Yamada S

References (27)

Title : Biochemical Evaluation of Laparoscopic Portoenterostomy for Treating Biliary Atresia and Redo for Failed Portoenterostomy - Tsukui_2022_J.Laparoendosc.Adv.Surg.Tech.A__
Author(s) : Tsukui T , Koga H , Cazares J , Yamada S , Murakami H , Shibuya S , Nakamura H , Ochi T , Tsuboi K , Lane G , Tanaka N , Miyano G , Okazaki T , Urao M , Yamataka A
Ref : J Laparoendosc Adv Surg Tech A , : , 2022
Abstract : Background: Postoperative outcomes of portoenterostomy (PE) and redo-PE were evaluated using selected biochemical markers (SBM) and biochemical status categories (BSC). Methods: Subjects were 70 consecutive PE performed for biliary atresia. SBM were aspartate aminotransferase (AST)/alanine aminotransferase (ALT), cholinesterase (ChE), and platelet count (PLT) assessed at 1, 2, 3, 6, and 12 months, and thence, annually for a maximum of 10 years. BSC were as follows: all SBM normal (N-SBM), normal AST/ALT (N-SLT), normal ChE (N-ChE), normal PC (N-PLT), all abnormal (A-SBM), abnormal AST/ALT (A-SLT), abnormal ChE (A-ChE), and abnormal PC (A-PLT). Subjects achieving jaundice clearance (JC) and surviving with native livers (SNL) also had gamma glutamyl transpeptidase assessed. Redo-PE indicated for failed PE was assessed postoperatively using the same SBM/BSC protocol. Results: PE were laparoscopic (LPE; n = 40) or open (OPE; n = 30). Mean age/weight at PE and duration of follow-up were similar. For JC, LPE = 34/40 (85.0%) and OPE = 22/30 (73.3%); P = .23. For SNL, LPE = 29/40 (72.5%) and OPE = 16/30 (53.3%); P = .10. LPE and OPE were similar for SBM/BSC, except for a single significant increase in ALT in OPE at 6 months. Redo-PE was performed 17-180 days (mean 67.1 days) after primary PE. AST was significantly increased at the last preredo assessment 3 months after primary PE; P < .05. After redo, AST decreased and SBM/BSC results were equivalent to nonredo subjects. Conclusion: Postoperative biochemical data for all PE cases were comparable; redo-PE would appear to be viable for restoring SBM, and AST could be valuable as a single marker of deterioration in redo cases.
ESTHER : Tsukui_2022_J.Laparoendosc.Adv.Surg.Tech.A__
PubMedSearch : Tsukui_2022_J.Laparoendosc.Adv.Surg.Tech.A__
PubMedID: 35939285

Title : Significance of furosemide in patients with cirrhosis treated with or without zinc acetate hydrate supplementation - Uchida_2022_Hepatol.Res__
Author(s) : Uchida Y , Uemura H , Tsuji S , Yamada S , Kouyama JI , Naiki K , Sugawara K , Nakao M , Nakayama N , Imai Y , Tomiya T , Mochida S
Ref : Hepatol Res , : , 2022
Abstract : BACKGROUND: The Japanese guidelines for the treatment of cirrhosis suggest zinc supplementation to prevent hepatic encephalopathy in patients with cirrhosis and zinc deficiency, although the factors that are associated with therapeutic efficacy remain unknown. METHOD: A total of 159 patients with chronic liver diseases but without previous zinc supplementation were analyzed. Factors associated with serum zinc levels as well as the therapeutic efficacy of zinc supplementation were evaluated. RESULT: Serum zinc levels decreased with the progression of liver diseases. A multiple linear regression analysis revealed that the serum levels of albumin and cholinesterase and the daily furosemide dose were independently associated with the serum zinc levels. The optimal furosemide cut-off dosage for patients with zinc deficiency (<60 microg/dL) was 5 mg/day. Among 34 patients receiving zinc acetate hydrate, overt hepatic encephalopathy occurred in 12 patients (35.4%). A multivariate analysis identified a minimal serum zinc level of 50 microg/dL after more than 12 weeks of zinc supplementation as a factor associated with overt encephalopathy development, while furosemide use was not associated. The Child-Pugh score at baseline was the only factor associated with the maintenance of sufficient serum zinc levels. CONCLUSION: Although the furosemide dose was negatively correlated with the serum zinc level in patients with chronic liver diseases, furosemide use was not associated with the occurrence of overt encephalopathy in those receiving zinc supplementation. Serum zinc levels of <=50 microg/dL were required to prevent overt encephalopathy development during zinc supplementation in both patients with and those without furosemide administration. This article is protected by copyright. All rights reserved.
ESTHER : Uchida_2022_Hepatol.Res__
PubMedSearch : Uchida_2022_Hepatol.Res__
PubMedID: 35113468

Title : Lipase-a single-nucleotide polymorphism rs143793106 is associated with increased risk of aggressive periodontitis by negative influence on the cytodifferentiation of human periodontal ligament cells - Matsumoto_2022_J.Periodontal.Res__
Author(s) : Matsumoto M , Fujihara C , Nantakeeratipat T , Kitagaki J , Yamamoto Y , Yamada S , Kitamura M , Murakami S
Ref : J Periodontal Res , : , 2022
Abstract : BACKGROUND AND OBJECTIVE: Aggressive periodontitis (AgP) is characterized by general health and rapid destruction of periodontal tissue. The familial aggregation of this disease highlights the involvement of genetic factors in its pathogeny. We conducted a genome-wide association study (GWAS) to identify AgP-related genes in a Japanese population, and the lipid metabolism-related gene, lipase-a, lysosomal acid type (LIPA), was suggested as an AgP candidate gene. However, there is no report about the expression and function(s) of LIPA in periodontal tissue. Hence, we studied the involvement of how LIPA and its single-nucleotide polymorphism (SNP) rs143793106 in AgP by functional analyses of LIPA and its SNP in human periodontal ligament (HPDL) cells. MATERIALS AND METHODS: GWAS was performed using the genome database of Japanese AgP patients, and the GWAS result was confirmed using Sanger sequencing. We examined the mRNA expression level of LIPA and the protein expression level of the encoded protein lysosomal acid lipase (LAL) in periodontium-composing cells using conventional and real-time polymerase chain reaction (PCR) and western blotting, respectively. Lentiviral vectors expressing LIPA wild-type (LIPA WT) and LIPA SNP rs143793106 (LIPA mut) were transfected into HPDL cells. Western blotting was performed to confirm the transfection. LAL activity of transfected HPDL cells was determined using the lysosomal acid lipase activity assay. Transfected HPDL cells were cultured in mineralization medium. During the cytodifferentiation of transfected HPDL cells, mRNA expression of calcification-related genes, alkaline phosphatase (ALPase) activity and calcified nodule formation were assessed using real-time PCR, ALPase assay, and alizarin red staining, respectively. RESULTS: The GWAS study identified 11 AgP-related candidate genes, including LIPA SNP rs143793106. The minor allele frequency of LIPA SNP rs143793106 in AgP patients was higher than that in healthy subjects. LIPA mRNA and LAL protein were expressed in HPDL cells; furthermore, they upregulated the cytodifferentiation of HPDL cells. LAL activity was lower in LIPA SNP-transfected HPDL cells during cytodifferentiation than that in LIPA WT-transfected HPDL cells. In addition, ALPase activity, calcified nodule formation, and calcification-related gene expression levels were lower during cytodifferentiation in LIPA SNP-transfected HPDL cells than those in LIPA WT-transfected HPDL cells. CONCLUSION: LIPA, identified as an AgP-related gene in a Japanese population, is expressed in HPDL cells and is involved in regulating cytodifferentiation of HPDL cells. LIPA SNP rs143793106 suppressed cytodifferentiation of HPDL cells by decreasing LAL activity, thereby contributing to the development of AgP.
ESTHER : Matsumoto_2022_J.Periodontal.Res__
PubMedSearch : Matsumoto_2022_J.Periodontal.Res__
PubMedID: 36494917

Title : Usefulness of the plasma branched-chain amino acid\/aromatic amino acid ratio for predicting future cardiac events in patients with heart failure - Hiraiwa_2020_J.Cardiol__
Author(s) : Hiraiwa H , Okumura T , Kondo T , Kato T , Kazama S , Ishihara T , Iwata E , Shimojo M , Kondo S , Aoki S , Kanzaki Y , Tanimura D , Sano H , Awaji Y , Yamada S , Murohara T
Ref : J Cardiol , : , 2020
Abstract : BACKGROUND: Heart failure (HF) is a hypercatabolic state that promotes branched-chain amino acid (BCAA) catabolic activity in the heart and skeletal muscle and reduces protein synthesis in the liver. Consequently, plasma free aromatic amino acids (AAAs) are increased. We investigated the prognostic value of the BCAA/AAA ratio (Fischer's ratio, FR) in patients with HF. METHODS: We enrolled 157 consecutive patients hospitalized for worsening HF (81 men, 76 women; mean +/- SD age 75 +/- 14 years). Plasma BCAA levels (i.e. total leucine, isoleucine, valine) and AAA levels (i.e. total tyrosine, phenylalanine) were measured at a time when the patients were stabilized (at discharge). FR was calculated as the combined plasma BCAA levels divided by the AAA level. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. RESULTS: The patients were divided into two groups based on the median FR (high-FR group: FR >/= 3.1, n = 78; low-FR group: FR < 3.1, n = 79). Compared with the high-FR group, low-FR patients were older, had more prior hospitalizations for HF, lower albumin and cholinesterase levels, and lower geriatric nutritional risk index (GNRI). Altogether, 46 cardiac events occurred during the follow-up period (221 +/- 135 days), including 14 cardiac deaths and 32 hospitalizations for worsening HF. In a Kaplan-Meier survival analysis, the low-FR group had more cardiac events than the high-FR group (log-rank, p < 0.001). The best cut-off value of FR was determined as 2.9 in the receiver operating characteristic curve for cardiac events. A multivariate Cox proportional hazards regression analysis showed that being in the low-FR group was an independent determinant of cardiac events from parameters of liver function tests and GNRI. CONCLUSIONS: FR might be useful for predicting future cardiac events in patients with HF, reflecting nutritional status which cannot be assessed by liver function tests and GNRI.
ESTHER : Hiraiwa_2020_J.Cardiol__
PubMedSearch : Hiraiwa_2020_J.Cardiol__
PubMedID: 32001073

Title : Feasibility of subtotal esophagectomy with systematic lymphadenectomy in selected elderly patients with esophageal cancer\; a propensity score matching analysis - Kanda_2019_BMC.Surg_19_143
Author(s) : Kanda M , Koike M , Tanaka C , Kobayashi D , Hayashi M , Yamada S , Nakayama G , Omae K , Kodera Y
Ref : BMC Surg , 19 :143 , 2019
Abstract : BACKGROUND: The global increase in elderly populations is accompanied by an increasing number of candidates for esophagectomy. Here we aimed to determine the postoperative outcomes after subtotal esophagectomy in elderly patients with esophageal cancer. METHODS: Patients (n = 432) with who underwent curative-intent transthoracic subtotal esophagectomy with 2- or 3-field lymphadenectomies for thoracic esophageal cancer were classified as follows: non-elderly (age < 75 years, n = 373) and elderly (age >/= 75 years, n = 59) and groups. To balance the essential variables including neoadjuvant treatment and stage of progression, we conducted propensity score analysis, and clinical characteristics, perioperative course and prognosis were compared. RESULTS: After two-to-one propensity score matching, 100 and 50 patients were classified in the non-elderly and elderly groups. The elderly group had more comorbidities and lower preoperative cholinesterase activities and prognostic nutrition indexes. Although incidences of postoperative pneumonia, arrhythmia and delirium were slightly increased in the elderly group, no significant differences were observed in overall incidence of postoperative complications, rates of repeat surgery and death caused by surgery, and length of postoperative hospital stay between the two groups. There were no significant differences in disease-free and disease-specific survival as well as overall survival between the two groups. CONCLUSION: Older age (>/=75 years) had limited impact on morbidity, disease recurrence, and survival after subtotal esophagectomy. Therefore, age should not prevent older patients from benefitting from surgery.
ESTHER : Kanda_2019_BMC.Surg_19_143
PubMedSearch : Kanda_2019_BMC.Surg_19_143
PubMedID: 31615499

Title : [Possible relationship between prescription medications and urinary dysfunction in elderly home health care patients] - Miyazaki_2019_Nihon.Ronen.Igakkai.Zasshi_56_301
Author(s) : Miyazaki S , Yamada S , Higashino S , Watanabe Y , Mizukami K
Ref : Nihon Ronen Igakkai Zasshi , 56 :301 , 2019
Abstract : AIM: Although urinary incontinence (UI) in the elderly appears to be related to polypharmacy, it is unclear whether multiple medications elevate UI quantitatively or qualitatively. There have been few studies on the association of polypharmacy with each type of UI. The present survey aimed to clarify these issues. METHOD: The subjects were elderly home health care patients >/=65 years of age taking >/=5 prescription medications and not being treated with anti-cancer agent. The visiting nurses filled out a questionnaire based on their nursing and medication records. Types of UI were evaluated according to a UI checklist. RESULTS: A total of 167 subjects (97 women, 70 men, mean age of 83.8 years) were eligible for the data analysis. Subjects talking 5-9 prescription medications accounted for 59.3%, while those talking>/=10 counted for 40.7%. Men talking >/=10 medications showed a slight but non-significant increased risk of UI. In women, alpha-adrenergic antagonists and benzodiazepines significantly increased the risk of stress UI and urge UI, respectively. Furthermore, alpha-adrenergic antagonists reduced the risk of functional UI, whereas acetylcholinesterase inhibitors elevated it. alpha-adrenergic antagonists in combination with benzodiazepines also significantly increased the risk of stress UI and urge UI, while alpha-adrenergic antagonists with acetylcholinesterase inhibitors increased the risk of stress UI. In men, there were no prescription medications that were particularly related to UI. CONCLUSIONS: The present results suggest that there are gender differences in prescription medications-induced UI. It is likely that the causing medications are different depending on the type of UI, and the combination of them significantly increase the risk of UI.
ESTHER : Miyazaki_2019_Nihon.Ronen.Igakkai.Zasshi_56_301
PubMedSearch : Miyazaki_2019_Nihon.Ronen.Igakkai.Zasshi_56_301
PubMedID: 31366751

Title : Effect of Royal Jelly on Mouse Isolated Ileum and Gastrointestinal Motility - Miyauchi-Wakuda_2019_J.Med.Food_22_789
Author(s) : Miyauchi-Wakuda S , Kagota S , Maruyama-Fumoto K , Wakuda H , Yamada S , Shinozuka K
Ref : J Med Food , 22 :789 , 2019
Abstract : Royal jelly (RJ) is widely used as a cosmetic or dietary supplement to relieve various health disorders, such as dry skin, fatigue, and menopause. RJ has been recommended to improve constipation on a commercial basis. However, the detailed mechanisms by which RJ influences intestinal motility and whether RJ improves constipation remain unclear. Therefore, we investigated the effects of RJ on the motility of mouse ileum both in vitro and in vivo. Using myograph methods, RJ dose-dependently induced contractions of isolated ileal segments, which were inhibited by treatment with atropine. Eserine sulfate, a cholinesterase inhibitor, enhanced the RJ-induced contractions, whereas RJ treated with acetylcholinesterase did not result in ileum contraction. RJ-induced contractions were not affected by N(G)-nitro-l-arginine methyl ester, a nitric oxide synthase inhibitor, although nicotine-induced contractions were significantly enhanced. In contrast, in a gastrointestinal (GI) transit model, single oral administration of 300 mg/kg RJ did not affect GI transit in both normal mice and the loperamide-induced constipation model mice. These results demonstrate that acetylcholine in RJ directly acted on the muscarinic receptors of the mouse intestinal smooth muscle, causing it to contract in vitro. In contrast, single oral administration of RJ did not improve constipation. This study is the first to evaluate the effects of RJ on the motility of mouse ileum in in vitro and in vivo experiments for the validation of application of RJ as a gentle laxative.
ESTHER : Miyauchi-Wakuda_2019_J.Med.Food_22_789
PubMedSearch : Miyauchi-Wakuda_2019_J.Med.Food_22_789
PubMedID: 31329014

Title : Risk Prediction of Postoperative Pneumonia After Subtotal Esophagectomy Based on Preoperative Serum Cholinesterase Concentrations - Kanda_2019_Ann.Surg.Oncol_26_3718
Author(s) : Kanda M , Koike M , Tanaka C , Kobayashi D , Hayashi M , Yamada S , Omae K , Kodera Y
Ref : Annals of Surgery Oncol , 26 :3718 , 2019
Abstract : BACKGROUND: Patients undergoing subtotal esophagectomy for esophageal cancer frequently experience postoperative pneumonia. Development of preoperatively determined predictors for postoperative pneumonia will facilitate identifying high-risk patients and will assist with informing patients about their risk of postoperative pneumonia, enabling physicians to estimate with greater accuracy, will result in tailoring perioperative management. METHODS: Postoperative pneumonia was defined according to the revised Uniform Pneumonia Score. We analyzed the data for 355 patients to compare 32 potential predictive variables associated with postoperative pneumonia after subtotal esophagectomy. RESULTS: Forty-one patients (11.5%) had postoperative pneumonia. Preoperative cholinesterase (ChE) concentrations demonstrated the greatest area under the curve value (0.662) to predict postoperative pneumonia (optimal cutoff value = 217 IU/l). Univariate analysis identified a continuous value of preoperative ChE concentration as a significant risk factor for postoperative pneumonia (P = 0.0014). Multivariable analysis using factors potentially relevant to pneumonia revealed that preoperative ChE concentration was one of independent risk factors for pneumonia after esophagectomy (P = 0.008). Patients with low ChE concentrations were at increased risk of postoperative pneumonia in most patient subgroups. Moreover, the odds ratios of low ChE concentrations were highest in patients undergoing neoadjuvant treatment. A combination of preoperative serum ChE concentrations and Brinkman index stratified patients into low, intermediate, and high risk of postoperative pneumonia. CONCLUSIONS: Our findings indicate that preoperative ChE concentrations, particularly in combination with Brinkman index, may serve simply as a determined predictor of pneumonia after subtotal esophagectomy and may facilitate physicians' efforts to reduce the incidence of postoperative pneumonia.
ESTHER : Kanda_2019_Ann.Surg.Oncol_26_3718
PubMedSearch : Kanda_2019_Ann.Surg.Oncol_26_3718
PubMedID: 31197518

Title : Pharmacological inhibition of adipose triglyceride lipase corrects high-fat diet-induced insulin resistance and hepatosteatosis in mice - Schweiger_2017_Nat.Commun_8_14859
Author(s) : Schweiger M , Romauch M , Schreiber R , Grabner GF , Hutter S , Kotzbeck P , Benedikt P , Eichmann TO , Yamada S , Knittelfelder O , Diwoky C , Doler C , Mayer N , De Cecco W , Breinbauer R , Zimmermann R , Zechner R
Ref : Nat Commun , 8 :14859 , 2017
Abstract : Elevated circulating fatty acids (FAs) contribute to the development of obesity-associated metabolic complications such as insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). Hence, reducing adipose tissue lipolysis to diminish the mobilization of FAs and lower their respective plasma concentrations represents a potential treatment strategy to counteract obesity-associated disorders. Here we show that specific inhibition of adipose triglyceride lipase (Atgl) with the chemical inhibitor, Atglistatin, effectively reduces adipose tissue lipolysis, weight gain, IR and NAFLD in mice fed a high-fat diet. Importantly, even long-term treatment does not lead to lipid accumulation in ectopic tissues such as the skeletal muscle or heart. Thus, the severe cardiac steatosis and cardiomyopathy that is observed in genetic models of Atgl deficiency does not occur in Atglistatin-treated mice. Our data validate the pharmacological inhibition of Atgl as a potentially powerful therapeutic strategy to treat obesity and associated metabolic disorders.
ESTHER : Schweiger_2017_Nat.Commun_8_14859
PubMedSearch : Schweiger_2017_Nat.Commun_8_14859
PubMedID: 28327588

Title : Genome Sequence of a Bacillus anthracis Outbreak Strain from Zambia, 2011 - Ohnishi_2014_Genome.Announc_2_e00116
Author(s) : Ohnishi N , Maruyama F , Ogawa H , Kachi H , Yamada S , Fujikura D , Nakagawa I , Hang'ombe MB , Thomas Y , Mweene AS , Higashi H
Ref : Genome Announc , 2 :e00116 , 2014
Abstract : In August 2011, an anthrax outbreak occurred among Hippopotamus amphibius hippopotamuses and humans in Zambia. Here, we report the draft genome sequence of the Bacillus anthracis outbreak strain CZC5, isolated from tissues of H. amphibius hippopotamuses that had died in the outbreak area.
ESTHER : Ohnishi_2014_Genome.Announc_2_e00116
PubMedSearch : Ohnishi_2014_Genome.Announc_2_e00116
PubMedID: 24604644
Gene_locus related to this paper: bacan-BA2392 , bacan-BA4324 , bacce-BC2171

Title : 3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis - Mori_2012_J.Neuroimmunol_245_75
Author(s) : Mori S , Kishi M , Kubo S , Akiyoshi T , Yamada S , Miyazaki T , Konishi T , Maruyama N , Shigemoto K
Ref : Journal of Neuroimmunology , 245 :75 , 2012
Abstract : This study investigated the effect of 3,4-diaminopyridine (3,4-DAP), a potent potentiator of transmitter release, on neuromuscular transmission in vivo in a mouse model of myasthenia gravis (MG) caused by antibodies against muscle-specific kinase (MuSK; MuSK-MG) and ex vivo in diaphragm muscle from these mice. 3,4-DAP significantly improved neuromuscular transmission, predominantly by increasing acetylcholine (ACh) release, supporting presynaptic potentiation as an effective treatment strategy for MuSK-MG patients who have defective transmitter release. In MuSK-MG, we suggest that only low-dose acetylcholinesterase (AChE) inhibitors be used to avoid side effects, and we propose that 3,4-DAP may be effective as a symptomatic therapy.
ESTHER : Mori_2012_J.Neuroimmunol_245_75
PubMedSearch : Mori_2012_J.Neuroimmunol_245_75
PubMedID: 22409941

Title : Antibodies against muscle-specific kinase impair both presynaptic and postsynaptic functions in a murine model of myasthenia gravis - Mori_2012_Am.J.Pathol_180_798
Author(s) : Mori S , Kubo S , Akiyoshi T , Yamada S , Miyazaki T , Hotta H , Desaki J , Kishi M , Konishi T , Nishino Y , Miyazawa A , Maruyama N , Shigemoto K
Ref : American Journal of Pathology , 180 :798 , 2012
Abstract : Antibodies against acetylcholine receptors (AChRs) cause pathogenicity in myasthenia gravis (MG) patients through complement pathway-mediated destruction of postsynaptic membranes at neuromuscular junctions (NMJs). However, antibodies against muscle-specific kinase (MuSK), which constitute a major subclass of antibodies found in MG patients, do not activate the complement pathway. To investigate the pathophysiology of MuSK-MG and establish an experimental autoimmune MG (EAMG) model, we injected MuSK protein into mice deficient in complement component five (C5). MuSK-injected mice simultaneously developed severe muscle weakness, accompanied by an electromyographic pattern such as is typically observed in MG patients. In addition, we observed morphological and functional defects in the NMJs of EAMG mice, demonstrating that complement activation is not necessary for the onset of MuSK-MG. Furthermore, MuSK-injected mice exhibited acetylcholinesterase (AChE) inhibitor-evoked cholinergic hypersensitivity, as is observed in MuSK-MG patients, and a decrease in both AChE and the AChE-anchoring protein collagen Q at postsynaptic membranes. These findings suggest that MuSK is indispensable for the maintenance of NMJ structure and function, and that disruption of MuSK activity by autoantibodies causes MG. This mouse model of EAMG could be used to develop appropriate medications for the treatment of MuSK-MG in humans.
ESTHER : Mori_2012_Am.J.Pathol_180_798
PubMedSearch : Mori_2012_Am.J.Pathol_180_798
PubMedID: 22142810

Title : Genetic variation in carboxylesterase genes and susceptibility to isoniazid-induced hepatotoxicity - Yamada_2010_Pharmacogenomics.J_10_524
Author(s) : Yamada S , Richardson K , Tang M , Halaschek-Wiener J , Cook VJ , Fitzgerald JM , Elwood K , Marra F , Brooks-Wilson A
Ref : Pharmacogenomics J , 10 :524 , 2010
Abstract : Treatment of latent tuberculosis infection (LTBI) generally includes isoniazid (INH), a drug that can cause serious hepatotoxicity. Carboxylesterases (CES) are important in the metabolism of a variety of substrates, including xenobiotics. We hypothesized that genetic variation in CES genes expressed in the liver could affect INH-induced hepatotoxicity. Three CES genes are known to be expressed in human liver: CES1, CES2 and CES4. Our aim was to systematically characterize genetic variation in these novel candidate genes and test whether it is associated with this adverse drug reaction. As part of a pilot study, 170 subjects with LTBI who received only INH were recruited, including 23 cases with hepatotoxicity and 147 controls. All exons and the promoters of CES1, CES2 and CES4 were bidirectionally sequenced. A large polymorphic deletion was found to encompass exons 2 to 6 of CES4. No significant association was found. Eleven single-nucleotide polymorphisms (SNPs) in CES1 were in high linkage disequilibrium with each other. One of these SNPs, C(-2)G, alters the translation initiation sequence of CES1 and represents a candidate functional polymorphism. Replication of this possible association in a larger sample set and functional studies will be necessary to determine if this CES1 variant has a role in INH-induced hepatotoxicity.
ESTHER : Yamada_2010_Pharmacogenomics.J_10_524
PubMedSearch : Yamada_2010_Pharmacogenomics.J_10_524
PubMedID: 20195289

Title : Liposomal formulations of glucagon-like peptide-1: improved bioavailability and anti-diabetic effect - Hanato_2009_Int.J.Pharm_382_111
Author(s) : Hanato J , Kuriyama K , Mizumoto T , Debari K , Hatanaka J , Onoue S , Yamada S
Ref : Int J Pharm , 382 :111 , 2009
Abstract : Glucagon-like peptide-1 (GLP-1), an incretin hormone, is recognized to be potent drug candidate for treatment of diabetes, however its clinical application has been highly limited, because of rapid enzymatic degradation by dipeptidyl-peptidase IV. To protect GLP-1 from enzymatic degradation and improve pharmacological effects, liposomal formulations of GLP-1 were prepared using three types of lyophilized empty liposomes such as anionic, neutral and cationic liposomes. Electron microscopic and dynamic light scattering experiments indicated the uniform size distribution of GLP-1-loaded liposomes with mean diameter of 130-210 nm, and inclusion of GLP-1 did not affect the dispersibility and morphology of each liposome. Of all liposomal formulations tested, anionic liposomal formulation exhibited the highest encapsulation efficiency of GLP-1 (ca. 80%). In intraperitoneal glucose tolerance testing in rats, marked improvement of hypoglycemic effects were observed in anionic liposomal formulation of GLP-1 (100 nmol/kg) with 1.7-fold higher increase of insulin secretion, as compared to GLP-1 solution. In pharmacokinetic studies, intravenous administration of anionic liposomal formulation of GLP-1 (100 nmol/kg) resulted in 3.6-fold higher elevation of serum GLP-1 level as compared to GLP-1 injection. Upon these findings, anionic liposomal formulation of GLP-1 would provide the improved pharmacokinetics and insulinotropic action, possibly leading to efficacious anti-diabetic medication.
ESTHER : Hanato_2009_Int.J.Pharm_382_111
PubMedSearch : Hanato_2009_Int.J.Pharm_382_111
PubMedID: 19698772

Title : Application of dual counter-current chromatography for rapid sample preparation of N-methylcarbamate pesticides in vegetable oil and citrus fruit - Ito_2006_J.Chromatogr.A_1108_20
Author(s) : Ito Y , Goto T , Yamada S , Matsumoto H , Oka H , Takahashi N , Nakazawa H , Nagase H
Ref : Journal of Chromatography A , 1108 :20 , 2006
Abstract : Dual counter-current chromatography (dual CCC) has been successfully applied to rapid sample preparation for the simultaneous determination of residual carbaryl, fenobucarb and methomyl in vegetable oil and citrus fruit. The citrus fruit samples were extracted with n-hexane solution containing stable isotopically labeled internal standards (methomyl-d3, fenobucarb-d3 and carbaryl-d9), and applied to dual CCC using a two-phase solvent system of n-hexane-acetonitrile to purify the carbamate pesticides from aliphatic sample matrix. The coiled column was rotated at 420 rpm, the lower mobile phase was introduced through the head toward the tail, and the upper mobile phase in the opposite direction. Due to the high partition efficiency of dual CCC, the lower phase fraction collected from 2 to 5 min after injection could be subjected to flow-injection tandem mass spectrometry directly after concentration. Repetitive sample injection can be performed at high reproducibility without a risk of contamination from the compounds retained in the column.
ESTHER : Ito_2006_J.Chromatogr.A_1108_20
PubMedSearch : Ito_2006_J.Chromatogr.A_1108_20
PubMedID: 16445929

Title : Mechanism of action of aripiprazole predicts clinical efficacy and a favourable side-effect profile - Hirose_2004_J.Psychopharmacol_18_375
Author(s) : Hirose T , Uwahodo Y , Yamada S , Miwa T , Kikuchi T , Kitagawa H , Burris KD , Altar CA , Nabeshima T
Ref : J Psychopharmacol , 18 :375 , 2004
Abstract : The antipsychotic efficacy of aripiprazole is not generally associated with extrapyramidal symptoms, cardiovascular effects, sedation or elevations in serum prolactin that characterize typical or atypical antipsychotics. The aim of this study was to clarify the mechanism of action of aripiprazole that underlies its favourable clinical profiles. The preclinical efficacy and side-effect profiles of aripiprazole were evaluated using several pharmaco-behavioural test systems in mice and rats, both in vivo and ex vivo, and compared with those of other conventional and atypical antipsychotics. Each of the antipsychotics induced catalepsy and inhibited apomorphine-induced stereotypy. The catalepsy liability ratios for these drugs were 6.5 for aripiprazole, 4.7 for both olanzapine and risperidone. The ptosis liability ratios for aripiprazole, olanzapine and risperidone were 14, 7.2 and 3.3, respectively. Aripiprazole slightly increased DOPA accumulation in the forebrain of reserpinised mice, reduced 5-HTP accumulation at the highest dose and exhibited a weaker inhibition of 5-methoxy-N,N-dimethyl-tryptamine-induced head twitches. Aripiprazole did not inhibit physostigmine- or norepinephrine-induced lethality in rats. In conclusion, aripiprazole shows a favourable preclinical efficacy and side-effect profile compared to a typical antipsychotics. This profile may result from its high affinity partial agonist activity at D2 and 5-HT1A receptors and its antagonism of 5-HT2A receptors.
ESTHER : Hirose_2004_J.Psychopharmacol_18_375
PubMedSearch : Hirose_2004_J.Psychopharmacol_18_375
PubMedID: 15358981

Title : Attenuation of scopolamine-induced and age-associated memory impairments by the sigma and 5-hydroxytryptamine(1A) receptor agonist OPC-14523 (1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2[1H]-quino linone monomethanesulfonate) - Tottori_2002_J.Pharmacol.Exp.Ther_301_249
Author(s) : Tottori K , Nakai M , Uwahodo Y , Miwa T , Yamada S , Oshiro Y , Kikuchi T , Altar CA
Ref : Journal of Pharmacology & Experimental Therapeutics , 301 :249 , 2002
Abstract : Sigma and 5-HT(1A) receptor stimulation can increase acetylcholine (ACh) release in the brain. Because ACh release facilitates learning and memory, we evaluated the degree to which OPC-14523 (1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2[1H]-quino linone monomethane sulfonate), a novel sigma and 5-HT(1A) receptor agonist, can augment ACh release and improve learning impairments in rats due to cholinergic- or age-related deficits. Single oral administration of OPC-14523 improved scopolamine-induced learning impairments in the passive-avoidance task and memory impairment in the Morris water maze. The chronic oral administration of OPC-14523 attenuated age-associated impairments of learning acquisition in the water maze and in the conditioned active-avoidance response test. OPC-14523 did not alter basal locomotion or inhibit acetylcholinesterase (AChE) activity at concentrations up to 100 microM and, unlike AChE inhibitors, did not cause peripheral cholinomimetic responses. ACh release in the dorsal hippocampus of freely moving rats increased after oral delivery of OPC-14523 and after local delivery of OPC-14523 into the hippocampus. The increases in hippocampal ACh release were blocked by the sigma receptor antagonist NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)-phenyl]-ethylamine). Thus, OPC-14523 improves scopolamine-induced and age-associated learning and memory impairments by enhancing ACh release, due to a stimulation of sigma and probably 5-HT(1A) receptors. Combined sigma/5-HT(1A) receptor agonism may be a novel approach to ameliorate cognitive disorders associated with age-associated cholinergic deficits.
ESTHER : Tottori_2002_J.Pharmacol.Exp.Ther_301_249
PubMedSearch : Tottori_2002_J.Pharmacol.Exp.Ther_301_249
PubMedID: 11907181

Title : Constitutive expression of mRNA for the same choline acetyltransferase as that in the nervous system, an acetylcholine-synthesizing enzyme, in human leukemic T-cell lines - Fujii_1999_Neurosci.Lett_259_71
Author(s) : Fujii T , Tajima S , Yamada S , Watanabe Y , Sato KZ , Matsui M , Misawa H , Kasahara T , Kawashima K
Ref : Neuroscience Letters , 259 :71 , 1999
Abstract : Both muscarinic and nicotinic acetylcholine (ACh) receptors are known to be present on the surface of lymphocytes. We have shown that variable amounts of ACh are detectable in the blood of various mammals including humans, and a major portion of blood ACh is localized in circulating mononuclear leukocytes in humans. In order to investigate which types of blood cell are the source of ACh in human blood, expression of mRNA for choline acetyltransferase (ChAT, EC 2.3.1.6), which catalyzes ACh synthesis, was analyzed using human leukemic cell lines as models of lymphocytes and the reverse transcription-polymerase chain reaction (RT-PCR) method. We observed that mRNA for the same ChAT as that in the nervous system is expressed constitutively in all the T-cell lines tested, but not in B-, pre-lymphoma or monocytic cell lines. Furthermore, only T-cell lines showed high ACh-synthesizing activities and intracellular ACh contents. These results suggest that the major portion of ACh in the circulating blood originates from T-lymphocytes.
ESTHER : Fujii_1999_Neurosci.Lett_259_71
PubMedSearch : Fujii_1999_Neurosci.Lett_259_71
PubMedID: 10025560

Title : Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines - Sato_1999_Neurosci.Lett_266_17
Author(s) : Sato KZ , Fujii T , Watanabe Y , Yamada S , Ando T , Kazuko F , Kawashima K
Ref : Neuroscience Letters , 266 :17 , 1999
Abstract : Previously, we reported that various levels of acetylcholine (ACh), currently known as a neurotransmitter, are detectable in the blood of several mammals including humans and that most blood ACh originates from T-lymphocytes. To investigate whether ACh in the blood acts on lymphocytes and participates in the modulation of immune responses, we have analyzed the expression of mRNA for muscarinic (Ms) ACh receptor subtypes and nicotinic (Nc) ACh receptor subunits using reverse transcription-polymerase chain reaction (RT-PCR) methods. The cells tested were human peripheral mononuclear leukocytes (MNLs) from seven healthy donors and eight leukemic cell lines, as models of lymphocytes. We detected mRNA expression for various neuronal Nc receptor subunits and Ms receptor subtypes in all of the MNL samples and in all of the cell lines tested. However, the expression pattern of mRNA for neuronal Nc receptor subunits (alpha2-alpha7 and beta2-beta4) and Ms receptor subtypes (m1-m5) varied among the individuals and cell lines. No expression of mRNA for three muscle-type Nc receptor subunits (alpha1, beta1 and epsilon) was observed in the MNLs and cell lines. These results indicate that both neuronal-type Nc and Ms ACh receptors are present on the surface of lymphocytes.
ESTHER : Sato_1999_Neurosci.Lett_266_17
PubMedSearch : Sato_1999_Neurosci.Lett_266_17
PubMedID: 10336173

Title : Induction of choline acetyltransferase mRNA in human mononuclear leukocytes stimulated by phytohemagglutinin, a T-cell activator - Fujii_1998_J.Neuroimmunol_82_101
Author(s) : Fujii T , Yamada S , Watanabe Y , Misawa H , Tajima S , Fujimoto K , Kasahara T , Kawashima K
Ref : Journal of Neuroimmunology , 82 :101 , 1998
Abstract : The induction of mRNA for choline acetyltransferase (ChAT), which catalyzes acetylcholine (ACh) synthesis was investigated in human mononuclear leukocytes (MNL) stimulated by phytohemagglutinin (PHA), a T-cell activator, using the reverse transcription-polymerase chain reaction. Stimulation of MNL by PHA induced the expression of ChAT mRNA, and potentiated ACh synthesis. ChAT mRNA induction required more time than the induction of interleukin-2 mRNA. Expression of the gene encoding the vesicular ACh transporter, which mediates ACh transport in cholinergic neurons, was not observed in PHA-stimulated MNL, suggesting that the mechanisms controlling ACh release from T-lymphocytes differ from those in cholinergic neurons. These findings demonstrate that activation of T-lymphocytes up-regulates ACh synthesis in the blood, and suggest that ACh plays an important role as a neuroimmunomodulator besides its role as a neurotransmitter.
ESTHER : Fujii_1998_J.Neuroimmunol_82_101
PubMedSearch : Fujii_1998_J.Neuroimmunol_82_101
PubMedID: 9526852

Title : Oral administration of KW-5092, a novel gastroprokinetic agent with acetylcholinesterase inhibitory and acetylcholine release enhancing activities, causes a dose-dependent increase in the blood acetylcholine content of beagle dogs - Yamada_1997_Neurosci.Lett_225_25
Author(s) : Yamada S , Fujii T , Kawashima K
Ref : Neuroscience Letters , 225 :25 , 1997
Abstract : Acetylcholine (ACh) was detected in the blood and plasma of beagle dogs using a specific, sensitive radioimmunoassay. The mean basal ACh contents in the blood and plasma of beagle dogs were 451 +/- 65 and 83.5 +/- 12.3 pg/ml (+/- SEM, n = 7), respectively, and were lower than the contents in humans reported previously by our laboratory. Oral administration of KW-5092 (10-30 mg/kg), a gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory and ACh release enhancing activities, caused a dose-dependent increase in the ACh content of both the blood and plasma, as well as several behavioral side effects due to peripheral cholinergic stimulation. The size of the increase in the plasma ACh content at each dose of KW-5092 was greater than that in the blood, indicating that KW-5092 caused the increase in the blood ACh content through elevation of the plasma ACh content, by inhibition of AChE and facilitation of ACh release. These results demonstrate that the blood ACh of beagle dogs is present mainly in the blood cells and to a lesser degree in the plasma, and that KW-5092 increased the blood ACh content mainly by increasing the plasma ACh concentration.
ESTHER : Yamada_1997_Neurosci.Lett_225_25
PubMedSearch : Yamada_1997_Neurosci.Lett_225_25
PubMedID: 9143009

Title : Localization and synthesis of acetylcholine in human leukemic T cell lines - Fujii_1996_J.Neurosci.Res_44_66
Author(s) : Fujii T , Tsuchiya T , Yamada S , Fujimoto K , Suzuki T , Kasahara T , Kawashima K
Ref : Journal of Neuroscience Research , 44 :66 , 1996
Abstract : In order to clarify the origin of acetylcholine (ACh) in human blood, we measured the content and synthesis activity of ACh in several human leukemic cell lines. The intracellular ACh content determined by a specific and sensitive radioimmunoassay in the human leukemic T cell lines, HSB-2, MOLT-3, and CEM, was 79.6, 36.2, and 9.5 pmol/10(6) cells, respectively. These values were 9-70-fold higher than those of other cell lines, including a helper T cell line, Jurkat. Stimulation of HSB-2 and MOLT-3 by phytohemagglutinin (PHA) increased both the intracellular content and release of ACh into the culture medium, but did not influence the intracellular content and release of ACh in CEM. ACh synthesis activity was found in all the T cell lines tested. Bromoacetylcholine (100 microM), a choline acetyltransferase (ChAT) inhibitor, and bromoacetyl-L-carnitine (100 microM), a carnitine acetyltransferase (CarAT) inhibitor, decreased ACh-synthesizing activity in MOLT-3, and HSB-2 and CEM, by about 50% and 30%, respectively, indicating that both ChAT, and to a lesser extent CarAt, are involved in ACh synthesis in T cells. These results suggest that T lymphocytes have the potential to synthesize and release ACh, which may play a role in regulating T cell-dependent immune responses.
ESTHER : Fujii_1996_J.Neurosci.Res_44_66
PubMedSearch : Fujii_1996_J.Neurosci.Res_44_66
PubMedID: 8926632

Title : Species differences in the concentration of acetylcholine, a neurotransmitter, in whole blood and plasma - Fujii_1995_Neurosci.Lett_201_207
Author(s) : Fujii T , Yamada S , Yamaguchi N , Fujimoto K , Suzuki T , Kawashima K
Ref : Neuroscience Letters , 201 :207 , 1995
Abstract : Various concentrations of acetylcholine (ACh) were detected in samples of bovine, goat, horse, porcine, rat and sheep blood and plasma using a specific, sensitive radioimmunoassay. The ACh levels in whole blood in bovine and horse samples were about 40- and ten-fold higher, respectively, than in humans, but levels comparable to those in humans were measured in porcine samples. Goat, rat and sheep samples had lower whole blood ACh concentrations than those of humans. When plasma samples were assayed, the ACh contents of bovine and porcine plasma were found to be about two- to five-fold those of human. On the other hand, levels in horse, goat, rat and sheep samples were much lower than in humans. The ratio of the ACh contents of plasma to whole blood was high in porcine and rat samples, indicating that porcine and rat blood ACh is distributed mostly in the plasma, while in the other species tested most of the ACh is present in the blood cells. These results demonstrate that variable levels of ACh are present in the blood of different species, and that the distribution of ACh in the blood constituents varies according to species.
ESTHER : Fujii_1995_Neurosci.Lett_201_207
PubMedSearch : Fujii_1995_Neurosci.Lett_201_207
PubMedID: 8786841

Title : [Toxicity and general pharmacological effects of 4-methylthiophenyl dipropyl phosphate] -
Author(s) : Okudaira H , Matsui S , Hayashi S , Yamada S , Isogai M , Shinozuka K , Hayashi E
Ref : Yakugaku Zasshi , 104 :374 , 1984
PubMedID: 6491875

Title : Recent advances in muscarinic receptor heterogeneity and regulation -
Author(s) : Roeske WR , Ehlert FJ , Barritt DS , Yamanaka K , Rosenberger LB , Yamada S , Yamamura S , Yamamura HI
Ref : Adv Biochem Psychopharmacol , 36 :15 , 1983
PubMedID: 6344563

Title : A pharmacological comparison of organophosphorus and carbamate anti- cholinesterase agents on guinea pig ileum -
Author(s) : Yamada S , Katsuoka M , Okudaira H , Hayashi E
Ref : Toxicol Appl Pharmacol , 64 :79 , 1982
PubMedID: 7112587

Title : An alteration in sensitivity to cholinergic agents on guinea-pig ilea and atria after repeated administration of an organophosphate and an antagonism by a carbamate - Yamada_1979_Arch.Int.Pharmacodyn.Ther_241_32
Author(s) : Yamada S , Okudaira H , Hayashi E
Ref : Archives Internationales de Pharmacodynamie et de Therapie , 241 :32 , 1979
Abstract : The effect of 4-methylthiophenyl dipropylphosphate (propaphos, organophosphorus insecticide) and 2-sec-butylphenyl-N-methylcarbamate (BPMC, carbamate insecticide) on the sensitivity to the effects of acetylcholine (ACh), carbachol (CCH) and nicotine was investigated on guinea-pig isolated ilea and atria. The response of these tissues to ACh was significantly enhanced in the presence of propaphos (3.3 x 10(-7) M) or BPMC (4.5 x 10(-6) M), while that to CCH was unaffected. The repeated administration of propaphos (5 mg/kg/day, p.o.) for 7 days had no effect on the contractile responses of guinea-pig ilea to potassium chloride. The responses of ilea and atria to ACh and nicotine were markedly increased by the administration of propaphos, and the values of ED50 and ED80 for their responses were significantly decreased. On the other hand, the response to CCH was decreased as was demonstrated by a significant increase in these values. Pretreatment with BPMC (25 mg/kg/day p.o., 7 days) significantly reduced the alteration in the responsiveness of the tissues to ACh, CCH and nicotine produced by the propaphos administration. The activity of cholinesterase (ChE) declined by 50--70% in blood and tissues from propaphos-treated animals, and its inhibition was significnatly reduced by the pretreatment with PBMC to 30--40%. These results indicate that changes in synaptic ChE activity, as reflected by the changes in ChE activity of blood and tissues, may be responsible for the alteration in sensitivity of ilea and atria to cholinergic agents produced by the repeated administration of propaphos and for the antagonism by BPMC.
ESTHER : Yamada_1979_Arch.Int.Pharmacodyn.Ther_241_32
PubMedSearch : Yamada_1979_Arch.Int.Pharmacodyn.Ther_241_32
PubMedID: 526070