Kobayashi Y

References (23)

Title : Association of Cholinesterase With Postoperative Pneumonia After Gastrectomy for Gastric Cancer - Kanno_2024_J.Surg.Res_296_123
Author(s) : Kanno H , Takano Y , Kai W , Takahashi S , Tsukihara S , Kobayashi Y , Hanyu N , Eto K
Ref : J Surg Res , 296 :123 , 2024
Abstract : INTRODUCTION: Cholinesterase is a classical marker that reflects nutritional and inflammatory status. The aim of the present study was to evaluate the association between serum cholinesterase levels and postoperative infectious complications in patients undergoing gastrectomy for gastric cancer. MATERIALS AND METHODS: This retrospective study comprised 108 patients who underwent gastrectomy for gastric cancer. We comprehensively investigated the association between clinicopathological variables and postoperative infectious complications after gastrectomy. Then patients were divided into the cholinesterase-high and -low groups to analyze their clinicopathological variables. Finally, we analyzed the types of infectious complications that were most associated with preoperative serum cholinesterase levels. RESULTS: Twenty-six patients (24%) developed postoperative infectious complications. Multivariate analysis revealed that serum cholinesterase levels (P = 0.026) and N stage (P = 0.009) were independent risk factors for postoperative infectious complications. In particular, the incidence of pneumonia (P = 0.001) was significantly higher in the cholinesterase-low group. Age (P = 0.023), cerebrovascular comorbidities (P = 0.006), serum cholinesterase levels (P = 0.013), and total gastrectomy (P = 0.017) were identified as independent risk factors for postoperative pneumonia. CONCLUSIONS: Preoperative serum cholinesterase levels were associated with postoperative pneumonia after gastrectomy for gastric cancer, suggesting the importance of preoperative nutritional assessment in gastric cancer surgery.
ESTHER : Kanno_2024_J.Surg.Res_296_123
PubMedSearch : Kanno_2024_J.Surg.Res_296_123
PubMedID: 38277947

Title : The influence of serum cholinesterase levels and sarcopenia on postoperative infectious complications in colorectal cancer surgery - Takano_2022_Surg.Today__
Author(s) : Takano Y , Haruki K , Kai W , Tsukihara S , Kobayashi Y , Ito D , Kanno H , Son K , Hanyu N , Eto K
Ref : Surg Today , : , 2022
Abstract : PURPOSE: Cholinesterase is a nutritional marker associated with sarcopenia. The present study evaluated the relationship between cholinesterase and postoperative infectious complications in patients undergoing colorectal resection for colorectal cancer. METHODS: The study involved 231 patients who had undergone colorectal resection for colorectal cancer. We retrospectively investigated the relationship between preoperative serum cholinesterase levels and postoperative infectious complications. Univariate and multivariate analyses were performed to identify independent risk factors for postoperative infectious complications. We then performed stratified analyses to assess the interaction between cholinesterase and clinical variables to predict postoperative infectious complications. RESULTS: In the multivariate analysis, the body mass index (P = 0.010), serum cholinesterase levels (P = 0.005), sarcopenia (P = 0.003) and blood loss (P < 0.001) were independent risk factors for postoperative infectious complications. In stratified analyses, the association between serum cholinesterase levels and postoperative infectious complications differed by the sarcopenia status (P(interaction) = 0.006). CONCLUSION: Preoperative serum cholinesterase levels may be useful for predicting postoperative infectious complications in colorectal cancer surgery. The association differs by the sarcopenia status, suggesting a potential interaction between nutritional markers and sarcopenia.
ESTHER : Takano_2022_Surg.Today__
PubMedSearch : Takano_2022_Surg.Today__
PubMedID: 36441399

Title : Structural basis of mutants of PET-degrading enzyme from Saccharomonospora viridis AHK190 with high activity and thermal stability - Emori_2021_Proteins_89_502
Author(s) : Emori M , Numoto N , Senga A , Bekker GJ , Kamiya N , Kobayashi Y , Ito N , Kawai F , Oda M
Ref : Proteins , 89 :502 , 2021
Abstract : The cutinase-like enzyme from the thermophile Saccharomonospora viridis AHK190, Cut190, is a good candidate to depolymerize polyethylene terephthalate (PET) efficiently. We previously developed a mutant of Cut190 (S226P/R228S), which we designated as Cut190* that has both increased activity and stability and solved its crystal structure. Recently, we showed that mutation of D250C/E296C on one of the Ca(2+) -binding sites resulted in a higher thermal stability while retaining its polyesterase activity. In this study, we solved the crystal structures of Cut190* mutants, Q138A/D250C-E296C/Q123H/N202H, designated as Cut190*SS, and its inactive S176A mutant, Cut190*SS_S176A, at high resolution. The overall structures were similar to those of Cut190* and Cut190*S176A reported previously. As expected, Cys250 and Cys296 were closely located to form a disulfide bond, which would assuredly contribute to increase the stability. Isothermal titration calorimetry experiments and 3D Reference Interaction Site Model calculations showed that the metal-binding properties of the Cut190*SS series were different from those of the Cut190* series. However, our results show that binding of Ca(2+) to the weak binding site, site 1, would be retained, enabling Cut190*SS to keep its ability to use Ca(2+) to accelerate the conformational change from the closed (inactive) to the open (active) form. While increasing the thermal stability, Cut190*SS could still express its enzymatic function. Even after incubation at 70 degreesC, which corresponds to the glass transition temperature of PET, the enzyme retained its activity well, implying a high applicability for industrial PET depolymerization using Cut190*SS.
ESTHER : Emori_2021_Proteins_89_502
PubMedSearch : Emori_2021_Proteins_89_502
PubMedID: 33340163
Gene_locus related to this paper: sacvd-c7mve8

Title : Acute myelomonocytic leukemia negative for alpha-naphthyl acetate esterase stain in a Holstein cow - Maezawa_2021_J.Vet.Med.Sci__
Author(s) : Maezawa M , Nakamichi A , Akiyama N , Tagawa M , Watanabe KI , Kobayashi Y , Inokuma H
Ref : J Vet Med Sci , : , 2021
Abstract : A 4-year, 7-month-old Holstein cow presented with anorexia. Physical examination revealed masses in the interscapular region and vagina. Blast cells were detected in the masses and peripheral blood by fine needle aspiration cytology and hematological examination. By bone marrow aspiration, blast cells constituted up to 24.2% of all nucleated cells, and 22% and 2% of non-erythroid cells stained positive for myeloperoxidase and alpha-naphthyl acetate esterase (ANAE), respectively. Pathological examination revealed the mass lesions consisted of a proliferation of tumor cells, which were positive for monocytic markers (HLA-DR and Iba-1). The cow was diagnosed with acute myelomonocytic leukemia (AMML). Even when tumor cells are ANAE-negative, AMML cannot be completely ruled out and should be considered when diagnosing cattle with leukemia/lymphoma.
ESTHER : Maezawa_2021_J.Vet.Med.Sci__
PubMedSearch : Maezawa_2021_J.Vet.Med.Sci__
PubMedID: 34511539

Title : Characterization of a poly(butylene adipate-co-terephthalate) hydrolase from the aerobic mesophilic bacterium Bacillus pumilus - Muroi_2017_Polym.Degrad.Stab_137_11
Author(s) : Muroi F , Tachibana Y , Soulenthone P , Yamamoto K , Mizuno T , Sakurai T , Kobayashi Y , Kasuya KI
Ref : Polymer Degradation and Stability , 137 :11 , 2017
Abstract : The use of biodegradable plastic films made of poly(butylene adipate-co-terephthalate) (PBAT) to improve crop production has been proposed. Because the film after use is expected to be degraded on site, it is important to understand the biodegradation mechanism of PBAT in aerobic and mild temperature conditions. We therefore isolated three PBAT-degrading strains, NKCM3201, NKCM3202, and NKCM3101, from soil environments. Phylogenetic analysis revealed that the strains are closely related to Bacillus pumilus. Strain NKCM3201, which degraded PBAT film at the fastest rate (12.2 mug/day/cm2) and grew well at 30 C to 40 C in aerobic conditions, was selected for further analysis. We cloned the 648-bp coding region of the PBAT hydrolase (PBATHBp) gene, which encodes a 215-amino acid protein containing a signal peptide of 34 residues. Mutation analyses revealed that PBATHBp belongs to the serine hydrolase superfamily, with a catalytic triad composed of Ser77, Asp133, and His156. Homology 3D modeling of PBATHBp using Bacillus subtilis 168 lipase as a template showed that the enzyme belongs to the alpha/beta hydrolase fold family, which lack a lid domain on its surface. PBATHBp hydrolyzed PBAT, poly(butylene succinate-co-adipate) (PBSA), poly(ethylene succinate) (PESu), and polycaprolactone (PCL) films at a degradation rate of 14.3, 3.3 x 10+2, 7.0 x 10+2, and 1.1x 10+2 mug/cm2/day, respectively. Liquid chromatography-mass spectrometry analysis of degradation products from PBAT revealed that PBATHBp hydrolyses ester bonds between butanediol and terephthalate (B-T bonds) at much slower rates than ester bonds between adipate and butanediol. This ester bond preference may explain the very slow PBAT degradation rate compared to PBSA, PESu, and PCL. This is the first report of a PBAT hydrolase from an aerobic mesophilic bacterium, and may contribute to our understanding of PBAT biodegradation under mild temperature conditions.
ESTHER : Muroi_2017_Polym.Degrad.Stab_137_11
PubMedSearch : Muroi_2017_Polym.Degrad.Stab_137_11
Gene_locus related to this paper: bacpu-q6rsn0

Title : Effect of distigmine on the contractile response of guinea pig urinary bladder to electrical field stimulation - Obara_2017_Eur.J.Pharmacol_809_209
Author(s) : Obara K , Kobayashi Y , Chino D , Tanaka Y
Ref : European Journal of Pharmacology , 809 :209 , 2017
Abstract : Distigmine bromide (distigmine) is a reversible carbamate group cholinesterase (ChE) inhibitor. Although mainly used clinically for the treatment of myasthenia gravis, distigmine is also indicated for detrusor underactivity in Japan. According to the pharmacological classification of distigmine, its therapeutic effect against detrusor underactivity appears to be produced by enhanced urinary bladder smooth muscle (UBSM) contractility due to an increased concentration of acetylcholine between parasympathetic nerve endings and UBSM cells. However, ATP as well as acetylcholine is also released from parasympathetic nerve endings that dominate UBSM. The present study was thus carried out to investigate the potentiating effects of distigmine on the two UBSM contractile components in response to parasympathetic nerve stimulation induced by electrical field stimulation (EFS). In isolated guinea pig UBSM tissues, EFS (1-16Hz) produced tetrodotoxin-sensitive, frequency-dependent contractions. The contractile responses to EFS were largely diminished by atropine (10-6M), and the remaining contractile components in the presence of atropine were virtually abolished by alpha,beta-methylene adenosine triphosphate (alpha,beta-mATP) (10-4M). Distigmine (10-6M) significantly potentiated EFS-induced contractile components generated in the presence of alpha,beta-mATP (10-4M), but did not potentiate EFS-induced contractile components generated in the presence of atropine (10-6M). These findings clearly indicate that distigmine strongly potentiates UBSM contraction selectively induced by parasympathetic nerve-derived acetylcholine, suggesting a potential mechanism by which distigmine restores detrusor underactivity.
ESTHER : Obara_2017_Eur.J.Pharmacol_809_209
PubMedSearch : Obara_2017_Eur.J.Pharmacol_809_209
PubMedID: 28511871

Title : Contributions of arylacetamide deacetylase and carboxylesterase 2 to flutamide hydrolysis in human liver - Kobayashi_2012_Drug.Metab.Dispos_40_1080
Author(s) : Kobayashi Y , Fukami T , Shimizu M , Nakajima M , Yokoi T
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 40 :1080 , 2012
Abstract : Flutamide, an antiandrogen drug, is widely used for the treatment of prostate cancer. The major metabolic pathways of flutamide are hydroxylation and hydrolysis. The hydrolyzed metabolite, 5-amino-2-nitrobenzotrifluoride (FLU-1), is further metabolized to N-hydroxy FLU-1, an assumed hepatotoxicant. Our previous study demonstrated that arylacetamide deacetylase (AADAC), one of the major serine esterases expressed in the human liver and gastrointestinal tract, catalyzes the flutamide hydrolysis. However, the enzyme kinetics in human tissue microsomes were not consistent with the kinetics by recombinant human AADAC. Thus, it seemed that AADAC is not the sole enzyme responsible for flutamide hydrolysis in human. In the present study, we found that recombinant carboxylesterase (CES) 2 could hydrolyze flutamide at low concentrations of flutamide. In the inhibition assay, the flutamide hydrolase activities at a flutamide concentration of 5 muM in human liver and jejunum microsomes were strongly inhibited by a selective CES2 inhibitor, 10 muM loperamide, with the residual activities of 22.9 +/- 3.5 and 18.6 +/- 0.7%, respectively. These results suggest that CES2 is also involved in the flutamide hydrolysis in human tissues. Using six individual human livers, the contributions of AADAC and CES2 to flutamide hydrolysis were estimated by using the relative activity factor. The relative contribution of CES2 was approximately 75 to 99% at the concentration of 5 muM flutamide. In contrast, the relative contribution of AADAC increased in parallel with the concentration of flutamide. Thus, CES2, rather than AADAC, largely contributed to the flutamide hydrolysis in clinical therapeutics.
ESTHER : Kobayashi_2012_Drug.Metab.Dispos_40_1080
PubMedSearch : Kobayashi_2012_Drug.Metab.Dispos_40_1080
PubMedID: 22446520

Title : Species differences in tissue distribution and enzyme activities of arylacetamide deacetylase in human, rat, and mouse - Kobayashi_2012_Drug.Metab.Dispos_40_671
Author(s) : Kobayashi Y , Fukami T , Nakajima A , Watanabe A , Nakajima M , Yokoi T
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 40 :671 , 2012
Abstract : Human arylacetamide deacetylase (AADAC) is a major esterase responsible for the hydrolysis of clinical drugs such as flutamide, phenacetin, and rifampicin. Thus, AADAC is considered to be a relevant enzyme in preclinical drug development, but there is little information about species differences with AADAC. This study investigated the species differences in the tissue distribution and enzyme activities of AADAC. In human, AADAC mRNA was highly expressed in liver and the gastrointestinal tract, followed by bladder. In rat and mouse, AADAC mRNA was expressed in liver at the highest level, followed by the gastrointestinal tract and kidney. The expression levels in rat tissues were approximately 7- and 10-fold lower than those in human and mouse tissues, respectively. To compare the catalytic efficiency of AADAC among three species, each recombinant AADAC was constructed, and enzyme activities were evaluated by normalizing with the expression levels of AADAC. Flutamide and phenacetin hydrolase activities were detected by the recombinant AADAC of all species. In flutamide hydrolysis, liver microsomes of all species showed similar catalytic efficiencies, despite the lower AADAC mRNA expression in rat liver. In phenacetin hydrolysis, rat liver microsomes showed approximately 4- to 6.5-fold lower activity than human and mouse liver microsomes. High rifampicin hydrolase activity was detected only by recombinant human AADAC and human liver and jejunum microsomes. Taken together, the results of this study clarified the species differences in the tissue distribution and enzyme activities of AADAC and facilitate our understanding of species differences in drug hydrolysis.
ESTHER : Kobayashi_2012_Drug.Metab.Dispos_40_671
PubMedSearch : Kobayashi_2012_Drug.Metab.Dispos_40_671
PubMedID: 22207054
Gene_locus related to this paper: human-AADAC , mouse-aryla , ratno-aryla

Title : A novel polymorphic allele of human arylacetamide deacetylase leads to decreased enzyme activity - Shimizu_2012_Drug.Metab.Dispos_40_1183
Author(s) : Shimizu M , Fukami T , Kobayashi Y , Takamiya M , Aoki Y , Nakajima M , Yokoi T
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 40 :1183 , 2012
Abstract : Human arylacetamide deacetylase (AADAC) is responsible for the hydrolysis of clinically used drugs such as flutamide, phenacetin, and rifamycins. Our recent studies suggested that human AADAC is a relevant enzyme pharmacologically and toxicologically. To date, the genetic polymorphisms that affect enzyme activity in AADAC have been unknown. In this study, we found single-nucleotide polymorphisms in the human AADAC gene in a liver sample that showed remarkably low flutamide hydrolase activity. Among them, g.13651G > A (V281I) and g.14008T > C (X400Q) were nonsynonymous. The latter would be predicted to cause a C-terminal one-amino acid (glutamine) extension. The AADAC*2 allele (g.13651G > A) was found in all populations investigated in this study (European American, African American, Korean, and Japanese), at allelic frequencies of 52.6 to 63.5%, whereas the AADAC*3 allele (g.13651G > A/g.14008T > C) was found in European American (1.3%) and African American (2.0%) samples. COS7 cells expressing AADAC.1 (wild-type) exhibited flutamide, phenacetin, and rifampicin hydrolase activities with intrinsic clearance (CLint) values of 1.31 +/- 0.06, 1.00 +/- 0.02, and 0.39 +/- 0.02 mul x min(-1) x unit(-1), respectively. AADAC.2, which is a protein produced from the AADAC*2 allele, showed moderately lower or similar CLint values, compared with AADAC.1, but AADAC.3 showed substantially lower CLint values (flutamide hydrolase, 0.21 +/- 0.02 mul x min(-1) x unit(-1); phenacetin hydrolase, 0.12 +/- 0.00 mul x min(-1) x unit(-1); rifampicin hydrolase, 0.03 +/- 0.01 mul x min(-1) x unit(-1), respectively). Microsomes from a liver sample genotyped as AADAC*3/AADAC*3 showed decreased enzyme activities, compared with those genotyped as AADAC*1/AADAC*1, AADAC*1/AADAC*2, and AADAC*2/AADAC*2. In conclusion, we found an AADAC allele that yielded decreased enzyme activity. This study should provide useful information on interindividual variations in AADAC enzyme activity.
ESTHER : Shimizu_2012_Drug.Metab.Dispos_40_1183
PubMedSearch : Shimizu_2012_Drug.Metab.Dispos_40_1183
PubMedID: 22415931
Gene_locus related to this paper: human-AADAC

Title : Human arylacetamide deacetylase is responsible for deacetylation of rifamycins: rifampicin, rifabutin, and rifapentine - Nakajima_2011_Biochem.Pharmacol_82_1747
Author(s) : Nakajima A , Fukami T , Kobayashi Y , Watanabe A , Nakajima M , Yokoi T
Ref : Biochemical Pharmacology , 82 :1747 , 2011
Abstract : Rifamycins such as rifampicin, rifabutin, and rifapentine are used for the treatment of tuberculosis and induce various drug-metabolizing enzymes. Rifamycins have been reported to be mainly deacetylated by esterase(s) expressed in human liver microsomes (HLM) to 25-deacetylrifamycins, but the responsible enzyme remained to be determined. In this study, we found that recombinant human arylacetamide deacetylase (AADAC) could efficiently deacetylate rifamycins, whereas human carboxylesterases, which are enzymes responsible for the hydrolysis of many prodrugs, showed no activity. The involvement of AADAC in the deacetylation of rifamycins in HLM was verified by the similarities of the K(m) and K(i) values and the inhibitory characteristics between recombinant AADAC and HLM. Rifamycins exhibited potent cytotoxicity to HepG2 cells, but their 25-deacetylated metabolites did not. Luciferase assay using a reporter plasmid containing CYP3A4 direct repeat 3 and everted repeat 6 motifs revealed that 25-deacetylrifamycins have lesser potency to transactivate CYP3A4 compared with the parent drugs. Supporting these results, HepG2 cells infected with a recombinant adenovirus expressing human AADAC showed low cytotoxicity and induction potency of CYP3A4 by rifamycins. In addition, CYP3A4 induction in human hepatocytes by rifamycins was increased by transfecting siRNA for human AADAC. Thus, we found that human AADAC was the enzyme responsible for the deacetylation of rifamycins and would affect the induction rate of drug-metabolizing enzymes by rifamycins and their induced hepatotoxicity.
ESTHER : Nakajima_2011_Biochem.Pharmacol_82_1747
PubMedSearch : Nakajima_2011_Biochem.Pharmacol_82_1747
PubMedID: 21856291
Gene_locus related to this paper: human-AADAC

Title : Arylacetamide deacetylase is a determinant enzyme for the difference in hydrolase activities of phenacetin and acetaminophen - Watanabe_2010_Drug.Metab.Dispos_38_1532
Author(s) : Watanabe A , Fukami T , Takahashi S , Kobayashi Y , Nakagawa N , Nakajima M , Yokoi T
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 38 :1532 , 2010
Abstract : Phenacetin was withdrawn from the market because it caused renal failure in some patients. Many reports indicated that the nephrotoxicity of phenacetin is associated with the hydrolyzed metabolite, p-phenetidine. Acetaminophen (APAP), the major metabolite of phenacetin, is also hydrolyzed to p-aminophenol, which is a nephrotoxicant. However, APAP is safely prescribed if used in normal therapeutic doses. This background prompted us to investigate the difference between phenacetin and APAP hydrolase activities in human liver. In this study, we found that phenacetin is efficiently hydrolyzed in human liver microsomes (HLM) [CL(int) 1.08 +/- 0.02 microl/(min . mg)], whereas APAP is hardly hydrolyzed [0.02 +/- 0.00 microl/(min . mg)]. To identify the esterase involved in their hydrolysis, the activities were measured using recombinant human carboxylesterase (CES) 1A1, CES2, and arylacetamide deacetylase (AADAC). Among these, AADAC showed a K(m) value (1.82 +/- 0.02 mM) similar to that of HLM (3.30 +/- 0.16 mM) and the highest activity [V(max) 6.03 +/- 0.14 nmol/(min . mg)]. In contrast, APAP was poorly hydrolyzed by the three esterases. The large contribution of AADAC to phenacetin hydrolysis was demonstrated by the prediction with a relative activity factor. In addition, the phenacetin hydrolase activity by AADAC was activated by flutamide (5-fold) as well as that in HLM (4-fold), and the activity in HLM was potently inhibited by eserine, a strong inhibitor of AADAC. In conclusion, we found that AADAC is the principal enzyme responsible for the phenacetin hydrolysis, and the difference of hydrolase activity between phenacetin and APAP is largely due to the substrate specificity of AADAC.
ESTHER : Watanabe_2010_Drug.Metab.Dispos_38_1532
PubMedSearch : Watanabe_2010_Drug.Metab.Dispos_38_1532
PubMedID: 20542992

Title : Biosynthesis of the salinosporamide A polyketide synthase substrate chloroethylmalonyl-coenzyme A from S-adenosyl-L-methionine - Eustaquio_2009_Proc.Natl.Acad.Sci.U.S.A_106_12295
Author(s) : Eustaquio AS , McGlinchey RP , Liu Y , Hazzard C , Beer LL , Florova G , Alhamadsheh MM , Lechner A , Kale AJ , Kobayashi Y , Reynolds KA , Moore BS
Ref : Proc Natl Acad Sci U S A , 106 :12295 , 2009
Abstract : Polyketides are among the major classes of bioactive natural products used to treat microbial infections, cancer, and other diseases. Here we describe a pathway to chloroethylmalonyl-CoA as a polyketide synthase building block in the biosynthesis of salinosporamide A, a marine microbial metabolite whose chlorine atom is crucial for potent proteasome inhibition and anticancer activity. S-adenosyl-L-methionine (SAM) is converted to 5'-chloro-5'-deoxyadenosine (5'-ClDA) in a reaction catalyzed by a SAM-dependent chlorinase as previously reported. By using a combination of gene deletions, biochemical analyses, and chemical complementation experiments with putative intermediates, we now provide evidence that 5'-ClDA is converted to chloroethylmalonyl-CoA in a 7-step route via the penultimate intermediate 4-chlorocrotonyl-CoA. Because halogenation often increases the bioactivity of drugs, the availability of a halogenated polyketide building block may be useful in molecular engineering approaches toward polyketide scaffolds.
ESTHER : Eustaquio_2009_Proc.Natl.Acad.Sci.U.S.A_106_12295
PubMedSearch : Eustaquio_2009_Proc.Natl.Acad.Sci.U.S.A_106_12295
PubMedID: 19590008

Title : Patients achieving clearance of HCV with interferon therapy recover from decreased retinol-binding protein 4 levels - Iwasa_2009_J.Viral.Hepat_16_716
Author(s) : Iwasa M , Hara N , Miyachi H , Tanaka H , Takeo M , Fujita N , Kobayashi Y , Kojima Y , Kaito M , Takei Y
Ref : J Viral Hepat , 16 :716 , 2009
Abstract : Retinol-binding protein 4 (RBP4) is a recently identified adipokine that is elevated in the blood in several insulin-resistant states. We investigated the association between plasma RBP4 and histological and biochemical characteristics of chronic hepatitis C (CHC), as well as changes in RBP4 levels following interferon therapy. Eighty-one patients with CHC infected with genotype 1 received treatment with peginterferon plus ribavirin. Histological data were available for 41 out of 81 patients before treatment, and the degree of fibrosis, inflammation and steatosis was assessed. Plasma levels of RBP4 were determined in serial samples (before, at the end of treatment, and at 6 months post-treatment). RBP4 levels were lower in CHC patients than in control subjects (34.6 +/- 12.3 microg/mL vs 46.2 +/- 10.5 microg/mL; P
ESTHER : Iwasa_2009_J.Viral.Hepat_16_716
PubMedSearch : Iwasa_2009_J.Viral.Hepat_16_716
PubMedID: 19302338

Title : [The effect of a cholinesterase inhibitor on the vitality in Alzheimer disease] -
Author(s) : Toba K , Moriya Y , Nakai R , Iwata A , Kobayashi Y , Sonohara K , Hasegawa H , Kozaki K
Ref : Nihon Ronen Igakkai Zasshi , 46 :269 , 2009
PubMedID: 19521049

Title : [Localized cerebral blood flow changes in response to ADL-related vitality in elderly patients with dementia using single photon emission computed tomography] - Sonohara_2008_Nippon.Ronen.Igakkai.Zasshi_45_615
Author(s) : Sonohara K , Toba K , Nakai R , Kobayashi Y , Moriya Y , Hasegawa H , Kozaki K , Matsuda H
Ref : Nippon Ronen Igakkai Zasshi , 45 :615 , 2008
Abstract : AIM: To clarify the area in the brain related to responsible for vitality and volition.
METHODS: We studied 123 outpatients (39 men, 84 women, 77.7+/-6.7 years old) who visited the Center for comprehensive care on memory disorders in Kyorin University Hospital. No patients were prescribed with anti-depressants, anti-anxiety agents, psychomimetics, acetylcholinesterase inhibitors, Chinese herbal medicines or cerebrovascular circulation modifying drugs. Patients with frontotemporal dementia or depression were excluded. ADL-related vitality and volition was measured by a vitality index. Cerebral brain blood flow was measured by single photon emission computed tomography (99mTc-ECD SPECT). Relative blood flow changes were calculated by Statistical Parametric Mapping (SPM). Absolute blood flow changes were calculated by a three-dimensional stereotaxic ROI template on anatomically standardised 99mTc-ECD SPECT (3D SRT). Statistically significant correlations between semi-quantitatively measured scores of vitality index and blood flow changes in SPM and 3D-SRT were tested and displayed on a brain map.
RESULTS: Analysis of relative and absolute blood flow showed that the common responsible area in the brain related to vitality was the frontal lobe, fronto-cingulate gyrus, temporal lobe, basal ganglia (caudate nucleus) and thalamus. Blood flow changes in the orbital gyrus were strongly correlated with vitality index specially in the frontal lobe.
CONCLUSION: ADL-related vitality is affected mainly by the blood flow in the frontal-subcortical circuit. However, deep white matter was also important to determine vitality and volition.
ESTHER : Sonohara_2008_Nippon.Ronen.Igakkai.Zasshi_45_615
PubMedSearch : Sonohara_2008_Nippon.Ronen.Igakkai.Zasshi_45_615
PubMedID: 19179793

Title : Regulation of hormone-sensitive lipase expression by saturated fatty acids and hormones in bovine mammary epithelial cells - Yonezawa_2008_Biochem.Biophys.Res.Commun_376_36
Author(s) : Yonezawa T , Haga S , Kobayashi Y , Katoh K , Obara Y
Ref : Biochemical & Biophysical Research Communications , 376 :36 , 2008
Abstract : Hormone-sensitive lipase was firstly identified as an epinephrine-induced lipase in adipocyte. HSL mRNA was detected by RT-PCR in cloned bovine mammary epithelial cells (bMEC) and bovine lactating mammary gland. Saturated fatty acids (stearate and palmitate), but not unsaturated fatty acids (oleate and linoleate) induced up-regulation of HSL mRNA in a time- and concentration-dependent manner in bMEC. Treatment with insulin (5-10 ng/ml), dexamethasone (50-250 nM) or GH (50 ng/ml) induced down-regulation of HSL. These results suggest that HSL was regulated by fatty acids and some hormones in mammary epithelial cells and thereby play an important role of lipid and energy metabolism.
ESTHER : Yonezawa_2008_Biochem.Biophys.Res.Commun_376_36
PubMedSearch : Yonezawa_2008_Biochem.Biophys.Res.Commun_376_36
PubMedID: 18755148

Title : ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe - Matsuyama_2006_Nat.Biotechnol_24_841
Author(s) : Matsuyama A , Arai R , Yashiroda Y , Shirai A , Kamata A , Sekido S , Kobayashi Y , Hashimoto A , Hamamoto M , Hiraoka Y , Horinouchi S , Yoshida M
Ref : Nat Biotechnol , 24 :841 , 2006
Abstract : Cloning of the entire set of an organism's protein-coding open reading frames (ORFs), or 'ORFeome', is a means of connecting the genome to downstream 'omics' applications. Here we report a proteome-scale study of the fission yeast Schizosaccharomyces pombe based on cloning of the ORFeome. Taking advantage of a recombination-based cloning system, we obtained 4,910 ORFs in a form that is readily usable in various analyses. First, we evaluated ORF prediction in the fission yeast genome project by expressing each ORF tagged at the 3' terminus. Next, we determined the localization of 4,431 proteins, corresponding to approximately 90% of the fission yeast proteome, by tagging each ORF with the yellow fluorescent protein. Furthermore, using leptomycin B, an inhibitor of the nuclear export protein Crm1, we identified 285 proteins whose localization is regulated by Crm1.
ESTHER : Matsuyama_2006_Nat.Biotechnol_24_841
PubMedSearch : Matsuyama_2006_Nat.Biotechnol_24_841
PubMedID: 16823372
Gene_locus related to this paper: schpo-APTH1 , schpo-KEX1 , schpo-PLG7 , schpo-SPAC4A8.06C , schpo-SPBC14C8.15 , schpo-SPBPB2B2.02 , schpo-SPCC5E4.05C , schpo-SPCC417.12 , schpo-yeld , schpo-yk68 , schpo-clr3

Title : Effects of pesticides on the peripheral and central nervous system in tobacco farmers in Malaysia: studies on peripheral nerve conduction, brain-evoked potentials and computerized posturography - Kimura_2005_Ind.Health_43_285
Author(s) : Kimura K , Yokoyama K , Sato H , Nordin RB , Naing L , Kimura S , Okabe S , Maeno T , Kobayashi Y , Kitamura F , Araki S
Ref : Ind Health , 43 :285 , 2005
Abstract : We examined the effects of pesticides on the central and peripheral nervous system in the setting of a tobacco farm at a developing country. Maximal motor and sensory nerve conduction velocities (MCV and SCV, respectively) in the median, sural and tibial nerves, postural sway, and brain-evoked potentials (auditory event-related and visual-evoked potentials) were measured in 80 male tobacco farmers and age- and sex-matched 40 controls in Kelantan, Malaysia. Median SCV (finger-wrist) in farmers using Delsen (mancozeb, dithiocarbamate fungicide), who showed significant decrease of serum cholinesterase activities, were significantly lower compared with the controls. Sural SCV in farmers using Fastac (alpha-cypermethrin, pyrethroid insecticide) and median MCV (elbow-wrist) in farmers using Tamex (butralin, dinitroaniline herbicide) were significantly slowed compared with their respective controls. In Delsen (mancozeb, dithiocarbamate) users, the power of postural sway of 0-1 Hz was significantly larger than that in the controls both in the anterior-posterior direction with eyes open and in the right-left direction with eyes closed. The former type of sway was also significantly increased in Tamaron (methamidophos, organophosphorus insecticide) users. In conclusion, nerve conduction velocities and postural sway seem to be sensitive indicators of the effects of pesticides on the central and peripheral nervous system.
ESTHER : Kimura_2005_Ind.Health_43_285
PubMedSearch : Kimura_2005_Ind.Health_43_285
PubMedID: 15895843

Title : Efficacy of long-term dietary restriction of total calories, fat, iron, and protein in patients with chronic hepatitis C virus - Iwasa_2004_Nutrition_20_368
Author(s) : Iwasa M , Iwata K , Kaito M , Ikoma J , Yamamoto M , Takeo M , Kuroda M , Fujita N , Kobayashi Y , Adachi Y
Ref : Nutrition , 20 :368 , 2004
Abstract : OBJECTIVES: A diet restrictive in total calories, fat, iron, and protein intake reduces serum alanine aminotransferase levels in patients with long-term hepatitis C virus infection. However, whether long-term dietary therapy causes adverse effects such as malnutrition and anemia due to a shortage of energy intake is not clear. We evaluated the balance of energy intake and changes in physical and hematologic indices of nutrition after a long-term dietary therapy.
METHODS: Twenty-two patients with long-term hepatitis C virus infection that did not respond to or who were able or unwilling to take interferon therapy were enrolled in this study. Our prescriptions included 7 mg/d or less of iron, 30 kcal. kg(-1). d(-1) of energy, 1.1 to 1.2 g. kg(-1). d(-1) of protein, and a fat energy fraction of 20%. Patients were followed for 24 mo.
RESULTS: Mean body fat percentage was 24.6% at entry and was significantly reduced after the diet prescription. Mean serum ferritin decreased significantly from 376 ng/mL at entry to 141 ng/mL after 24 mo. Mean serum alanine aminotransferase levels decreased significantly from 66 to 49 IU/L. Mean levels of hemoglobin, serum albumin, and cholinesterase did not change significantly during the follow-up period.
CONCLUSIONS: These results suggest that restriction of energy, fat, iron, and protein intakes is safely tolerated, so its long-term use should be recommended to patients with long-term infection with hepatitis C virus.
ESTHER : Iwasa_2004_Nutrition_20_368
PubMedSearch : Iwasa_2004_Nutrition_20_368
PubMedID: 15043853

Title : Molecular modeling of the dimeric structure of human lipoprotein lipase and functional studies of the carboxyl-terminal domain - Kobayashi_2002_Eur.J.Biochem_269_4701
Author(s) : Kobayashi Y , Nakajima T , Inoue I
Ref : European Journal of Biochemistry , 269 :4701 , 2002
Abstract : Lipoprotein lipase (LPL) plays a key role in lipid metabolism. Molecular modeling of dimeric LPL was carried out using insight ii based upon the crystal structures of human, porcine, and horse pancreatic lipase. The dimeric model reveals a saddle-shaped structure and the key heparin-binding residues in the amino-terminal domain located on the top of this saddle. The models of two dimeric conformations - a closed, inactive form and an open, active form - differ with respect to how surface-loop positions affect substrate access to the catalytic site. In the closed form, the surface loop covers the catalytic site, which becomes inaccessible to solvent. Large conformational changes in the open form, especially in the loop and carboxyl-terminal domain, allow substrate access to the active site. To dissect the structure-function relationships of the LPL carboxyl-terminal domain, several residues predicted by the model structure to be essential for the functions of heparin binding and substrate recognition were mutagenized. Arg405 plays an important role in heparin binding in the active dimer. Lys413/Lys414 or Lys414 regulates heparin affinity in both monomeric and dimeric forms. To evaluate the prediction that LPL forms a homodimer in a 'head-to-tail' orientation, two inactive LPL mutants - a catalytic site mutant (S132T) and a substrate-recognition mutant (W390A/W393A/W394A) - were cotransfected into COS7 cells. Lipase activity could be recovered only when heterodimerization occurred in a head-to-tail orientation. After cotransfection, 50% of the wild-type lipase activity was recovered, indicating that lipase activity is determined by the interaction between the catalytic site on one subunit and the substrate-recognition site on the other.
ESTHER : Kobayashi_2002_Eur.J.Biochem_269_4701
PubMedSearch : Kobayashi_2002_Eur.J.Biochem_269_4701
PubMedID: 12230584

Title : The complete genome sequence of the gram-positive bacterium Bacillus subtilis - Kunst_1997_Nature_390_249
Author(s) : Kunst F , Ogasawara N , Moszer I , Albertini AM , Alloni G , Azevedo V , Bertero MG , Bessieres P , Bolotin A , Borchert S , Borriss R , Boursier L , Brans A , Braun M , Brignell SC , Bron S , Brouillet S , Bruschi CV , Caldwell B , Capuano V , Carter NM , Choi SK , Cordani JJ , Connerton IF , Cummings NJ , Daniel RA , Denziot F , Devine KM , Dusterhoft A , Ehrlich SD , Emmerson PT , Entian KD , Errington J , Fabret C , Ferrari E , Foulger D , Fritz C , Fujita M , Fujita Y , Fuma S , Galizzi A , Galleron N , Ghim SY , Glaser P , Goffeau A , Golightly EJ , Grandi G , Guiseppi G , Guy BJ , Haga K , Haiech J , Harwood CR , Henaut A , Hilbert H , Holsappel S , Hosono S , Hullo MF , Itaya M , Jones L , Joris B , Karamata D , Kasahara Y , Klaerr-Blanchard M , Klein C , Kobayashi Y , Koetter P , Koningstein G , Krogh S , Kumano M , Kurita K , Lapidus A , Lardinois S , Lauber J , Lazarevic V , Lee SM , Levine A , Liu H , Masuda S , Mauel C , Medigue C , Medina N , Mellado RP , Mizuno M , Moestl D , Nakai S , Noback M , Noone D , O'Reilly M , Ogawa K , Ogiwara A , Oudega B , Park SH , Parro V , Pohl TM , Portelle D , Porwollik S , Prescott AM , Presecan E , Pujic P , Purnelle B , Rapoport G , Rey M , Reynolds S , Rieger M , Rivolta C , Rocha E , Roche B , Rose M , Sadaie Y , Sato T , Scanlan E , Schleich S , Schroeter R , Scoffone F , Sekiguchi J , Sekowska A , Seror SJ , Serror P , Shin BS , Soldo B , Sorokin A , Tacconi E , Takagi T , Takahashi H , Takemaru K , Takeuchi M , Tamakoshi A , Tanaka T , Terpstra P , Togoni A , Tosato V , Uchiyama S , Vandebol M , Vannier F , Vassarotti A , Viari A , Wambutt R , Wedler H , Weitzenegger T , Winters P , Wipat A , Yamamoto H , Yamane K , Yasumoto K , Yata K , Yoshida K , Yoshikawa HF , Zumstein E , Yoshikawa H , Danchin A
Ref : Nature , 390 :249 , 1997
Abstract : Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.
ESTHER : Kunst_1997_Nature_390_249
PubMedSearch : Kunst_1997_Nature_390_249
PubMedID: 9384377
Gene_locus related to this paper: bacsu-CAH , bacsu-cbxnp , bacsu-lip , bacsu-LIPB , bacsu-PKSR , bacsu-pnbae , bacsu-PPSE , bacsu-srf4 , bacsu-srfac , bacsu-YBAC , bacsu-YBDG , bacsu-ybfk , bacsu-ycgS , bacsu-yczh , bacsu-YDEN , bacsu-ydjp , bacsu-yfhM , bacsu-yisY , bacsu-YITV , bacsu-yjau , bacsu-YJCH , bacsu-MHQD , bacsu-yqjl , bacsu-yqkd , bacsu-YRAK , bacsu-YTAP , bacsu-YTMA , bacsu-YTPA , bacsu-ytxm , bacsu-yugF , bacsu-YUII , bacsu-YUKL , bacsu-YVAK , bacsu-YvaM , bacsu-RsbQ

Title : Systematic sequencing of the 283 kb 210 degrees-232 degrees region of the Bacillus subtilis genome containing the skin element and many sporulation genes - Mizuno_1996_Microbiology_142 ( Pt 11)_3103
Author(s) : Mizuno M , Masuda S , Takemaru K , Hosono S , Sato T , Takeuchi M , Kobayashi Y
Ref : Microbiology , 142 ( Pt 11) :3103 , 1996
Abstract : As part of the Bacillus subtilis genome sequencing project, we have determined a 283 kb contiguous sequence from 210 degrees to 232 degrees of the B. subtilis genome. This region contains the 48 kb skin element which is excised during sporulation by a site-specific recombinase. In this region, 310 complete ORFs and one tRNA gene were identified: 66 ORFs have been sequenced and characterized previously by other workers, e.g. acc, ans, bfm, blt, bmr, comE, comG, dnaK, rpoD and sin operons; cwiA, gpr and lysA genes; many sporulation genes and operons, spo0A, spoIIA, spoIIM, spoiiP, spoIIIA, spoIIIC, spoIVB, spoIVCA, spoIVCB and spoVA, etc. The products of 84 ORFs were found to display significant similarity to proteins with known function in data banks, e.g., proteins involved in nucleotide metabolism, lipid biosynthesis, amino acid transport (ABC transporter), phosphate-specific transport, the glycine cleavage system, the two-component regulatory system, cell wall autolysis, ferric uptake and sporulation. However, the functions of more than half of the ORFs (52%, 160 ORFs) are still unknown. In the skin element containing 60 ORFs, 32 ORFs (53%) encode proteins which have significant homology to gene products of the B. subtilis temperate phage phi 105 and/or the defective phage PBSX.
ESTHER : Mizuno_1996_Microbiology_142 ( Pt 11)_3103
PubMedSearch : Mizuno_1996_Microbiology_142 ( Pt 11)_3103
PubMedID: 8969508
Gene_locus related to this paper: bacsu-yqjl , bacsu-yqkd

Title : Molecular cloning and sequence analysis of the scpZ gene encoding the serine carboxypeptidase of Absidia zychae - Lee_1995_Curr.Genet_27_159
Author(s) : Lee BR , Takeuchi M , Kobayashi Y
Ref : Curr Genet , 27 :159 , 1995
Abstract : Carboxypeptidase Z is a serine carboxypeptidase secreted by Absidia zychae NRIC 1199. The cDNA and genomic DNA carrying the scpZ gene encoding carboxypeptidase Z were cloned and sequenced. The nucleotide sequences of the cDNA (1.4 kb) and the genomic DNA (3.3 kb) were analyzed and the intervening sequences were located by a comparison of the two. It was found that the scpZ gene was interrupted by 11 short introns, 50-75 nucleotides in length. Genomic Southern analysis showed that there was only one scpZ gene in the genome of A. zychae. The gene encoded a putative pre-pro-enzyme composed of 409 amino-acid residues of the mature carboxypeptidase Z (M(r) 45,421) and an additional N-terminal sequence of 51 amino-acid residues. The amino-acid sequence around the active serine residue of carboxypeptidase Z (-G-E-S-Y-G-G-) differed from the consensus (-G-E-S-Y-A-G-) which is conserved in most of the serine carboxypeptidases so far analyzed.
ESTHER : Lee_1995_Curr.Genet_27_159
PubMedSearch : Lee_1995_Curr.Genet_27_159
PubMedID: 7788719
Gene_locus related to this paper: abszy-SPCZ