start-ver=1.4 cd-journal=joma no-vol=30 cd-vols= no-issue=4 article-no= start-page=e70082 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=202512 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A Case of Retinopathy?Sensory Neuropathy Syndrome With a Novel Compound Heterozygous FLVCR1 Variant en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Aims: Retinopathy?sensory neuropathy syndrome (RETSNS), also known as posterior column ataxia with retinitis pigmentosa (PCARP), is a rare neurodegenerative disorder that is caused by biallelic pathogenic variants in FLVCR1. Here, we report a case of a Japanese patient with RETSNS.
Methods: Clinical, neuroradiological, and electrophysiological findings were documented. Whole-genome sequencing was performed. Subcloning was carried out to confirm compound heterozygosity. A functional assay was performed to assess the pathogenicity of the variants.
Results: The patient showed retinitis pigmentosa and sensory ataxia. Over the course of the disease, autonomic dysfunction has become increasingly evident. Despite consanguinity in the family, whole-genome sequencing identified two heterozygous variants in FLVCR1 (c.369T>G, p.Phe123Leu and c.733A>G, p.Asn245Asp). Cloning of the PCR product followed by Sanger sequencing indicated compound heterozygosity of the variants. Immunocytochemistry of HEK293FT cells transfected with plasmids containing wild-type or variant FLVCR1 cDNA demonstrated altered subcellular localization of the variant FLVCR1 proteins, characterized by reduced membrane localization.
Interpretation: We report a novel variant in FLVCR1 causing RETSNS. The functional assay supports the pathogenicity of the variants. en-copyright= kn-copyright= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KawanoTomohito en-aut-sei=Kawano en-aut-mei=Tomohito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TairaYuki en-aut-sei=Taira en-aut-mei=Yuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsuoAyaka en-aut-sei=Matsuo en-aut-mei=Ayaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OsakadaYosuke en-aut-sei=Osakada en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YunokiTaijun en-aut-sei=Yunoki en-aut-mei=Taijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama City General Medical Center kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=9 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=11 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=12 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=13 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=14 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= en-keyword=FLCVR1 kn-keyword=FLCVR1 en-keyword=functional analysis kn-keyword=functional analysis en-keyword=posterior column ataxia with retinitis pigmentosa kn-keyword=posterior column ataxia with retinitis pigmentosa en-keyword=subcellular localization kn-keyword=subcellular localization END start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=3 article-no= start-page=198 end-page=200 dt-received= dt-revised= dt-accepted= dt-pub-year=2025 dt-pub=20250108 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Long-Term Follow-Up of a Patient With SPG11 en-subtitle= kn-subtitle= en-abstract= kn-abstract=We present a case of a male patient with disease-causing variants in SPG11, a causative gene for autosomal recessive spastic paraplegia with a thin corpus callosum (ARHSP-TCC), as well as juvenile amyotrophic lateral sclerosis (ALS5) and Charcot?Marie?Tooth disease (CMT2X). A neurological examination at age 18 revealed dysarthria, muscle weakness in bilateral lower extremities, hyperreflexia in patellar reflex, hyporeflexia in Achilles reflex with an extensor plantar reflex, and intellectual disability. Magnetic resonance imaging revealed a thin corpus callosum and ears of the lynx sign. At the age of 26, weakness and muscle atrophy progressed. While no sensory disturbances were noted, there was a mild decrease in sensory nerve action potentials of the sural nerve over the 8?years between 18 and 26. Clinicians should be aware that SPG11 belongs to the same spectrum of disorders as ALS5 and CMT2X and presents various phenotypes depending on the stage of the disease. en-copyright= kn-copyright= en-aut-name=OsakadaYosuke en-aut-sei=Osakada en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YunokiTaijun en-aut-sei=Yunoki en-aut-mei=Taijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=MatsuokaChika en-aut-sei=Matsuoka en-aut-mei=Chika kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=FukuiYusuke en-aut-sei=Fukui en-aut-mei=Yusuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=TsunodaKeiichiro en-aut-sei=Tsunoda en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IshiuraHiroyuki en-aut-sei=Ishiura en-aut-mei=Hiroyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Tsuyama Chuo Hospital kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama City Hospital kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= END start-ver=1.4 cd-journal=joma no-vol=353 cd-vols= no-issue=1-2 article-no= start-page=185 end-page=186 dt-received= dt-revised= dt-accepted= dt-pub-year=2015 dt-pub=20156 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Selective disappearance of medial back muscles in a case of myotonic dystrophy type 1 en-subtitle= kn-subtitle= en-abstract= kn-abstract=Here, we report a unique case of late-onset myotonic dystrophy type 1 in a 64-year-old woman, with selective disappearance of the medial lower back muscles. We compared the clinical features of this patient with those of a cohort of 29 patients with myotonic dystrophy type 1 to clarify the correlation between clinical features and lower back muscle atrophy. After classification into three subgroups according to muscle atrophy pattern, medial muscle atrophy was present in 17.2% of the patients. Affected patients were older at onset than non-affected patients, and limb muscle power and respiratory function decreased with atrophy progression. en-copyright= kn-copyright= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurataTomoko en-aut-sei=Kurata en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science kn-affil= en-keyword=Myotonic dystrophy type 1 kn-keyword=Myotonic dystrophy type 1 en-keyword=Paraspinal muscles kn-keyword=Paraspinal muscles en-keyword=Late onset kn-keyword=Late onset END start-ver=1.4 cd-journal=joma no-vol=387 cd-vols= no-issue=15 article-no= start-page=70 end-page=74 dt-received= dt-revised= dt-accepted= dt-pub-year=2018 dt-pub=20184 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Familial and sporadic chronic progressive degenerative parietal ataxia en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background & objective: Parietal ataxia has been mainly reported as a consequence of acute ischemic stroke, while degenerative parietal ataxia has not been reported. Methods: We investigated clinical characteristics, neuroimaging data, and genetic analysis of patients with cerebellar ataxia plus parietal atrophy. Results: We identified seven patients, including five patients from two families, with chronic progressive cerebellar ataxia due to degenerative parietal atrophy but not stroke. Age at onset of ataxia was 57.6 +/- 6.9 years. All patients showed chronic progressive cerebellar ataxia with severity of ataxic gait > limb ataxia > dysarthria. Patients showed no cognitive dysfunction, muscle weakness, or parkinsonism, and only two patients showed mild sensory disturbances. The seven patients showed lateralized limb ataxia with greater contralateral parietal lobe atrophy by magnetic resonance imaging, and hypoperfusion by single photon emission computed tomography, without any abnormal cerebellar pathology (i.e., crossed cerebellar diaschisis). Pathogenic mutations in the microtubule-associated protein tau gene were not found using two single nucleotide polymorphisms. Conclusions: This is the first description showing unique clinical features of familial and sporadic chronic progressive degenerative parietal ataxia. en-copyright= kn-copyright= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurataTomoko en-aut-sei=Kurata en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=NomuraEmi en-aut-sei=Nomura en-aut-mei=Emi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=SatoKota en-aut-sei=Sato en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IkeuchiTakeshi en-aut-sei=Ikeuchi en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=KitaguchiMasataka en-aut-sei=Kitaguchi en-aut-mei=Masataka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= affil-num=1 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=2 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=3 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=4 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=5 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=6 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=7 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=8 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=9 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=10 en-affil=Department of Molecular Genetics, Bioresource Science Branch, Center of Bioresource, Brain Research Institute Niigata University kn-affil= affil-num=11 en-affil=Department of Neurology, Baba Memorial Hospital kn-affil= affil-num=12 en-affil=Departments of Neurology, Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= en-keyword=parietal ataxia kn-keyword=parietal ataxia en-keyword=parietal lobe atrophy kn-keyword=parietal lobe atrophy en-keyword=crossed cerebellar diaschisis kn-keyword=crossed cerebellar diaschisis en-keyword=MAPT kn-keyword=MAPT END start-ver=1.4 cd-journal=joma no-vol=56 cd-vols= no-issue=17 article-no= start-page=2343 end-page=2346 dt-received= dt-revised= dt-accepted= dt-pub-year=2017 dt-pub=20170901 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Successful Delayed Aortic Surgery for a Patient with Ischemic Stroke Secondary to Aortic Dissection en-subtitle= kn-subtitle= en-abstract= kn-abstract=The diagnosis of aortic dissection (AD) is sometimes difficult within the limited time window of recombinant tissue plasminogen activator (tPA) for ischemic stroke (IS). A 60-year-old man developed sudden left hemiparesis due to IS. During tPA infusion, his blood pressure dropped and consciousness declined. After transfer to our hospital, carotid duplex ultrasonography led to a diagnosis of AD. Emergency surgery was postponed because of the risk of hemorrhagic transformation. The patient successfully underwent aortic surgery on day 5 and was discharged with a remarkable improvement in his symptoms. Delayed surgery may avoid hemorrhagic transformation in patients with AD-induced IS who have received tPA. en-copyright= kn-copyright= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=TsunodaKeiichiro en-aut-sei=Tsunoda en-aut-mei=Keiichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ManabeYasuhiro en-aut-sei=Manabe en-aut-mei=Yasuhiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakahashiYoshiaki en-aut-sei=Takahashi en-aut-mei=Yoshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=YunokiTaijun en-aut-sei=Yunoki en-aut-mei=Taijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SatoKota en-aut-sei=Sato en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=KonoSyoichiro en-aut-sei=Kono en-aut-mei=Syoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil=Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=2 en-affil=Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University kn-affil= affil-num=3 en-affil=Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan kn-affil= affil-num=4 en-affil=Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama National Hospital Medical Center, Japan kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama National Hospital Medical Center, Japan kn-affil= affil-num=7 en-affil=Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan kn-affil= affil-num=8 en-affil=Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan kn-affil= affil-num=9 en-affil=Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama National Hospital Medical Center, Japan kn-affil= affil-num=11 en-affil=Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan kn-affil= affil-num=12 en-affil=Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan kn-affil= affil-num=13 en-affil=Departments of Neurology, Dentistry, and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Japan kn-affil= END start-ver=1.4 cd-journal=joma no-vol=58 cd-vols= no-issue=7 article-no= start-page=1033 end-page=1036 dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=20190401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Characteristic Clinical Features of Werner Syndrome with a Novel Compound Heterozygous WRN Mutation c.1720+1G>A Plus c.3139-1G>C en-subtitle= kn-subtitle= en-abstract= kn-abstract=Werner syndrome (WS) is an autosomal recessive progeroid disorder caused by mutations in the WRN gene (WRN). Most Japanese WS patients are born from a consanguineous marriage with homozygous WRN mutations. We herein report a rare WS patient born from non-consanguineous parents with compound heterozygous WRN mutations with a novel heterogeneous c.1720+1G>A substitution plus the most frequent heterogeneous c.3139-1G>C substitution among Japanese. Although the present case showed clinical characteristics common to previous Japanese WS patients, he had not developed any malignant tumors as of 43 years of age, suggesting that WS patients with this particular genetic mutation have a different phenotype than others. en-copyright= kn-copyright= en-aut-name=MatsumotoNamiko en-aut-sei=Matsumoto en-aut-mei=Namiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KishidaMasayuki en-aut-sei=Kishida en-aut-mei=Masayuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=SatoKota en-aut-sei=Sato en-aut-mei=Kota kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShangJingwei en-aut-sei=Shang en-aut-mei=Jingwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=WatanabeAki en-aut-sei=Watanabe en-aut-mei=Aki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YokoteKoutaro en-aut-sei=Yokote en-aut-mei=Koutaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=TakemotoMinoru en-aut-sei=Takemoto en-aut-mei=Minoru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OshimaJunko en-aut-sei=Oshima en-aut-mei=Junko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= affil-num=1 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama Citizen's Hospital kn-affil= affil-num=4 en-affil=Department of General Internal Medicine, Okayama Citizen's Hospital kn-affil= affil-num=5 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=10 en-affil=Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University kn-affil= affil-num=11 en-affil=Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University kn-affil= affil-num=12 en-affil=Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare kn-affil= affil-num=13 en-affil=Department of Pathology, University of Washington kn-affil= affil-num=14 en-affil=Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= en-keyword=werner syndrome kn-keyword=werner syndrome en-keyword=compound heterozygous kn-keyword=compound heterozygous en-keyword=Japanese kn-keyword=Japanese END start-ver=1.4 cd-journal=joma no-vol=73 cd-vols= no-issue=1 article-no= start-page=217 end-page=227 dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=20200107 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A New Serum Biomarker Set to Detect Mild Cognitive Impairment and Alzheimer’s Disease by Peptidome Technology en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background:
Because dementia is an emerging problem in the world, biochemical markers of cerebrospinal fluid (CSF) and radio-isotopic analyses are helpful for diagnosing Alzheimer’s disease (AD). Although blood sample is more feasible and plausible than CSF or radiological biomarkers for screening potential AD, measurements of serum amyloid- β (Aβ), plasma tau, and serum antibodies for Aβ1 - 42 are not yet well established.
Objective:
We aimed to identify a new serum biomarker to detect mild cognitive impairment (MCI) and AD in comparison to cognitively healthy control by a new peptidome technology.
Methods:
With only 1.5μl of serum, we examined a new target plate “BLOTCHIP?” plus a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) to discriminate control (n?=?100), MCI (n?=?60), and AD (n?=?99). In some subjects, cognitive Mini-Mental State Examination (MMSE) were compared to positron emission tomography (PET) with Pittsburgh compound B (PiB) and the serum probability of dementia (SPD). The mother proteins of candidate serum peptides were examined in autopsied AD brains.
Results:
Apart from Aβ or tau, the present study discovered a new diagnostic 4-peptides-set biomarker for discriminating control, MCI, and AD with 87% of sensitivity and 65% of specificity between control and AD (***p? Conclusion:
The present serum biomarker set provides a new, rapid, non-invasive, highly quantitative and low-cost clinical application for dementia screening, and also suggests an alternative pathomechanism of AD for neuroinflammation and neurovascular unit damage. en-copyright= kn-copyright= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShangJingwei en-aut-sei=Shang en-aut-mei=Jingwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=ShiXiaowen en-aut-sei=Shi en-aut-mei=Xiaowen kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HishikawaNozomi en-aut-sei=Hishikawa en-aut-mei=Nozomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=TakemotoMami en-aut-sei=Takemoto en-aut-mei=Mami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MoriharaRyuta en-aut-sei=Morihara en-aut-mei=Ryuta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=NakanoYumiko en-aut-sei=Nakano en-aut-mei=Yumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=IkedaMasaki en-aut-sei=Ikeda en-aut-mei=Masaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=IkedaYoshio en-aut-sei=Ikeda en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=OkamotoKoichi en-aut-sei=Okamoto en-aut-mei=Koichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=ShojiMikio en-aut-sei=Shoji en-aut-mei=Mikio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TakatamaMasamitsu en-aut-sei=Takatama en-aut-mei=Masamitsu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KojoMotohisa en-aut-sei=Kojo en-aut-mei=Motohisa kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=KurodaTakeshi en-aut-sei=Kuroda en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=OnoKenjiro en-aut-sei=Ono en-aut-mei=Kenjiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=KimuraNoriyuki en-aut-sei=Kimura en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=MatsubaraEtsuro en-aut-sei=Matsubara en-aut-mei=Etsuro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=OsakadaYosuke en-aut-sei=Osakada en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= en-aut-name=WakutaniYosuke en-aut-sei=Wakutani en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=22 ORCID= en-aut-name=TakaoYoshiki en-aut-sei=Takao en-aut-mei=Yoshiki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=23 ORCID= en-aut-name=HigashiYasuto en-aut-sei=Higashi en-aut-mei=Yasuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=24 ORCID= en-aut-name=AsadaKyoichi en-aut-sei=Asada en-aut-mei=Kyoichi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=25 ORCID= en-aut-name=SengaTakehito en-aut-sei=Senga en-aut-mei=Takehito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=26 ORCID= en-aut-name= LeeLyang-Ja en-aut-sei= Lee en-aut-mei=Lyang-Ja kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=27 ORCID= en-aut-name=TanakaKenji en-aut-sei=Tanaka en-aut-mei=Kenji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=28 ORCID= affil-num=1 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=3 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=5 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=8 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=9 en-affil=Department of Neurology, Okayama University kn-affil= affil-num=10 en-affil=Department of Neurology, Okayama City Hospital, Okayama kn-affil= affil-num=11 en-affil=Department of Neurology, Gunma University, Graduate School of Medicine kn-affil= affil-num=12 en-affil=Department of Neurology, Gunma University, Graduate School of Medicine kn-affil= affil-num=13 en-affil=Department of Neurology, Geriatrics Research Institute and Hospital kn-affil= affil-num=14 en-affil=Department of Neurology, Geriatrics Research Institute and Hospital kn-affil= affil-num=15 en-affil=Department of Neurology, Geriatrics Research Institute and Hospital kn-affil= affil-num=16 en-affil=Department of Neurology, Ako Chuo Hospital kn-affil= affil-num=17 en-affil=Division of Neurology, Department of Medicine, Showa University, School of Medicine kn-affil= affil-num=18 en-affil=Division of Neurology, Department of Medicine, Showa University, School of Medicine kn-affil= affil-num=19 en-affil=Department of Neurology, Faculty of Medicine, Oita University kn-affil= affil-num=20 en-affil=Department of Neurology, Faculty of Medicine, Oita University kn-affil= affil-num=21 en-affil=Department of Neurology, Kurashiki Heisei Hospital kn-affil= affil-num=22 en-affil=Department of Neurology, Kurashiki Heisei Hospital kn-affil= affil-num=23 en-affil=Department of Neurology, Kurashiki Heisei Hospital kn-affil= affil-num=24 en-affil=Department of Neurology, Himeji Central Hospital kn-affil= affil-num=25 en-affil=Membrane Protein and Ligand Analysis Center, Protosera Inc., kn-affil= affil-num=26 en-affil=Membrane Protein and Ligand Analysis Center, Protosera Inc., kn-affil= affil-num=27 en-affil=Membrane Protein and Ligand Analysis Center, Protosera Inc., kn-affil= affil-num=28 en-affil=Membrane Protein and Ligand Analysis Center, Protosera Inc., kn-affil= en-keyword=Alzheimer’s disease kn-keyword=Alzheimer’s disease en-keyword=biomarker kn-keyword=biomarker en-keyword=coagulation kn-keyword=coagulation en-keyword=complement kn-keyword=complement en-keyword=MALDI-TOF kn-keyword=MALDI-TOF en-keyword=mild cognitive impairment kn-keyword=mild cognitive impairment en-keyword=neuroinflammation kn-keyword=neuroinflammation en-keyword=peptidome kn-keyword=peptidome en-keyword=plasticity kn-keyword=plasticity END start-ver=1.4 cd-journal=joma no-vol=20 cd-vols= no-issue=5 article-no= start-page=e67 end-page=e69 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=201305 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=A novel familial prion disease causing pan-autonomic-sensory neuropathy and cognitive impairment en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=MatsuzonoKosuke en-aut-sei=Matsuzono en-aut-mei=Kosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=IkedaYoshio en-aut-sei=Ikeda en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=LiuWentao en-aut-sei=Liu en-aut-mei=Wentao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KurataTomoko en-aut-sei=Kurata en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=DeguchiShoko en-aut-sei=Deguchi en-aut-mei=Shoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= affil-num=1 en-affil= kn-affil= affil-num=2 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=3 en-affil= kn-affil= affil-num=4 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= affil-num=7 en-affil=Department of Neurology, Okayama University Graduate School of Medicine and Dentistry kn-affil= en-keyword=Prion disease kn-keyword=Prion disease en-keyword=Novelgene mutation kn-keyword=Novelgene mutation en-keyword=2bp deletion in codon 178 kn-keyword=2bp deletion in codon 178 en-keyword=stopcodon at codon 195 kn-keyword=stopcodon at codon 195 en-keyword=Sensoryneuropathy kn-keyword=Sensoryneuropathy en-keyword=HSAN kn-keyword=HSAN en-keyword=Pan-autonomicfailure kn-keyword=Pan-autonomicfailure en-keyword=Familial case kn-keyword=Familial case END start-ver=1.4 cd-journal=joma no-vol=92 cd-vols= no-issue=1 article-no= start-page=46 end-page=53 dt-received= dt-revised= dt-accepted= dt-pub-year=2014 dt-pub=201401 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Reducing Hemorrhagic Complication by Dabigatran Via Neurovascular Protection After Recanalization With Tissue Plasminogen Activator in Ischemic Stroke of Rat en-subtitle= kn-subtitle= en-abstract= kn-abstract=This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study. en-copyright= kn-copyright= en-aut-name=KonoSyoichiro en-aut-sei=Kono en-aut-mei=Syoichiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=OmoteYoshio en-aut-sei=Omote en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=YunokiTaijun en-aut-sei=Yunoki en-aut-mei=Taijun kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KurataTomoko en-aut-sei=Kurata en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkedaYoshio en-aut-sei=Ikeda en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol affil-num=2 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol affil-num=4 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol affil-num=5 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol affil-num=6 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol affil-num=7 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol affil-num=8 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol en-keyword=dabigatran kn-keyword=dabigatran en-keyword=hemorrhagic complication kn-keyword=hemorrhagic complication en-keyword=neurovascular unit kn-keyword=neurovascular unit en-keyword=pericyte kn-keyword=pericyte en-keyword=thrombolysis kn-keyword=thrombolysis en-keyword=tPA kn-keyword=tPA END start-ver=1.4 cd-journal=joma no-vol=43 cd-vols= no-issue=6 article-no= start-page=1639 end-page=1646 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=201206 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Clinical and Pathological Improvement in Stroke-Prone Spontaneous Hypertensive Rats Related to the Pleiotropic Effect of Cilostazol en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background and Purpose-Cerebral infarction is a major cause of death or decreasing activities of daily living. This study aimed to investigate the efficacy of commonly used antiplatelet drugs on stroke and motor and cognitive functions in relation to oxidative stress markers and insulin-like growth factor 1 receptor (IGF-1R). Methods-Stroke-prone spontaneously hypertensive rats were treated with vehicle, aspirin, clopidogrel, and cilostazol from 8 to 10 weeks of age. Physiological parameters, regional cerebral blood flow, and serum lipids were examined. Motor and cognitive functions were evaluated weekly by the Rotorod and water maze task. Spontaneous infarct volume, oxidative stress markers for lipid, protein, and DNA at the ischemic boundary zone of spontaneous infarction, and the IGF-1R-positive cell ratio in the hippocampus were immunohistochemically examined in brain sections. IGF-1R beta expression in the hippocampus was assessed by Western blotting. Results-The antiplatelet drugs, cilostazol and clopidogrel, reduced the spontaneous infarct volume more than aspirin. Only cilostazol improved motor and cognitive functions with a significant increase (P<0.05) in the memory-related IGF-1R-positive ratio and IGF-1R beta expression in the hippocampus. Cilostazol reduced the 4 oxidative stress markers in affected neurons in stroke-prone spontaneously hypertensive rats regardless of blood pressure, regional cerebral blood flow, or serum lipid levels. Conclusions-The present results suggest that a possible pleiotropic effect of cilostazol resulted in the reduction of spontaneous infarct volume and preservation of motor and spatial cognitive functions. The increase of IGF-1R-positive cells in the hippocampal CA1 region could partly explain the preservation of spatial cognitive function in stroke-prone spontaneously hypertensive rats. en-copyright= kn-copyright= en-aut-name=OmoteYoshio en-aut-sei=Omote en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TianFengFeng en-aut-sei=Tian en-aut-mei=FengFeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=KawaiHiromi en-aut-sei=Kawai en-aut-mei=Hiromi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KurataTomoko en-aut-sei=Kurata en-aut-mei=Tomoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci en-keyword=cerebral infarction kn-keyword=cerebral infarction en-keyword=cilostazol kn-keyword=cilostazol en-keyword=IGF-1R kn-keyword=IGF-1R en-keyword=oxidative stress kn-keyword=oxidative stress en-keyword=SHR-SP kn-keyword=SHR-SP END start-ver=1.4 cd-journal=joma no-vol=125 cd-vols= no-issue=2 article-no= start-page=159 end-page=162 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=20130801 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Guidelines for treatment of ischemic stroke kn-title=脳梗塞の治療ガイドライン en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name=出口健太郎 kn-aut-sei=出口 kn-aut-mei=健太郎 aut-affil-num=1 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name=阿部康二 kn-aut-sei=阿部 kn-aut-mei=康二 aut-affil-num=2 ORCID= affil-num=1 en-affil= kn-affil=岡山大学病院 神経内科 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科 神経内科学 END start-ver=1.4 cd-journal=joma no-vol=221 cd-vols= no-issue= article-no= start-page=47 end-page=55 dt-received= dt-revised= dt-accepted= dt-pub-year=2012 dt-pub=20120927 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Strong neuroprotection with a novel platinum nanoparticle against ischemic stroke- andtissue plasminogen activator-related brain damages in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Reactive oxygen species (ROS) are major exacerbation factor in acute ischemic stroke, and thrombolytic agent tissue plasminogen activator (tPA) may worsen motor function and cerebral infarcts. The platinum nanoparticle (nPt) is a novel ROS scavenger, and thus we examined the clinical and neuroprotective effects of nPt in ischemic mouse brains. Mice were subjected to transient middle cerebral artery occlusion (tMCAO) for 60 min and divided into the following four groups by intravenous administration upon reperfusion, vehicle, tPA, tPA + nPt, and nPt. At 48 h after tMCAO, motor function, infarct volume, immunohistochemical analyses of neurovascular unit (NVU), in vivo imaging of matrix metalloproteinase (MMP), and zymography for MMP-9 activity were examined. Superoxide anion generation at 2 h after tMCAO was also examined with hydroethidine (HEt). As a result, administration of tPA deteriorated the motor function and infarct volume as compared to vehicle. In vivo optical imaging of MMP showed strong fluorescent signals in affected regions of tMCAO groups. Immunohistochemical analyses revealed that tMCAO resulted in a minimal decrease of NAGO and occludin, but a great decrease of collagen IV and a remarkable increase of MMP-9. HEt stain showed increased ROS generation by tMCAO. All these results became pronounced with tPA administration, and were greatly reduced by nPt. The present study demonstrates that nPt treatment ameliorates neurological function and brain damage in acute cerebral infarction with neuroprotective effect on NVU and inactivation of MMP-9. The strong reduction of ROS production by nPt could account for these remarkable neurological and neuroprotective effects against ischemic stroke. en-copyright= kn-copyright= en-aut-name=TakamiyaM. en-aut-sei=Takamiya en-aut-mei=M. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=MiyamotoY. en-aut-sei=Miyamoto en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaT. en-aut-sei=Yamashita en-aut-mei=T. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=DeguchiK. en-aut-sei=Deguchi en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=OhtaY. en-aut-sei=Ohta en-aut-mei=Y. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=AbeK. en-aut-sei=Abe en-aut-mei=K. kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol affil-num=2 en-affil= kn-affil=Univ Tokyo, Grad Sch Frontier Sci, Dept Integrated Biosci affil-num=3 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Neurol affil-num=4 en-affil= kn-affil= affil-num=5 en-affil= kn-affil= affil-num=6 en-affil= kn-affil= en-keyword=platinum nanoparticle kn-keyword=platinum nanoparticle en-keyword=cerebral ischemia kn-keyword=cerebral ischemia en-keyword=free radical scavenger kn-keyword=free radical scavenger en-keyword=neuroprotection kn-keyword=neuroprotection en-keyword=matrix metalloproteinase-9 kn-keyword=matrix metalloproteinase-9 en-keyword=tissue plasminogen activator kn-keyword=tissue plasminogen activator END start-ver=1.4 cd-journal=joma no-vol=6 cd-vols= no-issue=8 article-no= start-page=1107 end-page=1114 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=20101116 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=In vivo imaging of autophagy in a mouse stroke model en-subtitle= kn-subtitle= en-abstract= kn-abstract=Recent studies have suggested that autophagy is involved in a neural death pathway following cerebral ischemia. In vivo detection of autophagy could be important for evaluating ischemic neural cell damage for human stroke patients. Using novel green fluorescent protein (GFP)-fused microtubule-associated protein 1 light chain 3 (LC3) transgenic (Tg) mice, in vivo imaging of autophagy was performed at 1, 3 and 6 d after 60 min transient middle cerebral artery occlusion (tMCAO). Ex vivo imaging of autophagy, testing of the autophagy inhibitor 3-methyladenine (3-MA), estern blot analysis, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and fluorescent analyses were performed on brain sections following tMCAO. In vivo fluorescent signals were detected above the ischemic hemisphere through the skull bone at 1, 3 and 6 d after tMCAO, with a peak at 1 d. Similar results were obtained with ex vivo fluorescence imaging. western blot analysis revealed maximum LC3-I and LC3-II expression at 1 d after tMCAO and fluorescence immunohistochemistry demonstrated that GFP-LC3-positive cells were primarily neuronal, not astroglial or microglial, cells. The number of GFP-LC3/TUNEL double-positive cells was greater in the peri-ischemic area than in the core. These results provided evidence of in vivo autophagy detection, with a peak at 1 d, in a live animal model following cerebral ischemia. This novel technique could be valuable for monitoring autophagic processes in vivo in live stroke patients, as well as for clarifying the detailed role of autophagy in the ischemic brain, as well as in other neurological diseases. en-copyright= kn-copyright= en-aut-name=TianFengFeng en-aut-sei=Tian en-aut-mei=FengFeng kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=OhtaYasuyuki en-aut-sei=Ohta en-aut-mei=Yasuyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=MorimotoNobutoshi en-aut-sei=Morimoto en-aut-mei=Nobutoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShangJingwei en-aut-sei=Shang en-aut-mei=Jingwei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=ZhangXuemei en-aut-sei=Zhang en-aut-mei=Xuemei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=LiuNing en-aut-sei=Liu en-aut-mei=Ning kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=IkedaYoshio en-aut-sei=Ikeda en-aut-mei=Yoshio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=MatsuuraTohru en-aut-sei=Matsuura en-aut-mei=Tohru kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= affil-num=1 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=2 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=3 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=4 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=5 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=6 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=7 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=8 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=9 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=10 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci affil-num=11 en-affil= kn-affil=Okayama Univ, Dept Neurol, Grad Sch Med Dent & Pharmaceut Sci en-keyword=autophagy kn-keyword=autophagy en-keyword=apoptosis kn-keyword=apoptosis en-keyword=GFP-LC3 Tg mice kn-keyword=GFP-LC3 Tg mice en-keyword=in vivo imaging kn-keyword=in vivo imaging en-keyword=tMCAO kn-keyword=tMCAO END start-ver=1.4 cd-journal=joma no-vol=122 cd-vols= no-issue=3 article-no= start-page=195 end-page=197 dt-received= dt-revised= dt-accepted= dt-pub-year=2010 dt-pub=20101201 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=Dissociation and protection of the neurovascular unit after thrombolysis and reperfusion in ischemic rat brain kn-title=ラット出血性梗塞モデルにおけるエダラボンのneurovascular unit保護効果 en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=YamashitaToru en-aut-sei=Yamashita en-aut-mei=Toru kn-aut-name=山下徹 kn-aut-sei=山下 kn-aut-mei=徹 aut-affil-num=1 ORCID= en-aut-name=KamiyaTatsushi en-aut-sei=Kamiya en-aut-mei=Tatsushi kn-aut-name=神谷達司 kn-aut-sei=神谷 kn-aut-mei=達司 aut-affil-num=2 ORCID= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name=出口健太郎 kn-aut-sei=出口 kn-aut-mei=健太郎 aut-affil-num=3 ORCID= en-aut-name=InabaToshiki en-aut-sei=Inaba en-aut-mei=Toshiki kn-aut-name=稲葉俊東 kn-aut-sei=稲葉 kn-aut-mei=俊東 aut-affil-num=4 ORCID= en-aut-name=ZhangHanzhe en-aut-sei=Zhang en-aut-mei=Hanzhe kn-aut-name=張漢哲 kn-aut-sei=張 kn-aut-mei=漢哲 aut-affil-num=5 ORCID= en-aut-name=ShangJingwei en-aut-sei=Shang en-aut-mei=Jingwei kn-aut-name=商敬偉 kn-aut-sei=商 kn-aut-mei=敬偉 aut-affil-num=6 ORCID= en-aut-name=MiyazakiKazunori en-aut-sei=Miyazaki en-aut-mei=Kazunori kn-aut-name=宮崎一徳 kn-aut-sei=宮崎 kn-aut-mei=一徳 aut-affil-num=7 ORCID= en-aut-name=OhtsukaAiji en-aut-sei=Ohtsuka en-aut-mei=Aiji kn-aut-name=大塚愛二 kn-aut-sei=大塚 kn-aut-mei=愛二 aut-affil-num=8 ORCID= en-aut-name=KatayamaYasuo en-aut-sei=Katayama en-aut-mei=Yasuo kn-aut-name=片山泰朗 kn-aut-sei=片山 kn-aut-mei=泰朗 aut-affil-num=9 ORCID= en-aut-name=AbeKoji en-aut-sei=Abe en-aut-mei=Koji kn-aut-name=阿部康二 kn-aut-sei=阿部 kn-aut-mei=康二 aut-affil-num=10 ORCID= affil-num=1 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経内科学 affil-num=2 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経内科学 affil-num=3 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経内科学 affil-num=4 en-affil= kn-affil=日本医科大学　第二内科 affil-num=5 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経内科学 affil-num=6 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経内科学 affil-num=7 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経内科学 affil-num=8 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　人体構成学 affil-num=9 en-affil= kn-affil=日本医科大学　第二内科 affil-num=10 en-affil= kn-affil=岡山大学大学院医歯薬学総合研究科　脳神経内科学 en-keyword=出血性梗塞 (hemorrhagic transformation) kn-keyword=出血性梗塞 (hemorrhagic transformation) en-keyword=tPA (tissue plasminogen activator) kn-keyword=tPA (tissue plasminogen activator) en-keyword=MMP-9 (matrix metalloproteinase-9) kn-keyword=MMP-9 (matrix metalloproteinase-9) en-keyword=フリーラジカル (free radical) kn-keyword=フリーラジカル (free radical) en-keyword=エダラボン (edaravone) kn-keyword=エダラボン (edaravone) END start-ver=1.4 cd-journal=joma no-vol= cd-vols= no-issue= article-no= start-page= end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2006 dt-pub=20060324 dt-online= en-article= kn-article= en-subject= kn-subject= en-title=組織再構築の足場としての多孔性ゼラチン-シロキサンハイブリッドの脳損傷部位への埋入 kn-title=Implantation of a new porous gelatin-siloxane hybrid into a brain lesion as a potential scaffold for tissue regeneration en-subtitle= kn-subtitle= en-abstract= kn-abstract= en-copyright= kn-copyright= en-aut-name=DeguchiKentaro en-aut-sei=Deguchi en-aut-mei=Kentaro kn-aut-name=出口健太郎 kn-aut-sei=出口 kn-aut-mei=健太郎 aut-affil-num=1 ORCID= affil-num=1 en-affil= kn-affil=岡山大学 END