Hasegawa T

References (22)

Title : Notum Leads to Potential Pro-survival of OSCC Through Crosstalk Between Shh and Wnt\/beta-catenin Signaling Via p-GSK3beta - Yang_2022_Int.J.Biochem.Cell.Biol__106316
Author(s) : Yang P , Li C , Zhou Q , Zhang X , Kou Y , Feng Q , Wang H , Su R , Hasegawa T , Liu H , Li M
Ref : International Journal of Biochemistryistry & Cell Biology , :106316 , 2022
Abstract : Notum, which belongs to the alpha/beta hydrolase family, is a deacylated extracellular protein that regulates the Wnt signaling pathway. Studies have found that Notum participates in the progression of colorectal cancer and hepatocellular carcinoma, but its role in oral squamous cell carcinoma (OSCC) is currently unclear. This study aimed to explore the role of Notum in regulating OSCC and further reveal the underlying mechanisms. Various approaches including bioinformatics analysis, enzyme-linked immunosorbent assay and immunohistochemical staining were used to detect the expression of Notum in OSCC cells and tissues. Cell counting kit-8 assay, clone formation assay, wound healing assay, transwell assay and in-gel zymography assay were explored to evaluate the regulation of Notum in OSCC proliferation and migration. Hoechst 33342/PI assay, cell immunofluorescence, flow cytometry and in vivo tumorigenesis experiment were applied for OSCC apoptosis. Real-time quantitative polymerase chain reaction analysis was performed for mRNA level while western blotting was conducted to detect protein expression. The results showed that Notum was highly expressed in OSCC tissues and cells, and Notum promoted the proliferation and migration of OSCC cells while it inhibited their apoptosis. Furthermore, signaling pathway analysis showed that Notum led to potential pro-survival of OSCC through crosstalk between sonic hedgehog (Shh) and Wnt/beta-catenin signaling via phosphorylation of glycogen synthase kinase-3 beta. These results will help to elucidate the mechanism and also provide new ideas for targeted treatment of OSCC.
ESTHER : Yang_2022_Int.J.Biochem.Cell.Biol__106316
PubMedSearch : Yang_2022_Int.J.Biochem.Cell.Biol__106316
PubMedID: 36280040

Title : Prednisolone induces osteocytes apoptosis by promoting Notum expression and inhibiting PI3K\/AKT\/GSK3beta\/beta-catenin pathway - Li_2021_J.Mol.Histol__
Author(s) : Li C , Yang P , Liu B , Bu J , Liu H , Guo J , Hasegawa T , Si H , Li M
Ref : J Mol Histol , : , 2021
Abstract : The apoptosis of mature osteocytes is the main factor causing damage to the microstructure of cortical bone in glucocorticoid-induced osteoporosis (GIOP). Our previous research found damaged areas and empty osteocytes lacunae in the tibial cortical bone of GIOP mice. However, the specific mechanism has not been clarified. Recently, a study showed that the quality of the cortical bone significantly increased by knocking out Notum, a gene encoding alpha/beta hydrolase. However, it is not clear whether Notum affects cortical bone remodeling by participating in glucocorticoids (GCs)-induced apoptosis of osteocytes. The present study aimed to explore the correlation between Notum, osteocytes apoptosis, and cortical bone quality in GIOP. Prednisolone acetate was intragastrically administered to mice for two weeks. Histochemical staining was applied to evaluate changes in GIOP and Notum expression. Osteocytes were stimulated with prednisolone, and cell viability was assessed via CCK8. Hoechst 33342/PI staining, flow cytometry, RT-PCR, and western blot were used to detect osteocytes apoptosis, siRNA transfection efficiency, and expressions of pathway related factors. The results showed that the number of empty osteocytes lacunae increased in GIOP mice. TUNEL-stained apoptotic osteocytes and Notum immuno-positive osteocytes were also observed. Furthermore, prednisolone was found to promote Notum expression and osteocytes apoptosis in vitro. Knocking down Notum via siRNA partially restored osteocytes apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3beta (GSK3beta)/beta-catenin pathway. These findings showed GCs-induced osteocytes apoptosis by promoting Notum expression and inhibiting PI3K/AKT/GSK3beta/beta-catenin pathway. Thus, Notum might be a potential therapeutic target for the treatment of GIOP.
ESTHER : Li_2021_J.Mol.Histol__
PubMedSearch : Li_2021_J.Mol.Histol__
PubMedID: 34297260

Title : Deficiency of TMEM53 causes a previously unknown sclerosing bone disorder by dysregulation of BMP-SMAD signaling - Guo_2021_Nat.Commun_12_2046
Author(s) : Guo L , Iida A , Bhavani GS , Gowrishankar K , Wang Z , Xue JY , Wang J , Miyake N , Matsumoto N , Hasegawa T , Iizuka Y , Matsuda M , Nakashima T , Takechi M , Iseki S , Yambe S , Nishimura G , Koseki H , Shukunami C , Girisha KM , Ikegawa S
Ref : Nat Commun , 12 :2046 , 2021
Abstract : Bone formation represents a heritable trait regulated by many signals and complex mechanisms. Its abnormalities manifest themselves in various diseases, including sclerosing bone disorder (SBD). Exploration of genes that cause SBD has significantly improved our understanding of the mechanisms that regulate bone formation. Here, we discover a previously unknown type of SBD in four independent families caused by bi-allelic loss-of-function pathogenic variants in TMEM53, which encodes a nuclear envelope transmembrane protein. Tmem53(-/-) mice recapitulate the human skeletal phenotypes. Analyses of the molecular pathophysiology using the primary cells from the Tmem53(-/-) mice and the TMEM53 knock-out cell lines indicates that TMEM53 inhibits BMP signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of BMP2-activated Smad proteins. Pathogenic variants in the patients impair the TMEM53-mediated blocking effect, thus leading to overactivated BMP signaling that promotes bone formation and contributes to the SBD phenotype. Our results establish a previously unreported SBD entity (craniotubular dysplasia, Ikegawa type) and contribute to a better understanding of the regulation of BMP signaling and bone formation.
ESTHER : Guo_2021_Nat.Commun_12_2046
PubMedSearch : Guo_2021_Nat.Commun_12_2046
PubMedID: 33824347
Gene_locus related to this paper: human-TMEM53

Title : Notum suppresses the osteogenic differentiation of periodontal ligament stem cells through the Wnt\/Beta catenin signaling pathway - Yang_2021_Arch.Oral.Biol_130_105211
Author(s) : Yang P , Li C , Kou Y , Jiang Y , Li D , Liu S , Lu Y , Hasegawa T , Li M
Ref : Archives of Oral Biology , 130 :105211 , 2021
Abstract : OBJECTIVES: The aims of this study were to explore: (i) the effect of Notum on periodontitis in vivo; (ii) the effect of Notum on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in vitro; and (iii) the potential mechanism of Notum in inhibiting the osteogenic differentiation of hPDLSCs. DESIGN: C57BL/6J mice were randomly assigned into two groups: control group (n = 4) and periodontitis group (n = 4). Immunohistochemical staining was used to evaluate the expression of Notum. In in vitro experiments, Western blot, qRT- PCR and ELISA were used to examine the expression of Notum in a lipopolysaccharide-induced inflammation model. Alkaline phosphatase staining was used to evaluate alkaline phosphatase activity. Western blot and qRT - PCR were used to measure the expression of osteogenic-related markers after adding human recombinant Notum and Notum inhibitor ABC99. In addition, LiCl, an agonist of the Wnt/Beta-catenin signaling pathway, was added to explore using Western blot whether Notum was involved in regulating the osteogenic differentiation of human periodontal ligament stem cells through the Wnt/Beta-catenin signaling pathway. RESULTS: Notum was highly expressed in periodontal tissues of mice and lipopolysaccharide-induced inflammation cell model. The protein and messenger ribonucleic acid levels of hPDLSCs osteogenic markers were reduced after adding human recombinant Notum. However, the inhibitory effect of Notum on the osteogenic differentiation of hPDLSCs could be significantly reversed by adding LiCl. CONCLUSION: These results demonstrated that Notum inhibited the osteogenic differentiation of hPDLSCs probably via the Wnt/Beta-catenin the downstream signaling pathway.
ESTHER : Yang_2021_Arch.Oral.Biol_130_105211
PubMedSearch : Yang_2021_Arch.Oral.Biol_130_105211
PubMedID: 34352447

Title : Logopenic aphasia due to Lewy body disease dramatically improved with donepezil - Kakinuma_2020_eNeurologicalSci_19_100241
Author(s) : Kakinuma K , Baba T , Ezura M , Endo K , Saito Y , Narita W , Iizuka O , Nishio Y , Kikuchi A , Hasegawa T , Aoki M , Suzuki K
Ref : eNeurologicalSci , 19 :100241 , 2020
Abstract : *Pathological basis of primary progressive aphasia is heterogeneous.*Logopenic primary progressive aphasia can precede dementia with Lewy bodies (DLB).*Cholinesterase inhibitor can improve logopenic aphasia with DLB.
ESTHER : Kakinuma_2020_eNeurologicalSci_19_100241
PubMedSearch : Kakinuma_2020_eNeurologicalSci_19_100241
PubMedID: 32455171

Title : Increased serum Wisteria floribunda agglutinin positive Mac-2 binding protein (Mac-2 binding protein glycosylation isomer) in chronic heart failure: a pilot study - Okada_2018_Heart.Vessels_33_385
Author(s) : Okada A , Kanzaki H , Hamatani Y , Takashio S , Takahama H , Amaki M , Hasegawa T , Sugano Y , Yasuda S , Anzai T
Ref : Heart Vessels , 33 :385 , 2018
Abstract : BACKGROUND: Serum Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA(+)-M2BP) or Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) is a novel biomarker currently applied for evaluating hepatic fibrosis. The aim of this study was to evaluate the utility of serum WFA(+)-M2BP level as a biomarker in chronic heart failure (HF) patients with abnormal liver function. METHODS AND RESULTS: Fifty chronic HF patients who underwent measurement of serum WFA(+)-M2BP were evaluated. The median value of serum WFA(+)-M2BP was 0.88 (interquartile range 0.48-1.29) cut-off index, and positive WFA(+)-M2BP (>/= 1.00 cut-off index) was observed in 22 (44%). Elevated WFA + -M2BP was associated with longer HF history, older age, female sex, valvular heart disease, decreased estimated glomerular filtration rate (eGFR), albumin, and cholinesterase. Stepwise multiple regression analysis showed that HF history, eGFR, and albumin were independent determinants of serum WFA(+)-M2BP values. Repeated measurements of serum WFA(+)-M2BP suggested association between the decrease of WFA(+)-M2BP and improvement of New York Heart Association (NYHA) functional class. CONCLUSIONS: Elevation of serum WFA(+)-M2BP showed a high prevalence in chronic HF patients with abnormal liver function with relation to HF history, decreased hepatic protein synthesis, and renal dysfunction. Our results suggest that serum WFA(+)-M2BP may be a novel biomarker of chronic HF.
ESTHER : Okada_2018_Heart.Vessels_33_385
PubMedSearch : Okada_2018_Heart.Vessels_33_385
PubMedID: 29098408

Title : Beta-glucuronidase activity is a sensitive biomarker to assess low-level organophosphorus insecticide exposure - Ueyama_2010_Toxicol.Lett_193_115
Author(s) : Ueyama J , Satoh T , Kondo T , Takagi K , Shibata E , Goto M , Kimata A , Saito I , Hasegawa T , Wakusawa S , Kamijima M
Ref : Toxicol Lett , 193 :115 , 2010
Abstract : Acetylcholinesterase and butyrylcholinesterase (BChE) activities in blood are widely used as the biomarkers for organophosphorus insecticide (OP) exposure. In the present study, we conducted a cross-sectional study to evaluate plasma beta-glucuronidase (BG), a sensitive biomarker candidate for OP exposure, BChE activities and urinary dialkyl phosphates (DAPs), OP metabolites. We assessed the relationship between these biomarker levels in the following groups: 32 controls (control), 21 pest control operators and their co-workers who had not sprayed OPs within 3 days prior to sample collection (PCO1), and 21 pest control operators who sprayed OPs within those 3 days (PCO2). Logarithmically transformed age-adjusted means of DAPs were 3.88, 5.62 and 6.45 nmol/g creatinine for control, PCO1 and PCO2, respectively (P<0.001 for difference, P<0.001 for trend). Logarithmically transformed age-adjusted means of BG were 1.40, 1.52 and 1.85 micromol/L/h for control, PCO1 and PCO2, respectively. BG activity, but not BChE, was increased according to their OP exposure level (P=0.038 for difference, P=0.026 for trend). It was concluded that plasma BG activity is more sensitive biomarker as well as urinary OP metabolites than BChE for low-level exposure in humans.
ESTHER : Ueyama_2010_Toxicol.Lett_193_115
PubMedSearch : Ueyama_2010_Toxicol.Lett_193_115
PubMedID: 20026393

Title : Genome sequence, comparative analysis, and population genetics of the domestic horse - Wade_2009_Science_326_865
Author(s) : Wade CM , Giulotto E , Sigurdsson S , Zoli M , Gnerre S , Imsland F , Lear TL , Adelson DL , Bailey E , Bellone RR , Blocker H , Distl O , Edgar RC , Garber M , Leeb T , Mauceli E , MacLeod JN , Penedo MC , Raison JM , Sharpe T , Vogel J , Andersson L , Antczak DF , Biagi T , Binns MM , Chowdhary BP , Coleman SJ , Della Valle G , Fryc S , Guerin G , Hasegawa T , Hill EW , Jurka J , Kiialainen A , Lindgren G , Liu J , Magnani E , Mickelson JR , Murray J , Nergadze SG , Onofrio R , Pedroni S , Piras MF , Raudsepp T , Rocchi M , Roed KH , Ryder OA , Searle S , Skow L , Swinburne JE , Syvanen AC , Tozaki T , Valberg SJ , Vaudin M , White JR , Zody MC , Lander ES , Lindblad-Toh K
Ref : Science , 326 :865 , 2009
Abstract : We report a high-quality draft sequence of the genome of the horse (Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
ESTHER : Wade_2009_Science_326_865
PubMedSearch : Wade_2009_Science_326_865
PubMedID: 19892987
Gene_locus related to this paper: horse-1plip , horse-2plrp , horse-ACHE , horse-BCHE , horse-f6pri5 , horse-f6qlk6 , horse-f6qsc5 , horse-f6r958 , horse-f6sfg0 , horse-f6uif6 , horse-f6un85 , horse-f6vxp7 , horse-f6wfs9 , horse-f6wzv8 , horse-f6x0i7 , horse-f6x5e5 , horse-f6zmg7 , horse-f7afw6 , horse-f7agv7 , horse-f7bj10 , horse-f7bk45 , horse-f7bvl6 , horse-f7c7a8 , horse-f7cdt1 , horse-f7cxj0 , horse-f6ut17 , horse-f6svq9 , horse-f6xgj6 , horse-f6s101 , horse-f6wfa7 , horse-f7cpx3 , horse-f7adj7 , horse-f6r609 , horse-f6y0j2 , horse-f6zvb2 , horse-f7e4g0 , horse-f6ti02 , horse-f6re01 , horse-f6xmp6 , horse-f6vts1 , horse-f6quf7 , horse-f6tn81 , horse-f7bm46 , horse-f6q1u3 , horse-f6zna7 , horse-f6q208 , horse-f7cuh0 , horse-f6tq73 , horse-f6xa70 , horse-f6qj19 , horse-f6wgf3 , horse-f7d8t6 , horse-f6ul42 , horse-f7am73 , horse-f7dme2

Title : Effect of the organophosphorus pesticide diazinon on glucose tolerance in type 2 diabetic rats - Ueyama_2008_Toxicol.Lett_182_42
Author(s) : Ueyama J , Kamijima M , Asai K , Mochizuki A , Wang D , Kondo T , Suzuki T , Takagi K , Kanazawa H , Miyamoto K , Wakusawa S , Hasegawa T
Ref : Toxicol Lett , 182 :42 , 2008
Abstract : We have reported that the toxicity of the organophosphorus pesticide diazinon (DZN) and its metabolites is increased in streptozotocin-induced diabetic rats (type 1 diabetic rats). In the present study, we have investigated the effect of DZN on glucose tolerance in genetic type 2 diabetic rats, Goto-Kakizaki (GK) rats. Oral glucose tolerance test (OGTT) (2g/(5 ml kg)) was assessed before, and 1 and 2 weeks after intraperitoneal injection of DZN (6.5 mg/kg) in Wistar and GK rats. DZN significantly increased the levels of glucose in plasma at designated blood sampling points in GK rats. The activity of hepatic drug-metabolizing enzymes and expression of hepatic cytochrome P450 (CYP) 1A2, CYP3A2 and CYP2D1, which oxidize DZN to DZN-oxon, a potent ChE inhibitor, were measured before DZN injection. There were no significant differences in the activity and expression of CYPs between both rat groups, indicating that the ability of metabolic activation might be almost the same in Wistar and GK rats. DZN dramatically decreased the activity of cholinesterase (ChE) in plasma by approximately 40% in both Wistar and GK rats. However, no significant differences in the activity of ChE in plasma were observed between Wistar and GK rats for 5 days after DZN injection. No massive necrotic and apoptotic areas, leukocyte infiltration and immunoreactive insulin-positive cells (beta-cells) were observed in pancreas 2 weeks after DZN injection. Moreover, DZN might not affect plasma insulin levels in Wistar and GK rats. These results suggest that DZN deteriorates the glucose tolerance in GK rats. It is unlikely that this phenomenon is due to differences in ChE activity and/or DZN-oxon production levels between Wistar and GK rats.
ESTHER : Ueyama_2008_Toxicol.Lett_182_42
PubMedSearch : Ueyama_2008_Toxicol.Lett_182_42
PubMedID: 18789379

Title : Constituents of Rhodiola rosea showing inhibitory effect on lipase activity in mouse plasma and alimentary canal - Kobayashi_2008_Planta.Med_74_1716
Author(s) : Kobayashi K , Yamada K , Murata T , Hasegawa T , Takano F , Koga K , Fushiya S , Batkhuu J , Yoshizaki F
Ref : Planta Med , 74 :1716 , 2008
Abstract : As a methanol extract of the rhizome of Rhodiola rosea inhibits the activity of lipase in isolated mouse plasma in vitro and in the mouse gastrointestinal tube in vivo, the active components in this plant were investigated. After fractionation and separation processes, rhodionin and rhodiosin were isolated as active ingredients. Their IC50 values were 0.093 mM and 0.133 mM in vitro, respectively. Both compounds significantly suppressed the elevation of the postprandial blood triglyceride level, e.g., by 45.6 % (150 mg/kg, 60 min after oral administration) and 57.6 % (200 mg/kg, 180 min after oral administration), respectively. Consequently, we anticipate the application of this plant and its constituents to the treatment of lifestyle-related diseases such as hyperlipidemia and exogeneous obesity and to health foods.
ESTHER : Kobayashi_2008_Planta.Med_74_1716
PubMedSearch : Kobayashi_2008_Planta.Med_74_1716
PubMedID: 18982538

Title : The PPARgamma-selective ligand BRL-49653 differentially regulates the fate choices of rat calvaria versus rat bone marrow stromal cell populations - Hasegawa_2008_BMC.Dev.Biol_8_71
Author(s) : Hasegawa T , Oizumi K , Yoshiko Y , Tanne K , Maeda N , Aubin JE
Ref : BMC Developmental Biology , 8 :71 , 2008
Abstract : BACKGROUND: Osteoblasts and adipocytes are derived from a common mesenchymal progenitor and an inverse relationship between expression of the two lineages is seen with certain experimental manipulations and in certain diseases, i.e., osteoporosis, but the cellular pathway(s) and developmental stages underlying the inverse relationship is still under active investigation. To determine which precursor mesenchymal cell types can differentiate into adipocytes, we compared the effects of BRL-49653 (BRL), a selective ligand for peroxisome proliferators-activated receptor (PPAR)gamma, a master transcription factor of adipogenesis, on osteo/adipogeneis in two different osteoblast culture models: the rat bone marrow (RBM) versus the fetal rat calvaria (RC) cell system.
RESULTS: BRL increased the number of adipocytes and corresponding marker expression, such as lipoprotein lipase, fatty acid-binding protein (aP2), and adipsin, in both culture models, but affected osteoblastogenesis only in RBM cultures, where a reciprocal decrease in bone nodule formation and osteoblast markers, e.g., osteopontin, alkaline phosphatase (ALP), bone sialoprotein, and osteocalcin was seen, and not in RC cell cultures. Even though adipocytes were histologically undetectable in RC cultures not treated with BRL, RC cells expressed PPAR and CCAAT/enhancer binding protein (C/EBP) mRNAs throughout osteoblast development and their expression was increased by BRL. Some single cell-derived BRL-treated osteogenic RC colonies were stained not only with ALP/von Kossa but also with oil red O and co-expressed the mature adipocyte marker adipsin and the mature osteoblast marker OCN, as well as PPAR and C/EBP mRNAs. CONCLUSION: The data show that there are clear differences in the capacity of BRL to alter the fate choices of precursor cells in stromal (RBM) versus calvarial (RC) cell populations and that recruitment of adipocytes can occur from multiple precursor cell pools (committed preadipocyte pool, multi-/bipotential osteo-adipoprogenitor pool and conversion of osteoprogenitor cells or osteoblasts into adipocytes (transdifferentiation or plasticity)). They also show that mechanisms beyond activation of PPARgamma by its ligand are required for changing the fate of committed osteoprogenitor cells and/or osteoblasts into adipocytes.
ESTHER : Hasegawa_2008_BMC.Dev.Biol_8_71
PubMedSearch : Hasegawa_2008_BMC.Dev.Biol_8_71
PubMedID: 18625072

Title : Anorectal sleeve micromanometry for the diagnosis of Hirschsprung's disease in newborns - Kawahara_2007_J.Pediatr.Surg_42_2075
Author(s) : Kawahara H , Kubota A , Hasegawa T , Okuyama H , Ueno T , Watanabe T , Morishita Y , Saka R , Fukuzawa M
Ref : J Pediatr Surg , 42 :2075 , 2007
Abstract : BACKGROUND/PURPOSE: An accurate diagnosis is mandatory for surgery in newborns with Hirschsprung's disease (HD). Acetylcholinesterase staining of rectal suction biopsy specimens is widely performed in the diagnosis of HD, but results are sometimes incorrect or atypical in newborns. We report the usefulness of our method of anorectal manometry using a specially designed sleeve microassembly for the diagnosis of neonatal HD.
METHODS: Anorectal manometry was conducted without sedation in 41 newborns, aged 2 to 30 days (19 newborns were within the first week of life), with abdominal distension. A silastic assembly with a 2-cm-long sleeve sensor and 5 side holes arrayed along the sleeve was designed to reduce the effects of displacement of pressure sensors relative to the anal sphincter. Rectoanal inhibitory reflex (RAIR) was examined with rectal balloon distension.
RESULTS: Thirty-two subjects who showed falls of anal sphincter pressure fulfilling the criteria for RAIR were diagnosed to be without HD. Nine patients without an appropriate RAIR were subsequently confirmed to have HD based on operative pathologic findings. Parameters of anal sphincter function did not differ significantly between the subjects with and without RAIR.
CONCLUSIONS: An anorectal sleeve micromanometric technique is useful in the diagnostic workup of newborns suspected of having HD.
ESTHER : Kawahara_2007_J.Pediatr.Surg_42_2075
PubMedSearch : Kawahara_2007_J.Pediatr.Surg_42_2075
PubMedID: 18082711

Title : Toxicity of diazinon and its metabolites increases in diabetic rats - Ueyama_2007_Toxicol.Lett_170_229
Author(s) : Ueyama J , Wang D , Kondo T , Saito I , Takagi K , Kamijima M , Nakajima T , Miyamoto K , Wakusawa S , Hasegawa T
Ref : Toxicol Lett , 170 :229 , 2007
Abstract : The effect of diazinon (DZN) on the activities of cholinesterase (ChE) in plasma and acetylcholinesterase (AChE) in erythrocyte and brain was investigated in normal and streptozotocin-induced diabetic rats. Hepatic drug-metabolizing enzyme activity was also estimated by measuring the systemic clearance of antipyrine, and the expression of hepatic cytochrome P450 (CYP) 3A2 and CYP1A2, which is closely related to the metabolism from DZN to DZN-oxon, a strong inhibitor of both ChE and AChE. No significant differences in the activities of ChE in plasma and AChE in erythrocyte were observed between normal and diabetic rats. Treatment with DZN significantly decreased these activities in diabetic rats more than in normal rats 6h after injection (6.5 mg/kg). Treatment with DZN significantly decreased the activity of AChE in brain of diabetic rats than normal rats 3h after injection (65 mg/kg), although no significant difference in the activity was found between normal and diabetic rats. The urinary recovery of diethylphosphate (DEP), a metabolite of DZN-oxon, was significantly increased in diabetic rats, but that of diethylthiophosphate (DETP), a metabolite of DZN, was unchanged. Significant increases in the systemic clearance of antipyrine and protein levels of hepatic CYP1A2, not CYP3A2, were observed in diabetic rats. These results suggest the possibility that a metabolite of DZN, DZN-oxon, causes higher toxicity in diabetic rats due to the enhancement of hepatic CYP1A2-mediated metabolism of DZN.
ESTHER : Ueyama_2007_Toxicol.Lett_170_229
PubMedSearch : Ueyama_2007_Toxicol.Lett_170_229
PubMedID: 17442507

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 : 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 : 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 : 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 : Effects of metrifonate on impairment of learning and dysfunction of cholinergic neuronal system in basal forebrain-lesioned rats - Itoh_1997_Behav.Brain.Res_83_165
Author(s) : Itoh A , Nitta A , Hirose M , Hasegawa T , Nabeshima T
Ref : Behavioural Brain Research , 83 :165 , 1997
Abstract : Several studies have indicated the possibility of using cholinesterase (ChE) inhibitors as therapeutic drugs for Alzheimer's disease. Metrifonate (MTF) is an organophosphorus compound that has been used in the treatment of schistosomiasis. In this study, we investigated the effects of MTF on the impairment of learning and memory, decreased ChE activity and extracellular acetylcholine (ACh) levels in basal forebrain (BF)-lesioned rats. The oral administration of MTF improved the BF-lesion-induced impairment of performance on passive avoidance task. Further, MTF reduced ChE activity in the cerebral cortex. In vivo brain microdialysis studies showed that MTF significantly increased the release of ACh, but decreased that of choline (Ch) in the cerebral cortex of BF-lesioned rats. These results indicated that MTF ameliorates the impairment of performance on passive avoidance task in BF-lesioned rats by increasing the extracellular ACh levels by inhibiting ChE. This suggested that MTF may be useful as a therapeutic drug for Alzheimer's disease.
ESTHER : Itoh_1997_Behav.Brain.Res_83_165
PubMedSearch : Itoh_1997_Behav.Brain.Res_83_165
PubMedID: 9062677

Title : Effects of metrifonate on memory impairment and cholinergic dysfunction in rats - Itoh_1997_Eur.J.Pharmacol_322_11
Author(s) : Itoh A , Nitta A , Katono Y , Usui M , Naruhashi K , Iida R , Hasegawa T , Nabeshima T
Ref : European Journal of Pharmacology , 322 :11 , 1997
Abstract : Metrifonate is an organophosphorous compound that has been used in the treatment of schistosomiasis. In this study, we investigated the effects of metrifonate on the impairment of learning and on central cholinergic dysfunction in scopolamine-treated and basal forebrain-lesioned rats. Oral administration of metrifonate (5.0-15.0 mg/kg) ameliorated the scopolamine- and basal forebrain. lesion-induced learning impairment in the water maze and passive avoidance tasks. Metrifonate (50 and 100 mg/kg) also significantly increased extracellular acetylcholine levels but decreased choline levels in the cerebral cortex of the basal forebrain-lesioned rats. The basal forebrain lesion decreased the cholinesterase activity in the cerebral cortex, and metrifonate (100 mg/kg) further reduced the cholinesterase activity. However, cholinesterase inhibition was not observed at the dose that ameliorated learning impairments. These results indicated that metrifonate ameliorated the impairment of learning in both scopolamine-treated and basal forebrain-lesioned rats by not only increasing extracellular acetylcholine levels by inhibiting cholinesterase, but also by undefined other mechanism(s). This finding suggests the usefulness of metrifonate for the therapy of Alzheimer's disease.
ESTHER : Itoh_1997_Eur.J.Pharmacol_322_11
PubMedSearch : Itoh_1997_Eur.J.Pharmacol_322_11
PubMedID: 9088864

Title : Age-related changes in learning and memory and cholinergic neuronal function in senescence accelerated mice (SAM) - Nitta_1995_Behav.Brain.Res_72_49
Author(s) : Nitta A , Naruhashi K , Umemura M , Hasegawa T , Furukawa S , Sekiguchi F , Ishibashi K , Nabeshima T
Ref : Behavioural Brain Research , 72 :49 , 1995
Abstract : The senescence-accelerated mouse (SAM) has been established as a murine model of accelerated aging. We investigated learning ability and memory in various tasks in a SAM strain, SAMP1TA, and in a control strain of SAMR1TA at the ages of 20, 30 and 40 weeks. We also measured choline acetyltransferase (ChAT) and cholinesterase (ChE) activity in the brains of these mice at the same ages. In a Y-maze task, in which short-term memory can be examined, there was no difference in learning ability between SAMP1TA and SAMR1TA at any age. Ability in latent learning and passive-avoidance tasks was less in SAMP1TA at 30 weeks of age than in age-matched SAMR1TA. The level of ChAT activity in the striatum of SAMP1TA was lower, than that of SAMR1TA at the ages of 20 and 30 weeks. At the ages of 40 and 50 weeks, ChE activity in the striatum of SAMP1TA was lower than that of SAMR1TA. These results suggest that SAMP1TA has a deficit, with cholinergic neuronal dysfunction, in learning ability and memory, as shown by impairment of performance in latent learning and long-term memory, but not in short-term memory.
ESTHER : Nitta_1995_Behav.Brain.Res_72_49
PubMedSearch : Nitta_1995_Behav.Brain.Res_72_49
PubMedID: 8788856

Title : Memory impairment and neural dysfunction after continuous infusion of anti-nerve growth factor antibody into the septum in adult rats - Nitta_1993_Neurosci_57_495
Author(s) : Nitta A , Murase K , Furukawa Y , Hayashi K , Hasegawa T , Nabeshima T
Ref : Neuroscience , 57 :495 , 1993
Abstract : Nerve growth factor is required for the survival and maintenance of cholinergic neurons in the central nervous system. The direct infusion into the rat's septum of an anti-nerve growth factor monoclonal antibody, which inhibits nerve growth factor bioactivity seven times more strongly than a polyclonal antibody, caused very severe damage to the hippocampal cholinergic system. Anti-nerve growth factor polyclonal antibody also neutralized endogenously occurring nerve growth factor. The infusion of anti-nerve growth factor polyclonal antibody produced a dysfunction of memory and decreased choline acetyltransferase activity and acetylcholinesterase staining in the hippocampus. The cholinergic dysfunction and impairment of memory recovered to the normal level two weeks after cessation of the infusion of the anti-nerve growth factor polyclonal antibody. These results suggest that a deficit of nerve growth factor in the adult brain causes neuronal dysfunction.
ESTHER : Nitta_1993_Neurosci_57_495
PubMedSearch : Nitta_1993_Neurosci_57_495
PubMedID: 7508574