... Japan Search for more papers by this author Norio Sakai Norio Sakai Division of Gene Regulation, Cancer Institute, Sapporo, Hokkaido, ... Japan Search for more papers by this author Norio Sakai Norio Sakai Division of Gene Regulation, Cancer Institute, Sapporo, Hokkaido, ...
Tópico(s): Advanced Fluorescence Microscopy Techniques
1997 - Springer Nature | The EMBO Journal
Hisato Iwata, Shinsuke Tanabe, Norio Sakai, Ryo Tatsukawa,
... their global transport and fateHisato Iwata, Shinsuke Tanabe, Norio Sakai, and Ryo TatsukawaCite this: Environ. Sci. Technol. 1993, ...
Tópico(s): Environmental Chemistry and Analysis
1993 - American Chemical Society | Environmental Science & Technology
Kazuo Sakai, Masayuki Nakamura, Shuichi Ueno, Akira Sano, Norio Sakai, Yasuhito Shirai, Naoaki Saito,
Enhancer/silencer activity of each allelic variant of the human serotonin transporter linked polymorphic region (5-HTTLPR) including newly found ones was measured in several cell lines including raphe-nucleus-derived RN46A. 5-HTTLR variants ligated in pGL-3 promoter vector increased luciferase activity in COS-7 cells and PC12 cells, where no significant differences among the variants were observed. In RN46 cell lines, however, 5-HTTLPRs decreased luciferase activity to 80–30%, acting as silencers ...
Tópico(s): Receptor Mechanisms and Signaling
2002 - Elsevier BV | Neuroscience Letters
Toshiaki Sasada, Fuminori Kobayashi, Norio Sakai, Takeo Konakahara,
We have developed a ZnCl2-catalyzed three-component coupling reaction involving a variety of functionalized enamines, triethyl orthoformate, and ammonium acetate, which leads to the production of 4,5-disubstituted pyrimidine derivatives in a single step. The procedure can be successfully applied to the efficient synthesis of mono- and disubstituted pyrimidine derivatives, using methyl ketone derivatives instead of enamines.
Tópico(s): Catalytic C–H Functionalization Methods
2009 - American Chemical Society | Organic Letters
Ken Araya, Norio Sakai, Ikuko Mohri, Kuriko Kagitani‐Shimono, Takeshi Okinaga, Yoshiko Hashii, Hideaki Ohta, Itsuko Nakamichi, Katsuyuki Aozasa, Masako Taniike, Keiichi Ozono,
The efficacy of hematopoietic stem cell transplantation (HSCT) for Hunter disease (deficiency of iduronate-2-sulfatase, IDS) remains unclear. We treated a 6-year-old male suffering from a severe type of Hunter disease with cord blood stem cell transplantation (CBSCT); however, he died at 10 months post-therapy due to a laryngeal post-transplantation lymphoproliferative disorder. During the follow-up period after CBSCT, his hyperactivity, estimated mental age, and brain MR findings had not improved. ...
Tópico(s): Neonatal Health and Biochemistry
2009 - Elsevier BV | Molecular Genetics and Metabolism
Mariko Nobukuni, Hideki Mochizuki, Satoshi Okada, Nobuhisa Kameyama, Anna Tanaka, Hikaru Yamamoto, Taku Amano, Takahiro Seki, Norio Sakai,
We investigated the effects of brefeldin A and ilimaquinone, inhibitors of membrane trafficking, using serotonin transporter (SERT)–expressing COS-7 cells. Both drugs significantly inhibited the serotonin uptake activity of SERT and caused SERT to be retained in the endoplasmic reticulum (ER), indicating that membrane trafficking is an important factor for SERT functional regulation. In agreement with previous reports, a C-terminal–deletion mutant of SERT (SERTΔCT) mostly localized to the ER and completely ...
Tópico(s): Neuroscience and Neuropharmacology Research
2009 - Elsevier BV | Journal of Pharmacological Sciences
We reported the basic concept of the pathology of leukodystrophy with emphasis on Krabbe disease. First, the normal process of myelination and the pathology of demyelination will be described, emphasizing the course inducing neuro-inflammation in its progression. After classifying metabolic leukodystrophy, the features of Krabbe disease (globoid-cell leukodystrophy) are explained as well as molecular cloning and mutation analysis of the galactocerebrosidase (GALC) gene. Finally, the experience of ...
Tópico(s): Carbohydrate Chemistry and Synthesis
2009 - Elsevier BV | Brain and Development
Takanobu Otomo, Takeshi Muramatsu, Tohru Yorifuji, Torayuki Okuyama, Hiroki Nakabayashi, Toshiyuki Fukao, Toshihiro Ohura, Makoto Yoshino, Akemi Tanaka, Nobuhiko Okamoto, Koji Inui, Keiichi Ozono, Norio Sakai,
Mucolipidosis (ML) II alpha/beta and III alpha/beta are autosomal recessive diseases caused by a deficiency of alpha and/or beta subunits of the enzyme N-acetylglucosamine-1-phosphotransferase, which is encoded by the GNPTAB gene. We analyzed the GNPTAB gene in 25 ML II and 15 ML III Japanese patients. In most ML II patients, the clinical conditions 'stand alone', 'walk without support' and 'speak single words' were impaired; however, the frequency of 'heart murmur', 'inguinal hernia' and 'hepatomegaly ...
Tópico(s): Cellular transport and secretion
2009 - Springer Nature | Journal of Human Genetics
Takanobu Otomo, Katsumi Higaki, Eiji Nanba, Keiichi Ozono, Norio Sakai,
Mucolipidosis II and III are progressive lysosomal storage disorders caused by a deficiency of N-acetylglucosamine-1-phosphotransferase, leading to massive accumulation of undigested substrates in lysosomes (inclusion bodies) in skin fibroblast. In this study, we demonstrated accumulation of autolysosomes and increased levels of p62 and ubiquitin proteins in cultured fibroblasts. These autophagic elevations were milder in mucolipidosis III compared with mucolipidosis II. Mitochondrial structure was ...
Tópico(s): Lysosomal Storage Disorders Research
2009 - Elsevier BV | Molecular Genetics and Metabolism
Norio Sakai, Junichi Asano, Yuki Kawada, Takeo Konakahara,
Abstract We have developed a Me 3 SiCl‐promoted coupling reaction of aryl‐ and alkylzinc compounds, in‐situ generated either by transmetalation of the corresponding organometallic reagents or by insertion of zinc metal into organic halides, with several N,O‐acetals, which leads to the preparation of a variety of natural and non‐natural amino acid derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Tópico(s): Catalytic Cross-Coupling Reactions
2009 - Wiley | European Journal of Organic Chemistry
Norio Sakai, Kohei Moritaka, Takeo Konakahara,
Abstract We have demonstrated a facile and direct synthesis of sulfide derivatives using acetals and ketals, derived from aromatic/conjugated aldehydes and aromatic ketones, with disulfides and the InBr 3 –Et 3 SiH reducing system. We also succeeded in developing an unprecedented one‐pot preparation of an aliphatic sulfide from a disulfide and an aliphatic acetal. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Tópico(s): Synthesis and Catalytic Reactions
2009 - Wiley | European Journal of Organic Chemistry
Norihiro Sato, K Sawada, M Kannonji, Takashi Tarumi, Norio Sakai, Masahiro Ieko, S Sakurama, Shunsaku Nakagawa, T Yasukouchi, SB Krantz,
Abstract To facilitate the investigation of the direct interaction between hematopoietic progenitors and colony-stimulating factors, we have developed a method to purify human marrow progenitor cells. Using density centrifugation, negative panning with concanavalin A coated plates, positive selection of CD34-positive cells with immunomagnetic microspheres, overnight adherence to a plastic dish, negative selection with a panel of monoclonal antibodies, and density centrifugation, human marrow progenitor ...
Tópico(s): Immunotherapy and Immune Responses
1991 - Elsevier BV | Blood
Takashi Muramatsu, Norio Sakai, Itaru Yanagihara, Minoru Yamada, T Nishigaki, Chikara Kokubu, Hiroko Tsukamoto, Makoto Ito, Koji Inui,
Abstract Farber disease is a rare lysosomal storage disease, characterized by the accumulation of ceramide in tissues due to acid ceramidase deficiency. Here we report the identification of three novel mutations in the acid ceramidase gene from two Japanese patients. Patient 1 showed joint problems at around 10 months of age and the patient is now emaciated, with multiple nodules and mild neurological problems at 10 years of age. Patient 2 had consanguineous parents and showed joint contractures ...
Tópico(s): Lysosomal Storage Disorders Research
2002 - Springer Science+Business Media | Journal of Inherited Metabolic Disease
Norio Sakai, Maki Hirasawa, Toshihiro Hamajima, Takeo Konakahara,
The copper(II) triflate- and hafnium(IV) triflate-catalyzed aminomethylation of indole (2) with an N-silyl-N,O-acetal 1 containing a trichloromethyl group provides the primary amine derivative (3a) in modest yield. When 1 equiv of trimethylchlorosilane (TMSCl) was added to the reaction mixture, the reaction proceeded smoothly, and the yield of 3a was dramatically improved (>90%). The use of this catalytic system permitted the introduction of an aminomethyl group onto indoles 2a-h bearing a variety of ...
Tópico(s): Asymmetric Hydrogenation and Catalysis
2002 - American Chemical Society | The Journal of Organic Chemistry
Motohiro Akagi, Koji Inui, Hiroko Tsukamoto, Norio Sakai, Takashi Muramatsu, Minoru Yamada, Kouzi Matsuzaki, Yu‐ichi Goto, Ikuya Nonaka, Shintaro Okada,
A T-to-G transition at nucleotide 9176 (T9176G) in the mitochondrial adenosine triphosphate 6 gene (MTATP6) was detected in two siblings with Leigh syndrome. Heteroplasmy was observed in the mother's leukocytes. The T9176G mutation changes a highly conserved leucine residue to an arginine in subunit 6 of ATPase and is maternally inherited like mutations in the other mitochondrial genes. Another mutation in the same codon (T9176C) has been previously reported in Leigh syndrome. This gives strong support ...
Tópico(s): ATP Synthase and ATPases Research
2002 - Elsevier BV | Neuromuscular Disorders
Naoki Irie, Norio Sakai, Takehiko Ueyama, Taketoshi Kajimoto, Yasuhito Shirai, Naoaki Saito,
RNA interference (RNAi), the targeted mRNA degradation induced by double-stranded RNA (dsRNA), is a powerful tool for analyzing gene function in many organisms. Recently, it has been shown that RNAi is also applicable to cultured mammalian cells by using short interfering RNA (siRNA) [Nature 411 (2001) 494]. To examine whether this siRNA method is useful for analyzing the subtype-specific functions of protein kinase C (PKC), we first prepared siRNAs which target human alphaPKC and human deltaPKC and applied ...
Tópico(s): MicroRNA in disease regulation
2002 - Elsevier BV | Biochemical and Biophysical Research Communications
Samuel S. Newton, Johannes Thome, Tanya L. Wallace, Yukihikko Shirayama, Lee Schlesinger, Norio Sakai, Jingshan Chen, Rachael L. Neve, Eric J. Nestler, Ronald S. Duman,
The cAMP response element-binding protein (CREB) is a critical integrator of neural plasticity that is responsive in a brain region-specific manner to a variety of environmental and pharmacological stimuli, including widely prescribed antidepressant medications. We developed inducible transgenic lines of mice that express either CREB or a dominant-negative mutant of CREB (mCREB) in forebrain regions and used these mice to determine the functional significance of this transcription factor in the learned ...
Tópico(s): Neuropeptides and Animal Physiology
2002 - Society for Neuroscience | Journal of Neuroscience
Takahiro Seki, Hiroaki Matsubayashi, Taku Amano, Kazuhiro Kitada, Tadao Serikawa, Norio Sakai, Masashi Sasa,
The tremor rat (tm/tm) is a genetic model of epilepsy that exhibits absence-like seizures characterized by 5–7 Hz spike–wave-like complexes in cortical and hippocampal electroencephalograms (EEGs). A deletion of the aspartoacylase (ASPA) gene and resultant high levels of N-acetyl-aspartate (NAA) in the brain have been found in tremor rats. We attempted to determine whether gene transfer of ASPA inhibited absence-like seizures in tremor rats using recombinant adenovirus. Recombinant adenovirus (5×107 ...
Tópico(s): Neurological disorders and treatments
2002 - Elsevier BV | Neuroscience Letters
Norio Sakai, Johannes Thome, Samuel S. Newton, Jingshan Chen, Max B. Kelz, Cathy Steffen, Eric J. Nestler, Ronald S. Duman,
To investigate the role of cAMP response element-binding protein (CREB) in the adaptive responses to psychotropic drugs, we have developed inducible, brain region-specific CREB transgenic mice using the tetracycline-regulated gene expression system. The tetracycline transactivator (tTA) was placed under the control of 1.8-kilobase neuron-specific enolase (NSE) promoter for this purpose. Different patterns of CREB overexpression were found in striatum, nucleus accumbens, and cingulate cortex in different ...
Tópico(s): Neuropeptides and Animal Physiology
2002 - American Society for Pharmacology and Experimental Therapeutics | Molecular Pharmacology
Norio Sakai, Toshihiro Hamajima, Takeo Konakahara,
A catalytic amount of copper(II) trifluoromethanesulfonate (Cu(OTf)2) in the presence of trimethylchlorosilane (TMSCl) effectively promoted the aminomethylation of indoles bearing a variety of functional groups with a N-silyl-N,O-acetal in good to excellent yields.
Tópico(s): Chemical Synthesis and Analysis
2002 - Elsevier BV | Tetrahedron Letters
Axel Goerke, Norio Sakai, Elisabeth Gutjahr, Walter A. Schlapkohl, J. Frederic Mushinski, Hermann Haller, Walter Kölch, Naoaki Saito, Harald Mischak,
Protein kinase C, a multigene family of phospholipid-dependent and diacylglycerol-activated Ser/Thr protein kinases, is a key component in many signal transduction pathways. The kinase activity was thought to be essential for a plethora of biological processes attributed to these enzymes. Here we show that at least one protein kinase C function, the induction of apoptosis by protein kinase Cδ, is independent of the kinase activity. Stimulation of green fluorescent protein-protein kinase Cδ fusion ...
Tópico(s): NF-κB Signaling Pathways
2002 - Elsevier BV | Journal of Biological Chemistry
Noriko Kodama, Kiyoshi Komuta, Norio Sakai, Hiroaki Nanba,
Natural killer (NK) cells are directly cytotoxic for tumor cells and play a primary role in regulating immune responses. We monitored levels of NK cell cytotoxic activity in cancer patients receiving D-Fraction extracted from maitake mushrooms (Grifola frondosa). Elevated levels of cytotoxic activity were maintained for one year. To elucidate the mechanisms underlying long-term activation of NK cells during treatment with D-Fraction, we examined tumor volume and levels of IFN-gamma and TNF-alpha in ...
Tópico(s): Polysaccharides and Plant Cell Walls
2002 - Pharmaceutical Society of Japan | Biological and Pharmaceutical Bulletin
Kaori Kashiwagi, Yasuhito Shirai, Masamitsu Kuriyama, Norio Sakai, Naoaki Saito,
The molecular mechanisms by which arachidonic acid (AA) and ceramide elicit translocation of protein kinase C (PKC) were investigated. Ceramide translocated εPKC from the cytoplasm to the Golgi complex, but with a mechanism distinct from that utilized by AA. Using fluorescence recovery after photobleaching, we showed that, upon treatment with AA, εPKC was tightly associated with the Golgi complex; ceramide elicited an accumulation of εPKC which was exchangeable with the cytoplasm. Stimulation with ...
Tópico(s): Cellular transport and secretion
2002 - Elsevier BV | Journal of Biological Chemistry
Y. Eto, Toya Ohashi, Yasunori Utsunomiya, Masazumi Fujiwara, Akari Mizuno, Koji Inui, Norio Sakai, Teruo Kitagawa, Yoshiyuki Suzuki, Satoshi Mochizuki, Makio Kawakami, Tatsuo Hosoya, Misao Ōwada, Hitoshi Sakuraba, Hirohisa Saito,
Summary Fabry Disease (α‐galactosidase A deficiency) is an X‐linked hereditary disorder leading to the pathological accumulation of globotriaosylceramide (GL‐3) in lysosomes, particularly in the vascular endothelium of the kidney, heart and brain. We report the results of an open‐label phase 2 study that was undertaken to evaluate whether ethnic differences exist that would affect agalsidase beta (Fabrazyme) treatment of Fabry patients in the Japanese population, relative to safety and efficacy. The ...
Tópico(s): Trypanosoma species research and implications
2003 - Springer Science+Business Media | Journal of Inherited Metabolic Disease
Chikara Kokubu, Bettina Wilm, Tomoko Kokubu, Matthias Wahl, Isabel Rodrigo, Norio Sakai, Fabio Santagati, Yoshihide Hayashizaki, Misao Suzuki, Ken–ichi Yamamura, Kuniya Abe, Kenji Imai,
Previous studies have indicated that the Undulated short-tail deletion mutation in mouse Pax1 (Pax1(Un-s)) not only ablates Pax1, but also disturbs a gene or genes nearby Pax1. However, which gene(s) is involved and how the Pax1(Un-s) phenotype is confined to the Pax1-positive tissues remain unknown. In the present study, we determined the Pax1(Un-s) deletion interval to be 125 kb and characterized genes around Pax1. We show that the Pax1(Un-s) mutation affects four physically linked genes within ...
Tópico(s): Genomics and Chromatin Dynamics
2003 - Oxford University Press | Genetics
Tsuguka Shiwa, Taku Amano, Hiroaki Matsubayashi, Takahiro Seki, Masashi Sasa, Norio Sakai,
To investigate the effect of cis-N-[4-[4-(1,2-benz-isozole-3-yl)-1-piperazinyl]butyl] cyclohexane-1,2-dicarboximide hydrochloride (perospirone), a novel antipsychotic agent with high affinities for D2/5-HT2 receptors, on the rat dorsal raphe (DR) neurons, an electrophysiological study was performed using the tight-seal whole-cell patch-clamp technique. Applications of perospirone at the concentration between 10−9 and 10−5 M hyperpolarized the membrane potential and inhibited spontaneous action potentials ...
Tópico(s): Pharmacological Receptor Mechanisms and Effects
2003 - Elsevier BV | Journal of Pharmacological Sciences
Norio Sakai, Maki Hirasawa, Takeo Konakahara,
The use of a novel InBr3–Et3N reagent system to promote addition reactions of 1-alkynes not only with a variety of aromatic or bulky aliphatic aldehydes but also with N,O-acetals is described. The corresponding propargylic alcohols or amines are produced in good to excellent yields.
Tópico(s): Chemical Synthesis and Analysis
2003 - Elsevier BV | Tetrahedron Letters
Hisato Iwata, Shinsuke Tanabe, Mari Aramoto, Norio Sakai, Ryo Tatsukawa,
Three surface sediments and two sediment cores were collected from the Gulf of Alaska, Bering Sea and Chukchi Sea, and analysed for persistent organochlorines (OCs). The geographical distributions of OCs showed different patterns according to their physicochemical properties. The concentrations of HCHs and HCB revealed rather uniform distribution, suggesting their more transportable nature in long-range atmospheric transport. On the other hand, DDTs and PCBs were predicted to be less transportable ...
Tópico(s): Marine and coastal ecosystems
1994 - Elsevier BV | Marine Pollution Bulletin
Norio Sakai, Koji Inui, Noriko Fujii, H. Fukushima, Junji Nishimoto, Itaru Yanagihara, Yuji Isegawa, Akihiro Iwamatsu, S Okada,
Human galactocerebrosidase, the enzyme deficient in Krabbe disease, was purified, through several hydrophobic column steps and gel filtration, 22,650-fold from human lymphocytes. Using information on its N-terminal and internal amino acid sequences, and the polymerase chain reaction method, we cloned a full-length cDNA for the enzyme. The deduced amino acid sequence matched all amino acid sequences determined. The 3780 nucleotide sequence included 2007 nucleotides which encoded a single chain peptide ...
Tópico(s): Trypanosoma species research and implications
1994 - Elsevier BV | Biochemical and Biophysical Research Communications
Norio Sakai, Yoshifumi Ogiso, Hisakazu Fujita, Hidemichi Watari, Takao Koike, Noboru Kuzumaki,
Recent extensive work on apoptosis has begun to reveal its molecular mechanisms. Several genes that regulate apoptosis have been identified. Among them, the BCL2 gene is considered to be an important gene that inhibits apoptosis. However, there must be other genes, yet to be identified, which suppress apoptosis. It has been suggested that the activation of RAS function by BCR-ABL fusion protein in chronic myelogenous leukemia may be an important mechanism in the BCR-ABL mediated transformation. ...
Tópico(s): Click Chemistry and Applications
1994 - Elsevier BV | Experimental Cell Research