A5113535904- Genetic Neurodegenerative Diseases
- Amyotrophic Lateral Sclerosis Research
- RNA Research and Splicing
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- Ion channel regulation and function
- Synthetic Organic Chemistry Methods
- Parkinson's Disease Mechanisms and Treatments
- Synthesis of Organic Compounds
- Receptor Mechanisms and Signaling
- Ion Transport and Channel Regulation
- Neurological disorders and treatments
- Neurological diseases and metabolism
- RNA modifications and cancer
- Cervical Cancer and HPV Research
- Cancer therapeutics and mechanisms
- Axial and Atropisomeric Chirality Synthesis
- Pancreatic function and diabetes
- Biochemical and Molecular Research
- Oxidative Organic Chemistry Reactions
- Medical Imaging and Pathology Studies
- Peptidase Inhibition and Analysis
- Synthesis and Reactions of Organic Compounds
- Ubiquitin and proteasome pathways
- Organic and Inorganic Chemical Reactions
Tokyo Medical and Dental University
2007-2024
Institute of Science Tokyo
2024
Institute of Neurological Sciences
2024
National Center of Neurology and Psychiatry
1991-2023
Kanazawa Medical University
2015
Municipal Tsuruga Hospital
2015
Nitobe Memorial Nakano General Hospital
2011-2012
The University of Texas MD Anderson Cancer Center
2010
The University of Tokyo
1985-2001
Gifu Municipal Hospital
2000
Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disorder caused by CAG repeat expansions within the voltage-gated calcium (Ca V ) 2.1 channel gene. It remains controversial whether mutation exerts neurotoxicity changing function of Ca or through gain-of-function mechanism associated with accumulation expanded polyglutamine protein. We generated three strains knockin (KI) mice carrying normal, expanded, hyperexpanded tracts in Cacna1a locus. The expressing ( Sca6 84Q developed...
Spinocerebellar ataxia type 31 ( SCA31 ) is an autosomal‐dominant cerebellar showing a Purkinje cell PC )‐predominant neurodegeneration in humans. The mutation complex penta‐nucleotide repeat containing TGGAA n , TAGAA TAAAA and TAGAATAAAA inserted intron shared by two different genes BEAN1 TK2 located the long arm of human chromosome 16. Previous studies have shown that critical component pathogenesis while three other repeats, also present normal Japanese, are not essential. Importantly,...
Abnormal expansions of GGGGCC repeat sequence in the noncoding region C9orf72 gene is most common cause familial amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). The expanded translated into dipeptide proteins (DPRs) by noncanonical repeat-associated non-AUG (RAN) translation. Since DPRs play central roles pathogenesis C9-ALS/FTD, we here investigate regulatory mechanisms RAN translation, focusing on effects RNA-binding (RBPs) targeting RNAs. Using C9-ALS/FTD model...
RNA guanine (G)-quadruplexes (rG4) are unique noncanonical structures composed of stacked quadruplexes that play diverse roles in regulating gene expression, from transcription to protein synthesis. This study proposes a new splice-switching therapy using G-quadruplex-inducing antisense oligonucleotides (G-ASOs) reinstate dystrophin expression Duchenne muscular dystrophy (DMD) models. G-ASOs consist two functionally independent domains enable the formation RNA/DNA hetero-G-quadruplex (hG4)...
Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disease caused by a small polyglutamine (polyQ) expansion (control: 4-20Q; SCA6: 20-33Q) in the carboxyl(C)-terminal cytoplasmic domain of alpha(1A) voltage-dependent calcium channel (Ca(v)2.1). Although 75-85-kDa Ca(v)2.1 C-terminal fragment (CTF) toxic cultured cells, its existence human brains and role SCA6 pathogenesis remains unknown. Here, we investigated whether polyQ alters expression pattern...
Abnormal expansions of GGGGCC repeat sequence in the noncoding region C9orf72 gene is most common cause familial amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). The expanded translated into dipeptide proteins (DPRs) by noncanonical repeat-associated non-AUG (RAN) translation. Since DPRs play central roles pathogenesis C9-ALS/FTD, we here investigate regulatory mechanisms RAN translation, focusing on effects RNA-binding (RBPs) targeting RNAs. Using C9-ALS/FTD model...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective reactions. XVII. Absolute structure-cytotoxic activity relationships of steganacin congeners and analogsKiyoshi Tomioka, Tsuneo Ishiguro, Hidemichi Mizuguchi, Nobuyasu Komeshima, Kenji Koga, Shigeru Tsukagoshi, Takashi Tsuruo, Tazuko Tashiro, Seiichi Tanida, Toyokazu KishiCite this: J. Med. Chem. 1991, 34, 1, 54–57Publication Date (Print):January 1991Publication History Published online1 May 2002Published inissue 1 January...
Spinocerebellar ataxia type 6 (SCA6) is an autosomal‐dominant neurodegenerative disorder caused by a small expansion of tri‐nucleotide (CAG) repeat encoding polyglutamine (polyQ) in the gene for α 1A voltage‐dependent calcium channel (Ca v 2.1). Thus, this disease one nine disorders called polyQ diseases. The Purkinje cell predominant neuronal loss characteristic neuropathology SCA6, and 75‐kDa carboxy‐terminal fragment (CTF) Ca 2.1 containing polyQ, which remains soluble normal brains,...
Abstract Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by autonomic nervous dysfunction and cerebellar ataxia or parkinsonism. Recently, expanded GAA repeats (≥250 repeat units) in intron 1 of FGF14 have been shown to be responsible for spinocerebellar type 27B (SCA27B), late-onset with an autosomal dominant inheritance. Patients SCA27B may also exhibit dysfunction, potentially overlapping the clinical presentations MSA patients. In this study, explore possible...
To date, there are few reports on gene products contributing to colon cancer progression. We used a trap comprised of an enhanced retroviral mutagen (ERM) cassette that includes tetracycline-responsive promoter upstream haemagglutinin (HA) tag and splice donor site. Integration the ERM within endogenous yields tetracycline-regulated HA-tagged transcript. transduced RKO cells expressing tetracycline trans-activator-off with ERM-encoding retrovirus screened for migration. One clone showed...
The human α1A voltage-dependent calcium channel (Cav2.1) is a pore-forming essential subunit embedded in the plasma membrane. Its cytoplasmic carboxyl(C)-tail contains small poly-glutamine (Q) tract, whose length normally 4∼19 Q, but when expanded up to 20∼33Q, tract causes an autosomal-dominant neurodegenerative disorder, spinocerebellar ataxia type 6 (SCA6). A recent study has shown that 75-kDa C-terminal fragment (CTF) containing polyQ remains soluble normal brains, becomes insoluble...
We attempted to purify a digitalislike factor from human urine. On the assumption that natural ligand for digitalis receptor should be searched on basis of effects intact cells, we used an inhibitory effect binding [3H]ouabain erythrocytes determine activity. A highly polar displacing activity was obtained by combination chromatographic procedures including reverse-phase high performance liquid chromatography. Urine-derived activity, competitive inhibitor ouabain erythrocytes, acted...
We were able to purify two distinct sodium pump inhibitors homogeneity from human urine based on [3H]ouabain-displacing activity intact erythrocytes. The polar and less compounds eluted off the C18 reverse-phase column with 18% 31% acetonitrile, respectively. compound cross-reacted very weakly specific antidigoxin antibody lacked a characteristic ultraviolet absorption peak between 190 300 nm. showed prominent digoxinlike immunoreactivity had an spectrum similar that of digoxin. examined...
The late prognosis after repair of an abdominal aortic aneurysm (AAA) may be affected by atherosclerosis, which involves various organs including the aorta.The influence organ dysfunction and atherosclerosis on long-term survival 338 consecutive patients undergoing successful elective AAA between 1980 1997 was analysed using Cox hazards model. Survival rate compared with that 349 revascularization for aortoiliac occlusive disease (AIOD) during same interval.Renal a previous history...
The alpha radioactive components in the Hemp-palm of Bontenchiku were determined with emphasis on measurement low-level 237Np by alpha-ray spectrometry after chemical separation. is a kind fishing gear for long-line used Fifth Fukuryu-Maru (Lucky Dragon). This was exposed to fallout from second thermonuclear test explosion (Bravo) at Bikini Atoll March 1954. content sample be 11.5 +/- 0.8 mBq g(-1), an activity ratio 237Np:239,240Pu and atom 237Np:239Pu estimated (2.2 0.2) x 10(-3) 0.42...