Morimoto T

References (10)

Title : Serum cholinesterase as a prognostic biomarker for acute heart failure - Shiba_2021_Eur.Heart.J.Acute.Cardiovasc.Care__
Author(s) : Shiba M , Kato T , Morimoto T , Yaku H , Inuzuka Y , Tamaki Y , Ozasa N , Seko Y , Yamamoto E , Yoshikawa Y , Kitai T , Yamashita Y , Iguchi M , Nagao K , Kawase Y , Morinaga T , Toyofuku M , Furukawa Y , Ando K , Kadota K , Sato Y , Kuwahara K , Kimura T
Ref : Eur Heart J Acute Cardiovasc Care , : , 2021
Abstract : AIMS: The association between serum cholinesterase and prognosis in acute heart failure (AHF) remains to be elucidated. We investigated the serum cholinesterase level at discharge from hospitalization for AHF and its association with clinical outcomes in patients with AHF. METHODS AND RESULTS: Among 4056 patients enrolled in the Kyoto Congestive Heart Failure multicentre registry, we analysed 2228 patients with available serum cholinesterase data. The study population was classified into three groups according to serum cholinesterase level at discharge: low tertile (<180 U/L, N = 733), middle tertile (<=180 U/L and <240 U/L, N = 746), and high tertile (<=240 U/L, N = 749). Patients in the low tertile had higher tricuspid pressure gradient, greater inferior vena cava diameter, and higher brain natriuretic peptide (BNP) levels than those in the high tertile. The cumulative 1-year incidence of the primary outcome measure (a composite endpoint of all-cause death and hospitalization for HF) was higher in the low and middle tertiles than in the high tertile [46.5% (low tertile) and 31.4% (middle tertile) vs. 22.1% (high tertile), P < 0.0001]. After adjustment for 26 variables, the excess risk of the low tertile relative to the high tertile for the primary outcome measure remained significant (hazard ratio 1.37, 95% confidence interval 1.10-1.70, P = 0.006). Restricted cubic spline models below the median of cholinesterase demonstrated incrementally higher hazards at low cholinesterase levels. CONCLUSIONS: Low serum cholinesterase levels are associated with congestive findings on echocardiography, higher BNP, and higher risks for a composite of all-cause death and HF hospitalization in patients with AHF.
ESTHER : Shiba_2021_Eur.Heart.J.Acute.Cardiovasc.Care__
PubMedSearch : Shiba_2021_Eur.Heart.J.Acute.Cardiovasc.Care__
PubMedID: 33580775

Title : Treatment with anagliptin, a DPP-4 inhibitor, decreases FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular disease who are receiving statin therapy - Furuhashi_2020_Cardiovasc.Diabetol_19_89
Author(s) : Furuhashi M , Sakuma I , Morimoto T , Higashiura Y , Sakai A , Matsumoto M , Sakuma M , Shimabukuro M , Nomiyama T , Arasaki O , Node K , Ueda S
Ref : Cardiovasc Diabetol , 19 :89 , 2020
Abstract : BACKGROUND: Fatty acid-binding protein 4 (FABP4) acts as a novel adipokine, and elevated FABP4 concentration is associated with obesity, insulin resistance and atherosclerosis. Dipeptidyl peptidase-4 (DPP-4) inhibitors, a class of antidiabetic drugs, have distinct structures among the drugs, possibly leading to a drug class effect and each drug effect. Sitagliptin, a DPP-4 inhibitor, has been reported to decrease FABP4 concentration in drug-naive and sulfonylurea-treated patients with type 2 diabetes mellitus. Anagliptin, another DPP-4 inhibitor, was shown to decrease low-density lipoprotein cholesterol (LDL-C) level to a greater extent than that by sitagliptin in the Randomized Evaluation of Anagliptin vs. Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial. AIM AND METHODS: As a sub-analysis study using data obtained from the REASON trial, we investigated the effects of treatment with anagliptin (n = 148, male/female: 89/59) and treatment with sitagliptin (n = 159, male/female: 93/66) for 52 weeks on FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular events who were receiving statin therapy. RESULTS: The DPP-4 inhibitor had been administered in 82% of the patients in the anagliptin group and 81% of the patients in sitagliptin group prior to randomization. Serum FABP4 level was significantly decreased by 7.9% by treatment with anagliptin (P = 0.049) and was not significantly decreased by treatment with sitagliptin (P = 0.660). Change in FABP4 level was independently associated with basal FABP4 level and changes in waist circumference and creatinine after adjustment of age, sex and the treatment group. CONCLUSION: Anagliptin decreases serum FABP4 concentration independent of change in hemoglobin A1c or LDL-C in patients with type 2 diabetes mellitus and dyslipidemia who are on statin therapy. Trial registration number NCT02330406.
ESTHER : Furuhashi_2020_Cardiovasc.Diabetol_19_89
PubMedSearch : Furuhashi_2020_Cardiovasc.Diabetol_19_89
PubMedID: 32539832

Title : Effect of Anagliptin and Sitagliptin on Low-Density Lipoprotein Cholesterol in Type 2 Diabetic Patients with Dyslipidemia and Cardiovascular Risk: Rationale and Study Design of the REASON Trial - Ueda_2018_Cardiovasc.Drugs.Ther_32_73
Author(s) : Ueda S , Shimabukuro M , Arasaki O , Node K , Nomiyama T , Morimoto T
Ref : Cardiovasc Drugs Ther , 32 :73 , 2018
Abstract : BACKGROUND: Reduction of low-density lipoprotein cholesterol (LDL-C) is important for patients with a high risk for atherosclerotic events, such as patients with diabetes and other risk factors. Anagliptin was reported to reduce LDL-C for 12 weeks in phase III trials regardless of the use of statins, but it is uncertain whether this effect is common to other dipeptidylpeptidase-4 (DPP-4) inhibitors. METHODS: A multicenter, randomized, open-label, parallel-group trial was conducted to confirm the superiority of anagliptin to sitagliptin in terms of the primary endpoint of reduction of LDL-C for 52 weeks in patients with type 2 diabetes and atherosclerotic vascular lesions, as well as the non-inferiority of anagliptin to sitagliptin in terms of change in hemoglobin A1c (HbA1c). Patients are randomly assigned to receive anagliptin or sitagliptin at a ratio of 1:1, with those in the anagliptin group receiving anagliptin 100 mg orally twice per day and those in the sitagliptin group receiving sitagliptin 50 mg orally once per day. During the trial period, hypoglycemic agents and anti-dyslipidemia drugs should not be added and neither should their dosages be changed. A total sample size of 300 was estimated to provide a power of 0.8 with a two-sided alpha of 0.05 for LDL-C, considering a 30% dropout rate. Pre-specified factors for subgroup analyses are HbA1c, use of DPP-4 inhibitors, sex, body mass index, LDL-C, age, and the presence of treatment for existing ischemic heart disease. DISCUSSION: If anagliptin were to be shown to reduce LDL-C in patients with type 2 diabetes and atherosclerotic vascular lesions despite pre-existing statin treatment, more intensive cholesterol management would be appropriate. TRIAL REGISTRATION: NCT02330406.
ESTHER : Ueda_2018_Cardiovasc.Drugs.Ther_32_73
PubMedSearch : Ueda_2018_Cardiovasc.Drugs.Ther_32_73
PubMedID: 29435776

Title : Interaction between anti-Alzheimer and antipsychotic drugs in modulating extrapyramidal motor disorders in mice - Shimizu_2015_J.Pharmacol.Sci_127_439
Author(s) : Shimizu S , Mizuguchi Y , Sobue A , Fujiwara M , Morimoto T , Ohno Y
Ref : J Pharmacol Sci , 127 :439 , 2015
Abstract : Antipsychotics are often used in conjunction with anti-Alzheimer drugs to treat the behavioral and psychological symptoms of dementia (BPSD). Here, we examined the effects of cholinesterase inhibitors (ChEIs), donepezil and galantamine, on antipsychotic-induced extrapyramidal side effects (EPS) in mice. The effects of serotonergic agents on the EPS drug interaction were also evaluated. Donepezil (0.3-3 mg/kg) did not induce EPS signs by itself; however, it significantly potentiated bradykinesia induction with a low dose of haloperidol (0.5 mg/kg) in dose-dependent and synergistic manners. Galantamine (0.3-3 mg/kg) elicited mild bradykinesia at a high dose and dose-dependently augmented haloperidol-induced bradykinesia. The EPS potentiation by galantamine was blocked by trihexyphenidyl (a muscarinic antagonist), but not by mecamylamine (a nicotinic antagonist). In addition, the bradykinesia potentiation by galantamine was significantly reduced by (+/-)-8-hydroxy-2-(di-n-propylamino)-tetralin (a 5-HT1A agonist), ritanserin (a 5-HT2 antagonist), and SB-258585 (a 5-HT6 antagonist). The present results give us a caution for the antipsychotics and ChEIs interaction in inducing EPS in the treatment of BPSD. In addition, second generation antipsychotics, which can stimulate 5-HT1A receptors or antagonize 5-HT2 and 5-HT6 receptors, seem to be favorable as an adjunctive therapy for BPSD.
ESTHER : Shimizu_2015_J.Pharmacol.Sci_127_439
PubMedSearch : Shimizu_2015_J.Pharmacol.Sci_127_439
PubMedID: 25850380

Title : The effect of carboxylesterase 1 (CES1) polymorphisms on the pharmacokinetics of oseltamivir in humans - Suzaki_2013_Eur.J.Clin.Pharmacol_69_21
Author(s) : Suzaki Y , Uemura N , Takada M , Ohyama T , Itohda A , Morimoto T , Imai H , Hamasaki H , Inano A , Hosokawa M , Tateishi M , Ohashi K
Ref : European Journal of Clinical Pharmacology , 69 :21 , 2013
Abstract : PURPOSE: The aim of this study was to examine whether carboxylesterase 1 (CES1A) genetic polymorphisms affect the pharmacokinetics of oseltamivir.
METHODS: Thirty healthy Japanese male and female subjects ranging in age from 20 to 36 years voluntarily participated in this study. These subjects were administered a single 75-mg dose of oseltamivir (Tamiflu(R)), and blood samples were collected predose and up to 24 h after oseltamivir administration. Oseltamivir and its active metabolite, oseltamivir carboxylate, were measured by liquid chromatography-time of flight/mass spectrometry with solid-phase extraction. The CES1A diplotypes [a combination of haplotypes A (CES1A3-CES1A1), B (CES1A2-CES1A1), C (CES1A3-CES1A1variant), and D (CES1A2-CES1A1variant)] were determined by PCR-restriction fragment length polymorphism analysis and direct sequencing.
RESULTS: All subjects completed the study according to the protocol, and no clinically meaningful adverse events were attributable to the administration of oseltamivir. No significant differences in the pharmacokinetic parameters of oseltamivir and oseltamivir carboxylate were observed according to CES1A genotype. In one subject, the peak concentration and area under the concentration-time curve (AUC) of oseltamivir were approximately tenfold higher than the mean values of the other subjects.
CONCLUSIONS: In our study, the known interindividual variability in oseltamivir metabolism was not explained by CES1A genetic polymorphisms, but are likely the result of other factors. While one subject was found to exhibit an approximate tenfold higher AUC than the other subjects, no abnormal behaviors were associated with the increased oseltamivir plasma concentrations. Further studies are required to reveal the cause of individual differences in CES1A metabolism and the abnormal behavioral effects of oseltamivir.
ESTHER : Suzaki_2013_Eur.J.Clin.Pharmacol_69_21
PubMedSearch : Suzaki_2013_Eur.J.Clin.Pharmacol_69_21
PubMedID: 22673926

Title : Crystal structures of Lymnaea stagnalis AChBP in complex with neonicotinoid insecticides imidacloprid and clothianidin - Ihara_2008_Invert.Neurosci_8_71
Author(s) : Ihara M , Okajima T , Yamashita A , Oda T , Hirata K , Nishiwaki H , Morimoto T , Akamatsu M , Ashikawa Y , Kuroda S , Mega R , Kuramitsu S , Sattelle DB , Matsuda K
Ref : Invert Neurosci , 8 :71 , 2008
Abstract : Neonicotinoid insecticides, which act on nicotinic acetylcholine receptors (nAChRs) in a variety of ways, have extremely low mammalian toxicity, yet the molecular basis of such actions is poorly understood. To elucidate the molecular basis for nAChR-neonicotinoid interactions, a surrogate protein, acetylcholine binding protein from Lymnaea stagnalis (Ls-AChBP) was crystallized in complex with neonicotinoid insecticides imidacloprid (IMI) or clothianidin (CTD). The crystal structures suggested that the guanidine moiety of IMI and CTD stacks with Tyr185, while the nitro group of IMI but not of CTD makes a hydrogen bond with Gln55. IMI showed higher binding affinity for Ls-AChBP than that of CTD, consistent with weaker CH-pi interactions in the Ls-AChBP-CTD complex than in the Ls-AChBP-IMI complex and the lack of the nitro group-Gln55 hydrogen bond in CTD. Yet, the NH at position 1 of CTD makes a hydrogen bond with the backbone carbonyl of Trp143, offering an explanation for the diverse actions of neonicotinoids on nAChRs.
ESTHER : Ihara_2008_Invert.Neurosci_8_71
PubMedSearch : Ihara_2008_Invert.Neurosci_8_71
PubMedID: 18338186

Title : The Whole-genome sequencing of the obligate intracellular bacterium Orientia tsutsugamushi revealed massive gene amplification during reductive genome evolution - Nakayama_2008_DNA.Res_15_185
Author(s) : Nakayama K , Yamashita A , Kurokawa K , Morimoto T , Ogawa M , Fukuhara M , Urakami H , Ohnishi M , Uchiyama I , Ogura Y , Ooka T , Oshima K , Tamura A , Hattori M , Hayashi T
Ref : DNA Research , 15 :185 , 2008
Abstract : Scrub typhus ('Tsutsugamushi' disease in Japanese) is a mite-borne infectious disease. The causative agent is Orientia tsutsugamushi, an obligate intracellular bacterium belonging to the family Rickettsiaceae of the subdivision alpha-Proteobacteria. In this study, we determined the complete genome sequence of O. tsutsugamushi strain Ikeda, which comprises a single chromosome of 2 008 987 bp and contains 1967 protein coding sequences (CDSs). The chromosome is much larger than those of other members of Rickettsiaceae, and 46.7% of the sequence was occupied by repetitive sequences derived from an integrative and conjugative element, 10 types of transposable elements, and seven types of short repeats of unknown origins. The massive amplification and degradation of these elements have generated a huge number of repeated genes (1196 CDSs, categorized into 85 families), many of which are pseudogenes (766 CDSs), and also induced intensive genome shuffling. By comparing the gene content with those of other family members of Rickettsiacea, we identified the core gene set of the family Rickettsiaceae and found that, while much more extensive gene loss has taken place among the housekeeping genes of Orientia than those of Rickettsia, O. tsutsugamushi has acquired a large number of foreign genes. The O. tsutsugamushi genome sequence is thus a prominent example of the high plasticity of bacterial genomes, and provides the genetic basis for a better understanding of the biology of O. tsutsugamushi and the pathogenesis of 'Tsutsugamushi' disease.
ESTHER : Nakayama_2008_DNA.Res_15_185
PubMedSearch : Nakayama_2008_DNA.Res_15_185
PubMedID: 18508905
Gene_locus related to this paper: oriti-b3cqy7

Title : Protective effect of donepezil on retinal ganglion cells in vitro and in vivo - Miki_2006_Curr.Eye.Res_31_69
Author(s) : Miki A , Otori Y , Morimoto T , Okada M , Tano Y
Ref : Current Eye Research , 31 :69 , 2006
Abstract : The neuroprotective effect of donepezil, an acetylcholinesterase inhibitor on retinal ganglion cells (RGCs), was examined. The survival of purified RGCs after exposure to glutamate with or without donepezil (10(- 7) M to 10(- 5) M) was measured after 3 days in culture. In vivo, the neuroprotective effect of donepezil was examined by quantifying the number of viable RGCs 7 days after axotomy in adult rats. In vitro, donepezil dose-dependently reduced RGC death caused by glutamate toxicity. Oral administration of donepezil (10 mg kg(-1) day(-1)) significantly reduced RGC death after axotomy. In conclusion, donepezil exerts a protective effect on RGCs both in vitro and in vivo.
ESTHER : Miki_2006_Curr.Eye.Res_31_69
PubMedSearch : Miki_2006_Curr.Eye.Res_31_69
PubMedID: 16421021

Title : Calcium-dependent transmitter secretion from fibroblasts: modulation by synaptotagmin I - Morimoto_1995_Neuron_15_689
Author(s) : Morimoto T , Popov S , Buckley KM , Poo MM
Ref : Neuron , 15 :689 , 1995
Abstract : Following endocytic uptake of acetylcholine (ACh), CHO fibroblasts exhibit Ca(2+)-dependent spontaneous quantal ACh release and depolarization-evoked ACh release, as detected by a whole-cell voltage-clamped myocyte in contact with the fibroblast. CHO fibroblasts transfected with synaptotagmin I, an integral membrane protein of synaptic vesicles, showed a reduced spontaneous quantal ACh release and an enhanced Ca(2+)-evoked ACh release, as compared with control cells. Biochemical and ultrastructural studies of endocytic activity using horseradish peroxidase as a marker further confirmed the inhibitory action of synaptotagmin I on spontaneous vesicular exocytosis and on elevated exocytosis induced by Ca2+. Through inhibition of exocytosis at the resting intracellular concentration of Ca2+ and removal of the inhibition upon depolarization-induced Ca2+ entry, synaptotagmin I could enhance the efficiency of excitation-secretion coupling.
ESTHER : Morimoto_1995_Neuron_15_689
PubMedSearch : Morimoto_1995_Neuron_15_689
PubMedID: 7546747

Title : The effect of acetylcholinesterase inhibitor (SDZ ENA 713) for r-CBF and focal cerebral ischaemia - Tsujimoto_1993_Acta.Neurochir.(Wien)_124_127
Author(s) : Tsujimoto S , Sakaki T , Morimoto T , Tominaga M
Ref : Acta Neurochir (Wien) , 124 :127 , 1993
Abstract : The purpose of the present study was to examine the effect of Acetylcholinesterase inhibitor (AChEI) on r-CBF (group A) and its protecting effect on focal ischaemic cell damage (group B). The pial arterial diameter and the r-CBF were measured with a width analyzer and with a laser Doppler flowmeter through a cat cranial window on the ectosylvian gyrus. The ischaemic area was measured histologically. We used intravenous injection of AChEI([-])(S)-N-ethyl-3-[(1-dimethyl- amino)ethyl]-N-methyl-phenylcarbamate, SDZENA 713, Sands Pharmacy) to block AChE. Twenty minutes after injection AChEI (0.6 mg/kg) the pial arteriole dilated 108.5 +/- 1.8% and the r-CBF increased 115.4 +/- 2.6%. The pial arteriole dilated maximally to 137.6 +/- 6.5% at 120 minutes after injection and the r-CBF increased maximally to 137.1 +/- 19.5% at 60 minutes after injection. The protecting effect was evaluated using cats and 1 hour of occlusion of the middle cerebral artery (MCA). Twenty minutes after injection of AChEI, the pial arteriole dilated to 116.7 +/- 2.4% and the r-CBF increased to 111.9 +/- 2.6% significantly. During MCA occlusion the r-CBF decreased to 24.7-41.4% in group B and 25.1-32.6% in sham group (group C). The pial arteriole dilated 145.0-184.0% in group C and 150.7-171.6% in group B during MCA occlusion and 30 minutes after reperfusion the pial arteriole returned to 120.0 +/- 3.3% in group C and 123.4 +/- 11.3% in group B. There were no significant changes in the r-CBF and the vessel diameter between group B and C during the 2 hours after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
ESTHER : Tsujimoto_1993_Acta.Neurochir.(Wien)_124_127
PubMedSearch : Tsujimoto_1993_Acta.Neurochir.(Wien)_124_127
PubMedID: 8304058