Hara T

References (12)

Title : Is there any correlation between liver graft regeneration and recipient's pretransplant skeletal muscle mass?-a study in extended left lobe graft living-donor liver transplantation - Pravisani_2020_Hepatobiliary.Surg.Nutr_9_183
Author(s) : Pravisani R , Soyama A , Ono S , Baccarani U , Isola M , Takatsuki M , Hidaka M , Adachi T , Hara T , Hamada T , Pecquenard F , Risaliti A , Eguchi S
Ref : Hepatobiliary Surg Nutr , 9 :183 , 2020
Abstract : Background: The end-stage liver disease causes a metabolic dysfunction whose most prominent clinical feature is the loss of skeletal muscle mass (SMM). In living-donor liver transplantation (LDLT), liver graft regeneration (GR) represents a crucial process to normalize the portal hypertension and to meet the metabolic demand of the recipient. Limited data are available on the correlation between pre-LDLT low SMM and GR. Methods: Retrospective study on a cohort of 106 LDLT patients receiving an extended left liver lobe graft. The skeletal muscle index (SMI) at L3 level was used for muscle mass measurement, and the recommended cut-off values of the Japanese Society of Hepatology guidelines were used as criteria for defining low muscularity. GR was evaluated as rate of volume increase at 1 month post-LT [graft regeneration rate (GRR)]. Results: The median GRR at 1 month post-LT was 91% (IQR, 65-128%) and a significant correlation with graft volume-to-recipient standard liver volume ratio (GV/SLV) (rho -0.467, P<0.001), graft-to-recipient weight ratio (GRWR) (rho -0.414, P<0.001), donor age (rho -0.306, P=0.001), 1 month post-LT cholinesterase serum levels (rho 0.397, P=0.002) and pre-LT low muscularity [absent vs. present GRR 97.5% (73.1-130%) vs. 83.5% (45.2-110.9%), P=0.041] was noted. Moreover in male recipients, but not in women, it was shown a direct correlation with pre-LT SMI (rho 0.352, P=0.020) and inverse correlation with 1 month post-LT SMI variation (rho -0.301, P=0.049). A low GRR was identified as an independent prognostic factor for recipient overall survival (HR 6.045, P<0.001). Conclusions: Additionally to the hemodynamic factors of portal circulation and the quality of the graft, the metabolic status of the recipients has a significant role in the GR process. A pre-LT low SMM is associated with impaired GRR and this negative impact is more evident in male recipients.
ESTHER : Pravisani_2020_Hepatobiliary.Surg.Nutr_9_183
PubMedSearch : Pravisani_2020_Hepatobiliary.Surg.Nutr_9_183
PubMedID: 32355676

Title : Serum concentration of full-length- and carboxy-terminal fragments of endothelial lipase predicts future cardiovascular risks in patients with coronary artery disease - Nagao_2019_J.Clin.Lipidol_13_839
Author(s) : Nagao M , Miyashita K , Mori K , Irino Y , Toh R , Hara T , Hirata KI , Shinohara M , Nakajima K , Ishida T
Ref : J Clin Lipidol , 13 :839 , 2019
Abstract : BACKGROUND: Endothelial lipase (EL), a regulator of plasma high-density lipoprotein cholesterol (HDL-C), is secreted as a 68-kDa mature glycoprotein, and then cleaved by proprotein convertases. However, the clinical significance of the circulating EL fragments remains unclear. OBJECTIVE: The objective of this study was to analyze the impact of serum EL fragments on HDL-C levels and major adverse cardiovascular events (MACE). METHODS: Using novel monoclonal antibodies (RC3A6) against carboxy-terminal EL protein, we have established a new enzyme-linked immunosorbent assay (ELISA) system, which can detect both full-length EL protein (full EL) and carboxy-terminal truncated fragments (total EL) in serum. The previous sandwich ELISA detected only full EL. The full and total EL mass were measured in 556 patients with coronary artery disease. Among them, 272 patients who underwent coronary intervention were monitored for 2 years for MACE. RESULTS: There was a significant correlation between serum full and total EL mass (R = 0.45, P < .0001). However, the total EL mass showed a stronger inverse correlation with serum HDL-cholesterol concentration than the full EL mass (R = -0.17 vs -0.02). Kaplan-Meier analysis documented an association of serum total EL mass and MACE (log-rank P = .037). When an optimal cutoff value was set at 96.23 ng/mL, total EL mass was an independent prognostic factor for MACE in the Cox proportional hazard model (HR; 1.75, 95% CI; 1.10-2.79, P = .018). CONCLUSION: Serum total EL mass could be a predictor for MACE in patients with coronary artery disease. This novel ELISA will be useful for further clarifying the impact of EL on HDL metabolism and atherosclerosis.
ESTHER : Nagao_2019_J.Clin.Lipidol_13_839
PubMedSearch : Nagao_2019_J.Clin.Lipidol_13_839
PubMedID: 31473149

Title : Effects of super-hard rice bread blended with black rice bran on amyloid beta peptide production and abrupt increase in postprandial blood glucose levels in mice - Nakamura_2016_Biosci.Biotechnol.Biochem__1
Author(s) : Nakamura S , Hara T , Joh T , Kobayashi A , Yamazaki A , Kasuga K , Ikeuchi T , Ohtsubo K
Ref : Biosci Biotechnol Biochem , :1 , 2016
Abstract : Alzheimer's disease and type 2 diabetes are very serious diseases with the latter having been suggested to cause the former. We prepared super-hard rice bread blended with black rice bran (SRBBB), which contained a high amount of resistant starch that showed strong inhibitory activities against beta-secretase and acetylcholinesterase even after heating. Black rice bran showed greater beta-secretase inhibitory activity (3.6-fold) than Koshihikari rice. The bran contained more oleic acid and anthocyanin, meaning that it is potentially a biofunctional food with a high antioxidant capacity. Furthermore, aged mice, which were fed a SRBBB diet for four weeks, showed lower amyloid beta 40 peptide in the blood than mice fed a commercial diet (p < 0.01). Additionally, their initial blood glucose levels (BGLs) after 12 weeks of being fed SRBBB were significantly lower than those in the control group. Taken together, our results indicate SRBBB shows promise for inhibiting not only amyloid beta production, but also abrupt increases in postprandial BGLs.
ESTHER : Nakamura_2016_Biosci.Biotechnol.Biochem__1
PubMedSearch : Nakamura_2016_Biosci.Biotechnol.Biochem__1
PubMedID: 27696976

Title : Endothelial lipase modulates pressure overload-induced heart failure through alternative pathway for fatty acid uptake - Nakajima_2013_Hypertension_61_1002
Author(s) : Nakajima H , Ishida T , Satomi-Kobayashi S , Mori K , Hara T , Sasaki N , Yasuda T , Toh R , Tanaka H , Kawai H , Hirata K
Ref : Hypertension , 61 :1002 , 2013
Abstract : Lipoprotein lipase has been considered as the only enzyme capable of generating lipid-derived fatty acids for cardiac energy. Endothelial lipase is another member of the triglyceride lipase family and hydrolyzes high-density lipoproteins. Although endothelial lipase is expressed in the heart, its function remains unclear. We assessed the role of endothelial lipase in the genesis of heart failure. Pressure overload-induced cardiac hypertrophy was generated in endothelial lipase(-/-) and wild-type mice by ascending aortic banding. Endothelial lipase expression in cardiac tissues was markedly elevated in the early phase of cardiac hypertrophy in wild-type mice, whereas lipoprotein lipase expression was significantly reduced. Endothelial lipase(-/-) mice showed more severe systolic dysfunction with left-ventricular dilatation compared with wild-type mice in response to pressure overload. The expression of mitochondrial fatty acid oxidation-related genes, such as carnitine palmitoyltransferase-1 and medium-chain acyl coenzyme A dehydrogenase, was significantly lower in the heart of endothelial lipase(-/-) mice than in wild-type mice. Also, endothelial lipase(-/-) mice had lower myocardial adenosine triphosphate levels than wild-type mice after aortic banding. In cultured cardiomyocytes, endothelial lipase was upregulated by inflammatory stimuli, whereas lipoprotein lipase was downregulated. Endothelial lipase-overexpression in cardiomyocytes resulted in an upregulation of fatty acid oxidation-related enzymes and intracellular adenosine triphosphate accumulation in the presence of high-density lipoprotein. Endothelial lipase may act as an alternative candidate to provide fatty acids to the heart and regulate cardiac function. This effect seemed relevant particularly in the diseased heart, where lipoprotein lipase action is downregulated.
ESTHER : Nakajima_2013_Hypertension_61_1002
PubMedSearch : Nakajima_2013_Hypertension_61_1002
PubMedID: 23460280

Title : Targeted deletion of endothelial lipase increases HDL particles with anti-inflammatory properties both in vitro and in vivo - Hara_2011_J.Lipid.Res_52_57
Author(s) : Hara T , Ishida T , Kojima Y , Tanaka H , Yasuda T , Shinohara M , Toh R , Hirata K
Ref : J Lipid Res , 52 :57 , 2011
Abstract : Previous studies have shown that targeted deletion of endothelial lipase (EL) markedly increases the plasma high density lipoprotein cholesterol (HDL-C) level in mice. However, little is known about the functional quality of HDL particles after EL inhibition. Therefore, the present study assessed the functional quality of HDL isolated from EL(-/-) and wild-type (WT) mice. Anti-inflammatory functions of HDL from EL(-/-) and WT mice were evaluated by in vitro assays. The HDL functions such as PON-1 or PAF-AH activities, inhibition of cytokine-induced vascular cell adhesion molecule-1 expression, inhibition of LDL oxidation, and the ability of cholesterol efflux were similar in HDL isolated from WT and EL(-/-) mice. In contrast, the lipopolysaccharide-neutralizing capacity of HDL was significantly higher in EL(-/-) mice than that in WT mice. To evaluate the anti-inflammatory actions of HDL in vivo, lipopolysaccharide-induced systemic inflammation was generated in these mice. EL(-/-) mice showed higher survival rate and lower expression of inflammatory markers than WT mice. Intravenous administration of HDL isolated from EL(-/-) mice significantly improved the mortality after lipopolysaccharide injection in WT mice. In conclusion, targeted disruption of EL increased HDL particles with preserved anti-inflammatory and anti-atherosclerotic functions. Thus, EL inhibition would be a useful strategy to raise 'good' cholesterol in the plasma.
ESTHER : Hara_2011_J.Lipid.Res_52_57
PubMedSearch : Hara_2011_J.Lipid.Res_52_57
PubMedID: 20926433

Title : Lipoprotein lipase activator NO-1886 improves fatty liver caused by high-fat feeding in streptozotocin-induced diabetic rats - Kusunoki_2004_Metabolism_53_260
Author(s) : Kusunoki M , Tsutsumi K , Inoue Y , Hara T , Miyata T , Nakamura T , Ogawa H , Sakakibara F , Fukuzawa Y , Okabayashi N , Kato K , Ikeda H , Kurokawa T , Ishikawa T , Otake K , Nakaya Y
Ref : Metabolism , 53 :260 , 2004
Abstract : NO-1886 is a lipoprotein lipase (LPL) activator. Administration of NO-1886 results in an increase in plasma high-density lipoprotein cholesterol (HDL-C) and a decrease in plasma triglyceride (TG) levels. The aim of this study was to ascertain whether NO-1886 improves fatty liver caused by high-fat feeding in streptozotocin (STZ)-induced diabetic rats. Administration of NO-1886 resulted in increased plasma HDL-C levels and decreased TG levels without affecting total cholesterol and glucose levels in the diabetic rats. NO-1886 dose-dependently decreased liver TG contents and cholesterol contents, resulting in improvement of fatty liver. NO-1886 also reduced plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) that accompany fatty liver. The liver cholesterol contents were inversely correlated with plasma HDL-C levels (r = -0.5862, P <.001) and were positively correlated with plasma TG levels (r = 0.4083, P <.003). The liver TG contents were inversely correlated with plasma HDL-C levels (r = -0.6195, P <.001) and were positively correlated with plasma TG levels (r = 0.5837, P <.001). There was no correlation between plasma cholesterol levels, and cholesterol and TG contents in liver. These results indicate that reducing plasma TG levels and elevating in HDL-C levels may result in improving fatty liver.
ESTHER : Kusunoki_2004_Metabolism_53_260
PubMedSearch : Kusunoki_2004_Metabolism_53_260
PubMedID: 14767881

Title : Design, synthesis and structure-Activity relationships of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease - Toda_2003_Bioorg.Med.Chem_11_1935
Author(s) : Toda N , Tago K , Marumoto S , Takami K , Ori M , Yamada N , Koyama K , Naruto S , Abe K , Yamazaki R , Hara T , Aoyagi A , Abe Y , Kaneko T , Kogen H
Ref : Bioorganic & Medicinal Chemistry , 11 :1935 , 2003
Abstract : We have designed and synthesized a dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT) as a novel class of treatment drugs for Alzheimer's disease on the basis of a hypothetical model of the AChE active site. Dual inhibitions of AChE and SERT would bring about greater therapeutic effects than AChE inhibition alone and avoid adverse peripheral effects caused by excessive AChE inhibition. Compound (S)-6j exhibited potent inhibitory activities against AChE (IC(50)=101 nM) and SERT (IC(50)=42 nM). Furthermore, (S)-6j showed inhibitory activities of both AChE and SERT in mice brain following oral administration.
ESTHER : Toda_2003_Bioorg.Med.Chem_11_1935
PubMedSearch : Toda_2003_Bioorg.Med.Chem_11_1935
PubMedID: 12670645

Title : A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease - Toda_2003_Bioorg.Med.Chem_11_4389
Author(s) : Toda N , Tago K , Marumoto S , Takami K , Ori M , Yamada N , Koyama K , Naruto S , Abe K , Yamazaki R , Hara T , Aoyagi A , Abe Y , Kaneko T , Kogen H
Ref : Bioorganic & Medicinal Chemistry , 11 :4389 , 2003
Abstract : Alzheimer's disease (AD) has been treated with acetylcholinesterase (AChE) inhibitors such as donepezil. However, the clinical usefulness of AChE inhibitors is limited mainly due to their adverse peripheral effects. Depression seen in AD patients has been treated with serotonin transporter (SERT) inhibitors. We considered that combining SERT and AChE inhibition could improve the clinical usefulness of AChE inhibitors. In a previous paper, we found a potential dual inhibitor, 1, of AChE (IC50=101 nM) and SERT (IC50=42 nM), but its AChE inhibition activity was less than donepezil (IC50=10 nM). Here, we report the conformationally restricted (R)-18a considerably enhanced inhibitory activity against AChE (IC50=14 nM) and SERT (IC50=6 nM).
ESTHER : Toda_2003_Bioorg.Med.Chem_11_4389
PubMedSearch : Toda_2003_Bioorg.Med.Chem_11_4389
PubMedID: 13129577

Title : Pharmacological characterization of RS-1259, an orally active dual inhibitor of acetylcholinesterase and serotonin transporter, in rodents: possible treatment of Alzheimer's disease - Abe_2003_J.Pharmacol.Sci_93_95
Author(s) : Abe Y , Aoyagi A , Hara T , Abe K , Yamazaki R , Kumagae Y , Naruto S , Koyama K , Marumoto S , Tago K , Toda N , Takami K , Yamada N , Ori M , Kogen H , Kaneko T
Ref : J Pharmacol Sci , 93 :95 , 2003
Abstract : A dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT), RS-1259 (4-[1S)-methylamino-3-(4-nitrophenoxy)]propylphenyl N,N-dimethylcarbamate (fumaric acid)(1/2)salt), was newly synthesized. RS-1259 simultaneously inhibited AChE and SERT in the brain following an oral administration in mice and rats. Actual simultaneous elevation of extracellular levels of 5-HT and ACh in the rat hippocampus was confirmed by microdialysis. The compound was as effective as SERT inhibitors such as fluoxetine and fluvoxamine in a 5-hydroxytryptophan-enhancing test in mice. Spatial memory deficits in the two-platform task of a water maze in aged rats were ameliorated by RS-1259 as well as donepezil. Both RS-1259 and donepezil increased the awake episodes in the daytime electroencephalogram of rats. Although RS-1259 was weaker than donepezil in enhancing central cholinergic transmission, as observed by ACh elevation in the hippocampus and memory enhancement in aged rats, the efficacy of RS-1259 on the consciousness level, which reflects the whole activity in the brain, was almost the same as that of donepezil. These results suggest that both cholinergic and serotonergic systems are involved in maintaining brain arousal and that a dual inhibitor of AChE and SERT may be useful for the treatment of cognitive disorders associated with reduced brain activity such as in Alzheimer's disease.
ESTHER : Abe_2003_J.Pharmacol.Sci_93_95
PubMedSearch : Abe_2003_J.Pharmacol.Sci_93_95
PubMedID: 14501158

Title : Design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter targeting potential agents for Alzheimer's disease - Kogen_2002_Org.Lett_4_3359
Author(s) : Kogen H , Toda N , Tago K , Marumoto S , Takami K , Ori M , Yamada N , Koyama K , Naruto S , Abe K , Yamazaki R , Hara T , Aoyagi A , Abe Y , Kaneko T
Ref : Org Lett , 4 :3359 , 2002
Abstract : Highly efficient acetylcholinesterase (AChE) and serotonin transporter (SERT) dual inhibitors, (S)-4 and (R)-13 were designed and synthesized on the basis of the hypothetical model of AChE active site. Both compounds showed potent inhibitory activities against AChE and SERT. [structure: see text]
ESTHER : Kogen_2002_Org.Lett_4_3359
PubMedSearch : Kogen_2002_Org.Lett_4_3359
PubMedID: 12323018

Title : Comparative studies of larval and pupal phenoloxidase of the housefly, Musca domestica L - Hara_1993_Comp.Biochem.Physiol.B_106_287
Author(s) : Hara T , Miyoshi T , Tsukamoto T
Ref : Comparative Biochemistry & Physiology B , 106 :287 , 1993
Abstract : 1. Larval and pupal phenoloxidase of the housefly, Musca domestica L. resembled each other in some enzymatic properties, such as optimal pH, pH stability, optimal temperature and thermal stability. 2. The pI values of both enzymes were 4.85, as determined by isoelectric focusing. The molecular weights of two enzymes had a similar value (320,000 and 330,000 for larval and pupal phenoloxidase, respectively) and the molecular weights of these subunits had the same value of 60,000. 3. The aminio acid compositions of two enzymes were very similar. N-terminal amino acid sequences of larval and pupal enzymes were Glu-Glu-Ala-Thr-Val-Val-Pro-Asp-Gly- and Ala-Thr-Val-Val-Pro-Asp-Gly-Tyr-Phe-Met-, respectively, and the residues 3-9 (larval phenoloxidase) were in agreement with the residues 1-7 (pupal phenoloxidase).
ESTHER : Hara_1993_Comp.Biochem.Physiol.B_106_287
PubMedSearch : Hara_1993_Comp.Biochem.Physiol.B_106_287
PubMedID: 8174350

Title : Pregnancy decreases the threshold for cocaine-induced convulsions in the rat - Morishima_1993_J.Lab.Clin.Med_122_748
Author(s) : Morishima HO , Masaoka T , Hara T , Tsuji A , Cooper TB
Ref : Journal of Laboratory & Clinical Medicine , 122 :748 , 1993
Abstract : The objective of this study was to test our hypothesis that pregnancy modifies the central nervous and cardiovascular toxicity of cocaine. Ten chronically catheterized term pregnant rats and 13 chronically catheterized nonpregnant female rats were infused with cocaine (2 mg/kg/min) intravenously to observe the sequential toxic manifestation of cocaine from mild central nervous stimulation (hyper-locomotor activities) to fatal cardiovascular collapse. Arterial blood samples were withdrawn at the onset of major toxic signs or symptoms--namely convulsion, hypotension, and circulatory collapse--for determination of cocaine concentrations and plasma cholinesterase activity. The dosage and plasma concentrations of cocaine associated with the onset of convulsions and cardiovascular depression were significantly lower in pregnant rats when compared with the nonpregnant animals. The mean time required to develop convulsions in the pregnant rat was significantly shorter (21 minutes) than that in the nonpregnant animal (33 minutes). However, once convulsive activity had developed, the time interval to achieve circulatory collapse was similar in both groups. Although the baseline plasma cholinesterase activity was higher in the pregnant rats than in the nonpregnant ones, the values in the samples obtained from the pregnant group at the onset of circulatory collapse were similar to the baseline values for the nonpregnant group. These findings suggest that a higher enzyme activity does not protect the development of toxic manifestations in the pregnant rat as compared to the nonpregnant animal when cocaine was administered at the same infusion rate.
ESTHER : Morishima_1993_J.Lab.Clin.Med_122_748
PubMedSearch : Morishima_1993_J.Lab.Clin.Med_122_748
PubMedID: 8245693