Ohnishi T

References (6)

Title : Conversion of carlactone to carlactonoic acid is a conserved function of MAX1 homologs in strigolactone biosynthesis - Yoneyama_2018_New.Phytol_218_1522
Author(s) : Yoneyama K , Mori N , Sato T , Yoda A , Xie X , Okamoto M , Iwanaga M , Ohnishi T , Nishiwaki H , Asami T , Yokota T , Akiyama K , Nomura T
Ref : New Phytol , 218 :1522 , 2018
Abstract : Strigolactones (SLs) are a class of plant hormones which regulate shoot branching and function as host recognition signals for symbionts and parasites in the rhizosphere. However, steps in SL biosynthesis after carlactone (CL) formation remain elusive. This study elucidated the common and diverse functions of MAX1 homologs which catalyze CL oxidation. We have reported previously that ArabidopsisMAX1 converts CL to carlactonoic acid (CLA), whereas a rice MAX1 homolog has been shown to catalyze the conversion of CL to 4-deoxyorobanchol (4DO). To determine which reaction is conserved in the plant kingdom, we investigated the enzymatic function of MAX1 homologs in Arabidopsis, rice, maize, tomato, poplar and Selaginella moellendorffii. The conversion of CL to CLA was found to be a common reaction catalyzed by MAX1 homologs, and MAX1s can be classified into three types: A1-type, converting CL to CLA; A2-type, converting CL to 4DO via CLA; and A3-type, converting CL to CLA and 4DO to orobanchol. CLA was detected in root exudates from poplar and Selaginella, but not ubiquitously in other plants examined in this study, suggesting its role as a species-specific signal in the rhizosphere. This study provides new insights into the roles of MAX1 in endogenous and rhizosphere signaling.
ESTHER : Yoneyama_2018_New.Phytol_218_1522
PubMedSearch : Yoneyama_2018_New.Phytol_218_1522
PubMedID: 29479714

Title : Long-term effect of galantamine on cognitive function in patients with Alzheimer's disease versus a simulated disease trajectory: an observational study in the clinical setting - Nakagawa_2017_Neuropsychiatr.Dis.Treat_13_1115
Author(s) : Nakagawa R , Ohnishi T , Kobayashi H , Yamaoka T , Yajima T , Tanimura A , Kato T , Yoshizawa K
Ref : Neuropsychiatr Dis Treat , 13 :1115 , 2017
Abstract : BACKGROUND: Long-term maintenance of cognitive function is an important goal of treatment for Alzheimer's disease (AD), but evidence about the long-term efficacy of cholinesterase inhibitors is sparse. To evaluate the long-term efficacy and safety of galantamine for AD in routine clinical practice, we conducted a 72-week post-marketing surveillance study. The effect of galantamine on cognitive function was estimated in comparison with a simulated disease trajectory. PATIENTS AND
METHODS: Patients with mild-to-moderate AD received flexible dosing of galantamine (16-24 mg/day) during this study. Cognitive function was assessed by the mini mental state examination (MMSE) and the clinical status was determined by the Clinical Global Impression-Improvement (CGI-I). Changes of the MMSE score without treatment were estimated in each patient using Mendiondo's model. Generalized linear mixed model analysis was performed to compare the simulated MMSE scores with the actual scores.
RESULTS: Of the 661 patients who were enrolled, 642 were evaluable for safety and 554 were assessed for efficacy. The discontinuation rate was 46.73%. Cognitive decline indicated by the mean change of actual MMSE scores was significantly smaller than the simulated decline. Individual analysis demonstrated that >70% of patients had better actual MMSE scores than their simulated scores. Significant improvement of CGI-I was also observed during the observation period. Adverse events occurred in 28.5% of patients and were serious in 8.41%. The reported events generally corresponded with the safety profile of galantamine in previous studies. CONCLUSION: These findings support the long-term efficacy of galantamine for maintaining cognitive function and the clinical state in AD patients. Treatment with galantamine was generally safe. Importantly, this study revealed that galantamine improved cognitive function above the predicted level in >70% of the patients.
ESTHER : Nakagawa_2017_Neuropsychiatr.Dis.Treat_13_1115
PubMedSearch : Nakagawa_2017_Neuropsychiatr.Dis.Treat_13_1115
PubMedID: 28458553

Title : The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer's disease: a Bayesian network meta-analysis - Kobayashi_2016_Int.J.Geriatr.Psychiatry_31_892
Author(s) : Kobayashi H , Ohnishi T , Nakagawa R , Yoshizawa K
Ref : Int J Geriatr Psychiatry , 31 :892 , 2016
Abstract : BACKGROUND: Comparative evidence for efficacy and safety of second-generation cholinesterase inhibitors (ChEIs) is still sparse. OBJECTIVES: The purpose of this research is to compare three ChEIs, donepezil, galantamine and rivastigmine, in patients with mild-to-moderate Alzheimer's disease (AD).
METHODS: We conducted a systematic review for published articles and included randomised, double-blind, placebo-controlled trials and head-to-head randomised trials evaluating the efficacy and safety of ChEIs in patients with AD. We examined Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog), Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of Change plus caregiver's input (CIBIC+) and Clinical Global Impression of Change (CGIC) as efficacy endpoints. Withdrawals due to adverse events and number of patients experiencing nausea, vomiting, diarrhoea and dizziness were examined as safety profiles. Network meta-analyses were sequentially performed for efficacy and safety outcomes based on drug/dose treatment conditions.
RESULTS: Among the 21 trials included, network meta-analysis showed that all treatments were significantly more efficacious than placebo in cognition measured by ADAS-Cog. All treatments except galantamine were significantly more efficacious than placebo in global change in CIBIC+ or CGIC. Across all conditions, no significant efficacy was observed in neuropsychiatric symptoms measured by NPI. Derived hierarchies in the efficacy of treatment conditions were variables across efficacy and safety.
CONCLUSIONS: Our analysis is the first attempt to incorporate available direct and indirect evidence. The results suggest that ChEIs should have significant efficacy for cognition and global change assessment, but the efficacy on neuropsychiatric symptoms is questionable in patients with mild-to-moderate AD.
ESTHER : Kobayashi_2016_Int.J.Geriatr.Psychiatry_31_892
PubMedSearch : Kobayashi_2016_Int.J.Geriatr.Psychiatry_31_892
PubMedID: 26680338

Title : The prediction of response to Galantamine treatment in Patients with mild to moderate Alzheimer's Disease - Ohnishi_2014_Curr.Alzheimer.Res_11_110
Author(s) : Ohnishi T , Sakiyama Y , Okuri Y , Kimura Y , Sugiyama N , Saito T , Takahashi M , Kobayashi T
Ref : Curr Alzheimer Res , 11 :110 , 2014
Abstract : The prediction of efficacy in long-term treatment of acetylcholinesterase inhibitors (AChEIs) is a major clinical issue, although no consistently strong predictive factors have emerged thus far. The present analyses aimed to identify factors for predicting long-term outcome of galantamine treatment. Analyses were conducted with data from a 24 weeks randomized, double-blind, placebo controlled trial to evaluate the efficacy and the safety of galantamine in the treatment of 303 patients with mild to moderate AD. Patients were divided into responders (4 or more point improvement of ADAScog scores at 24 weeks of treatment) and non-responders. We explored whether patients' background (e.g. sex, age, and duration of disease) and scores of cognitive scales at early stage, are relevant to the long-term response to AChEIs. Predictive values were estimated by the logistic regression model. The responder rate was 31.7%. We found that changes in scores of ADAS-J cog subscales between week 4 and baseline, especially word recognition, can be a good variable to predict subsequent response to galantamine, with approximately 75% of predictive performance. Characteristics of patients, including demographic characteristics, severity of disease and neuropsychological features before treatment were poorly predictive. The present study indicate that initial response to galantamine administration in patients with mild to moderate AD seems to be a reliable predictor of response of consequent galantamine treatment. Patients who show improvement of episodic memory function during the first 4 weeks of galantamine administration may be likely to particularly benefit from galantamine treatment.
ESTHER : Ohnishi_2014_Curr.Alzheimer.Res_11_110
PubMedSearch : Ohnishi_2014_Curr.Alzheimer.Res_11_110
PubMedID: 24156269

Title : Carlactone is converted to carlactonoic acid by MAX1 in Arabidopsis and its methyl ester can directly interact with AtD14 in vitro - Abe_2014_Proc.Natl.Acad.Sci.U.S.A_111_18084
Author(s) : Abe S , Sado A , Tanaka K , Kisugi T , Asami K , Ota S , Kim HI , Yoneyama K , Xie X , Ohnishi T , Seto Y , Yamaguchi S , Akiyama K , Nomura T
Ref : Proc Natl Acad Sci U S A , 111 :18084 , 2014
Abstract : Strigolactones (SLs) stimulate seed germination of root parasitic plants and induce hyphal branching of arbuscular mycorrhizal fungi in the rhizosphere. In addition, they have been classified as a new group of plant hormones essential for shoot branching inhibition. It has been demonstrated thus far that SLs are derived from carotenoid via a biosynthetic precursor carlactone (CL), which is produced by sequential reactions of DWARF27 (D27) enzyme and two carotenoid cleavage dioxygenases CCD7 and CCD8. We previously found an extreme accumulation of CL in the more axillary growth1 (max1) mutant of Arabidopsis, which exhibits increased lateral inflorescences due to SL deficiency, indicating that CL is a probable substrate for MAX1 (CYP711A1), a cytochrome P450 monooxygenase. To elucidate the enzymatic function of MAX1 in SL biosynthesis, we incubated CL with a recombinant MAX1 protein expressed in yeast microsomes. MAX1 catalyzed consecutive oxidations at C-19 of CL to convert the C-19 methyl group into carboxylic acid, 9-desmethyl-9-carboxy-CL [designated as carlactonoic acid (CLA)]. We also identified endogenous CLA and its methyl ester [methyl carlactonoate (MeCLA)] in Arabidopsis plants using LC-MS/MS. Although an exogenous application of either CLA or MeCLA suppressed the growth of lateral inflorescences of the max1 mutant, MeCLA, but not CLA, interacted with Arabidopsis thaliana DWARF14 (AtD14) protein, a putative SL receptor, as shown by differential scanning fluorimetry and hydrolysis activity tests. These results indicate that not only known SLs but also MeCLA are biologically active in inhibiting shoot branching in Arabidopsis.
ESTHER : Abe_2014_Proc.Natl.Acad.Sci.U.S.A_111_18084
PubMedSearch : Abe_2014_Proc.Natl.Acad.Sci.U.S.A_111_18084
PubMedID: 25425668
Gene_locus related to this paper: arath-AtD14

Title : Biosynthesis and degradation of the endocannabinoid 2-arachidonoylglycerol - Ueda_2011_Biofactors_37_1
Author(s) : Ueda N , Tsuboi K , Uyama T , Ohnishi T
Ref : Biofactors , 37 :1 , 2011
Abstract : 2-Arachidonoylglycerol (2-AG) is a monoacylglycerol (MAG) molecule containing an esterified arachidonic acid chain at sn-2 position of the glycerol backbone. Together with structurally similar N-arachidonoylethanolamine (anandamide), 2-AG has been extensively studied as an endogenous ligand of cannabinoid receptors (an endocannabinoid) in brain and other mammalian tissues. Accumulating evidence demonstrates that the endocannabinoid system, including the central-type cannabinoid receptor CB1 and 2-AG, is responsible for synaptic retrograde signaling in the central nervous system. As 2-AG is rapidly formed from membrane phospholipids on cellular stimuli and degraded to arachidonic acid and glycerol, the enzymes catalyzing its biosynthesis and degradation are believed to play crucial roles in the regulation of its tissue levels. The major biosynthetic pathway appears to consist of sequential hydrolyses of inositol phospholipids via diacylglycerol (DAG) by alpha-type phospholipase C and DAG lipase, while MAG lipase is a principal enzyme in the degradation. In this short review, we will briefly outline rapid advances in enzymological research on the biosynthetic and degradative pathways of 2-AG.
ESTHER : Ueda_2011_Biofactors_37_1
PubMedSearch : Ueda_2011_Biofactors_37_1
PubMedID: 21328621