015.03.
43. Ogata H, Matsuse Dai, Ryo Yamasaki, Jun-ichi Kira, A nationwide survey of combined central and peripheral demyelination in Japan., J Neurol Neurosurg Psychiatry (in press)., J Neurol Neurosurg Psychiatry (in press)., 2015.03.
44. Katayama K, Misawa S, Sato Y, Jun-ichi Kira, Japanese POEMS syndrome with Thalidomide (J-POST) Trial: study protocol for a phase II/III multicentre, randomised, double-blind, placebo-controlled trial., BMJ Open (in press), BMJ Open (in press)., 2015.01.
45. Shinoda K, Sun X, Oyamada A, Jun-ichi Kira, CD30 ligand is a new therapeutic target for central nervous system autoimmunity., J Autoimmunity 57: 14-23, 2015., J Autoimmunity 57: 14-23, 2015., 2015.01.
46. Isobe N, Yonekawa T, Takuya Matsushita, Jun-ichi Kira, Distinct features of IgG2 aquaporin-4 antibody carriers with neuromyelitis optica., Clin Exp Neuroimmunol (in press)., Clin Exp Neuroimmunol (in press), 2015.03.
47. Niino M, Sato S, Fukazawa T, Jun-ichi Kira, Latitude and HLA-DRB1 alleles independently affect the emergence of cerebrospinal fluid IgG abnormality in multiple sclerosis., Multiple Sclerosis 21:1112-20, 2015. , Multiple Sclerosis 21:1112-20, 2015. , 2015.03.
48. Doi H, Inamizu S, Saito B, Jun-ichi Kira, Analysis of cerebral lobar microbleeds and decreased cerebral blood flow in a memory clinic setting., Intern Med 54:1027-1033, 2015., Intern Med 54:1027-1033, 2015., 2015.04.
49. Akinori Uruha, Yukiko K Hayashi, Yasushi Oya, Jun-ichi Kira, Ichizo Nishino, Necklace cytoplasmic bodies in hereditary myopathy with early respiratory failure., J Neurol Neurosurg Psychiatry , 10.1136/jnnp-2014-309009, JNNP (in press)., 2014.09.
50. Doi H, Song ZY, Yoshimura Satoshi, Jun-ichi Kira, Distinct cytokine and T helper cell profiles between patients with multiple sclerosis who had or had not received interferon-beta., Clin Exp Neuroimmunol 5: 321-327, 2014., Clin Exp Neuroimmunol 5: 321-327, 2014., 2014.09.
51. Niino M, Mifune N, Kohriyama T, Jun-ichi Kira, Association of cognitive impairment with magnetic resonance imaging findings and social activities in patients with multiple sclerosis. , Clin Exp Neuroimmunol 5: 328-335, 2014., Clin Exp Neuroimmunol 5: 328-335, 2014., 2014.07.
52. Kinoshita M, Kondo Y, Yoshida K, Jun-ichi Kira, Corpus callosum atrophy in patients with hereditary diffuse leukoencephalopathy with neuroaxonal spheroids: An MRI-based study., Intern Med 53: 21-27, 2014., Intern Med 53: 21-27, 2014., 2014.04.
53. Yoshimura Satoshi, Takuya Matsushita, Masaki Katsuhisa, Jun-ichi Kira, Genetic and infeactious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients., PLos ONE 2014 Apr 15;9(4):e95367, PLos ONE 2014 Apr 15;9(4):e95367, 2014.04.
54. Arahata H, Yasumasa Ohyagi, Ryo Yamasaki, Jun-ichi Kira, Early inhibition of tumor necrosis factor-α and interleukin-6 in muscle tissue as a therapy for dystrophinopathy in mdx mice., Clin Exp Neuroimmunol 5: 371-377, 2014., 5: 371-377, 2014., 2014.07.
55. Cui YW, Masaki Katsuhisa, Ryo Yamasaki, Jun-ichi Kira, Extensive dysregulations of oligodendrocytic and astrocytic connexins are associated with disease progression in an amyotrophic lateral sclerosis mouse model., J Neuroinflam Clin (in press)., in press., 2014.03.
56. kobayakawa Y, Sakuni K, Kajitani K, Jun-ichi Kira, Galactin-1 deficiency improves axonal swelling of motor neurons in SOD1G93A transgenic mice., Neuropathol Appl Neurobiol (in press)., in press., 2014.01.
57. Jun-ichi Kira, Itoyama Y, Kikuchi S, Hao Q, Fingolimod (FTY720) therapy in Japanese patients with relapsing multiple sclerosis over 12-months: results of a phase 2 observational extension., BMC Neurology , 14: 21, 2014., 2014.01.
58. Niino M, Mifune N, Kohriyama T, Jun-ichi Kira, Apathy/depression, but not subjective fatigure, is related with cognitive dysfunction in patients with multiple sclerosis., BMC Neurology , 14: 3, 2014., 2014.01.
59. Cui YW, Yuji Kawano, Ryo Yamasaki, Jun-ichi Kira, Decreased CCR2 and CD62L expressions on peripheral blood classical monocytes in amyotrophic lateral sclerosis. , Clin Exp Neuroimmunol (in press), in press., 2013.08.
60. Ainiding G, Yuji Kawano, Sato S, Jun-ichi Kira, Interleukin 2 receptor α chain gene polymorphisms and risks of multiple sclerosis and neuromyelitis optica in southern Japanese., J Neurol Sci, 337: 147-150, 2014. , 2013.08.
61. Yonekawa T, Hiroyuki Murai, Takuya Matsushita, Jun-ichi Kira, A nationwide survey of hypertrophic pachymeningitis in Japan., J Neurol Neurosurg Psychiatry (in press), in press., 2013.08.
62. Jun-ichi Kira, Ryo Yamasaki, Yoshimura Satoshi, Yuji Kawano, Efficacy of methylprednisolone pulse therapy for acute relapse in Japanese patients with multiple sclerosis and neuromyelitis optica: a multicenter retrospective analysis: 1. Whole group analysis., Clin Exp Neuroimmunol , 4: 305-317, 2013. , 2013.08.
63. Yuji Kawano, Takuya Matsushita, Isobe N, Jun-ichi Kira, The protein kinase C-η polymorphism rs2230500 does not confer disease susceptibility to multiple sclerosis or neuromyelitis optica., Clin Exp Neuroimmunol , 4: 283-287, 2013., 2013.08.
64. Masaki Katsuhisa, Suzuki SO, Takuya Matsushita, Ryo Yamasaki, Jun-ichi Kira, Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica, PLoS ONE (in press), in Press., 2013.08.
65. Yoshimura Satoshi, Yonekawa T, Isobe N, Jun-ichi Kira, Bacterial infectious burden and prevalence of idiopathic central nervous system demyelinating diseases in Japanese., Clin Exp Neuroimmunol , 4: 351-2, 2013., 2013.08.
66. Cui YW, Yuji Kawano, Shi N, Jun-ichi Kira, Alterations in chemokine receptor expressions on peripheral blood monocytes in multiple sclerosis and neuromyelitis optica., Clin Exp Neuroimmunol , 4: 201-205, 2013., 2013.07.
67. Araki Y, Kinoshira M, Motoyama R, Takuya Matsushita, Jun-ichi Kira, Month of birth in multiple sclerosis with and without longitudinally extensive spinal cord lesions: A study of a Japanese national survey., J Neurol Sci , 330: 67-70, 2013., 2013.08.
68. Watanabe M, Ryo Yamasaki, Yuji Kawano, Imamura S, Jun-ichi Kira, Anti-KIR4.1 Antibodies in Japanese Patients with Multiple Sclerosis, Clin Exp Neuroimmunol , 4: 241-242, 2013., 2013.07.
69. Kawamura N, Ryo Yamasaki, Takuya Matsushita, Yonekawa T, Jun-ichi Kira, Anti-neurofascin antibody in patients with combined central and peripheral demyelination., Neurology , 81: 714-722, 2013., 2013.08.
70. Kanamori Y, Hironaga, Hagiwara K, Taira Uehara, Jun-ichi Kira, Minimum norm estimates analysis in MEG can delineate the onset of interictal epileptic discharges: a comparison with ECoG findings., Neuro Image: Clinical (in press), in press., 2013.07.
71. Kamada T, Sun W, Takase K, Hiroshi Shigeto, Jun-ichi Kira, Spontaneous Seizures in a Rat Model of Multiple Prenatal Freeze Lesioning., Epilepsy Res , 105: 280-291, 2013., 2013.07.
72. Kanamori Y, Isobe N, Yonekawa T, Takuya Matsushita, Jun-ichi Kira, Multimodality evoked potentials for discrimination of atopic myelitis and multiple sclerosis., Clin Exp Neuroimmunol , 4: 29-35, 2013., 2013.04.
73. Huang J, Yoshimura Satoshi, Isobe N, Jun-ichi Kira, Distinct genetic profiles between Japanese multiple sclerosis patients with and without Barkhof brain lesions., Clin Exp Neuroimmunol , 4: 173-180, 2013., 2013.07.
74. Takuya Matsushita, Takahisa Tateishi, Isobe N, Yonekawa T, Jun-ichi Kira, Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis., PLoS ONE (in press), in Press., 2013.04.
75. Isobe N, Takuya Matsushita, Yonekawa T, Jun-ichi Kira, Clinical relevance of serum aquaporin-4 levels in neuromyelitis optica., Neurochem Res , 38: 997-1001, 2013., 2013.05.
76. Huang J, Yoshimura Satoshi, Isobe N, Jun-ichi Kira, A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese., Multiple Sclerosis , 19: 1696-1703, 2013., 2013.04.
77. Carroll W, Saida T, Kim H, Jun-ichi Kira, A guide to facilitate the early treatment of patients with idiopathic demyelinating disease (multiple sclerosis and neuromyelitis optica)., Multiple Sclerosis , Mult Scler 19: 1371-1380, 2013., 2013.10.
78. Kikuchi H, Mifune N, Niino M, Jun-ichi Kira, Structural equation modeling of factors contributing to quality of life in Japanese patients with multipe sclerosis., BMC Neurology , 13:10-19, 2013., 2013.01.
79. Nagara Y, Takahisa Tateishi, HAYASHI SHINTARO, Jun-ichi Kira, Impaired cytoplastic-nuclear transport of hypoxia-inducible factor-1αin amgotrophic lateral sclerosis., Brain Pathol , Brain Pathol 23: 534-46, 2013., 2013.05.
80. 上原 平, Yamasaki T, Okamoto T, Jun-ichi Kira, Efficiency of a “small-world” brain network depends on consciousness level: a resting-state fMRI study., Cerebral Cortex (in press), in press, 2013.01.
81. Nakamichi K, Kishida S, Tanaka K, Jun-ichi Kira, Sequential changes in the non-coding control region sequences of JC polyomaviruses from the cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy., Arch Virol , 158: 639-50, 2013., 2013.03.
82. Yoshimura Satoshi, Isobe N, Takuya Matsushita, Jun-ichi Kira, Genetic and infectious profiles of Japanese multiple sclerosis patients., PLoS ONE (in press), in press, 2013.01.
83. Yoshimura Satoshi, Isobe N, Takuya Matsushita, Jun-ichi Kira, Distinct genetic and infectious profiles in Japanese neuromyelitis optica patients according to anti-aquaporin-4 antibody status., J Neurol Neurosurg Psychiatry , 84: 29-34, 2013., 2013.01.
84. Soejima N, Yasumasa Ohyagi, Nakamura N, Jun-ichi Kira, Intracellular accumulation of toxic turn amyloid-β is associated with endoplasmic reticulum stress in Alzheimer’s disease., Current Alzheimer Research, 10: 11-20, 2013., 2012.12.
85. Saida T, Kikuchi S, Itoyama Y, Jun-ichi Kira, A randomized, controlled trial of fingolimod (FTY 720) in Japanese patients with multiple sclerosis., Multiple Sclerosis , 18:1269-1277, 2012., 2012.12.
86. Saida T, Itoyama Y, Tashiro K, Jun-ichi Kira, Intramuscular interferon bata-la is effective in Japanese patients with relapsiny-remittingz multiple sclerosis: a pre-treatment versus treatment comparison study of gadolinium-enhanced MRI brain lesions., Multiple Sclerosis , 18:1782-1790, 2012., 2012.12.
87. Isobe N, Takuya Matsushita, Yonekawa T, Jun-ichi Kira, Quantitative assays for anti-aquaporin-4 antibody with subclass analysis in neuromyelitis optica., Multiple Sclerosis , 18:1541-1551, 2012., 2012.12.
88. Kakumoto K, Matsumoto S, Nakahara I, Jun-ichi Kira, Rapid formation of cerebral microbleeds after carotid artery stenting., Cerebrovascular Diseases EXTRA, 2: 9-16, 2012., 2012.12.
89. Sato S, Isobe N, Yoshimura S, Jun-ichi Kira, HLA-DPB1 0201 is associated with susceptibility to atopic myelitis in Japanese., J Neuroimmunol, 251:110-113, 2012., 2012.12.
90. Masaki K, Suzuki SO, Matsushita T, Yonekawa T, Matsuoka T, Isobe N, Motomura K, Wu XM, Tabira T, Iwaki T, Kira J, Extensive loss of connexins in Baló's disease: evidence for an auto-antibody-independent astrocytopathy via impaired astrocyte-oligodendrocyte/myelin interaction., Acta Neuropathol, 123: 887-900, 2012, 2012.06.
91. Riwanti Estiasari, Matsushita T, Masaki K, Akiyama T, Yonekawa T, Isobe N, Kira J, Comparison of clinical, immunological and neuroimaging features between anti-aquaporin-4 antibody-positive and –negative Sjögren’s syndrome patients with central nervous system manifestations, Multiple Sclerosis , 18: 807-816, 2012, 2012.06.
92. Ainiding G, Yamashita K, Torii T, Furuta K, Isobe N, Matsushita T, Masaki K, Matsumoto S, Kira J, Clinical disability progression and platelet GP IIb/IIIa values in patients with atopic myelitis, J Neuroimmunol, 246: 108-112, 2012, 2012.05.
93. Isobe N, Kanamori Y, Yonekawa T, Matsushita T, Shigetou H, Kawamura N, Kira J, First diagnostic criteria for atopic myelitis with special reference to discrimination from myelitis-onset multiple sclerosis., J Neurol Sci , 316: 30-35, 2012, 2012.05.
94. Fukunaga Kawamura M, Yamasaki R, Kawamura N, Tateishi T, Nagara Y, Matsushita T, Ohyagi Y, Kira J , Impaired recruitment of neuroprotective microglia and T cells during acute neuronal injury coincides with increased neuronal vulnerability in an amyotrophic lateral sclerosis model., Exp Neurol 234: 437-445, 2012, 234: 437-445, 2012, 2012.04.
95. Yamasaki T, Goto Y, Ohyagi Y, Monji A, Munetsuna S, Minohara M, Kira J, Kanba S, Tobimatsu S, Selective impairment of optic flow perception in amnestic mild cognitive impairment: evidence from event-related potentials, J Alzheimer’s Disease, 28: 695-708, 2012, 2012.03.
96. Dashjamts T, Yosiura T, Hiwatashi A, Yamashita K, Monji A, Ohyagi Y, Kamano H, Kawashima T, Kira J, Honda H, Simultaneous actrial spin labeling cerebral blood flow and morphologyical assessments for detection of Alzheimer’s disease., Acad Radiol, 18: 1492-1499, 2011, 2011.12.
97. Kawamura N*, Pia H*, Minohara M, Matsushita T, Kusunoki S, Matsumoto H, Ikenaka K, Mizunoe Y, Kira J, Campylobacter jejuni DNA-binding protein from starved cells in Guillain-Barré syndrome., J Neuroimmunol, 240-241: 74-78, 2011, 2011.12, 1.
98. McElroy JP, Isobe N, Gourraud PAFD, Cailler GSJ, Matsushita T, Kohriyama T, Miyamoto K, Nakatsuji Y, Miki T, Hauser SL, Oksenberg JR, Kira J, SNP based analysis of the HLA locus in Japanese multiple sclerosis patients, Gene and Immunity, 12: 523-530, 2011, 2011.10.
99. Matsuoka T, Suzuki SO, Suenaga T, Iwaki T, Kira J, Reappresal of aquaporin-4 astrocytopathy in Asian neuromyelitis optica and multiple sclerosis patients., Brain Pathol, 21: 516-532, 2011, 2011.09.
100. Matsuse D, Kitada M, Ogura F, Wakao S, Kohama M, Kira J, Tabata Y, Dezawa M, Combined transplantation of bone marrow stroma cell-derived neural progenitor cells with a collagen sponge and fibroblast growth factor (bFGF) releasing microspheres enhances recovery after cerebral ischemia in rats, Tissue Engineering, 17: 1993-2004, 2011, 2011.08.
101. Pineda AAM*, Minohara M*, Kawamura N, Matsushita T, Yamasaki R, Sun X, Piao H, Shimokawa H, Kira J, Preventive and therapeutic effects of the selective Rho-kinase inhibitor fasudil on experimental autoimmune neuritis, J Neurol Sci, 306: 115-120, 2011, 2011.07.
102. Fang L*, Isobe N*, Yoshimura S, Yonekawa T, Matsushita T, Masaki K, Doi H, Ochi K, Miyamoto K, Kawano Y, Kira J, Interleukin-7 receptor alpha gene polymorphism influences multiple sclerosis risk in Asians, Neurology , 76: 2125-2127, 2011, 2011.06, IL-7Rα鎖の多型が多発性硬化症の疾患感受性と有意に相関することをアジア人種で初めて明らかにした。.
103. Shigetou H, Sakata A, Morioka T, Takase K, Hagiwara H, Kamada T, Kanamori Y, Hashiguchi K, Tobimatsu S, Yamashita N, Kira J, Peri-orbital electrodes as a supplemental recording for detection of ictal discharges in medial temporal lobe epilepsy, Neurology Asia , 16: 303-307, 2011, 2011.04.
104. Murai H, Yamashita N, Watanabe M, Nomura Y, Motomura , Yoshikawa H, Kawaguchi N, Onodera H, Araga S, Isobe N, Nakamura Y, Nagai M, Kira J, Characteristics of myasthenia gravis according to onset-age: third Japanese nationwide survey, J Neurol Sci, 305: 97-102, 2011, 2011.03.
105. Yonekawa T, Matsushita T, Minohara M, Isobe N, Masaki K, Yoshimura S, Nishimura S, Kira J, T cell reactivities to myelin protein-derived peptides in neuromyelitis optica patients with anti-aquaporin-4 antibody, Neurology Asia, 16: 139-142, 2011, 2011.02.
106. Himeno E, Ohyagi Y, Ma L, Nakamura N, Miyoshi K, Sakae N, Motomura K, Soejima N, Yamasaki R, Hashimoto T, Tabira T, LaFerla FM, Kira J, Apomorphine treatment for Alzheimer's mice promoting amyloid-Β degradation
Ann Neurol
, Annals of Neurology, 69, 248-256, 69:248-256, 2011, 2011.02.
107. Kikuchi H, Mifune N, Niino M, Ohbu S, Kira J, Kohriyama T, Ota K, Tanaka M, Ochi H, Nakane S, Maezawa M, Kikuchi S, Impact and characteristics of quality of life in Japanese patients with multiple sclerosi., Qual Life Res, 20: 119-131, 2011, 2011.02.
108. Doi H, Matsushita T, Isobe N, Tateishi T, Kira J, Analysis of cerebrospinal fluid cytokines and growth factors in multiple sclerosis patients with and without chronic headaches, Neurology Asia, 16: 65-70, 2011, 2011.01.
109. Ma L, Ohyagi Y, Nakamura N, Iinuma KM, Miyoshi K, Himeno E, Soejima N, Yanagihara YT, Sakae N, Yamasaki R, Kira J, Activation of glutathione peroxidase and inhibition of p53-related apoptosis by apomorphine, J Alzheimer’s Disease, 27: 225-237, 2011, 2011.01.
110. Piao H, Minohara M, Kawamura N, Li W, Matsushita T, Yamasaki R, Mizunoe Y, Kira J, Tissue binding patterns and in vitro effects of Campylobacter jejuni DNA-binding protein form starved cells., Neurochem Res, 36, 58-66, 36:58-66, 2011, 2011.01.
111. Yamasaki R, Tanaka M, Fukunaga M, Tateishi T, Kikuchi H, Motomura K, Matsushita T, Ohyagi Y, Kira J, Restoration of microglial function by granulocyte-colony stimulating factor in ALS model mice., J Neuroimmnol , 229, 51-62, 229:51-62, 2010, 2010.12.
112. Kai N, Kawajiri M, Seki N, Tanaka N, Kira J, Tobimatsu S, Naito S, Efficiancy of high-frequency magnetic stimulation of the sacral root in patients with urinary in continence following a nadical prostatectomy, LUTS, 3, 10-14, LUTS3: 10-14, 2010, 2010.12.
113. Matsuoka T, Suzuki SO, Iwaki T, Tabira T, Ordinario AT, Kira J, Aquaporin-4 astrocytopathy in Baló's disease., Acta Neuropathol, 120, 651-660, 120: 651-660, 2010, 2010.11.
114. Yoshiura T, Hiwatashi A, Yamashita K, Ohyagi Y, Monji A, Takayama Y, Kamano N, Kawashima T, Kira J, Honda H, Deterioration of abstract reasoning ability in mild cognitive impairment and Alzheimer’s disease: correlation with regional grey matter volume loss revealed by diffeomorphic anatomical registration through exponentiated lie algebra analysis. , Eur Radiol, 21: 419-425, 2010, 2010.11.
115. Yoshimura S, Ochi H, Isobe N, Matsushita T, Motomura K, Matsuoka T, Minohara M, Kira J, Altered production of brain-derived neurotrophic factor by peripheral blood immune cells in multiple sclerosis., Mult Scler , 16, 1178-1188, 16: 1178-1188, 2010, 2010.10.
116. Ohshima S, Tsuboi Y, Yamamoto A, Kawakami M, Farrer MJ, Kira J, Shii H, Autonomic failures in Pery syndrome with DCTN1 mutation., Parkinsonism Relat Disord , 16: 612-614, 2010, 2010.10.
117. Piero P, Longo MR, Scalia F, Polosa R, Kira J, Falsaperla R, Recurrent Hopkins syndrome: a case report and review of the literature., J Neurol Sci , 297: 89-91., 2010.10.
118. Matsuse D, Kitada M, Kohama M, Nishikawa K, Makinoshima H, Wakao S, Fujiyoshi Y, Heike T, Nakahata T, Akutsu H, Umezawa A, Harigae H, Kira J, Dezawa M, Human umbilical cord-derived mesenchymal stromal cells differentiate into functional Schwann cells that sustain peripheral nerve regeneration., J Neuropathol Exp Neurol , 69, 973-985, 69:973-985, 2010, 2010.09.
119. Matsushita T, Isobe N, Kawajiri M, Mogi M, Tsukada K, Horiuchi M, Yamasaki R, Ohyagi Y, Kira J, CSF angiotensin II and angiotensin-converting enzyme levels in anti-aquaporin-4 autoimmunit, J Neurol Sci, 295: 41-5, 2010.08.
120. Tateishi T, Yamasaki R, Tanaka M, Matsushita T, Kikuchi H, Isobe N, Ohyagi Y, Kira J, CSF chemokine alterations related to the clinical course of amyotrophic lateral sclerosis., Journal of Neuroimmunology, 222: 76-81, 2010, 2010.08.
121. Hagiwara K, Okamoto T, Shigeto H, Ogata K, Somehara Y, Matsushita T, Kira J, Tobimatsu S, Oscillatory gamma synchronization binds the primary and secondary somatosensory areas in humans, Neuroimage, 51(1):412-20. , 2010.05.
122. Matsumoto S, Nakahara I, Higashi T, Iwamuro Y, Watanabe Y, Takezawa M, Murata D, Yokota T, Kira J, Yamada T, Fibro-fatty volume of culprit lesions by virtual HistologyTM intravascular ultrasound is associated with the amount of debris during carotid artery stenting, Cerebrovascular Diseases, 29(5):468-75, 2010, 2010.05.
123. Matsushita T, Isobe N, Piao H, Matsuoka T, Ishizu T, Doi H, Masaki K, Yoshimura T, Yamasaki R, Ohyagi Y, Kira J, Reappraisal of brain MRI features in multiple sclerosis and neuromyelitis optica patients according to anti-aquaporin-4 antibody status, J Neurol Sci, 291(1-2):37-43., 2010.04.
124. Isobe N, Matsushita T, Yamasaki R, Ramagopalan SV, Kawano Y, Nishimura Y, Ebers GC, Kira J, Influence of HLA-DRB1 alleles on the susceptibility and resistance to multiple sclerosis in Japanese patients with respect to anti-aquaporin 4 antibody status, Multiple Sclerosis, 16: 147-155, 2010, 2010.03.
125. Tateishi T, Hokonohara T, Yamasaki R, Miura S, Kikuchi H, Iwaki A, Tashiro H, Furuya H, Nagara Y, Ohyagi Y, Nukina N, Iwaki T, Fukumaki Y, Kira J, Multiple system degeneration with basophilic inclusions in Japanese ALS patients with FUS mutation, Acta Neuropathol, 119(3):355-364, 2010, 2010.03.
126. Ueda M*, Kawamura N*, Tateishi T, Motomura K, Sakae N, Ohyagi Y, Kira J, Phenotypic spectrum of hereditary neuralgic amyotrophy caused by the SEPT9 R88W mutation, J Neurol Neurosurg Psychiatry, 81: 94-96, 2010, 2010.01.
127. Kihara Y, Matsushita T, Kita Y, Uematsu S, Akira S, Kira J, Ishii S, Shimizu T, Targeted lipidomics reveals mPGES-1-PGE2 as a therapeutic target for multiple sclerosis, Proc Nat Acad Sci USA, 106: 21807-21812, 2009, 2009.12.
128. Matsumoto S, Nakahara I, Higashi T, Iwamoto Y, Watanabe Y, Takahashi K, Ando M, Takezawa M, Kira J, Near-infrared soectroscopy in carotid artery stenting predicts cerebral hyperpefusion syndrome, Neurology 1512-1518, 2009, Neurology 1512-1518, 2009, 2009.12.
129. Matsushita T, Isobe N, Matsuoka T, Shi N, Kawano Y, Wu X-M, Yoshiura T, Nakao Y, Ishizu T, Kira J, Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative optico spinal multiple sclerosis in Japanese, Multiple Sclerosis 15: 834-847, 2009, Multiple Sclerosis 15: 834-847, 2009, 2009.12.
130. Okada K, Matsushita T, Kira J: Tsui S, B-cell activating factor of the TNF family is up-regulated in neuromyelitis optica., Neurology , 74: 177-178, 2010, 2009.12.
131. Piao H*, Minohara M*, Kawamura N, Li W, Mizunoe Y, Umehara F, Goto Y, Kusunoki S, Matsushita T, Ikenaka K, Maejima T, Nabekura J, Yamasaki R, Kira J, Induction of paranodal myelin detachment and sodium channel loss in vivo by Campylobacter jejuni DNA-binding protein from starved cells (C-Dps) in myelinated nerve fibers., Journal of Neurological Science, 288: 54-62, 2010, 2009.12.
132. Wu XM, Wang C, Zhang KN, Lin AY, Kira J, Hu GZ, Qu XH, Xiong YQ, Cao WF, Gong LY, Association of susceptibility to multiple sclerosis in Southern Han Chinese with HLA-DRB1, -DPB1 alleles and DRB1-DPB1 haplotypes: distinct from other populations.
, Multiple Sclerosis, 15: 1422-1430, 2009, 2009.12.
133. Isobe N, Kira J, Kawamura N, Ishizu T, Arimura K, Kawano Y, Neural damage associated with atopic diathesis: a nationwide survey in Japan, Neurology 73: 790-797, 2009, 73: 790-797, 2009, 2009.09.
134. Qiu W, Wu JS, Zhang MN, Matsushita T, Kira J, Carroll WM, Mastaglia L, Kermode AG, Longitudinally extensive myelopathy in Caucasians: a West Australian study of 26 cases from the Perth Demyelinating disease database., J Neurol Neurosurgery Psychiatry 81: 209-212, 2010, 81: 209-212, 2010, 2009.08.
135. Matsushita T, Isobe N, Matsuoka T, Ishizu T, Kawano Y, Yoshiura T, Ohyagi Y, Kira J, Extensive vasogenic edema of anti-aquaporin-4 antibody-related brain lesions, Muliple Sclerosis: 15(9):1113-7, 2009, Muliple Sclerosis: 15(9):1113-7, 2009, 2009.07.
136. Watanabe A*, Matsushita T*, Doi H, Matsuoka T, Shigeto H, Isobe N, Kawano Y, Tobimatsu S, Kira J, Multimodality evoked potential study of anti-aquaporin-4 antibody-positive and –negative multiple sclerosis patients, J Neurol Sci, 281: 34-40, 2009.06.
137. Doi H, Matsushita T, Isobe N, Ishizu T, Ohyagi Y, Kira J, Frequency of chronic headaches in Japanese patients with multiple sclerosis with special reference to opticospinal and common forms of multiple sclerosis, Headache, 49: 1513-1520, 2009, 2009.04.
138. Matsumoto S, Nakahara I, Higashi T, Iwamoto Y, Watanabe Y, Takahashi K, Ando M, Takezawa M, Kira J, Near-infrared soectroscopy in carotid artery stenting predicts cerebral hyperpefusion syndrome, Neurology, 72: 1512-1518, 2009, 2009.04.
139. Kawajiri M, Mogi M, Higaki N, Matsuoka T, Ohyagi Y, Tsukada K, Kahara K, Horiuchi M, Miki T, Kira J, Angiotensin-converting anzyme (ACE) and ACE2 levels in the cerebrospinal fluid of patients with multiple sclerosis, Multiple Sclerosis, 15: 262-265, 2009, 2009.03.
140. Ohshima S, Shin J, Yuasa K, Nishiyama A, Kira J, Okada T, Takeda S, Transduction efficiency and immune response with AAV8 vector in dog skeletal muscle, Molecular therapy, 17:73-80, 2009, 2009.03.
141. Ma L, Ohyagi Y, Miyoshi K, Sakae N, Motomura K, Taniwaki T, Furuya H, Takeda K, Tabira T, Kira J, Increase in p53 Protein Levels by Presenilin 1 Gene Mutations and its Inhibitors, Journal of Alzheimer's disease, 16: 565-575, 2009, 2009.03.
142. Doi H, Matsushita T, Isobe N, Matsuoka T, Minohara M, Ochi H, Kira J, Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody, Multiple Sclerosis, 15: 304-310, 2009, 2009.03.
143. Ikezoe K, Furuya H, Arahata H, Nakagawa M, Tateishi T, Fujii N, Kira J, Amyloid-B accumulation caused by chloroquine injections produces ER stress and autophagosome formation in rat skeletal muscle, Acta Neuropathol, Acta Neuropathol 117: 575-582, 2009, 2009.02.
144. Ishizu T*, Kira J*, Osoegawa M, Fukazawa T, Kikuchi S, Fujihara K, Matsui M, Kohriyama T, Sobue G, Yamamura T, Itoyama Y, Saida T, Sakata K, Heterogeneity and continuum of multiple sclerosis phenotypes in Japanese according to the results of the fourth nationwide survey, J Neurol Sci, J Neurol Sci 280: 22-28, 2009, 2009.02.
145. Matsuoka T, Matsushita T, Osoegawa M, Kawano Y, Minohara M, Mihara F, Nishimura Y, Ohyagi Y, Kira J, Association of the HLA-DRB1 alleles with characteristic MRI features of Asian multiple sclerosis.
, Tissue Antigens , 72: 171-176, 2009, 2009.01.
146. Osoegawa M*, Kira J*, Fukazawa K, Kikuchi S, Kohriyama T, Sobue G, Yamamura T, Itoyama Y, Saida T, Sakata K, Ochi H, Matsuoka T(Equal contribution), Temporal changes and geographical differences in multiple sclerosis phenotypes in Japanese: nationwide survey results over 30 years, Multiple Sclerosis, 15: 159-173, 2009, 2009.01.
147. Shi N, Kawano Y, Matsuoka T, Mei F-J, Ishizu T, Ohyagi Y, Kira J, Increase of CD4+ TNFα+ IL-2- T cells in cerebrospinal fluid of multiple sclerosis patients, Multiple Sclerosis, 15: 120-123, 2009, 2009.01.
148. Tanaka.M, Matsushita T, Tateishi T, Ochi H, Kawano Y, Mei F-J, Minohara M, Murai H, Kira J, Distinct CSF cytolcine/chemokaine profiles in atopic myelitis and other causes of myelitis., Neurology, 71(13):974-81, 2008.12.
149. Oishi A, Tobimatsu S, Ogata K, Taniwaki T, Kinukawa N, Toyoshiba H, Kira J, Differential contributions of spinal and cortical motoneurons to input-output properties of human small hand muscle, Neurol Res, Neurol Res 30: 1106-1113, 2008, 2008.08.
150. Takakura Y, Yamaguchi N, Satoh K, Kira J, Nishida N, Bone marrow stroma cells are susceptible to prion infection., Biochem Biophys Res Commun, Biochem Biophys Res Commun 377: 957-961, 2009, 2008.08.
151. Kawajiri M, Magi M, Higaki N, Tateishi T, Ohyagi Y, Horiuchi M, Miki T, Kira J, Reduced angiotensin II levels in the cerebrospinal fluid of patients with awyotroplic lateral sclerosis, Acta Neurol Scand, 119: 341-344, 2009, 2008.08.
152. Tanaka M, Ishizu, Ochi H, Kawano Y, Ohyagi Y, Kira J, Intrathecal upregulation of IFN-γ and MIP-Iβ in juvenile muscular atrophy of the distal upper axtremity, J Neurol Sci, 275: 74-77, 2008, 2008.07.
153. Sakae N, Yamasaki N, Kitaichi K, Fukuda T, Yamada M, Yoshikawa H, Hiranita T, Tatsumi Y, Kira J, Yamamoto T, Miyakawa T, Nakayama K , Mice lacking the schizophrenia-associated protein FEZ1 manifest by hyperactivity and enhanced responsiveness to psychostimulants, Hum Mol Genet, 3191-3203, 2008, 2008.07.
154. Takase K, Shigeto H, Suzuki S, Kikuchi H, Ohyagi Y, Kira J, Cortical kindling in a focal freeze lesion rat model., Journal of Clinical Neuroscience, 16: 94-98, 2009, 2008.07.
155. Kira J,* Isobe N,* Kawano Y, Osoegawa M, Ohyagi Y, Mihara F, Murai H:*Equal contribution., Atopic myelitis with focal amyotrophy: a possible link to Hopkins syndrome.
, J Neurol Sci, 143-51, 2008

, 2008.06.
156. Iwaki A, Kawano Y, Miura S, Shibata H, Matsuse D, Li W, Furuya H, Ohyagi Y, Taniwaki T, Kira J, Fukumaki Y, Heterozygous deletion of ITPRI, but not SUMF1 in spinocerebellar ataxia type 16.

, J Med Genet , 45(1):32-5, 2008.05.
157. Furuya H, Ikezoe K, Wang L, Ohyagi Y, Motomura K, Fuji N, Kira J, Fukumaki Y, A unique case of fibrodysplasia ossificans progressive with an ACVR1 mutation, G 356D, other than the common mutation (R 206H)., Am J Med Genet , 146A(4):459-463, 2008.05.
158. Matsuoka T, Matsushita T, Osoegawa M, Ochi H, Kawano Y, Mihara F, Ohyagi Y, Kira J, Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings.
, Journal of the Neurological Sciences, 115-25, 2008, 2008.05.
159. Takase K, Shigeto H, Suzuki S, Kikuchi H, Kira J, Prenatal freeze lesioning produces epileptogenic focal cortical dysplasia., Epilepsia, 49: 997-1010, 2008, 2008.04.
160. Matsushita T, Matsuoka T, Ishizu T, Kikuchi H, Osoegawa M, Kawano Y, Mihara F, Ohyagi Y, Kira J, Anterior periventricular linear lesions in optic-spinal multiple sclerosis: a combined neuroimaging and neuropathological study., Multiple Sclerosis, 14: 343-53, 2008.03.
161. Matsuoka T, Matsushita T, Osoegawa M, Ochi H, Kawano Y, Mihara F, Ohyagi Y, Kira J, Heterogeneity and continuum of multiple sclerosis in Japanese according to magnetic resonance imaging findings., J Neurol Sci, 266(1-2):115-25., 2008.03.
162. Furuya H, Ikezoe K, Wang L, Ohyagi Y, Motomura K, Fuji N, Kira J, Fukumaki Y, A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H)., Am J Med Genet A., 146A(4):459-63., 2008.02.
163. 188. Iwaki A, Kawano Y, Miura S, Shibata H, Matsuse D, Li W, Furuya H, Ohyagi Y, Taniwaki T, Kira J, Fukumaki Y, Heterozygous deletion of ITPR1, but not SUMF1, in spinocerebellar ataxia type 16., J Med Genet., 45(1):32-5., 2008.01.
164. Kira J, Isobe N, Kawano Y, Osoegawa M, Ohyagi Y, Mihara F, Murai H, Atopic myelitis with focal amyotrophy: A possible link to Hopkins syndrome., Neurol Sci., 269(1-2):143-51., 2008.01.
165. Yokomine K, Nakatsura T, Senju S, Nakagata N, Minohara M, Kira J, Motomura Y, KuboT, Sasaki Y, Nishimura Y, Regression of intestinal adenomas by vaccination with heat shock protein 105-pulsed bone marrow-derived dendritic cells in ApcMin/+mice., Cancer Science , 98: 1930-1935, 2007.12.
166. Ikezoe K, Nakamori M, Furuya H, Arahata H, Kanemoto S, Kimura T, Imaizumi K, Takahashi M, Sakoda S, Fujii N, Kira J, Endoplasmic reticulum stress in myotonic dystrophy type 1 muscle, Acta Neuropathologica, 114: 527-535, 2007.11.
167. Yamasaki R, Zhang J, Koshiishi I, Sastradipura-Suniarti DF, Wu Z, Peters C, von Figura K, Saftig P, Uchiyama Y, Kira J, Utsumi H, Nakanishi H , Involvement of lysosomal storage-induced p38 MAP kinase activation in overproduction of nitric oxide by microglia in cathepsin D-deficient mice., Mol Cell Neurosci, 35: 573-584, 2007.08.
168. Arimura K, Nakagawa M, Izumo S, Usuku K, Itoyama Y, Kira J, Osame M, Safety and efficacy of interferon-a in 167 patients with human T-cell lymphotropic virus type 1-associated myelopathy., J Neurovirol, 13: 364-372, 2007.08.
169. Arimura K, Nakagawa M, Izumo S, Usuku K, Itoyama Y, Kira J, Osame M, Safety and efficacy of interferon-alpha in 167 patients with human T-cell lymphotropic virus type 1-associated myelopathy., J Neurovirol., 13: 364-372, 2007.08.
170. Taniwaki T, Okayama A, Yoshiura T, Togao O, Nakamura Y, Ogata K, Shigeto H, Ohyagi Y, Kira J, Tobimatsu S, Age-related alterations of the functional interactions within the basal ganglia and cerebellar motor loops in vivo., Neuroimage, 36: 1263-1276, 2007.07.
171. Kurokawa-Kuroda T, Ogata K, Suga R, Goto Y, Taniwaki T, Kira J, Tobimatsu S, Altered soleus responses to magnetic stimulation in pure cerebellar ataxia., Clin Neruophysiol, 118: 1198-1203, 2007.06.
172. Matsuoka T, Matsushita T, Kawano Y, Osoegawa M, Ochi H, Ishizu T, Minohara M, Kikuchi H, Mihara F, Ohyagi Y, Kira J, Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in Japanese, Brain, 130: 1206-1223, 2007.05, [URL].
173. Pineda AAM, Ogata K, Osoegawa M, Murai H, Shigeto H, Tobimatsu S, Kira J, A distinct subgroup of chronic inflammatory demyelinating disease with CNS demyelination and a favorable response to immunotherapy., J Neurol Sci, 255: 1-6, 2007.04.
174. Li W, Minohara M, Su JJ, Matsuoka T, Osoegawa M, Ishizu T, Kira J, Helicobacter pylori is a potential protective factor against conventional type multiple sclerosis in the Japanese population, J Neuroimmunol, 184: 227-231, 2007.03.
175. Tashiro K, Ogata K, Yamasaki T, Kuroda T, Goto Y, Munetsima S, Kinukawa N, Kira J, Tobimatsu S, Repetitive transcranial magnetic stimulation alters optic flow perception., Neuroreport, 18: 229-233, 2007.02.
176. Ohyagi Y, Tsuruta Y, Motomura K, Miyoshi K, Kikuchi H, Iwaki T, Taniwaki T, Kira J, Intraneuronal amyloid β42 enhanced by heating but counteracted by formic acid., J Neurosci Methods, 159: 134-138, 2007.01.
177. Shi N, Kawano Y, Tateishi T, Kikuchi H, Osoegawa M, Ohyagi Y, Kira J, Increased IL-13-producing T cells in ALS: positive correlations with disease severity and progression rate, J Neuroimmunol, 182: 232-235, 2007.01.
178. Ohyagi Y, Tsuruta Y, Motomura K, Miyoshi K, Kikuchi H, Iwaki T, Taniwaki T, Kira J, Intraneuronal amyloid β42 enhanced by heating but counteracted by formic acid, J Neurosci Meth, 159: 134-138, 2007.01.
179. Sun X, Minohara M, Kikuchi S, Ishizu T, Tanaka M, Piao H, Osoegawa M, Ohyagi Y, Shimokawa H, Kira J, The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental allergic encephalomyelitis., J Neuroimmunol, 180: 126-134, 2006.11.
180. Tashiro K, Ogata K, Goto Y, Taniwaki T, Okayama A, Kira J, Tobimatsu S, EEG findings in early-stage corticobasal degeneration and progressive supranuclear palsy: A retrospective study and literature review, Clin Neurophysiol, 117: 2236-2242, 2006, 2006.10.
181. Miura S, Shibata H, Furuya H, Ohyagi Y, Osoegawa M, Miyoshi Y, Matsunaga H, Shibata A, Matsumoto N, Iwaki A, Taniwaki T, Yamada T, Kikuchi H, Kira J, Fukumaki Y, The contactin 4 gene locus at 3p26 is a candidate gene of SCA16, Neurology, 67: 1236-1241, 2006.10.
182. Ikezoe K, Ohshima S, Osoegawa M, Ogawa K, Nagata K, Kira J, Expression of granulysin in infiltrating cells in polymyositis and inclusion body myositis: its possible relationship to steroid resistance in polymyositis., J Neurol Neurosurg Psychiatry, 77: 1187-1190, 2006.10.
183. Minohara M, , Osoegawa M, , Ohyagi Y, Kira J, Upregulation of myeloperoxidase in patients with opticospinal multiple sclerosis: positive correlation with disease severity., J Neuroimmunol, 178: 156-160, 2006.09.
184. Tanaka M, Kikuchi H, Ishizu T, Minohara M, Osoegawa M, Motomura K, Tateishi T, , Intrathecal upregulation of G-CSF and its neuroprotective actions on motor neurons in amyotrophic lateral sclerosis, J Neuropathol Exp Neurol, 65: 816-825, 2006.08.
185. Mei F-J, Osoegawa M, Ochi H, Minohara M, Shi N, Murai H, Ishizu T, Taniwaki T, Kira J, Long-term favorable response to interferon beta-1b is linked to cytokine deviation toward the Th2 and Tc2 sides in Japanese patients with multiple sclerosis., J Neurol Sci, 246: 71-77, 2006.07.
186. Taniwaki T, Okayama A, Yoshima T, Nakayama Y, Yamasaki T, Igata K, Kira J, , Functional network of the basal ganglia and cerebellar motor loops in vivo: different activation patterns between self-initiated and externally-triggered movements, NeuroImage, 31: 745-753, 2006.06.
187. Ishizu T, Minohara M, Ichiyama T, Kira R, Tanaka M, Osoegawa M, Hara T, Furukawa S, Kira J, CSF cytokine and chemokine profiles in acute disseminated encephalomyelitis., J Neuroimmunol, 175: 52-58, 2006.06.
188. Yokomine K, Nakatsura T, Minohara M, Kira J, Kubo T, Sasaki Y, Nishimura Y, Immunization with heat shock protein 105-pulsed dentritic cells leads to tumor rejection in mice., Biochem Biophys Res Comm, 343: 269-278, 2006.04.
189. Su J-J, Osoegawa M, Minohara M, Tanaka M, Ishizu T, Mihara F, Taniwaki T, Kira J, Upregulation of vascular grouth factors in multiple sclerosis: correlation with MRI findings., J Neurol Sci, 243: 21-30, 2006.04.
190. Tashiro K, Kikuchi S, Itoyama Y, Tokumaru Y, Sobue G, Murai E, Akiguchi I, Nakashima K, Kira J, Hirayama K, Nationwide survey of juvenile muscular atrophy of distal upper extremity (Hirayama disease) in Japan., Amyotrophic Lateral Sclerosis, 7: 38-45, 2006.03.
191. Furuya H, Yamada T, Ohyagi Y, Ikezoe K, Miyoshi Y, Fujii N, Kira J, Neurological signs and symptoms in patients with chronic PCB poisoning (Yusho accident) for more than 36 years., J Dermatol Sci , 10.1016/j.descs.2005.03.007, S39-S44, Suppl 1: S39-S44, 2005.12.
192. Osoegawa M, Niino M, Tanaka M, Kikuchi S, Murai H, Fukazawa T, Minohara M, Miyagishi R, Taniwaki T, Tashiro K, Kira J, Comparison of the clinical course of opticospinal and conventional forms of multiple sclerosis in Japan., Intern Med , 10.2169/internalmedicine.44.934, 44, 9, 934-938, 44: 934-938, 2005.09.
193. Furuya H, Yamada T, Murai H, Ikezoe K, Ohyagi Y, Matsumoto T, Miyoshi Y, Fujii N, Kira J, Usefulness of manual muscle testing of pronator teres and supinator muscles in assessing cervical radiculopathy., Fukuoka Acta Med , 96: 319-325, 2005.08.
194. Oishi A, Tobimatsu S, Arakawa K, Taniwaki T, Kira J, Ocular dominancy in conjugate eye movements at reading distance., Neurosicence Research , 10.1016/j.neures.2005.03.013, 52, 3, 263-268, 52: 263-268, 2005.07.
195. Nakagawa M, Kuwabata Y, Taniwaki T, Sasaki M, Koga H, Kaneko K, Hayashi K, Kira J Honda H, PET evaluation of the relationship between D2 receptor binding and glucose metabolism in patients with parkinsonism., Ann Nucl Med , 10.1007/BF02984618, 19, 4, 267-275, 19: 267-275, 2005.06.
196. Ishizu T, Osoegawa M, Mei F-J, Kikuchi H, Tanaka M, Takakura Y, Minohara M, Murai H, Mihara F, Taniwaki T, Kira J, Intrathecal activation of the IL-7/IL-8 axis in opticospinal multiple sclerosis., Brain , 10.1093/brain/awh453, 128, 988-1002, 128: 988-1002, 2005.05.
197. Iijima M, Yamamoto M, Hirayama M, Tanaka F, Katsuno M, Mori K, Koike H, Hattori N, Arimura K, Nakagawa M, Yoshikawa H, Hayasaka K, Onodera O, Baba M, Yasuda H, Saito T, Nakazato M, Nakashima K, Kira J, Kaji R, Oka N, Sobue G, Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP., Neurology , 64, 8, 1471-1475, 64: 1471-1475, 2005.04.
198. Osoegawa M, Miyagishi R, Ochi H, Nakamura I, Niino M, Kikuchi S, Murai H, Fukazawa T, Minohara M, Tashiro K, Kira J, Platelet-activating factor receptor gene polymorphism in Japanese patients with multiple sclerosis., J Neuroimmunol , 10.1016/j.jneuroim.2004.12.014, 161, 1-2, 195-198, 161: 195-198, 2005.04.