|Ryo Yamasaki||Last modified date：2018.06.25|
Associate Professor / Neurology / Neurological Institute / Faculty of Medical Sciences
|Ryo Yamasaki||Last modified date：2018.06.25|
|1.||Mitsuru Watanabe, Ryo Yamasaki, Jun-Ichi Kira, Relationship between Th1 cells and astrocytic connexin 43 gap junctions in multiple sclerosis, Clinical and Experimental Neuroimmunology, 10.1111/cen3.12384, 8, 2, 101-102, 2017.05.|
|2.||Koji Shinoda, Takuya Matsushita, Yuri Nakamura, Katsuhisa Masaki, Ryo Yamasaki, hiroo yamaguchi, Osamu Togao, Akio Hiwatashi, Jun-Ichi Kira, HLA-DRB1*04:05 allele is associated with intracortical lesions on three-dimensional double inversion recovery images in Japanese patients with multiple sclerosis, Multiple Sclerosis, 10.1177/1352458517707067, 1352458517707067, 2017.05, BACKGROUND: Cortical lesions (CLs) frequently observed in Caucasian patients with multiple sclerosis (MS) contribute to disability. However, it remains unclear whether CLs are associated with clinical features and genetic risk factors, such as HLA-DRB1*15:01 and -DRB1*04:05 in Asian MS patients.
OBJECTIVE: To elucidate the frequency of CLs and their association with HLA-DRB1 and DPB1 alleles in Japanese MS patients.
METHODS: Three-dimensional double inversion recovery imaging and clinical information were retrospectively obtained from 92 Japanese MS patients.
RESULTS: CLs of any type, intracortical lesions (ICLs), and leukocortical lesions (LCLs) were detected in 39.1%, 26.1%, and 28.3% of patients, respectively. MS patients with ICLs had a significantly higher frequency of secondary progression and greater Expanded Disability Status Scale (EDSS) scores than those without ICLs. Similar trends were observed with CLs and LCLs. The number of all three lesion types positively correlated with EDSS scores. The frequency and number of ICLs were significantly higher in HLA-DRB1*15:01 carriers than in HLA-DRB1*15:01 non-carriers, but significantly lower in HLA-DRB1*04:05 carriers than in HLA-DRB1*04:05 non-carriers. Multivariate logistic regression analysis revealed a negative association of HLA-DRB1*04:05 with ICLs.
CONCLUSION: ICLs are associated with greater disease severity in Japanese MS patients and are partly suppressed by the HLA-DRB1*04:05 allele..
|3.||Haruki Koike, Masato Kadoya, Ken Ichi Kaida, Shohei Ikeda, Yuichi Kawagashira, Masahiro Iijima, Daisuke Kato, Hidenori Ogata, Ryo Yamasaki, Noriyuki Matsukawa, Jun-Ichi Kira, Masahisa Katsuno, Gen Sobue, Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies, Journal of Neurology, Neurosurgery and Psychiatry, 10.1136/jnnp-2016-314895, 88, 6, 465-473, 2017.06, Objective To investigate the morphological features of chronic inflammatory demyelinating polyneuropathy (CIDP) with autoantibodies directed against paranodal junctional molecules, particularly focusing on the fine structures of the paranodes. Methods We assessed sural nerve biopsy specimens obtained from 9 patients with CIDP with anti-neurofascin-155 antibodies and 1 patient with anti-contactin-1 antibodies. 13 patients with CIDP without these antibodies were also examined to compare pathological findings. Results Characteristic light and electron microscopy findings in transverse sections from patients with anti-neurofascin-155 and anti-contactin-1 antibodies indicated a slight reduction in myelinated fibre density, with scattered myelin ovoids, and the absence of macrophage-mediated demyelination or onion bulbs. Teased-fibre preparations revealed that segmental demyelination tended to be found in patients with relatively higher frequencies of axonal degeneration and was tandemly found at consecutive nodes of Ranvier in a single fibre. Assessment of longitudinal sections by electron microscopy revealed that detachment of terminal myelin loops from the axolemma was frequently found at the paranode in patients with anti-neurofascin-155 and anti-contactin-1 antibody-positive CIDP compared with patients with antibody-negative CIDP. Patients with anti-neurofascin-155 antibodies showed a positive correlation between the frequencies of axo-glial detachment at the paranode and axonal degeneration, as assessed by teased-fibre preparations (p<0.05). Conclusions Paranodal dissection without classical macrophage-mediated demyelination is the characteristic feature of patients with CIDP with autoantibodies to paranodal axo-glial junctional molecules..|
|4.||Koji Yamashita, Hiwatashi Akio, Osamu Togao, kazufumi kikuchi, hiroo yamaguchi, Yuriko Suzuki, Ryotaro Kamei, Ryo Yamasaki, Jun-Ichi Kira, Hiroshi Honda, Cerebral blood flow laterality derived from arterial spin labeling as a biomarker for assessing the disease severity of parkinson's disease, Journal of Magnetic Resonance Imaging, 10.1002/jmri.25489, 45, 6, 1821-1826, 2017.06, Purpose: To evaluate cerebral blood flow (CBF) laterality derived from arterial spin labeling (ASL) in early-stage Parkinson's disease (PD) patients compared with those with advanced stages. Materials and Methods: Thirty-eight patients with PD (21 patients in early stages, 17 patients in advanced stages) were retrospectively studied. The CBF maps derived from 3T ASL data were co-registered to the corresponding 3DT1WI using SPM 12 software. Caudate nucleus (CN), putamen (PT), globus pallidus (GP), and thalamus (TH) were manually traced on the representative axial slices of 3DT1WI. CBF of the CN, PT, GP, and TH was measured using corresponding pixels on the co-registered CBF maps. A laterality index (LI) was calculated as the ratio of the contralateral CBF to primary affected side CBF. Each LI was compared between early and advanced stages of PD using the Mann-Whitney U-test. The LIs were also compared between each stage of PD. Results: In the CN, the LIs were significantly higher in early stages (mean LI ± SD, 95% confidence interval = 1.06 ± 0.14, 1.00–1.13) than in advanced stages (0.94 ± 0.14, 0.87–1.01; P < 0.05). We also observed a tendency toward decreased LIs with disease severity (1.10 ± 0.14, 0.99–1.21 for Hoehn and Yahr stage I; 1.04 ± 0.14, 0.92–1.12 for stage II; 0.96 ± 0.11, 0.89–1.10 for stage III; 0.93 ± 0.17, 0.81–1.05 for stage IV). Conclusion: The evaluation of CBF laterality pattern in the CN using ASL may be useful for assessing the disease severity of PD patients. Level of Evidence: 3. J. MAGN. RESON. IMAGING 2017;45:1821–1826..|
|5.||Tomohiro Ohgomori, Ryo Yamasaki, Hideyuki Takeuchi, Kenji Kadomatsu, Jun-Ichi Kira, Shozo Jinno, Differential involvement of vesicular and glial glutamate transporters around spinal α-motoneurons in the pathogenesis of SOD1G93A mouse model of amyotrophic lateral sclerosis, Neuroscience, 10.1016/j.neuroscience.2017.05.014, 356, 114-124, 2017.07, From a view point of the glutamate excitotoxicity theory, several studies have suggested that abnormal glutamate homeostasis via dysfunction of glial glutamate transporter-1 (GLT-1) may underlie neurodegeneration in amyotrophic lateral sclerosis (ALS). However, the detailed role of GLT-1 in the pathogenies of ALS remains controversial. To assess this issue, here we elucidated structural alterations associated with dysregulation of glutamate homeostasis using SOD1G93A mice, a genetic model of familial ALS. We first examined the viability of α-motoneurons in the lumbar spinal cord of SOD1G93A mice. Measurement of the soma size and density indicated that α-motoneurons might be intact at 9 weeks of age (presymptomatic stage), then soma shrinkage began at 15 weeks of age (progressive stage), and finally neuronal density declined at 21 weeks of age (end stage). Next, we carried out the line profile analysis, and found that the coverage of α-motoneurons by GLT-1-positive (GLT-1+) astrocytic processes was decreased only at 21 weeks of age, while the reduction of coverage of α-motoneurons by synaptophysin-positive (SYP+) presynaptic terminals began at 15 weeks of age. Interestingly, the coverage of α-motoneurons by VGluT2+ presynaptic terminals was transiently increased at 9 weeks of age, and then gradually decreased towards 21 weeks of age. On the other hand, there were no time-dependent alterations in the coverage of α-motoneurons by GABAergic presynaptic terminals. These findings suggest that VGluT2 and GLT-1 may be differentially involved in the pathogenesis of ALS via abnormal glutamate homeostasis at the presymptomatic stage and end stage of disease, respectively..|
|6.||Yu Hashimoto, Koji Shinoda, Eizo Tanaka, Taira Uehara, Takuya Matsushita, Ryo Yamasaki, Jun-Ichi Kira, Re-emergence of a tumefactive demyelinating lesion after initiation of fingolimod therapy, Journal of the Neurological Sciences, 10.1016/j.jns.2017.06.002, 379, 167-168, 2017.08.|
|7.||Hiwatashi Akio, Osamu Togao, Koji Yamashita, kazufumi kikuchi, Ryotato Kamei, Daichi Momosaka, Hidenori Ogata, Ryo Yamasaki, Masami Yoneyama, Jun-Ichi Kira, Hiroshi Honda, Lumbar plexus in patients with chronic inflammatory demyelinating polyneuropathy
Evaluation with 3D nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement imaging (3D SHINKEI), European Journal of Radiology, 10.1016/j.ejrad.2017.05.031, 93, 95-99, 2017.08, Purpose To evaluate whether 3D SHINKEI in the lumbar plexus could identify patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Materials and methods Twenty-one patients with CIDP and 15 non-CIDP patients were studied in this retrospective study. The SNR, contrast-to-noise ratio (CNR), contrast ratio (CR) and the size of the lumbar ganglions and roots were measured. Statistical analyses were performed with Mann-Whitney U test and receiver operating characteristics (ROC) analysis. Results The SNRs of the ganglions and roots were larger in patients with CIDP (8.30 ± 4.87 and 8.24 ± 4.92) than in non-CIDP patients (4.95 ± 2.05 and 5.08 ± 1.97, P < 0.0001, respectively). The CNRs of the ganglions and roots were larger in patients with CIDP (40.79 ± 43.19 and 37.16 ± 48.31) than in non-CIDP patients (25.90 ± 10.41 and 18.37 ± 32.83, P < 0.0001, respectively). The CRs of the ganglions and roots were larger in patients with CIDP (0.74 ± 0.13 and 0.66 ± 0.17) than in non-CIDP patients (0.72 ± 0.12 and 0.50 ± 0.17, P = 0.004 and P < 0.0001, respectively). The sizes of the ganglions and the roots were larger in patients with CIDP (6.62 ± 1.81 mm and 5.76 ± 3.24 mm) than in non-CIDP patients (5.23 ± 1.17 mm and 4.24 ± 1.11 mm, P < 0.0001, respectively). ROC analysis showed the best diagnostic performance with the CNR of the roots. Conclusion Patients with CIDP could be distinguished from controls on 3D SHINKEI..
|8.||Tomohiro Ohgomori, Ryo Yamasaki, Hideyuki Takeuchi, Kenji Kadomatsu, Jun-Ichi Kira, Shozo Jinno, Differential activation of neuronal and glial STAT3 in the spinal cord of the SOD1(G93A) mouse model of amyotrophic lateral sclerosis, European Journal of Neuroscience, 10.1111/ejn.13650, 46, 4, 2001-2014, 2017.08, Signal transducer and activator of transcription (STAT) proteins are activated by phosphorylation in the spinal cord of patients suffering from amyotrophic lateral sclerosis (ALS). The major scope of our study is a comprehensive histological characterization of the mechanisms underlying neuronal and glial STAT3 activation in the pathogenesis of ALS using SOD1(G93A) mice. We calculated the fold changes (FCs, ratios vs. appropriate controls) of the numerical densities of the following phosphorylated STAT3-positive (pSTAT3)(+) cells - choline acetyltransferase (ChAT)(+) α-motoneurons, ionized calcium-binding adapter molecule 1 (Iba1)(+) microglia, and S100β(+) astrocytes in SOD1(G93A) mice. The FCs of pSTAT3(+) microglia and pSTAT3(+) astrocytes were increased from 9 to 15 weeks of age and then plateaued until 21 weeks. In contrast, the FCs of pSTAT3(+) α-motoneurons peaked at 9 weeks and then decreased until 21 weeks. The immunoreactivity for nonphosphorylated neurofilament protein (SMI-32), a marker of axonal impairment, was decreased in pSTAT3(+) α-motoneurons compared with pSTAT3(-) α-motoneurons at 9 weeks of age. We then compared the following pharmacological models - the chronic administration of 3,3'-iminodipropionitrile (IDPN), which models axonal impairment, and the acute administration of lipopolysaccharide (LPS), which is a model of neuroinflammation. The FCs of pSTAT3(+) α-motoneurons were increased in IDPN-treated mice, while those of pSTAT3(+) microglia were increased in LPS-treated mice. The FCs of pSTAT3(+) astrocytes were higher in SOD1(G93A) mice at 9 weeks compared with IDPN- and LPS-treated mice. Our results indicate that axonopathy and neuroinflammation may trigger the respective activation of neuronal and glial STAT3, which is observed during ALS pathogenesis..|
|9.||Tomohiro Ohgomori, Ryo Yamasaki, Hideyuki Takeuchi, Kenji Kadomatsu, Jun-Ichi Kira, Shozo Jinno, Differential activation of neuronal and glial STAT3 in the spinal cord of the SOD1G93A mouse model of amyotrophic lateral sclerosis, European Journal of Neuroscience, 10.1111/ejn.13650, 46, 4, 2001-2014, 2017.08, Signal transducer and activator of transcription (STAT) proteins are activated by phosphorylation in the spinal cord of patients suffering from amyotrophic lateral sclerosis (ALS). The major scope of our study is a comprehensive histological characterization of the mechanisms underlying neuronal and glial STAT3 activation in the pathogenesis of ALS using SOD1G93A mice. We calculated the fold changes (FCs, ratios vs. appropriate controls) of the numerical densities of the following phosphorylated STAT3-positive (pSTAT3)+ cells – choline acetyltransferase (ChAT)+ α-motoneurons, ionized calcium-binding adapter molecule 1 (Iba1)+ microglia, and S100β+ astrocytes in SOD1G93A mice. The FCs of pSTAT3+ microglia and pSTAT3+ astrocytes were increased from 9 to 15 weeks of age and then plateaued until 21 weeks. In contrast, the FCs of pSTAT3+ α-motoneurons peaked at 9 weeks and then decreased until 21 weeks. The immunoreactivity for nonphosphorylated neurofilament protein (SMI-32), a marker of axonal impairment, was decreased in pSTAT3+ α-motoneurons compared with pSTAT3− α-motoneurons at 9 weeks of age. We then compared the following pharmacological models – the chronic administration of 3,3′-iminodipropionitrile (IDPN), which models axonal impairment, and the acute administration of lipopolysaccharide (LPS), which is a model of neuroinflammation. The FCs of pSTAT3+ α-motoneurons were increased in IDPN-treated mice, while those of pSTAT3+ microglia were increased in LPS-treated mice. The FCs of pSTAT3+ astrocytes were higher in SOD1G93A mice at 9 weeks compared with IDPN- and LPS-treated mice. Our results indicate that axonopathy and neuroinflammation may trigger the respective activation of neuronal and glial STAT3, which is observed during ALS pathogenesis..|
|10.||Mitsunori Shimmura, Taira Uehara, kenichiro yamashita, Hiroshi Shigeto, Ryo Yamasaki, Kinya Ishikawa, Jun-Ichi Kira, Slowed abduction during smooth pursuit eye movement in episodic ataxia type 2 with a novel CACNA1A mutation, Journal of the Neurological Sciences, 10.1016/j.jns.2017.07.040, 381, 4-6, 2017.10.|
|11.||Koji Tanaka, Shoji Matsumoto, Hiroyuki Murai, Ryo Yamasaki, Jun-Ichi Kira, Measurement Conditions of End-Diastolic Ratio of Common Carotid Arteries Alter Diagnostic Ability for Large Artery Intracranial Occlusive Disease, Journal of Stroke and Cerebrovascular Diseases, 10.1016/j.jstrokecerebrovasdis.2017.05.038, 26, 10, 2421-2426, 2017.10, Background End-diastolic ratio, calculated by the side-to-side ratio of end-diastolic flow velocities of the common carotid arteries, is an indicator for large artery intracranial occlusive disease. However, the diagnostic ability of end-diastolic ratios derived from different measurement conditions is unclear. Methods End-diastolic ratios were measured twice by single carotid duplex ultrasonography. End-diastolic ratio1st was calculated from separate end-diastolic flow velocities measured during routine assessment. End-diastolic ratio2nd was calculated almost simultaneously without head rotation. For each end-diastolic ratio, the measurement conditions and prediction ability for occlusions of the internal carotid artery or proximal portion of the middle cerebral artery using an established cutoff of 1.4 or greater were compared. Results Two hundred thirty-three patients (147 men, median 67 years) were registered, with available intracranial artery information in 158 patients (67.8%) and occlusions detected in 7 patients (4.4%). End-diastolic ratio1st was significantly higher than end-diastolic ratio2nd (median 1.21 versus 1.08, P <.001). Compared with end-diastolic ratio1st, end-diastolic ratio2nd had a significantly shorter time interval (median 709 versus 28 seconds, P <.001) and smaller pulse rate difference (1.54 ± 5.10 versus.25 ± 4.63 beats per minute, P =.004). To predict occlusions, the sensitivity, specificity, and overall accuracy for end-diastolic ratio1st of 1.4 or greater were 85.7%, 70.9%, and 71.5%, respectively, and for end-diastolic ratio2nd of 1.4 or greater were 85.7%, 98.0%, and 97.5%, respectively. End-diastolic ratio2nd had better specificity and overall accuracy than end-diastolic ratio1st (P <.001). Conclusions End-diastolic ratio varies with measurement conditions. Combined end-diastolic flow velocities measurement may improve diagnostic ability for large artery intracranial occlusive disease..|
|12.||Daisuke Kondo, Koji Shinoda, kenichiro yamashita, Ryo Yamasaki, Akihiro Hashiguchi, Hiroshi Takashima, Jun-Ichi Kira, A novel mutation in FGD4 causes Charcot–Marie–Tooth disease type 4H with cranial nerve involvement, Neuromuscular Disorders, 10.1016/j.nmd.2017.07.011, 27, 10, 959-961, 2017.10, Charcot–Marie–Tooth disease type 4H (CMT4H) is a rare variant of autosomal recessive hereditary neuropathy. It is caused by FGD4 mutations and characterized by early infantile onset, slowly progressive distal muscle weakness, scoliosis, and myelin outfoldings visible in nerve biopsy samples. Here, we report a 65-year-old male born to consanguineous parents, who carries a novel homozygous FGD4 c.724C>T nonsense mutation. He developed lower limb weakness in his teens, which progressed slowly and was accompanied by diplopia, bilateral hearing loss, and erectile dysfunction from his twenties. At the age of 65, he was wheelchair-bound and had mild scoliosis, bilateral ophthalmoplegia, facial muscle weakness, inner ear hearing loss, distal-dominant weakness, and sensory disturbance, but no cognitive deterioration. Magnetic resonance imaging revealed enlarged bilateral trigeminal and facial nerves. Accordingly, we believe that this mutation causes slowly progressive sensorimotor neuropathy with apparent cranial nerve involvement, thereby further expanding the clinical spectrum of CMT4H..|
|13.||Tatsuo Mano, Kenichi Nagata, Takashi Nonaka, Airi Tarutani, Tomohiro Imamura, Tadafumi Hashimoto, Taro Bannai, Kagari Koshi-Mano, Takeyuki Tsuchida, Ryo Ohtomo, Junko Takahashi-Fujigasaki, Satoshi Yamashita, Yasumasa Ohyagi, Ryo Yamasaki, Shoji Tsuji, Akira Tamaoka, Takeshi Ikeuchi, Takaomi C. Saido, Takeshi Iwatsubo, Toshikazu Ushijima, Shigeo Murayama, Masato Hasegawa, Atsushi Iwata, Neuron-specific methylome analysis reveals epigenetic regulation and tau-related dysfunction of BRCA1 in Alzheimer’s disease, Proceedings of the National Academy of Sciences of the United States of America, 10.1073/pnas.1707151114, 114, 45, E9645-E9654, 2017.11, Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by pathology of accumulated amyloid β (Aβ) and phosphorylated tau proteins in the brain. Postmortem degradation and cellular complexity within the brain have limited approaches to molecularly define the causal relationship between pathological features and neuronal dysfunction in AD. To overcome these limitations, we analyzed the neuron-specific DNA methylome of postmortem brain samples from AD patients, which allowed differentially hypomethylated region of the BRCA1 promoter to be identified. Expression of BRCA1 was significantly up-regulated in AD brains, consistent with its hypomethylation. BRCA1 protein levels were also elevated in response to DNA damage induced by Aβ. BRCA1 became mislocalized to the cytoplasm and highly insoluble in a tau-dependent manner, resulting in DNA fragmentation in both in vitro cellular and in vivo mouse models. BRCA1 dysfunction under Aβ burden is consistent with concomitant deterioration of genomic integrity and synaptic plasticity. The Brca1 promoter region of AD model mice brain was similarly hypomethylated, indicating an epigenetic mechanism underlying BRCA1 regulation in AD. Our results suggest deterioration of DNA integrity as a central contributing factor in AD pathogenesis. Moreover, these data demonstrate the technical feasibility of using neuron-specific DNA methylome analysis to facilitate discovery of etiological candidates in sporadic neurodegenerative diseases..|
|14.||Ryo Yamasaki, Astroglial phagocytosis in central nervous system health and disease, Clinical and Experimental Neuroimmunology, 10.1111/cen3.12413, 8, 4, 285-286, 2017.11, Phagocytosis by astrocytes is important in the developing brain and in central nervous system lesions. Astroglial phagocytosis usually contributes to the repair of damaged lesions, but, depending on the local milieu, astrocytes can become activated “A1” type astroglia, which release neurotoxic substances and accelerate regional damage..|
|15.||Mitsuhiko Katoh, Bao Wu, Huy Bang Nguyen, Truc Quynh Thai, Ryo Yamasaki, Haiyan Lu, Anna M. Rietsch, Musab M. Zorlu, Youichi Shinozaki, Yurika Saitoh, Sei Saitoh, Takashi Sakoh, Kazuhiro Ikenaka, Schuichi Koizumi, Richard M. Ransohoff, Nobuhiko Ohno, Polymorphic regulation of mitochondrial fission and fusion modifies phenotypes of microglia in neuroinflammation, Scientific Reports, 10.1038/s41598-017-05232-0, 7, 1, 2017.12, Microglia are the resident macrophages of the central nervous system and play complex roles in the milieu of diseases including the primary diseases of myelin. Although mitochondria are critical for cellular functions and survival in the nervous system, alterations in and the roles of mitochondrial dynamics and associated signaling in microglia are still poorly understood. In the present study, by combining immunohistochemistry and 3D ultrastructural analyses, we show that mitochondrial fission/fusion in reactive microglia is differentially regulated from that in monocyte-derived macrophages and the ramified microglia of normal white matter in myelin disease models. Mouse cerebral microglia in vitro demonstrated that stimulation of TLR4 with lipopolysaccharide, widely used to examine microglial reactions, caused the activation of the mitochondrial fission protein, dynamin-related protein 1 (Drp1) and enhanced production of reactive oxygen species (ROS). The increase in the ROS level activated 5′ adenosine monophosphate-activated protein kinase (AMPK), and facilitated elongation of mitochondria along the microtubule tracks. These results suggest that the polymorphic regulation of mitochondrial fission and fusion in reactive microglia is mediated by distinct signaling under inflammatory conditions, and modulates microglial phenotypes through the production of ROS..|
|16.||Yuko Yamagishi, Hidekazu Suzuki, Masahiro Sonoo, Satoshi Kuwabara, Takanori Yokota, Kyoichi Nomura, Atsuro Chiba, Ryuji Kaji, Takashi Kanda, Kenichi Kaida, Shu Ichi Ikeda, Tatsuro Mutoh, Ryo Yamasaki, Hiroshi Takashima, Makoto Matsui, Kazutoshi Nishiyama, Gen Sobue, Susumu Kusunoki, Markers for Guillain-Barré syndrome with poor prognosis
a multi-center study, Journal of the Peripheral Nervous System, 10.1111/jns.12234, 22, 4, 433-439, 2017.12, Guillain-Barré syndrome (GBS) is an acute monophasic neuropathy. Prognostic tools include the modified Erasmus GBS outcome score (mEGOS), Erasmus GBS respiratory insufficiency score (EGRIS), and the increase in serum IgG levels (ΔIgG) 2 weeks after intravenous immunoglobulin (IVIg) treatment. Given that proportions of GBS subtypes differ between Western countries and Japan, the usefulness of these tools in Japan or other countries remains unknown. We enrolled 177 Japanese patients with GBS from 15 university hospitals and retrospectively obtained mEGOS and EGRIS for all and ΔIgG status for 79 of them. High mEGOS scores on admission or on day 7 were significantly associated with poorer outcomes (unable to walk independently at 6 months). High EGRIS scores (≥5 points) were associated with an increased risk for mechanical ventilation. Patients with ΔIgG <1,108 mg/dl had significantly poorer outcomes. We suggest that mEGOS, EGRIS, and ΔIgG in GBS are clinically relevant in Japan..
|17.||Ryo Yamasaki, Jun-Ichi Kira, The contribution of glial inflammation in the pathogenesis of multiple sclerosis, Neuro-Ophthalmology Japan, 10.11476/shinkeiganka.35.4, 35, 1, 4-10, 2018.01, Multiple sclerosis (MS) is one of the most prominent demyelinating disorders with a phenotype of relapsing and remitting neurological deficits. The recurrence of relapse contributes to the accumulation of neuronal damage, which leads to the transition of the disease into secondaryprogressive MS (SPMS). The mechanisms of SPMS are unknown, making the invention of new therapeutic options for SPMS difficult. In the progressive phase, "glial inflammation" is assumed to be the major player in neurodegeneration. Recently, our group and others have shown that gap junction proteins called connexins are important in the pathomechanisms of SPMS in the context of "glial inflammation". The expression of glia in connexins differs between cell types. Astroglial connexins are down regulated in the acute phase and up regulated in the chronic phase of MS, while oligodendroglial connexins are down regulated through the course of the disease. The modification and malfunction of gap junction connexins are thought to play roles in the pathomechanisms of SPMS. Further elucidation of their mechanisms may provide clues useful for the invention of new therapeutic options for SPMS..|
|18.||Atsushi Fujita, Hidenori Ogata, Ryo Yamasaki, Takuya Matsushita, Jun-Ichi Kira, Parallel fluctuation of anti-neurofascin 155 antibody levels with clinico-electrophysiological findings in patients with chronic inflammatory demyelinating polyradiculoneuropathy, Journal of the Neurological Sciences, 10.1016/j.jns.2017.11.035, 384, 107-112, 2018.01, Background The long-term clinical course and closely related biomarkers in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with anti-neurofascin 155 (NF155) antibodies remain to be elucidated. Methods We retrospectively studied the longitudinal clinical courses of three Japanese male anti-NF155 antibody-positive CIDP patients. Anti-NF155 antibody levels were measured by flow cytometry using HEK293 cell lines stably expressing human NF155. Results All three patients presented with chronic progressive sensorimotor disturbance, with ages at onset of 16, 26, and 34 years old, and they were followed for 58, 31, and 38 months, respectively, from the onset. All patients had postural tremor and generalized decreased deep tendon reflexes. Peak cerebrospinal fluid protein levels were > 400 mg/dl, and nerve conduction studies (NCS) showed severe demyelination patterns. Combined immunotherapies including intravenous immunoglobulin, plasma exchange, corticosteroids, and other immunosuppressants ameliorated clinical severity and NCS abnormalities, with improvements of > 10 kg in grip strength and at least 20% in F-wave latencies. However, their symptoms exacerbated after the immunotherapies were tapered. Anti-NF155 antibody levels varied in parallel with the clinical and electrophysiological changes, or preceded them. Conclusion The patients’ clinical courses suggest that anti-NF155 antibody levels and NCS findings could be disease activity markers in anti-NF155 antibody-positive CIDP..|
|19.||Hidenori Ogata, Ryo Yamasaki, Anti-neurofascin 155 antibody-related neuropathy, Clinical and Experimental Neuroimmunology, 10.1111/cen3.12444, 9, 1, 54-64, 2018.02, Chronic inflammatory demyelinating polyneuropathy (CIDP) is an intractable inflammatory disease affecting peripheral nerves. The etiology of CIDP remains to be established, but it is regarded as a mixture of heterogeneous conditions presenting a variety of clinical and electrophysiological manifestations. In recent years, autoantibodies against paranodal cell adhesion molecules, such as neurofascin 155 (NF155), contactin 1 and contactin-associated protein 1, have been detected in subsets of CIDP patients. The clinical characteristics of anti-NF155 antibody-positive CIDP have been delineated, and include a younger onset age, higher frequency of distal muscle weakness, sensory ataxia and tremor, higher cerebrospinal fluid protein levels, more conspicuous demyelination on nerve conduction studies, and nerve root hypertrophy on magnetic resonance neurography, when compared with anti-NF155 antibody-negative CIDP patients. Predominant elevation of immunoglobulin G4 subclass is also a characteristic of this disease. Sural nerve biopsy specimens of anti-NF155 antibody-positive CIDP patients show axo-glial detachment in paranodes without inflammatory cell infiltrates or onion bulb formation. While intravenous immunoglobulin is not as effective as expected against anti-NF155 antibody-positive CIDP patients, other immunotherapies, such as corticosteroids, plasmapheresis and B-cell depletion therapy, seem to be effective. Early diagnosis and treatment is important for preventing secondary axonal degeneration. The present review summarizes the emerging details of anti-NF155 antibody-related neuropathy..|
|20.||Ryo Yamasaki, Connexins in health and disease, Clinical and Experimental Neuroimmunology, 10.1111/cen3.12433, 9, 30-36, 2018.03, Gap junctions or hemichannels are expressed on all cells in our body, and have a highly significant role in homeostasis and in disease states. There are 21 connexins found in humans and they have distinct characteristics that compensate for each other. The anatomical expression pattern also differs between each connexin; some of them are expressed together and some are not. Genetically mutated connexin genes induce inheritable diseases, but acquired disorders can also be caused by primary or secondary connexin dysfunctions. In the central nervous system, glial cells are the main connexin-expressing cells. They utilize connexin gap junctions to assemble glial networks. The present review not only describes the basic structures and functions of connexins, it also examines the relationships between connexins and their role in disease pathology..|
|21.||Hiroyuki Ishiura, Koichiro Doi, Jun Mitsui, Jun Yoshimura, Miho Kawabe Matsukawa, Asao Fujiyama, Yasuko Toyoshima, Akiyoshi Kakita, Hitoshi Takahashi, Yutaka Suzuki, Sumio Sugano, Wei Qu, Kazuki Ichikawa, Hideaki Yurino, Koichiro Higasa, Shota Shibata, Aki Mitsue, Masaki Tanaka, Yaeko Ichikawa, Yuji Takahashi, Hidetoshi Date, Takashi Matsukawa, Junko Kanda, Fumiko Kusunoki Nakamoto, Mana Higashihara, Koji Abe, Ryoko Koike, Mutsuo Sasagawa, Yasuko Kuroha, Naoya Hasegawa, Norio Kanesawa, Takayuki Kondo, Takefumi Hitomi, Masayoshi Tada, Hiroki Takano, Yutaka Saito, Kazuhiro Sanpei, Osamu Onodera, Masatoyo Nishizawa, Masayuki Nakamura, Takeshi Yasuda, Yoshio Sakiyama, Mieko Otsuka, Akira Ueki, Ken Ichi Kaida, Jun Shimizu, Ritsuko Hanajima, Toshihiro Hayashi, Yasuo Terao, Ryo Yamasaki, Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy, Nature Genetics, 10.1038/s41588-018-0067-2, 50, 4, 581-590, 2018.04, Epilepsy is a common neurological disorder, and mutations in genes encoding ion channels or neurotransmitter receptors are frequent causes of monogenic forms of epilepsy. Here we show that abnormal expansions of TTTCA and TTTTA repeats in intron 4 of SAMD12 cause benign adult familial myoclonic epilepsy (BAFME). Single-molecule, real-time sequencing of BAC clones and nanopore sequencing of genomic DNA identified two repeat configurations in SAMD12. Intriguingly, in two families with a clinical diagnosis of BAFME in which no repeat expansions in SAMD12 were observed, we identified similar expansions of TTTCA and TTTTA repeats in introns of TNRC6A and RAPGEF2, indicating that expansions of the same repeat motifs are involved in the pathogenesis of BAFME regardless of the genes in which the expanded repeats are located. This discovery that expansions of noncoding repeats lead to neuronal dysfunction responsible for myoclonic tremor and epilepsy extends the understanding of diseases with such repeat expansion..|
|22.||Guzailiayi Maimaitijiang, Koji Shinoda, yuri nakamura, Katsuhisa Masaki, Takuya Matsushita, Noriko Isobe, Ryo Yamasaki, Yasunobu Yoshikai, Jun-Ichi Kira, Association of decreased percentage of Vδ2+Vγ9+ γδ T cells with disease severity in multiple sclerosis, Frontiers in Immunology, 10.3389/fimmu.2018.00748, 9, APR, 2018.04, We recently reported that deletion-type copy number variations of the T cell receptor (TCR) γ, α, and δ genes greatly enhanced susceptibility to multiple sclerosis (MS). However, the effect of abnormal TCR γδ gene rearrangement on MS pathogenesis remains unknown. In the present study, we aimed to clarify γδ TCR repertoire alterations and their relationship to clinical and immunological parameters in MS patients by comprehensive flow cytometric immunophenotyping. Peripheral blood mononuclear cells obtained from 30 untreated MS patients in remission and 23 age- and sex-matched healthy controls (HCs) were stained for surface markers and intracellular cytokines after stimulation with phorbol 12-myristate 13-acetate and ionomycin, and analyzed by flow cytometry. MS patients showed significantly decreased percentages of Vδ2+ and Vδ2+Vγ9+ cells in γδ T cells (pcorr = 0.0297 and pcorr = 0.0288, respectively) and elevated Vδ1/Vδ2 ratios compared with HCs (p = 0.0033). The percentages of interferon (IFN)-γ+Vδ2+ and interleukin (IL)-17A+IFN-γ+Vδ2+ cells in γδ T cells, as well as IFN-γ+ cells in Vδ2+ γδ T cells, were significantly lower in MS patients than in HCs (pcorr < 0.0009, pcorr = 0.0135, and pcorr = 0.0054, respectively). The percentages of Vδ2+ and Vδ2+Vγ9+ cells in γδ T cells were negatively correlated with both the Expanded Disability Status Scale score (r = -0.5006, p = 0.0048; and r = -0.5040, p = 0.0045, respectively) and Multiple Sclerosis Severity Score (r = -0.4682, p = 0.0091; and r = -0.4706, p = 0.0087, respectively), but not with age at disease onset, disease duration, or annualized relapse rate. In HCs, the percentages of Vδ2+ and Vδ2+Vγ9+ cells of total CD3+ T cells had strong positive correlations with the percentage of CD25+CD127low/- cells in CD4+ T cells (r = 0.7826, p < 0.0001; and r = 0.7848, p < 0.0001, respectively), whereas such correlations were totally absent in MS patients. These findings suggest that decreased Vδ2+Vγ9+ γδ T cells are associated with disability in MS. Therefore, the Vδ1/Vδ2 ratio might be a candidate biomarker for predicting disease severity in MS..|
|23.||Tomohiro Ohgomori, Ryo Yamasaki, Jun-Ichi Kira, Shozo Jinno, Upregulation of Vesicular Glutamate Transporter 2 and STAT3 Activation in the Spinal Cord of Mice Receiving 3,3′-Iminodipropionitrile, Neurotoxicity Research, 10.1007/s12640-017-9822-x, 33, 4, 768-780, 2018.05, Chronic administration of 3,3′-iminodipropionitrile (IDPN) causes axonal impairment. Although controversy still remains, it has been suggested that IDPN intoxication mimics the axonopathy of amyotrophic lateral sclerosis (ALS). Interestingly, recent studies including our own showed that signal transducer and activator of transcription 3 (STAT3) in spinal α-motoneurons was activated in both IDPN-treated mice and SOD1G93A mice, a genetic model of familial ALS. Because activation of STAT3 occurs in response to various stimuli, such as axonal injury, ischemia, and excessive glutamate, here we focused on a potential link between phosphorylated STAT3 (pSTAT3, an active form) and vesicular glutamate transporter 2 (VGluT2, a regulator of glutamate storage and release) in IDPN-treated mice and SOD1G93A mice. Impairment of axonal transport was confirmed by western blot analysis: the expression levels of phosphorylated neurofilament H were elevated in both models. As shown in SOD1G93A mice, the expression frequencies of VGluT2 in synaptophysin-positive (SYP)+ presynaptic terminals around spinal α-motoneurons were significantly higher in IDPN-treated mice than in vehicle controls. The coverages of spinal α-motoneurons by VGluT2+ presynaptic terminals were more elevated around pSTAT3+ cells than around pSTAT3− cells in IDPN-treated mice and SOD1G93A mice. Considering that excessive glutamate is shown to be involved in axonal impairment and STAT3 activation, the present results suggest that IDPN-induced upregulation of VGluT2 may result in an increase in glutamate, which might cause axonopathy and induction of pSTAT3. The link between upregulation of VGluT2 and activation of STAT3 via glutamate may represent a common pathological feature of IDPN-treated mice and SOD1G93A mice..|
|24.||Fumie Hayashi, Shintaro Hayashi, Dai Matsuse, Ryo Yamasaki, Keiji Yonekura, Jun-Ichi Kira, Hopkins syndrome following the first episode of bronchial asthma associated with enterovirus D68
A case report, BMC Neurology, 10.1186/s12883-018-1075-7, 18, 1, 2018.05, Background: Hopkins syndrome (HS) is a rare disorder presenting with acute flaccid paralysis of the limbs following an asthma attack. Neurologists encounter a diagnostic challenge if patients without a history of bronchial asthma develop neurologic features mimicking HS following acute respiratory distress. We report a case of HS occurring after a first episode of bronchial asthma associated with enterovirus D68 infection. Case presentation: A 5-year-old girl developed acute respiratory distress. On the fourth hospital day, both her legs became paralyzed except for slight muscle contraction in the right lower limb. Tendon reflexes in the lower limbs were diminished and there was a positive Babinski sign on the right. Sensation was normal in all modalities, and there was no uro-rectal disturbance. Spinal magnetic resonance imaging identified T2-hyperintense lesions with spinal cord edema, mainly involving the bilateral T11 to L1 anterior horns, with left side dominance extending to the left posterior horn. The neurological and neuro-radiological findings of our case were suggestive of HS; however, she had no history of bronchial asthma. An acetylcholine inhalation challenge eventually proved the presence of reversible airway hyper-responsiveness, allowing us to diagnose HS. We identified enterovirus D68 in the patient's intratracheal aspirates using a sensitive polymerase chain reaction assay. Intravenous immunoglobulin administrations at 2 g/kg2 for 5 consecutive days were repeated every month up to four times. After these treatments, the muscle strength of her right lower limb slightly improved while her left lower leg remained completely paralyzed. Conclusion: This case emphasizes the importance of provocation tests to reveal the presence of airway hyper-responsiveness when a child shows neurological signs mimicking HS following acute respiratory distress. Furthermore, the present case suggests a possible link between HS and acute flaccid paralysis following lower respiratory tract infection by enterovirus D68..
|25.||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, 10.1177/1352458517734072, 24, 6, 819-820, 2018.05.
|26.||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..|
|27.||Ryo Yamasaki, Cerebral blood flow laterality derived from arterial spin labeling as a biomarker for assessing the disease severity of parkinson's disease., J Magn Reson Imaging., 2017.06.|
|28.||Ryo Yamasaki, Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies., J Neurol Neurosurg Psychiatry, 2017.06.|
|29.||Ryo Yamasaki, Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer's Disease., J Alzheimer's disease, 2017.05.|
|30.||Ryo Yamasaki, Differential involvement of vesicular and glial glutamate transporters around spinal α-motoneurons in the pathogenesis of SOD1(G93A) mouse model of amyotrophic lateral sclerosis., Neuroscience, 2017.05.|
|31.||Ryo Yamasaki, Early and extensive spinal white matter involvement in neuromyelitis optica., Brain Pathol, 2017.05.|
|32.||Ryo Yamasaki, HLA-DRB1*04:05 allele is associated with intracortical lesions on three-dimensional double inversion recovery images in Japanese patients with multiple sclerosis., Mult Scler, 2017.05.|
|33.||Ryo Yamasaki, Early strong intrathecal inflammation in cerebellar type multiple system atrophy by cerebrospinal fluid cytokine/chemokine profiles: a case control study., J Neuroinflammation, 2017.04, Background: The pathology of multiple system atrophy cerebellar-type (MSA-C) includes glial inflammation; however cerebrospinal fluid (CSF) inflammatory cytokine profiles have not been investigated. In this study, we determined CSF cytokine/chemokine/growth factor profiles in MSA-C and compared them with those in hereditary spinocerebellar ataxia (SCA). Methods: We collected clinical data and CSF from 20 MSA-C patients, 12 hereditary SCA patients, and 15 patients with other non-inflammatory neurological diseases (OND), and measured 27 cytokines/chemokines/growth factors using a multiplexed fluorescent bead-based immunoassay. The size of each part of the hindbrain and hot cross bun sign (HCBS) in the pons were studied by magnetic resonance imaging.Results: Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-7, IL-12, and IL-13 levels were significantly higher in MSA-C and SCA compared with OND. In MSA-C, IL-5, IL-6, IL-9, IL-12, IL-13, platelet-derived growth factor-bb, macrophage inflammatory protein (MIP)-1α, and GM-CSF levels positively correlated with anteroposterior diameters of the pontine base, vermis, or medulla oblongata. By contrast, in SCA patients, IL-12 and MIP-1α showed significant negative correlations with anteroposterior diameters of the pontine base, and unlike MSA-C, there was no cytokine with a positive correlation in SCA. IL-6 was significantly higher in MSA-C patients with the lowest grade of HCBS compared with those with the highest grade. Macrophage chemoattractant protein-1 (MCP-1) had a significant negative correlation with disease duration only in MSA-C patients. Tumor necrosis factor-alpha, IL-2, IL-15, IL-4, IL-5, IL-10, and IL-8 were all significantly lower in MSA-C and SCA compared with OND, while IL-1ra, an anti-inflammatory cytokine, was elevated only in MSA-C. IL-1β and IL-8 had positive correlations with Unified Multiple System Atrophy Rating Scale part 1 and 2, respectively, in MSA-C.Conclusions: Although CSF cytokine/chemokine/growth factor profiles were similar between MSA-C and SCA, pro-inflammatory cytokines, such as IL-6, GM-CSF, and MCP-1, correlated with the disease stage in a way higher at the beginning only in MSA-C, reflecting early stronger intrathecal inflammation..|
|34.||Ryo Yamasaki, Evaluation of chronic inflammatory demyelinating polyneuropathy: 3D nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement imaging (3D SHINKEI)., Eur Radiol, 2017.02.|
|35.||Ryo Yamasaki, IgG4 anti-neurofascin155 antibodies in chronic inflammatory demyelinating polyradiculoneuropathy: Clinical significance and diagnostic utility of a conventional assay., J Neuroimmunol, 2016.11.|
|36.||Ryo Yamasaki, Th1 cells downregulate connexin 43 gap junctions in astrocytes via microglial activation., Sci Rep, 2016.12.|
|37.||Ryo Yamasaki, Allergic Inflammation Leads to Neuropathic Pain via Glial Cell Activation., J Neurosci, 2016.11, Allergic and atopic disorders have increased over the past few decades and have been associated with neuropsychiatric conditions, such as autism spectrum disorder and asthmatic amyotrophy. Myelitis presenting with neuropathic pain can occur in patients with atopic disorder; however, the relationship between allergic inflammation and neuropathic pain, and the underlying mechanism, remains to be established. We studied whether allergic inflammation affects the spinal nociceptive system. We found that mice with asthma, atopic dermatitis, or atopic diathesis had widespread and significantly more activated microglia and astroglia in the spinal cord than those without atopy, and displayed tactile allodynia. Microarray analysis of isolated microglia revealed a dysregulated phenotype showing upregulation of M1 macrophage markers and downregulation of M2 markers in atopic mice. Among the cell surface protein genes, endothelin receptor type B (EDNRB) was most upregulated. Immunohistochemical analysis revealed that EDNRB expression was en- hanced in microglia and astroglia, whereas endothelin-1, an EDNRB ligand, was increased in serum, lungs, and epidermis of atopic mice. No EDNRA expression was found in the spinal cord. Expression of FBJ murine osteosarcoma viral oncogene homolog B was significantly higher in the dorsal horn neurons of asthma mice than nonatopic mice. The EDNRB antagonist BQ788 abolished glial and neural activation and allodynia. We found increased serum endothelin-1 in atopic patients with myelitis and neuropathic pain, and activation of spinal microglia and astroglia with EDNRB upregulation in an autopsied case. These results suggest that allergic inflammation induces diffuse glial activation, influencing the nociceptive system via the EDNRB pathway..|
|38.||Ryo Yamasaki, Recurrent Hemorrhagic Venous Infarctions Caused by Thrombosis of a Pontine Developmental Venous Anomaly and Protein S Mutation., Cerebrovasc Dis, 2016.11.|
|39.||Ryo Yamasaki, Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2., Ann Neurol, 2016.03.|
|40.||Ryo Yamasaki, Efficacy of intravenous methylprednisolone pulse therapy in patients with multiple sclerosis and neuromyelitis optica., Mult Scler, 2016.09.|
|41.||Ryo Yamasaki, Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2., Ann Neurol., 2016.04.|
|42.||Ryo Yamasaki, Early and Extensive Spinal White Matter Involvement in Neuromyelitis Optica., Brain Pathol, 10.1111/bpa.12386, 2016.04.|
|43.||Ryo Yamasaki, Evaluation of chronic inflammatory demyelinating polyneuropathy: 3D nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement imaging (3D SHINKEI)., Eur Radiol. , 2016.04.|
|44.||Ryo Yamasaki, Copy number variations in multiple sclerosis and neuromyelitis optica, ANNALS OF NEUROLOGY, 10.1002/ana.24511, 78, 5, 762-774, 2015.11.|
|45.||Ryo Yamasaki, Characterization of IgG4 anti-neurofascin 155 antibody-positive polyneuropathy., Ann Clin Transl Neurol., S79-S79, 2015.10.|
|46.||Ryo Yamasaki, A nationwide survey of combined central and peripheral demyelination in Japan., J Neurol Neurosurg Psychiatry (in press)., 2015.03.|
|47.||Ryo Yamasaki, Decreased serum vitamin D levels in Japanese patients with multiple sclerosis, JOURNAL OF NEUROIMMUNOLOGY, 10.1016/j.jneuroim.2015.01.007, 279, 40-45, 2015.02.|
|48.||Ryo Yamasaki, Richard Ransohoff, Differential roles of microglia and monocytes in the inflamed central nervous system., J Exp Med, 2014.07.|
|49.||Ryo Yamasaki, Masaki Katsuhisa, HAYASHI SHINTARO, Satoshi O Suzuki, Jun-ichi Kira, Extensive dysregulations of oligodendrocytic and astrocytic connexins are associated with disease progression in an amyotrophic lateral sclerosis mouse model., J Neuroinflammation, 2014.03, Non-cell-autonomous motor neuronal death is suggested in a mutant Cu/Zn superoxide dismutase 1 (mSOD1)-mediated amyotrophic lateral sclerosis (ALS) model, in which glial cells play significant roles in disease progression. Connexins (Cxs) form homotypic or heterotypic gap junctions (GJs) and allow direct intercellular communications among nervous tissue cells. The role of Cxs in motor neuron disease has never been investigated; therefore, we aimed to evaluate alterations of Cxs in mSOD1-transgenic (mSOD1-Tg) mice in comparison with their non-transgenic (non-Tg) littermates at the same ages.
We pathologically evaluated temporal changes to astrocytic Cx43/Cx30 and oligodendrocytic Cx47/Cx32 immunoreactivities at presymptomatic, disease-progressive, and end stages, relative to aquaporin-4 (AQP4), glial fibrillary acidic protein (GFAP), excitatory amino acid transporter-2 (EAAT2), myelin-oligodendrocyte glycoprotein (MOG), and Nogo-A immunoreactivities, and observed neuronal loss by NeuN and neurofilament immunostaining, and microglial response by Iba-1 immunostaining. We also performed quantitative immunoblotting and real-time PCR analyses for Cxs.
The mSOD1-Tg mice showed neuronal and axonal loss in the anterior horns of the lumbar spinal cord accompanied by increased activation of microglia compared with non-Tg mice at the disease-progressive and end stages. Expression patterns of Cxs were not different between mSOD1-Tg and non-Tg mice at the presymptomatic stage, but immunoreactivities for GFAP, Cx43, Cx30 and AQP4 were increased in the anterior horns of mSOD1-Tg mice at the disease-progressive and end stages. By contrast, Cx47 and Cx32 immunoreactivities were markedly diminished in Nogo-A-positive oligodendrocytes in the anterior horns of mSOD1-Tg mice at the disease-progressive and end stages, especially in oligodendrocytes showing SOD1 accumulation. EAAT2 immunoreactivity was also diminished in the anterior horns of mSOD1-Tg mice at the disease-progressive and end stages. Quantitative immunoblotting revealed a significant reduction in Cx47 and Cx32 protein levels in mSOD1-Tg mice at the disease-progressive and end stages. The levels of Cx47 and Cx32 mRNAs were also decreased at these stages.
Our findings indicate that oligodendrocytic and astrocytic GJ proteins in the anterior horns of spinal cord in mSOD1-Tg mice are profoundly affected at the disease-progressive and end stages, where disruption of GJs among glial cells may exacerbate motor neuronal death..
|50.||Ryo Yamasaki, Yuji Kawano, Takuya Matsushita, Yoshimura Satoshi, Hiroyuki Murai, Jun-ichi Kira, Interleukin 2 receptor α chain gene polymorphisms and risks of multiple sclerosis and neuromyelitis optica in southern Japanese., J Neurol Sci, 2014.02, Interleukin 2 receptor α subunit (IL2RA) is a genetic risk for multiple sclerosis (MS) in Caucasians. However, the association between MS and IL2RA in Japanese idiopathic demyelinating diseases of the central nervous system has not been examined.
To determine whether IL2RA gene polymorphisms confer risks of developing MS or neuromyelitis optica (NMO) in a Japanese population.
DNA samples were obtained from 115 MS patients, 75 NMO/NMO spectrum disorder (NMOSD) patients, and 238 healthy controls. The single nucleotide polymorphisms (SNPs) rs2104286, rs12722489, and rs7090512 were genotyped by real-time PCR using TaqMan SNP genotyping assays.
No significant associations of the three IL2RA SNPs with the development of the diseases were observed. In MS patients only, the annualized relapse rates were significantly higher for the rs2104286-TT genotype than for the non-TT (CT+CC) genotype and for the rs12722489-CC genotype than for the non-CC genotype in females (p = 0.0138 for both), but not in males.
Although the possibility that IL2RA is a risk factor for MS development was not confirmed in this Japanese population, IL2RA gene polymorphisms were able to modify the disease activity in female MS patients, but had no influence on either susceptibility or disease phenotype in NMO/NMOSD patients..
|51.||Ryo Yamasaki, Tomomi Yonekawa, Hiroyuki Murai, Takuya Matsushita, Masaki Katsuhisa, Noriko Isobe, Jun-ichi Kira, A nationwide survey of hypertrophic pachymeningitis in Japan., J Neurol Neurosurg Psychiatry, 2013.11, To clarify the prevalence, frequent causes and distinct features of hypertrophic pachymeningitis (HP) according to background conditions in a nationwide survey in Japan.
The study began with a preliminary survey to determine the approximate number of HP patients diagnosed from 1 January 2005 to 31 December 2009, and was followed by a questionnaire survey for clinical and laboratory findings. HP was defined as a condition with thickening of the cranial or spinal dura mater with inflammation, evidenced by MRI or histology.
Crude HP prevalence was 0.949/100 000 population. The mean age at onset was 58.3±15.8 years. Among 159 cases for whom detailed data were collated, antineutrophil cytoplasmic antibody (ANCA)-related HP was found in 54 cases (34.0%) and IgG4/multifocal fibrosclerosis (MFS)-related HP in 14 cases (8.8%). Seventy cases (44.0%) were classified as 'idiopathic' and 21 (13.2%) as 'others'. ANCA-related HP cases showed a female preponderance, a higher age of onset, and higher frequencies of otological symptoms and elevated systemic inflammatory biomarkers, but lower frequencies of diplopia compared with idiopathic HP. IgG4/MFS-related HP cases showed a marked male predominance; all had cranial HP while none had isolated spinal HP or decreased sensation.
HP is not extremely rare. ANCA-related HP is the most frequent form, followed by IgG4/MFS-related HP. Both forms have unique features, which may help to differentiate background causes..
|52.||Ryo Yamasaki, Masaki Katsuhisa, Satoshi O Suzuki, Takuya Matsushita, 松岡 健, Toru Iwaki, Jun-ichi Kira, Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica, PLoS One, 10.1371/journal.pone.0072919., 8, 8, e72919, 2013.08.|
|53.||Ryo Yamasaki, Nobutoshi Kawamura, Takuya Matsushita, Matsuse Dai, Hiroyuki Murai, Jun-ichi Kira, Anti-neurofascin antibody in patients with combined central and peripheral demyelination., Neurology, 2013.08, We aimed to identify the target antigens for combined central and peripheral demyelination (CCPD).
We screened target antigens by immunohistochemistry and immunoblotting using peripheral nerve tissues to identify target antigens recognized by serum antibodies from selected CCPD and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cases. We then measured the level of antibody to the relevant antigen in 7 patients with CCPD, 16 patients with CIDP, 20 patients with multiple sclerosis, 20 patients with Guillain-Barré syndrome, 21 patients with other neuropathies, and 23 healthy controls (HC) by ELISA and cell-based assays using HEK293 cells.
At the initial screening, sera from 2 patients with CCPD showed cross-like binding to sciatic nerve sections at fixed intervals, with nearly perfect colocalization with neurofascin immunostaining at the node and paranode. ELISA with recombinant neurofascin revealed significantly higher mean optical density values in the CCPD group than in other disease groups and HC. Anti-neurofascin antibody positivity rates were 86% in patients with CCPD, 10% in patients with multiple sclerosis, 25% in patients with CIDP, 15% in patients with Guillain-Barré syndrome, and 0% in patients with other neuropathies and HC. The cell-based assay detected serum anti-neurofascin antibody in 5 of 7 patients with CCPD; all others were negative. CSF samples examined from 2 patients with CCPD were both positive. In anti-neurofascin antibody-positive CCPD patients, including those with a limited response to corticosteroids, IV immunoglobulin or plasma exchange alleviated the symptoms.
Anti-neurofascin antibody is frequently present in patients with CCPD. Recognition of this antibody may be important, because patients with CCPD who are antibody positive respond well to IV immunoglobulin or plasma exchange..
|54.||Saitoh BY, Ryo Yamasaki, Hayashi S, Yoshimura S, Tateishi T, Ohyagi Y, Murai H, Iwaki T, Yoshida K, Kira JI, A case of hereditary diffuse leukoencephalopathy with axonal spheroids caused by a de novo mutation in CSF1R masquerading as primary progressive multiple sclerosis., Mult Scler., 2013.05.|
|55.||Huang J, Yoshimura S, Isobe N, Matsushita T, Yonekawa T, Sato S, Ryo Yamasaki, Kira JI, A NOTCH4 missense mutation confers resistance to multiple sclerosis in Japanese., Mult Scler., 2013.04.|
|56.||Matsushita T, Tateishi T, Isobe N, Yonekawa T, Ryo Yamasaki, Matsuse D, Murai H, Kira J, Characteristic cerebrospinal fluid cytokine/chemokine profiles in neuromyelitis optica, relapsing remitting or primary progressive multiple sclerosis., PLoS One, 2013.04.|
|57.||Soejima N, Yasumasa Ohyagi, Nakamura N, Himeno E, Iinuma KM, Sakae N, Tabira T, Ryo Yamasaki, Murakami K, Irie K, Kinoshita N, LaFeria FM, Kiyohara Y, Iwaki T, Kira J, Intracellular accumulation of toxic turn amyloid-β is associated with endoplasmic reticulum stress in Alzheimer's disease., Curr Alzheimer Res, 2013.01.|
|58.||Nagara Y, Tateishi T, Ryo Yamasaki, Hayashi S, kawamura M, Kikuchi H, Iinuma KM, Tanaka M, Iwaki T, Matsushita T, Ohyagi Y, Kira JI, Impaired Cytoplasmic-Nuclear Transport of Hypoxia-Inducible Factor-1α in Amyotrophic Lateral Sclerosis., Brain Pathol, 2013.01.|
|59.||Schafer DP, Lehman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B, Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner., Neuron, 2012.05.|
|60.||Kawamura MF, 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., Journal of experimental neurology, 2012.04.|
|61.||Uehara T, Murai H, Ryo Yamasaki, Kikuchi H, Shigeto H, Ohyagi Y, Kira J, Thymoma-associated progressive encephalomyelitis with rigidity and myoclonus successfully treated with thymectomy and intravenous immunoglobulin., Eur Neurol., 2011.11.|
|62.||Pineda AA, Minohara M, Kawamura N, Matsushita T, Ryo Yamasaki, Sun X, Piao H, Shimokara H, Kira J, Preventive and therapeutic effects of the selective Rho-kinase inhibitor fasudil on experimental autoimmune neuritis., J Neurol Sci., 2011.07.|
|63.||Ma L, Ohyagi Y, Nakamura N, Iinuma KM, Miyoshi K, Himeno E, Soejima N, Yanagihara YT, Sakae N, Ryo Yamasaki, Kira J, Activation of glutathione peroxidase and inhibition of p53-related apoptosis by apomorphine., J Alzheimers Dis, 2011.06.|
|64.||Hagiwara K, Tominaga K, Okada Y, Kido M, Ryo Yamasaki, Shida N, Yamashita Y, Post-streptococcal chorea in an adult with bilateral striatal encephalitis., J Clin Neurosci., 2011.05.|
|65.||Himeno E, Ohyagi Y, Ma L, Nakamura N, Miyoshi K, Sakae N, Motomura K, Soejima N, Ryo Yamasaki, Hashimoto T, Tabira T, LaFeria FM, Kira J, Apomorphine treatment in Alzheimer mice promoting amyloid-β degradation., Ann Neurol., 2011.02.|
|66.||Ryo Yamasaki, Piao H, Minohara M, Kawamura N, Li W, Matsushita T, Mizunoe Y, Kira J, Tissue binding patterns and in vitro effects of Campylobacter jejuni DNA-binding protein from starved cells., Neurochem Res, 2011.01.|
|67.||Ryo Yamasaki, 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 Neuroimmunol. , 2010.12.|
|68.||Tateishi T, Ryo Yamasaki, Tanaka M, Matsushita T, Kikuchi H, Isobe N, Ohyagi Y, Kira J, CSF chemokine alterations related to the clinical course of amyotrophic lateral sclerosis., J Neuroimmunol., 2010.05.|
|69.||Matsushita T, Isobe N, Piao H, Matsuoka T, Ishizu T, Doi H, Masaki K, Yoshiura T, Ryo Yamasaki, Ohyagi Y, Kira J, Reappraisal of brain MRI features in patients with multiple sclerosis and neuromyelitis optica according to anti-aquaporin-4 antibody status., J Neurol Sci., 2010.04.|
|70.||Tateishi T, Hokonohara T, Ryo Yamasaki, 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., 2010.03.|
|71.||Piao H, Minohara M, Kawamura N, Li W, Mizunoe Y, Umehara F, Goto Y, Kusunoki S, Matsushita T, Ikenaka K, Maejima T, Nabekura J, Ryo Yamasaki, 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., J Neurol Sci., 2010.01.|
|72.||Yoshida F, Miyagi Y, Kishimoto J, Morioka T, Murakami N, Hashiguchi K, Samura K, Sakae N, Ryo Yamasaki, Kawaguchi M, Sasaki T, Subthalamic nucleus stimulation does not cause deterioration of preexisting hallucinations in Parkinson's disease patients., Stereotact Funct Neurosurg., 2009.01.|
|73.||Ryo Yamasaki, Jian Zhang, Ichiro Koshiishi, Dewi F. Sastradipura Suniarti, Zhou Wu, Christoph Peters, Michael Schwake, Yasuo Uchiyama, Jun-ichi Kira, Paul Saftig, Hideo Utsumi, Hiroshi Nakanishi , Involvement of lysosomal storage-induced p38 MAP kinase activation in the overproduction of nitric oxide by microglia in the cathepsin D-deficient mice. , Molecular and Cellular Neuroscience , 2007.08.|
|74.||Shimizu T, Hayashi Y, Ryo Yamasaki, Yamada J, Zhang J, Ukai K, Koike M, Mine K, von Figura K, Peters C, Saftig P, Fukuda T, Uchiyama Y, Nakanishi H, Proteolytic degradation of glutamate decarboxylase mediates disinhibition of hippocampal CA3 pyramidal cells in cathepsin D-deficient mice., J Neurochem. , 2005.08.|
|75.||Kawamura T, Morioka T, Nishio S, Fukui K, Yamasaki R, Matsuo M, Temporal lobe epilepsy associated with hippocampal sclerosis and a contralateral middle fossa arachnoid cyst., Seizure., 2002.01.|