Shimada H

References (17)

Title : First-in-human in vivo undefined imaging and quantification of monoacylglycerol lipase in the brain: a PET study with (18)F-T-401 - Takahata_2022_Eur.J.Nucl.Med.Mol.Imaging__
Author(s) : Takahata K , Seki C , Kimura Y , Kubota M , Ichise M , Sano Y , Yamamoto Y , Tagai K , Shimada H , Kitamura S , Matsuoka K , Endo H , Shinotoh H , Kawamura K , Zhang MR , Takado Y , Higuchi M
Ref : Eur J Nucl Med Mol Imaging , : , 2022
Abstract : PURPOSE: Monoacylglycerol lipase (MAGL) regulates cannabinoid neurotransmission and the pro-inflammatory arachidonic acid pathway by degrading endocannabinoids. MAGL inhibitors may accordingly act as cannabinoid-potentiating and anti-inflammatory agents. Although MAGL dysfunction has been implicated in neuropsychiatric disorders, it has never been visualized in vivo in human brain. The primary objective of the current study was to visualize MAGL in the human brain using the novel PET ligand (18)F-T-401. METHODS: Seven healthy males underwent 120-min dynamic (18)F-T-401-PET scans with arterial blood sampling. Six subjects also underwent a second PET scan with (18)F-T-401 within 2 weeks of the first scan. For quantification of MAGL in the human brain, kinetic analyses using one- and two-tissue compartment models (1TCM and 2TCM, respectively), along with multilinear analysis (MA1) and Logan graphical analysis, were performed. Time-stability and test-retest reproducibility of (18)F-T-401-PET were also evaluated. RESULTS: (18)F-T-401 showed rapid uptake and gradual washout from the brain. Logan graphical analysis showed linearity in all subjects, indicating reversible radioligand kinetics. Using a metabolite-corrected arterial input function, MA1 estimated regional total distribution volume (V(T)) values by best identifiability. V(T) values were highest in the cerebral cortex, moderate in the thalamus and putamen, and lowest in white matter and the brainstem, which was in agreement with regional MAGL expression in the human brain. Time-stability analysis showed that MA1 estimated V(T) values with a minimal bias even using truncated 60-min scan data. Test-retest reliability was also excellent with the use of MA1. CONCLUSIONS: Here, we provide the first demonstration of in vivo visualization of MAGL in the human brain. (18)F-T-401 showed excellent test-retest reliability, reversible kinetics, and stable estimation of V(T) values consistent with known regional MAGL expressions. PET with (18)F-T-401-PET is promising tool for measurement of central MAGL.
ESTHER : Takahata_2022_Eur.J.Nucl.Med.Mol.Imaging__
PubMedSearch : Takahata_2022_Eur.J.Nucl.Med.Mol.Imaging__
PubMedID: 35022846
Gene_locus related to this paper: human-MGLL

Title : Differentiation Between Dementia With Lewy Bodies And Alzheimer's Disease Using Voxel-Based Morphometry Of Structural MRI: A Multicenter Study - Matsuda_2019_Neuropsychiatr.Dis.Treat_15_2715
Author(s) : Matsuda H , Yokoyama K , Sato N , Ito K , Nemoto K , Oba H , Hanyu H , Kanetaka H , Mizumura S , Kitamura S , Shinotoh H , Shimada H , Suhara T , Terada H , Nakatsuka T , Kawakatsu S , Hayashi H , Asada T , Ono T , Goto T , Shigemori K
Ref : Neuropsychiatr Dis Treat , 15 :2715 , 2019
Abstract : Background: The differential diagnosis of dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) is particularly important because DLB patients respond better to cholinesterase inhibitors but sometimes exhibit sensitivity to neuroleptics, which may cause worsening of clinical status. Antemortem voxel-based morphometry (VBM) using structural MRI has previously revealed that patients with DLB have normal hippocampal volume, but atrophy in the dorsal mesopontine area. Objectives: The aim of this multicenter study was to determine whether VBM of the brain stem in addition to that of medial temporal lobe structures improves the differential diagnosis of AD and DLB. Methods: We retrospectively chose 624 patients who were clinically diagnosed with either DLB (239 patients) or AD (385 patients) from 10 institutes using different MR scanners with different magnetic field strengths. In all cases, VBM was performed on 3D T1-weighted images. The degree of local atrophy was calculated using Z-score by comparison with a database of normal volumes of interest (VOIs) in medial temporal lobe (MTL) and the dorsal brain stem (DBS). The discrimination of DLB and AD was evaluated using Z-score values in these two VOIs. MRI data from 414 patients were used as the training data set to determine the classification criteria, with the MRI data from the remaining 210 patients used as the test data set. Results: The DLB and AD patients did not differ with respect to mean age or Mini-Mental State Examination scores. Z-index scores showed that there was significantly more atrophy in MTL of AD patients, compared to DLB patients and in DBS of DLB patients, compared to AD patients. The discrimination accuracies of VBM were 63.3% in the test data set and 73.4% in the training data set. Conclusion: VBM of DBS in addition to that of MTL improves the differentiation of DLB and AD.
ESTHER : Matsuda_2019_Neuropsychiatr.Dis.Treat_15_2715
PubMedSearch : Matsuda_2019_Neuropsychiatr.Dis.Treat_15_2715
PubMedID: 31571887

Title : Voxel-Based Acetylcholinesterase PET Study in Early and Late Onset Alzheimer's Disease - Hirano_2018_J.Alzheimers.Dis_62_1539
Author(s) : Hirano S , Shinotoh H , Shimada H , Ota T , Sato K , Tanaka N , Zhang MR , Higuchi M , Fukushi K , Irie T , Kuwabara S , Suhara T
Ref : J Alzheimers Dis , 62 :1539 , 2018
Abstract : BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by chronic progressive cognitive decline and displays underlying brain cholinergic dysfunction, providing a rationale for treatment with cholinomimetic medication. The clinical presentations and courses of AD patients may differ by age of onset. OBJECTIVE: The objective of the present study was to illustrate the regional differences of brain acetylcholinesterase (AChE) activity as quantified by N-[11C]methylpiperidinyl-4-acetate ([11C]MP4A) and PET using parametric whole brain analysis and clarify those differences as a function of age. METHODS: 22 early onset AD (EOAD) with age at onset under 65, the remaining 26 as late onset AD (LOAD), and 16 healthy controls (HC) were enrolled. Voxel-based AChE activity estimation of [11C]MP4A PET images was conducted by arterial input and unconstrained nonlinear least-squares method with subsequent parametrical analyses. Statistical threshold was set as Family Wise Error corrected, p-value <0.05 on cluster-level and cluster extent over 30 voxels. RESULTS: Voxel-based group comparison showed that, compared to HC, both EOAD and LOAD showed cortical AChE decrement in parietal, temporal, and occipital cortices, with wider and stringent cortical involvement in the EOAD group, most prominently demonstrated in the temporal region. There was no significant correlation between age and regional cerebral AChE activity except for a small left superior temporal region in the AD group (Brodmann's area 22, Zmax = 5.13, 396 voxels), whereas no significant cluster was found in the HC counterpart. CONCLUSION: Difference in cortical cholinergic dysfunction between EOAD and LOAD may shed some light on the cholinomimetic drug efficacy in AD.
ESTHER : Hirano_2018_J.Alzheimers.Dis_62_1539
PubMedSearch : Hirano_2018_J.Alzheimers.Dis_62_1539
PubMedID: 29562505

Title : PET measurement of brain acetylcholinesterase activities in cortex and subcortical areas -
Author(s) : Shimada H , Hirano S , Shinotoh H , Irie T , Suhara T
Ref : Int J Geriatr Psychiatry , 31 :952 , 2016
PubMedID: 26555765

Title : Dementia with Lewy bodies can be well-differentiated from Alzheimer's disease by measurement of brain acetylcholinesterase activity-a [(11) C]MP4A PET study - Shimada_2015_Int.J.Geriatr.Psychiatry_30_1105
Author(s) : Shimada H , Hirano S , Sinotoh H , Ota T , Tanaka N , Sato K , Yamada M , Fukushi K , Irie T , Zhang MR , Higuchi M , Kuwabara S , Suhara T
Ref : Int J Geriatr Psychiatry , 30 :1105 , 2015
Abstract : OBJECTIVE: To investigate the diagnostic performance of brain acetylcholinesterase (AChE) activity measurement using N-[(11) C]-methyl-4-piperidyl acetate (MP4A) and PET in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).
METHODS: Participants were 14 DLB patients, 25 AD patients and 18 age-matched healthy controls (HC). All subjects underwent PET scans and MP4A to measure regional brain AChE activity. We performed anatomical standardization of each brain image, and k3 values, an index of AChE activity, in each voxel were estimated by nonlinear least squares analysis. Volumes of interest (VOIs) were identified on parametric k3 images in frontal, temporal, parietal and occipital cortices, and in anterior and posterior cingulate gyri (ACG and PCG). In each VOI, the differential diagnostic performance between AD and DLB of k3 values was assessed by area under the curve (AUC) of the receiver-operating characteristic. Voxel-based statistical analyses were also performed.
RESULTS: Mean cortical AChE activities in AD patients (-8.2% compared with normal mean) and DLB patients (-27.8%) were lower than HCs (p < 0.05, p < 0.001, respectively). There was a significant difference in mean cortical AChE activities between AD and DLB patients (p < 0.001). All regional brain AChE activities of defined VOIs except ACG were able to well discriminate DLB from AD, and notably performance was the most significant in PCG (AUC = 0.989, 95% CI: 0.965-1.000).
CONCLUSIONS: Brain cholinergic deficit is consistently prominent in DLB compared with AD. PET measurement of brain AChE activity may be useful for the differential diagnosis between DLB and AD. Copyright (c) 2015 John Wiley & Sons, Ltd.
ESTHER : Shimada_2015_Int.J.Geriatr.Psychiatry_30_1105
PubMedSearch : Shimada_2015_Int.J.Geriatr.Psychiatry_30_1105
PubMedID: 26280153

Title : In vivo detection of neuropathologic changes in presymptomatic MAPT mutation carriers: a PET and MRI study - Miyoshi_2010_Parkinsonism.Relat.Disord_16_404
Author(s) : Miyoshi M , Shinotoh H , Wszolek ZK , Strongosky AJ , Shimada H , Arakawa R , Higuchi M , Ikoma Y , Yasuno F , Fukushi K , Irie T , Ito H , Suhara T
Ref : Parkinsonism Relat Disord , 16 :404 , 2010
Abstract : BACKGROUND: Microglial activation and disrupted neurotransmissions may herald symptomatic manifestations in neurodegenerative tauopathies. METHODS: We investigated microglial activation with [(11)C]DAA1106 positron emission tomography (PET), striatal dopaminergic function with l-[beta-(11)C]dopa PET, acetylcholinesterase (AChE) activity with [(11)C]N-methylpiperidin-4-yl acetate PET, and morphologic brain changes with MRI in three persons (aged 38-41 years) with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), who were presymptomatic gene carriers (PGCs) from an American kindred with pallidopontonigral degeneration. The results from these 3 PGCs were compared with [(11)C]DAA1106 PET results from age-matched 9 healthy volunteers (HV), and with l-[beta-(11)C]dopa and [(11)C]MP4A PET results from 10 HV. Values considered significant were more than 2 SDs greater or less than the normal control mean, as the number of subjects was small for group comparisons. RESULTS: Glial activities were increased in the frontal cortex of one PGC, the occipital cortex of two PGCs, and the posterior cingulate cortex of one PGC, although none of the PGCs showed overt glial activation in the brain. Only one of the PGCs showed reduced AChE activity in the temporo-parietal cortex. Three PGCs showed low dopamine synthesis rates in the putamen. Hippocampal atrophy was observed in two PGCs. CONCLUSIONS: Hippocampal atrophy and striatal dopaminergic dysfunction may be early disease processes in the pathogenesis of FTDP-17. Neuroinflammation may also be an in vivo signature of tau pathology at a prodromal stage, although current PET techniques may not constantly reveal it as the earliest neuroimaging abnormality.
ESTHER : Miyoshi_2010_Parkinsonism.Relat.Disord_16_404
PubMedSearch : Miyoshi_2010_Parkinsonism.Relat.Disord_16_404
PubMedID: 20452812

Title : Cholinergic imaging in corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia - Hirano_2010_Brain_133_2058
Author(s) : Hirano S , Shinotoh H , Shimada H , Aotsuka A , Tanaka N , Ota T , Sato K , Ito H , Kuwabara S , Fukushi K , Irie T , Suhara T
Ref : Brain , 133 :2058 , 2010
Abstract : Corticobasal syndrome, progressive supranuclear palsy and frontotemporal dementia are all part of a disease spectrum that includes common cognitive impairment and movement disorders. The aim of this study was to characterize brain cholinergic deficits in these disorders. We measured brain acetylcholinesterase activity by [11C] N-methylpiperidin-4-yl acetate and positron emission tomography in seven patients with corticobasal syndrome (67.6+/-5.9 years), 12 with progressive supranuclear palsy (68.5+/-4.1 years), eight with frontotemporal dementia (59.8+/-6.9 years) and 16 healthy controls (61.2+/-8.5 years). Two-tissue compartment three-parameter model and non-linear least squares analysis with arterial input function were performed. k3 value, an index of acetylcholinesterase activity, was calculated voxel-by-voxel in the brain of each subject. The k3 images in each disease group were compared with the control group by using Statistical Parametric Mapping 2. Volume of interest analysis was performed on spatially normalized k3 images. The corticobasal syndrome group showed decreased acetylcholinesterase activity (k3 values) in the paracentral region, frontal, parietal and occipital cortices (P<0.05, cluster corrected). The group with progressive supranuclear palsy had reduced acetylcholinesterase activity in the paracentral region and thalamus (P<0.05, cluster corrected). The frontotemporal dementia group showed no significant differences in acetylcholinesterase activity. Volume of interest analysis showed mean cortical acetylcholinesterase activity to be reduced by 17.5% in corticobasal syndrome (P<0.001), 9.4% in progressive supranuclear palsy (P<0.05) and 4.4% in frontotemporal dementia (non-significant), when compared with the control group. Thalamic acetylcholinesterase activity was reduced by 6.4% in corticobasal syndrome (non-significant), 24.0% in progressive supranuclear palsy (P<0.03) and increased by 3.3% in frontotemporal dementia (non-significant). Both corticobasal syndrome and progressive supranuclear palsy showed brain cholinergic deficits, but their distribution differed somewhat. Significant brain cholinergic deficits were not seen in frontotemporal dementia, which may explain the unresponsiveness of this condition to cholinergic modulation therapy.
ESTHER : Hirano_2010_Brain_133_2058
PubMedSearch : Hirano_2010_Brain_133_2058
PubMedID: 20558417

Title : Living donor liver transplantation for Dorfman-Chanarin syndrome with 1 year follow-up: case report - Takeda_2010_Transplant.Proc_42_3858
Author(s) : Takeda K , Tanaka K , Kumamoto T , Morioka D , Endo I , Togo S , Shimada H
Ref : Transplant Proc , 42 :3858 , 2010
Abstract : A 27-year-old Japanese man underwent liver transplantation because of uncompensated cirrhosis due to Dorfman-Chanarin syndrome (DCS). At birth, the patient displayed ichthyosis and liver dysfunction. Moreover, mental retardation appeared and intracytoplasmic vacuoles were observed within peripheral blood neutrophils. A fatty liver was also noticed, leading to the diagnosis of DCS. When he was referred to our hospital, his American Society of Anesthesiologists score was 3. The findings of computed tomography showed liver atrophy, splenomegaly, and ascites. The Child-Pugh score was B, and the Model for End-stage Liver Disease score was 14. The pathophysiology was DCS with uncompensated liver cirrhosis. Therefore, living donor liver transplantation (LDLT) was performed from the patient's brother. The histological appearance of the resected liver revealed macrovesicular steatosis in most hepatocytes with excess fibrous tissue in the portal areas. These findings were compatible with nonalcoholic steatohepatitis. Although the patient's mental retardation and characteristic appearance have not improved, good liver function has been maintained since LDLT. An outpatient protocol liver biopsy performed at 12 months after LDLT did not show recurrence of macrovesicular steatosis.
ESTHER : Takeda_2010_Transplant.Proc_42_3858
PubMedSearch : Takeda_2010_Transplant.Proc_42_3858
PubMedID: 21094870
Gene_locus related to this paper: human-ABHD5

Title : Estimation of plasma IC50 of donepezil for cerebral acetylcholinesterase inhibition in patients with Alzheimer disease using positron emission tomography - Ota_2010_Clin.Neuropharmacol_33_74
Author(s) : Ota T , Shinotoh H , Fukushi K , Kikuchi T , Sato K , Tanaka N , Shimada H , Hirano S , Miyoshi M , Arai H , Suhara T , Irie T
Ref : Clinical Neuropharmacology , 33 :74 , 2010
Abstract : OBJECTIVES: Estimate the value of in vivo plasma IC50 of donepezil, the concentration of donepezil in plasma that inhibits brain acetylcholinesterase (AChE) activity by 50% at the steady-state conditions of donepezil between the plasma and the brain. METHODS: N-[C] methylpiperidin-4-yl acetate ([C]MP4A) positron emission tomography was performed in 16 patients with probable Alzheimer disease (AD) before and during the treatment of donepezil (5 mg/day) with a mean interval of 5.3 months. The plasma IC50 value of donepezil was estimated from plasma donepezil concentrations and cerebral cortical mean AChE inhibition rates measured by positron emission tomography, using one-parameter model. RESULTS: Donepezil reduced AChE activity uniformly in the cerebral cortex compared with the baseline in each AD patient, and the mean reduction rate in the cerebral cortex was 34.6%. The donepezil concentrations in the plasma ranged from 18.5 to 43.9 ng/mL with a mean of 28.9 +/- 7.3 ng/mL. The plasma IC50 value was estimated to be 53.6 +/- 4.0 ng/mL. CONCLUSIONS: Once the plasma IC50 of donepezil is determined, the brain AChE inhibition rate could be estimated from the plasma concentration of donepezil in each subject based on the plasma IC50. Now that the mean donepezil concentrations in the plasma, when the patients took 5 mg/day, remained 28.9 ng/mL, approximately half of the plasma IC50, higher dose of donepezil might provide further benefits for patients with AD. This technique can be also applied to measure the in vivo plasma IC50 of other cholinesterase inhibitors such as rivastigmine and galantamine.
ESTHER : Ota_2010_Clin.Neuropharmacol_33_74
PubMedSearch : Ota_2010_Clin.Neuropharmacol_33_74
PubMedID: 19935404

Title : Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET - Shimada_2009_Neurology_73_273
Author(s) : Shimada H , Hirano S , Shinotoh H , Aotsuka A , Sato K , Tanaka N , Ota T , Asahina M , Fukushi K , Kuwabara S , Hattori T , Suhara T , Irie T
Ref : Neurology , 73 :273 , 2009
Abstract : OBJECTIVE: To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB). METHODS: Participants included 18 patients with PD, 21 patients with PDD/DLB, and 26 healthy controls. The PD group consisted of nine patients with early PD, each with a disease duration of less than 3 years, five of whom were de novo PD patients, and nine patients with advanced PD, each with a disease duration greater than or equal to 3 years. The PDD/DLB group consisted of 10 patients with PDD and 11 patients with DLB. All subjects underwent PET scans with N-[11C]-methyl-4-piperidyl acetate to measure brain acetylcholinesterase (AChE) activity. Brain AChE activity levels were estimated voxel-by-voxel in a three-compartment analysis using the arterial input function, and compared among our subject groups through both voxel-based analysis using the statistical parametric mapping software SPM5 and volume-of-interest analysis. RESULTS: Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = -12%) (false discovery rate-corrected p value <0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = -27%) (p < 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced. CONCLUSIONS: Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies.
ESTHER : Shimada_2009_Neurology_73_273
PubMedSearch : Shimada_2009_Neurology_73_273
PubMedID: 19474411

Title : The transcriptional landscape of the mammalian genome - Carninci_2005_Science_309_1559
Author(s) : Carninci P , Kasukawa T , Katayama S , Gough J , Frith MC , Maeda N , Oyama R , Ravasi T , Lenhard B , Wells C , Kodzius R , Shimokawa K , Bajic VB , Brenner SE , Batalov S , Forrest AR , Zavolan M , Davis MJ , Wilming LG , Aidinis V , Allen JE , Ambesi-Impiombato A , Apweiler R , Aturaliya RN , Bailey TL , Bansal M , Baxter L , Beisel KW , Bersano T , Bono H , Chalk AM , Chiu KP , Choudhary V , Christoffels A , Clutterbuck DR , Crowe ML , Dalla E , Dalrymple BP , de Bono B , Della Gatta G , di Bernardo D , Down T , Engstrom P , Fagiolini M , Faulkner G , Fletcher CF , Fukushima T , Furuno M , Futaki S , Gariboldi M , Georgii-Hemming P , Gingeras TR , Gojobori T , Green RE , Gustincich S , Harbers M , Hayashi Y , Hensch TK , Hirokawa N , Hill D , Huminiecki L , Iacono M , Ikeo K , Iwama A , Ishikawa T , Jakt M , Kanapin A , Katoh M , Kawasawa Y , Kelso J , Kitamura H , Kitano H , Kollias G , Krishnan SP , Kruger A , Kummerfeld SK , Kurochkin IV , Lareau LF , Lazarevic D , Lipovich L , Liu J , Liuni S , McWilliam S , Madan Babu M , Madera M , Marchionni L , Matsuda H , Matsuzawa S , Miki H , Mignone F , Miyake S , Morris K , Mottagui-Tabar S , Mulder N , Nakano N , Nakauchi H , Ng P , Nilsson R , Nishiguchi S , Nishikawa S , Nori F , Ohara O , Okazaki Y , Orlando V , Pang KC , Pavan WJ , Pavesi G , Pesole G , Petrovsky N , Piazza S , Reed J , Reid JF , Ring BZ , Ringwald M , Rost B , Ruan Y , Salzberg SL , Sandelin A , Schneider C , Schonbach C , Sekiguchi K , Semple CA , Seno S , Sessa L , Sheng Y , Shibata Y , Shimada H , Shimada K , Silva D , Sinclair B , Sperling S , Stupka E , Sugiura K , Sultana R , Takenaka Y , Taki K , Tammoja K , Tan SL , Tang S , Taylor MS , Tegner J , Teichmann SA , Ueda HR , van Nimwegen E , Verardo R , Wei CL , Yagi K , Yamanishi H , Zabarovsky E , Zhu S , Zimmer A , Hide W , Bult C , Grimmond SM , Teasdale RD , Liu ET , Brusic V , Quackenbush J , Wahlestedt C , Mattick JS , Hume DA , Kai C , Sasaki D , Tomaru Y , Fukuda S , Kanamori-Katayama M , Suzuki M , Aoki J , Arakawa T , Iida J , Imamura K , Itoh M , Kato T , Kawaji H , Kawagashira N , Kawashima T , Kojima M , Kondo S , Konno H , Nakano K , Ninomiya N , Nishio T , Okada M , Plessy C , Shibata K , Shiraki T , Suzuki S , Tagami M , Waki K , Watahiki A , Okamura-Oho Y , Suzuki H , Kawai J , Hayashizaki Y
Ref : Science , 309 :1559 , 2005
Abstract : This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
ESTHER : Carninci_2005_Science_309_1559
PubMedSearch : Carninci_2005_Science_309_1559
PubMedID: 16141072
Gene_locus related to this paper: mouse-abhd1 , mouse-abhd3 , mouse-abhd4 , mouse-acot4 , mouse-adcl4 , mouse-DGLB , mouse-ephx3 , mouse-Kansl3 , mouse-lipli , mouse-LIPN , mouse-Ppgb , mouse-q3uuq7 , mouse-srac1 , mouse-Tex30 , mouse-tmco4 , mouse-tmm53 , mouse-f172a

Title : Chlorophyllase as a serine hydrolase: identification of a putative catalytic triad - Tsuchiya_2003_Plant.Cell.Physiol_44_96
Author(s) : Tsuchiya T , Suzuki T , Yamada T , Shimada H , Masuda T , Ohta H , Takamiya K
Ref : Plant Cell Physiol , 44 :96 , 2003
Abstract : Chlorophyllases (Chlases), cloned so far, contain a lipase motif with the active serine residue of the catalytic triad of triglyceride lipases. Inhibitors specific for the catalytic serine residue in serine hydrolases, which include lipases effectively inhibited the activity of the recombinant Chenopodium album Chlase (CaCLH). From this evidence we assumed that the catalytic mechanism of hydrolysis by Chlase might be similar to those of serine hydrolases that have a catalytic triad composed of serine, histidine and aspartic acid in their active site. Thus, we introduced mutations into the putative catalytic residue (Ser162) and conserved amino acid residues (histidine, aspartic acid and cysteine) to generate recombinant CaCLH mutants. The three amino acid residues (Ser162, Asp191 and His262) essential for Chlase activity were identified. These results indicate that Chlase is a serine hydrolase and, by analogy with a plausible catalytic mechanism of serine hydrolases, we proposed a mechanism for hydrolysis catalyzed by Chlase.
ESTHER : Tsuchiya_2003_Plant.Cell.Physiol_44_96
PubMedSearch : Tsuchiya_2003_Plant.Cell.Physiol_44_96
PubMedID: 12552153
Gene_locus related to this paper: cheal-CACLH

Title : Magnesium insertion by magnesium chelatase in the biosynthesis of zinc bacteriochlorophyll a in an aerobic acidophilic bacterium Acidiphilium rubrum - Masuda_1999_J.Biol.Chem_274_33594
Author(s) : Masuda T , Inoue K , Masuda M , Nagayama M , Tamaki A , Ohta H , Shimada H , Takamiya K
Ref : Journal of Biological Chemistry , 274 :33594 , 1999
Abstract : To elucidate the mechanism for formation of zinc-containing bacteriochlorophyll a in the photosynthetic bacterium Acidiphilium rubrum, we isolated homologs of magnesium chelatase subunits (bchI, -D, and -H). A. rubrum bchI and -H were encoded by single genes located on the clusters bchP-orf168-bchI-bchD-orf320-crtI and bchF-N-B-H-L as in Rhodobacter capsulatus, respectively. The deduced sequences of A. rubrum bchI, -D, and -H had overall identities of 59. 8, 40.5, and 50.7% to those from Rba. capsulatus, respectively. When these genes were introduced into bchI, bchD, and bchH mutants of Rba. capsulatus for functional complementation, all mutants were complemented with concomitant synthesis of bacteriochlorophyll a. Analyses of bacteriochlorophyll intermediates showed that A. rubrum cells accumulate magnesium protoporphyrin IX monomethyl ester without detectable accumulation of zinc protoporphyrin IX or its monomethyl ester. These results indicate that a single set of magnesium chelatase homologs in A. rubrum catalyzes the insertion of only Mg(2+) into protoporphyrin IX to yield magnesium protoporphyrin IX monomethyl ester. Consequently, it is most likely that zinc-containing bacteriochlorophyll a is formed by a substitution of Zn(2+) for Mg(2+) at a step in the bacteriochlorophyll biosynthesis after formation of magnesium protoporphyrin IX monomethyl ester.
ESTHER : Masuda_1999_J.Biol.Chem_274_33594
PubMedSearch : Masuda_1999_J.Biol.Chem_274_33594
PubMedID: 10559247
Gene_locus related to this paper: aciru-Q9WXB1

Title : Cloning of chlorophyllase, the key enzyme in chlorophyll degradation: finding of a lipase motif and the induction by methyl jasmonate - Tsuchiya_1999_Proc.Natl.Acad.Sci.U.S.A_96_15362
Author(s) : Tsuchiya T , Ohta H , Okawa K , Iwamatsu A , Shimada H , Masuda T , Takamiya K
Ref : Proc Natl Acad Sci U S A , 96 :15362 , 1999
Abstract : Chlorophyllase (Chlase) is the first enzyme involved in chlorophyll (Chl) degradation and catalyzes the hydrolysis of ester bond to yield chlorophyllide and phytol. In the present study, we isolated the Chlase cDNA. We synthesized degenerate oligo DNA probes based on the internal amino acid sequences of purified Chlase from Chenopodium album, screened the C. album cDNA library, and cloned a cDNA (CaCLH, C. album chlorophyll-chlorophyllido hydrolase). The deduced amino acid sequence (347 aa residues) had a lipase motif overlapping with an ATP/GTP-binding motif (P-loop). CaCLH possibly was localized in the extraplastidic part of the cell, because a putative signal sequence for endoplasmic reticulum is at the N terminus. The amino acid sequence shared 37% identity with a function-unknown gene whose mRNA is inducible by coronatine and methyl jasmonate (MeJA) in Arabidopsis thaliana (AtCLH1). We expressed the gene products of AtCLH1 and of CaCLH in Escherichia coli, and they similarly exhibited Chlase activity. Moreover, we isolated another full-length cDNA based on an Arabidopsis genomic fragment and expressed it in E. coli, demonstrating the presence of the second Arabidopsis CLH gene (AtCLH2). No typical feature of signal sequence was identified in AtCLH1, whereas AtCLH2 had a typical signal sequence for chloroplast. AtCLH1 mRNA was induced rapidly by a treatment of MeJA, which is known to promote senescence and Chl degradation in plants, and a high mRNA level was maintained up to 9 h. AtCLH2, however, did not respond to MeJA.
ESTHER : Tsuchiya_1999_Proc.Natl.Acad.Sci.U.S.A_96_15362
PubMedSearch : Tsuchiya_1999_Proc.Natl.Acad.Sci.U.S.A_96_15362
PubMedID: 10611389
Gene_locus related to this paper: arath-clh1 , arath-clh2 , cheal-CACLH

Title : Factors affecting neostigmine reversal of vecuronium block during sevoflurane anaesthesia - Morita_1997_Anaesthesia_52_538
Author(s) : Morita T , Kurosaki D , Tsukagoshi H , Shimada H , Sato H , Goto F
Ref : Anaesthesia , 52 :538 , 1997
Abstract : We examined the influence of the concentration of sevoflurane and the degree of muscle block at the time of reversal on the activity of neostigmine. Ninety ASA 1-2 patients were anaesthetised with 0.2, 0.7 or 1.2 MAC of sevoflurane (30 patients each) in 66% nitrous oxide in oxygen. The electromyographic (EMG) response of the adductor digiti minimi was monitored at 20-s intervals after train-of-four stimulation of the ulnar nerve. The initial neuromuscular block was produced by vecuronium 100 micrograms.kg-1. When the amplitude of the first response (T1) values had recovered to 10%, 25% or 40% of the control, neostigmine 40 micrograms.kg-1 was administered. The train-of-four ratio values were recorded at 1-min intervals during the subsequent 15-min period. Higher endtidal concentrations (p < 0.0001) and more pronounced block at the time of reversal (p < 0.0001) were associated with a delayed recovery in the train-of-four ratio. In addition, the train-of-four ratio 15 min after neostigmine administration was more dependent on the sevoflurane concentration than on the degree of block present (p < 0.0001). These results confirm that neostigmine (40 micrograms.kg-1) can reverse vecuronium-induced but not sevoflurane-induced neuromuscular block.
ESTHER : Morita_1997_Anaesthesia_52_538
PubMedSearch : Morita_1997_Anaesthesia_52_538
PubMedID: 9203879

Title : Biologically active acylglycerides from the berries of saw-palmetto (Serenoa repens) - Shimada_1997_J.Nat.Prod_60_417
Author(s) : Shimada H , Tyler VE , McLaughlin JL
Ref : Journal of Natural Products , 60 :417 , 1997
Abstract : Brine shrimp lethality-directed fractionation of the 95% EtOH extract of the powdered, dried berries of Serenoa repens (Bart.) Small (saw-palmetto) (Palmae) led to the isolation of two monoacylglycerides, 1-monolaurin (1) and 1-monomyristin (2). Compounds 1 and 2 showed moderate biological activities in the brine shrimp lethality test and against renal (A-498) and pancreatic (PACA-2) human tumor cells; borderline cytotoxicity was exhibited against human prostatic (PC-3) cells. The fruits and extracts of saw-palmetto are taken orally as an herbal medicine to prevent prostatic hyperplasias.
ESTHER : Shimada_1997_J.Nat.Prod_60_417
PubMedSearch : Shimada_1997_J.Nat.Prod_60_417
PubMedID: 9134750

Title : Effects of dithiocarbamates and cadmium on the enzymatic activities in liver, kidney and blood of mice - Funakoshi_1995_Toxicol.Lett_78_183
Author(s) : Funakoshi T , Ohta O , Shimada H , Kojima S
Ref : Toxicology Letters , 78 :183 , 1995
Abstract : The effects of N-benzyl-D-glucamine dithiocarbamate (BGD), diethyldithiocarbamate (DDTC), and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) on the enzymatic activities in mice were studied. The mice were given i.v. injections of these chelating agents (1 mmol/kg) and 3 h later the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (gamma-GTP), alkaline phosphatase (ALP), leucine aminopeptidase (LAP), and cholinesterase (ChE) in the liver, kidney, and blood were determined. These enzymatic activities were little changed by treatment with these chelating agents. Cadmium (Cd) administration markedly decreased the activities of AST and ALT in the liver and kidney and greatly increased these enzymatic activities in blood. The changes in the enzymatic activities by treatment with Cd were prevented by injection of BGD (1 mmol/kg). These results indicate that BGD, DDTC, and HBGD were not toxic to the liver or kidney of mice and that BGD treatment protected against the acute hepatic and renal toxicity induced by Cd.
ESTHER : Funakoshi_1995_Toxicol.Lett_78_183
PubMedSearch : Funakoshi_1995_Toxicol.Lett_78_183
PubMedID: 7624888