Kimura T

References (43)

Title : Quantification of lipoprotein lipase in mouse plasma with a sandwich enzyme-linked immunosorbent assay - Kimura_2024_J.Lipid.Res_65_100532
Author(s) : Kimura T , Miyashita K , Fukamachi I , Fukamachi K , Ogura K , Yokoyama E , Tsunekawa K , Nagasawa T , Ploug M , Yang Y , Song W , Young SG , Beigneux AP , Nakajima K , Murakami M
Ref : J Lipid Res , 65 :100532 , 2024
Abstract : To support in vivo and in vitro studies of intravascular triglyceride metabolism in mice, we created rat monoclonal antibodies (mAbs) against mouse LPL. Two mAbs, mAbs 23A1 and 31A5, were used to develop a sandwich ELISA for mouse LPL. The detection of mouse LPL by the ELISA was linear in concentrations ranging from 0.31 ng/ml to 20 ng/ml. The sensitivity of the ELISA made it possible to quantify LPL in serum and in both pre-heparin and post-heparin plasma samples (including in grossly lipemic samples). LPL mass and activity levels in the post-heparin plasma were lower in Gpihbp1(-/-) mice than in wild-type mice. In both groups of mice, LPL mass and activity levels were positively correlated. Our mAb-based sandwich ELISA for mouse LPL will be useful for any investigator who uses mouse models to study LPL-mediated intravascular lipolysis.
ESTHER : Kimura_2024_J.Lipid.Res_65_100532
PubMedSearch : Kimura_2024_J.Lipid.Res_65_100532
PubMedID: 38608546
Gene_locus related to this paper: mouse-lipli

Title : Impact of Total Parenteral Nutrition on Preoperative Management of Pediatric Living-Donor Liver Transplantation for Biliary Atresia Under 2 Years Old - Ueno_2024_Transplant.Proc__
Author(s) : Ueno T , Takase K , Deguchi K , Nomura M , Watanabe M , Kamiyama M , Tazuke Y , Kimura T , Okuyama H
Ref : Transplant Proc , : , 2024
Abstract : BACKGROUND: Liver failure and gastrointestinal bleeding occur in the end-stage of biliary atresia (BA). Living-donor liver transplantation (LDLT) is a standard treatment in Japan. Our program actively provides pre-transplant total parenteral nutrition (TPN) for such patients, and here we report its efficiency and safety. METHODS: Patients with BA for whom LDLT was indicated were identified. Those with a long-term external central venous catheter and TPN, longer than 4 weeks before LDLT, were analyzed. Ascites was controlled with diuretics. TPN indications, efficacy, and complications were assessed along with patient growth, biochemical markers, and gastrointestinal bleeding. RESULTS: Fourteen patients were included in the study, of whom 8 were girls and 6 were boys. The median age at LDLT was 0.9 years. Body weight (BW) at TPN initiation averaged 6799 g, and the median serum total bilirubin was 9.5 mg per dL. The median catheterization duration was 54 days, and 1 patient received home TPN. Indications for TPN were gastrointestinal bleeding and/or massive esophageal varices in 4 patients and poor nutritional status in 10 patients. No complications were observed except for 1 catheter infection and 1 catheter occlusion. The median final body weight before LDLT was 7906 g. The mean rate of BW gain was significantly higher after TPN than before (149 vs 32 g/wk, respectively, P = .0002). Mean prothrombin time and levels of albumin, cholinesterase, and total bilirubin were not significantly different at the start and end of TPN. CONCLUSIONS: Pre-transplant TPN was safe and effective for patients with end-stage BA.
ESTHER : Ueno_2024_Transplant.Proc__
PubMedSearch : Ueno_2024_Transplant.Proc__
PubMedID: 38326201

Title : Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells - Song_2022_J.Clin.Invest_132_
Author(s) : Song W , Beigneux AP , Winther AL , Kristensen KK , Gronnemose AL , Yang Y , Tu Y , Munguia P , Morales J , Jung H , de Jong PJ , Jung CJ , Miyashita K , Kimura T , Nakajima K , Murakami M , Birrane G , Jiang H , Tontonoz P , Ploug M , Fong LG , Young SG
Ref : J Clinical Investigation , 132 : , 2022
Abstract : GPIHBP1, an endothelial cell (EC) protein, captures lipoprotein lipase (LPL) within the interstitial spaces (where it is secreted by myocytes and adipocytes) and transports it across ECs to its site of action in the capillary lumen. GPIHBP1's 3-fingered LU domain is required for LPL binding, but the function of its acidic domain (AD) has remained unclear. We created mutant mice lacking the AD and found severe hypertriglyceridemia. As expected, the mutant GPIHBP1 retained the capacity to bind LPL. Unexpectedly, however, most of the GPIHBP1 and LPL in the mutant mice was located on the abluminal surface of ECs (explaining the hypertriglyceridemia). The GPIHBP1-bound LPL was trapped on the abluminal surface of ECs by electrostatic interactions between the large basic patch on the surface of LPL and negatively charged heparan sulfate proteoglycans (HSPGs) on the surface of ECs. GPIHBP1 trafficking across ECs in the mutant mice was normalized by disrupting LPL-HSPG electrostatic interactions with either heparin or an AD peptide. Thus, GPIHBP1's AD plays a crucial function in plasma triglyceride metabolism; it sheathes LPL's basic patch on the abluminal surface of ECs, thereby preventing LPL-HSPG interactions and freeing GPIHBP1-LPL complexes to move across ECs to the capillary lumen.
ESTHER : Song_2022_J.Clin.Invest_132_
PubMedSearch : Song_2022_J.Clin.Invest_132_
PubMedID: 35229724

Title : GPIHBP1 autoantibody is an independent risk factor for the recurrence of hypertriglyceridemia-induced acute pancreatitis - Zhang_2022_J.Clin.Lipidol__
Author(s) : Zhang G , Yang Q , Mao W , Hu Y , Pu N , Deng H , Yu X , Zhang J , Zhou J , Ye B , Li G , Li B , Ke L , Tong Z , Murakami M , Kimura T , Nakajima K , Cao W , Liu Y , Li W
Ref : J Clin Lipidol , : , 2022
Abstract : BACKGROUND: GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, is a crucial partner for lipoprotein lipase (LPL) in plasma triglyceride metabolism. GPIHBP1 autoantibodies block LPL binding to GPIHBP1 and lead to severe hypertriglyceridemia (HTG) and HTG-induced acute pancreatitis (HTG-AP). We sought to define the incidence of GPIHBP1 autoantibodies in patients with HTG-AP. OBJECTIVE: We determined the incidence of GPIHBP1 autoantibody in HTG-AP patients, and compared the clinical features and long-term outcomes between GPIHBP1 autoantibody-positive and negative groups. METHODS: An enzyme-linked immunosorbent assay was used to screen for GPIHBP1 autoantibody in 116 HTG-AP patients hospitalized from Jan 1, 2015 to Aug 31, 2019. All patients were followed up for 24 months. The primary outcome was the recurrence rate of HTG-AP during the two-year follow-up period. The incidence of recurrent episodes was analyzed by the Kaplan-Meier method and multivariable Cox regression was used to identify risk factors. RESULTS: GPIHBP1 autoantibodies were present in 17 of 116 study patients (14.66%). The 2-year recurrence rate of HTG-AP was much higher in the GPIHBP1 autoantibody-positive group (35%, 6 in 17) than in the negative group (4%, 4 in 99). The multivariable Cox regression analysis showed that GPIHBP1 autoantibody was an independent risk factor for HTG-AP recurrence in two years. CONCLUSIONS: The presence of GPIHBP1 autoantibody is common in patients with HTG-AP, and is an independent risk factor for two-year recurrence of HTG-AP.
ESTHER : Zhang_2022_J.Clin.Lipidol__
PubMedSearch : Zhang_2022_J.Clin.Lipidol__
PubMedID: 36064883

Title : Serum cholinesterase as a prognostic biomarker for acute heart failure - Shiba_2021_Eur.Heart.J.Acute.Cardiovasc.Care__
Author(s) : Shiba M , Kato T , Morimoto T , Yaku H , Inuzuka Y , Tamaki Y , Ozasa N , Seko Y , Yamamoto E , Yoshikawa Y , Kitai T , Yamashita Y , Iguchi M , Nagao K , Kawase Y , Morinaga T , Toyofuku M , Furukawa Y , Ando K , Kadota K , Sato Y , Kuwahara K , Kimura T
Ref : Eur Heart J Acute Cardiovasc Care , : , 2021
Abstract : AIMS: The association between serum cholinesterase and prognosis in acute heart failure (AHF) remains to be elucidated. We investigated the serum cholinesterase level at discharge from hospitalization for AHF and its association with clinical outcomes in patients with AHF. METHODS AND RESULTS: Among 4056 patients enrolled in the Kyoto Congestive Heart Failure multicentre registry, we analysed 2228 patients with available serum cholinesterase data. The study population was classified into three groups according to serum cholinesterase level at discharge: low tertile (<180 U/L, N = 733), middle tertile (<=180 U/L and <240 U/L, N = 746), and high tertile (<=240 U/L, N = 749). Patients in the low tertile had higher tricuspid pressure gradient, greater inferior vena cava diameter, and higher brain natriuretic peptide (BNP) levels than those in the high tertile. The cumulative 1-year incidence of the primary outcome measure (a composite endpoint of all-cause death and hospitalization for HF) was higher in the low and middle tertiles than in the high tertile [46.5% (low tertile) and 31.4% (middle tertile) vs. 22.1% (high tertile), P < 0.0001]. After adjustment for 26 variables, the excess risk of the low tertile relative to the high tertile for the primary outcome measure remained significant (hazard ratio 1.37, 95% confidence interval 1.10-1.70, P = 0.006). Restricted cubic spline models below the median of cholinesterase demonstrated incrementally higher hazards at low cholinesterase levels. CONCLUSIONS: Low serum cholinesterase levels are associated with congestive findings on echocardiography, higher BNP, and higher risks for a composite of all-cause death and HF hospitalization in patients with AHF.
ESTHER : Shiba_2021_Eur.Heart.J.Acute.Cardiovasc.Care__
PubMedSearch : Shiba_2021_Eur.Heart.J.Acute.Cardiovasc.Care__
PubMedID: 33580775

Title : Significance of a family-6 carbohydrate-binding module in a modular feruloyl esterase for removing ferulic acid from insoluble wheat arabinoxylan - Mamiya_2020_Enzyme.Microb.Technol_138_109546
Author(s) : Mamiya A , Sakka M , Kosugi A , Katsuzaki H , Tanaka A , Kunitake E , Kimura T , Sakka K
Ref : Enzyme Microb Technol , 138 :109546 , 2020
Abstract : Ruminiclostridium josui Fae1A is a modular enzyme consisting of an N-terminal signal peptide, family-1 carbohydrate esterase module (CE1), family-6 carbohydrate-binding module (CBM6), and dockerin module in that order. Recombinant CE1 and CBM6 polypeptides were collectively and separately produced as RjFae1A, RjCE1, and RjCBM6. RjFae1A showed higher feruloyl esterase activity than RjCE1 towards insoluble wheat arabinoxylan, but the latter was more active towards small synthetic substrates than the former. This suggests that CBM6 in RjFae1A plays an important role in releasing ferulic acid from the native substrate. RjCBM6 showed a higher affinity for soluble wheat arabinoxylan than for rye arabinoxylan and beechwood xylan in native affinity polyacrylamide gel electrophoresis. Isothermal titration calorimetry analysis demonstrated that RjCBM6 recognized a xylopyranosyl residue at the nonreducing ends of xylooligosaccharides. Moreover, it showed exceptional affinity for 2(3)-alpha-l-arabinofuranosyl-xylotriose (A(2)XX) among the tested branched arabinoxylooligosaccharides. Fluorometric titration analysis demonstrated that xylobiose and A(2)XX competitively bound to RjCBM6, and both bound to the same site in RjCBM6. RjCBM6's preference for the xylopyranosyl residue at the nonreducing end of xylan chains explains why the positive effect of CBM6 on RjFae1A activity was observed only during short incubation but not after extended incubation.
ESTHER : Mamiya_2020_Enzyme.Microb.Technol_138_109546
PubMedSearch : Mamiya_2020_Enzyme.Microb.Technol_138_109546
PubMedID: 32527521

Title : Prognostic significance of serum cholinesterase in patients with acute decompensated heart failure: a prospective comparative study with other nutritional indices - Seo_2019_Am.J.Clin.Nutr_110_330
Author(s) : Seo M , Yamada T , Tamaki S , Morita T , Furukawa Y , Iwasaki Y , Kawasaki M , Kikuchi A , Kawai T , Abe M , Nakamura J , Yamamoto K , Kayama K , Kawahira M , Tanabe K , Kimura T , Ueda K , Sakamoto D , Sakata Y , Fukunami M
Ref : Am J Clin Nutr , 110 :330 , 2019
Abstract : BACKGROUND: Nutritional status is associated with poor outcomes in patients with heart failure. Serum cholinesterase (CHE) concentration, a marker of malnutrition, was reported to be a prognostic factor in patients with chronic heart failure. The geriatric nutritional risk index (GNRI), the controlling nutritional status (CONUT) score, and the prognostic nutritional index (PNI) are established objective nutritional indices. OBJECTIVE: The aim of this study was to clarify the prognostic significance of CHE concentration and to compare it with other well-established objective nutritional indices in patients with acute decompensated heart failure (ADHF). METHODS: We prospectively enrolled 371 consecutive patients admitted for ADHF with survival discharge. Laboratory data including CHE and the objective nutritional indices were obtained at discharge. The primary endpoint of this study was all-cause mortality. RESULTS: During a mean +/- SD follow-up period of 2.5 +/- 1.4 y, 112 patients died. CHE concentration was significantly associated with all-cause mortality independently of GNRI, CONUT score, or PNI, after adjustment for major confounders including other nutritional indices, such as age, sex, systolic blood pressure, BMI, left ventricular ejection fraction, history of hypertension, diabetes mellitus, dyslipidemia, prior heart failure hospitalization, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, beta-blocker use, statin use, hemoglobin, sodium, blood urea nitrogen, albumin, C-reactive protein, and brain natriuretic peptide concentrations via multivariable Cox analysis. Kaplan-Meier analysis revealed that the risk of all-cause mortality significantly increased in accordance with CHE stratum [lowest tertile: 53%, adjusted HR: 6.92; 95% CI: 3.87, 12.36, compared with middle tertile: 28%, adjusted HR: 2.72; 95% CI: 1.45, 5.11, compared with highest tertile: 11%, adjusted HR: 1.0 (reference), P < 0.0001]. CHE showed the best area under the curve value (0.745) for the prediction of all-cause mortality compared with the other objective nutritional indices. Net reclassification improvement afforded by adding CHE to the fully adjusted multivariable model was statistically significant for all-cause mortality (0.330; 95% CI: 0.112, 0.549, P = 0.0030). CONCLUSION: CHE is a simple, strong prognostic marker for the prediction of all-cause mortality in patients with ADHF.
ESTHER : Seo_2019_Am.J.Clin.Nutr_110_330
PubMedSearch : Seo_2019_Am.J.Clin.Nutr_110_330
PubMedID: 31161211

Title : Perinatal veterinary medicine-related evaluation in hematological and serum biochemical profiles of experimental beagles throughout pregnancy and parturition - Kimura_2018_Animal.Model.Exp.Med_1_282
Author(s) : Kimura T , Kotani K
Ref : Animal Model Exp Med , 1 :282 , 2018
Abstract : Background: The aims of this study were (a) to ascertain age-related changes in the reference values in hematological and serum biochemical examinations of beagles, and (b) to clarify the changes in these findings, including acute phase proteins and oxidative stress, throughout pregnancy and after parturition. Methods: Clinicopathological parameters were measured in young beagles at 6, 9 and 12 months and in adult beagles aged from 24 to 60 months. Likewise, pregnant beagles were investigated throughout the pregnancy and after parturition. Results: Apparent age-related changes were found in erythrocytic parameters during the growth and development of beagles. Most of the parameters (total protein, albumin, blood urea nitrogen, creatinine, urate, alkaline phosphatase (ALP) and creatine kinase (CK) exhibited age-dependent transitions. White cell count significantly increased after 30 days of pregnancy. The values of erythrocytic parameters moderately decreased during the second half of the pregnancy. Triglycerides, total cholesterol, free cholesterol and phospholipid concentrations increased in the mid- and late stages of pregnancy. ALP, lactate dehydrogenase, CK and cholinesterase activities markedly increased during pregnancy and/or after parturition. C-reactive protein (CRP) concentrations gradually increased and reached a maximum after 30-40 days of pregnancy. Serum amyloid A (SAA) levels markedly increased at 30 days of pregnancy before subsiding, and then increased again 3 days after parturition. Reactive oxygen metabolites (d-ROMs) showed significant increases after 30 and 40 days of pregnancy. Conclusions: Reference values for hematological and serum biochemical examinations should be used for health evaluation of dogs, taking sex, age and the stage of pregnancy into consideration. Measurements of CRP, SAA and d-ROM levels are also useful for assessing maternal conditions in mid-pregnancy.
ESTHER : Kimura_2018_Animal.Model.Exp.Med_1_282
PubMedSearch : Kimura_2018_Animal.Model.Exp.Med_1_282
PubMedID: 30891578

Title : Design, synthesis, and pharmacological evaluation of a novel series of hormone sensitive lipase inhibitor - Ogiyama_2017_Bioorg.Med.Chem_25_4817
Author(s) : Ogiyama T , Yamaguchi M , Kurikawa N , Honzumi S , Terayama K , Nagaoka N , Yamamoto Y , Kimura T , Sugiyama D , Inoue SI
Ref : Bioorganic & Medicinal Chemistry , 25 :4817 , 2017
Abstract : HSL inhibition is a promising approach to the treatment of dyslipidemia. As a result of re-optimization of lead compound 2, we identified novel compound 25a exhibiting potent inhibitory activity against HSL enzyme and cell with high selectivity for cholinesterases (AChE and BuChE). Reflecting its potent in vitro activity, compound 25a exhibited antilipolytic effect in rats at 1mg/kg p.o., which indicated that this novel compound is the most potent orally active HSL inhibitor. Moreover, compound 25a did not show bioactivation liability.
ESTHER : Ogiyama_2017_Bioorg.Med.Chem_25_4817
PubMedSearch : Ogiyama_2017_Bioorg.Med.Chem_25_4817
PubMedID: 28756012
Gene_locus related to this paper: human-LIPE

Title : Role of Hormone-sensitive Lipase in Leptin-Promoted Fat Loss and Glucose Lowering - Takanashi_2017_J.Atheroscler.Thromb_24_1105
Author(s) : Takanashi M , Taira Y , Okazaki S , Takase S , Kimura T , Li CC , Xu PF , Noda A , Sakata I , Kumagai H , Ikeda Y , Iizuka Y , Yahagi N , Shimano H , Osuga JI , Ishibashi S , Kadowaki T , Okazaki H
Ref : J Atheroscler Thromb , 24 :1105 , 2017
Abstract : AIM: Myriad biological effects of leptin may lead to broad therapeutic applications for various metabolic diseases, including diabetes and its complications; however, in contrast to its anorexic effect, the molecular mechanisms underlying adipopenic and glucose-lowering effects of leptin have not been fully understood. Here we aim to clarify the role of hormone-sensitive lipase (HSL) in leptin's action. METHODS: Wild-type (WT) and HSL-deficient (HSLKO) mice were made hyperleptinemic by two commonly-used methods: adenovirus-mediated overexpression of leptin and continuous subcutaneous infusion of leptin by osmotic pumps. The amount of food intake, body weights, organ weights, and parameters of glucose and lipid metabolism were measured. RESULTS: Hyperleptinemia equally suppressed the food intake in WT and HSLKO mice. On the other hand, leptin-mediated fat loss and glucose-lowering were significantly blunted in the absence of HSL when leptin was overexpressed by recombinant adenovirus carrying leptin. By osmotic pumps, the fat-losing and glucose-lowering effects of leptin were milder due to lower levels of hyperleptinemia; although the difference between WT and HSLKO mice did not reach statistical significance, HSLKO mice had a tendency to retain more fat than WT mice in the face of hyperleptinemia. CONCLUSIONS: We clarify for the first time the role of HSL in leptin's effect using a genetic model: leptin-promoted fat loss and glucose-lowering are at least in part mediated via HSL-mediated lipolysis. Further studies to define the pathophysiological role of adipocyte lipases in leptin action may lead to a new therapeutic approach to circumvent leptin resistance.
ESTHER : Takanashi_2017_J.Atheroscler.Thromb_24_1105
PubMedSearch : Takanashi_2017_J.Atheroscler.Thromb_24_1105
PubMedID: 28413180

Title : The role of plasma lipoprotein lipase, hepatic lipase and GPIHBP1 in the metabolism of remnant lipoproteins and small dense LDL in patients with coronary artery disease - Muraba_2017_Clin.Chim.Acta_476_146
Author(s) : Muraba Y , Koga T , Shimomura Y , Ito Y , Hirao Y , Kobayashi J , Kimura T , Nakajima K , Murakami M
Ref : Clinica Chimica Acta , 476 :146 , 2017
Abstract : BACKGROUND: The relationship between plasma lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), glycosylphosphatidylinositol anchored HDL binding protein1 (GPIHBP1) concentration and the metabolism of remnant lipoproteins (RLP) and small dense LDL (sdLDL) in patients with coronary artery disease (CAD) is not fully elucidated. METHODS: One hundred patients who underwent coronary angiography were enrolled. The plasma LPL, HTGL and GPIHBP1 concentrations were determined by ELISA. The time dependent changes in those lipases, lipids and lipoproteins were studied at a time-point just before, and 15min, 4h and 24h after heparin administration. RESULTS: The LPL concentration exhibited a significant positive correlation with HDL-C, and inversely correlated with TG and RLP-C. The HTGL concentration was positively correlated with RLP-C and sdLDL-C. The HTGL ratio of the pre-heparin/post-heparin plasma concentration and sdLDL-C/LDL-C ratio were significantly greater in CAD patients than in non-CAD patients. GPIHBP1 was positively correlated with LPL and inversely correlated with RLP-C and sdLDL-C. CONCLUSION: The HTGL concentration was positively correlated with RLP-C and sdLDL-C, while LPL and GPIHBP1 were inversely correlated with RLP-C and sdLDL-C. These results suggest that elevated HTGL is associated with increased CAD risk, while elevated LPL is associated with a reduction of CAD risk.
ESTHER : Muraba_2017_Clin.Chim.Acta_476_146
PubMedSearch : Muraba_2017_Clin.Chim.Acta_476_146
PubMedID: 29174344
Gene_locus related to this paper: human-LIPC , human-LPL

Title : Lipoprotein-associated phospholipase A2 is related to risk of subclinical atherosclerosis but is not supported by Mendelian randomization analysis in a general Japanese population - Ueshima_2016_Atherosclerosis_246_141
Author(s) : Ueshima H , Kadowaki T , Hisamatsu T , Fujiyoshi A , Miura K , Ohkubo T , Sekikawa A , Kadota A , Kadowaki S , Nakamura Y , Miyagawa N , Okamura T , Kita Y , Takashima N , Kashiwagi A , Maegawa H , Horie M , Yamamoto T , Kimura T , Kita T
Ref : Atherosclerosis , 246 :141 , 2016
Abstract : OBJECTIVE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme predominantly bound to low-density lipoprotein (LDL). Lp-PLA2 is recognized as playing a key role in inflammatory processes and the development of atherosclerosis. This study aimed to investigate whether Lp-PLA2 is related to subclinical atherosclerosis, independently from traditional risk factors, in a general Japanese population by analyses of both the observational study and Mendelian randomization using V279F polymorphism. METHODS AND
RESULTS: We cross-sectionally examined community-based sample of 929 Japanese men aged 40-79 years, without statin treatment, who were randomly selected from the resident registration. Multiple regression analyses of Lp-PLA2 activity and concentration were undertaken separately for men aged 40-49 years and 50-79 years, to clarify interactions of age and Lp-PLA2. Lp-PLA2 activity for men aged 50-79 years was significantly and positively related to intima-media thickness (IMT) (P = 0.013) and plaque index (P = 0.008) independent of traditional risk factors including small LDL particles, but not to coronary artery calcification (CAC) score. Associations with Lp-PLA2 concentration were qualitatively similar to those of activity. Corresponding relationships were not observed in men aged 40-49 years. Mendelian randomization analyses based on V279F genotype did not show any significant associations with subclinical atherosclerosis, although the homozygote and heterozygote of V279F showed low Lp-PLA2 activity and concentration.
CONCLUSIONS: Lp-PLA2 activity in Japanese men aged 50-79 years was associated significantly and positively with IMT and plaque in the carotid artery but Mendelian randomization did not support that Lp-PLA2 is a causative factor for subclinical atherosclerosis.
ESTHER : Ueshima_2016_Atherosclerosis_246_141
PubMedSearch : Ueshima_2016_Atherosclerosis_246_141
PubMedID: 26775119

Title : Impact of pretreatment serum cholinesterase level in unresectable advanced hepatocellular carcinoma patients treated with sorafenib - Takeda_2013_Mol.Clin.Oncol_1_241
Author(s) : Takeda H , Nishikawa H , Iguchi E , Ohara Y , Sakamoto A , Hatamaru K , Henmi S , Saito S , Nasu A , Komekado H , Kita R , Kimura T , Osaki Y
Ref : Mol Clin Oncol , 1 :241 , 2013
Abstract : The value of serum cholinesterase (ChE) level as a predictive marker in sorafenib therapy for advanced hepatocellular carcinoma (HCC) has not yet been investigated. The present retrospective study therefore analyzed the impact of the serum ChE level in 93 patients with advanced HCC treated with sorafenib. Patients were categorized into two groups: group A with pretreatment serum ChE >/=140 IU/l (n=46) and group B with pretreatment serum ChE <140 IU/l (n=47). The correlation between clinicopathological findings, including serum ChE level, and overall survival (OS) and liver damage during sorafenib therapy was investigated. The median OS of the patients was 275 days, while OS was markedly higher in group A compared to group B (P=0.002). In 70 Child-Pugh A patients, serum ChE level was a significant prognostic predictor in multivariate analysis [P=0.019, hazard ratio (HR) =2.612; 95% confidence interval (CI), 1.174-5.810]. During sorafenib treatment, 22 patients developed liver dysfunction of grade 3 or higher. Only two group A patients (4.3%) developed liver dysfunction, compared to 20 group B patients (42.6%) (P<0.001). Multivariate analysis demonstrated that the pretreatment serum ChE level was the strongest predictor of liver damage (P=0.002, HR=0.061, 95% CI: 0.010-0.373), indicating serum ChE <140 IU/l to be the only independent predictor associated with severe liver function damage during sorafenib treatment in 70 patients with grade A Child-Pugh (P= 0.016; HR= 0.122; 95% CI, 0.022-0.676). In conclusion, lower serum ChE level is a significant predictor of poor prognosis and severe liver damage in HCC patients treated with sorafenib. Advanced HCC patients with lower serum ChE levels, including those with a Child-Pugh A pretreatment liver function score, should be given sorafenib therapy with caution.
ESTHER : Takeda_2013_Mol.Clin.Oncol_1_241
PubMedSearch : Takeda_2013_Mol.Clin.Oncol_1_241
PubMedID: 24649154

Title : Two cases of Alzheimer's disease showing deterioration of behavioral and psychological symptoms of dementia induced by switching from rivastigmine to donepezil - Kimura_2013_Neuropsychiatr.Dis.Treat_9_49
Author(s) : Kimura T , Takamatsu J
Ref : Neuropsychiatr Dis Treat , 9 :49 , 2013
Abstract : Rivastigmine, galantamine, and memantine, in addition to donepezil, which has been on the market over 10 years, have been available for the treatment of Alzheimer's disease (AD) since 2011 in Japan, leading a new stage in the medical treatment of AD. We studied two AD patients showing sudden deterioration of behavioral and psychological symptoms of dementia (BPSD) associated with switching from rivastigmine to donepezil after the clinical trial of rivastigmine. In the patients, rivastigmine seemed to be more beneficial than donepezil for the control of BPSD. Although It was not obvious whether their different responses to the two cholinesterase inhibitors were due to the different pharmacological profiles, ie, the presence of inhibition of butyrylcholinesterase in rivastigmine, a particular cholinesterase inhibitor might be more effective in particular AD cases. Further investigations are needed to confirm the difference, and to identify the measures for selecting the most appropriate medication for each AD patient.
ESTHER : Kimura_2013_Neuropsychiatr.Dis.Treat_9_49
PubMedSearch : Kimura_2013_Neuropsychiatr.Dis.Treat_9_49
PubMedID: 23293526

Title : The synthesis and structure-activity relationship of substituted N-phenyl anthranilic acid analogs as amyloid aggregation inhibitors - Simons_2009_Bioorg.Med.Chem.Lett_19_654
Author(s) : Simons LJ , Caprathe BW , Callahan M , Graham JM , Kimura T , Lai Y , LeVine H, 3rd , Lipinski W , Sakkab AT , Tasaki Y , Walker LC , Yasunaga T , Ye Y , Zhuang N , Augelli-Szafran CE
Ref : Bioorganic & Medicinal Chemistry Lett , 19 :654 , 2009
Abstract : It is believed that beta-amyloid aggregation is an important event in the development of Alzheimer's disease. In the course of our studies to identify beta-amyloid aggregation inhibitors, a series of N-phenyl anthranilic acid analogs were synthesized and studied for beta-amyloid inhibition activity. The synthesis, structure-activity relationship, and in vivo activity of these analogs are discussed.
ESTHER : Simons_2009_Bioorg.Med.Chem.Lett_19_654
PubMedSearch : Simons_2009_Bioorg.Med.Chem.Lett_19_654
PubMedID: 19121939

Title : Initial synthesis and characterization of an alpha7 nicotinic receptor cellular membrane affinity chromatography column: effect of receptor subtype and cell type - Moaddel_2008_Anal.Chem_80_48
Author(s) : Moaddel R , Oliveira RV , Kimura T , Hyppolite P , Juhaszova M , Xiao Y , Kellar KJ , Bernier M , Wainer IW
Ref : Analytical Chemistry , 80 :48 , 2008
Abstract : In this study, cellular membrane fragments from SH-EP1-pCEP4-halpha7 and alpha7 HEK-293 cell lines were used to synthesize cellular membrane affinity chromatography (CMAC) columns containing functional alpha7 nicotinic acetylcholine receptors, CMAC(alpha7 nAChR) columns. The synthesis of stable columns required the addition of cholesterol to the 2% cholate solubilization/immobilization (s/i) buffer and to the mobile phase. In addition, when membranes from the SH-EP1 cell line were used, l-alpha-phosphatidylserine and l-alpha-phosphatidylethanolamine also had to be added to the s/i buffer. A CMAC(alpha4beta2 nAChR) column was prepared using membrane fragments from a SH-EP1-pCEP4-halpha4beta2 cell line, and this process required the addition of l-alpha-phosphatidylserine and l-alpha-phosphatidylethanolamine to the s/i buffer, but not cholesterol. The s/i buffers from the three columns were compared with the s/i buffer utilized in the preparation of a CMAC(alpha4beta2 nAChR) column prepared using an alpha4beta2 HEK-293 cell line, which required no additions to the 2% cholate s/i buffer. The data demonstrate that both cell type and receptor type affect the protocol required to produce a stable CMAC column and that, at the current time, the development of an optimum immobilization protocol is an empirical process. The results are also consistent with the observation that the alpha7 nAChR is localized in lipid rafts in both of these cell lines and that the cholate detergent removed cholesterol from these microdomains.
ESTHER : Moaddel_2008_Anal.Chem_80_48
PubMedSearch : Moaddel_2008_Anal.Chem_80_48
PubMedID: 18062706

Title : Functional polymorphisms in carboxylesterase1A2 (CES1A2) gene involves specific protein 1 (Sp1) binding sites - Yoshimura_2008_Biochem.Biophys.Res.Commun_369_939
Author(s) : Yoshimura M , Kimura T , Ishii M , Ishii K , Matsuura T , Geshi E , Hosokawa M , Muramatsu M
Ref : Biochemical & Biophysical Research Communications , 369 :939 , 2008
Abstract : Carboxylesterase 1 (CES1) is involved in metabolic activation of a variety of prodrugs into active derivatives and plays an important role in pharmacokinetics. We previously reported that a single nucleotide polymorphism (SNP), -816A/C of the CES1A2 gene associates with the responsiveness to an angiotensin-converting enzyme (ACE) inhibitor, imidapril, whose activity is achieved by CES1. To identify relevant functional polymorphisms, we re-sequenced the CES1A2 promoter region ( approximately 1kb) in 100 Japanese hypertensive patients. Altogether 10 SNPs and one insertion/deletion (I/D) were identified, among which seven SNPs and one I/D residing between -62 and -32 were in almost complete linkage disequilibrium (D'=1.00, r2=0.97). They consisted a minor and a major haplotype, the allele frequencies of which were 22% and 74%, respectively. The minor haplotype possessed two putative Sp1 binding sites while the major haplotype did not have any Sp1 binding site. The minor haplotype had a higher transcription and Sp1 binding activities than the major haplotype, invitro. The original -816A/C was in high linkage disequilibrium with these haplotypes (D'=0.92, r2=0.85), and well agreed with the efficacy of imidapril medication. These results suggest that the Sp1 binding site variation in the CES1A2 promoter is functional, and are good candidates for the pharmacogenetic studies of CES1-activated drugs.
ESTHER : Yoshimura_2008_Biochem.Biophys.Res.Commun_369_939
PubMedSearch : Yoshimura_2008_Biochem.Biophys.Res.Commun_369_939
PubMedID: 18328811
Gene_locus related to this paper: human-CES1

Title : Nafamostat is hydrolysed by human liver cytosolic long-chain acyl-CoA hydrolase - Yamaori_2007_Xenobiotica_37_260
Author(s) : Yamaori S , Ukena E , Fujiyama N , Funahashi T , Kimura T , Yamamoto I , Ohshima T , Matsumura K , Oda M , Watanabe K
Ref : Xenobiotica , 37 :260 , 2007
Abstract : Although the authors recently reported that nafamostat, a clinically used serine protease inhibitor, was mainly hydrolysed by carboxylesterase in human liver microsomes, the involvement of human liver cytosol has not been elucidated. The current study examined the in vitro metabolism of nafamostat with human liver cytosols. Kinetic analysis indicated that the Vmax and Km values in the liver cytosols were 9.82 nmolmin(-1) mg(-1) protein and 197 microM for a liver sample HL-1, and 15.1 nmolmin(-1) mg(-1) protein and 157 microM for HL-2, respectively. The Vmax/Km values in both cytosols were at least threefold higher than those in the corresponding microsomes. The liver cytosolic activity for nafamostat hydrolysis was inhibited by phenylmethylsulfonyl fluoride (PMSF) (43% inhibition at 100 microM), whereas diisopropyl fluorophosphate (DFP) and bis(p-nitrophenyl)phosphate (BNPP) failed to inhibit the activity. Furthermore, the hydrolytic activity was also reduced by palmitoyl-CoA (67% inhibition at 100 microM) but not by acetyl-CoA. Effects of PMSF, DFP and BNPP on cytosolic palmitoyl-CoA hydrolytic activity were comparable with those of the cytosolic nafamostat hydrolytic activity. In addition, the palmitoyl-CoA hydrolytic activity was competitively inhibited by nafamostat with the apparent Ki value of 164 microM for the liver cytosol from HL-2. These results suggest that an isoform of long-chain acyl-CoA hydrolase may be responsible for the nafamostat hydrolysis in human liver cytosol.
ESTHER : Yamaori_2007_Xenobiotica_37_260
PubMedSearch : Yamaori_2007_Xenobiotica_37_260
PubMedID: 17624024

Title : Ameliorative effects of a neuroprotective agent, T-817MA, on place learning deficits induced by continuous infusion of amyloid-beta peptide (1-40) in rats - Nguyen_2007_Hippocampus_17_443
Author(s) : Nguyen PT , Kimura T , Ho SA , Tran AH , Ono T , Nishijo H
Ref : Hippocampus , 17 :443 , 2007
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline due to neuronal loss and neural network dysfunction. It has been postulated that progressive neuronal loss in AD is consequence of the neurotoxic properties of the amyloid-beta peptide (Abeta). In the present study, we investigated the effect of T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy] propyl}-3-azetidinol maleate), a newly synthesized neurotrophic compound, on place learning deficits in rats with hippocampal damages. To induce granule cell loss in the dentate gyrus (DG) of the hippocampus, Abeta (1-40) was continuously infused (300 pmol/day) into the cerebral ventricle using a mini-osmotic pump for 5 weeks. Three weeks after the Abeta infusion, the rats were tested in a place learning task, which required them to alternatively visit two diametrically opposed areas in an open field to obtain intracranial self-stimulation reward. The results indicated that the Abeta-infused rats without treatment of T-817MA displayed learning impairment in the task; their performance level was significantly inferior to that of the vehicle rats. Treatment of T-817MA (8.4 mg/kg/day, p.o.) significantly improved the task performance of the Abeta-infused rats. Furthermore, T-817MA prevented granule cell loss due to Abeta-infusion, which was correlated to task performance of the rats. However, other cognitive enhancer, an acetylcholinesterase inhibitor, had no such effects. The results demonstrated that T-817MA ameliorated learning deficits induced by Abeta infusion, which might be attributed to neuroprotection in the hippocampus.
ESTHER : Nguyen_2007_Hippocampus_17_443
PubMedSearch : Nguyen_2007_Hippocampus_17_443
PubMedID: 17397046

Title : Role of lipoprotein-associated lysophospholipids in migratory activity of coronary artery smooth muscle cells - Damirin_2007_Am.J.Physiol.Heart.Circ.Physiol_292_H2513
Author(s) : Damirin A , Tomura H , Komachi M , Liu JP , Mogi C , Tobo M , Wang JQ , Kimura T , Kuwabara A , Yamazaki Y , Ohta H , Im DS , Sato K , Okajima F
Ref : American Journal of Physiology Heart Circ Physiol , 292 :H2513 , 2007
Abstract : The migration of vascular smooth muscle cells (SMCs) is a hallmark of the pathogenesis of atherosclerosis and restenosis after angioplasty. Plasma low-density lipoprotein (LDL), but not high-density lipoprotein (HDL), induced the migration of human coronary artery SMCs (CASMCs). Among bioactive lipids postulated to be present in LDL, lysophosphatidic acid (LPA) appreciably mimicked the LDL action. In fact, the LDL-induced migration was markedly inhibited by pertussis toxin, an LPA receptor antagonist Ki-16425, and a small interfering RNA (siRNA) targeted for LPA(1) receptors. Moreover, LDL contains a higher amount of LPA than HDL does. HDL markedly inhibited LPA- and platelet-derived growth factor (PDGF)-induced migration, and sphingosine 1-phosphate (S1P), the content of which is about fourfold higher in HDL than in LDL, mimicked the HDL action. The inhibitory actions of HDL and S1P were suppressed by S1P(2) receptor-specific siRNA. On the other hand, the degradation of the LPA component of LDL by monoglyceride lipase or the antagonism of LPA receptors by Ki-16425 allowed LDL to inhibit the PDGF-induced migration. The inhibitory effect of LDL was again suppressed by S1P(2) receptor-specific siRNA. In conclusion, LPA/LPA(1) receptors and S1P/S1P(2) receptors mediate the stimulatory and inhibitory migration response to LDL and HDL, respectively. The balance of not only the content of LPA and S1P in lipoproteins but also the signaling activity between LPA(1) and S1P(2) receptors in the cells may be critical in determining whether the lipoprotein is a positive or negative regulator of CASMC migration.
ESTHER : Damirin_2007_Am.J.Physiol.Heart.Circ.Physiol_292_H2513
PubMedSearch : Damirin_2007_Am.J.Physiol.Heart.Circ.Physiol_292_H2513
PubMedID: 17237247

Title : Involvement of human blood arylesterases and liver microsomal carboxylesterases in nafamostat hydrolysis - Yamaori_2006_Drug.Metab.Pharmacokinet_21_147
Author(s) : Yamaori S , Fujiyama N , Kushihara M , Funahashi T , Kimura T , Yamamoto I , Sone T , Isobe M , Ohshima T , Matsumura K , Oda M , Watanabe K
Ref : Drug Metab Pharmacokinet , 21 :147 , 2006
Abstract : Metabolism of nafamostat, a clinically used serine protease inhibitor, was investigated with human blood and liver enzyme sources. All the enzyme sources examined (whole blood, erythrocytes, plasma and liver microsomes) showed nafamostat hydrolytic activity. V(max) and K(m) values for the nafamostat hydrolysis in erythrocytes were 278 nmol/min/mL blood fraction and 628 microM; those in plasma were 160 nmol/min/mL blood fraction and 8890 microM, respectively. Human liver microsomes exhibited a V(max) value of 26.9 nmol/min/mg protein and a K(m) value of 1790 microM. Hydrolytic activity of the erythrocytes and plasma was inhibited by 5, 5'-dithiobis(2-nitrobenzoic acid), an arylesterase inhibitor, in a concentration-dependent manner. In contrast, little or no suppression of these activities was seen with phenylmethylsulfonyl fluoride (PMSF), diisopropyl fluorophosphate (DFP), bis(p-nitrophenyl)phosphate (BNPP), BW284C51 and ethopropazine. The liver microsomal activity was markedly inhibited by PMSF, DFP and BNPP, indicating that carboxylesterase was involved in the nafamostat hydrolysis. Human carboxylesterase 2 expressed in COS-1 cells was capable of hydrolyzing nafamostat at 10 and 100 microM, whereas recombinant carboxylesterase 1 showed significant activity only at a higher substrate concentration (100 microM). The nafamostat hydrolysis in 18 human liver microsomes correlated with aspirin hydrolytic activity specific for carboxylesterase 2 (r=0.815, p<0.01) but not with imidapril hydrolysis catalyzed by carboxylesterase 1 (r=0.156, p=0.54). These results suggest that human arylesterases and carboxylesterase 2 may be predominantly responsible for the metabolism of nafamostat in the blood and liver, respectively.
ESTHER : Yamaori_2006_Drug.Metab.Pharmacokinet_21_147
PubMedSearch : Yamaori_2006_Drug.Metab.Pharmacokinet_21_147
PubMedID: 16702735

Title : A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity - Geshi_2005_Hypertens.Res_28_719
Author(s) : Geshi E , Kimura T , Yoshimura M , Suzuki H , Koba S , Sakai T , Saito T , Koga A , Muramatsu M , Katagiri T
Ref : Hypertens Res , 28 :719 , 2005
Abstract : Imidapril is an angiotensin-converting enzyme inhibitor that is widely used in treating hypertension, although the responses vary among individuals. We investigated whether a single nucleotide polymorphism at position -816 of the carboxylesterase 1 (CES1) gene, which activates imidapril in the liver, is involved in the responsiveness to imidapril medication. A total of 105 Japanese hypertensives with systolic/diastolic blood pressures (SBP/DBP) of 140/90 mmHg or higher were prescribed 5-10 mg/day of imidapril. At baseline, blood pressure levels were not different between patients with and those without the -816C allele (AA vs. AC+ CC groups). After 8 weeks of treatment, we classified the responders and non-responders based on the decline in their blood pressures, and found that the responder rate was significantly higher in the AC+CC group than in the AA group (p=0.0331). Also, the reduction in SBP was significantly greater in the AC+CC group than in the AA group (24.7+/-11.8 vs. 17.6+/-16.8 mmHg, p=0.0184). Furthermore, an in vitro reporter assay revealed that the -816C construct had significantly higher promoter activity (p<0.0001). These findings suggest that the A(-816)C polymorphism affects the transcriptional activity, and that this may account for the responsiveness to imidapril.
ESTHER : Geshi_2005_Hypertens.Res_28_719
PubMedSearch : Geshi_2005_Hypertens.Res_28_719
PubMedID: 16419644
Gene_locus related to this paper: human-CES1

Title : Purkinje cell long-term depression is prevented by T-588, a neuroprotective compound that reduces cytosolic calcium release from intracellular stores - Kimura_2005_Proc.Natl.Acad.Sci.U.S.A_102_17160
Author(s) : Kimura T , Sugimori M , Llinas RR
Ref : Proc Natl Acad Sci U S A , 102 :17160 , 2005
Abstract : Long-term depression (LTD) of the parallel-fiber (PF) Purkinje synapse induced by four different experimental paradigms could be prevented in rat cerebellar slices by T-588, a neuroprotective compound. The paradigms consisted of pairing PF activation with climbing-fiber activation, direct depolarization, glutamic iontophoretic depolarization, or caffeine. In all cases, LTD was determined by patch-clamp recording of PF excitatory postsynaptic currents at the Purkinje cell somata. T-588 at 1 muM prevented the triggering of LTD reversibly and did not generate LTD on its own. Two-photon calcium-sensitive dye imaging demonstrated that T-588 reduces intracellular calcium concentration ([Ca(2+)](i)) increase by blocking calcium release from intracellular stores. Because [Ca(2+)](i) increase has been widely shown to trigger LTD and glutamate excitotoxicity, we propose that LTD may act as a neuroprotective mechanism. As such, LTD would serve to decrease glutamatergic-receptor sensitivity to limit deleterious [Ca(2+)](i) increase rather than to act as a mechanism for cerebellar learning.
ESTHER : Kimura_2005_Proc.Natl.Acad.Sci.U.S.A_102_17160
PubMedSearch : Kimura_2005_Proc.Natl.Acad.Sci.U.S.A_102_17160
PubMedID: 16278299

Title : Portal hypertensive gastropathy after surgery for biliary atresia - Sasaki_2005_Surg.Today_35_385
Author(s) : Sasaki T , Hasegawa T , Shimizu Y , Kimura T , Soh H , Fukuzawa M
Ref : Surg Today , 35 :385 , 2005
Abstract : PURPOSE: To clarify the correlation between portal hypertensive gastropathy (PHG) and clinical features after surgery for biliary atresia (BA).
METHODS: Routine upper gastrointestinal endoscopies were done over 3 years in 27 children who underwent surgery for BA. We reviewed the recorded endoscopic findings, and retrospectively diagnosed PHG according to McCormack's criteria. The differences in clinical features, such as endoscopically treated gastroesophageal varices and the results of routine laboratory tests, were compared between the children with PHG (PHG group) and those without PHG (non-PHG group).
RESULTS: Nine (33%) of the 27 children had PHG. Although there was no significant difference in age between the PHG and non-PHG groups, the frequency of past endoscopic variceal treatments was significantly higher in the PHG group (3.0 +/- 3.0 vs 0.6 +/- 1.5 times, P = 0.01). The PHG group also had lower white blood cell and platelet counts, at 3008 +/- 2411 vs 5527 +/- 2938/mm3 (P < 0.05) and 6.0 +/- 3.4 vs 13.9 +/- 4.7 x 10(4)/mm3 (P = 0.0001), respectively; higher serum aspartate aminotransferase, total bile acid, and total bilirubin levels at 80 +/- 31 vs 46 +/- 29 U/l (P < 0.05), 161 +/- 93 vs 64 +/- 88 U/l (P < 0.05), and 4.8 +/- 5.6 vs 1.0 +/- 0.8 mg/dl (P < 0.01), respectively; and lower prothrombin time, albumin, and cholinesterase levels, at 66 +/- 16 vs 79% +/- 14% (P < 0.05), 3.6 +/- 0.8 vs 4.1 +/- 0.5 g/dl (P < 0.05), and 2158 +/- 925 vs 3376 +/- 700 U/l (P < 0.001), respectively. CONCLUSION: Portal hypertensive gastropathy was found in 33% of children after surgery for BA. The factors contributing to the development of PHG were frequent endoscopic treatments of gastroesophageal varices, liver dysfunction, and hypersplenism.
ESTHER : Sasaki_2005_Surg.Today_35_385
PubMedSearch : Sasaki_2005_Surg.Today_35_385
PubMedID: 15864420

Title : Proposal of fibrosis index using image analyzer as a quantitative histological evaluation of liver fibrosis in biliary atresia - Tanano_2003_Pediatr.Surg.Int_19_52
Author(s) : Tanano H , Hasegawa T , Kimura T , Sasaki T , Kawahara H , Kubota A , Okada A
Ref : Pediatr Surg Int , 19 :52 , 2003
Abstract : This study was designed to elucidate whether the fibrosis index (FI), which was measured as a ratio of histological fibrotic tissue area to the whole area using an image analyzer, could reflect liver function and long-term prognosis in biliary atresia (BA). Liver biopsies were performed in 46 BA patients at hepatic portoenterostomy (HPE) and stoma closure. The chronological difference rate of FI (FIDR) was the monthly FI difference between HPE and stoma closure. FI at HPE and stoma closure was significantly higher than in the control. FI at HPE and at stoma closure significantly correlated with gammaGTP or T.Bil, D.Bil, cholinesterase and total bile acid, respectively. FIDR in jaundice-free group was significantly lower than in jaundiced group at 5 years after HPE. FIDR in V-2 (varices with red-color sign) was significantly higher than in V-0 (no varices) or V-1 (varices without red-color sign). ICG-K value significantly correlated with FIDR. FI at stoma closure or FIDR was significantly lower in living patients than in patients who eventually died or underwent liver transplantation. In conclusion, FI can reflect the degree of cholestasis in BA. FIDR would be useful for predicting long-term outcome in BA.
ESTHER : Tanano_2003_Pediatr.Surg.Int_19_52
PubMedSearch : Tanano_2003_Pediatr.Surg.Int_19_52
PubMedID: 12721724

Title : Distributions of gamma-aminobutyric acid immunoreactive and acetylcholinesterase-containing cells in the primary olfactory system in the terrestrial slug Limax marginatus - Ito_2003_Zoolog.Sci_20_1337
Author(s) : Ito I , Watanabe S , Kimura T , Kirino Y , Ito E
Ref : Zoolog Sci , 20 :1337 , 2003
Abstract : The tentacular ganglion, the primary olfactory system of terrestrial slugs, exhibits spontaneous oscillations with a spatial coherence. The digit-like extensions (digits) of the tentacular ganglion presumably house the cell bodies of the neurons underlying the oscillations. The present study was designed to identify the anatomical and physiological determinants of these oscillations with a special focus on whether the neurons located in the digits contribute to the coherent oscillations. We recorded field potentials from the spatially separated sites in the digits in the terrestrial slug Limax marginatus. We also simultaneously recorded tentacular nerve to monitor the coherent oscillations. The spatially separated regions in the digits oscillated at the same frequency as the tentacular nerve, indicating a single coherent activity. To study the neural networks underlying the coherent oscillations, we examined the distributions of acetylcholinesterase (AChE)-containing and gamma-aminobutyric acid immunoreactive (GABA-ir) neurons. AChE-containing and GABA-ir fibers were found to connect the neurons in a branch of the digits with those in other branches. We also used a vital staining technique with 1,1'-didodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate to examine the projections of neurons in the digits. Large stained cells were detected in many branches of the digits after placing the dye on one of the cell masses located in right and left sides of the tentacular ganglion. They were detected in the cell masses and in many branches of the digits after placing the dye on a branch of the digits. Our results showed that the slug primary olfactory system has highly interconnected neural networks.
ESTHER : Ito_2003_Zoolog.Sci_20_1337
PubMedSearch : Ito_2003_Zoolog.Sci_20_1337
PubMedID: 14624031

Title : Indication for redo hepatic portoenterostomy for insufficient bile drainage in biliary atresia: re-evaluation in the era of liver transplantation - Hasegawa_2003_Pediatr.Surg.Int_19_256
Author(s) : Hasegawa T , Kimura T , Sasaki T , Okada A , Mushiake S
Ref : Pediatr Surg Int , 19 :256 , 2003
Abstract : To determine the role of redo hepatic portoenterostomy (HPE) in biliary atresia (BA) patients with insufficient bile excretion after the initial HPE, 25 patients (type I, correctable: 2; type III, uncorrectable: 23) undergoing the initial HPE at 25 to 119 days of age were studied. Four patients achieved disappearance of jaundice (total bilirubin [T.Bil] < 2 mg/dl) postoperatively. A redo HPE was performed at 2 to 8 months of age with sufficient and extensive removal of granulation and scar tissue at the hepatic hilum. Five patients became free of jaundice in 3 to 6 months (group 1), while the remaining 20 did not (group 2). Disappearance of jaundice after the initial HPE had been achieved in 2 of 5 patients (40%) in group 1 and 2 of 20 (10%) in group 2 ( P < 0.05). Age, serum T.Bil, aspartate aminotransferase albumin, prothrombin time, cholinesterase, total cholesterol, and Fischer's ratio at redo HPE showed no significant differences between the two groups. On liver histology obtained at redo HPE, cirrhosis and hepatocyte degeneration were seen in 1 of 5 cases (20%) in group 1 and 12 of 20 (60%) in group 2 ( P < 0.05). Redo HPE may thus be effective in BA patients with insufficient bile drainage who achieved disappearance of jaundice after the initial HPE and have not developed cirrhosis.
ESTHER : Hasegawa_2003_Pediatr.Surg.Int_19_256
PubMedSearch : Hasegawa_2003_Pediatr.Surg.Int_19_256
PubMedID: 12682751

Title : Complete genome structure of the thermophilic cyanobacterium Thermosynechococcus elongatus BP-1 - Nakamura_2002_DNA.Res_9_123
Author(s) : Nakamura Y , Kaneko T , Sato S , Ikeuchi M , Katoh H , Sasamoto S , Watanabe A , Iriguchi M , Kawashima K , Kimura T , Kishida Y , Kiyokawa C , Kohara M , Matsumoto M , Matsuno A , Nakazaki N , Shimpo S , Sugimoto M , Takeuchi C , Yamada M , Tabata S
Ref : DNA Research , 9 :123 , 2002
Abstract : The entire genome of a thermophilic unicellular cyanobacterium, Thermosynechococcus elongatus BP-1, was sequenced. The genome consisted of a circular chromosome 2,593,857 bp long, and no plasmid was detected. A total of 2475 potential protein-encoding genes, one set of rRNA genes, 42 tRNA genes representing 42 tRNA species and 4 genes for small structural RNAs were assigned to the chromosome by similarity search and computer prediction. The translated products of 56% of the potential protein-encoding genes showed sequence similarity to experimentally identified and predicted proteins of known function, and the products of 34% of these genes showed sequence similarity to the translated products of hypothetical genes. The remaining 10% lacked significant similarity to genes for predicted proteins in the public DNA databases. Sixty-three percent of the T. elongatus genes showed significant sequence similarity to those of both Synechocystis sp. PCC 6803 and Anabaena sp. PCC 7120, while 22% of the genes were unique to this species, indicating a high degree of divergence of the gene information among cyanobacterial strains. The lack of genes for typical fatty acid desaturases and the presence of more genes for heat-shock proteins in comparison with other mesophilic cyanobacteria may be genomic features of thermophilic strains. A remarkable feature of the genome is the presence of 28 copies of group II introns, 8 of which contained a presumptive gene for maturase/reverse transcriptase. A trace of genome rearrangement mediated by the group II introns was also observed.
ESTHER : Nakamura_2002_DNA.Res_9_123
PubMedSearch : Nakamura_2002_DNA.Res_9_123
PubMedID: 12240834
Gene_locus related to this paper: theeb-q8dg48 , theeb-TLL0292 , theeb-TLL0340 , theeb-TLL0918 , theeb-TLL0989 , theeb-TLL1717 , theeb-TLL2163 , theeb-TLR0492 , theeb-TLR1045 , theeb-TLR1157 , theeb-TLR1274 , theeb-TLR1393 , theeb-TLR1423 , theeb-TLR1685 , theeb-TLR1725 , theeb-TLR1892 , theeb-TLR1982 , theeb-TLR2038 , theeb-TLR2066

Title : Role of plasma thrombopoietin level in thrombocytopenia of postoperative biliary atresia patients - Hasegawa_2002_J.Pediatr.Surg_37_1195
Author(s) : Hasegawa T , Sasaki T , Kimura T , Okada A
Ref : J Pediatr Surg , 37 :1195 , 2002
Abstract : BACKGROUND/PURPOSE: To evaluate if thrombocytopenia may be related to plasma thrombopoietin level (P-TPO) in postoperative biliary atresia (BA). METHODS: Forty-three postoperative BA patients aged 1 to 20 years were included. P-TPO was measured by enzyme immunoassay. P-TPO was compared with platelet counts (Plt), Child's classification, presence of splenomegaly, and liver function tests. RESULTS: P-TPO significantly correlated with Plt, child's classification, serum albumin, and cholinesterase level, respectively. In 4 patients undergoing portal decompression procedure, preoperative and postoperative Plt and P-TPO were 87.5 +/- 69.1 x 10(3) and 50.3 +/- 28.0, 118.8 +/- 62.3 x 10(3)/mm3, and 53.0 +/- 55.0 pg/mL, respectively, without significant difference. In 6 patients undergoing liver transplantation (LTx), Plt and P-TPO after LTx was 157.5 +/- 83.5 x 10(3) and 143.5 +/- 75.2, respectively, which were significantly higher than those before LTx (55.0 +/- 15.6 x 10(3)/mm3 and 53.2 +/- 32.9 pg/mL). CONCLUSION: Thrombocytopenia in postoperative BA may be caused by decreased plasma TPO level in accordance with the severity of liver dysfunction rather than hypersplenism.
ESTHER : Hasegawa_2002_J.Pediatr.Surg_37_1195
PubMedSearch : Hasegawa_2002_J.Pediatr.Surg_37_1195
PubMedID: 12149701

Title : Poster: Pharmacological characterization of (2r)-n-[1-(6-aminopyridin-2-ylmethyl)piperidin-4-yl]-2-[(lr)-3,3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamide, a novel muscarinic M3 receptor antagonist with high selectivity over M2 receptors -
Author(s) : Hirose H , Kimura T , Fujikawa T , Numazawa T , Aoki I , Ohtake N , Nishikibe M , Mase T , Noguchi K
Ref : Life Sciences , 68 :2627 , 2001

Title : Prognostic factors in elderly patients with unresectable non-small cell lung cancer - Kimura_2001_Anticancer.Res_21_1379
Author(s) : Kimura T , Kudoh S , Hirata K , Takifuji N , Negoro S , Yoshikawa J
Ref : Anticancer Research , 21 :1379 , 2001
Abstract : BACKGROUND The number of elderly patients with lung cancer is rapidly increasing and their management is an important issue. PATIENTS AND METHODS: 109 patients aged over 75 years with unresectable non-small cell lung cancer were assessed to define the prognostic factors. The median age was 80 years in a range of 76 to 95. The overall median survival time was 6.3 months. Fifty-one patients underwent chemotherapy and/or thoracic radiotherapy whilst the others received best supportive care. RESULTS: Multivariate Cox regression model showed performance status (PS) (p = 0.0063) and stage of disease (p = 0.0158) to be independent prognostic factors for survival. In seventy-six patients with a good PS of 0-1, choice of treatment (p = 0.0225) and hyponatremia (p = 0.0302) were the predictors for survival.
CONCLUSIONS: PS, treatment and serum sodium level were important factors for survival, and most patients with good PS were able to undergo the treatment and have a good outcome.
ESTHER : Kimura_2001_Anticancer.Res_21_1379
PubMedSearch : Kimura_2001_Anticancer.Res_21_1379
PubMedID: 11396218

Title : Plasma endothelin-1 level as a marker reflecting the severity of portal hypertension in biliary atresia - Hasegawa_2001_J.Pediatr.Surg_36_1609
Author(s) : Hasegawa T , Kimura T , Sasaki T , Okada A
Ref : J Pediatr Surg , 36 :1609 , 2001
Abstract : BACKGROUND/PURPOSE: The aim of this study was to examine if the plasma endothelin-1 (ET-1), a potent vasoconstrictor, level may reflect the severity of portal hypertension associated with liver cirrhosis in biliary atresia (BA). METHODS: Forty-eight postoperative BA patients aged 6 months to 20 years were studied. Plasma ET-1 was measured by a sandwich method of enzyme immunoassay. ET-1 was compared with Child's score and laboratory data. ET-1 levels were compared among groups of patients with various degrees of histologic fibrosis and portal hypertension. RESULTS: Plasma ET-1 was 5.3 +/- 3.5 pg/mL in BA, higher than in controls (3.1 +/- 0.8, n = 27; P <.05). ET-1 correlated with Child's score, serum total bilirubin, direct bilirubin, aspartate aminotransferase, albumin, prothrombin time, hepaplastin test, fibrinogen, cholinesterase, total cholesterol, Fischer's molar ratio, prealubumin, and hyaluronic acid, respectively (P <.05). ET-1 also correlated with the severity of histologic fibrosis, gastroesophageal varices, the presence of splenomegaly, ascites, venous dilatation on the abdominal wall, or pulmonary vascular abnormalities. In 4 patients undergoing liver transplantation (LTx), ET-1 after LTx was lower than that before LTx (P <.05).
ESTHER : Hasegawa_2001_J.Pediatr.Surg_36_1609
PubMedSearch : Hasegawa_2001_J.Pediatr.Surg_36_1609
PubMedID: 11685683

Title : Complete genomic sequence of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. strain PCC 7120 - Kaneko_2001_DNA.Res_8_205
Author(s) : Kaneko T , Nakamura Y , Wolk CP , Kuritz T , Sasamoto S , Watanabe A , Iriguchi M , Ishikawa A , Kawashima K , Kimura T , Kishida Y , Kohara M , Matsumoto M , Matsuno A , Muraki A , Nakazaki N , Shimpo S , Sugimoto M , Takazawa M , Yamada M , Yasuda M , Tabata S
Ref : DNA Research , 8 :205 , 2001
Abstract : The nucleotide sequence of the entire genome of a filamentous cyanobacterium, Anabaena sp. strain PCC 7120, was determined. The genome of Anabaena consisted of a single chromosome (6,413,771 bp) and six plasmids, designated pCC7120alpha (408,101 bp), pCC7120beta (186,614 bp), pCC7120gamma (101,965 bp), pCC7120delta (55,414 bp), pCC7120epsilon (40,340 bp), and pCC7120zeta (5,584 bp). The chromosome bears 5368 potential protein-encoding genes, four sets of rRNA genes, 48 tRNA genes representing 42 tRNA species, and 4 genes for small structural RNAs. The predicted products of 45% of the potential protein-encoding genes showed sequence similarity to known and predicted proteins of known function, and 27% to translated products of hypothetical genes. The remaining 28% lacked significant similarity to genes for known and predicted proteins in the public DNA databases. More than 60 genes involved in various processes of heterocyst formation and nitrogen fixation were assigned to the chromosome based on their similarity to the reported genes. One hundred and ninety-five genes coding for components of two-component signal transduction systems, nearly 2.5 times as many as those in Synechocystis sp. PCC 6803, were identified on the chromosome. Only 37% of the Anabaena genes showed significant sequence similarity to those of Synechocystis, indicating a high degree of divergence of the gene information between the two cyanobacterial strains.
ESTHER : Kaneko_2001_DNA.Res_8_205
PubMedSearch : Kaneko_2001_DNA.Res_8_205
PubMedID: 11759840
Gene_locus related to this paper: anasp-ALL0111 , anasp-ALL0193 , anasp-ALL0254 , anasp-ALL0316 , anasp-ALL0955 , anasp-ALL0969 , anasp-ALL1161 , anasp-ALL1205 , anasp-ALL1353 , anasp-ALL1695 , anasp-ALL2050 , anasp-ALL2056 , anasp-ALL2058 , anasp-ALL2068 , anasp-ALL2529 , anasp-ALL2533 , anasp-ALL2753 , anasp-ALL2761 , anasp-ALL3898 , anasp-ALL4221 , anasp-ALL4875 , anasp-ALL8511 , anasp-ALR0039 , anasp-ALR0079 , anasp-ALR0130 , anasp-ALR0235 , anasp-ALR0851 , anasp-ALR1077 , anasp-ALR1270 , anasp-ALR1352 , anasp-ALR1362 , anasp-ALR1709 , anasp-ALR2045 , noss1-ALR3140 , anasp-ALR3514 , anasp-ALR3685 , anasp-ALR3911 , anasp-ALR4625 , anasp-ALR5028 , anasp-AROE , anasp-q8ymv5 , anasp-q8yxx2 , anasp-y1448 , noss1-ALL3113 , noss1-ALL4967 , noss1-ALR4786 , noss1-q8yrg0 , noss1-y2406

Title : Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana - Tabata_2000_Nature_408_823
Author(s) : Tabata S , Kaneko T , Nakamura Y , Kotani H , Kato T , Asamizu E , Miyajima N , Sasamoto S , Kimura T , Hosouchi T , Kawashima K , Kohara M , Matsumoto M , Matsuno A , Muraki A , Nakayama S , Nakazaki N , Naruo K , Okumura S , Shinpo S , Takeuchi C , Wada T , Watanabe A , Yamada M , Yasuda M , Sato S , de la Bastide M , Huang E , Spiegel L , Gnoj L , O'Shaughnessy A , Preston R , Habermann K , Murray J , Johnson D , Rohlfing T , Nelson J , Stoneking T , Pepin K , Spieth J , Sekhon M , Armstrong J , Becker M , Belter E , Cordum H , Cordes M , Courtney L , Courtney W , Dante M , Du H , Edwards J , Fryman J , Haakensen B , Lamar E , Latreille P , Leonard S , Meyer R , Mulvaney E , Ozersky P , Riley A , Strowmatt C , Wagner-McPherson C , Wollam A , Yoakum M , Bell M , Dedhia N , Parnell L , Shah R , Rodriguez M , See LH , Vil D , Baker J , Kirchoff K , Toth K , King L , Bahret A , Miller B , Marra M , Martienssen R , McCombie WR , Wilson RK , Murphy G , Bancroft I , Volckaert G , Wambutt R , Dusterhoft A , Stiekema W , Pohl T , Entian KD , Terryn N , Hartley N , Bent E , Johnson S , Langham SA , McCullagh B , Robben J , Grymonprez B , Zimmermann W , Ramsperger U , Wedler H , Balke K , Wedler E , Peters S , van Staveren M , Dirkse W , Mooijman P , Lankhorst RK , Weitzenegger T , Bothe G , Rose M , Hauf J , Berneiser S , Hempel S , Feldpausch M , Lamberth S , Villarroel R , Gielen J , Ardiles W , Bents O , Lemcke K , Kolesov G , Mayer K , Rudd S , Schoof H , Schueller C , Zaccaria P , Mewes HW , Bevan M , Fransz P
Ref : Nature , 408 :823 , 2000
Abstract : The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.
ESTHER : Tabata_2000_Nature_408_823
PubMedSearch : Tabata_2000_Nature_408_823
PubMedID: 11130714
Gene_locus related to this paper: arath-At5g11650 , arath-At5g16120 , arath-at5g18630 , arath-AT5G20520 , arath-At5g21950 , arath-AT5G27320 , arath-CXE15 , arath-F1N13.220 , arath-F14F8.240 , arath-q3e9e4 , arath-q8lae9 , arath-Q8LFB7 , arath-q9ffg7 , arath-q9fij5 , arath-Q9LVU7 , arath-q66gm8 , arath-SCPL34 , arath-B9DFR3 , arath-a0a1p8bcz0

Title : Sequence and analysis of chromosome 3 of the plant Arabidopsis thaliana - Salanoubat_2000_Nature_408_820
Author(s) : Salanoubat M , Lemcke K , Rieger M , Ansorge W , Unseld M , Fartmann B , Valle G , Blocker H , Perez-Alonso M , Obermaier B , Delseny M , Boutry M , Grivell LA , Mache R , Puigdomenech P , de Simone V , Choisne N , Artiguenave F , Robert C , Brottier P , Wincker P , Cattolico L , Weissenbach J , Saurin W , Quetier F , Schafer M , Muller-Auer S , Gabel C , Fuchs M , Benes V , Wurmbach E , Drzonek H , Erfle H , Jordan N , Bangert S , Wiedelmann R , Kranz H , Voss H , Holland R , Brandt P , Nyakatura G , Vezzi A , D'Angelo M , Pallavicini A , Toppo S , Simionati B , Conrad A , Hornischer K , Kauer G , Lohnert TH , Nordsiek G , Reichelt J , Scharfe M , Schon O , Bargues M , Terol J , Climent J , Navarro P , Collado C , Perez-Perez A , Ottenwalder B , Duchemin D , Cooke R , Laudie M , Berger-Llauro C , Purnelle B , Masuy D , de Haan M , Maarse AC , Alcaraz JP , Cottet A , Casacuberta E , Monfort A , Argiriou A , Flores M , Liguori R , Vitale D , Mannhaupt G , Haase D , Schoof H , Rudd S , Zaccaria P , Mewes HW , Mayer KF , Kaul S , Town CD , Koo HL , Tallon LJ , Jenkins J , Rooney T , Rizzo M , Walts A , Utterback T , Fujii CY , Shea TP , Creasy TH , Haas B , Maiti R , Wu D , Peterson J , Van Aken S , Pai G , Militscher J , Sellers P , Gill JE , Feldblyum TV , Preuss D , Lin X , Nierman WC , Salzberg SL , White O , Venter JC , Fraser CM , Kaneko T , Nakamura Y , Sato S , Kato T , Asamizu E , Sasamoto S , Kimura T , Idesawa K , Kawashima K , Kishida Y , Kiyokawa C , Kohara M , Matsumoto M , Matsuno A , Muraki A , Nakayama S , Nakazaki N , Shinpo S , Takeuchi C , Wada T , Watanabe A , Yamada M , Yasuda M , Tabata S
Ref : Nature , 408 :820 , 2000
Abstract : Arabidopsis thaliana is an important model system for plant biologists. In 1996 an international collaboration (the Arabidopsis Genome Initiative) was formed to sequence the whole genome of Arabidopsis and in 1999 the sequence of the first two chromosomes was reported. The sequence of the last three chromosomes and an analysis of the whole genome are reported in this issue. Here we present the sequence of chromosome 3, organized into four sequence segments (contigs). The two largest (13.5 and 9.2 Mb) correspond to the top (long) and the bottom (short) arms of chromosome 3, and the two small contigs are located in the genetically defined centromere. This chromosome encodes 5,220 of the roughly 25,500 predicted protein-coding genes in the genome. About 20% of the predicted proteins have significant homology to proteins in eukaryotic genomes for which the complete sequence is available, pointing to important conserved cellular functions among eukaryotes.
ESTHER : Salanoubat_2000_Nature_408_820
PubMedSearch : Salanoubat_2000_Nature_408_820
PubMedID: 11130713
Gene_locus related to this paper: arath-MES17 , arath-AT3G12150 , arath-At3g61680 , arath-AT3g62590 , arath-CXE12 , arath-eds1 , arath-SCP25 , arath-F1P2.110 , arath-F1P2.140 , arath-F11F8.28 , arath-F14D17.80 , arath-F16B3.4 , arath-SCP27 , arath-At3g50790 , arath-At3g05600 , arath-PAD4 , arath-At3g51000 , arath-SCP16 , arath-gid1 , arath-GID1B , arath-Q9LUG8 , arath-Q84JS1 , arath-Q9SFF6 , arath-q9m236 , arath-q9sr22 , arath-q9sr23 , arath-SCP7 , arath-SCP14 , arath-SCP15 , arath-SCP17 , arath-SCP36 , arath-SCP37 , arath-SCP39 , arath-SCP40 , arath-SCP49 , arath-T19F11.2

Title : Complete genome structure of the nitrogen-fixing symbiotic bacterium Mesorhizobium loti - Kaneko_2000_DNA.Res_7_331
Author(s) : Kaneko T , Nakamura Y , Sato S , Asamizu E , Kato T , Sasamoto S , Watanabe A , Idesawa K , Ishikawa A , Kawashima K , Kimura T , Kishida Y , Kiyokawa C , Kohara M , Matsumoto M , Matsuno A , Mochizuki Y , Nakayama S , Nakazaki N , Shimpo S , Sugimoto M , Takeuchi C , Yamada M , Tabata S
Ref : DNA Research , 7 :331 , 2000
Abstract : The complete nucleotide sequence of the genome of a symbiotic bacterium Mesorhizobium loti strain MAFF303099 was determined. The genome of M. loti consisted of a single chromosome (7,036,071 bp) and two plasmids, designated as pMLa (351,911 bp) and pMLb (208, 315 bp). The chromosome comprises 6752 potential protein-coding genes, two sets of rRNA genes and 50 tRNA genes representing 47 tRNA species. Fifty-four percent of the potential protein genes showed sequence similarity to genes of known function, 21% to hypothetical genes, and the remaining 25% had no apparent similarity to reported genes. A 611-kb DNA segment, a highly probable candidate of a symbiotic island, was identified, and 30 genes for nitrogen fixation and 24 genes for nodulation were assigned in this region. Codon usage analysis suggested that the symbiotic island as well as the plasmids originated and were transmitted from other genetic systems. The genomes of two plasmids, pMLa and pMLb, contained 320 and 209 potential protein-coding genes, respectively, for a variety of biological functions. These include genes for the ABC-transporter system, phosphate assimilation, two-component system, DNA replication and conjugation, but only one gene for nodulation was identified.
ESTHER : Kaneko_2000_DNA.Res_7_331
PubMedSearch : Kaneko_2000_DNA.Res_7_331
PubMedID: 11214968
Gene_locus related to this paper: meslo-acoc , meslo-EphB , meslo-est , meslo-lipest , meslo-MLL0014 , meslo-MLL0351 , meslo-MLL0537 , meslo-mll0601 , meslo-MLL0618 , meslo-MLL1209 , meslo-MLL1226 , meslo-mll1328 , meslo-MLL1329 , meslo-MLL1495 , meslo-MLL1869 , meslo-mll1900 , meslo-MLL2018 , meslo-MLL2072 , meslo-mll2481 , meslo-mll2689 , meslo-MLL2788 , meslo-MLL3556 , meslo-MLL3568 , meslo-MLL3682 , meslo-mll3776 , meslo-MLL4497 , meslo-MLL4552 , meslo-MLL5128 , meslo-mll5179 , meslo-mll5392 , meslo-MLL5717 , meslo-mll5743 , meslo-MLL6746 , meslo-MLL6752 , meslo-mll6871 , meslo-MLL7643 , meslo-mll7742 , meslo-MLL9722 , meslo-MLR0094 , meslo-mlr0145 , meslo-mlr0170 , meslo-MLR0240 , meslo-mlr0493 , meslo-MLR0937 , meslo-mlr0978 , meslo-MLR0992 , meslo-MLR1612 , meslo-mlr1789 , meslo-mlr1864 , meslo-mlr2176 , meslo-MLR2262 , meslo-mlr2612 , meslo-mlr2710 , meslo-mlr3034 , meslo-MLR3538 , meslo-mlr3816 , meslo-mlr4436 , meslo-MLR4903 , meslo-MLR5045 , meslo-MLR5063 , rhilo-dhaa , meslo-MLR6087 , meslo-MLR6657 , meslo-mlr6682 , meslo-mlr6683 , meslo-MLR6684 , meslo-MLR6787 , meslo-MLR6993 , meslo-mlr6999 , meslo-mlr7206 , meslo-mlr7232 , meslo-mlr7803 , meslo-MLR9053 , meslo-mlr9622 , meslo-mlr9641 , rhilo-MLL0076 , rhilo-MLL1824 , rhilo-MLL7123 , rhilo-MLL8374 , rhilo-MLR1247 , rhilo-MLR2444 , rhilo-MLR4383 , rhilo-MLR8175 , rhilo-q98nf6 , rhilo-q98nf8 , rhilo-q988i9

Title : GA strategy for variable selection in QSAR studies: application of GA- based region selection to a 3D-QSAR study of acetylcholinesterase inhibitors - Hasegawa_1999_J.Chem.Inf.Comput.Sci_39_112
Author(s) : Hasegawa K , Kimura T , Funatsu K
Ref : J Chem Inf Comput Sci , 39 :112 , 1999
Abstract : Comparative molecular field analysis (CoMFA) with partial least squares (PLS) is one of the most frequently used tools in three-dimensional quantitative structure-activity relationships (3D-QSAR) studies. Although many successful CoMFA applications have proved the value of this approach, there are some problems in its proper application. Especially, the inability of PLS to handle the low signal-to-noise ratio (sample-to-variable ratio) has attracted much attention from QSAR researchers as an exciting research target, and several variable selection methods have been proposed. More recently, we have developed a novel variable selection method for CoMFA modeling (GARGS: genetic algorithm-based region selection), and its utility has been demonstrated in the previous paper (Kimura, T., et al. J. Chem. Inf. Comput. Sci. 1998, 38, 276-282). The purpose of this study is to evaluate whether GARGS can pinpoint known molecular interactions in 3D space. We have used a published set of acetylcholinesterase (AChE) inhibitors as a test example. By applying GARGS to a data set of AChE inhibitors, several improved models with high internal prediction and low number of field variables were obtained. External validation was performed to select a final model among them. The coefficient contour maps of the final GARGS model were compared with the properties of the active site in AChE and the consistency between them was evaluated.
ESTHER : Hasegawa_1999_J.Chem.Inf.Comput.Sci_39_112
PubMedSearch : Hasegawa_1999_J.Chem.Inf.Comput.Sci_39_112
PubMedID: 10094610

Title : Effects of oral clonidine on heart rate changes after neostigmine- atropine administration - Kimura_1998_Anesthesiology_88_1507
Author(s) : Kimura T , Tanaka M , Nishikawa T
Ref : Anesthesiology , 88 :1507 , 1998
Abstract : BACKGROUND Clonidine reduces heart rate (HR) responses to atropine, whereas neostigmine causes bradycardia. This study was designed to determine whether clonidine premedication would reduce tachycardia after neostigmine-atropine administration. METHODS: Fifty adult patients without cardiovascular disorders who were scheduled for elective surgeries were randomly assigned to receive approximately 5 microg/kg (oral clonidine clonidine group, n=25) or no clonidine (control group, n=25) 90 min before induction of general anesthesia. After tracheal intubation, anesthesia was maintained with N2O and 12% isoflurane in oxygen while patients were paralyzed with vecuronium and mechanically ventilated. When surgeries were completed, adequate spontaneous respiration, responses to verbal commands, and sustained tetanus by stimulating the ulnar nerve were confirmed, and patients' tracheas were extubated. Then a mixture of 0.05 mg/kg neostigmine and 0.02 mg/kg atropine was administered intravenously over 20 s under stable hemodynamic condition (systolic blood pressure and HR within +/-5% of preceding values), and blood pressure and HR were measured noninvasively at 1-min intervals for 10 min. RESULTS: Increases in HR in the clonidine group were significantly less 1-4 min after neostigmine--atropine injections compared with HR values in the control group. A maximum increase in HR of the clonidine group was also significantly less than the control group (15+/-7 vs. 23+/-10 beats/min; means+/-SD), whereas absolute values of mean blood pressure were similar. Severe bradycardia (HR < 50 beats/min) developed in no patients in either group.
CONCLUSIONS: Premedication with 5 microg/kg oral clonidine attenuates the initial increases in HR without subsequent decreases in HR.
ESTHER : Kimura_1998_Anesthesiology_88_1507
PubMedSearch : Kimura_1998_Anesthesiology_88_1507
PubMedID: 9637644

Title : Cloning of genes involved in carbazole degradation of Pseudomonas sp. strain CA10: nucleotide sequences of genes and characterization of meta-cleavage enzymes and hydrolase - Sato_1997_J.Bacteriol_179_4841
Author(s) : Sato SI , Ouchiyama N , Kimura T , Nojiri H , Yamane H , Omori T
Ref : Journal of Bacteriology , 179 :4841 , 1997
Abstract : The DNA fragment encoding meta-cleavage enzymes and the meta-cleavage compound hydrolase, involved in carbazole degradation, was cloned from the carbazole-utilizing bacterium Pseudomonas sp. strain CA10. DNA sequence analysis of this 2.6-kb SmaI-SphI fragment revealed that there were three open reading frames (ORF1, ORF2, and ORF3, in this gene order). ORF1 and ORF2 were indispensable for meta-cleavage activity for 2'-aminobiphenyl-2,3-diol and its easily available analog, 2,3-dihydroxybiphenyl, and were designated carBa and carBb, respectively. The alignment of CarBb with other meta-cleavage enzymes indicated that CarBb may have a non-heme iron cofactor coordinating site. On the basis of the phylogenetic tree, CarBb was classified as a member of the protocatechuate 4,5-dioxygenase family. This unique extradiol dioxygenase, CarB, had significantly higher affinity and about 20-times-higher meta-cleavage activity for 2,3-dihydroxybiphenyl than for catechol derivatives. The putative polypeptide encoded by ORF3 was homologous with meta-cleavage compound hydrolases in other bacteria, and ORF3 was designated carC. The hydrolase activity of CarC for 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid, the meta-cleavage compound of 2,3-dihydroxybiphenyl, was 40 times higher than that for 2-hydroxy-6-oxohepta-2,4-dienoic acid, the meta-cleavage compound of 3-methylcatechol. Alignment analysis and the phylogenetic tree indicate that CarC has greatest homologies with hydrolases involved in the monoaromatic compound degradation pathway. These results suggest the possibility that CarC is a novel type of hydrolase.
ESTHER : Sato_1997_J.Bacteriol_179_4841
PubMedSearch : Sato_1997_J.Bacteriol_179_4841
PubMedID: 9244273
Gene_locus related to this paper: psesp-Q9AQN6 , psest-bpdF

Title : Sequence analysis of the genome of the unicellular cyanobacterium Synechocystis sp. strain PCC6803. II. Sequence determination of the entire genome and assignment of potential protein-coding regions - Kaneko_1996_DNA.Res_3_109
Author(s) : Kaneko T , Sato S , Kotani H , Tanaka A , Asamizu E , Nakamura Y , Miyajima N , Hirosawa M , Sugiura M , Sasamoto S , Kimura T , Hosouchi T , Matsuno A , Muraki A , Nakazaki N , Naruo K , Okumura S , Shimpo S , Takeuchi C , Wada T , Watanabe A , Yamada M , Yasuda M , Tabata S
Ref : DNA Research , 3 :109 , 1996
Abstract : The sequence determination of the entire genome of the Synechocystis sp. strain PCC6803 was completed. The total length of the genome finally confirmed was 3,573,470 bp, including the previously reported sequence of 1,003,450 bp from map position 64% to 92% of the genome. The entire sequence was assembled from the sequences of the physical map-based contigs of cosmid clones and of lambda clones and long PCR products which were used for gap-filling. The accuracy of the sequence was guaranteed by analysis of both strands of DNA through the entire genome. The authenticity of the assembled sequence was supported by restriction analysis of long PCR products, which were directly amplified from the genomic DNA using the assembled sequence data. To predict the potential protein-coding regions, analysis of open reading frames (ORFs), analysis by the GeneMark program and similarity search to databases were performed. As a result, a total of 3,168 potential protein genes were assigned on the genome, in which 145 (4.6%) were identical to reported genes and 1,257 (39.6%) and 340 (10.8%) showed similarity to reported and hypothetical genes, respectively. The remaining 1,426 (45.0%) had no apparent similarity to any genes in databases. Among the potential protein genes assigned, 128 were related to the genes participating in photosynthetic reactions. The sum of the sequences coding for potential protein genes occupies 87% of the genome length. By adding rRNA and tRNA genes, therefore, the genome has a very compact arrangement of protein- and RNA-coding regions. A notable feature on the gene organization of the genome was that 99 ORFs, which showed similarity to transposase genes and could be classified into 6 groups, were found spread all over the genome, and at least 26 of them appeared to remain intact. The result implies that rearrangement of the genome occurred frequently during and after establishment of this species.
ESTHER : Kaneko_1996_DNA.Res_3_109
PubMedSearch : Kaneko_1996_DNA.Res_3_109
PubMedID: 8905231
Gene_locus related to this paper: synsp-ester , synsp-PHBC , synsp-prxc , synsp-Q55130 , synsp-SLL0482 , synsp-sll0553 , synsp-SLL0992 , synsp-sll1305 , synsp-SLL1969 , synsp-SLR0825 , synsp-slr1235 , synsp-SLR1506 , synsp-SLR1771 , synsp-SLR1807 , synsp-slr1827 , synsp-slr1916 , synsp-slr1917 , synsp-slr1932 , synsp-SLR1944 , synsp-SLR2053 , synsp-todF , syny3-dlhh , syny3-P73192 , syny3-p73194 , syny3-y249 , syny3-y264

Title : A new cognition-enhancing agent, (R)-(-)-1-(benzo[b]thiophen-5-yl)- 2-[2-(N,N-diethylamino)ethoxy]ethanol hydrochloride. Effects on memory impairment in rats generated by cerebral embolization and basal forebrain lesions - Ono_1995_Biol.Pharm.Bull_18_1779
Author(s) : Ono S , Yamafuji T , Chaki H , Todo Y , Maekawa M , Kitamura K , Kimura T , Nakada Y , Mozumi K , Narita H
Ref : Biol Pharm Bull , 18 :1779 , 1995
Abstract : The title compound (T-588) has been evaluated for its ameliorating effect on memory impairment generated by cerebral embolization and by a basal forebrain (BF) lesion in male Wistar rats. The memory and learning deficits induced by injection of carbon-microspheres into the internal carotid artery were significantly improved by T-588 at oral dose of 3-10 mg/kg, as determined by an active avoidance response assay, whereas the reference drugs (tacrine, idebenone and indeloxazine) proved almost inactive in the same assay procedure. As far as the embolization was concerned, a significant decrease in cerebral acetylcholine and monoamines was observed. The effect on the memory impairment caused by an electrolytic lesion of the BF was assessed by a passive avoidance task. T-588 exhibited a bell-shaped dose-response curve and was most active at 1 mg/kg (oral dose), while tacrine showed equal activity at 10 mg/kg.
ESTHER : Ono_1995_Biol.Pharm.Bull_18_1779
PubMedSearch : Ono_1995_Biol.Pharm.Bull_18_1779
PubMedID: 8787808

Title : Characterization of acetylcholinesterase-inhibition by itopride - Iwanaga_1994_Jpn.J.Pharmacol_66_317
Author(s) : Iwanaga Y , Kimura T , Miyashita N , Morikawa K , Nagata O , Itoh Z , Kondo Y
Ref : Japanese Journal of Pharmacology , 66 :317 , 1994
Abstract : Itopride is a gastroprokinetic benzamide derivative. This agent inhibited both electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BCHE). The IC50 of itopride with AChE (2.04 +/- 0.27 microM) was, however, 100-fold less than that with BCHE, whereas in the case of neostigmine with AChE (11.3 +/- 3.4 nM), it was 10-fold less. The recovery of AChE activity inhibited by 10(-7) M neostigmine was partial, but that inhibited by up to 3 x 10(-5) M itopride was complete when the reaction mixture was subjected to ultrafiltration. Double reciprocal plots of the experimental data showed that both Km and Vmax were affected by itopride, suggesting that the inhibition is a "mixed" type, although primarily being an uncompetitive one. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE. However, in the presence of a low dose of diisopropyl fluorophosphate, just enough to inhibit BCHE but not AChE, the IC50s of itopride against ChE activities were found to be about 0.5 microM. In conclusion, itopride exerts reversible and a "mixed" type of inhibition preferably against AChE. The IC50 of itopride for electric eel and guinea pig gastrointestinal AChE inhibition was 200 times and 50 times as large as that of neostigmine, respectively.
ESTHER : Iwanaga_1994_Jpn.J.Pharmacol_66_317
PubMedSearch : Iwanaga_1994_Jpn.J.Pharmacol_66_317
PubMedID: 7869618

Title : Effects of perivascular nerve stimulation on the contraction and automaticity of the blood-perfused canine papillary muscle - Endoh_1972_Br.J.Pharmacol_45_603
Author(s) : Endoh M , Hashimoto K , Kimura T
Ref : British Journal of Pharmacology , 45 :603 , 1972
Abstract : 1. Effects of ventricular perivascular nerve stimulation (p.n.s.) on the ventricular contractility and idioventricular rate were investigated with the blood-perfused papillary muscle of the canine right ventricle.2. Perivascular nerve stimulation of supramaximal voltage and 1 msec pulse-duration caused a definite positive inotropic response at a frequency of 1 Hz, which gradually reached a maximum at 15 to 20 Hz when the papillary muscle was electrically driven at 120 beats/min at a constant temperature of 38-39 degrees C. The frequency-response curve was sigmoid.3. The spontaneous regular idioventricular rate of 46+/-4 beats/min was accelerated to at most 60+/-4 beats/min (n=11) by p.n.s. The stimulus frequency-response relations between chronotropic and inotropic responses to p.n.s. were almost the same.4. Tetrodotoxin blocked completely the responses to p.n.s. while it had little or no effect on the inotropic response to exogenous noradrenaline.5. Positive inotropic responses to p.n.s. were diminished by beta-adrenoceptor blocking agents (alprenolol, propranolol and pindolol) and were enhanced during infusion of cocaine.6. In reserpine- or guanethidine-pretreated muscles, p.n.s. as well as field stimulation produced negative inotropic responses, which were enhanced by physostigmine and were blocked by atropine.7. Hexamethonium enhanced slightly the positive inotropic responses to p.n.s. as well as field stimulation.8. It was concluded that the perivascular nerves of the coronary artery of the canine ventricle are mainly composed of postganglionic adrenergic fibres but there are also pre- and postganglionic cholinergic nerve fibres.
ESTHER : Endoh_1972_Br.J.Pharmacol_45_603
PubMedSearch : Endoh_1972_Br.J.Pharmacol_45_603
PubMedID: 5085234