Saito Y

References (43)

Title : Identification of Lipolytic Enzymes Using High-Throughput Single-cell Screening and Sorting of a Metagenomic Library - Alma'abadi_2022_N.Biotechnol__
Author(s) : Alma'abadi A , Behzad H , Alarawi M , Conchouso D , Saito Y , Hosokawa M , Nishikawa Y , Kogawa M , Takeyama H , Mineta K , Gojobori T
Ref : N Biotechnol , : , 2022
Abstract : The demand for novel, robust microbial biocatalysts for use in industrial and pharmaceutical applications continues to increase rapidly. As a result, there is a need to develop advanced tools and technologies to exploit the vast metabolic potential of unculturable microorganisms found in various environments. Single-cell and functional metagenomics studies can explore the enzymatic potential of entire microbial communities in a given environment without the need to culture the microorganisms. This approach has contributed substantially to the discovery of unique microbial genes for industrial and medical applications. Functional metagenomics involves the extraction of microbial DNA directly from environmental samples, constructing expression libraries comprising the entire microbial genome, and screening of the libraries for the presence of desired phenotypes. In this study, lipolytic enzymes from the Red Sea were targeted. A high-throughput single-cell microfluidic platform combined with a laser-based fluorescent screening bioassay was employed to discover new genes encoding lipolytic enzymes. Analysis of the metagenomic library led to the identification of three microbial genes encoding lipases based on their functional similarity and sequence homology to known lipases. The results demonstrated that microfluidics is a robust technology that can be used for screening in functional metagenomics. The results also indicate that the Red Sea is a promising, under-investigated source of new genes and gene products.
ESTHER : Alma'abadi_2022_N.Biotechnol__
PubMedSearch : Alma'abadi_2022_N.Biotechnol__
PubMedID: 35636700

Title : Logopenic aphasia due to Lewy body disease dramatically improved with donepezil - Kakinuma_2020_eNeurologicalSci_19_100241
Author(s) : Kakinuma K , Baba T , Ezura M , Endo K , Saito Y , Narita W , Iizuka O , Nishio Y , Kikuchi A , Hasegawa T , Aoki M , Suzuki K
Ref : eNeurologicalSci , 19 :100241 , 2020
Abstract : *Pathological basis of primary progressive aphasia is heterogeneous.*Logopenic primary progressive aphasia can precede dementia with Lewy bodies (DLB).*Cholinesterase inhibitor can improve logopenic aphasia with DLB.
ESTHER : Kakinuma_2020_eNeurologicalSci_19_100241
PubMedSearch : Kakinuma_2020_eNeurologicalSci_19_100241
PubMedID: 32455171

Title : The apocarotenoid metabolite zaxinone regulates growth and strigolactone biosynthesis in rice - Wang_2019_Nat.Commun_10_810
Author(s) : Wang JY , Haider I , Jamil M , Fiorilli V , Saito Y , Mi J , Baz L , Kountche BA , Jia KP , Guo X , Balakrishna A , Ntui VO , Reinke B , Volpe V , Gojobori T , Blilou I , Lanfranco L , Bonfante P , Al-Babili S
Ref : Nat Commun , 10 :810 , 2019
Abstract : Carotenoid cleavage dioxygenases (CCDs) form hormones and signaling molecules. Here we show that a member of an overlooked plant CCD subfamily from rice, that we name Zaxinone Synthase (ZAS), can produce zaxinone, a novel apocarotenoid metabolite in vitro. Loss-of-function mutants (zas) contain less zaxinone, exhibit retarded growth and showed elevated levels of strigolactones (SLs), a hormone that determines plant architecture, mediates mycorrhization and facilitates infestation by root parasitic weeds, such as Striga spp. Application of zaxinone can rescue zas phenotypes, decrease SL content and release and promote root growth in wild-type seedlings. In conclusion, we show that zaxinone is a key regulator of rice development and biotic interactions and has potential for increasing crop growth and combating Striga, a severe threat to global food security.
ESTHER : Wang_2019_Nat.Commun_10_810
PubMedSearch : Wang_2019_Nat.Commun_10_810
PubMedID: 30778050

Title : The genome sequence of sweet cherry (Prunus avium) for use in genomics-assisted breeding - Shirasawa_2017_DNA.Res_24_499
Author(s) : Shirasawa K , Isuzugawa K , Ikenaga M , Saito Y , Yamamoto T , Hirakawa H , Isobe S
Ref : DNA Research , 24 :499 , 2017
Abstract : We determined the genome sequence of sweet cherry (Prunus avium) using next-generation sequencing technology. The total length of the assembled sequences was 272.4 Mb, consisting of 10,148 scaffold sequences with an N50 length of 219.6 kb. The sequences covered 77.8% of the 352.9 Mb sweet cherry genome, as estimated by k-mer analysis, and included >96.0% of the core eukaryotic genes. We predicted 43,349 complete and partial protein-encoding genes. A high-density consensus map with 2,382 loci was constructed using double-digest restriction site-associated DNA sequencing. Comparing the genetic maps of sweet cherry and peach revealed high synteny between the two genomes; thus the scaffolds were integrated into pseudomolecules using map- and synteny-based strategies. Whole-genome resequencing of six modern cultivars found 1,016,866 SNPs and 162,402 insertions/deletions, out of which 0.7% were deleterious. The sequence variants, as well as simple sequence repeats, can be used as DNA markers. The genomic information helps us to identify agronomically important genes and will accelerate genetic studies and breeding programs for sweet cherries. Further information on the genomic sequences and DNA markers is available in DBcherry (http://cherry.kazusa.or.jp (8 May 2017, date last accessed)).
ESTHER : Shirasawa_2017_DNA.Res_24_499
PubMedSearch : Shirasawa_2017_DNA.Res_24_499
PubMedID: 28541388
Gene_locus related to this paper: pruav-a0a6p5tfl8 , pruav-a0a6p5sn52 , pruav-a0a6p5tmj7

Title : Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein - Hashimoto_2016_Nat.Commun_7_12808
Author(s) : Hashimoto T , Horikawa DD , Saito Y , Kuwahara H , Kozuka-Hata H , Shin IT , Minakuchi Y , Ohishi K , Motoyama A , Aizu T , Enomoto A , Kondo K , Tanaka S , Hara Y , Koshikawa S , Sagara H , Miura T , Yokobori S , Miyagawa K , Suzuki Y , Kubo T , Oyama M , Kohara Y , Fujiyama A , Arakawa K , Katayama T , Toyoda A , Kunieda T
Ref : Nat Commun , 7 :12808 , 2016
Abstract : Tardigrades, also known as water bears, are small aquatic animals. Some tardigrade species tolerate almost complete dehydration and exhibit extraordinary tolerance to various physical extremes in the dehydrated state. Here we determine a high-quality genome sequence of Ramazzottius varieornatus, one of the most stress-tolerant tardigrade species. Precise gene repertoire analyses reveal the presence of a small proportion (1.2% or less) of putative foreign genes, loss of gene pathways that promote stress damage, expansion of gene families related to ameliorating damage, and evolution and high expression of novel tardigrade-unique proteins. Minor changes in the gene expression profiles during dehydration and rehydration suggest constitutive expression of tolerance-related genes. Using human cultured cells, we demonstrate that a tardigrade-unique DNA-associating protein suppresses X-ray-induced DNA damage by approximately 40% and improves radiotolerance. These findings indicate the relevance of tardigrade-unique proteins to tolerability and tardigrades could be a bountiful source of new protection genes and mechanisms.
ESTHER : Hashimoto_2016_Nat.Commun_7_12808
PubMedSearch : Hashimoto_2016_Nat.Commun_7_12808
PubMedID: 27649274
Gene_locus related to this paper: ramva-a0a1d1uki4 , ramva-a0a1d1uvm7 , ramva-a0a1d1ula4 , ramva-a0a1d1v5e3 , ramva-a0a1d1unv1 , ramva-a0a1d1vjq5 , ramva-a0a1d1vlp2 , ramva-a0a1d1vh75 , ramva-a0a1d1vzz5

Title : Effects of donepezil and serotonin reuptake inhibitor on acute regression during adolescence in Down syndrome - Tamasaki_2016_Brain.Dev_38_113
Author(s) : Tamasaki A , Saito Y , Ueda R , Ohno K , Yokoyama K , Satake T , Sakuma H , Takahashi Y , Kondoh T , Maegaki Y
Ref : Brain Dev , 38 :113 , 2016
Abstract : A 14-year-old boy with Down syndrome (DS) showed a gradual decline in his daily activities and feeding capacities, and a marked deterioration triggered by a streptococcal infection was observed at the age of 15years. He became bedridden, accompanied by sleep disturbance, sustained upward gaze, and generalized rigidity. Magnetic resonance imaging showed unremarkable findings, but antiglutamate receptor autoantibodies were positive in his cerebrospinal fluid. Treatment with thiamine infusion and steroid pulse therapy showed little effect, but gross motor dysfunction and appetite loss were ameliorated by the administration of l-DOPA and serotonin reuptake inhibitors. Thereafter, autistic behaviors predominated, including loss of social interaction, oral tendency, water phobia, and aggressiveness. Initiation of donepezil, an acetylcholinesterase inhibitor, resulted in the disappearance of these symptoms and total recovery of the patient to his previous psychosocial levels. We hypothesize that the acute regression in adolescence represents a process closely related to the defects of serotonergic and cholinergic systems that are innate to DS brains and not just a nonspecific comorbidity of depression or limbic encephalitis.
ESTHER : Tamasaki_2016_Brain.Dev_38_113
PubMedSearch : Tamasaki_2016_Brain.Dev_38_113
PubMedID: 26143664

Title : Juvenile hormone (JH) esterase activity but not JH epoxide hydrolase activity is downregulated in larval Adoxophyes honmai following nucleopolyhedroviruses infection - Saito_2015_J.Insect.Physiol_80_71
Author(s) : Saito Y , Kamita SG , Hammock BD , Kunimi Y , Inoue MN , Nakai M
Ref : J Insect Physiol , 80 :71 , 2015
Abstract : Juvenile hormones (JHs) and ecdysteroids are critical insect developmental hormones. JH esterase (JHE) and JH epoxide hydrolase (JHEH) are JH-selective enzymes that metabolize JH and thus regulate the titer of JH. Baculoviruses are known to alter host endocrine regulation. The nucleopolyhedroviruses, AdhoNPV and AdorNPV, are known to have slow and fast killing activity against Adoxophyes honmai (Lepidoptera: Tortricidae), respectively. Here we found that when penultimate (4th) instar A. honmai are inoculated with AdhoNPV or AdorNPV, the mean survival time is 9.7 and 8.2 days, respectively. The larvae molted once but did not pupate. The AdhoNPV- or AdorNPV-infected larvae did not show a dramatic increase in JHE activity as was found in mock-infected larvae, instead they showed a marked decrease in JHE activity. In contrast, both viral infections had no effect on JHEH activity. In order to further characterize the JHE activity, the JHE-coding sequence of A. honmai (ahjhe) was cloned and confirmed to encode a biologically active JHE. Quantitative real-time PCR analysis of ahjhe expression in 4th and 5th instar A. honmai revealed that AdhoNPV and AdorNPV are able to reduce ahjhe expression levels.
ESTHER : Saito_2015_J.Insect.Physiol_80_71
PubMedSearch : Saito_2015_J.Insect.Physiol_80_71
PubMedID: 25727179
Gene_locus related to this paper: adoho-a0a0g4dcw7

Title : The vestibulo- and preposito-cerebellar cholinergic neurons of a ChAT-tdTomato transgenic rat exhibit heterogeneous firing properties and the expression of various neurotransmitter receptors - Zhang_2014_Eur.J.Neurosci_39_1294
Author(s) : Zhang Y , Kaneko R , Yanagawa Y , Saito Y
Ref : European Journal of Neuroscience , 39 :1294 , 2014
Abstract : Cerebellar function is regulated by cholinergic mossy fiber inputs that are primarily derived from the medial vestibular nucleus (MVN) and prepositus hypoglossi nucleus (PHN). In contrast to the growing evidence surrounding cholinergic transmission and its functional significance in the cerebellum, the intrinsic and synaptic properties of cholinergic projection neurons (ChPNs) have not been clarified. In this study, we generated choline acetyltransferase (ChAT)-tdTomato transgenic rats, which specifically express the fluorescent protein tdTomato in cholinergic neurons, and used them to investigate the response properties of ChPNs identified via retrograde labeling using whole-cell recordings in brainstem slices. In response to current pulses, ChPNs exhibited two afterhyperpolarisation (AHP) profiles and three firing patterns; the predominant AHP and firing properties differed between the MVN and PHN. Morphologically, the ChPNs were separated into two types based on their soma size and dendritic extensions. Analyses of the firing responses to time-varying sinusoidal current stimuli revealed that ChPNs exhibited different firing modes depending on the input frequencies. The maximum frequencies in which each firing mode was observed were different between the neurons that exhibited distinct firing patterns. Analyses of the current responses to the application of neurotransmitter receptor agonists revealed that the ChPNs expressed (i) AMPA- and NMDA-type glutamate receptors, (ii) GABAA and glycine receptors, and (iii) muscarinic and nicotinic acetylcholine receptors. The current responses mediated by these receptors of MVN ChPNs were not different from those of PHN ChPNs. These findings suggest that ChPNs receive various synaptic inputs and encode those inputs appropriately across different frequencies.
ESTHER : Zhang_2014_Eur.J.Neurosci_39_1294
PubMedSearch : Zhang_2014_Eur.J.Neurosci_39_1294
PubMedID: 24593297

Title : Lipoprotein subfractions highly associated with renal damage in familial lecithin:cholesterol acyltransferase deficiency - Kuroda_2014_Arterioscler.Thromb.Vasc.Biol_34_1756
Author(s) : Kuroda M , Holleboom AG , Stroes ES , Asada S , Aoyagi Y , Kamata K , Yamashita S , Ishibashi S , Saito Y , Bujo H
Ref : Arterioscler Thromb Vasc Biol , 34 :1756 , 2014
Abstract : OBJECTIVE: In familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD), deposition of abnormal lipoproteins in the renal stroma ultimately leads to renal failure. However, fish-eye disease (FED) does not lead to renal damage although the causative mutations for both FLD and FED lie within the same LCAT gene. This study was performed to identify the lipoproteins important for the development of renal failure in genetically diagnosed FLD in comparison with FED, using high-performance liquid chromatography with a gel filtration column. APPROACH AND
RESULTS: Lipoprotein profiles of 9 patients with LCAT deficiency were examined. Four lipoprotein fractions specific to both FLD and FED were identified: (1) large lipoproteins (>80 nm), (2) lipoproteins corresponding to large low-density lipoprotein (LDL), (3) lipoproteins corresponding to small LDL to large high-density lipoprotein, and (4) to small high-density lipoprotein. Contents of cholesteryl ester and triglyceride of the large LDL in FLD (below detection limit and 45.8+/-3.8%) and FED (20.7+/-6.4% and 28.0+/-6.5%) were significantly different, respectively. On in vitro incubation with recombinant LCAT, content of cholesteryl ester in the large LDL in FLD, but not in FED, was significantly increased (to 4.2+/-1.4%), whereas dysfunctional high-density lipoprotein was diminished in both FLD and FED.
CONCLUSIONS: Our novel analytic approach using high-performance liquid chromatography with a gel filtration column identified large LDL and high-density lipoprotein with a composition specific to FLD, but not to FED. The abnormal lipoproteins were sensitive to treatment with recombinant LCAT and thus may play a causal role in the renal pathology of FLD.
ESTHER : Kuroda_2014_Arterioscler.Thromb.Vasc.Biol_34_1756
PubMedSearch : Kuroda_2014_Arterioscler.Thromb.Vasc.Biol_34_1756
PubMedID: 24876348
Gene_locus related to this paper: human-LCAT

Title : Effect of acotiamide on gastric emptying in healthy adult humans - Zai_2014_Eur.J.Clin.Invest_44_1215
Author(s) : Zai H , Matsueda K , Kusano M , Urita Y , Saito Y , Kato H
Ref : European Journal of Clinical Investigation , 44 :1215 , 2014
Abstract : BACKGROUND: Acotiamide is a first-in-class drug that is used to treat functional dyspepsia (FD). It is considered that acotiamide acts as an antagonist on muscarinic autoreceptors in the enteric nervous system and inhibits acetylcholinesterase activity. We examined the effect of acotiamide on gastric emptying in healthy adult humans. MATERIALS AND
METHODS: Twelve healthy adult males were enrolled in this double-blind crossover study. Acotiamide or placebo was administered orally in the 12 subjects 30 min before ingestion of a nutritional liquid meal (400 Kcal/400 mL). Six of the 12 participants took 100 mg of acotiamide or placebo, and six of the 12 participants took 300 mg of acotiamide or placebo in a double-blind crossover fashion. All subjects underwent measurement of gastric emptying by the (13) C breath test.
RESULTS: After the meal with placebo was ingested, the %dose/h curve ascended. The %dose/h curve after a meal with 100 or 300 mg of acotiamide ascended in an identical manner compared with the results with placebo. No significant differences were observed at any studied time point, and there were no significant changes in gastric emptying parameters (gastric emptying coefficient, t-1/2ex and t-lag ex).
CONCLUSIONS: A single administration of 100 or 300 mg of acotiamide did not affect gastric emptying after a liquid meal in healthy adult humans. Acotiamide has profound effects on restoring delayed gastric emptying and impaired accommodation in patients with FD but may have no effect on gastric emptying in healthy subjects. Such pharmacological actions have not been observed in previous gastroprokinetic studies.
ESTHER : Zai_2014_Eur.J.Clin.Invest_44_1215
PubMedSearch : Zai_2014_Eur.J.Clin.Invest_44_1215
PubMedID: 25370953

Title : Development of monoclonal antibodies to human microsomal epoxide hydrolase and analysis of preneoplastic antigen-like molecules - Duan_2012_Toxicol.Appl.Pharmacol_260_17
Author(s) : Duan H , Yoshimura K , Kobayashi N , Sugiyama K , Sawada J , Saito Y , Morisseau C , Hammock BD , Akatsuka T
Ref : Toxicol Appl Pharmacol , 260 :17 , 2012
Abstract : Microsomal epoxide hydrolase (mEH) is a drug metabolizing enzyme which resides on the endoplasmic reticulum (ER) membrane and catalyzes the hydration of reactive epoxide intermediates that are formed by cytochrome P450s. mEH is also thought to have a role in bile acid transport on the plasma membrane of hepatocytes. It is speculated that efficient execution of such multiple functions is secured by its orientation and association with cytochrome P450 enzymes on the ER membrane and formation of a multiple transport system on the plasma membrane. In certain disease status, mEH loses its association with the membrane and can be detected as distinct antigens in the cytosol of preneoplastic foci of liver (preneoplastic antigen), in the serum in association with hepatitis C virus infection (AN antigen), or in some brain tumors. To analyze the antigenic structures of mEH in physiological and pathological conditions, we developed monoclonal antibodies against different portions of mEH. Five different kinds of antibodies were obtained: three, anti-N-terminal portions; one anti-C-terminal; and one, anti-conformational epitope. By combining these antibodies, we developed antigen detection methods which are specific to either the membrane-bound form or the linearized form of mEH. These methods detected mEH in the culture medium released from a hepatocellular carcinoma cell line and a glioblastoma cell line, which was found to be a multimolecular complex with a unique antigenic structure different from that of the membrane-bound form of mEH. These antibodies and antigen detection methods may be useful to study pathological changes of mEH in various human diseases.
ESTHER : Duan_2012_Toxicol.Appl.Pharmacol_260_17
PubMedSearch : Duan_2012_Toxicol.Appl.Pharmacol_260_17
PubMedID: 22310175

Title : A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia - Matsueda_2012_Gut_61_821
Author(s) : Matsueda K , Hongo M , Tack J , Saito Y , Kato H
Ref : Gut , 61 :821 , 2012
Abstract : OBJECTIVE: To determine the efficacy of acotiamide, an acetylcholinesterase inhibitor, in patients with functional dyspepsia (FD) in a 4-week trial. METHODS: A multicentre, randomised, placebo-controlled, parallel-group, phase III trial was carried out, in which patients with FD received 100 mg of acotiamide or placebo three times a day for 4 weeks, with 4 weeks post-treatment follow-up. The primary efficacy end points were global assessment of overall treatment efficacy (OTE) and elimination rate of all three meal-related symptoms (postprandial fullness, upper abdominal bloating and early satiation), as derived from daily diaries. Secondary efficacy end points were individual symptom scores and quality of life. Adverse events were monitored. RESULTS: 52.2% of those receiving acotiamide and 34.8% in the placebo group (p<0.001) were classified as responders according to a global assessment of OTE. Over 4 weeks, the elimination rate for all three meal-related symptoms was 15.3% among patients receiving acotiamide compared with 9.0% in the placebo group (p=0.004). The significant benefit of acotiamide over placebo in OTE and elimination rate was maintained during the 4 week post-treatment follow-up. All other secondary efficacy end points, including quality of life, were significantly improved with 100 mg of acotiamide as compared with placebo. The number needed to treat was 6 for OTE and 16 for symptom elimination rate. The incidence of adverse events was similar between the acotiamide group and placebo group and no significant cardiovascular effects due to treatment were seen. CONCLUSIONS: Over 4 weeks, acotiamide significantly improved symptom severity and eliminated meal-related symptoms in patients with FD. TRIAL REGISTRATION NUMBER: http://ClinicalTrials.gov number, NCT00761358.
ESTHER : Matsueda_2012_Gut_61_821
PubMedSearch : Matsueda_2012_Gut_61_821
PubMedID: 22157329

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 : Clinical trial: dose-dependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia - 100 mg t.i.d. is an optimal dosage - Matsueda_2010_Neurogastroenterol.Motil_22_618
Author(s) : Matsueda K , Hongo M , Tack J , Aoki H , Saito Y , Kato H
Ref : Neurogastroenterol Motil , 22 :618 , 2010
Abstract : BACKGROUND: Acotiamide is a selective acetylcholinesterase inhibitor and enhances the actions of cholinergic neurons localized in the stomach. METHODS: The present two studies were conducted to examine the optimal dosage of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia (FD) in Japan. KEY RESULTS: The improvement rate of 'subjects global assessment of overall treatment efficacy (OTE)' at the final evaluation was approximately 10% higher in the acotiamide 100 mg group than that in the placebo group with good reproducibility though there was no significant differences at primary endpoint. The elimination rate of postprandial fullness in the acotiamide 100 mg group was significantly higher compared to placebo group. In addition, the post hoc analysis showed that in patients whose main complaints are meal-related symptoms such as postprandial fullness, upper abdominal bloating and/or early satiety, the improvement rate of 'OTE' at final evaluation in acotiamide 100 mg group was significantly superior to that in the placebo group. CONCLUSIONS & INFERENCES: These results suggest that acotiamide possesses efficacy on FD and more specifically its meal-related symptoms of FD.
ESTHER : Matsueda_2010_Neurogastroenterol.Motil_22_618
PubMedSearch : Matsueda_2010_Neurogastroenterol.Motil_22_618
PubMedID: 20059698

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 : A major urinary protein of the domestic cat regulates the production of felinine, a putative pheromone precursor - Miyazaki_2006_Chem.Biol_13_1071
Author(s) : Miyazaki M , Yamashita T , Suzuki Y , Saito Y , Soeta S , Taira H , Suzuki A
Ref : Chemical Biology , 13 :1071 , 2006
Abstract : Domestic cats spray urine with species-specific odor for territorial marking. Felinine (2-amino-7-hydroxy-5,5-dimethyl-4-thiaheptanoic acid), a putative pheromone precursor, is excreted in cat urine. Here, we report that cauxin, a carboxylesterase excreted as a major urinary component, regulates felinine production. In vitro enzyme assays indicated that cauxin hydrolyzed the felinine precursor 3-methylbutanol-cysteinylglycine to felinine and glycine. Cauxin and felinine were excreted age dependently after 3 months of age. The age-dependent increases in cauxin and felinine excretion were significantly correlated. In mature cats, cauxin and felinine levels were sex-dependently correlated and were higher in males than in females. In headspace gas of cat urine, 3-mercapto-3-methyl-1-butanol, 3-mercapto-3-methylbutyl formate, 3-methyl-3-methylthio-1-butanol, and 3-methyl-3-(2-methyldisulfanyl)-1-butanol were identified as candidates for felinine derivatives. These findings demonstrate that cauxin-dependent felinine production is a cat-specific metabolic pathway, and they provide information for the biosynthetic mechanisms of species-specific molecules in mammals.
ESTHER : Miyazaki_2006_Chem.Biol_13_1071
PubMedSearch : Miyazaki_2006_Chem.Biol_13_1071
PubMedID: 17052611
Gene_locus related to this paper: felca-CAUXIN

Title : Catalytically inactive lipoprotein lipase overexpression increases insulin sensitivity in mice - Shibasaki_2006_Horm.Metab.Res_38_491
Author(s) : Shibasaki M , Bujo H , Takahashi K , Murakami K , Unoki H , Saito Y
Ref : Hormone & Metabolic Research , 38 :491 , 2006
Abstract : Abnormalities in lipoprotein lipase (LPL) function contribute to the development of hypertriglyceridemia, one of the characteristic disorders observed in the metabolic syndrome. In addition to the hydrolyzing activity of triglycerides, LPL modulates various cellular functions via its binding ability to the cell surface. Here we show the effects of catalytically inactive LPL overexpression on high-fat diet (HFD)-induced decreased systemic insulin sensitivity in mice. The binding capacity of catalytically inactive G188E-LPL to C2C12 skeletal muscle cells was not significantly different from that of wild type LPL. Insulin-stimulated IRS-1 phosphorylation and glucose uptake were increased by addition of wild type or mutant LPL in C2C12 cells. After 10 weeks' of HFD feeding, mice had significantly higher blood glucose levels than chow-fed mice in insulin tolerance tests. The blood glucose levels after insulin injection was significantly decreased in mutated LPL-overexpressing mice (G188E mice), as well as in wild type LPL-overexpressing mice (WT mice). Overexpression of catalytically inactive LPL, as well as wild type LPL, improved impaired insulin sensitivity in mice. These results show that decreased expression of LPL possibly causes the insulin resistance, in addition to hypertriglyceridemia, in metabolic syndrome.
ESTHER : Shibasaki_2006_Horm.Metab.Res_38_491
PubMedSearch : Shibasaki_2006_Horm.Metab.Res_38_491
PubMedID: 16941273

Title : Polymorphisms in four genes related to triglyceride and HDL-cholesterol levels in the general Japanese population in 2000 - Arai_2005_J.Atheroscler.Thromb_12_240
Author(s) : Arai H , Yamamoto A , Matsuzawa Y , Saito Y , Yamada N , Oikawa S , Mabuchi H , Teramoto T , Sasaki J , Nakaya N , Itakura H , Ishikawa Y , Ouchi Y , Horibe H , Egashira T , Hattori H , Shirahashi N , Kita T
Ref : J Atheroscler Thromb , 12 :240 , 2005
Abstract : We studied the association of six common polymorphisms of four genes related to lipid metabolism with serum lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the genes for cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (LIPC), and apolipoprotein CIII (APOC3), and studied 2267 individuals randomly selected from the participants of Serum Lipid Survey 2000. There was a significant association of CETP polymorphism (D442G, Int14 +1 G --> A, and TaqIB), LPL polymorphism (S447X), and LIPC polymorphism (-514 --> CT) with HDL-cholesterol levels. We also found a significant association of LPL polymorphism (S447X) and APOC3 polymorphism (SstI) with triglyceride levels. This is the largest database showing the association of common genetic variants in lipid metabolism with serum lipid levels in the general Japanese population. Further study is necessary to elucidate the role of these gene polymorphisms in cardiovascular events.
ESTHER : Arai_2005_J.Atheroscler.Thromb_12_240
PubMedSearch : Arai_2005_J.Atheroscler.Thromb_12_240
PubMedID: 16205020

Title : Haplotype structures of EPHX1 and their effects on the metabolism of carbamazepine-10,11-epoxide in Japanese epileptic patients - Nakajima_2005_Eur.J.Clin.Pharmacol_61_25
Author(s) : Nakajima Y , Saito Y , Shiseki K , Fukushima-Uesaka H , Hasegawa R , Ozawa S , Sugai K , Katoh M , Saitoh O , Ohnuma T , Kawai M , Ohtsuki T , Suzuki C , Minami N , Kimura H , Goto Y , Kamatani N , Kaniwa N , Sawada J
Ref : European Journal of Clinical Pharmacology , 61 :25 , 2005
Abstract : OBJECTIVE: Microsomal epoxide hydrolase (mEH) is an enzyme that detoxifies reactive epoxides and catalyzes the biotransformation of carbamazepine-10,11-epoxide (CBZ-epoxide) to carbamazepine-10,11-diol (CBZ-diol). Utilizing single nucleotide polymorphisms (SNPs) of the EPHX1 gene encoding mEH, we identified the haplotypes of EPHX1 blocks and investigated the association between the block haplotypes and CBZ-epoxide metabolism.
METHODS: SNPs of EPHX1 were analyzed by means of polymerase chain reaction amplification and DNA sequencing using DNA extracted from the blood leukocytes of 96 Japanese epileptic patients, including 58 carbamazepine-administered patients. The plasma concentrations of CBZ and its four metabolites were determined using high-performance liquid chromatography.
RESULTS: From sequencing all 9 exons and their surrounding introns, 29 SNPs were found in EPHX1. The SNPs were separated into three blocks on the basis of linkage disequilibrium, and the block haplotype combinations (diplotypes) were assigned. Using plasma CBZ-diol/CBZ-epoxide ratios (diol/epoxide ratios) indicative of the mEH activity, the effects of the diplotypes in each EPHX1 block were analyzed on CBZ-epoxide metabolism. In block 2, the diol/epoxide ratios increased significantly depending on the number of haplotype *2 bearing Y113H (P=0.0241). In block 3, the ratios decreased depending on the number of haplotype *2 bearing H139R (P=0.0351). Also, an increasing effect of a *1 subtype, *1c, was observed on the ratio. CONCLUSION: These results show that some EPHX1 haplotypes are associated with altered CBZ-epoxide metabolism. This is the first report on the haplotype structures of EPHX1 and their potential in vivo effects.
ESTHER : Nakajima_2005_Eur.J.Clin.Pharmacol_61_25
PubMedSearch : Nakajima_2005_Eur.J.Clin.Pharmacol_61_25
PubMedID: 15692831

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 3.1.1.1)], 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 : Mutations in Japanese subjects with primary hyperlipidemia--results from the Research Committee of the Ministry of Health and Welfare of Japan since 1996 - Maruyama_2004_J.Atheroscler.Thromb_11_131
Author(s) : Maruyama T , Yamashita S , Matsuzawa Y , Bujo H , Takahashi K , Saito Y , Ishibashi S , Ohashi K , Shionoiri F , Gotoda T , Yamada N , Kita T
Ref : J Atheroscler Thromb , 11 :131 , 2004
Abstract : Primary hyperlipidemia is caused by various molecular defects in lipid metabolism. The Research Committee on Primary Hyperlipidemia organized by the Ministry of Health and Welfare of Japan (present: the Ministry of Health, Labour and Welfare) has investigated reported mutations in Japanese patients with primary hyperlipidemia and related disorders (including hypolipidemia), and has created a database based on the questionnaire sent to the members of council board of the Japan Atherosclerosis Society. Mutations in the following genes were investigated: low density lipoprotein receptor, lecithin: cholesteryl acyltransferase, lipoprotein lipase (LPL), hepatic lipase, apolipoproteins A-I, A-II, A-IV, B, C-II, C-III and E, microsomal triglyceride transfer protein, and cholesterol ester transfer protein (CETP). Until 1998, 922 patients with primary hyperlipidemia and related disorders has been registered with the Research Committee, and 190 mutations in 15 genes had been reported, showing a marked variation in Japanese patients with primary hyperlipidemia and related disorders. So-called "common mutations" have been described in Japanese patients with familial hypercholesterolemia, LPL deficiency and CETP deficiency. The genetic defect of familial combined hyperlipidemia (FCHL) is still unknown although FCHL is speculated to be the most prevalent genetic hyperlipidemia, and further investigations should be performed to elucidate the molecular mechanisms of FCHL
ESTHER : Maruyama_2004_J.Atheroscler.Thromb_11_131
PubMedSearch : Maruyama_2004_J.Atheroscler.Thromb_11_131
PubMedID: 15256764

Title : Biosynthesis and compositional regulation of poly[(3-hydroxybutyrate)-co-(3-hydroxyhexanoate)] in recombinant ralstonia eutropha expressing mutated polyhydroxyalkanoate synthase genes - Tsuge_2004_Macromol.Biosci_4_238
Author(s) : Tsuge T , Saito Y , Kikkawa Y , Hiraishi T , Doi Y
Ref : Macromol Biosci , 4 :238 , 2004
Abstract : A new strategy for bacterial polyhydroxyalkanoate (PHA) production by recombinant Ralstonia eutropha PHB(-)4 harboring mutated PHA synthase genes (phaC(Ac)) from Aeromona caviae was investigated. The strain harboring wild-type phaC(Ac) gene produced a PHA copolymer consisting of (R)-3-hydroxybutyrate and (R)-3-hydroxyhexanoate [P(3HB-co-3HHx)] with 3.5 mol-% of 3HHx fraction from soybean oil. When the mutants of phaC(Ac) gene were applied to this production system, 3HHx fraction in copolymers was varied in the range of 0-5.1 mol-%. Thus, the regulation of PHA copolymer compositions has been achieved by the use of mutated PHA synthase genes.
ESTHER : Tsuge_2004_Macromol.Biosci_4_238
PubMedSearch : Tsuge_2004_Macromol.Biosci_4_238
PubMedID: 15468213
Gene_locus related to this paper: aerca-PHAC

Title : Residue Analysis of the Fungicide Benthiavalicarb-isopropyl and Its Degradation Products in Upland Field Soil - Mizutani_2004_J.Pestic.Sci_29_177
Author(s) : Mizutani H , Suzuki J , Saito Y , Ikeda M , Yagi A
Ref : Journal of Pesticide Science , 29 :87 , 2004
Abstract : A method for residue analysis of benthiavalicarb-isopropyl, its diastereomer, and its four degradation products in soil by HPLC was established. The method of extraction under reflux with a mixture of acetone and ammonium chloride solution was optimal for most of the compounds. The limit of quantification in two soils was 0.01 to 0.02 mg/kg for the compounds, and the recovery rates of the compounds from the soils were 74 to 113%. But for the degradation product having an amino group, the rate of recovery from one soil only was good. The level of benthiavalicarb-isopropyl in two upland field soils decreased rapidly.
ESTHER : Mizutani_2004_J.Pestic.Sci_29_177
PubMedSearch : Mizutani_2004_J.Pestic.Sci_29_177
PubMedID:

Title : PKC-independent inhibition of neuronal nicotinic acetylcholine receptors by diacylglycerol - Andoh_2004_Brain.Res_1013_125
Author(s) : Andoh T , Itoh H , Higashi T , Saito Y , Ishiwa D , Kamiya Y , Yamada Y
Ref : Brain Research , 1013 :125 , 2004
Abstract : Diacylglycerol modulates cell functions primarily through activation of protein kinase C (PKC). In a previous study, however, we found that a diacylglycerol analogue, 1-oleoyl-2-acetylglycerol (OAG), accelerated desensitization of neuronal nicotinic acetylcholine receptors (nAchRs) independently of PKC activation in PC12 cells. In the present study, we investigated whether other analogues and endogenous diacylglycerol exert similar effects on neuronal nAchRs and characterized the modulation by diacylglycerol. We measured the nicotine-induced whole-cell current in the absence and presence of diacylglycerol analogues in PC12 cells. We also investigated the effects of a blockade of metabolic pathways of diacylglycerol by inhibiting diacylglycerol lipase and kinase. We found that all four diacylglycerol analogues studied promoted desensitization and depressed the nondesensitized component of the nicotine-induced current. These effects seemed independent of PKC activation because they were not antagonized by the PKC inhibitors staurosporine or bisindolylmaleimide I; one analogue that lacks the PKC-stimulating action was also effective. The effects of diacylglycerol analogues were not antagonized by high doses of nicotine and were independent of the membrane potential. Similar modulatory effects were observed by treatment with RHC80267, a blocker of diacylglycerol lipase, and R59949, an inhibitor of diacylglycerol kinase, in the presence of staurosporine. These results suggest that diacylglycerol, both exogenously applied and endogenously produced, modulates neuronal nAchRs independently of PKC activation in PC12 cells; further, these effects seemed consistent with a noncompetitive and voltage-independent block. They raised the possibility that PKC-independent inhibition of neuronal nAchRs by diacylglycerol may be a novel modulatory process.
ESTHER : Andoh_2004_Brain.Res_1013_125
PubMedSearch : Andoh_2004_Brain.Res_1013_125
PubMedID: 15196975

Title : Non-synonymous single nucleotide alterations in the microsomal epoxide hydrolase gene and their functional effects - Maekawa_2003_Xenobiotica_33_277
Author(s) : Maekawa K , Itoda M , Hanioka N , Saito Y , Murayama N , Nakajima O , Soyama A , Ishida S , Ozawa S , Ando M , Sawada J
Ref : Xenobiotica , 33 :277 , 2003
Abstract : 1. By sequencing genomic DNA from 72 established cell lines derived from Japanese individuals, we detected 25 single nucleotide alterations in the microsomal epoxide hydrolase (EPHX1) gene. Of them, five were exonic alterations resulting in amino acid alterations (77C>G, T26S; 128G>C, R43T; 337T>C, Y113H; 416A>G, H139R; 823A>G, T275A). The T26S, R43T, Y113H and H139R substitutions were found at relatively high frequencies and seemed to be polymorphic, and T26S and T275A were novel. 2. To examine the effects of these amino acid alterations on EPHX1 function, EPHX1 cDNA constructs of wild-type and five variants were transfected into COS-1 cells, and their hydrolytic activities for cis-stilbene oxide were determined in vitro. Although all of the transfectants expressed EPHX1 mRNA and protein at similar levels, the variant H139R protein was expressed at a significantly higher level (128% of the wild-type). K(m) values were not significantly different between the wild-type and variants. 3. Increase (140%) in the enzymatic activity (V(max)) of the variant H139R was accompanied by the increased EPHX1 protein level without any significant change in the intrinsic EPHX1 activity. On the other hand, the variant R43T showed increased values for V(max) and clearance (V(max)/K(m)) (around 130%) both on a microsomal protein basis and on a EPHX1 protein basis. 4. These results suggest that R43T as well as H139R increase epoxide hydrolase activity.
ESTHER : Maekawa_2003_Xenobiotica_33_277
PubMedSearch : Maekawa_2003_Xenobiotica_33_277
PubMedID: 12637245

Title : Twelve novel single nucleotide polymorphisms in the CES2 gene encoding human carboxylesterase 2 (hCE-2) - Kim_2003_Drug.Metab.Pharmacokinet_18_327
Author(s) : Kim SR , Nakamura T , Saito Y , Sai K , Nakajima T , Saito H , Shirao K , Minami H , Ohtsu A , Yoshida T , Saijo N , Ozawa S , Sawada J
Ref : Drug Metab Pharmacokinet , 18 :327 , 2003
Abstract : Twelve novel single nucleotide polymorphisms (SNPs) were found in the CES2 gene from 153 Japanese individuals, who were administered irinotecan or steroidal drugs. The detected SNPs were as follows:1) SNP, MPJ6_CS2001; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CTGGAACAACTCG/CCTCCCCTCGGAA-3'. 2) SNP, MPJ6_CS2002; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-AACCACCACCGCT/CGATCCTAGCAGG-3'. 3) SNP, MPJ6_CS2003; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-AAATGTTTGTCAA/GGTGGATAAATGA-3'. 4) SNP, MPJ6_CS2004; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CCTCCTATCGATC/GCCCCAGCGCGCT-3'. 5) SNP, MPJ6_CS2005; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-GCCAGTCCCATCC/TGGACCACACACA-3'. 6) SNP, MPJ6_CS2006; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-GCTGGGCAACCCG/AGGCTGAGCGGGG-3'. 7) SNP, MPJ6_CS2007; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CAAGCACGCAACC/TGGCAACTGGGGC-3'. 8) SNP, MPJ6_CS2008; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CATGGAGAGTGGC/TGTGGCCCTCCTG-3'. 9) SNP, MPJ6_CS2009; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CCTGTTCTTGGCC/TAGGGCCTTGGGC-3'. 10) SNP, MPJ6_CS2010; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-CCCATCCCCAGCT/AACAGACTCTCTC-3'. 11) SNP, MPJ6_CS2011; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-TCCACCTGGGGTA/GGATGTTGCCTCC-3'. 12) SNP, MPJ6_CS2013; GENE NAME, CES2; ACCESSION NUMBER, NT_010498.13; LENGTH, 25 bases; 5'-GGACTGGGGACCG/AAGGTCTCGGGGG-3'The frequencies were 0.029 for MPJ6_CS2004 and CS2013, 0.026 for MPJ6_CS2009, 0.013 for MPJ6_CS2001, 0.007 for MPJ6_CS2003, and 0.003 for the other 7 SNPs. Among these SNPs, MPJ6_CS2005 (100C>T) resulted in an amino acid alteration (R34W), and MPJ6_CS2007 (579C>T) and MPJ6_CS2008 (765C>T) were synonymous (T193T and G255G, respectively). Furthermore, MPJ6_CS2011 (IVS8-2A>G) resulted in variation at ther 3' splice acceptor site.
ESTHER : Kim_2003_Drug.Metab.Pharmacokinet_18_327
PubMedSearch : Kim_2003_Drug.Metab.Pharmacokinet_18_327
PubMedID: 15618752
Gene_locus related to this paper: human-CES2

Title : Five novel single nucleotide polymorphisms in the EPHX1 gene encoding microsomal epoxide hydrolase - Shiseki_2003_Drug.Metab.Pharmacokinet_18_150
Author(s) : Shiseki K , Itoda M , Saito Y , Nakajima Y , Maekawa K , Kimura H , Goto Y , Saitoh O , Katoh M , Ohnuma T , Kawai M , Sugai K , Ohtsuki T , Suzuki C , Minami N , Ozawa S , Sawada J
Ref : Drug Metab Pharmacokinet , 18 :150 , 2003
Abstract : Five novel single nucleotide polymorphisms (SNPs) were found in the EPHX1 gene from 96 Japanese epileptic patients. The detected SNPs were as follows: 1) SNP, MPJ6_EX1009; GENE NAME, EPHX1 ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-CCTCACTTCAGTG/ACTGGGCTTTGCC-3'. 2) SNP, MPJ6_EX1013; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-TCCGCAGCCAGGG/CAGGACGACAGCA-3'. 3) SNP, MPJ6_EX1026; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-GTTCTCCCTGGAC/TGACCTGCTGACC-3'. 4) SNP, MPJ6_EX1028; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-AGGCAGGGGGACG/AGCCAGTCTTGGG-3'. 5) SNP, MPJ6_EX1030; GENE NAME, EPHX1; ACCESSION NUMBER, NT_004525.12; LENGTH, 25 bases; 5'-TGAAAAGTGGGTG/AAGGTTCAAGTAC-3'. The frequencies were 0.016 for MPJ6_EX1028 (IVS8+54G>A) and 0.005 for the other SNPs. The SNP MPJ6_EX1013 (130G>C) results in an amino acid alteration (E44Q). The other three SNPs in the coding region, MPJ6_EX1009 (30G>A), MPJ6_EX1026 (1056C>T), and MPJ6_EX1030 (1239G>A) result in synonymous changes (V10V, D352D, and V413V, respectively).
ESTHER : Shiseki_2003_Drug.Metab.Pharmacokinet_18_150
PubMedSearch : Shiseki_2003_Drug.Metab.Pharmacokinet_18_150
PubMedID: 15618730
Gene_locus related to this paper: human-EPHX1

Title : A novel frameshift mutation in exon 6 (the site of Asn 291) of the lipoprotein lipase gene in type I hyperlipidemia - Kobayashi_1999_Clin.Chim.Acta_285_173
Author(s) : Kobayashi J , Nagashima I , Taira K , Hikita M , Tamura K , Bujo H , Morisaki N , Saito Y
Ref : Clinica Chimica Acta , 285 :173 , 1999
Abstract : A new heterozygous lipoprotein lipase gene defect has been identified in a type I hyperlipidemic patient at the position of notable amino acid Asn 291. The patient is a 33-year-old male. His body mass index (BMI) was 18.5 kg/m2. The total cholesterol (TC), triglycerides (TG) and high density lipoprotein-cholesterol (HDL-C) concentration from his fasting plasma were 4.8, 11.9 and 0.4 mmol/l, respectively. The lipoprotein lipase (LPL) activity and mass in the postheparin plasma (PHP) from the patient were 0.58 mmol/ml/h (normal range: 7.7+/-2.6) and 244 ng/ml (normal range: 192+/-30), respectively. The hepatic lipase activity of the PHP from the patient was 10.6 mmol/ml/h (normal range: 9.9+/-3.6). DNA analysis of the LPL gene revealed that this patient had a heterozygous one nucleotide deletion of A coding Asn 291, resulting in a premature termination of the LPL protein at amino acid residue 303. The other abnormality in the LPL gene of the proband was an amino acid residue 194 defect (Ile194-->Thr), which is known to cause a defective enzyme. A medium-chain triglyceride (MCT) loading test was conducted to find how this triglyceride affects plasma lipoprotein metabolism in this patient in a short term (Fig. 3). The plasma total cholesterol (TC) or high density lipoprotein (HDL)-C levels did not change significantly after oral administration of a fatty meal containing long chain triglycerides (LCT) or MCT. The plasma TG level, on the other hand, increased from 11.9 to 19.2 mmol/l (+61%) at 6 h after loading a fatty meal containing LCT, whereas the plasma TG levels tended to even decrease at 6 h after oral administration of an MCT, tricaprin (from 11.6 to 10.5 mmol/l (-9.4%)). These results suggest that MCT, as opposed to LCT, is useful for treatment of type I hyperlipidemia with a novel mutation at the notable amino acid Asn 291 of the LPL gene.
ESTHER : Kobayashi_1999_Clin.Chim.Acta_285_173
PubMedSearch : Kobayashi_1999_Clin.Chim.Acta_285_173
PubMedID: 10481934
Gene_locus related to this paper: human-LPL

Title : Lipoprotein lipase mass and activity in post-heparin plasma from subjects with intra-abdominal visceral fat accumulation - Kobayashi_1998_Clin.Endocrinol.(Oxf)_48_515
Author(s) : Kobayashi J , Tashiro J , Murano S , Morisaki N , Saito Y
Ref : Clinical Endocrinology (Oxf) , 48 :515 , 1998
Abstract : OBJECTIVES: The purpose of this study was to investigate the possibility of impaired lipolysis of triglyceride-rich lipoproteins in patients with abdominal visceral fat accumulation by assessing two major lipolytic enzymes in the plasma, lipoprotein lipase (LPL) and hepatic lipase (HL). DESIGN AND PATIENTS: A total of 31 patients [20 men, 11 women, age 50 +/- 7 years old, body mass index (BMI) 26 +/- 2 kg/m2 (mean +/- sd)] were analyzed. Visceral fat and subcutaneous fat areas were evaluated using a computerized tomographic (CT) method at the level of the umbilicus. Total lipolytic activity in the postheparin plasma (PHP) was measured using Triton X-100-emulsified triolein and LPL activity was calculated as the activity in whole plasma inhibited by the 5D2 monoclonal antibody for LPL. LPL enzyme mass was determined by a sandwich enzyme immunoassay.
RESULTS: The visceral fat area was found to be negatively correlated with LPL mass (V vs LPL mass, r = -0.37, P = 0.04) in PHP and had a tendency toward negative correlation with the LPL activity in the PHP (V vs LPL activity, r = -0.29, P = 0.12). Subcutaneous fat area, on the other hand, did not show any correlation with LPL activity (r = 0.13, P = 0.49) or mass (r = 0.22, P = 0.25) in the PHP. The visceral fat area was found to be positively correlated with fasting serum insulin levels (r = 0.67, P < 0.01). Body mass index (BMI) was not correlated with LPL mass or activity in the PHP. Multi-regressional analysis showed that abdominal visceral fat could be correlated with LPL mass in the PHP, independently of fasting serum insulin. The HL activity from PHP of the patients did not show significant correlation with visceral fat area, subcutaneous fat area or body mass index.
CONCLUSIONS: Fat distribution affects LPL mass and activity, either directly or via another metabolic abnormality such as insulin resistance, leading to impaired hydrolysis of triglycerides in chylomicrons and very low density lipoproteins (VLDL) in these subjects.
ESTHER : Kobayashi_1998_Clin.Endocrinol.(Oxf)_48_515
PubMedSearch : Kobayashi_1998_Clin.Endocrinol.(Oxf)_48_515
PubMedID: 9640420

Title : A naturally occurring mutation at the second base of codon asparagine 43 in the proposed N-linked glycosylation site of human lipoprotein lipase: in vivo evidence that asparagine 43 is essential for catalysis and secretion - Kobayashi_1994_Biochem.Biophys.Res.Commun_205_506
Author(s) : Kobayashi J , Inadera H , Fujita Y , Talley G , Morisaki N , Yoshida S , Saito Y , Fojo SS , Brewer HB, Jr.
Ref : Biochemical & Biophysical Research Communications , 205 :506 , 1994
Abstract : The patient was a 20-year-old male. His fasting plasma triglyceride and cholesterol levels were 1258 mg/dl and 138 mg/dl, respectively. The lipoprotein lipase (LPL) activity and mass from postheparin plasma of the patient were 0.00 mumol/ml/h (normal range: 5.51 +/- 1.12) and 23 ng/ml (normal range: 220 +/- 42), respectively. DNA sequence analysis of the LPL gene from the patient revealed a homozygous nucleotide change: a A-->G transition at nucleotide position 383, resulting in an amino acid substitution of Ser for Asn43, which is believed to be an N-linked glycosylation site of the LPL mature protein. Expression studies of this mutant LPL cDNA produced an inactive LPL protein which was not secreted into the media.
ESTHER : Kobayashi_1994_Biochem.Biophys.Res.Commun_205_506
PubMedSearch : Kobayashi_1994_Biochem.Biophys.Res.Commun_205_506
PubMedID: 7999071

Title : Entire nucleotide sequence for Bacillus brevis Nagano Grs2 gene encoding gramicidin S synthetase 2: a multifunctional peptide synthetase - Saito_1994_J.Biochem_116_357
Author(s) : Saito F , Hori K , Kanda M , Kurotsu T , Saito Y
Ref : J Biochem , 116 :357 , 1994
Abstract : Bacillus brevis Nagano grs2 gene, which encodes gramicidin S synthetase 2 (GS2) catalyzing activation and combination of four constituent amino acids of gramicidin S, namely, proline, valine, ornithine, and leucine, has been sequenced. The open reading frame of grs2 gene specifies a 4,450-amino acid protein with a calculated molecular weight of 508,658. There are four domains with a mean of 1,042 amino acid residues containing a repeated sequence of about 600 amino acids, which is highly homologous to the amino-terminal half of gramicidin S synthetase 1 (GS1) (about 40-50% identity). Three domains of grs2 protein, excluding the first one, show homology over the entire sequences of 1,042 amino acids, but the first domain only shows homology in the conserved 600-amino acid sequence. The last 300-amino acid sequence of grs2 protein following the fourt domain has no homology with any of the above sequences. Translation products of subcloned fragments containing the third or the fourth domain catalyzed ornithine- or leucine-dependent ATP-32Pi exchange, respectively. These results, together with a previous report on a proline-activation domain indicated that the repeated and conserved domains are the individual activation sites of the constituent amino acids; the activation sites are arranged in the order of peptide elongation on GS2. Several motifs of grs2 protein are conserved among the multiple domains of peptide synthetases and aminoacyl or acyl adenylate-forming enzymes.
ESTHER : Saito_1994_J.Biochem_116_357
PubMedSearch : Saito_1994_J.Biochem_116_357
PubMedID: 7822255
Gene_locus related to this paper: bacbr-grsb

Title : A missense mutation (Ala334-->Thr) in exon 7 of the lipoprotein lipase gene in a case with type I hyperlipidemia - Kobayashi_1993_Biochem.Biophys.Res.Commun_191_1046
Author(s) : Kobayashi J , Sasaki N , Tashiro J , Inadera H , Saito Y , Yoshida S
Ref : Biochemical & Biophysical Research Communications , 191 :1046 , 1993
Abstract : The patient is a 34-year-old female. Her fasting plasma triglyceride and cholesterol levels were 7523 mg/dl and 818 mg/dl, respectively, at 35 weeks' gestation. The lipoprotein lipase (LPL) activity and mass from postheparin plasma of the proband were 0.02 (normal range: 5.51 +/- 1.12 mu mol/ml/h) and 168 ng/ml (normal range: 220 +/- 42 ng/ml), respectively, indicating that the LPL of the patient would be functionally defective LPL. DNA sequence analysis of the LPL gene from the patient revealed a homozygous nucleotide change: a G--> A transition at nucleotide position of 1255 resulting in an amino acid substitution of Thr for Ala 334. This is the first natural missense mutation identified in exon 7 of the LPL gene.
ESTHER : Kobayashi_1993_Biochem.Biophys.Res.Commun_191_1046
PubMedSearch : Kobayashi_1993_Biochem.Biophys.Res.Commun_191_1046
PubMedID: 8096693
Gene_locus related to this paper: human-LPL

Title : A heterozygous mutation (the codon for Ser447----a stop codon) in lipoprotein lipase contributes to a defect in lipid interface recognition in a case with type I hyperlipidemia - Kobayashi_1992_Biochem.Biophys.Res.Commun_182_70
Author(s) : Kobayashi J , Nishida T , Ameis D , Stahnke G , Schotz MC , Hashimoto H , Fukamachi I , Shirai K , Saito Y , Yoshida S
Ref : Biochemical & Biophysical Research Communications , 182 :70 , 1992
Abstract : Previously, we reported a case with type I hyperlipidemia due to a lipid interface recognition deficiency in lipoprotein lipase (LPL) (1). The LPL from postheparin plasma of this patient did not hydrolyze TritonX-100-triolein or very low density lipoprotein-triolein but did hydrolyze tributyrin and LysoPC-triolein substrates. Sequence analysis of the probands DNA revealed a heterozygous nucleotide change: a C----G transversion at position of 1595, resulting in changing the codon for Ser447 to a stop codon. Expression studies of this mutant LPLcDNA in Cos-1 cells produced and secreted considerable amounts of LPL mass in the culture media. The mutated LPL hydrolyzed much less TritonX-100-triolein than wild type LPL, whereas hydrolysis of tributyrin and LysoPC--triolein was the same with both the mutant and wild type LPL. These results suggest that this mutation might be responsible for the property of the LPL with a defect in lipid interface recognition in the type I patient we reported.
ESTHER : Kobayashi_1992_Biochem.Biophys.Res.Commun_182_70
PubMedSearch : Kobayashi_1992_Biochem.Biophys.Res.Commun_182_70
PubMedID: 1731801

Title : The nucleotide sequence for a proline-activating domain of gramicidin S synthetase 2 gene from Bacillus brevis - Hori_1991_J.Biochem_110_111
Author(s) : Hori K , Yamamoto Y , Tokita K , Saito F , Kurotsu T , Kanda M , Okamura K , Furuyama J , Saito Y
Ref : J Biochem , 110 :111 , 1991
Abstract : A fragment encoding proline-activating domain (grs 2-pro) of gramicidin S synthetase 2 (GS 2) was found in an 8.1-kilobase pairs (kb) DNA fragment of Bacillus brevis Nagano, which contained the full length of GS 1 gene (grs 1). The clones designated GS719 and GS708, which expressed gramicidin S synthetase 1, were elucidated to express immunoreactive proteins to GS 2 antibodies with approximate molecular weights of 115,000, 105,000 (GS719), and 110,000 (GS708). The partial purification of the gene products of these clones was carried out using DEAE-Sepharose CL-6B column chromatography. The immunoreactive proteins to GS 2 antibodies were separated from gramicidin S synthetase 1 protein and had specific proline-dependent ATP-32PPi exchange activity. The nucleotide sequence for the proline-activating domain in the 8.1-kb insert was determined. This fragment was 2,879 base pairs long, and encoded 959 amino acids. The calculated molecular weight of 111,671 was consistent with the apparent molecular weight of 115,000 found in SDS-PAGE of the immunoreactive products to GS 2 antibodies. The open reading frame for this protein followed grs 1 gene, though two were separated by a 73-base pair noncoding sequence, and remained open to the end.(ABSTRACT TRUNCATED AT 250 WORDS)
ESTHER : Hori_1991_J.Biochem_110_111
PubMedSearch : Hori_1991_J.Biochem_110_111
PubMedID: 1939016
Gene_locus related to this paper: bacbr-grsb

Title : Molecular defect in familial lecithin:cholesterol acyltransferase (LCAT) deficiency: a single nucleotide insertion in LCAT gene causes a complete deficient type of the disease - Bujo_1991_Biochem.Biophys.Res.Commun_181_933
Author(s) : Bujo H , Kusunoki J , Ogasawara M , Yamamoto T , Ohta Y , Shimada T , Saito Y , Yoshida S
Ref : Biochemical & Biophysical Research Communications , 181 :933 , 1991
Abstract : Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a hereditary disorder with clinical manifestations including corneal opacity, premature atherosclerosis and renal failure. In this study, we analyzed the molecular base underlying a case of Japanese LCAT deficiency, in which both LCAT mass and activity of the proband were nearly absent. DNA blot hybridization analysis showed no gross rearrangement in the LCAT gene of the proband. The nucleotide sequence analysis of the cloned LCAT gene demonstrated only an extra nucleotide "C" insertion at the first exon, when compared to the sequence of wild type. This single base insertion caused a shift of the following reading frame, probably resulting in a truncated abnormal LCAT polypeptide that consist of only 16 amino acids. The direct sequence analysis of PCR-amplified DNA showed only the same insertion, indicating that the LCAT-deficient proband is a homozygote for the mutant allele. These results indicate that the clinical and biochemical feature of the patient is mainly caused by a complete deficiency of the enzyme based on a homozygous abnormality of LCAT gene.
ESTHER : Bujo_1991_Biochem.Biophys.Res.Commun_181_933
PubMedSearch : Bujo_1991_Biochem.Biophys.Res.Commun_181_933
PubMedID: 1662503

Title : Characterization and location of the L-proline activating fragment from the multifunctional gramicidin S synthetase 2 - Kurotsu_1991_J.Biochem_109_763
Author(s) : Kurotsu T , Hori K , Kanda M , Saito Y
Ref : J Biochem , 109 :763 , 1991
Abstract : Gramicidin S synthetase 2 (GS2) derived from Bacillus brevis is a multifunctional single polypeptide (Mr 280,000) with a 4'-phosphopantetheine residue covalently bound to the enzyme. When GS2 was treated with trypsin or chymotrypsin, fragments with some activity were liberated. The molecular mass of the L-proline activating fragment was 114 kDa on SDS-PAGE. This fragment, when incubated with gramicidin S synthetase 1 (GS1) in the presence of phenylalanine and proline, produced D-Phe-L-Pro dipeptide. The fragment accepted D-phenylalanine from GS1 in the absence of L-proline. The L-proline activating fragment was shown to lack pantothenic acid by microbiological assay. On the other hand, the L-leucine activating fragment, which was partially purified, contained a large amount of pantothenic acid, although it did not form the D-Phe-L-Pro dipeptide. These results indicate that the L-proline activating site is located near an acceptor site for D-phenylalanine on GS2, but that it is not adjacent to a 4'-phosphopantetheine group. The N-terminal sequence (15 amino acid residues) of the L-proline activating fragment obtained by trypsin treatment was identical with that of GS2, indicating that the L-proline activating site is located at the N-terminus of the native synthetase. The N-terminal sequence of GS2 has been matched with the amino acid sequence deduced from the nucleotide sequence 71 bp downstream of the stop codon of the GS1 gene except that the first initiator methionine was not detected.
ESTHER : Kurotsu_1991_J.Biochem_109_763
PubMedSearch : Kurotsu_1991_J.Biochem_109_763
PubMedID: 1917901
Gene_locus related to this paper: bacbr-grsb

Title : Poster: Cholesterol ester hydrolyzing activity by pseudo choline esterase {PchE} and its role in lipoprotein metabolism -
Author(s) : Shirai K , Inadera H , Kurosawa H , Saito Y , Yoshida S
Ref : In: Cholinesterases: Structure, Function, Mechanism, Genetics, and Cell Biology , (Massoulie J, Barnard EA, Chatonnet A, Bacou F, Doctor BP, Quinn DM) American Chemical Society, Washington, DC :390 , 1991
PubMedID:

Title : Lipoprotein lipase with a defect in lipid interface recognition in a case with type I hyperlipidaemia - Kobayashi_1989_Eur.J.Clin.Invest_19_424
Author(s) : Kobayashi J , Shirai K , Saito Y , Yoshida S
Ref : European Journal of Clinical Investigation , 19 :424 , 1989
Abstract : Defective lipoprotein lipase (LpL) was found in the postheparin plasma (PHP) of a patient with severe hypertriglyceridaemia. The patient was a 14-year-old girl with a maximum plasma triglyceride (TG) level of 3600 mg d-1 who had been suffering from recurrent pancreatitis. The patient's LpL purified from the PHP by heparin-Sepharose and phenyl-Sepharose chromatographies hydrolysed tributryrin, but not triolein emulsified with Triton X-100 and phosphatidylcholine (PC), or in chylomicrons, whereas normal LpL hydrolysed these substrates. Moreover, unlike normal LpL, LpL from the patient did not associate with VLDL, as shown by Sepharose 4B column chromatography. The patient's LpL hydrolysed triolein emulsified with lysophospholipid at a normal rate in the presence of apolipoprotein CII. These findings suggest that this patient has LpL with a normal catalytic site for tributyrin but with a defect in lipid interface recognition resulting in loss of ability to recognize VLDL or chylomicrons, but not of triolein emulsified with lysophospholipid.
ESTHER : Kobayashi_1989_Eur.J.Clin.Invest_19_424
PubMedSearch : Kobayashi_1989_Eur.J.Clin.Invest_19_424
PubMedID: 2511018
Gene_locus related to this paper: human-LPL

Title : Beneficial effects of FKS-508 (AF102B), a selective M1 agonist, on the impaired working memory in AF64A-treated rats - Nakahara_1989_Jpn.J.Pharmacol_51_539
Author(s) : Nakahara N , Iga Y , Saito Y , Mizobe F , Kawanishi G
Ref : Japanese Journal of Pharmacology , 51 :539 , 1989
Abstract : The effects of FKS-508 [AF102B; cis-2-methylspiro(1,3-oxathiolane-5,3')quinuclidine], a selective M1 muscarinic receptor agonist, were examined to predict the possible activity on memory disorders using a T-maze and radial-arm maze task in experimental amnesia models. The amnesia models were produced by bilateral intracerebroventricular injection of ethylcholine aziridinium ion (AF64A), a selective cholinotoxin, in rats. Repeated administrations of FKS-508 (5 mg/kg/day, i.p.) for 5 weeks significantly ameliorated impaired performance of AF64A-treated rats (AF64A-rats) in a delayed alternation task in the T-maze. Repeated administrations of FKS-508 (1 and 5 mg/kg/day, p.o.) for 5 weeks significantly ameliorated acquisition failures of AF64A-rats in a radial-arm maze task. Single administration of FKS-508 (1 and 5 mg/kg, p.o.) significantly reduced the incorrect choices of AF64A-rats in a radial-arm maze task with 6 hr-delay time. No abnormalities in general behaviors, such as loss of appetite and ataxia, were observed in rats treated with FKS-508 repeatedly during 5 weeks. Our present results showed that FKS-508 can ameliorate memory impairments in AF64A-rats with central cholinergic hypofunction without causing any behavioral abnormalities. FKS-508 may be considered as a candidate for the clinical examination of the cholinergic hypothesis of senile dementia of the Alzheimer type.
ESTHER : Nakahara_1989_Jpn.J.Pharmacol_51_539
PubMedSearch : Nakahara_1989_Jpn.J.Pharmacol_51_539
PubMedID: 2615046

Title : Heterogeneity of muscarinic autoreceptors and heteroreceptors in the rat brain: effects of a novel M1 agonist, AF102B - Ono_1988_Eur.J.Pharmacol_155_77
Author(s) : Ono S , Saito Y , Ohgane N , Kawanishi G , Mizobe F
Ref : European Journal of Pharmacology , 155 :77 , 1988
Abstract : The effects of oxotremorine and AF102B (cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine), a novel M1-selective muscarinic agonist, on acetylcholine (ACh) and dopamine (DA) release from superfused rat hippocampal and striatal synaptosomes were investigated. Synaptosomes that had been prelabeled with [3H]choline or [3H]DA were depolarized by high K+. Oxotremorine and AF102B decreased the K+-evoked [3H]ACh release from hippocampal synaptosomes and increased the K+-evoked [3H]DA release from striatal synaptosomes. The dose-response curves showed that AF102B was far less potent than oxotremorine at the hippocampal presynaptic muscarinic receptors (autoreceptors). On the other hand, AF102B was more potent than oxotremorine at the muscarinic receptors on the striatal dopaminergic terminals (heteroreceptors). Pirenzepine, a selective M1 antagonist, counteracted the effects of oxotremorine on [3H]DA release more potently than it did the effects of oxotremorine on [3H]ACh release. Our results suggest that AF102B and pirenzepine discriminate pharmacologically between muscarinic autoreceptors and heteroreceptors.
ESTHER : Ono_1988_Eur.J.Pharmacol_155_77
PubMedSearch : Ono_1988_Eur.J.Pharmacol_155_77
PubMedID: 3243333

Title : Simplified cleanup and gas chromatographic determination of organophosphorus pesticides in crops - Sasaki_1987_J.Assoc.Off.Anal.Chem_70_460
Author(s) : Sasaki K , Suzuki T , Saito Y
Ref : J Assoc Off Analytical Chemistry , 70 :460 , 1987
Abstract : A simple and efficient cleanup method for gas chromatographic determination of 23 organophosphorus pesticides in crops including onion is described. The sample was extracted with acetone. The extract was purified with coagulating solution, which contained ammonium chloride and phosphoric acid, and then filtered by suction. The filtrate was diluted with NaCl solution and reextracted with benzene. The organic layer was evaporated and injected into a gas chromatograph equipped with a flame photometric detector (FPD) and fused silica capillary columns (0.53 mm id) coated with silicone equivalent to OV-1701, OV-1, and SE-52. Onion extract, which contained FPD interferences, was cleaned up on a disposable silica cartridge. Recoveries of most organophosphorus pesticides from spiked crops: mandarin orange, tomato, spinach, sweet pepper, broccoli, lettuce, and onion at levels of 0.02-0.28 ppm, exceeded 80%, but the water-soluble pesticides dichlorvos and dimethoate gave poor recoveries in all crops; the nonpolar pesticides disulfoton, chlorpyrifos, fenthion, prothiophos, and leptophos were not recovered quantitatively in spinach, sweet pepper, broccoli, and lettuce. IBP, edifenphos, phosmet, and pyridaphenthion were not recovered from onion because of adsorption to the silica cartridge. The detection limits ranged from 1.25 to 17.5 ppb on a crop basis.
ESTHER : Sasaki_1987_J.Assoc.Off.Anal.Chem_70_460
PubMedSearch : Sasaki_1987_J.Assoc.Off.Anal.Chem_70_460
PubMedID: 3610958

Title : Ester synthesis at extraordinarily low temperature of -3 degrees C by modified lipase in benzene - Takahashi_1985_Biochem.Int_10_627
Author(s) : Takahashi K , Yoshimoto T , Tamaura Y , Saito Y , Inada Y
Ref : Biochemistry International , 10 :627 , 1985
Abstract : The lipoprotein lipase from Pseudomonas fluorescens was modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine. The modified lipase in which 55% of the amino groups in the enzyme molecule were coupled with polyethylene glycol was found to be soluble in benzene and catalyzed the reactions of ester synthesis, ester exchange, aminolysis and ester hydrolysis in benzene. The modified lipase had an extraordinary temperature-dependency: enzymic activity for methyl laurate synthesis from methyl alcohol and lauric acid increased with decreasing temperature and attained the maximum at the extremely low temperature of -3 degrees C. The optimum temperature for hydrolysis of methyl laurate was as low as -4 degrees C.
ESTHER : Takahashi_1985_Biochem.Int_10_627
PubMedSearch : Takahashi_1985_Biochem.Int_10_627
PubMedID: 3927919

Title : Ester synthesis catalyzed by polyethylene glycol-modified lipase in benzene - Inada_1984_Biochem.Biophys.Res.Commun_122_845
Author(s) : Inada Y , Nishimura H , Takahashi K , Yoshimoto T , Saha AR , Saito Y
Ref : Biochemical & Biophysical Research Communications , 122 :845 , 1984
Abstract : Lipoprotein lipase, which catalyzes hydrolysis of emulsified triglycerides or water-insoluble esters, was modified with 2,4-bis(o-methoxy-polyethylene glycol)-6-chloro-s-triazine(activated PEG2). The modified lipase, in which 55% of the total amino groups in the lipase molecule, was soluble in organic solvents such as benzene, toluene, chloroform and dioxane. The modified lipase could catalyze ester synthesis reaction in benzene. When very hydrophobic substrates of lauryl alcohol and stearic acid were used, the ester synthesis reaction proceeded efficiently in the transparent benzene solution with the maximum activity of approximate 5.0 mumoles/min/mg of protein. Ester exchange and aminolysis reactions were also conducted with the modified lipase in benzene.
ESTHER : Inada_1984_Biochem.Biophys.Res.Commun_122_845
PubMedSearch : Inada_1984_Biochem.Biophys.Res.Commun_122_845
PubMedID: 6431976