Yamamoto N

References (16)

Title : Exploration of DPP-IV Inhibitory Peptide Design Rules Assisted by the Deep Learning Pipeline That Identifies the Restriction Enzyme Cutting Site - Guan_2023_ACS.Omega_8_39662
Author(s) : Guan C , Luo J , Li S , Tan ZL , Wang Y , Chen H , Yamamoto N , Zhang C , Lu Y , Chen J , Xing XH
Ref : ACS Omega , 8 :39662 , 2023
Abstract : The mining of antidiabetic dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (DPP-IV-IPs) is currently a costly and laborious process. Due to the absence of rational peptide design rules, it relies on cumbersome screening of unknown enzyme hydrolysates. Here, we present an enhanced deep learning model called bidirectional encoder representation (BERT)-DPPIV, specifically designed to classify DPP-IV-IPs and explore their design rules to discover potent candidates. The end-to-end model utilizes a fine-tuned BERT architecture to extract structural/functional information from input peptides and accurately identify DPP-IV-Ips from input peptides. Experimental results in the benchmark data set showed BERT-DPPIV yielded state-of-the-art accuracy and MCC of 0.894 and 0.790, surpassing the 0.797 and 0.594 obtained by the sequence-feature model. Furthermore, we leveraged the attention mechanism to uncover that our model could recognize the restriction enzyme cutting site and specific residues that contribute to the inhibition of DPP-IV. Moreover, guided by BERT-DPPIV, proposed design rules for DPP-IV inhibitory tripeptides and pentapeptides were validated, and they can be used to screen potent DPP-IV-IPs.
ESTHER : Guan_2023_ACS.Omega_8_39662
PubMedSearch : Guan_2023_ACS.Omega_8_39662
PubMedID: 37901493

Title : Clinical Significance of PLA2G2A Expression in Gastric Cancer Patients who Receive Gastrectomy and Adjuvant S-1 - Hatori_2021_Anticancer.Res_41_3583
Author(s) : Hatori S , Sakamaki K , Yokohori T , Kimura Y , Hiroshima Y , Hashimoto I , Komori K , Watanabe H , Kano K , Fujikawa H , Aoyama T , Numata M , Yamada T , Tamagawa H , Yamamoto N , Ogata T , Shizawa M , Yukawa N , Morinaga S , Rino Y , Masuda M , Saeki H , Miyagi Y , Oshima T
Ref : Anticancer Research , 41 :3583 , 2021
Abstract : BACKGROUND/AIM: This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated. RESULTS: No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049). CONCLUSION: PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.
ESTHER : Hatori_2021_Anticancer.Res_41_3583
PubMedSearch : Hatori_2021_Anticancer.Res_41_3583
PubMedID: 34230154

Title : Klebsormidium flaccidum genome reveals primary factors for plant terrestrial adaptation - Hori_2014_Nat.Commun_5_3978
Author(s) : Hori K , Maruyama F , Fujisawa T , Togashi T , Yamamoto N , Seo M , Sato S , Yamada T , Mori H , Tajima N , Moriyama T , Ikeuchi M , Watanabe M , Wada H , Kobayashi K , Saito M , Masuda T , Sasaki-Sekimoto Y , Mashiguchi K , Awai K , Shimojima M , Masuda S , Iwai M , Nobusawa T , Narise T , Kondo S , Saito H , Sato R , Murakawa M , Ihara Y , Oshima-Yamada Y , Ohtaka K , Satoh M , Sonobe K , Ishii M , Ohtani R , Kanamori-Sato M , Honoki R , Miyazaki D , Mochizuki H , Umetsu J , Higashi K , Shibata D , Kamiya Y , Sato N , Nakamura Y , Tabata S , Ida S , Kurokawa K , Ohta H
Ref : Nat Commun , 5 :3978 , 2014
Abstract : The colonization of land by plants was a key event in the evolution of life. Here we report the draft genome sequence of the filamentous terrestrial alga Klebsormidium flaccidum (Division Charophyta, Order Klebsormidiales) to elucidate the early transition step from aquatic algae to land plants. Comparison of the genome sequence with that of other algae and land plants demonstrate that K. flaccidum acquired many genes specific to land plants. We demonstrate that K. flaccidum indeed produces several plant hormones and homologues of some of the signalling intermediates required for hormone actions in higher plants. The K. flaccidum genome also encodes a primitive system to protect against the harmful effects of high-intensity light. The presence of these plant-related systems in K. flaccidum suggests that, during evolution, this alga acquired the fundamental machinery required for adaptation to terrestrial environments.
ESTHER : Hori_2014_Nat.Commun_5_3978
PubMedSearch : Hori_2014_Nat.Commun_5_3978
PubMedID: 24865297
Gene_locus related to this paper: kleni-a0a1y1i5c5 , kleni-a0a1y1i3f9 , kleni-a0a1y1hnk2 , kleni-a0a1y1hsz2 , kleni-a0a1y1hva2 , kleni-a0a1y1i2g3 , kleni-a0a1y1i4h5 , kleni-a0a1y1i9h9

Title : Total cholesterol level for assessing pancreatic insufficiency due to chronic pancreatitis - Hirano_2014_Gut.Liver_8_563
Author(s) : Hirano K , Saito T , Mizuno S , Tada M , Sasahira N , Isayama H , Matsukawa M , Umefune G , Akiyama D , Saito K , Kawahata S , Takahara N , Uchino R , Hamada T , Miyabayashi K , Mohri D , Sasaki T , Kogure H , Yamamoto N , Nakai Y , Koike K
Ref : Gut Liver , 8 :563 , 2014
Abstract : BACKGROUND/AIMS: To determine the nutritional markers important for assessing the degree of pancreatic insufficiency due to chronic pancreatitis in routine clinical practice.
METHODS: A total of 137 patients with chronic pancreatitis were followed up for more than 1 year. They were divided into two groups: a pancreatic diabetes mellitus (DM) group, consisting of 47 patients undergoing medical treatment for DM of pancreatic origin, and a nonpancreatic DM group, consisting of 90 other patients (including 86 patients without DM). Serum albumin, prealbumin, total cholesterol, cholinesterase, magnesium, and hemoglobin were compared between the two groups.
RESULTS: The total cholesterol was significantly lower in the pancreatic than the nonpancreatic DM group (164 mg/dL vs 183 mg/dL, respectively; p=0.0028). Cholinesterase was significantly lower in the former group (263 U/L vs 291 U/L, respectively; p=0.016). Among the 37 patients with nonalcoholic pancreatitis, there was no difference in the cholinesterase levels between the pancreatic and nonpancreatic (296 U/L vs 304 U/L, respectively; p=0.752) DM groups, although cholesterol levels remained lower in the former (165 mg/dL vs 187 mg/dL, respectively; p=0.052).
CONCLUSIONS: Cholinesterase levels are possibly affected by concomitant alcoholic liver injury. The total cholesterol level should be considered when assessing pancreatic insufficiency due to chronic pancreatitis.
ESTHER : Hirano_2014_Gut.Liver_8_563
PubMedSearch : Hirano_2014_Gut.Liver_8_563
PubMedID: 25228979

Title : Synthesis of (-)-homogalanthamine from naltrexone - Yamamoto_2011_J.Org.Chem_76_2257
Author(s) : Yamamoto N , Fujii H , Imaide S , Hirayama S , Nemoto T , Inokoshi J , Tomoda H , Nagase H
Ref : J Org Chem , 76 :2257 , 2011
Abstract : Acetylcholinesterase inhibitor (-)-homogalanthamine 3 was synthesized from u opioid antagonist naltrexone (2) in 16% total yield. The synthesis features Grob fragmentation as a key reaction, which was especially accelerated in the presence of 15-crown-5
ESTHER : Yamamoto_2011_J.Org.Chem_76_2257
PubMedSearch : Yamamoto_2011_J.Org.Chem_76_2257
PubMedID: 21381712

Title : Association of carboxylesterase 1A genotypes with irinotecan pharmacokinetics in Japanese cancer patients - Sai_2010_Br.J.Clin.Pharmacol_70_222
Author(s) : Sai K , Saito Y , Tatewaki N , Hosokawa M , Kaniwa N , Nishimaki-Mogami T , Naito M , Sawada J , Shirao K , Hamaguchi T , Yamamoto N , Kunitoh H , Tamura T , Yamada Y , Ohe Y , Yoshida T , Minami H , Ohtsu A , Matsumura Y , Saijo N , Okuda H
Ref : British Journal of Clinical Pharmacology , 70 :222 , 2010
Abstract : WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Association of UDP-glucuronosyltransferase 1A1 (UGT1A1) genetic polymorphisms *6 and *28 with reduced clearance of SN-38 and severe neutropenia in irinotecan therapy was demonstrated in Japanese cancer patients. * The detailed gene structure of CES1 has been characterized. * Possible functional SNPs in the promoter region have been reported. WHAT THIS STUDY ADDS * Association of functional CES1 gene number with AUC ratio [(SN-38 + SN-38G)/irinotecan], an in vivo index of CES activity, was observed in patients with irinotecan monotherapy. * No significant effects of major CES1 SNPs on irinotecan PK were detected. AIMS Human carboxylesterase 1 (CES1) hydrolyzes irinotecan to produce an active metabolite SN-38 in the liver. The human CES1 gene family consists of two functional genes, CES1A1 (1A1) and CES1A2 (1A2), which are located tail-to-tail on chromosome 16q13-q22.1 (CES1A2-1A1). The pseudogene CES1A3 (1A3) and a chimeric CES1A1 variant (var1A1) are also found as polymorphic isoforms of 1A2 and 1A1, respectively. In this study, roles of CES1 genotypes and major SNPs in irinotecan pharmacokinetics were investigated in Japanese cancer patients. METHODS CES1A diplotypes [combinations of haplotypes A (1A3-1A1), B (1A2-1A1), C (1A3-var1A1) and D (1A2-var1A1)] and the major SNPs (-75T>G and -30G>A in 1A1, and -816A>C in 1A2 and 1A3) were determined in 177 Japanese cancer patients. Associations of CES1 genotypes, number of functional CES1 genes (1A1, 1A2 and var1A1) and major SNPs, with the AUC ratio of (SN-38 + SN-38G)/irinotecan, a parameter of in vivo CES activity, were analyzed for 58 patients treated with irinotecan monotherapy. RESULTS The median AUC ratio of patients having three or four functional CES1 genes (diplotypes A/B, A/D or B/C, C/D, B/B and B/D; n= 35) was 1.24-fold of that in patients with two functional CES1 genes (diplotypes A/A, A/C and C/C; n= 23) [median (25th-75th percentiles): 0.31 (0.25-0.38) vs. 0.25 (0.20-0.32), P= 0.0134]. No significant effects of var1A1 and the major SNPs examined were observed. CONCLUSION This study suggests a gene-dose effect of functional CES1A genes on SN-38 formation in irinotecan-treated Japanese cancer patients.
ESTHER : Sai_2010_Br.J.Clin.Pharmacol_70_222
PubMedSearch : Sai_2010_Br.J.Clin.Pharmacol_70_222
PubMedID: 20653675
Gene_locus related to this paper: human-CES1

Title : Nicotinic receptor stimulation protects nigral dopaminergic neurons in rotenone-induced Parkinson's disease models - Takeuchi_2009_J.Neurosci.Res_87_576
Author(s) : Takeuchi H , Yanagida T , Inden M , Takata K , Kitamura Y , Yamakawa K , Sawada H , Izumi Y , Yamamoto N , Kihara T , Uemura K , Inoue H , Taniguchi T , Akaike A , Takahashi R , Shimohama S
Ref : Journal of Neuroscience Research , 87 :576 , 2009
Abstract : Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic (DA) neuronal cell loss in the substantia nigra. Although the entire pathogenesis of PD is still unclear, both environmental and genetic factors contribute to neurodegeneration. Epidemiologic studies show that prevalence of PD is lower in smokers than in nonsmokers. Nicotine, a releaser of dopamine from DA neurons, is one of the candidates of antiparkinson agents in tobacco. To assess the protective effect of nicotine against rotenone-induced DA neuronal cell toxicity, we examined the neuroprotective effects of nicotine in rotenone-induced PD models in vivo and in vitro. We observed that simultaneous subcutaneous administration of nicotine inhibited both motor deficits and DA neuronal cell loss in the substantia nigra of rotenone-treated mice. Next, we analyzed the molecular mechanisms of DA neuroprotective effect of nicotine against rotenone-induced toxicity with primary DA neuronal culture. We found that DA neuroprotective effects of nicotine were inhibited by dihydro-beta-erythroidine (DHbetaE), alpha-bungarotoxin (alphaBuTx), and/or PI3K-Akt/PKB (protein serine/threonine kinase B) inhibitors, demonstrating that rotenone-toxicity on DA neurons are inhibited via activation of alpha4beta2 or alpha7 nAChRs-PI3K-Akt/PKB pathway or pathways. These results suggest that the rotenone mouse model may be useful for assessing candidate antiparkinson agents, and that nAChR (nicotinic acetylcholine receptor) stimulation can protect DA neurons against degeneration.
ESTHER : Takeuchi_2009_J.Neurosci.Res_87_576
PubMedSearch : Takeuchi_2009_J.Neurosci.Res_87_576
PubMedID: 18803299

Title : The Rice Annotation Project Database (RAP-DB): 2008 update - Tanaka_2008_Nucleic.Acids.Res_36_D1028
Author(s) : Tanaka T , Antonio BA , Kikuchi S , Matsumoto T , Nagamura Y , Numa H , Sakai H , Wu J , Itoh T , Sasaki T , Aono R , Fujii Y , Habara T , Harada E , Kanno M , Kawahara Y , Kawashima H , Kubooka H , Matsuya A , Nakaoka H , Saichi N , Sanbonmatsu R , Sato Y , Shinso Y , Suzuki M , Takeda J , Tanino M , Todokoro F , Yamaguchi K , Yamamoto N , Yamasaki C , Imanishi T , Okido T , Tada M , Ikeo K , Tateno Y , Gojobori T , Lin YC , Wei FJ , Hsing YI , Zhao Q , Han B , Kramer MR , McCombie RW , Lonsdale D , O'Donovan CC , Whitfield EJ , Apweiler R , Koyanagi KO , Khurana JP , Raghuvanshi S , Singh NK , Tyagi AK , Haberer G , Fujisawa M , Hosokawa S , Ito Y , Ikawa H , Shibata M , Yamamoto M , Bruskiewich RM , Hoen DR , Bureau TE , Namiki N , Ohyanagi H , Sakai Y , Nobushima S , Sakata K , Barrero RA , Souvorov A , Smith-White B , Tatusova T , An S , An G , S OO , Fuks G , Messing J , Christie KR , Lieberherr D , Kim H , Zuccolo A , Wing RA , Nobuta K , Green PJ , Lu C , Meyers BC , Chaparro C , Piegu B , Panaud O , Echeverria M
Ref : Nucleic Acids Research , 36 :D1028 , 2008
Abstract : The Rice Annotation Project Database (RAP-DB) was created to provide the genome sequence assembly of the International Rice Genome Sequencing Project (IRGSP), manually curated annotation of the sequence, and other genomics information that could be useful for comprehensive understanding of the rice biology. Since the last publication of the RAP-DB, the IRGSP genome has been revised and reassembled. In addition, a large number of rice-expressed sequence tags have been released, and functional genomics resources have been produced worldwide. Thus, we have thoroughly updated our genome annotation by manual curation of all the functional descriptions of rice genes. The latest version of the RAP-DB contains a variety of annotation data as follows: clone positions, structures and functions of 31 439 genes validated by cDNAs, RNA genes detected by massively parallel signature sequencing (MPSS) technology and sequence similarity, flanking sequences of mutant lines, transposable elements, etc. Other annotation data such as Gnomon can be displayed along with those of RAP for comparison. We have also developed a new keyword search system to allow the user to access useful information. The RAP-DB is available at: http://rapdb.dna.affrc.go.jp/ and http://rapdb.lab.nig.ac.jp/.
ESTHER : Tanaka_2008_Nucleic.Acids.Res_36_D1028
PubMedSearch : Tanaka_2008_Nucleic.Acids.Res_36_D1028
PubMedID: 18089549
Gene_locus related to this paper: orysa-Q9FW17 , orysa-Q0JK71 , orysa-B9EWJ8 , orysa-Q5N7L1 , orysa-pir7a , orysa-q2qyj1 , orysj-q6yse8 , orysa-q6yzk1 , orysa-Q8S0U8 , orysa-q33aq0 , orysa-Q0J0A4 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-b9fi05 , orysj-b9fkb0 , orysj-cgep , orysj-q0djj0 , orysj-q0dud7 , orysj-q0jaf0 , orysj-q0jga1 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q0iq98 , orysj-b9gbs4 , orysj-b9gbs1 , orysj-pla4 , orysj-pla1

Title : Structural organization and characterization of the regulatory element of the human carboxylesterase (CES1A1 and CES1A2) genes - Hosokawa_2008_Drug.Metab.Pharmacokinet_23_73
Author(s) : Hosokawa M , Furihata T , Yaginuma Y , Yamamoto N , Watanabe N , Tsukada E , Ohhata Y , Kobayashi K , Satoh T , Chiba K
Ref : Drug Metab Pharmacokinet , 23 :73 , 2008
Abstract : Mammalian carboxylesterases comprise a multigene family, the gene products of which are localized in the endoplasmic reticulum. The carboxylesterases catalyze the hydrolysis of various xenobiotics and endogenous substrates such as ester, amide and thioester bonds and are thought to function mainly in drug metabolism. We have suggested the possibility that individual variation of human liver carboxylesterase activity causes the difference in expression levels of CES1A isozymes. However, little is known about the transcriptional regulation of human carboxylesterase genes. In the present study, we isolated two CES genes encoding human carboxylesterase CES1A, which were designated as CES1A1 (AB119997) and CES1A2 (AB119998). These genes were identical except for exon 1 and the 5' regulatory element. We investigated the transcriptional regulation of these two CES genes. A reporter gene assay and electrophoretic mobility shift assay demonstrated that Sp1 and C/EBPalpha could bind to each responsive element of the CES1A1 promoter but that the Sp1 and C/EBP could not bind to the responsive element of the CES1A2 promoter. Thus, CES1A1 mRNA expression level is much higher than the expression level of CES1A2 mRNA in the liver and lung. It is thought that these results provide information on individual variation of human carboxylesterase isozymes.
ESTHER : Hosokawa_2008_Drug.Metab.Pharmacokinet_23_73
PubMedSearch : Hosokawa_2008_Drug.Metab.Pharmacokinet_23_73
PubMedID: 18305377
Gene_locus related to this paper: human-CES1

Title : Genomic structure and transcriptional regulation of the rat, mouse, and human carboxylesterase genes - Hosokawa_2007_Drug.Metab.Rev_39_1
Author(s) : Hosokawa M , Furihata T , Yaginuma Y , Yamamoto N , Koyano N , Fujii A , Nagahara Y , Satoh T , Chiba K
Ref : Drug Metabolism Reviews , 39 :1 , 2007
Abstract : The mammalian carboxylesterases (CESs) comprise a multigene family which gene products play important roles in biotransformation of ester- or amide-type prodrugs. Since expression level of CESs may affect the pharmacokinetic behavior of prodrugs in vivo, it is important to understand the transcriptional regulation mechanism of the CES genes. However, little is known about the gene structure and transcriptional regulation of the mammalian CES genes. In the present study, to investigate the transcriptional regulation of the promoter region of the CES1 and CES2 genes were isolated from mouse, rat and human genomic DNA by PCR amplification. A TATA box was not found the transcriptional start site of all CES promoter. These CES promoters share several common binding sites for transcription factors among the same CES families, suggesting that the orthologous CES genes have evolutionally conserved transcriptional regulatory mechanisms. The result of present study suggested that the mammalian CES promoters were at least partly conserved among the same CES families, and some of the transcription factors may play similar roles in transcriptional regulation of the human and murine CES genes.
ESTHER : Hosokawa_2007_Drug.Metab.Rev_39_1
PubMedSearch : Hosokawa_2007_Drug.Metab.Rev_39_1
PubMedID: 17364878
Gene_locus related to this paper: human-CES1 , human-CES2 , human-CES3 , human-CES4A , human-CES5A

Title : Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana - Itoh_2007_Genome.Res_17_175
Author(s) : Itoh T , Tanaka T , Barrero RA , Yamasaki C , Fujii Y , Hilton PB , Antonio BA , Aono H , Apweiler R , Bruskiewich R , Bureau T , Burr F , Costa de Oliveira A , Fuks G , Habara T , Haberer G , Han B , Harada E , Hiraki AT , Hirochika H , Hoen D , Hokari H , Hosokawa S , Hsing YI , Ikawa H , Ikeo K , Imanishi T , Ito Y , Jaiswal P , Kanno M , Kawahara Y , Kawamura T , Kawashima H , Khurana JP , Kikuchi S , Komatsu S , Koyanagi KO , Kubooka H , Lieberherr D , Lin YC , Lonsdale D , Matsumoto T , Matsuya A , McCombie WR , Messing J , Miyao A , Mulder N , Nagamura Y , Nam J , Namiki N , Numa H , Nurimoto S , O'Donovan C , Ohyanagi H , Okido T , Oota S , Osato N , Palmer LE , Quetier F , Raghuvanshi S , Saichi N , Sakai H , Sakai Y , Sakata K , Sakurai T , Sato F , Sato Y , Schoof H , Seki M , Shibata M , Shimizu Y , Shinozaki K , Shinso Y , Singh NK , Smith-White B , Takeda J , Tanino M , Tatusova T , Thongjuea S , Todokoro F , Tsugane M , Tyagi AK , Vanavichit A , Wang A , Wing RA , Yamaguchi K , Yamamoto M , Yamamoto N , Yu Y , Zhang H , Zhao Q , Higo K , Burr B , Gojobori T , Sasaki T
Ref : Genome Res , 17 :175 , 2007
Abstract : We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is approximately 32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene.
ESTHER : Itoh_2007_Genome.Res_17_175
PubMedSearch : Itoh_2007_Genome.Res_17_175
PubMedID: 17210932
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9FYP7 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-cbp3 , orysa-cbpx , orysa-Q6YSZ8 , orysa-Q9FW17 , orysa-Q84QZ6 , orysa-Q0JK71 , orysa-B9EWJ8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q658B2 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-pir7a , orysa-q2qnj4 , orysa-q2qyj1 , orysa-q2r077 , orysa-Q4VWY7 , orysa-q5smv5 , orysa-q5z901 , orysa-Q5ZBI5 , orysa-q6atz0 , orysa-q6i5q3 , orysa-q6j657 , orysa-q6k4q2 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q8LQS5 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8W3C6 , orysa-Q9LHX5 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q69j38 , orysa-q69y21 , orysa-q75hy1 , orysa-q75hy2 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q652g4 , orysa-q688m8 , orysa-Q6H8G1 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-b9fi05 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q0jga1 , orysj-q0jhi5 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q0iq98 , orysj-b9gbs4 , orysj-b9gbs1

Title : Haplotypes and a novel defective allele of CES2 found in a Japanese population - Kim_2007_Drug.Metab.Dispos_35_1865
Author(s) : Kim SR , Sai K , Tanaka-Kagawa T , Jinno H , Ozawa S , Kaniwa N , Saito Y , Akasawa A , Matsumoto K , Saito H , Kamatani N , Shirao K , Yamamoto N , Yoshida T , Minami H , Ohtsu A , Saijo N , Sawada J
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 35 :1865 , 2007
Abstract : Human carboxylesterase 2 (hCE-2) is a member of the serine esterase superfamily and is responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. hCE-2 also activates an anticancer drug, irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin, CPT-11), into its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). In this study, a comprehensive haplotype analysis of the CES2 gene, which encodes hCE-2, in a Japanese population was conducted. Using 21 single nucleotide polymorphisms (SNPs), including 4 nonsynonymous SNPs, 100C>T (Arg(34)Trp, *2), 424G>A (Val(142)Met, *3), 1A>T (Met(1)Leu, *5), and 617G>A (Arg(206)His, *6), and a SNP at the splice acceptor site of intron 8 (IVS8-2A>G, *4), 20 haplotypes were identified in 262 Japanese subjects. In 176 Japanese cancer patients who received irinotecan, associations of CES2 haplotypes and changes in a pharmacokinetic parameter, (SN-38 + SN-38G)/CPT-11 area under the plasma concentration curve (AUC) ratio, were analyzed. No significant association was found among the major haplotypes of the *1 group lacking nonsynonymous or defective SNPs. However, patients with nonsynonymous SNPs, 100C>T (Arg(34)Trp) or 1A>T (Met(1)Leu), showed substantially reduced AUC ratios. In vitro functional characterization of the SNPs was conducted and showed that the 1A>T SNP affected translational but not transcriptional efficiency. These findings are useful for further pharmacogenetic studies on CES2-activated prodrugs.
ESTHER : Kim_2007_Drug.Metab.Dispos_35_1865
PubMedSearch : Kim_2007_Drug.Metab.Dispos_35_1865
PubMedID: 17640957
Gene_locus related to this paper: human-CES2

Title : Functional characterization of three naturally occurring single nucleotide polymorphisms in the CES2 gene encoding carboxylesterase 2 (HCE-2) - Kubo_2005_Drug.Metab.Dispos_33_1482
Author(s) : Kubo T , Kim SR , Sai K , Saito Y , Nakajima T , Matsumoto K , Saito H , Shirao K , Yamamoto N , Minami H , Ohtsu A , Yoshida T , Saijo N , Ohno Y , Ozawa S , Sawada J
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 33 :1482 , 2005
Abstract : Twelve single nucleotide polymorphisms (SNPs) in the human CES2 gene, which encodes a carboxylesterase, hCE-2 [human carboxylesterase 2 (EC], have been reported in the Japanese. In this report, we have examined functional alterations of three SNPs, a nonsynonymous SNP (100C>T, R34W), an SNP at the splice acceptor site in intron 8 (IVS8-2A>G), and one newly discovered nonsynonymous SNP (424G>A, V142M). For the two nonsynonymous SNPs, the corresponding variant cDNAs were expressed in COS-1 cells. Both the R34W and V142M variants showed little esterase activities toward the anticancer agent irinotecan and two typical carboxylesterase substrates, p-nitrophenol acetate and 4-methylumbelliferyl acetate, although increased levels of cDNA-mediated protein expression were observed by Western blotting as compared with the wild type. To investigate a possible splicing aberration in IVS8-2A>G, an in vitro splicing assay was utilized and transcripts derived from CES2 gene fragments of the wild type and IVS8-2A>G were compared. Sequence analysis of the cloned transcripts revealed that IVS8-2A>G yielded mostly aberrantly spliced transcripts, including a deleted exon or a 32-bp deletion proximal to the 5' end of exon 9, which resulted in truncated hCE-2 proteins. These results suggested that 100C>T (R34W), 424G>A (V142M), and IVS8-2A>G are functionally deficient SNPs.
ESTHER : Kubo_2005_Drug.Metab.Dispos_33_1482
PubMedSearch : Kubo_2005_Drug.Metab.Dispos_33_1482
PubMedID: 16033949

Title : Discovery of acetylcholinesterase peripheral anionic site ligands through computational refinement of a directed library - Dickerson_2005_Biochemistry_44_14845
Author(s) : Dickerson TJ , Beuscher AEt , Rogers CJ , Hixon MS , Yamamoto N , Xu Y , Olson AJ , Janda KD
Ref : Biochemistry , 44 :14845 , 2005
Abstract : The formation of beta-amyloid plaques in the brain is a key neurodegenerative event in Alzheimer's disease. Small molecules capable of binding to the peripheral anionic site of acetylcholinesterase (AChE) have been shown to inhibit the AChE-induced aggregation of the beta-amyloid peptide. Using the combination of a computational docking model and experimental screening, five compounds that completely blocked the amyloidogenic effect of AChE were rapidly identified from an approximately 200-member library of compounds designed to disrupt protein-protein interactions. Critical to this docking model was the inclusion of two explicit water molecules that are tightly bound to the enzyme. Interestingly, none of the tested compounds inhibited the related enzyme butyrylcholinesterase (BuChE) up to their aqueous solubility limits. These compounds are among the most potent inhibitors of amyloid beta-peptide aggregation and are equivalent only to propidium, a well-characterized AChE peripheral anionic site binder and aggregation inhibitor.
ESTHER : Dickerson_2005_Biochemistry_44_14845
PubMedSearch : Dickerson_2005_Biochemistry_44_14845
PubMedID: 16274232

Title : Significance of serum type IV collagen level of hepatectomized patients with chronic liver damage - Shimahara_2002_World.J.Surg_26_451
Author(s) : Shimahara Y , Yamamoto N , Uyama N , Okuyama H , Momoi H , Kamikawa T , Terajima H , Iimuro Y , Yamamoto Y , Ikai I , Kushihata F , Kiyochi H , Kobayashi N , Yamaoka Y
Ref : World J Surg , 26 :451 , 2002
Abstract : Type IV collagen, one of the serum markers for hepatic fibrosis, was measured perioperatively in patients with and without chronic liver damage to investigate whether this parameter changes in response to acute stress to the liver and can predict the surgical risk of hepatic resection. The serum type IV collagen level was significantly elevated in patients with liver cirrhosis. There were significant correlations between serum type IV collagen levels and the indocyanine green clearance test and cholinesterase activity, although the correlation coefficients were not high. The size of the resected hepatic mass was not the primary factor to influence the postoperative serum type IV collagen level. In patients with liver cirrhosis, the postoperative serum type IV collagen level increased significantly compared to that in patients with normal liver or chronic hepatitis. Postoperative liver failure occurred in 0%, 11.6%, and 44.4% of patients with preoperative serum type IV collagen levels of <150, < or = 150 to 300, and > or = 300 ng/ml, respectively. In those with postoperative liver failure, the serum type IV collagen levels were significantly higher both pre- and postoperatively compared to those in patients with uneventful courses. Several preoperative liver function tests indicated that type IV collagen is an independent risk factor for postoperative liver failure. Thus perioperative measurement of the serum type IV collagen levels seemed to be useful for predicting the risk of hepatic resection in patients with chronic liver damage.
ESTHER : Shimahara_2002_World.J.Surg_26_451
PubMedSearch : Shimahara_2002_World.J.Surg_26_451
PubMedID: 11910479

Title : Association of a G994 -->T missense mutation in the plasma platelet-activating factor acetylhydrolase gene with risk of abdominal aortic aneurysm in Japanese - Unno_2002_Ann.Surg_235_297
Author(s) : Unno N , Nakamura T , Mitsuoka H , Uchiyama T , Yamamoto N , Saito T , Sugatani J , Miwa M , Nakamura S
Ref : Annals of Surgery , 235 :297 , 2002
Abstract : OBJECTIVE: To investigate a possible association with plasma platelet activating factor acetylhydrolase (PAF-AH) gene mutation with the risk of abdominal aortic aneurysm (AAA). SUMMARY BACKGROUND DATA: Plasma platelet activating factor acetylhydrolase is known to catalyze platelet activating factor (PAF), thereby inactivating its inflammatory function. Deficiency of this enzyme is caused by a missense mutation (G994 -->T) in exon 9 of the plasma PAF-AH gene.
METHODS: We did a case-control study including 131 patients (median age 73.4 [range 50-84] years) and 106 controls matched for age and sex. Genomic DNA was analyzed for the mutant allele by a specific polymerase-chain reaction. Plasma PAF-AH activity was measured in both groups.
RESULTS: The frequency of the mutant allele (T allele) in the plasma PAF-AH gene in AAA patients was significantly higher than in control subjects. The association of the missense mutation with AAA was statistically significant and independent of other risk factors. Among AAA patients with normal genomic type, plasma PAF-AH activity was strongly correlated to the plasma concentration of low density lipoprotein cholesterol (LDL-C), while the correlation was not observed among AAA patients with heterozygotes genotype. Patients having AAA with both T allele and hyperlipidemia were more likely to have other atherosclerotic diseases such as ischemic heart disease, stroke and peripheral arterial occlusive diseases than patients with the normal genomic type and normal lipid level.
CONCLUSIONS: The genetic mutation of plasma PAF-AH gene appear to be an independent risk factor for AAA. Our findings need to be confirmed in a larger, prospective study including patients from different populations.
ESTHER : Unno_2002_Ann.Surg_235_297
PubMedSearch : Unno_2002_Ann.Surg_235_297
PubMedID: 11807372