Kobayashi T

References (45)

Title : Different cholinergic cell groups in the basal forebrain regulate social interaction and social recognition memory - Okada_2021_Sci.Rep_11_13589
Author(s) : Okada K , Nishizawa K , Kobayashi T , Sakata S , Hashimoto K , Kobayashi K
Ref : Sci Rep , 11 :13589 , 2021
Abstract : Social behaviour is a complex construct that is reported to include several components of social approach, interaction and recognition memory. Alzheimer's disease (AD) is mainly characterized by progressive dementia and is accompanied by cognitive impairments, including a decline in social ability. The cholinergic system is a potential constituent for the neural mechanisms underlying social behaviour, and impaired social ability in AD may have a cholinergic basis. However, the involvement of cholinergic function in social behaviour has not yet been fully understood. Here, we performed a selective elimination of cholinergic cell groups in the basal forebrain in mice to examine the role of cholinergic function in social interaction and social recognition memory by using the three-chamber test. Elimination of cholinergic neurons in the medial septum (MS) and vertical diagonal band of Broca (vDB) caused impairment in social interaction, whereas ablating cholinergic neurons in the nucleus basalis magnocellularis (NBM) impaired social recognition memory. These impairments were restored by treatment with cholinesterase inhibitors, leading to cholinergic system activation. Our findings indicate distinct roles of MS/vDB and NBM cholinergic neurons in social interaction and social recognition memory, suggesting that cholinergic dysfunction may explain social ability deficits associated with AD symptoms.
ESTHER : Okada_2021_Sci.Rep_11_13589
PubMedSearch : Okada_2021_Sci.Rep_11_13589
PubMedID: 34193944

Title : Effect of UGT1A1, CYP3A and CES Activities on the Pharmacokinetics of Irinotecan and its Metabolites in Patients with UGT1A1 Gene Polymorphisms - Yokokawa_2021_Eur.J.Drug.Metab.Pharmacokinet__
Author(s) : Yokokawa A , Kaneko S , Endo S , Minowa Y , Ayukawa H , Hirano R , Nagashima F , Naruge D , Okano N , Kobayashi T , Kawai K , Furuse J , Furuta T , Shibasaki H
Ref : Eur J Drug Metab Pharmacokinet , : , 2021
Abstract : BACKGROUND AND OBJECTIVES: Irinotecan (CPT-11) is metabolized to an active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) by carboxylesterase (CES). SN-38 is then converted to the inactive metabolite SN-38 glucuronide (SN-38G) by glucuronosyltransferase 1A1 (UGT1A1). Genetic polymorphisms in UGT1A1 have been associated with altered SN-38 pharmacokinetics, which increase the risk of toxicity in patients. CPT-11 is also converted to 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC) and 7-ethyl-10-(4-amino-1-piperidino) carbonyloxycamptothecin (NPC) by cytochrome P450 3A (CYP3A), and this route also affects the plasma concentration of SN-38. We evaluated the activities of UGT1A1, CYP3A, and CES and the factors affecting the pharmacokinetics of plasma SN-38 in patients with UGT1A1 gene polymorphisms. METHODS: Three male patients aged 56, 65, and 49 years were recruited for the analysis. All patients had pancreatic cancer, received FOLFIRINOX, and had UGT1A1*6/*6 (patients 1 and 3) or *6/*28 (patient 2) genetic polymorphisms. The rate constants for evaluating the enzyme activity were determined from the measured plasma concentration of CPT-11 and its metabolites using a two-compartment model by WinNonlin. RESULTS: The area under the plasma concentration-time curve (AUC) of SN-38 was patient 1 > patient 2 > patient 3. The rate constants obtained from the model analysis indicated the respective enzyme activities of UGT1A1 (k57), CYP3A (k13 + k19), and CES (k15). The order of values for UGT1A1 activity was patient 2 > patient 3 > patient 1. Since UGT1A1 activity was low in patient 1 with a high AUC of SN-38, it can be said that the increase in plasma concentration was due to a decrease in UGT1A1 activity. Conversely, the order of values for CYP3A and CES activities was patient 3 > patient 1 > patient 2 and patient 2 > patient 1 > patient 3, respectively. Patient 3 had the lowest AUC of SN-38, caused by a lower level of CES activity and increased CYP3A activity. CONCLUSION: In this study, we indicated that the plasma AUC of SN-38 and AUC ratio of SN-38G/SN-38 may depend on changes in the activities of CYP3A, CES, and UGT1A1. Using pharmacokinetic analysis, it is possible to directly evaluate enzyme activity and consider what kind of enzyme variation causes the increase in the AUC of SN-38.
ESTHER : Yokokawa_2021_Eur.J.Drug.Metab.Pharmacokinet__
PubMedSearch : Yokokawa_2021_Eur.J.Drug.Metab.Pharmacokinet__
PubMedID: 33619631

Title : Hemorrhoidectomy for elderly patients aged 75 years or more, before and after studies - Yamamoto_2020_Ann.Med.Surg.(Lond)_55_88
Author(s) : Yamamoto M , Ikeda M , Matsumoto T , Takemoto M , Sumimoto R , Kobayashi T , Ohdan H
Ref : Ann Med Surg (Lond) , 55 :88 , 2020
Abstract : Background: The incidence of hemorrhoids requiring hemorrhoidectomy among the elderly has been increasing. Old age is sometimes considered a contraindication for surgery. The relationship between age and complications of hemorrhoidectomy for elderly patients is not well established. This study aimed to compare the clinicopathological features and postoperative outcomes of hemorrhoidectomy in the elderly (>/=75 years old) and non-elderly patients (<75 years old). Methods: A total of 100 patients who underwent hemorrhoidectomy for hemorrhoids of Goligher classification grades 3 and 4 at our institution between 2014 and 2018 were enrolled. The clinical characteristics were compared between the elderly and non-elderly patients. Pain scores were measured at 6, 12, 24, and 48 h after surgery. The risk factors for postoperative complications were identified. Results: A total of 34 patients were classified as elderly patients. In the elderly group, aspartate aminotransferase levels were higher while the albumin levels and cholinesterase levels were lower and the platelet counts were significantly lower. The blood urea nitrogen levels were higher and estimated glomerular filtration rates and hemoglobin levels were significantly lower in the elderly group. The pain scores significantly decreased at 48 h postoperatively compared to those recorded at 6 h postoperatively in both groups. Multivariate analysis identified Goligher classification grade 4 and high neutrophil to lymphocyte ratio at the indicators of complications. Conclusions: Hemorrhoids due to impairment of liver function and kidney function were dominant in elderly patients. Aging itself was not a risk factor for postoperative complications.
ESTHER : Yamamoto_2020_Ann.Med.Surg.(Lond)_55_88
PubMedSearch : Yamamoto_2020_Ann.Med.Surg.(Lond)_55_88
PubMedID: 32477502

Title : Combined use of irinotecan and p53 activator enhances growth inhibition of mesothelioma cells - Han_2020_FEBS.Open.Bio_10_2375
Author(s) : Han B , Lee-Okada HC , Ishimine M , Orita H , Nishikawa K , Takagaki T , Kajino K , Yokomizo T , Hino O , Kobayashi T
Ref : FEBS Open Bio , 10 :2375 , 2020
Abstract : Malignant mesothelioma (MM) is an aggressive malignant neoplasm which rapidly invades pleural tissues and has a poor prognosis. Here, we explore enhancement of the effect of irinotecan [camptothecin-11 (CPT-11)] by the p53-dependent induction of carboxylesterase 2 (CES2), a CPT-11-activating enzyme, in MM. The level of CES2 mRNA was greatly increased on treatment with nutlin-3a. A combination of CPT-11 and nutlin-3a inhibited the growth of MM cells more effectively than either drug alone. Knocking down CES2 in MM cells reduced the effect of the drug combination, and its forced expression in MESO4 cells enhanced the growth inhibitory activity of CPT-11 in the absence of nutlin-3a. Enhancement of the growth inhibitory activity of CPT-11 by nutlin-3a suggests a possible new combinatorial MM chemotherapy regimen.
ESTHER : Han_2020_FEBS.Open.Bio_10_2375
PubMedSearch : Han_2020_FEBS.Open.Bio_10_2375
PubMedID: 32961616

Title : Genome-wide Identification of Tebufenozide Resistant Genes in the smaller tea tortrix, Adoxophyes honmai (Lepidoptera: Tortricidae) - Uchibori-Asano_2019_Sci.Rep_9_4203
Author(s) : Uchibori-Asano M , Jouraku A , Uchiyama T , Yokoi K , Akiduki G , Suetsugu Y , Kobayashi T , Ozawa A , Minami S , Ishizuka C , Nakagawa Y , Daimon T , Shinoda T
Ref : Sci Rep , 9 :4203 , 2019
Abstract : The smaller tea tortrix, Adoxophyes honmai, has developed strong resistance to tebufenozide, a diacylhydrazine-type (DAH) insecticide. Here, we investigated its mechanism by identifying genes responsible for the tebufenozide resistance using various next generation sequencing techniques. First, double-digest restriction site-associated DNA sequencing (ddRAD-seq) identified two candidate loci. Then, synteny analyses using A. honmai draft genome sequences revealed that one locus contained the ecdysone receptor gene (EcR) and the other multiple CYP9A subfamily P450 genes. RNA-seq and direct sequencing of EcR cDNAs found a single nucleotide polymorphism (SNP), which was tightly linked to tebufenozide resistance and generated an amino acid substitution in the ligand-binding domain. The binding affinity to tebufenozide was about 4 times lower in in vitro translated EcR of the resistant strain than in the susceptible strain. RNA-seq analyses identified commonly up-regulated genes in resistant strains, including CYP9A and choline/carboxylesterase (CCE) genes. RT-qPCR analysis and bioassays showed that the expression levels of several CYP9A and CCE genes were moderately correlated with tebufenozide resistance. Collectively, these results suggest that the reduced binding affinity of EcR is the main factor and the enhanced detoxification activity by some CYP9As and CCEs plays a supplementary role in tebufenozide resistance in A. honmai.
ESTHER : Uchibori-Asano_2019_Sci.Rep_9_4203
PubMedSearch : Uchibori-Asano_2019_Sci.Rep_9_4203
PubMedID: 30862839

Title : Comparison of effects of anagliptin and alogliptin on serum lipid profile in type 2 diabetes mellitus patients - Kurozumi_2018_J.Diabetes.Investig_9_360
Author(s) : Kurozumi A , Okada Y , Arao T , Kobayashi T , Masuda D , Yamashita S , Tanaka Y
Ref : J Diabetes Investig , 9 :360 , 2018
Abstract : INTRODUCTION: Anagliptin (ANA) improves dyslipidemia in addition to blood glucose levels. However, there are no comparative studies on the effects of ANA and other dipeptidyl peptidase-4 inhibitors on serum lipid profile. We compared the effects of ANA on serum lipid profile with those of alogliptin (ALO) in type 2 diabetes mellitus outpatients. MATERIALS AND METHODS: The study participants were 87 type 2 diabetes mellitus patients who had been treated with dipeptidyl peptidase-4 inhibitors for >/=8 weeks and had a low-density lipoprotein cholesterol (LDL-C) level of >/=120 mg/dL. Participants were switched to either 200 mg/day ANA or 25 mg/day ALO for 24 weeks. RESULTS: There was no significant difference in percentage change in LDL-C level at 24 weeks between the ANA and ALO groups. Treatment with ANA for 12 weeks significantly decreased LDL-C levels, one of the secondary end-points. Treatment with ANA for 24 weeks significantly improved apolipoprotein B-100 levels, and the percentage change in LDL-C levels at 24 weeks correlated significantly with the percentage change in apolipoprotein B-100 levels in the ANA group. CONCLUSIONS: The LDL-C-lowering effects of ANA and ALO at 24 weeks were almost similar in patients with type 2 diabetes mellitus. However, the results showed a tendency for a decrease in LDL-C level at 24 weeks in the ANA group, and that such improvement was mediated, at least in part, through the suppression of apolipoprotein B-100 synthesis.
ESTHER : Kurozumi_2018_J.Diabetes.Investig_9_360
PubMedSearch : Kurozumi_2018_J.Diabetes.Investig_9_360
PubMedID: 28853228

Title : The Relationship between TP53 Gene Status and Carboxylesterase 2 Expression in Human Colorectal Cancer - Ishimine_2018_Dis.Markers_2018_5280736
Author(s) : Ishimine M , Lee HC , Nakaoka H , Orita H , Kobayashi T , Mizuguchi K , Endo M , Inoue I , Sato K , Yokomizo T
Ref : Dis Markers , 2018 :5280736 , 2018
Abstract : Irinotecan (CPT-11) is an anticancer prodrug that is activated by the carboxylesterase CES2 and has been approved for the treatment of many types of solid tumors, including colorectal cancer. Recent studies with cell lines show that CES2 expression is regulated by the tumor suppressor protein p53. However, clinical evidence for this regulatory mechanism in cancer is lacking. In this study, we examined the relationship between TP53 gene status and CES2 expression in human colorectal cancer. Most colorectal cancer specimens (70%; 26 of 37) showed lower CES2 mRNA levels (>/=1.5-fold lower) than the adjacent normal tissue, and only 30% (12 of 37) showed similar (<1.5-fold lower) or higher CES2 mRNA levels. However, TP53 gene sequencing revealed no relationship between CES2 downregulation and TP53 mutational status. Moreover, while colorectal cancer cells expressing wild-type p53 exhibited p53-dependent upregulation of CES2, PRIMA-1(MET), a drug that restores the transcriptional activity of mutant p53, failed to upregulate CES2 expression in cells with TP53 missense mutations. These results, taken together, suggest that CES2 mRNA expression is decreased in human colorectal cancer independently of p53.
ESTHER : Ishimine_2018_Dis.Markers_2018_5280736
PubMedSearch : Ishimine_2018_Dis.Markers_2018_5280736
PubMedID: 29651325

Title : Evaluation of the risk factors and prognostic factors of hepatectomy for hepatocellular carcinoma in patients aged 80 years or more - Hamaoka_2017_J.Hepatobiliary.Pancreat.Sci_24_58
Author(s) : Hamaoka M , Kobayashi T , Ishiyama K , Ohira M , Tahara H , Kuroda S , Iwako H , Okimoto S , Honmyo N , Ohdan H
Ref : J Hepatobiliary Pancreat Sci , 24 :58 , 2017
Abstract : BACKGROUND: The risk factors of postoperative complications and prognostic factors of hepatocellular carcinoma in patients aged >/=80 years have not yet been defined. We aimed to identify these factors in this patient population.
METHODS: This single-center, retrospective cohort study included 625 patients who underwent curative hepatectomy from January 2004 to December 2013. Elderly patients were defined as those aged >/=80 years. Clinicopathological data and outcomes after hepatectomy for 60 elderly patients and 565 non-elderly patients were compared.
RESULTS: The elderly group had more comorbidities than the non-elderly group. Liver function, surgical data, tumor factors, the incidence of postoperative complications, disease-free survival rate, and overall survival rate did not differ significantly between the two groups. Results of multivariate analysis showed that the levels of cholinesterase, total cholesterol, and hemoglobin A1c were predictors of complications in the elderly group. The Child-Pugh grade, protein induced in vitamin K absence or antagonists-II level, and multiple tumors were significantly associated with disease-free survival.
CONCLUSIONS: Although elderly patients had more comorbidities, their postoperative complications and prognosis were comparable to those of the non-elderly patients. Hepatectomy may be justified for elderly patients, but it is important to evaluate levels of cholinesterase, total cholesterol, and hemoglobin A1c preoperatively.
ESTHER : Hamaoka_2017_J.Hepatobiliary.Pancreat.Sci_24_58
PubMedSearch : Hamaoka_2017_J.Hepatobiliary.Pancreat.Sci_24_58
PubMedID: 27860361

Title : Genome sequence of Aspergillus luchuensis NBRC 4314 - Yamada_2016_DNA.Res_23_507
Author(s) : Yamada O , Machida M , Hosoyama A , Goto M , Takahashi T , Futagami T , Yamagata Y , Takeuchi M , Kobayashi T , Koike H , Abe K , Asai K , Arita M , Fujita N , Fukuda K , Higa KI , Horikawa H , Ishikawa T , Jinno K , Kato Y , Kirimura K , Mizutani O , Nakasone K , Sano M , Shiraishi Y , Tsukahara M , Gomi K
Ref : DNA Research , 23 :507 , 2016
Abstract : Awamori is a traditional distilled beverage made from steamed Thai-Indica rice in Okinawa, Japan. For brewing the liquor, two microbes, local kuro (black) koji mold Aspergillus luchuensis and awamori yeast Saccharomyces cerevisiae are involved. In contrast, that yeasts are used for ethanol fermentation throughout the world, a characteristic of Japanese fermentation industries is the use of Aspergillus molds as a source of enzymes for the maceration and saccharification of raw materials. Here we report the draft genome of a kuro (black) koji mold, A. luchuensis NBRC 4314 (RIB 2604). The total length of nonredundant sequences was nearly 34.7 Mb, comprising approximately 2,300 contigs with 16 telomere-like sequences. In total, 11,691 genes were predicted to encode proteins. Most of the housekeeping genes, such as transcription factors and N-and O-glycosylation system, were conserved with respect to Aspergillus niger and Aspergillus oryzae An alternative oxidase and acid-stable alpha-amylase regarding citric acid production and fermentation at a low pH as well as a unique glutamic peptidase were also found in the genome. Furthermore, key biosynthetic gene clusters of ochratoxin A and fumonisin B were absent when compared with A. niger genome, showing the safety of A. luchuensis for food and beverage production. This genome information will facilitate not only comparative genomics with industrial kuro-koji molds, but also molecular breeding of the molds in improvements of awamori fermentation.
ESTHER : Yamada_2016_DNA.Res_23_507
PubMedSearch : Yamada_2016_DNA.Res_23_507
PubMedID: 27651094
Gene_locus related to this paper: 9euro-a0a146f3d2

Title : Three extracellular dipeptidyl peptidases found in Aspergillus oryzae show varying substrate specificities - Maeda_2016_Appl.Microbiol.Biotechnol_100_4947
Author(s) : Maeda H , Sakai D , Kobayashi T , Morita H , Okamoto A , Takeuchi M , Kusumoto K , Amano H , Ishida H , Yamagata Y
Ref : Applied Microbiology & Biotechnology , 100 :4947 , 2016
Abstract : Three extracellular dipeptidyl peptidase genes, dppB, dppE, and dppF, were unveiled by sequence analysis of the Aspergillus oryzae genome. We investigated their differential enzymatic profiles, in order to gain an understanding of the diversity of these genes. The three dipeptidyl peptidases were expressed using Aspergillus nidulans as the host. Each recombinant enzyme was purified and subsequently characterized. The enzymes displayed similar optimum pH values, but optimum temperatures, pH stabilities, and substrate specificities varied. DppB was identified as a Xaa-Prolyl dipeptidyl peptidase, while DppE scissile substrates were similar to the substrates for Aspergillus fumigatus DPPV (AfDPPV). DppF was found to be a novel enzyme that could digest both substrates for A. fumigatus DPPIV and AfDPPV. Semi-quantitative PCR revealed that the transcription of dppB in A. oryzae was induced by protein substrates and repressed by the addition of an inorganic nitrogen source, despite the presence of protein substrates. The transcription of dppE depended on its growth time, while the transcription of dppF was not affected by the type of the nitrogen source in the medium, and it started during the early stage of the fungal growth. Based on these results, we conclude that these enzymes may represent the nutrition acquisition enzymes. Additionally, DppF may be one of the sensor peptidases responsible for the detection of the protein substrates in A. oryzae environment. DppB may be involved in nitrogen assimilation control, since the transcription of dppB was repressed by NaNO3, despite the presence of protein substrates.
ESTHER : Maeda_2016_Appl.Microbiol.Biotechnol_100_4947
PubMedSearch : Maeda_2016_Appl.Microbiol.Biotechnol_100_4947
PubMedID: 26846741

Title : Distinct roles of basal forebrain cholinergic neurons in spatial and object recognition memory - Okada_2015_Sci.Rep_5_13158
Author(s) : Okada K , Nishizawa K , Kobayashi T , Sakata S , Kobayashi K
Ref : Sci Rep , 5 :13158 , 2015
Abstract : Recognition memory requires processing of various types of information such as objects and locations. Impairment in recognition memory is a prominent feature of amnesia and a symptom of Alzheimer's disease (AD). Basal forebrain cholinergic neurons contain two major groups, one localized in the medial septum (MS)/vertical diagonal band of Broca (vDB), and the other in the nucleus basalis magnocellularis (NBM). The roles of these cell groups in recognition memory have been debated, and it remains unclear how they contribute to it. We use a genetic cell targeting technique to selectively eliminate cholinergic cell groups and then test spatial and object recognition memory through different behavioural tasks. Eliminating MS/vDB neurons impairs spatial but not object recognition memory in the reference and working memory tasks, whereas NBM elimination undermines only object recognition memory in the working memory task. These impairments are restored by treatment with acetylcholinesterase inhibitors, anti-dementia drugs for AD. Our results highlight that MS/vDB and NBM cholinergic neurons are not only implicated in recognition memory but also have essential roles in different types of recognition memory.
ESTHER : Okada_2015_Sci.Rep_5_13158
PubMedSearch : Okada_2015_Sci.Rep_5_13158
PubMedID: 26246157

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

Title : Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist - Haga_2012_Nature_482_547
Author(s) : Haga K , Kruse AC , Asada H , Yurugi-Kobayashi T , Shiroishi M , Zhang C , Weis WI , Okada T , Kobilka BK , Haga T , Kobayashi T
Ref : Nature , 482 :547 , 2012
Abstract : The parasympathetic branch of the autonomic nervous system regulates the activity of multiple organ systems. Muscarinic receptors are G-protein-coupled receptors that mediate the response to acetylcholine released from parasympathetic nerves. Their role in the unconscious regulation of organ and central nervous system function makes them potential therapeutic targets for a broad spectrum of diseases. The M2 muscarinic acetylcholine receptor (M2 receptor) is essential for the physiological control of cardiovascular function through activation of G-protein-coupled inwardly rectifying potassium channels, and is of particular interest because of its extensive pharmacological characterization with both orthosteric and allosteric ligands. Here we report the structure of the antagonist-bound human M2 receptor, the first human acetylcholine receptor to be characterized structurally, to our knowledge. The antagonist 3-quinuclidinyl-benzilate binds in the middle of a long aqueous channel extending approximately two-thirds through the membrane. The orthosteric binding pocket is formed by amino acids that are identical in all five muscarinic receptor subtypes, and shares structural homology with other functionally unrelated acetylcholine binding proteins from different species. A layer of tyrosine residues forms an aromatic cap restricting dissociation of the bound ligand. A binding site for allosteric ligands has been mapped to residues at the entrance to the binding pocket near this aromatic cap. The structure of the M2 receptor provides insights into the challenges of developing subtype-selective ligands for muscarinic receptors and their propensity for allosteric regulation.
ESTHER : Haga_2012_Nature_482_547
PubMedSearch : Haga_2012_Nature_482_547
PubMedID: 22278061

Title : Neuronally expressed Ras-family GTPase Di-Ras modulates synaptic activity in Caenorhabditis elegans - Tada_2012_Genes.Cells_17_778
Author(s) : Tada M , Gengyo-Ando K , Kobayashi T , Fukuyama M , Mitani S , Kontani K , Katada T
Ref : Genes Cells , 17 :778 , 2012
Abstract : Ras-family GTPases regulate a wide variety of cellular functions including cell growth and differentiation. Di-Ras, which belongs to a distinct subfamily of Ras-family GTPases, is expressed predominantly in brain, but the role of Di-Ras in nervous systems remains totally unknown. Here, we report that the Caenorhabditis elegans Di-Ras homologue drn-1 is expressed specifically in neuronal cells and involved in synaptic function at neuromuscular junctions. Loss of function of drn-1 conferred resistance to the acetylcholinesterase inhibitor aldicarb and partially suppressed the aldicarb-hypersensitive phenotypes of heterotrimeric G-protein mutants, in which acetylcholine release is up-regulated. drn-1 mutants displayed no apparent defects in the axonal distribution of the membrane-bound second messenger diacylglycerol (DAG), which is a key stimulator of acetylcholine release. Finally, we have identified EPAC-1, a C. elegans Epac homologue, as a binding partner for DRN-1. Deletion mutants of epac-1 displayed an aldicarb-resistant phenotype as drn-1 mutants. Genetic analysis of drn-1 and epac-1 showed that they acted in the same pathway to control acetylcholine release. Furthermore, DRN-1 and EPAC-1 were co-immunoprecipitated. These findings suggest that DRN-1 may function cooperatively with EPAC-1 to modulate synaptic activity in C. elegans.
ESTHER : Tada_2012_Genes.Cells_17_778
PubMedSearch : Tada_2012_Genes.Cells_17_778
PubMedID: 22897658

Title : Efficient synthesis of 6-O-palmitoyl-1,2-O-isopropylidene-alpha-D-glucofuranose in an organic solvent system by lipase-catalyzed esterification - Kobayashi_2010_Biotechnol.Lett_32_1679
Author(s) : Kobayashi T , Ehara T , Mizuoka T , Adachi S
Ref : Biotechnol Lett , 32 :1679 , 2010
Abstract : In order to synthesize a sugar ester at high concentration, 1,2-O-isopropylidene-alpha-D-glucofuranose (IpGlc), which is one of the sugar acetals and is more hydrophobic than unmodified glucose, was esterified with palmitic acid at 40 degrees C using immobilized lipase from Candida antarctica in some organic solvents or their mixtures. Acetone + t-butyl alcohol (3:1 v/v) improved both the initial reaction rate and yield after 80 h: the product reached its maximum value (240 mmol/kg solvent; ca. 110 g/kg solvent) when 400 mmol IpGlc/kg solvent and 1,200 mmol palmitic acid/kg solvent were used in this solvent mixture.
ESTHER : Kobayashi_2010_Biotechnol.Lett_32_1679
PubMedSearch : Kobayashi_2010_Biotechnol.Lett_32_1679
PubMedID: 20574832

Title : Preoperative evaluation of patients with liver cirrhosis undergoing open heart surgery - Murashita_2009_Gen.Thorac.Cardiovasc.Surg_57_293
Author(s) : Murashita T , Komiya T , Tamura N , Sakaguchi G , Kobayashi T , Furukawa T , Matsushita A , Sunagawa G
Ref : Gen Thorac Cardiovasc Surg , 57 :293 , 2009
Abstract : OBJECTIVE: Clinical outcomes after open heart surgery in patients with liver cirrhosis are not satisfactory. For evaluating hepatic function, the Child-Pugh classification has been widely used. It has been reported that open heart surgery can be performed safely in patients with mild liver cirrhosis. In this study, we examined the clinical outcomes after open heart surgery in patients with liver cirrhosis and evaluated the usefulness of the Child-Pugh classification. METHODS: There were 12 liver cirrhosis patients who underwent open heart surgery between January 2002 and December 2006 at our institution. The severity of cirrhosis was graded according to the Child-Pugh classification. We reviewed clinical outcomes, such as postoperative mortality and morbidity, and tried to determine the risk factors. Finally, we assessed the usefulness of the Child-Pugh classification. RESULTS: Six patients were classified as having Child class A, and the other six patients were classified as B. The overall mortality of group A was 50%, and that of group B was 17%. Postoperative major morbidities occurred in half of the patients of Child class A and in all of the patients of Child class B. Patients who experienced major morbidities had markedly lower levels of serum cholinesterase (106 +/- 46 vs. 199 +/- 72 IU/l; P = 0.02) and lower platelet level (7.5 +/- 2.9 vs. 11.9 +/- 3.6 x 104/microl; P = 0.04). CONCLUSION: The mortality and morbidity rates were high even in the Child class A patients. The Child classification may be an insufficient method for evaluating hepatic function. We have to assess other factors, such as the serum cholinesterase level or the platelet count.
ESTHER : Murashita_2009_Gen.Thorac.Cardiovasc.Surg_57_293
PubMedSearch : Murashita_2009_Gen.Thorac.Cardiovasc.Surg_57_293
PubMedID: 19533274

Title : Continuous synthesis of glyceryl ferulate using immobilized Candida antarctica lipase - Matsuo_2008_J.Oleo.Sci_57_375
Author(s) : Matsuo T , Kobayashi T , Kimura Y , Hosoda A , Taniguchi H , Adachi S
Ref : J Oleo Sci , 57 :375 , 2008
Abstract : Glyceryl ferulate was synthesized through condensation of ferulic acid and glycerol at 50 degrees C in glycerols with different water contents using an immobilized lipase from Candida antarctica in a batch reactor, and condensation in the glycerol with a 7.5% (w/w) water content was shown to be the favorite. The solubility of ferulic acid was higher at higher temperature in glycerol with a lower water content. The viscosity was lower at higher temperature for the glycerol with a higher water content. The condensation was carried out using a batch reactor at a temperature from 50 degrees C to 90 degrees C. These observations indicated that the condensation at 80 degrees C in the glycerol with a 7.5% (w/w) water content was the most adequate for continuously synthesizing glyceryl ferulate. A reactor system was constructed for the continuous synthesis and was steadily operated to realize a productivity of 430 kg/(m(3)-reactor(day) without any decrease in the conversion for at least 6 days.
ESTHER : Matsuo_2008_J.Oleo.Sci_57_375
PubMedSearch : Matsuo_2008_J.Oleo.Sci_57_375
PubMedID: 18536506

Title : Brain acetylcholinesterase activity in FTDP-17 studied by PET -
Author(s) : Hirano S , Shinotoh H , Kobayashi T , Tsuboi Y , Wszolek ZK , Aotsuka A , Tanaka N , Ota T , Fukushi K , Tanada S , Irie T
Ref : Neurology , 66 :1276 , 2006
PubMedID: 16636254

Title : The crystal structure of polyhydroxybutyrate depolymerase from Penicillium funiculosum provides insights into the recognition and degradation of biopolyesters - Hisano_2006_J.Mol.Biol_356_993
Author(s) : Hisano T , Kasuya K , Tezuka Y , Ishii N , Kobayashi T , Shiraki M , Oroudjev E , Hansma H , Iwata T , Doi Y , Saito T , Miki K
Ref : Journal of Molecular Biology , 356 :993 , 2006
Abstract : Polyhydroxybutyrate is a microbial polyester that can be produced from renewable resources, and is degraded by the enzyme polyhydroxybutyrate depolymerase. The crystal structures of polyhydroxybutyrate depolymerase from Penicillium funiculosum and its S39 A mutant complexed with the methyl ester of a trimer substrate of (R)-3-hydroxybutyrate have been determined at resolutions of 1.71 A and 1.66 A, respectively. The enzyme is comprised of a single domain, which represents a circularly permuted variant of the alpha/beta hydrolase fold. The catalytic residues Ser39, Asp121, and His155 are located at topologically conserved positions. The main chain amide groups of Ser40 and Cys250 form an oxyanion hole. A crevice is formed on the surface of the enzyme, to which a single polymer chain can be bound by predominantly hydrophobic interactions with several hydrophobic residues. The structure of the S39A mutant-trimeric substrate complex reveals that Trp307 is responsible for the recognition of the ester group adjacent to the scissile group. It is also revealed that the substrate-binding site includes at least three, and possibly four, subsites for binding monomer units of polyester substrates. Thirteen hydrophobic residues, which are exposed to solvent, are aligned around the mouth of the crevice, forming a putative adsorption site for the polymer surface. These residues may contribute to the sufficient binding affinity of the enzyme for PHB granules without a distinct substrate-binding domain.
ESTHER : Hisano_2006_J.Mol.Biol_356_993
PubMedSearch : Hisano_2006_J.Mol.Biol_356_993
PubMedID: 16405909
Gene_locus related to this paper: penfu-PHAZ

Title : Molecular characterization of lipoprotein lipase, hepatic lipase and pancreatic lipase genes: effects of fasting and refeeding on their gene expression in red sea bream Pagrus major - Oku_2006_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_145_168
Author(s) : Oku H , Koizumi N , Okumura T , Kobayashi T , Umino T
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , 145 :168 , 2006
Abstract : To investigate the nutritional regulation of lipid metabolism in fish, molecular characterization of lipases was conducted in red sea bream Pagrus major, and the effects of fasting and refeeding on their gene expression was examined. Together with data from a previous study, a total of four lipase genes were identified and characterized as lipoprotein lipase (LPL), hepatic lipase (HL) and pancreatic lipase (PL). These four lipase genes, termed LPL1, LPL2, HL and PL, share a high degree of similarity. LPL1 and LPL2 genes were expressed in various tissues including adipose tissue, gill, heart and hepatopancreas. HL gene was exclusively expressed in hepatopancreas. PL gene expression was detected in hepatopancreas and adipose tissue. Red sea bream LPL1 and LPL2 gene expression levels in hepatopancreas were increased during 48 h of fasting and decreased after refeeding, whereas no significant change in the expression levels of LPL1 and LPL2 was observed in adipose tissue, indicating that LPL1 and LPL2 gene expression is regulated in a tissue-specific manner in response to the nutritional state of fish. HL and PL gene expression was not affected by fasting and refeeding. The results of this study suggested that LPL, HL and PL gene expression is under different regulatory mechanisms in red sea bream with respect to the tissue-specificities and their nutritional regulation.
ESTHER : Oku_2006_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_145_168
PubMedSearch : Oku_2006_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_145_168
PubMedID: 16904358
Gene_locus related to this paper: pagma-q0eda6 , pagma-a0a0g2qus7

Title : D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol alters cellular cholesterol homeostasis by modulating the endosome lipid domains - Makino_2006_Biochemistry_45_4530
Author(s) : Makino A , Ishii K , Murate M , Hayakawa T , Suzuki Y , Suzuki M , Ito K , Fujisawa T , Matsuo H , Ishitsuka R , Kobayashi T
Ref : Biochemistry , 45 :4530 , 2006
Abstract : D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP) is a frequently used inhibitor of glycosphingolipid biosynthesis. However, some interesting characteristics of D-PDMP cannot be explained by the inhibition of glycolipid synthesis alone. In the present study, we showed that d-PDMP inhibits the activation of lysosomal acid lipase by late endosome/lysosome specific lipid, bis(monoacylglycero)phosphate (also called as lysobisphosphatidic acid), through alteration of membrane structure of the lipid. When added to cultured fibroblasts, D-PDMP inhibits the degradation of low-density lipoprotein (LDL) and thus accumulates both cholesterol ester and free cholesterol in late endosomes/lysosomes. This accumulation results in the inhibition of LDL-derived cholesterol esterification and the decrease of cell surface cholesterol. We showed that D-PDMP alters cellular cholesterol homeostasis in a glycosphingolipid-independent manner using L-PDMP, a stereoisomer of D-PDMP, which does not inhibit glycosphingolipid synthesis, and mutant melanoma cell which is defective in glycolipid synthesis. Altering cholesterol homeostasis by D-PDMP explains the unique characteristics of sensitizing multidrug resistant cells by this drug.
ESTHER : Makino_2006_Biochemistry_45_4530
PubMedSearch : Makino_2006_Biochemistry_45_4530
PubMedID: 16584188

Title : Novel intracellular 3-hydroxybutyrate-oligomer hydrolase in Wautersia eutropha H16 - Kobayashi_2005_J.Bacteriol_187_5129
Author(s) : Kobayashi T , Uchino K , Abe T , Yamazaki Y , Saito T
Ref : Journal of Bacteriology , 187 :5129 , 2005
Abstract : Wautersia eutropha H16 (formerly Ralstonia eutropha) mobilizes intracellularly accumulated poly(3-hydroxybutyrate) (PHB) with intracellular poly(3-hydroxybutyrate) depolymerases. In this study, a novel intracellular 3-hydroxybutyrate-oligomer hydrolase (PhaZc) gene was cloned and overexpressed in Escherichia coli. Then PhaZc was purified and characterized. Immunoblot analysis with polyclonal antiserum against PhaZc revealed that most PhaZc is present in the cytosolic fraction and a small amount is present in the poly(3-hydroxybutyrate) inclusion bodies of W. eutropha. PhaZc degraded various 3-hydroxybutyrate oligomers at a high specific activity and artificial amorphous poly(3-hydroxybutyrate) at a lower specific activity. Native PHB granules and semicrystalline PHB were not degraded by PhaZc. A PhaZ deletion mutation enhanced the deposition of PHB in the logarithmic phase in nutrient-rich medium. PhaZc differs from the hydrolases of W. eutropha previously reported and is a novel type of intracellular 3-hydroxybutyrate-oligomer hydrolase, and it participates in the mobilization of PHB along with other hydrolases.
ESTHER : Kobayashi_2005_J.Bacteriol_187_5129
PubMedSearch : Kobayashi_2005_J.Bacteriol_187_5129
PubMedID: 16030206
Gene_locus related to this paper: alceu-q4w8c9

Title : Properties of a novel intracellular poly(3-hydroxybutyrate) depolymerase with high specific activity (PhaZd) in Wautersia eutropha H16 - Abe_2005_J.Bacteriol_187_6982
Author(s) : Abe T , Kobayashi T , Saito T
Ref : Journal of Bacteriology , 187 :6982 , 2005
Abstract : A novel intracellular poly(3-hydroxybutyrate) (PHB) depolymerase (PhaZd) of Wautersia eutropha (formerly Ralstonia eutropha) H16 which shows similarity with the catalytic domain of the extracellular PHB depolymerase in Ralstonia pickettii T1 was identified. The positions of the catalytic triad (Ser190-Asp266-His330) and oxyanion hole (His108) in the amino acid sequence of PhaZd deduced from the nucleotide sequence roughly accorded with those of the extracellular PHB depolymerase of R. pickettii T1, but a signal peptide, a linker domain, and a substrate binding domain were missing. The PhaZd gene was cloned and the gene product was purified from Escherichia coli. The specific activity of PhaZd toward artificial amorphous PHB granules was significantly greater than that of other known intracellular PHB depolymerase or 3-hydroxybutyrate (3HB) oligomer hydrolases of W. eutropha H16. The enzyme degraded artificial amorphous PHB granules and mainly released various 3-hydroxybutyrate oligomers. PhaZd distributed nearly equally between PHB inclusion bodies and the cytosolic fraction. The amount of PHB was greater in phaZd deletion mutant cells than the wild-type cells under various culture conditions. These results indicate that PhaZd is a novel intracellular PHB depolymerase which participates in the mobilization of PHB in W. eutropha H16 along with other PHB depolymerases.
ESTHER : Abe_2005_J.Bacteriol_187_6982
PubMedSearch : Abe_2005_J.Bacteriol_187_6982
PubMedID: 16199568

Title : Synthesis of esters by immobilized-lipase-catalyzed condensation reaction of sugars and fatty acids in water-miscible organic solvent - Adachi_2005_J.Biosci.Bioeng_99_87
Author(s) : Adachi S , Kobayashi T
Ref : J Biosci Bioeng , 99 :87 , 2005
Abstract : A lipase-catalyzed condensation reaction in an organic solvent is a promising means of synthesizing esters. Reaction equilibrium constant, which is usually defined on the basis of reactant concentration, is an important parameter for estimating equilibrium yield. It is shown that the constant is markedly, affected by some factors, such as the hydration of a sugar substrate and the interaction of a reactant with a solvent. To reasonably design the reaction system or determine the reaction conditions, attention should be paid to these factors. From the viewpoint of kinetics, substrate selectivity for carboxylic acids also numerically correlates to the electrical and steric properties of these acids. Reactor systems for continuously producing esters through an immobilized-lipase-catalyzed condensation reaction are developed.
ESTHER : Adachi_2005_J.Biosci.Bioeng_99_87
PubMedSearch : Adachi_2005_J.Biosci.Bioeng_99_87
PubMedID: 16233762

Title : Genome sequencing and analysis of Aspergillus oryzae - Machida_2005_Nature_438_1157
Author(s) : Machida M , Asai K , Sano M , Tanaka T , Kumagai T , Terai G , Kusumoto K , Arima T , Akita O , Kashiwagi Y , Abe K , Gomi K , Horiuchi H , Kitamoto K , Kobayashi T , Takeuchi M , Denning DW , Galagan JE , Nierman WC , Yu J , Archer DB , Bennett JW , Bhatnagar D , Cleveland TE , Fedorova ND , Gotoh O , Horikawa H , Hosoyama A , Ichinomiya M , Igarashi R , Iwashita K , Juvvadi PR , Kato M , Kato Y , Kin T , Kokubun A , Maeda H , Maeyama N , Maruyama J , Nagasaki H , Nakajima T , Oda K , Okada K , Paulsen I , Sakamoto K , Sawano T , Takahashi M , Takase K , Terabayashi Y , Wortman JR , Yamada O , Yamagata Y , Anazawa H , Hata Y , Koide Y , Komori T , Koyama Y , Minetoki T , Suharnan S , Tanaka A , Isono K , Kuhara S , Ogasawara N , Kikuchi H
Ref : Nature , 438 :1157 , 2005
Abstract : The genome of Aspergillus oryzae, a fungus important for the production of traditional fermented foods and beverages in Japan, has been sequenced. The ability to secrete large amounts of proteins and the development of a transformation system have facilitated the use of A. oryzae in modern biotechnology. Although both A. oryzae and Aspergillus flavus belong to the section Flavi of the subgenus Circumdati of Aspergillus, A. oryzae, unlike A. flavus, does not produce aflatoxin, and its long history of use in the food industry has proved its safety. Here we show that the 37-megabase (Mb) genome of A. oryzae contains 12,074 genes and is expanded by 7-9 Mb in comparison with the genomes of Aspergillus nidulans and Aspergillus fumigatus. Comparison of the three aspergilli species revealed the presence of syntenic blocks and A. oryzae-specific blocks (lacking synteny with A. nidulans and A. fumigatus) in a mosaic manner throughout the genome of A. oryzae. The blocks of A. oryzae-specific sequence are enriched for genes involved in metabolism, particularly those for the synthesis of secondary metabolites. Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.
ESTHER : Machida_2005_Nature_438_1157
PubMedSearch : Machida_2005_Nature_438_1157
PubMedID: 16372010
Gene_locus related to this paper: aspor-Q2U722 , aspfn-b8mvx2 , aspfn-b8mwk1 , aspfn-b8n1a4 , aspfn-b8n5l3 , aspfn-b8n7y0 , aspfn-b8n829 , aspfn-b8ncj5 , aspfn-b8nhj9 , aspfn-b8njx6 , aspfn-b8nsk2 , aspfu-q4wj61 , aspor-axe1 , aspor-CPI , aspor-cutas , aspor-cuti2 , aspor-DPPIV , aspor-faec , aspor-MDLB , aspor-ppme1 , aspor-q2tw11 , aspor-q2tw16 , aspor-q2tw28 , aspor-q2twc4 , aspor-q2twg0 , aspor-q2twj3 , aspor-q2twv2 , aspor-q2twv4 , aspor-q2tx21 , aspor-q2txq8 , aspor-q2tya1 , aspor-q2tyh6 , aspor-q2tyn9 , aspor-q2typ0 , aspor-q2tyq4 , aspor-q2tyv8 , aspor-q2tz03 , aspor-q2tzh3 , aspor-q2tzr5 , aspor-q2tzv9 , aspor-q2u0k7 , aspor-q2u0q2 , aspor-q2u0r6 , aspor-q2u1a5 , aspor-q2u1a6 , aspor-q2u1k0 , aspor-q2u1k8 , aspor-q2u1m8 , aspor-q2u2a1 , aspor-q2u2a4 , aspor-q2u3a3 , aspor-q2u3a6 , aspor-q2u3k5 , aspor-q2u3l6 , aspor-q2u4a0 , aspor-q2u4e0 , aspor-q2u4f6 , aspor-q2u4g6 , aspor-q2u4h9 , aspor-q2u4w9 , aspor-q2u4y8 , aspor-q2u5f5 , aspor-q2u5n3 , aspor-q2u5y8 , aspor-q2u6h7 , aspor-q2u6j5 , aspor-q2u6m8 , aspor-q2u6m9 , aspor-q2u6n6 , aspor-q2u7i2 , aspor-q2u7v0 , aspor-q2u8j8 , aspor-q2u8r1 , aspor-q2u8r4 , aspor-q2u8t5 , aspor-q2u8z3 , aspor-q2u9a1 , aspor-q2u9n5 , aspor-q2u144 , aspor-q2u161 , aspor-q2u185 , aspor-q2u199 , aspor-q2u212 , aspor-q2u331 , aspor-q2u348 , aspor-q2u400 , aspor-q2u453 , aspor-q2u489 , aspor-q2u704 , aspor-q2u728 , aspor-q2u798 , aspor-q2u822 , aspor-q2u854 , aspor-q2u875 , aspor-q2u908 , aspor-q2ua10 , aspor-q2ua48 , aspor-q2uab6 , aspor-q2uak9 , aspor-q2uaq4 , aspor-q2ub32 , aspor-q2ub76 , aspor-q2uba1 , aspor-q2ubd6 , aspor-q2ubm2 , aspor-q2ubr2 , aspor-q2uc28 , aspor-q2uc65 , aspor-q2uc77 , aspor-q2uc98 , aspor-q2uck0 , aspor-q2ucy7 , aspor-q2ud03 , aspor-q2ud06 , aspor-q2ud08 , aspor-q2ud23 , aspor-q2udn5 , aspor-q2udr0 , aspor-q2uec1 , aspor-q2uef3 , aspor-q2uf10 , aspor-q2uf27 , aspor-q2uf48 , aspor-q2ufd8 , aspor-q2ufe5 , aspor-q2ufm4 , aspor-q2ufr3 , aspor-q2ufz8 , aspor-q2ug78 , aspor-q2ugd6 , aspor-q2uge1 , aspor-q2ugg7 , aspor-q2ugi2 , aspor-q2ugl2 , aspor-q2ugy9 , aspor-q2uh24 , aspor-q2uh73 , aspor-q2uhe4 , aspor-q2uhf0 , aspor-q2uhj6 , aspor-q2uhn1 , aspor-q2uhq0 , aspor-q2ui56 , aspor-q2uib2 , aspor-q2uib5 , aspor-q2uie9 , aspor-q2uih1 , aspor-q2uii1 , aspor-q2uik9 , aspor-q2uiq0 , aspor-q2uiu1 , aspor-q2uix9 , aspor-q2uiy5 , aspor-q2uiz4 , aspor-q2uj89 , aspor-q2uja2 , aspor-q2uju3 , aspor-q2uk31 , aspor-q2uk42 , aspor-q2ukb6 , aspor-q2ukq7 , aspor-q2ul81 , aspor-q2uli9 , aspor-q2ulr2 , aspor-q2ulv7 , aspor-q2umf3 , aspor-q2umv2 , aspor-q2umx6 , aspor-q2unw5 , aspor-q2up23 , aspor-q2up89 , aspor-q2upe6 , aspor-q2upi1 , aspor-q2upl1 , aspor-q2upw4 , aspor-q2uq56 , aspor-q2uqb4 , aspor-q2uqm7 , aspor-q2ur58 , aspor-q2ur64 , aspor-q2ur80 , aspor-q2ur83 , aspor-q2ure7 , aspor-q2urf3 , aspor-q2urg5 , aspor-q2urq0 , aspor-q2urt4 , aspor-q2uru5 , aspor-q2usi0 , aspor-q2usp7 , aspor-q2usq8 , aspor-q2usv6 , aspor-q2uta5 , aspor-q2uu89 , aspor-q2uub4 , aspor-q2uux8 , aspor-q2uv29 , aspor-TGLA , aspor-q2ue03 , aspor-q2uj83 , aspno-a0a0l1j1c9

Title : Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus - Nierman_2005_Nature_438_1151
Author(s) : Nierman WC , Pain A , Anderson MJ , Wortman JR , Kim HS , Arroyo J , Berriman M , Abe K , Archer DB , Bermejo C , Bennett J , Bowyer P , Chen D , Collins M , Coulsen R , Davies R , Dyer PS , Farman M , Fedorova N , Feldblyum TV , Fischer R , Fosker N , Fraser A , Garcia JL , Garcia MJ , Goble A , Goldman GH , Gomi K , Griffith-Jones S , Gwilliam R , Haas B , Haas H , Harris D , Horiuchi H , Huang J , Humphray S , Jimenez J , Keller N , Khouri H , Kitamoto K , Kobayashi T , Konzack S , Kulkarni R , Kumagai T , Lafon A , Latge JP , Li W , Lord A , Lu C , Majoros WH , May GS , Miller BL , Mohamoud Y , Molina M , Monod M , Mouyna I , Mulligan S , Murphy L , O'Neil S , Paulsen I , Penalva MA , Pertea M , Price C , Pritchard BL , Quail MA , Rabbinowitsch E , Rawlins N , Rajandream MA , Reichard U , Renauld H , Robson GD , Rodriguez de Cordoba S , Rodriguez-Pena JM , Ronning CM , Rutter S , Salzberg SL , Sanchez M , Sanchez-Ferrero JC , Saunders D , Seeger K , Squares R , Squares S , Takeuchi M , Tekaia F , Turner G , Vazquez de Aldana CR , Weidman J , White O , Woodward J , Yu JH , Fraser C , Galagan JE , Asai K , Machida M , Hall N , Barrell B , Denning DW
Ref : Nature , 438 :1151 , 2005
Abstract : Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.
ESTHER : Nierman_2005_Nature_438_1151
PubMedSearch : Nierman_2005_Nature_438_1151
PubMedID: 16372009
Gene_locus related to this paper: aspfc-b0xp50 , aspfc-b0xu40 , aspfc-b0xzj6 , aspfc-dpp5 , aspfu-apth1 , aspfu-axe1 , aspfu-CBPYA , aspfu-faec , aspfu-kex1 , aspfu-ppme1 , aspfu-q4wa39 , aspfu-q4wa78 , aspfu-q4wf56 , aspfu-q4wg73 , aspfu-q4wk44 , aspfu-q4wkh6 , aspfu-q4wnx3 , aspfu-q4wpb9 , aspfu-q4wqv2 , aspfu-q4wub2 , aspfu-q4wxr1 , aspfu-q4x0n6 , aspfu-q4x1n0 , aspfu-q5vjg7 , neofi-a1cwa6 , neofi-a1dfr9 , aspfm-a0a084bf80 , aspfu-fmac

Title : Insertional mutagenesis and characterization of a polyketide synthase gene (PKS1) required for melanin biosynthesis in Bipolaris oryzae - Moriwaki_2004_FEMS.Microbiol.Lett_238_1
Author(s) : Moriwaki A , Kihara J , Kobayashi T , Tokunaga T , Arase S , Honda Y
Ref : FEMS Microbiology Letters , 238 :1 , 2004
Abstract : A polyketide synthase gene named PKS1, involved in the melanin biosynthesis pathway of the phytopathogenic fungus Bipolaris oryzae, was isolated using restriction enzyme-mediated integration. Sequence analysis showed that the PKS1 encodes a putative protein that has 2155 amino acids and significant similarity to other fungal polyketide synthases. Targeted disruption of the PKS1 gene showed that it is necessary for melanin biosynthesis in B. oryzae. Northern blot analysis showed that PKS1 transcripts were specifically enhanced by near-ultraviolet radiation (300-400 nm) and that its temporal transcriptional patterns were similar to those of THR1 and SCD1 genes involved in the melanin biosynthesis pathway of B. oryzae.
ESTHER : Moriwaki_2004_FEMS.Microbiol.Lett_238_1
PubMedSearch : Moriwaki_2004_FEMS.Microbiol.Lett_238_1
PubMedID: 15336395
Gene_locus related to this paper: 9pleo-q6l715

Title : Roles of poly(3-hydroxybutyrate) depolymerase and 3HB-oligomer hydrolase in bacterial PHB metabolism - Sugiyama_2004_Curr.Microbiol_48_424
Author(s) : Sugiyama A , Kobayashi T , Shiraki M , Saito T
Ref : Curr Microbiol , 48 :424 , 2004
Abstract : Many poly-3-hydroxybutyrate (PHB)-degrading enzymes have been studied. But biological roles of 3HB-oligomer hydrolases (3HBOHs) and how PHB depolymerases (PHBDPs) and 3HBOHs cooperate in PHB metabolism are not fully elucidated. In this study, several PHBDPs and 3HBOHs from three types of bacteria were purified, and their substrate specificity, kinetic properties, and degradation products were investigated. From the results, PHBDP and 3HBOH seemed to play a role in PHB metabolism in three types of bacteria, as follows: (A) In Ralstonia pickettii T1, an extracellular PHBDP degrades extracellular PHB to various-sized 3HB-oligomers, which an extracellular 3HBOH hydrolyzes to 3HB-monomers. (B) In Acidovorax sp. SA1, an extracellular PHBDP hydrolyzes extracellular PHB to small 3HB-oligomers (dimer and trimer), which an intracellular 3HBOH efficiently degrades to 3HB in the cell. (C) In Ralstonia eutropha H16, an intracellular 3HBOH helps in the degradation of intracellular PHB inclusions by PHBDP.
ESTHER : Sugiyama_2004_Curr.Microbiol_48_424
PubMedSearch : Sugiyama_2004_Curr.Microbiol_48_424
PubMedID: 15170237
Gene_locus related to this paper: ralpi-hboh2 , cupnh-hboh

Title : Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D - Matsuzaki_2004_Nature_428_653
Author(s) : Matsuzaki M , Misumi O , Shin IT , Maruyama S , Takahara M , Miyagishima SY , Mori T , Nishida K , Yagisawa F , Yoshida Y , Nishimura Y , Nakao S , Kobayashi T , Momoyama Y , Higashiyama T , Minoda A , Sano M , Nomoto H , Oishi K , Hayashi H , Ohta F , Nishizaka S , Haga S , Miura S , Morishita T , Kabeya Y , Terasawa K , Suzuki Y , Ishii Y , Asakawa S , Takano H , Ohta N , Kuroiwa H , Tanaka K , Shimizu N , Sugano S , Sato N , Nozaki H , Ogasawara N , Kohara Y , Kuroiwa T
Ref : Nature , 428 :653 , 2004
Abstract : Small, compact genomes of ultrasmall unicellular algae provide information on the basic and essential genes that support the lives of photosynthetic eukaryotes, including higher plants. Here we report the 16,520,305-base-pair sequence of the 20 chromosomes of the unicellular red alga Cyanidioschyzon merolae 10D as the first complete algal genome. We identified 5,331 genes in total, of which at least 86.3% were expressed. Unique characteristics of this genomic structure include: a lack of introns in all but 26 genes; only three copies of ribosomal DNA units that maintain the nucleolus; and two dynamin genes that are involved only in the division of mitochondria and plastids. The conserved mosaic origin of Calvin cycle enzymes in this red alga and in green plants supports the hypothesis of the existence of single primary plastid endosymbiosis. The lack of a myosin gene, in addition to the unexpressed actin gene, suggests a simpler system of cytokinesis. These results indicate that the C. merolae genome provides a model system with a simple gene composition for studying the origin, evolution and fundamental mechanisms of eukaryotic cells.
ESTHER : Matsuzaki_2004_Nature_428_653
PubMedSearch : Matsuzaki_2004_Nature_428_653
PubMedID: 15071595
Gene_locus related to this paper: cyam1-m1vi61 , cyam1-m1vhh9

Title : Electrical and mechanical properties and mode of innervation in scorpionfish sound-producing muscle fibres - Kobayashi_2004_J.Exp.Biol_207_3757
Author(s) : Kobayashi T , Daimon T , Shirakawa I , Chaen S , Sugi H
Ref : J Exp Biol , 207 :3757 , 2004
Abstract : To obtain information about the neural mechanism underlying sound production in teleost fish, we studied the electrical and mechanical properties and mode of innervation in the swimbladder muscle (SBM) fibres of scorpionfish Sebastiscus marmoratus. Action potentials of the SBM fibres in response to direct electrical stimulation neither exhibited overshoot nor propagated along the fibre. Stimulation of the motor nerve, however, uniformly evoked action potentials along the fibre. When neuromuscular transmission was blocked by curare, motor nerve stimulation uniformly evoked endplate potentials along the fibre. These results indicate that action potentials propagate along the nerve branches but not along the SBM fibre membrane. In accordance with the above results, histochemical studies showed that motor nerve branches run along the SBM fibres to form many endplates with cholinesterase activity, indicating multiterminal innervation. The SBM consisted of about 600 fibres, while its motor nerve contained about 100 axons, giving an innervation ratio of about 1:6. Like mammalian fast muscle fibres, the SBM fibres exhibited a low succinic dehydrogenase activity and a high ATPase activity. These results are discussed in connection with the function of the SBM fibres in producing sound.
ESTHER : Kobayashi_2004_J.Exp.Biol_207_3757
PubMedSearch : Kobayashi_2004_J.Exp.Biol_207_3757
PubMedID: 15371483

Title : Purification and properties of an intracellular 3-hydroxybutyrate-oligomer hydrolase (PhaZ2) in Ralstonia eutropha H16 and its identification as a novel intracellular poly(3-hydroxybutyrate) depolymerase - Kobayashi_2003_J.Bacteriol_185_3485
Author(s) : Kobayashi T , Shiraki M , Abe T , Sugiyama A , Saito T
Ref : Journal of Bacteriology , 185 :3485 , 2003
Abstract : An intracellular 3-hydroxybutyrate (3HB)-oligomer hydrolase (PhaZ2(Reu)) of Ralstonia eutropha was purified from Escherichia coli harboring a plasmid containing phaZ2(Reu). The purified enzyme hydrolyzed linear and cyclic 3HB-oligomers. Although it did not degrade crystalline poly(3-hydroxybutyrate) (PHB), the purified enzyme degraded artificial amorphous PHB at a rate similar to that of the previously identified intracellular PHB (iPHB) depolymerase (PhaZ1(Reu)). The enzyme appeared to be an endo-type hydrolase, since it actively hydrolyzed cyclic 3HB-oligomers. However, it degraded various linear 3HB-oligomers and amorphous PHB in the fashion of an exo-type hydrolase, releasing one monomer unit at a time. PhaZ2 was found to bind to PHB inclusion bodies and as a soluble enzyme to cell-free supernatant fractions in R. eutropha; in contrast, PhaZ1 bound exclusively to the inclusion bodies. When R. eutropha H16 was cultivated in a nutrient-rich medium, the transient deposition of PHB was observed: the content of PHB was maximized in the log growth phase (12 h, ca. 14% PHB of dry cell weight) and decreased to a very low level in the stationary phase (ca. 1% of dry cell weight). In each phaZ1-null mutant and phaZ2-null mutant, the PHB content in the cell increased to ca. 5% in the stationary phase. A double mutant lacking both phaZ1 and phaZ2 showed increased PHB content in the log phase (ca. 20%) and also an elevated PHB level (ca. 8%) in the stationary phase. These results indicate that PhaZ2 is a novel iPHB depolymerase, which participates in the mobilization of PHB in R. eutropha along with PhaZ1.
ESTHER : Kobayashi_2003_J.Bacteriol_185_3485
PubMedSearch : Kobayashi_2003_J.Bacteriol_185_3485
PubMedID: 12775684
Gene_locus related to this paper: cupnh-hboh

Title : Regiospecific analysis by ethanolysis of oil with immobilized Candida antarctica lipase - Shimada_2003_Lipids_38_1281
Author(s) : Shimada Y , Ogawa J , Watanabe Y , Nagao T , Kawashima A , Kobayashi T , Shimizu S
Ref : Lipids , 38 :1281 , 2003
Abstract : A mixture of oil/ethanol (1:3, w/w) was shaken at 30 degrees C with 4% immobilized Candida antarctica lipase by weight of the reaction mixture. The reaction regiospecifically converted FA at the 1- and 3-positions to FA ethyl esters, and the lipase acted on C14-C24 FA to a similar degree. The content of 2-MAG reached a maximum after 4 h; the content was 28-29 mol% based on the total amount of FA in the reaction mixture at 59-69% ethanolysis. Only 2-MAG were present in the reaction mixture during the first 4 h, and 1(3)-MAG were detected after 7 h. After removal of ethanol from the 4-h reaction mixture by evaporation, 2-MAG were fractionated by silica gel column chromatography. The contents of FA in the 2-MAG obtained by ethanolysis of several oils coincided well with FA compositions at the 2-position, which was analyzed by Grignard degradation. It was shown that ethanolysis of oil with C. antarctica lipase can be applied to analysis of FA composition at the 2-position in TAG.
ESTHER : Shimada_2003_Lipids_38_1281
PubMedSearch : Shimada_2003_Lipids_38_1281
PubMedID: 14870932
Gene_locus related to this paper: canar-LipB

Title : Cloning and sequencing of an intracellular D(-)-3-hydroxybutyrate oligomer hydrolase from Acidovorax sp. strain SA1 and purification of the enzyme - Sugiyama_2002_Curr.Microbiol_45_123
Author(s) : Sugiyama A , Shiraki M , Kobayashi T , Morikawa G , Yamamoto M , Yamaoka M , Saito T
Ref : Curr Microbiol , 45 :123 , 2002
Abstract : The gene of an intracellular D(-)-3-hydroxybutyrate oligomer hydrolase (i3HBOH) was cloned and sequenced from a poly(3-hydroxybutyrate) (PHB)-degrading bacterium, Acidovorax sp. strain SA1. The i3HBOH gene has 876 nucleotides corresponding to the deduced sequence of 292 amino acids. In this amino acid sequence, the general lipase box sequence (G-X(1)-S-X(2)-G) was found, whose serine residue was determined to the active sites serine by site-directed mutagenesis. An i3HBOH was purified to electrophoretical homogeneity from SA1. The molecular mass of the purified enzyme was estimated to be 32 kDa by SDS-PAGE. The N-terminal amino acid sequence of the purified enzyme corresponded to the deduced N-terminal amino acid sequence in the cloned i3HBOH gene. This is the first cloning and sequencing of an intracellular D(-)-3-hydroxybutyrate oligomer hydrolase gene to date.
ESTHER : Sugiyama_2002_Curr.Microbiol_45_123
PubMedSearch : Sugiyama_2002_Curr.Microbiol_45_123
PubMedID: 12070691

Title : Lipase production in two-step fed-batch culture of organic solvent-tolerant Pseudomonas aeruginosa LST-03 - Ito_2001_J.Biosci.Bioeng_91_245
Author(s) : Ito T , Kikuta H , Nagamori E , Honda H , Ogino H , Ishikawa H , Kobayashi T
Ref : J Biosci Bioeng , 91 :245 , 2001
Abstract : Efficient lipase production by two-step fed-batch culture of an organic solvent-tolerant bacterium, Pseudomonas aeruginosa LST-03, was investigated. When FB synthetic medium was used in flask culture, no lipase activity was detected, whereas lipase was produced at 2.3 I.U./ml in C2 complex medium. However, lipase production was induced in FB medium when a fatty acid was added to the culture broth in the stationary phase. Among fatty acids tested, long chain saturated fatty acids, such as C18 (stearic acid) and C20 (arachidic acid), were found to function as effective inducers for the production of lipase, giving an activity level almost the same as that obtained in C2 medium in flask culture. Two-step lipase production, comprised of a growth phase in fed-batch mode and a production phase in which lipase was induced by the addition of 5% (v/v) stearic acid, was carried out in a jar-fermentor. In the growth phase, the maximum cell concentration at 16 h was only 20 in terms of the optical density at 660 nm (OD660), and a low level of lipase production (8 I.U./ml) was obtained after 167 h. This was considered to be due to the exhaustion of several medium components brought about by the use of an unsuitable medium or feeding solution. After analyzing the contents of the compounds in the culture broth by inductively coupled plasma spectrometry for metal ions and HPLC for anions, a modified FB medium was designed. When this modified FB medium was used in two-step fed-batch culture, the maximum cell concentration reached an OD660 of 55 (30.2 g-dry cells/l) at 16.5 h, and lipase was produced at 96 I.U./ml after 35 h, which is approximately 40 times higher than the production level obtained in flask culture using C2 medium.
ESTHER : Ito_2001_J.Biosci.Bioeng_91_245
PubMedSearch : Ito_2001_J.Biosci.Bioeng_91_245
PubMedID: 16232983

Title : Enhanced insulin secretion and improved glucose tolerance in mice lacking CD26 - Marguet_2000_Proc.Natl.Acad.Sci.U.S.A_97_6874
Author(s) : Marguet D , Baggio L , Kobayashi T , Bernard AM , Pierres M , Nielsen PF , Ribel U , Watanabe T , Drucker DJ , Wagtmann N
Ref : Proc Natl Acad Sci U S A , 97 :6874 , 2000
Abstract : A subset of prolyl oligopeptidases, including dipeptidyl-peptidase IV (DPP IV or CD26, EC ), specifically cleave off N-terminal dipeptides from substrates having proline or alanine in amino acid position 2. This enzyme activity has been implicated in the regulation of the biological activity of multiple hormones and chemokines, including the insulinotropic peptides glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Targeted inactivation of the CD26 gene yielded healthy mice that have normal blood glucose levels in the fasted state, but reduced glycemic excursion after a glucose challenge. Levels of glucose-stimulated circulating insulin and the intact insulinotropic form of GLP-1 are increased in CD26(-/-) mice. A pharmacological inhibitor of DPP IV enzymatic activity improved glucose tolerance in wild-type, but not in CD26(-/-), mice. This inhibitor also improved glucose tolerance in GLP-1 receptor(-/-) mice, indicating that CD26 contributes to blood glucose regulation by controlling the activity of GLP-1 as well as additional substrates. These data reveal a critical role for CD26 in physiological glucose homeostasis, and establish it as a potential target for therapy in type II diabetes.
ESTHER : Marguet_2000_Proc.Natl.Acad.Sci.U.S.A_97_6874
PubMedSearch : Marguet_2000_Proc.Natl.Acad.Sci.U.S.A_97_6874
PubMedID: 10823914

Title : Biochemical and genetic characterization of an extracellular poly(3-hydroxybutyrate) depolymerase from Acidovorax sp strain TP4 - Kobayashi_1999_J.Environ.Polym.Degr_7_281
Author(s) : Kobayashi T , Sugiyama A , Kawase Y , Saito T , Mergaert J , Swings J
Ref : J Environ Polym Degr , 7 :9 , 1999
Abstract : To determine the properties of enzymes from bacteria that degrade polypropiolactone (PPL), we isolated 13 PPL-degrading bacteria from pond water, river water, and soil. Nine of these strains were identified as Acidovorax sp., three as Variovorax paradoxus, and one as Sphingomonas paucimobilis. All the isolates also degraded poly(3-hydroxybutyrate) (PHB). A PPL-degrading enzyme was purified to electrophoretical homogeneity from one of these bacteria, designated Acidovorax sp. TP4. The purified enzyme also degraded PHB. The molecular weight of the enzyme was estimated as about 50,000. The enzyme activity was inhibited by diisopropylfluorophosphate, dithiothreitol, and Triton X-100. The structural gene of the depolymerase was cloned in Escherichia coli. The nucleotide sequence of the cloned DNA fragment contained an open reading frame (1476 bp) specifying a protein with a deduced molecular weight of 50,961 (491 amino acids). The deduced overall sequence was very similar to that of a PHB depolymerase of Comamonas acidovorans YM1609. From these results it was concluded that the isolated PPL-degrading enzyme belongs to the class of PHB depolymerases. A conserved amino acid sequence, Gly-X1-Ser-X2-Gly (lipase box), was found at the N-terminal side of the amino acid sequence. Site-directed mutagenesis of the TP4 enzyme confirmed that 20Ser in the lipase box was essential for the enzyme activity. This is the first report of the isolation a PHB depolymerase from Acidovorax.
ESTHER : Kobayashi_1999_J.Environ.Polym.Degr_7_281
PubMedSearch : Kobayashi_1999_J.Environ.Polym.Degr_7_281
Gene_locus related to this paper: acisp-Q9ZNH8

Title : Reduction of the scopolamine-induced impairment of passive-avoidance performance by sigma receptor agonist in mice - Senda_1997_Physiol.Behav_61_257
Author(s) : Senda T , Matsuno K , Kobayashi T , Mita S
Ref : Physiology & Behavior , 61 :257 , 1997
Abstract : We examined the ameliorating effects of several sigma receptor agonists on scopolamine-induced memory impairment in mice. Scopolamine was administered IP 30 min before the training session. Each sigma receptor agonist was administered 60 min before or immediately after the training session, or 60 min before the retention test in the passive-avoidance performance experiments. (+)-N-Allylnormetazocine ((+)-SKF-10,047), a prototype sigma 1 receptor agonist, showed an ameliorating effect on the scopolamine-induced memory impairment in these 3 administration schedules, and (-)-SKF-10,047, a stereoisomer with low affinity for the sigma 1 receptor subtype, failed to reduce this memory impairment in mice. In addition, 1,3-di(2-toly1)guanidine (DTG) and (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperizine ((+)-3-PPP), nonselective sigma receptor agonists, did not affect this memory impairment. Physostigmine, an acetylcholinesterase (AChE) inhibitor, alleviated the scopolamine-induced memory impairment in all these drug administration schedules. In addition, (+)-SKF-10,047-induced antiamnesic effect was antagonized by the concurrent administration of haloperidol, a sigma receptor antagonist, or N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy) phenyl)ethylamine monohydrochloride (NE-100), a selective sigma 1 receptor antagonist. These findings indicate that the sigma 1 receptor agonist has ameliorating effects on all phases of learning and memory processes. This profile of sigma 1 receptor agonist is similar to that of an AChE inhibitor.
ESTHER : Senda_1997_Physiol.Behav_61_257
PubMedSearch : Senda_1997_Physiol.Behav_61_257
PubMedID: 9035256

Title : Different effects of cholinergic agents on responses recorded from the cat visual cortex and lateral geniculate nucleus dorsalis - Arakawa_1997_Electroencephalogr.Clin.Neurophysiol_104_375
Author(s) : Arakawa K , Tobimatsu S , Kato M , Kobayashi T
Ref : Electroencephalography & Clinical Neurophysiology , 104 :375 , 1997
Abstract : We investigated the effect of cholinergic agents on the cat visual evoked potentials (VEPs) recorded from the primary visual cortex (V1) and lateral geniculate nucleus dorsalis (LGNd) to determine on which level of the visual pathway the cholinergic system acts. VEPs to the alternation of 0.1 cycles per degree sinusoidal gratings at 1 and 4 Hz were recorded from N2O-anesthetized cats directly from the surface of V1 and LGNd. The depth of recording in LGNd was determined by the site where the maximal response was obtained by 1 Hz stimulation. VEPs to 4 Hz stimulation, which showed sinusoidal waveforms and were analyzed by fast Fourier transforms, were used as indicators for modulation by cholinergic agents. Physostigmine, an acetylcholinesterase inhibitor, 0.7 mg/kg i.v., suppressed the amplitude of the responses more at V1 (suppression ratio: mean +/- SD, 85.4 +/- 9.3%) than at LGNd (32.4 +/- 30.7%) (P < 0.05). Conversely, scopolamine, a muscarinic receptor blocker, 0.7 mg/kg i.v., increased the amplitude of the responses more at V1 (enhancement ratio: mean +/- SD, 60.3 +/- 22.3%) than at LGNd (-22.2 +/- 22.5%) (P < 0.05). These results indicate that the V1 changes reflect a direct cortical cholinergic effect, probably by modulating the cholinergic projection from the nucleus basalis of Meynert to V1.
ESTHER : Arakawa_1997_Electroencephalogr.Clin.Neurophysiol_104_375
PubMedSearch : Arakawa_1997_Electroencephalogr.Clin.Neurophysiol_104_375
PubMedID: 9246076

Title : Pharmacokinetics and safety of JTP-4819, a novel specific orally active prolyl endopeptidase inhibitor, in healthy male volunteers - Umemura_1997_Br.J.Clin.Pharmacol_43_613
Author(s) : Umemura K , Kondo K , Ikeda Y , Kobayashi T , Urata Y , Nakashima M
Ref : British Journal of Clinical Pharmacology , 43 :613 , 1997
Abstract : AIMS To investigate the pharmacokinetics and safety profile of JTP-4819, (-)-(2S)-1-benzylaminocarbonyl-[(2S)-2-glycoloylpyrrolidinyl ]-2-pyrrolidinecarboxamide, a novel specific orally active prolyl endopeptidase (PEP) inhibitor. METHODS: JTP-4819 was given orally to 28 healthy male volunteers at single doses of 30 mg (n = 6), 60 mg (n = 6), 120 mg (n = 6) and placebo (n = 3) and multiple doses of 60 mg three times daily (n = 5) and placebo (n = 2) for 7 days to investigate its safety and pharmacokinetics following a preliminary safety evaluation of 3, 10 and 30 mg doses in six healthy volunteers. With the single dose of 60 mg, a cross-over study was conducted to examine the effect of food on the bioavailability of the drug. The concentrations of JTP-4819 in plasma and urine were determined by electrospray ionization-liquid chromatography/mass spectrometry (ESI-LC/MS) method. RESULTS: In the multiple-dose study, the cholinesterase activity was gradually increased and reached above the normal range on days 4 to 8 in all five subjects given JTP-4819 and gradually returned to normal range after completion of dosing. The elevation of plasma cholinesterase activity was considered to be an action of JTP-4819, but this remains to be verified. There were no other abnormal findings in objective symptoms and laboratory findings including blood pressure, heart rate, electrocardiogram, body temperature, haematology, blood chemistry and urinalysis. The Cmax of JTP-4819 at 30, 60 and 120 mg in fasting state were 474, 887 and 1,649 ng ml-1, respectively, at 1 h after administration, and the t1/2 was about 2 h. AUC increased in proportion to the given doses. The cumulative urinary recoveries within 24 h were approximately 66%, Cmax, AUC, t1/2 and urinary recovery were not affected by food intake. In the multiple-dose study, there was no drug accumulation trend in plasma.
CONCLUSIONS: These results indicate that JTP-4819 has acceptable pharmacodynamic and pharmacokinetics profiles for clinical use without any serious adverse events as we verified in healthy young male volunteers.
ESTHER : Umemura_1997_Br.J.Clin.Pharmacol_43_613
PubMedSearch : Umemura_1997_Br.J.Clin.Pharmacol_43_613
PubMedID: 9205821

Title : Enhancement of acetylcholine release by SA4503, a novel sigma 1 receptor agonist, in the rat brain - Kobayashi_1996_J.Pharmacol.Exp.Ther_279_106
Author(s) : Kobayashi T , Matsuno K , Nakata K , Mita S
Ref : Journal of Pharmacology & Experimental Therapeutics , 279 :106 , 1996
Abstract : We found that 1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride (SA4503), a potent and selective sigma 1 receptor agonist, significantly enhanced the cerebral acetylcholine (ACh) release in the rat using in vivo brain microdialysis technique. Interestingly, the significant enhancement of ACh release elicited by SA4503 was observed in the rat frontal cortex and hippocampus, although the striatal ACh release was unchanged. This cortical ACh release was fully reversed by haloperidol, a prototype sigma receptor antagonist, or by N, N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride, a putative sigma 1 receptor antagonist. In addition, this enhanced ACh release by SA4503 was inhibited by tetrodotoxin, a Na+ channel blocker. However, tetrahydroaminoacridine, an acetylcholinesterase inhibitor, significantly increased the extracellular ACh level in the rat frontal cortex and weakly increased the hippocampal level. This compound also showed the significant increase of extracellular ACh level in the rat striatum. Moreover, tetrahydroaminoacridine markedly produced cholinomimetic side-effects, such as hypothermia, tremor, miosis and lacrimation. However, SA4503 did not produce these cholinomimetic side-effects. These findings suggest that SA4503 enhances the ACh release that is mediated through a novel mechanism, namely sigma 1 receptor subtype. Furthermore, SA4503 has regional differences in the enhancement of cerebral ACh release, and did not produce cholinomimetic side-effects. These profiles are different from tetrahydroaminoacridine.
ESTHER : Kobayashi_1996_J.Pharmacol.Exp.Ther_279_106
PubMedSearch : Kobayashi_1996_J.Pharmacol.Exp.Ther_279_106
PubMedID: 8858982

Title : Ameliorating effect of SA4503, a novel sigma 1 receptor agonist, on memory impairments induced by cholinergic dysfunction in rats - Senda_1996_Eur.J.Pharmacol_315_1
Author(s) : Senda T , Matsuno K , Okamoto K , Kobayashi T , Nakata K , Mita S
Ref : European Journal of Pharmacology , 315 :1 , 1996
Abstract : We found a potent and selective sigma 1 receptor agonist, SA4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydro-chloride), with high affinity for the sigma 1 receptor subtype (IC50 = 17 nM), but low affinity for the sigma 2 receptor subtype (IC50 = 1800 nM). The binding activity and selectivity of SA4503 resembled those of (+)-pentazocine, a prototype sigma 1 receptor agonist. We have previously shown that the sigma 1 receptor agonist activated central cholinergic functions. Therefore, we examined the effects of SA4503 on the cholinergic dysfunction-induced memory impairments in a passive avoidance task. Scopolamine, a muscarinic acetylcholine receptor antagonist, produced memory impairment, when it was administered 30 min before the training session of the passive avoidance task in rats. Single administration of SA4503 significantly reduced the scopolamine-induced memory impairment. In addition, the lesioning by injection of alpha-amino-3-hydroxy-5-isoxazole acetic acid (ibotenic acid) into the basal forebrain area produced memory impairment in rats. Repeated administration of SA4503 after lesioning of the basal forebrain area ameliorated the basal forebrain lesion-induced memory impairment. Moreover, the ameliorating effect of SA4503 against the scopolamine-induced memory impairment was antagonized by both 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-buta none (haloperidol), a sigma receptor antagonist, and N,N-dipropyl-2- [4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100), a putative sigma 1 receptor antagonist. These results suggest that SA4503 has an anti-amnesic effect against cholinergic dysfunction-induced memory impairment, and that the effect of SA4503 is mediated by the sigma 1 receptor subtype.
ESTHER : Senda_1996_Eur.J.Pharmacol_315_1
PubMedSearch : Senda_1996_Eur.J.Pharmacol_315_1
PubMedID: 8960858

Title : Galactosialidosis: clinical and molecular analysis of 19 Japanese patients. -
Author(s) : Takano T , Shimmoto M , Fukuhara Y , Itoh K , Kase R , Takiyama N , Kobayashi T , Oshima A , Sakuraba H , Suzuki Y
Ref : Brain Dysfunction , 4 :271 , 1991
Gene_locus related to this paper: human-CTSA

Title : Nucleotide sequence of the pldB gene and characteristics of deduced amino acid sequence of lysophospholipase L2 in Escherichia coli - Kobayashi_1985_J.Biochem_98_1017
Author(s) : Kobayashi T , Kudo I , Karasawa K , Mizushima H , Inoue K , Nojima S
Ref : J Biochem , 98 :1017 , 1985
Abstract : The nucleotide sequence of the pldB gene of Escherichia coli K-12, which codes for lysophospholipase L2 located in the inner membrane, was determined. The deduced amino acid sequence of lysophospholipase L2 contains 340 amino acid residues, resulting in a protein with a molecular weight of 38,934. It is characterized by a high content of arginine residues (36 out of 340 residues). The amino acid sequence near the NH2-terminus of the protein is composed of a large number of polar or charged amino acid residues, suggesting that this region cannot be a signal peptide. The hydropathy profile of the deduced amino acid sequence of lysophospholipase L2 was studied. Most of the region was rather hydrophilic, and there was no stretch of hydrophobic amino acid region, such as might be predicted to traverse the lipid bilayer. These results are consistent with the experimental observation that lysophospholipase L2 is extracted by salt solution from the membrane fraction, and it may be classified as a peripheral membrane protein. Computer analysis showed that there is no homology in amino acid sequences between lysophospholipase L2 and other extracellular phospholipases, as well as detergent-resistant phospholipase A, which is another membrane-bound phospholipase in E. coli and whose DNA sequence was determined (Homma, H., Kobayashi, T., Chiba, N., Karasawa, K., Mizushima, H., Kudo, I., Inoue, K., Ideka, H., Sekiguchi, M., & Nojima, S. (1984) J. Biochem. 96, 1655-1664). This is the first report of the primary structure of a lysophospholipase.
ESTHER : Kobayashi_1985_J.Biochem_98_1017
PubMedSearch : Kobayashi_1985_J.Biochem_98_1017
PubMedID: 3908445
Gene_locus related to this paper: ecoli-pldb

Title : Purification and characterization of lysophospholipase L2 of Escherichia coli K-12 - Karasawa_1985_J.Biochem_98_1117
Author(s) : Karasawa K , Kudo I , Kobayashi T , Sa-Eki T , Inoue K , Nojima S
Ref : J Biochem , 98 :1117 , 1985
Abstract : Lysophospholipase L2, which is bound to the inner membrane of Escherichia coli K-12, was produced in a large amount in cells bearing its cloned structural gene. Starting from these cells, the lysophospholipase L2 was purified approximately 700-fold to near homogeneity by solubilization with KCl, ammonium sulfate fractionation, chromatofocusing in the presence of a zwitterionic detergent, CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate), and heparin-Sepharose affinity column chromatography. The final preparation showed a single protein band with a molecular weight of 38,500 daltons in SDS-polyacrylamide gel electrophoresis. The amino acid sequence of the NH2-terminal portion of the purified enzyme was determined. It was in complete agreement with that deduced from the nucleotide sequence of the structural gene, pldB [Kobayashi, T., Kudo, I., Karasawa, K., Mizushima, H., Inoue, K., & Nojima, S. (1985) J. Biochem. 98, 1017-1025.] The purified enzyme hydrolyzes 2-acyl glycerophosphoethanolamine (GPE) and 2-acyl glycerophosphocholine (GPC) more effectively than 1-acyl GPE and 1-acyl GPC, but does not attack diacylphospholipids. The enzyme also catalyzes the transfer of an acyl group from lysophospholipid to phosphatidylglycerol for formation of acyl phosphatidylglycerol. The acyl group was more effectively transferred from 2-acyl lysophospholipid than from the 1-acyl derivative. This enzyme was heat-labile and was inactivated at 55 degrees C within 5 min. The present paper shows clearly that lysophospholipase L2 is a different enzyme protein from lysophospholipase L1 which was formerly purified from the supernatant of the wild strain of E. coli K-12 homogenates [Doi, O. & Nojima, S. (1975) J. Biol. Chem. 250, 5208-5214].
ESTHER : Karasawa_1985_J.Biochem_98_1117
PubMedSearch : Karasawa_1985_J.Biochem_98_1117
PubMedID: 3908447

Title : [On the neuromuscular paralyzing action of tetrodotoxin] -
Author(s) : Cheymol J , Kobayashi T , Bourillet F , Tetreault L
Ref : Archives Internationales de Pharmacodynamie et de Therapie , 134 :28 , 1961
PubMedID: 13878853