Ito H

References (17)

Title : An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer's disease - Kainuma_2022_Front.Pharmacol_13_991982
Author(s) : Kainuma M , Ouma S , Kawakatsu S , Iritani O , Yamashita KI , Ohara T , Hirano S , Suda S , Hamano T , Hieda S , Yasui M , Yoshiiwa A , Shiota S , Hironishi M , Wada-Isoe K , Sasabayashi D , Yamasaki S , Murata M , Funakoshi K , Hayashi K , Shirafuji N , Sasaki H , Kajimoto Y , Mori Y , Suzuki M , Ito H , Ono K , Tsuboi Y
Ref : Front Pharmacol , 13 :991982 , 2022
Abstract : Background: Alzheimer's disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently effective. Novel treatments for mild AD are of utmost importance. Objective: To assess the effectiveness of hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), in the treatment of mild AD. Methods: This exploratory, open-label, randomized, multicenter trial enrolled patients with mild AD whose score on the Mini Mental State Examination (MMSE) was over 21points. All participants had been taking the same dosage of AChEI for more than 3 months. The participants were randomly assigned to an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI. The primary outcome was the change from baseline to 6 months post treatment initiation on the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version(ADAS-Jcog). The secondary outcomes were change from baseline of the Instrumental Activity of Daily Life (IADL), Apathy scale, and Neuropsychiatric Inventory (NPI) -Q score. Results: Among the 77 enrollees, the data of 69(34 HJG and 35 control)were available for analysis. The difference in the change of ADAS-Jcog from baseline to 6 months of the HJG and control groups was 1.29 (90% Confidence interval (CI), -0.74 to 3.32 p = 0.293). In the subgroup analysis, the differences in the change from baseline to 3 and 6 months for women were 3.70 (90% CI ,0.50 to 6.91, p = 0.059) and 2.90 (90% CI,0.09 to 5.71, p = 0.090), respectively. For patients over 65 years, the difference at 3 months was 2.35 (90%CI, 0.01 to 4.68 p = 0.099). No significant differences were found between the HJG and control groups in IADL score, Apathy scale, or NPI-Q score. Conclusion: Although not conclusive, our data indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it delays the deterioration of the cognitive dysfunction of mild Altzheimer's disease patients. Clinical Trial Registration: Japan Registry of clinical trials, identifier jRCTs 071190018.
ESTHER : Kainuma_2022_Front.Pharmacol_13_991982
PubMedSearch : Kainuma_2022_Front.Pharmacol_13_991982
PubMedID: 36313371

Title : Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus - Lawrenson_2016_Nat.Commun_7_12675
Author(s) : Lawrenson K , Kar S , McCue K , Kuchenbaeker K , Michailidou K , Tyrer J , Beesley J , Ramus SJ , Li Q , Delgado MK , Lee JM , Aittomaki K , Andrulis IL , Anton-Culver H , Arndt V , Arun BK , Arver B , Bandera EV , Barile M , Barkardottir RB , Barrowdale D , Beckmann MW , Benitez J , Berchuck A , Bisogna M , Bjorge L , Blomqvist C , Blot W , Bogdanova N , Bojesen A , Bojesen SE , Bolla MK , Bonanni B , Borresen-Dale AL , Brauch H , Brennan P , Brenner H , Bruinsma F , Brunet J , Buhari SA , Burwinkel B , Butzow R , Buys SS , Cai Q , Caldes T , Campbell I , Canniotto R , Chang-Claude J , Chiquette J , Choi JY , Claes KB , Cook LS , Cox A , Cramer DW , Cross SS , Cybulski C , Czene K , Daly MB , Damiola F , Dansonka-Mieszkowska A , Darabi H , Dennis J , Devilee P , Diez O , Doherty JA , Domchek SM , Dorfling CM , Dork T , Dumont M , Ehrencrona H , Ejlertsen B , Ellis S , Engel C , Lee E , Evans DG , Fasching PA , Feliubadalo L , Figueroa J , Flesch-Janys D , Fletcher O , Flyger H , Foretova L , Fostira F , Foulkes WD , Fridley BL , Friedman E , Frost D , Gambino G , Ganz PA , Garber J , Garcia-Closas M , Gentry-Maharaj A , Ghoussaini M , Giles GG , Glasspool R , Godwin AK , Goldberg MS , Goldgar DE , Gonzalez-Neira A , Goode EL , Goodman MT , Greene MH , Gronwald J , Guenel P , Haiman CA , Hall P , Hallberg E , Hamann U , Hansen TV , Harrington PA , Hartman M , Hassan N , Healey S , Heitz F , Herzog J , Hogdall E , Hogdall CK , Hogervorst FB , Hollestelle A , Hopper JL , Hulick PJ , Huzarski T , Imyanitov EN , Isaacs C , Ito H , Jakubowska A , Janavicius R , Jensen A , John EM , Johnson N , Kabisch M , Kang D , Kapuscinski M , Karlan BY , Khan S , Kiemeney LA , Kjaer SK , Knight JA , Konstantopoulou I , Kosma VM , Kristensen V , Kupryjanczyk J , Kwong A , de la Hoya M , Laitman Y , Lambrechts D , Le N , De Leeneer K , Lester J , Levine DA , Li J , Lindblom A , Long J , Lophatananon A , Loud JT , Lu K , Lubinski J , Mannermaa A , Manoukian S , Le Marchand L , Margolin S , Marme F , Massuger LF , Matsuo K , Mazoyer S , McGuffog L , McLean C , McNeish I , Meindl A , Menon U , Mensenkamp AR , Milne RL , Montagna M , Moysich KB , Muir K , Mulligan AM , Nathanson KL , Ness RB , Neuhausen SL , Nevanlinna H , Nord S , Nussbaum RL , Odunsi K , Offit K , Olah E , Olopade OI , Olson JE , Olswold C , O'Malley D , Orlow I , Orr N , Osorio A , Park SK , Pearce CL , Pejovic T , Peterlongo P , Pfeiler G , Phelan CM , Poole EM , Pylkas K , Radice P , Rantala J , Rashid MU , Rennert G , Rhenius V , Rhiem K , Risch HA , Rodriguez G , Rossing MA , Rudolph A , Salvesen HB , Sangrajrang S , Sawyer EJ , Schildkraut JM , Schmidt MK , Schmutzler RK , Sellers TA , Seynaeve C , Shah M , Shen CY , Shu XO , Sieh W , Singer CF , Sinilnikova OM , Slager S , Song H , Soucy P , Southey MC , Stenmark-Askmalm M , Stoppa-Lyonnet D , Sutter C , Swerdlow A , Tchatchou S , Teixeira MR , Teo SH , Terry KL , Terry MB , Thomassen M , Tibiletti MG , Tihomirova L , Tognazzo S , Toland AE , Tomlinson I , Torres D , Truong T , Tseng CC , Tung N , Tworoger SS , Vachon C , van den Ouweland AM , van Doorn HC , van Rensburg EJ , Van't Veer LJ , Vanderstichele A , Vergote I , Vijai J , Wang Q , Wang-Gohrke S , Weitzel JN , Wentzensen N , Whittemore AS , Wildiers H , Winqvist R , Wu AH , Yannoukakos D , Yoon SY , Yu JC , Zheng W , Zheng Y , Khanna KK , Simard J , Monteiro AN , French JD , Couch FJ , Freedman ML , Easton DF , Dunning AM , Pharoah PD , Edwards SL , Chenevix-Trench G , Antoniou AC , Gayther SA
Ref : Nat Commun , 7 :12675 , 2016
Abstract : A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 x 10(-20)), ER-negative BC (P=1.1 x 10(-13)), BRCA1-associated BC (P=7.7 x 10(-16)) and triple negative BC (P-diff=2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 x 10(-3)) and ABHD8 (P<2 x 10(-3)). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3'-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
ESTHER : Lawrenson_2016_Nat.Commun_7_12675
PubMedSearch : Lawrenson_2016_Nat.Commun_7_12675
PubMedID: 27601076

Title : Anagliptin in the treatment of type 2 diabetes: safety, efficacy, and patient acceptability - Nishio_2015_Diabetes.Metab.Syndr.Obes_8_163
Author(s) : Nishio S , Abe M , Ito H
Ref : Diabetes Metab Syndr Obes , 8 :163 , 2015
Abstract : Anagliptin is a novel dipeptidyl peptidase-4 inhibitor that has been available in Japan since 2012. Because anagliptin is not generally used in countries other than Japan, there are only a small number of reports investigating the effects of anagliptin. In the present article, we review the safety and efficacy of anagliptin according to data obtained from preclinical trials and postmarketing studies. The usual dose of anagliptin is 200 mg daily, and increases in the dose up to 400 mg daily have been approved in cases in which the blood glucose-lowering effect is insufficient. In a Phase II trial, the reduction in the HbA1c values from baseline after 12 weeks monotherapy with 200 mg and 400 mg of daily anagliptin was 0.75%+/-0.50% and 0.82%+/-0.46%, respectively, and more than 40% of the subjects receiving anagliptin at a dose of 200 mg or 400 mg daily achieved an HbA1c level below 6.9%. Furthermore, the levels of HbA1c, fasting blood glucose, and postprandial blood glucose were significantly decreased at 52 weeks compared with the baseline values in a Phase III trial investigating the effects of anagliptin included in combination therapy with other oral antidiabetic agents. In a pooled analysis of Phase II and Phase II/III trials, the goal achievement rates for an HbA1c level below 7.0% at 12 weeks were 40.3%, 39.4%, 30.0%, and 34.8% in the patients treated with anagliptin combined with alpha-glucosidase inhibitors, thiazolidinediones, sulfonylureas, and biguanides, respectively. Meanwhile, the serum lipid concentrations significantly improved after the administration of anagliptin in a pooled analysis of Phase III trials, and no serious adverse effects have been reported in preclinical trials. Therefore, the use of anagliptin in patients with type 2 diabetes is considered to be safe and effective for both monotherapy and combination therapy.
ESTHER : Nishio_2015_Diabetes.Metab.Syndr.Obes_8_163
PubMedSearch : Nishio_2015_Diabetes.Metab.Syndr.Obes_8_163
PubMedID: 25834461

Title : The genetic organization of the capsular polysaccharide biosynthesis region of Actinobacillus pleuropneumoniae serotype 14 - Ito_2015_J.Vet.Med.Sci_77_583
Author(s) : Ito H
Ref : J Vet Med Sci , 77 :583 , 2015
Abstract : The genetic organization of the gene involved in the capsular polysaccharide (CPS) biosynthesis of Actinobacillus pleuropneumoniae serotype 14 has been determined. The DNA region for the CPS biosynthesis of serotype 14 (cps14) comprised 9 open reading frames, designated as cps14AB1B2B3CDEFG genes, encoding Cps14A to Cps14G protein, respectively. Cps14A was similar to CpsA of A. pleuropneumoniae serotypes 1, 4 and 12; the Cps14B1 and Cps14B2 were similar to CpsB of A. pleuropneumoniae serotypes 1, 4 and 12, suggesting that CPS structure of A. pleuropneumoniae serotype 14 would belong to Group I including A. pleuropneumoniae serotypes 1, 4, 12 and 15. Surprisingly, the overall nucleotide sequence, deduced amino acid sequence, and the genetic organization of the cps14 were nearly identical to those of Actinobacillus suis. This study will provide the molecular basic knowledge for development of diagnostics and vaccine of A. pleuropneumoniae serotype 14.
ESTHER : Ito_2015_J.Vet.Med.Sci_77_583
PubMedSearch : Ito_2015_J.Vet.Med.Sci_77_583
PubMedID: 25648373
Gene_locus related to this paper: actpl-a0a0h5ahc5

Title : Clinically meaningful treatment responses after switching to galantamine and with addition of memantine in patients with Alzheimer's disease receiving donepezil - Kano_2013_Neuropsychiatr.Dis.Treat_9_259
Author(s) : Kano O , Ito H , Takazawa T , Kawase Y , Murata K , Iwamoto K , Nagaoka T , Hirayama T , Miura K , Nagata R , Kiyozuka T , Aoyagi J , Sato R , Eguchi T , Ikeda K , Iwasaki Y
Ref : Neuropsychiatr Dis Treat , 9 :259 , 2013
Abstract : Clinical trials have shown the benefits of acetylcholinesterase inhibitors, such as donepezil and galantamine, and an N-methyl-D-aspartate receptor antagonist, memantine, in patients with Alzheimer's disease (AD). However, little is known regarding the effects of switching from donepezil 5 mg/day to galantamine 16 or 24 mg/day, or regarding the effects of adding memantine to established therapy compared with increasing the dose of donepezil. This report discusses two studies conducted to evaluate treatment with galantamine and memantine with respect to cognitive benefits and caregiver evaluations in patients with AD receiving donepezil 5 mg/day for more than 6 months. Patients with mild or moderate AD (scores 10-22 on the Mini-Mental State Examination) were enrolled in the Galantamine Switch study and switched to galantamine (maximum doses 16 mg versus 24 mg). Patients with moderate to severe AD (Mini-Mental State Examination scores 3-14) were enrolled in the Donepezil Increase versus Additional Memantine study and either had their donepezil dose increased to 10 mg/day or memantine 20 mg/day added to their existing donepezil dose. Patients received the study treatment for 28 weeks and their Disability Assessment for Dementia, Mental Function Impairment Scale, Cohen-Mansfield Agitation Inventory, and Neuropsychiatric Inventory scores were assessed with assistance from their caregivers. For the Galantamine Switch study after 8 weeks, agitation evaluated by the Cohen-Mansfield Agitation Inventory improved in both the 16 mg and 24 mg groups compared with baseline. However, there were no significant differences between the two galantamine groups. Agitation was also less in patients in the additional memantine group than in the donepezil increase group. In summary, switching to galantamine from donepezil and addition of memantine in patients with AD receiving donepezil were both safe and meaningful treatment options, and particularly efficacious for suppression of agitation.
ESTHER : Kano_2013_Neuropsychiatr.Dis.Treat_9_259
PubMedSearch : Kano_2013_Neuropsychiatr.Dis.Treat_9_259
PubMedID: 23431041

Title : Pancreatic lipase inhibitory gallotannins from Galla Rhois with inhibitory effects on adipocyte differentiation in 3T3-L1 cells - Kwon_2013_Molecules_18_10629
Author(s) : Kwon OJ , Bae JS , Lee HY , Hwang JY , Lee EW , Ito H , Kim TH
Ref : Molecules , 18 :10629 , 2013
Abstract : Activity-guided isolation of a methanolic extract of Galla Rhois using pancreatic lipase and 3T3-L1 adipocytes led to the isolation of seven phenolic compounds: protoaphin-fb (1), 2-O-digalloyl-1,3,4,6-tetra-O-galloyl-beta-D-glucose (2), 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (3), 1,2,4,6-tetra-O-galloyl-beta-D-glucose (4), 3-hydroxy-5-methoxy-phenol 1-O-beta-D-glucoside (5), methylgallate (6), and gallic acid (7). Their structures were established on the basis of NMR and MS spectroscopic data interpretation. All isolates were evaluated for their inhibitory effects on pancreatic lipase, and compounds 1-5 exhibited potent inhibitory effects on this enzyme, with IC50 values ranging from 30.6 +/- 2.4 to 3.5 +/- 0.5 mM. In addition, the highly galloylated compound 2 was also found to induce potent inhibition of adipocyte differentiation in 3T3-L1 cells.
ESTHER : Kwon_2013_Molecules_18_10629
PubMedSearch : Kwon_2013_Molecules_18_10629
PubMedID: 24002138

Title : Domperidone effective in preventing rivastigmine-related gastrointestinal disturbances in patients with Alzheimer's disease - Kano_2013_Neuropsychiatr.Dis.Treat_9_1411
Author(s) : Kano O , Urita Y , Ito H , Takazawa T , Kawase Y , Murata K , Hirayama T , Miura K , Ishikawa Y , Kiyozuka T , Aoyagi J , Iwasaki Y
Ref : Neuropsychiatr Dis Treat , 9 :1411 , 2013
Abstract : OBJECTIVE: While acetylcholinesterase inhibitors, such as donepezil, galantamine, and rivastig-mine, are beneficial in treating behavioral symptoms of patients with Alzheimer's disease (AD), their dose-limiting effects include gastrointestinal disturbances, such as nausea, vomiting, and diarrhea. We aimed to predict the occurrence of these gastrointestinal disturbances with rivastigmine therapy for optimal drug choice and improved compliance. MATERIALS AND
METHODS: Thirty patients with mild-to-moderate AD (scores 10-22 on the MiniMental State Examination) were administered a rivastigmine 18 mg patch with domperidone 30 mg (RWD) and without domperidone (RWOD; n = 15 each) for 20 weeks. Gastrointestinal disturbances were evaluated using a frequency scale for symptoms of gastroesophageal reflux disease (FSSG), Bristol stool form scale, laboratory data (hemoglobin, albumin, total cholesterol), body weight, and amount of food intake.
RESULTS: After 12 weeks, FSSG scores were higher in the RWOD group compared to baseline scores; however, no significant differences were noted between the RWD and RWOD groups. We then subdivided each group based on high and low baseline scores; the RWOD high-score (>/=4) subgroup showed increased FSSG after 12 weeks compared with the baseline score. In both RWD and RWOD groups, the low-score (</=3) subgroups showed no changes during the dose-escalation phase. CONCLUSION: For AD patients with higher FSSG scores at baseline, domperidone was effective in preventing rivastigmine-related gastrointestinal disturbances.
ESTHER : Kano_2013_Neuropsychiatr.Dis.Treat_9_1411
PubMedSearch : Kano_2013_Neuropsychiatr.Dis.Treat_9_1411
PubMedID: 24092978

Title : Steroids from Dysoxylum grande (Meliaceae) leaves - Wah_2013_Steroids_78_210
Author(s) : Wah LK , Abas F , Cordell GA , Ito H , Ismail IS
Ref : Steroids , 78 :210 , 2013
Abstract : Seven new 23-oxo-cholestane derivatives named as grandol A (1), B (2), C (3), D (4), E (5), F (6), and G (7) were isolated from Dysoxylum grande leaves alongside with a new 3,4-secodammar-4(28)-en-3-oic acid derivative (8). The structures of the compounds were elucidated based on the interpretation of spectroscopic data, and their relative configurations were established by NOESY 2D NMR data. All of the isolates were tested for anti-acetylcholinesterase activity using thin layer chromatography (TLC)-bioautography with fast blue B salt. Only grandol A (1) and B (2) showed positive results, with clear discoloration at a concentration of 12.5ppm. However, the obtained IC(50) values for grandol A and B, when using Ellman's method, were not significant (>200mug/ml).
ESTHER : Wah_2013_Steroids_78_210
PubMedSearch : Wah_2013_Steroids_78_210
PubMedID: 23178158

Title : Production and properties of lipase of Aeromonas sobria - Takahashi_2012_Microbiol.Immunol_56_295
Author(s) : Takahashi E , Ito H , Kobayashi H , Yamanaka H , Takeda Y , Balakrish Nair G , Arimoto S , Negishi T , Okamoto K
Ref : Microbiol Immunol , 56 :295 , 2012
Abstract : Aeromonas have been isolated from a wide variety of aquatic environments. However the number of Aeromonas in sea water is extremely small compared to that in fresh water. In in vitro culture, Aeromonas can grow in mediums containing NaCl at a concentration of 3.0%, this concentration corresponding to that of sea water. It is unclear why the number of Aeromonas is low in sea water. Exoproteins of bacteria are thought to be important for bacterial growth and survival in the environment. Previously, the present authors have shown that mediums containing 3.0% NaCl suppress production of two proteases, serine protease and metalloprotease. In this experiment, other exoproteins whose production is influenced by the amount of NaCl in the medium were analyzed. A protein whose production is repressed in medium containing 3.0% NaCl was found and purified. Biological assay of the purified protein showed that it degrades tributyrin and hydrolyzes para-nitrophenyl-fatty acylesters. These results show that the protein is a lipase. Subsequently, the nucleotide sequence of the gene encoding the lipase was determined and the amount of mRNA of the lipase gene in the cells measured. It was found that transcription of the gene is not inhibited by NaCl in the medium. This result indicates that the lipase might be synthesized, but the folding process to become an active structure does not progress smoothly in a medium containing 3.0% NaCl.
ESTHER : Takahashi_2012_Microbiol.Immunol_56_295
PubMedSearch : Takahashi_2012_Microbiol.Immunol_56_295
PubMedID: 22376235

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 : Acetylcholinesterase inhibitor acting on the brain improves detrusor overactivity caused by cerebral infarction in rats - Nakai_2006_Neurosci_142_475
Author(s) : Nakai M , Akino H , Kaneda T , Matsuta Y , Shiyama R , Tanase K , Ito H , Aoki Y , Oyama N , Miwa Y , Yokoyama O
Ref : Neuroscience , 142 :475 , 2006
Abstract : PURPOSE: The functional contribution of the cholinergic pathway in the frontal cortex to micturition was evaluated following cerebral ischemia. Furthermore, it was examined whether reactivation of this regulatory system using acetylcholinesterase inhibitor could improve detrusor overactivity.
METHODS: Left middle cerebral artery occlusion (MCAO) was performed in female Sprague-Dawley rats. Choline acetyltransferase (ChAT) activities after MCAO were assayed to assess the damage to cholinergic neurons. ChAT activities in the bilateral cortex, hippocampus, and pons were calculated by measuring the conversion of 1-[14C] acetyl-coenzyme A to [14C] acetylcholine. Effects on cystometrography of i.v. or i.c.v. donepezil hydrochloride (DON), a centrally acting acetylcholinesterase inhibitor, were investigated in conscious sham-operated (SO) and cerebral infarcted (CI) rats. To investigate whether DON in the forebrain was affected, we decerebrated rats after CI or SO, and investigated the effects on cystometrography of i.v. DON.
RESULTS: Bladder capacity was markedly decreased after MCAO, and remained below half of the pre-occlusion capacity. The greatest increase in bladder capacity was attained at 1.2 x 10(-2) nM/kg of DON given i.v., with a change of 52.8% (P < 0.05). In cases of i.c.v. DON, the greatest increase in bladder capacity was at the dose of 6 x 10(-2) pmol with the change of 95.8% (P < 0.01). The activity of ChAT was decreased in the left cortex and hippocampus 24 h after MCAO (P < 0.05). In decerebrated rats, low dose of DON did not change micturition parameters.
CONCLUSIONS: These results suggest that by upregulation of the forebrain muscarinic inhibitory mechanism, acetylcholinesterase inhibitor improves detrusor overactivity by cerebral infarction.
ESTHER : Nakai_2006_Neurosci_142_475
PubMedSearch : Nakai_2006_Neurosci_142_475
PubMedID: 16905267

Title : Development and application of serum cholinesterase activity measurement using benzoylthiocholine iodide - Osawa_2005_Clin.Chim.Acta_351_65
Author(s) : Osawa S , Kariyone K , Ichihara F , Arai K , Takagasa N , Ito H
Ref : Clinica Chimica Acta , 351 :65 , 2005
Abstract : BACKGROUND: Measurement of cholinesterase activity in serum is important to identify substantial liver disease and damage by pesticides, and to assess the degree of development of fatty liver and preoperative risk. Many procedures using various artificial substrates have been developed but suffer from problems with substrate specificity and interference by endogenous substances.
METHODS: An assay pseudocholinesterase (ChE, EC acylcholine acylhydrolase) activity was developed using a stable substrate specific to ChE, benzoylthiocholine iodide (BZTC). The thiocholine generated by hydrolysis of BZTC by ChE activity reacts with 2, 2'-dipyridildisulfide (2-PDS) to produce 2-thiopyridine (2-TP), which is measured at 340 nm. Optimum pH, buffer types and concentrations, substrate concentrations, and optimum conditions of the color reaction were investigated. The substrate specificity, test interferences, correlation with other measurement methods, and reference interval were evaluated.
RESULTS: The optimum pH of this method was 7.8, and 3-[4-(2-hydroxyethyl)-1-piperazinyl] propanesulfonic acid (EPPS) buffer solution was selected. Constant activity was shown at buffer concentrations >200 mmol/l, and the maximum activity was shown at a substrate concentration of 0.2 mmol/l. When a Hill plot was utilized, the Hill number was 1.08 and 1.09. The reaction velocity at this substrate concentration was 94% of V(max). The K(m) of ChE to BZTC was between 1.2 x 10(-2) and 1.3 x 10(-2) mmol/l. The range was 0-300 U/l. The coefficients of variation (CV) for 20 measurements of serum containing 53.1, 96.6, and 270.7 U/l of ChE were 0.82%, 0.76%, and 0.54%, respectively. The relative reactivity of acetylcholinesterase (AChE) to this substrate was 2%. The correlation factors of this method to three other methods were between 0.993 and 0.998.
CONCLUSIONS: This method provides excellent specificity, reproducibility, a wide measurement range, and minimal interference from endogenous substances to common serum analytes. Correlation of this method with conventional methods was good. Because the reagents are stable after preparation, this assay is useful for routine analysis.
ESTHER : Osawa_2005_Clin.Chim.Acta_351_65
PubMedSearch : Osawa_2005_Clin.Chim.Acta_351_65
PubMedID: 15563872

Title : The genome sequence and structure of rice chromosome 1 - Sasaki_2002_Nature_420_312
Author(s) : Sasaki T , Matsumoto T , Yamamoto K , Sakata K , Baba T , Katayose Y , Wu J , Niimura Y , Cheng Z , Nagamura Y , Antonio BA , Kanamori H , Hosokawa S , Masukawa M , Arikawa K , Chiden Y , Hayashi M , Okamoto M , Ando T , Aoki H , Arita K , Hamada M , Harada C , Hijishita S , Honda M , Ichikawa Y , Idonuma A , Iijima M , Ikeda M , Ikeno M , Ito S , Ito T , Ito Y , Iwabuchi A , Kamiya K , Karasawa W , Katagiri S , Kikuta A , Kobayashi N , Kono I , Machita K , Maehara T , Mizuno H , Mizubayashi T , Mukai Y , Nagasaki H , Nakashima M , Nakama Y , Nakamichi Y , Nakamura M , Namiki N , Negishi M , Ohta I , Ono N , Saji S , Sakai K , Shibata M , Shimokawa T , Shomura A , Song J , Takazaki Y , Terasawa K , Tsuji K , Waki K , Yamagata H , Yamane H , Yoshiki S , Yoshihara R , Yukawa K , Zhong H , Iwama H , Endo T , Ito H , Hahn JH , Kim HI , Eun MY , Yano M , Jiang J , Gojobori T
Ref : Nature , 420 :312 , 2002
Abstract : The rice species Oryza sativa is considered to be a model plant because of its small genome size, extensive genetic map, relative ease of transformation and synteny with other cereal crops. Here we report the essentially complete sequence of chromosome 1, the longest chromosome in the rice genome. We summarize characteristics of the chromosome structure and the biological insight gained from the sequence. The analysis of 43.3 megabases (Mb) of non-overlapping sequence reveals 6,756 protein coding genes, of which 3,161 show homology to proteins of Arabidopsis thaliana, another model plant. About 30% (2,073) of the genes have been functionally categorized. Rice chromosome 1 is (G + C)-rich, especially in its coding regions, and is characterized by several gene families that are dispersed or arranged in tandem repeats. Comparison with a draft sequence indicates the importance of a high-quality finished sequence.
ESTHER : Sasaki_2002_Nature_420_312
PubMedSearch : Sasaki_2002_Nature_420_312
PubMedID: 12447438
Gene_locus related to this paper: orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5NA74 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q94D81 , orysa-cbp , orysa-Q5VQE5 , orysa-Q8RZ95 , orysa-Q9AWW1 , orysa-Q9AS70 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q943F9 , orysa-B9EWJ8 , orysa-Q5N8H1 , orysa-Q5NAI4 , orysa-Q94DP8 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q5N7J6 , orysa-Q8RYV9 , orysa-Q5SNH3 , orysa-Q94DD0 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-Q4VWY7 , orysa-q5jlm9 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5vnp5 , orysa-Q5VP27 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-q5zc23 , orysa-Q5ZCR3 , orysa-Q8L562 , orysa-Q8L570 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q9LHX5 , orysa-Q94E46 , orysa-Q656F2 , orysi-a2wn01 , orysi-b8a7e6 , orysi-b8a7e7 , orysj-b9eya5 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q94d71

Title : Effect of prolonged administration of a urinary kinase inhibitor, ebelactone B on the development of deoxycorticosterone acetate-salt hypertension in rats - Ito_1999_Br.J.Pharmacol_126_613
Author(s) : Ito H , Majima M , Nakajima S , Hayashi I , Katori M , Izumi T
Ref : British Journal of Pharmacology , 126 :613 , 1999
Abstract : The effect of prolonged administration of a carboxypeptidase Y-like kininase inhibitor, ebelactone B (EB) (2-ethyl-3, 11-dihydroxy-4, 6, 8, 10, 12-pentamethyl-9-oxo-6-tetradecenoic 1, 3-lactone), on the development of deoxycorticosterone acetate (DOCA)-salt hypertension was tested. The systolic blood pressure (SBP) of non-treated 6-week-old Sprague-Dawley strain rats was gradually increased by DOCA-salt treatment from 137+/-2 mmHg (n=11) to 195+/-7 mmHg at 10 weeks of age. With daily oral administration of lisinopril (5 mg kg(-1), twice a day), which is an inhibitor of angiotensin converting enzyme, a major kininase in plasma, the development of hypertension was not suppressed. By contrast, administration of EB (5 mg kg(-1), twice a day), completely inhibited the development of hypertension (SBP: 146+/-1 mmHg, n=5, 10 weeks old). The reduced SBP at 10 weeks of age was equal to the SBP before any treatment (142+/-1 mmHg, n=5). Direct determination of mean blood pressure (MBP) in conscious, unrestrained rats confirmed that MBP elevation was completely inhibited by EB. Continuous subcutaneous infusion (5 mg kg(-1) day(-1)) of HOE140, a bradykinin B2 receptor antagonist, restored the elevation of SBP, which was suppressed by EB. The weights of left ventricle of DOCA-salt treated rats 10-weeks-old (0.36+/-0.02 g 100 g body weight(-1), n=11) was significantly reduced by EB (0.27+/-0.01, n=5), as were the sodium levels in serum, cerebrospinal fluid and erythrocyte. These findings suggested that EB is effective in preventing salt-related hypertension presumably by eliminating sodium retention.
ESTHER : Ito_1999_Br.J.Pharmacol_126_613
PubMedSearch : Ito_1999_Br.J.Pharmacol_126_613
PubMedID: 10188971

Title : A novel nonsense mutation in exon 1 and a transition in intron 3 of the lipoprotein lipase gene - Nakamura_1996_J.Atheroscler.Thromb_3_17
Author(s) : Nakamura T , Suehiro T , Yasuoka N , Yamamoto M , Ito H , Yamano T , Hashimoto K
Ref : J Atheroscler Thromb , 3 :17 , 1996
Abstract : We examined the lipoprotein lipase (LPL) gene by single strand conformation polymorphism (SSCP) and by restriction fragment length polymorphism (RFLP) analysis in 106 patients with hypertriglyceridemia to screen for novel mutations and to study the contribution of LPL genetic defects in hypertriglyceridemia. We found a single incidence of a homozygous novel nonsense mutation (216G-->A; -14Tryptophan-->stop codon) in exon 1 and 6 cases heterozygous for a single transition (C-->T) at six bp upstream from splicing acceptor site of intron 3. These mutations were not found in 105 normolipidemic controls. The proband homozygous for the nonsense mutation in exon 1, a 74 year old woman, had mild hyperchylomicronemia and her post-heparin plasma showed no LPL protein. However, four heterozygous among family members did not demonstrate hypertriglyceridemia. The frequency of heterozygosity for the C-->T transition in intron 3 was significantly different from that in normolipidemic controls. Therefore, it was suggested that the mutation is involved in hypertriglyceridemia. All of the heterozygotes were men with 4 patients having impaired glucose tolerance or diabetes mellitus. These observations suggest that this polymorphism in intron 3 combined with other as yet undefined factors may be related to hypertriglyceridemia.
ESTHER : Nakamura_1996_J.Atheroscler.Thromb_3_17
PubMedSearch : Nakamura_1996_J.Atheroscler.Thromb_3_17
PubMedID: 9225235

Title : Acetylcholine and adenosine activate the G protein-gated muscarinic K+ channel in ferret ventricular myocytes - Ito_1995_Naunyn.Schmiedebergs.Arch.Pharmacol_351_610
Author(s) : Ito H , Hosoya Y , Inanobe A , Tomoike H , Endoh M
Ref : Naunyn Schmiedebergs Arch Pharmacol , 351 :610 , 1995
Abstract : The properties of the K+ channel activated by acetylcholine (ACh) and adenosine (Ado) were examined in single ferret ventricular myocytes using patch-clamp techniques. In the whole-cell configuration, ACh and Ado induced an inwardly rectifying K+ current and shortened the action potential duration. The effect of ACh was blocked by atropine, while the Ado effect was interrupted by 8-cyclopentyl,1,2-dipropyl xanthine, a specific Ado A1 receptor antagonist. In cell-attached recordings, ACh and Ado added to the pipette solution activated a single population of inwardly rectifying K+ channels, distinct from the iK1 channel. The channel had a slope conductance of approximately 40 pS in symmetrical 150 mM K+ solutions and a mean open time of 0.8 ms. Excision of the patch into the inside-out patch configuration in guanosine triphosphate (GTP)-free solution abolished the channel activity. The channel was reversibly reactivated by adding GTP to the intracellular side of the patch. GTP gamma S activated the channel irreversibly. When the inside-out patch was treated with the A protomer of pertussis toxin (PTX), intracellular GTP no longer activated the K+ channel. The results show that ferret ventricular myocytes possess a K+ channel activated by both muscarinic and Ado A1 receptors. Its electrophysiological properties and the gating by a PTX-sensitive G protein in a membrane-delimited fashion are identical with those of the muscarinic K+ channels in nodal and atrial tissues of other species. In conclusion, the G protein-gated muscarinic K+ channel is expressed in ferret ventricular myocardium and may underlie the direct negative inotropism of ACh and Ado in this tissue.
ESTHER : Ito_1995_Naunyn.Schmiedebergs.Arch.Pharmacol_351_610
PubMedSearch : Ito_1995_Naunyn.Schmiedebergs.Arch.Pharmacol_351_610
PubMedID: 7675119