Tashiro M

References (7)

Title : Acute Respiratory Infection in Human Dipeptidyl Peptidase 4-Transgenic Mice Infected with Middle East Respiratory Syndrome Coronavirus - Iwata-Yoshikawa_2019_J.Virol_93_
Author(s) : Iwata-Yoshikawa N , Okamura T , Shimizu Y , Kotani O , Sato H , Sekimukai H , Fukushi S , Suzuki T , Sato Y , Takeda M , Tashiro M , Hasegawa H , Nagata N
Ref : J Virol , 93 : , 2019
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) infection can manifest as a mild illness, acute respiratory distress, organ failure, or death. Several animal models have been established to study disease pathogenesis and to develop vaccines and therapeutic agents. Here, we developed transgenic (Tg) mice on a C57BL/6 background; these mice expressed human CD26/dipeptidyl peptidase 4 (hDPP4), a functional receptor for MERS-CoV, under the control of an endogenous hDPP4 promoter. We then characterized this mouse model of MERS-CoV. The expression profile of hDPP4 in these mice was almost equivalent to that in human tissues, including kidney and lung; however, hDPP4 was overexpressed in murine CD3-positive cells within peripheral blood and lymphoid tissues. Intranasal inoculation of young and adult Tg mice with MERS-CoV led to infection of the lower respiratory tract and pathological evidence of acute multifocal interstitial pneumonia within 7 days, with only transient loss of body weight. However, the immunopathology in young and adult Tg mice was different. On day 5 or 7 postinoculation, lungs of adult Tg mice contained higher levels of proinflammatory cytokines and chemokines associated with migration of macrophages. These results suggest that the immunopathology of MERS-CoV infection in the Tg mouse is age dependent. The mouse model described here will increase our understanding of disease pathogenesis and host mediators that protect against MERS-CoV infection.IMPORTANCE Middle East respiratory syndrome coronavirus (MERS-CoV) infections are endemic in the Middle East and a threat to public health worldwide. Rodents are not susceptible to the virus because they do not express functional receptors; therefore, we generated a new animal model of MERS-CoV infection based on transgenic mice expressing human DPP4 (hDPP4). The pattern of hDPP4 expression in this model was similar to that in human tissues (except lymphoid tissue). In addition, MERS-CoV was limited to the respiratory tract. Here, we focused on host factors involved in immunopathology in MERS-CoV infection and clarified differences in antiviral immune responses between young and adult transgenic mice. This new small-animal model could contribute to more in-depth study of the pathology of MERS-CoV infection and aid development of suitable treatments.
ESTHER : Iwata-Yoshikawa_2019_J.Virol_93_
PubMedSearch : Iwata-Yoshikawa_2019_J.Virol_93_
PubMedID: 30626685

Title : Non Susceptibility of Neonatal and Adult Rats against the Middle East Respiratory Syndrome Coronavirus - Iwata-Yoshikawa_2016_Jpn.J.Infect.Dis_69_510
Author(s) : Iwata-Yoshikawa N , Fukushi S , Fukuma A , Suzuki T , Takeda M , Tashiro M , Hasegawa H , Nagata N
Ref : Jpn J Infect Dis , 69 :510 , 2016
Abstract : The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a suitable model for MERS-CoV infection. Immunohistochemical analysis identified dipeptidyl peptidase 4 (DPP4), a known receptor for MERS-CoV on type I pneumocytes from infected rats. Whereas adult rats developed antibodies against MERS-CoV spike protein after intranasal inoculation, there was no evidence of viral replication in the lungs of adult, young, or neonatal rats after intranasal inoculation with MERS-CoV. In addition, human DPP4-expressing rat kidney fibroblasts, but not rat DPP4-expressing cells, were susceptible to MERS-CoV. Taken together, these results suggest that the rat is not a useful animal model for studying MERS-CoV infection.
ESTHER : Iwata-Yoshikawa_2016_Jpn.J.Infect.Dis_69_510
PubMedSearch : Iwata-Yoshikawa_2016_Jpn.J.Infect.Dis_69_510
PubMedID: 27000459

Title : Cholinergic deficit and response to donepezil therapy in Parkinson's disease with dementia - Hiraoka_2012_Eur.Neurol_68_137
Author(s) : Hiraoka K , Okamura N , Funaki Y , Hayashi A , Tashiro M , Hisanaga K , Fujii T , Takeda A , Yanai K , Iwata R , Mori E
Ref : Eur Neurol , 68 :137 , 2012
Abstract : BACKGROUND: Although donepezil, an acetylcholinesterase inhibitor, has been proved to be effective in ameliorating cognitive impairment in Parkinson's disease with dementia (PDD), the responsiveness of patients to donepezil therapy varies. [5-(11)C-methoxy]donepezil, the radiolabeled form of donepezil, is a ligand for positron emission tomography (PET), which can be exploited for the quantitative analysis of donepezil binding to acetylcholinesterase and for cholinergic imaging. OBJECTIVES: To investigate the deficits of the cholinergic system in the brain in PDD and its association with response to donepezil therapy. METHODS: Twelve patients with PDD and 13 normal control subjects underwent [5-(11)C-methoxy]donepezil-PET imaging. For patients with PDD, daily administration of donepezil was started after [5-(11)C-methoxy]donepezil-PET imaging and continued for 3 months. RESULTS: In the PDD group, the mean total distribution volume of the cerebral cortices was 22.7% lower than that of the normal control group. The mean total distribution volume of the patients with PDD was significantly correlated with improvement of visuoperceptual function after 3 months of donepezil therapy. CONCLUSION: The results suggest that donepezil therapy is more effective in patients with less decrease in acetylcholinesterase, a binding site of donepezil, at least in the specific cognitive domain.
ESTHER : Hiraoka_2012_Eur.Neurol_68_137
PubMedSearch : Hiraoka_2012_Eur.Neurol_68_137
PubMedID: 22832236

Title : Quantitative analysis of donepezil binding to acetylcholinesterase using positron emission tomography and [5-(11)C-methoxy]donepezil - Hiraoka_2009_Neuroimage_46_616
Author(s) : Hiraoka K , Okamura N , Funaki Y , Watanuki S , Tashiro M , Kato M , Hayashi A , Hosokai Y , Yamasaki H , Fujii T , Mori E , Yanai K , Watabe H
Ref : Neuroimage , 46 :616 , 2009
Abstract : The aim of this study was to establish kinetic analysis of [5-(11)C-methoxy]donepezil ([(11)C]donepezil), which was developed for the in-vivo visualization of donepezil binding to acetylcholinesterase (AChE) using positron emission tomography (PET). Donepezil is an AChE inhibitor that is widely prescribed to ameliorate the cognitive impairment of patients with dementia. Six healthy subjects took part in a dynamic study involving a 60-min PET scan after intravenous injection of [(11)C]donepezil. The total distribution volume (tDV) of [(11)C]donepezil was quantified by compartmental kinetic analysis and Logan graphical analysis. A one-tissue compartment model (1TCM) and a two-tissue compartment model (2TCM) were applied in the kinetic analysis. Goodness of fit was assessed with chi(2) criterion and Akaike's Information Criterion (AIC). Compared with a 1TCM, goodness of fit was significantly improved by a 2TCM. The tDVs provided by Logan graphical analysis were slightly lower than those provided by a 2TCM. The rank order of the mean tDVs in 10 regions was in line with the AChE activity reported in a previous post-mortem study. Logan graphical analysis generated voxel-wise images of tDV, revealing the overall distribution pattern of AChE in individual brains. Significant correlation was observed between tDVs calculated with and without metabolite correction for plasma time-activity curves, indicating that metabolite correction could be omitted. In conclusion, this method enables quantitative analysis of AChE and direct investigation of the pharmacokinetics of donepezil in the human brain.
ESTHER : Hiraoka_2009_Neuroimage_46_616
PubMedSearch : Hiraoka_2009_Neuroimage_46_616
PubMedID: 19286462

Title : In vivo visualization of donepezil binding in the brain of patients with Alzheimer's disease - Okamura_2008_Br.J.Clin.Pharmacol_65_472
Author(s) : Okamura N , Funaki Y , Tashiro M , Kato M , Ishikawa Y , Maruyama M , Ishikawa H , Meguro K , Iwata R , Yanai K
Ref : British Journal of Clinical Pharmacology , 65 :472 , 2008
Abstract : WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Deficit in central cholinergic neurotransmission is a consistent change associated with Alzheimer's disease (AD). * Donepezil hydrochloride exhibits selective inhibition of acetylcholinesterase (AChE) and is widely used for the treatment of AD. * The biodistribution of donepezil in the brain after administration is not precisely understood in vivo. * There is no method to measure the amount of binding of orally administered donepezil to AChE. WHAT THIS STUDY ADDS: * This study clearly visualizes the distribution of donepezil in human brain using [(11)C]-donepezil and positron emission tomography. * This study demonstrates prominent reduction of the donepezil binding site in the AD brain. * This study provides methodology to measure the AChE binding occupancy of orally administered donepezil and provides a new surrogate marker for evaluation and prediction of response to donepezil treatment. AIMS: The aims of this study were to visualize in vivo binding of donepezil to acetylcholinesterase (AChE) in the brain and to establish a method for measuring the amount of binding of orally administered donepezil.
METHODS: [5-(11)C-methoxy]-donepezil ([(11)C]-donepezil) was radiolabelled as a positron emission tomography (PET) tracer. The biodistribution of [(11)C]-donepezil was measured by PET in 10 AD patients and six elderly normal subjects. Two AD patients underwent additional PET measurements after oral administration of donepezil for 6 months.
RESULTS: [(11)C]-donepezil-PET images demonstrated high densities of tracer distribution in AChE-rich brain regions such as the striatum, thalamus, and cerebellum. Compared with elderly normal subjects, patients with mild AD exhibited about 18-20% reduction of donepezil binding in the neocortex and hippocampus, while patients with moderate AD exhibited about 24-30% reduction of donepezil binding throughout the brain. Orally administered donepezil (5 mg day(-1)) induced 61.6-63.3% reduction of donepezil binding in AD brains. The distribution volume of [(11)C]-donepezil in the hippocampus was significantly correlated with MMSE scores in AD patients.
CONCLUSIONS: [(11)C]-donepezil-PET enables quantitative measurement of donepezil binding in the brain. AD patients exhibited reduction of donepezil binding in the brain, even in the early stage of disease. Longitudinal evaluation by this technique enables determination of AChE binding occupancy of orally administered donepezil.
ESTHER : Okamura_2008_Br.J.Clin.Pharmacol_65_472
PubMedSearch : Okamura_2008_Br.J.Clin.Pharmacol_65_472
PubMedID: 18070217

Title : [Anesthetic managements of a patient with congenital myotonia (Becker type)] - Hayashida_2004_Masui_53_1293
Author(s) : Hayashida S , Yanagi F , Tashiro M , Terasaki H
Ref : Masui , 53 :1293 , 2004
Abstract : A 55-year-old woman with congenital myotonia (Becker type), diagnosed by muscle biopsy and gene examination, underwent a right lower lobectomy assisted with thoracoscopy for lung cancer. After epidural tube replacement at T 9-10, general anesthesia was introduced with propofol 2.5 mg x kg(-1) and fentanyl 2.5 mcg x kg(-1). Vecuronium was administered prudently for muscle relaxation assessed with T 1 response (%) and train-of-four (TOF) ratio (%). T 1 response decreased to 50% 3 min and disappeared 4 min after vecuronium administration. Then she was intubated with a double lumen endobronchial tube. T 1 increased 25% within 27 min and 75% in 40 min. Surgery was uneventful and completed in 180 min. At the end of the operation, there was neither fading of twitch responses nor tetanic responses, and TOF ratio returned to 100%. An acetylcholinesterase inhibitor was not given. She was extubated when normal spontaneous breathing, clear consciousness and adequate pharyngeal reflex were present 25 min after discontinuing propofol. There were no perioperative adverse events including hyperthermia and myoglobinuria related to malignant hyperthermia. In conclusion, we managed the anesthesia for a patient with congenital myotonia (Becker type) with thoracic epidural anesthesia and total intravenous anesthesia. Non-depolarizing muscle relaxant could be used safely at the same dose as that used in non-myotonic patients, and did not cause malignant hyperthermia.
ESTHER : Hayashida_2004_Masui_53_1293
PubMedSearch : Hayashida_2004_Masui_53_1293
PubMedID: 15587185

Title : Evaluation of the Binding Characteristics of [5-(11)C-methoxy]Donepezil in the Rat Brain for In Vivo Visualization of Acetylcholinesterase - Funaki_2003_J.Pharmacol.Sci_91_105
Author(s) : Funaki Y , Kato M , Iwata R , Sakurai E , Tashiro M , Ido T , Yanai K
Ref : J Pharmacol Sci , 91 :105 , 2003
Abstract : Donepezil, an acetylcholinesterase (AChE) inhibitor, has not been evaluated for its binding characteristics using a radioactive tracer, although its inhibitory action on AChE has been studied. The aim of this research is to examine whether AChE can be visualized in vivo and in vitro with [(11)C]donepezil. [5-(11)C-methoxy]Donepezil was synthesized by O-methylation using [(11)C]methyl triflate. The binding of [(11)C]donepezil to brain homogenates was higher in the brain stem and striatum, and it was lowest in the cerebellum. The in vitro autoradiographic study successfully demonstrated the specific binding of [(11)C]donepezil to AChE in the rat brain. The IC(50) value of binding was approximately 10 nM, which is comparable to the reported value for inhibiting enzyme activity (6 nM). Saturation experiments revealed that the B(max) and K(d) of [(11)C]donepezil binding in vitro are 65 fmol/mg tissue and 39.8 nM, respectively. In accordance with the in vitro bindings, the in vivo distribution of [(11)C]donepezil was heterogeneous in the rat brain. In the blocking experiments, the heterogeneous distribution disappeared in the presence of a large amount of unlabeled donepezil. These data suggest that [5-(11)C-methoxy]donepezil can be potentially useful to image AChE non-invasively in the human brain by positron emission tomography.
ESTHER : Funaki_2003_J.Pharmacol.Sci_91_105
PubMedSearch : Funaki_2003_J.Pharmacol.Sci_91_105
PubMedID: 12686754