Yoshimura T

References (10)

Title : Follow-up of Clinical Symptoms and Blood Concentration in Donepezil Overdose -
Author(s) : Mori K , Hirose T , Matsumura T , Yoshimura T
Ref : Prim Care Companion CNS Disord , 25 : , 2023
PubMedID: 37788804

Title : Protein-anchoring strategy for delivering acetylcholinesterase to the neuromuscular junction - Ito_2012_Mol.Ther_20_1384
Author(s) : Ito M , Suzuki Y , Okada T , Fukudome T , Yoshimura T , Masuda A , Takeda S , Krejci E , Ohno K
Ref : Mol Ther , 20 :1384 , 2012
Abstract : Acetylcholinesterase (AChE) at the neuromuscular junction (NMJ) is anchored to the synaptic basal lamina via a triple helical collagen Q (ColQ). Congenital defects of ColQ cause endplate AChE deficiency and myasthenic syndrome. A single intravenous administration of adeno-associated virus serotype 8 (AAV8)-COLQ to Colq(-/-) mice recovered motor functions, synaptic transmission, as well as the morphology of the NMJ. ColQ-tailed AChE was specifically anchored to NMJ and its amount was restored to 89% of the wild type. We next characterized the molecular basis of this efficient recovery. We first confirmed that ColQ-tailed AChE can be specifically targeted to NMJ by an in vitro overlay assay in Colq(-/-) mice muscle sections. We then injected AAV1-COLQ-IRES-EGFP into the left tibialis anterior and detected AChE in noninjected limbs. Furthermore, the in vivo injection of recombinant ColQ-tailed AChE protein complex into the gluteus maximus muscle of Colq(-/-) mice led to accumulation of AChE in noninjected forelimbs. We demonstrated for the first time in vivo that the ColQ protein contains a tissue-targeting signal that is sufficient for anchoring itself to the NMJ. We propose that the protein-anchoring strategy is potentially applicable to a broad spectrum of diseases affecting extracellular matrix molecules.
ESTHER : Ito_2012_Mol.Ther_20_1384
PubMedSearch : Ito_2012_Mol.Ther_20_1384
PubMedID: 22371845

Title : [Histochemical findings of and fine structural changes in motor endplates in diseases with neuromuscular transmission abnormalities] - Yoshimura_2011_Brain.Nerve_63_719
Author(s) : Yoshimura T , Motomura M , Tsujihata M
Ref : Brain Nerve , 63 :719 , 2011
Abstract : We herein review the histochemical findings and fine structural changes of motor endplates associated with diseases causing neuromuscular transmission abnormalities. In anti-acetylcholine receptor (AChR) antibody-positive myasthenia gravis (MG), type 2 fiber atrophy is observed, and the motor endplates show a reduction in the nerve terminal area, simplification of the postsynaptic membrane, decreased number of acetylcholine receptors, and deposition of immune complexes. In anti-MuSK antibody-positive MG, the fine structure shows a decrease in the postsynaptic membrane length, but the secondary synaptic cleft is preserved. There is no decrease in the number of AChRs, and there are no deposits of immune complexes at the motor endplates. Patients with Lambert-Eaton myasthenic syndrome show type 2 fiber atrophy, their motor endplates show a decrease in both the mean postsynaptic area and postsynaptic membrane length in the brachial biceps muscle. Congenital myasthenic syndrome with episodic apnea is characterized only by small-sized synaptic vesicles; the postsynaptic area is preserved. In subjects with congenital myasthenic syndrome with acetylcholinesterase deficiency, quantitative electron microscopy reveals a significant decrease in the nerve terminal size and presynaptic membrane length; further, the Schwann cell processes extend into the primary synaptic cleft, and partially or completely occlude the presynaptic membrane. The postsynaptic folds are degenerated, and associated with pinocytotic vesicles and labyrinthine membranous networks. Patients with slow-channel congenital myasthenia syndrome show type 1 fiber predominance, and their junctional folds are typically degenerated with widened synaptic space and loss of AChRs. Patients with AChR deficiency syndrome caused by recessive mutations in AChR subunits also show type 1 fiber predominance, and while most junctional folds are normal, some are simplified and have smaller than normal endplates. Rapsin and MuSK mutations cause type 1 fiber predominance, and the small postsynaptic area is associated with AChR decrease.
ESTHER : Yoshimura_2011_Brain.Nerve_63_719
PubMedSearch : Yoshimura_2011_Brain.Nerve_63_719
PubMedID: 21747142

Title : Investigation of the metabolism of rufinamide and its interaction with valproate - Williams_2011_Drug.Metab.Lett_5_280
Author(s) : Williams ET , Carlson JE , Lai WG , Wong YN , Yoshimura T , Critchley DJ , Narurkar M
Ref : Drug Metab Lett , 5 :280 , 2011
Abstract : Rufinamide was evaluated in vitro to determine which enzyme(s) are responsible for rufinamide hydrolysis and whether valproate, one of its metabolites (valproyl-CoA), and/or the rufinamide hydrolysis product (CGP 47292) could inhibit hydrolysis. Rufinamide hydrolysis was mediated primarily by human carboxylesterase (hCE) 1 and was nonsaturable up to 500 muM. Two-thirds of rufinamide hydrolysis was estimated to occur in human microsomes and one-third in cytosol. Valproate was a selective inhibitor for hCE1 compared to hCE2 and inhibition had a greater impact on rufinamide hydrolysis in microsomes than in cytosol. Valproyl-CoA caused similar inhibition of rufinamide hydrolysis in both microsomes and cytosol. Carboxylesterases were not significantly inhibited by CGP 47292. Inhibition of in vitro rufinamide hydrolysis by valproate could offer an explanation for the observed in vivo drug-drug interaction between the two antiepileptic drugs.
ESTHER : Williams_2011_Drug.Metab.Lett_5_280
PubMedSearch : Williams_2011_Drug.Metab.Lett_5_280
PubMedID: 22022867

Title : Comparative genome analysis of Lactobacillus reuteri and Lactobacillus fermentum reveal a genomic island for reuterin and cobalamin production - Morita_2008_DNA.Res_15_151
Author(s) : Morita H , Toh H , Fukuda S , Horikawa H , Oshima K , Suzuki T , Murakami M , Hisamatsu S , Kato Y , Takizawa T , Fukuoka H , Yoshimura T , Itoh K , O'Sullivan DJ , McKay LL , Ohno H , Kikuchi J , Masaoka T , Hattori M
Ref : DNA Research , 15 :151 , 2008
Abstract : Lactobacillus reuteri is a heterofermentative lactic acid bacterium that naturally inhabits the gut of humans and other animals. The probiotic effects of L. reuteri have been proposed to be largely associated with the production of the broad-spectrum antimicrobial compound reuterin during anaerobic metabolism of glycerol. We determined the complete genome sequences of the reuterin-producing L. reuteri JCM 1112(T) and its closely related species Lactobacillus fermentum IFO 3956. Both are in the same phylogenetic group within the genus Lactobacillus. Comparative genome analysis revealed that L. reuteri JCM 1112(T) has a unique cluster of 58 genes for the biosynthesis of reuterin and cobalamin (vitamin B(12)). The 58-gene cluster has a lower GC content and is apparently inserted into the conserved region, suggesting that the cluster represents a genomic island acquired from an anomalous source. Two-dimensional nuclear magnetic resonance (2D-NMR) with (13)C(3)-glycerol demonstrated that L. reuteri JCM 1112(T) could convert glycerol to reuterin in vivo, substantiating the potential of L. reuteri JCM 1112(T) to produce reuterin in the intestine. Given that glycerol is shown to be naturally present in feces, the acquired ability to produce reuterin and cobalamin is an adaptive evolutionary response that likely contributes to the probiotic properties of L. reuteri.
ESTHER : Morita_2008_DNA.Res_15_151
PubMedSearch : Morita_2008_DNA.Res_15_151
PubMedID: 18487258
Gene_locus related to this paper: lacfe-c0wz89 , lacre-a5vi88 , lacre-b3xl59 , lacre-b3xl60 , lacre-b3xlh0 , lacre-b3xps7 , lacre-q4jle7 , lacre-q4jlf2 , lacre-q4jll5 , lacre-q6wu85 , lacrj-b2g622

Title : A novel lipolytic enzyme, YcsK (LipC), located in the spore coat of Bacillus subtilis, is involved in spore germination - Masayama_2007_J.Bacteriol_189_2369
Author(s) : Masayama A , Kuwana R , Takamatsu H , Hemmi H , Yoshimura T , Watabe K , Moriyama R
Ref : Journal of Bacteriology , 189 :2369 , 2007
Abstract : The predicted amino acid sequence of Bacillus subtilis ycsK exhibits similarity to the GDSL family of lipolytic enzymes. Northern blot analysis showed that ycsK mRNA was first detected from 4 h after the onset of sporulation and that transcription of ycsK was dependent on SigK and GerE. The fluorescence of the YcsK-green fluorescent protein fusion protein produced in sporulating cells was detectable in the mother cell but not in the forespore compartment under fluorescence microscopy, and the fusion protein was localized around the developing spores dependent on CotE, SafA, and SpoVID. Inactivation of the ycsK gene by insertion of an erythromycin resistance gene did not affect vegetative growth or spore resistance to heat, lysozyme, or chloroform. The germination of ycsK spores in a mixture of L-asparagine, D-glucose, D-fructose, and potassium chloride and LB medium was also the same as that of wild-type spores, but the mutant spores were defective in L-alanine-stimulated germination. In addition, zymogram analysis demonstrated that the YcsK protein heterologously expressed in Escherichia coli showed lipolytic activity. We therefore propose that ycsK should be renamed lipC. This is the first study of a bacterial spore germination-related lipase.
ESTHER : Masayama_2007_J.Bacteriol_189_2369
PubMedSearch : Masayama_2007_J.Bacteriol_189_2369
PubMedID: 17220230

Title : Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to Rat - Matsui_1999_Drug.Metab.Dispos_27_1406
Author(s) : Matsui K , Mishima M , Nagai Y , Yuzuriha T , Yoshimura T
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 27 :1406 , 1999
Abstract : Donepezil hydrochloride (Aricept) is a drug for the treatment of Alzheimer's disease. The absorption, distribution, metabolism, and excretion of donepezil were investigated in male Sprague-Dawley rats after a single oral administration. Orally administered (14)C-labeled donepezil was absorbed rapidly. The plasma level of unchanged donepezil declined more rapidly than that of radioactivity, and the brain level of radioactivity declined almost in parallel with the plasma level of unchanged donepezil. The ratio of donepezil to total radioactivity in brain was 86.9 to 93.0%, indicating low permeability of the metabolites through the blood-brain barrier. No heterogeneous localization of radioactivity was recognized in the brain and the concentration in each part of the brain was 1.74 to 2.24 times the plasma concentration. Cumulative biliary, urinary, and fecal excretion of radioactivity in bile duct-cannulated rats was 72.9, 24.4, and 8.84%, respectively, of the administered radioactivity at 48 h after administration. These results indicate that the absorption of donepezil is almost complete, and that its metabolites are mainly excreted into feces through the bile and some of them are subject to enterohepatic circulation. The metabolism of donepezil was extensive in rats and involved O-demethylation, aromatic hydroxylation, N-dealkylation, N-oxidation, and glucuronide conjugation of O-demethylate. The structures of the metabolites were determined by mass spectrometry and (1)H-NMR analysis. In plasma, urine, and bile, O-glucuronides accounted for the majority of the radioactivity, and in brain, unchanged donepezil was mostly detected. No metabolites were found in brain. There was no notable accumulation of radioactivity in whole blood and tissues.
ESTHER : Matsui_1999_Drug.Metab.Dispos_27_1406
PubMedSearch : Matsui_1999_Drug.Metab.Dispos_27_1406
PubMedID: 10570021

Title : Simultaneous determination of donepezil (aricept) enantiomers in human plasma by liquid chromatography-electrospray tandem mass spectrometry - Matsui_1999_J.Chromatogr.B.Biomed.Sci.Appl_729_147
Author(s) : Matsui K , Oda Y , Nakata H , Yoshimura T
Ref : Journal of Chromatography B Biomed Sci Appl , 729 :147 , 1999
Abstract : A rapid, sensitive and enantioselective LC-MS-MS method using deuterium-labeled internal standard was developed and evaluated for the simultaneous quantitative determination of donepezil enantiomers in human plasma without interconversion during clean-up process and measurement. The use of an avidin column allowed the separation of donepezil enantiomers, which were specifically detected by MS-MS without interference from its metabolites and plasma constituents. Evaluation of this assay method shows that samples can be assayed with acceptable accuracy and precision within the range from 0.0206 ng/ml to 51.6 ng/ml for both R-donepezil and S-donepezil. This analytical method was applied to the simultaneous quantitation of donepezil enantiomers in human plasma.
ESTHER : Matsui_1999_J.Chromatogr.B.Biomed.Sci.Appl_729_147
PubMedSearch : Matsui_1999_J.Chromatogr.B.Biomed.Sci.Appl_729_147
PubMedID: 10410937

Title : Correlation of the intrinsic clearance of donepezil (Aricept) between in vivo and in vitro studies in rat, dog and human - Matsui_1999_Xenobiotica_29_1059
Author(s) : Matsui K , Taniguchi S , Yoshimura T
Ref : Xenobiotica , 29 :1059 , 1999
Abstract : 1. Donepezil hydrochloride (Aricept) is used for the treatment of Alzheimer's disease. Here the correlation of the intrinsic clearance (Cl(int)) of donepezil between the in vivo and in vitro states was studied in rat, dog and human. 2. In an experiment with 14C-donepezil and human microsomes the routes of metabolism were identified as N-dealkylation and O-demethylation, and no unknown metabolites were detected. 3. The Cl(int) of donepezil in the male rat, female rat, dog and human liver microsomes were 33.7, 13.4, 37.0 and 6.35 microl/min/mg microsomal protein respectively, and sex difference in rat and interspecies difference in the estimated Cl(int) were found. 4. After a single intravenous administration to the male rat, female rat and dog, total plasma clearance (ClP(total)) was 78.6, 29.5 and 88.3 ml/min/kg respectively, and a sex difference was observed in rat. 5. After a single oral administration to the male rat, dog and healthy volunteer, ClP(total) was 140, 105 and 2.35 ml/min/kg respectively, and remarkable differences were observed between animals and man. 6. The contribution of renal clearance to blood clearance (Cl(r)) was low in all species. The predicted in vitro hepatic clearance (Cl(h-pre)) was in the rank order: male rat (15.91 ml/min/kg) > dog (7.96) > female rat (7.67) > human (1.04). Although Cl(h-pre) was underestimated, Cl(h-pre) was significantly correlated with that of ClB(total) in the different animal species and in man, indicating that the in vitro-in vivo ranking order was conserved.
ESTHER : Matsui_1999_Xenobiotica_29_1059
PubMedSearch : Matsui_1999_Xenobiotica_29_1059
PubMedID: 10598742

Title : Lambert-Eaton myasthenic syndrome associated with idiopathic thrombocytopenic purpura and diffuse panbronchiolitis: long-term remission after a course of intravenous immunoglobulin combined with low-dose prednisolone - Takata_1999_Am.J.Med.Sci_318_353
Author(s) : Takata T , Koide S , Ogata K , Motomura M , Yoshimura T , Hanajima R , Sakurai M , Kanazawa I
Ref : American Journal of Medicine Sci , 318 :353 , 1999
Abstract : We report a case of Lambert-Eaton myasthenic syndrome (LEMS) associated with idiopathic thrombocytopenic purpura (ITP) and diffuse panbronchiolitis (DPB). An extensive search for malignancy yielded negative results. Interestingly, ITP and DPB developed simultaneously when the patient suffered from myasthenic symptoms. This is the first report in the Japanese or English literature of an association of LEMS, ITP, and DPB. The use of cholinesterase blocker alone did not improve the myasthenic symptoms, and the symptoms and signs relapsed with the tapering of prednisolone (PSL) dosage. However, after administration of immunoglobulin (IVIG) (0.4 g/kg/day x 5 days), low-dose PSL (20 mg/day) alleviated the LEMS and ITP, and the diseases have remained in remission for 8 months without additional IVIG. We suspect that there is a synergistic relationship between IVIG and PSL.
ESTHER : Takata_1999_Am.J.Med.Sci_318_353
PubMedSearch : Takata_1999_Am.J.Med.Sci_318_353
PubMedID: 10555101