Watanabe H

References (26)

Title : Aphasic mild cognitive impairment in prodromal dementia with Lewy bodies - Watanabe_2023_Front.Neurol_14_1128566
Author(s) : Watanabe H , Hikida S , Ikeda M , Mori E
Ref : Front Neurol , 14 :1128566 , 2023
Abstract : INTRODUCTION: This study aimed to determine the characteristics of aphasic mild cognitive impairment (aphasic MCI), which is characterized by a progressive and relatively prominent language impairment compared with other cognitive impairments, in the prodromal phase of dementia with Lewy bodies (DLB). METHODS: Of the 26 consecutive patients with aphasic MCI who had been prospectively recruited at our hospital, 8 patients were diagnosed with prodromal DLB and underwent language, neurological, neuropsychological, and neuroimaging (N-isopropyl-p-[(123)I] iodoamphetamine single-photon emission computed tomography; IMP-SPECT) testing. Three of these patients also underwent cholinesterase inhibitor therapy with donepezil. RESULTS: In our aphasic MCI cohort, the clinical diagnosis of probable prodromal DLB accounted for more than 30% of cases; therefore, the presence of language impairment in prodromal DLB was not very uncommon. Five patients were diagnosed with progressive anomic aphasia and three with logopenic progressive aphasia. Anomic aphasia was characterized by apparent anomia but relatively preserved repetition and comprehension ability and logopenic progressive aphasia by anomia, phonemic paraphasia, and impaired repetition. IMP-SPECT revealed hypoperfusion of the temporal and parietal lobes in the left hemisphere in all but one patient. All patients who underwent cholinesterase inhibitor therapy with donepezil showed improvement in general cognitive function, including language function. DISCUSSION: The clinical and imaging features of aphasic MCI in prodromal DLB are similar to those observed in Alzheimer's disease. Progressive fluent aphasia, such as progressive anomic aphasia and logopenic progressive aphasia, is one of the clinical presentations in prodromal state of DLB. Our findings provide further insight into the clinical spectrum of prodromal DLB and may contribute to the development of medication for progressive aphasia caused by cholinergic insufficiency.
ESTHER : Watanabe_2023_Front.Neurol_14_1128566
PubMedSearch : Watanabe_2023_Front.Neurol_14_1128566
PubMedID: 37077573

Title : Clinical Significance of PLA2G2A Expression in Gastric Cancer Patients who Receive Gastrectomy and Adjuvant S-1 - Hatori_2021_Anticancer.Res_41_3583
Author(s) : Hatori S , Sakamaki K , Yokohori T , Kimura Y , Hiroshima Y , Hashimoto I , Komori K , Watanabe H , Kano K , Fujikawa H , Aoyama T , Numata M , Yamada T , Tamagawa H , Yamamoto N , Ogata T , Shizawa M , Yukawa N , Morinaga S , Rino Y , Masuda M , Saeki H , Miyagi Y , Oshima T
Ref : Anticancer Research , 41 :3583 , 2021
Abstract : BACKGROUND/AIM: This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated. RESULTS: No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049). CONCLUSION: PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.
ESTHER : Hatori_2021_Anticancer.Res_41_3583
PubMedSearch : Hatori_2021_Anticancer.Res_41_3583
PubMedID: 34230154

Title : Autism-associated variants of neuroligin 4X impair synaptogenic activity by various molecular mechanisms - Yumoto_2020_Mol.Autism_11_68
Author(s) : Yumoto T , Kimura M , Nagatomo R , Sato T , Utsunomiya S , Aoki N , Kitaura M , Takahashi K , Takemoto H , Watanabe H , Okano H , Yoshida F , Nao Y , Tomita T
Ref : Mol Autism , 11 :68 , 2020
Abstract : BACKGROUND: Several genetic alterations, including point mutations and copy number variations in NLGN genes, have been associated with psychiatric disorders, such as autism spectrum disorder (ASD) and X-linked mental retardation (XLMR). NLGN genes encode neuroligin (NL) proteins, which are adhesion molecules that are important for proper synaptic formation and maturation. Previously, we and others found that the expression level of murine NL1 is regulated by proteolytic processing in a synaptic activity-dependent manner. METHODS: In this study, we analyzed the effects of missense variants associated with ASD and XLMR on the metabolism and function of NL4X, a protein which is encoded by the NLGN4X gene and is expressed only in humans, using cultured cells, primary neurons from rodents, and human induced pluripotent stem cell-derived neurons. RESULTS: NL4X was found to undergo proteolytic processing in human neuronal cells. Almost all NL4X variants caused a substantial decrease in the levels of mature NL4X and its synaptogenic activity in a heterologous culture system. Intriguingly, the L593F variant of NL4X accelerated the proteolysis of mature NL4X proteins located on the cell surface. In contrast, other variants decreased the cell-surface trafficking of NL4X. Notably, protease inhibitors as well as chemical chaperones rescued the expression of mature NL4X. LIMITATIONS: Our study did not reveal whether these dysfunctional phenotypes occurred in individuals carrying NLGN4X variant. Moreover, though these pathological mechanisms could be exploited as potential drug targets for ASD, it remains unclear whether these compounds would have beneficial effects on ASD model animals and patients. CONCLUSIONS: These data suggest that reduced amounts of the functional NL4X protein on the cell surface is a common mechanism by which point mutants of the NL4X protein cause psychiatric disorders, although different molecular mechanisms are thought to be involved. Furthermore, these results highlight that the precision medicine approach based on genetic and cell biological analyses is important for the development of therapeutics for psychiatric disorders.
ESTHER : Yumoto_2020_Mol.Autism_11_68
PubMedSearch : Yumoto_2020_Mol.Autism_11_68
PubMedID: 32873342

Title : Primary Progressive Aphasia as a Prodromal State of Dementia With Lewy Bodies: A Case Report - Watanabe_2020_Front.Neurol_11_49
Author(s) : Watanabe H , Ikeda M , Mori E
Ref : Front Neurol , 11 :49 , 2020
Abstract : Dementia with Lewy bodies (DLB) is the second most common form of dementia in the elderly, and various clinical symptoms, including olfactory dysfunction, dysautonomia, depression, and rapid eye movement sleep behavior disorders (RBD), occur in patients with the prodromal state of DLB. We herein describe a case of a 72-years-old right-handed woman who exhibited primary progressive aphasia (PPA) as a prodromal state of DLB and took cholinesterase inhibitors (donepezil). At 4.5 years after aphasia onset, she exhibited all the core clinical features of DLB, including visual hallucinations, fluctuating cognition, RBD, and Parkinsonism, as well as progressive language impairment. She showed reduced dopamine transporter (DAT) uptake (assessed by DAT single-photon emission computed tomography imaging) in the striatum and decreased cardiac uptake (determined by (123)I-metaiodobenzylguanidine myocardial scintigraphy), which are indicative biomarkers of DLB. Thus, this patient met all the criteria for probable DLB. Notably, the unique feature of this case was the presentation of PPA, which is seldom observed in typical DLB. Moreover, cholinergic enhancement (donepezil, 5 mg daily) improved her language function and global cognitive function, although mild aphasia remained. The findings provide valuable insights into the spectrum of the prodromal state of DLB and shed light on the development of the medication for PPA caused by cholinergic insufficiency.
ESTHER : Watanabe_2020_Front.Neurol_11_49
PubMedSearch : Watanabe_2020_Front.Neurol_11_49
PubMedID: 32132965

Title : Polysaccharide hydrolase of the hadal zone amphipods Hirondellea gigas - Kobayashi_2018_Biosci.Biotechnol.Biochem_82_1123
Author(s) : Kobayashi H , Nagahama T , Arai W , Sasagawa Y , Umeda M , Hayashi T , Nikaido I , Watanabe H , Oguri K , Kitazato H , Fujioka K , Kido Y , Takami H
Ref : Biosci Biotechnol Biochem , 82 :1123 , 2018
Abstract : Hirondellea species are common inhabitants in the hadal region deeper than 7,000 m. We found that Hirondellea gigas thrived in the Challenger Deep possessed polysaccharide hydrolases as digestive enzymes. To obtain various enzymes of other H. gigas, we captured amphipods from the Japan Trench, and Izu-Ogasawara (Bonin) Trench. A phylogenetic analysis based on the cytochrome oxidase I gene showed close relationships among amphipods, despite the geographic distance between the localities. However, several differences in enzymatic properties were observed in these H. gigas specimens. We also carried out RNA sequencing of H. gigas from the Izu-Ogasawara Trench. The cellulase gene of H. gigas was highly homologous to cellobiohydrolase of Glucosyl Hydrolase family 7 (GH7). On the other hand, enzymatic properties of H. gigas's cellulase were different from those of typical GH7 cellobiohydrolase. Thus, these results indicate that hadal-zone amphipod can be good candidates as the new enzyme resource.
ESTHER : Kobayashi_2018_Biosci.Biotechnol.Biochem_82_1123
PubMedSearch : Kobayashi_2018_Biosci.Biotechnol.Biochem_82_1123
PubMedID: 29623763
Gene_locus related to this paper: 9crus-a0a2p2i2d2 , 9crus-a0a2p2ic40

Title : Allying with armored snails: the complete genome of gammaproteobacterial endosymbiont - Nakagawa_2014_ISME.J_8_40
Author(s) : Nakagawa S , Shimamura S , Takaki Y , Suzuki Y , Murakami S , Watanabe T , Fujiyoshi S , Mino S , Sawabe T , Maeda T , Makita H , Nemoto S , Nishimura S , Watanabe H , Watsuji TO , Takai K
Ref : Isme J , 8 :40 , 2014
Abstract : Deep-sea vents harbor dense populations of various animals that have their specific symbiotic bacteria. Scaly-foot gastropods, which are snails with mineralized scales covering the sides of its foot, have a gammaproteobacterial endosymbiont in their enlarged esophageal glands and diverse epibionts on the surface of their scales. In this study, we report the complete genome sequencing of gammaproteobacterial endosymbiont. The endosymbiont genome displays features consistent with ongoing genome reduction such as large proportions of pseudogenes and insertion elements. The genome encodes functions commonly found in deep-sea vent chemoautotrophs such as sulfur oxidation and carbon fixation. Stable carbon isotope ((13)C)-labeling experiments confirmed the endosymbiont chemoautotrophy. The genome also includes an intact hydrogenase gene cluster that potentially has been horizontally transferred from phylogenetically distant bacteria. Notable findings include the presence and transcription of genes for flagellar assembly, through which proteins are potentially exported from bacterium to the host. Symbionts of snail individuals exhibited extreme genetic homogeneity, showing only two synonymous changes in 19 different genes (13 810 positions in total) determined for 32 individual gastropods collected from a single colony at one time. The extremely low genetic individuality in endosymbionts probably reflects that the stringent symbiont selection by host prevents the random genetic drift in the small population of horizontally transmitted symbiont. This study is the first complete genome analysis of gastropod endosymbiont and offers an opportunity to study genome evolution in a recently evolved endosymbiont.
ESTHER : Nakagawa_2014_ISME.J_8_40
PubMedSearch : Nakagawa_2014_ISME.J_8_40
PubMedID: 23924784
Gene_locus related to this paper: 9gamm-s6bga5

Title : A DKP Cyclo(L-Phe-L-Phe) Found in Chicken Essence Is a Dual Inhibitor of the Serotonin Transporter and Acetylcholinesterase - Tsuruoka_2012_PLoS.One_7_e50824
Author(s) : Tsuruoka N , Beppu Y , Koda H , Doe N , Watanabe H , Abe K
Ref : PLoS ONE , 7 :e50824 , 2012
Abstract : Diketopiperazines (DKPs) are naturally-occurring cyclic dipeptides with a small structure and are found in many organisms and in large amounts in some foods and beverages. We found that a chicken essence beverage, which is popular among Southeast Asians as a traditional remedy and a rich source of DKPs, inhibited the serotonin transporter (SERT) and suppressed serotonin uptake from rat brain synaptosomes, which prompted us to isolate and identify the active substance(s). We purified a SERT inhibitor from the chicken essence beverage and identified it as the DKP cyclo(L-Phe-L-Phe). Interestingly, it was a naturally occurring dual inhibitor that inhibited both SERT and acetylcholinesterase (AChE) in vitro. The DKP increased extracellular levels of the cerebral monoamines serotonin, norepinephrine, and dopamine in the medial prefrontal cortex and acetylcholine in the ventral hippocampus of freely moving rats when administered orally. Moreover, cyclo(L-Phe-L-Phe) significantly shortened escape latency in the water maze test in depressed mice previously subjected to a repeated open-space swimming task, which induces a depression-like state. Cyclo(L-Phe-L-Phe) also significantly improved accuracy rates in a radial maze test in rats and increased step-through latencies in a passive avoidance test in mice with scopolamine-induced amnesia. These animal test results suggest that cyclo(L-Phe-L-Phe), which is present abundantly in some foods such as chicken essence, may abrogate the onset of depression and, thus, contribute to preventing the development of Alzheimer's disease and other dementia, because senile depression is a risk factor for dementia.
ESTHER : Tsuruoka_2012_PLoS.One_7_e50824
PubMedSearch : Tsuruoka_2012_PLoS.One_7_e50824
PubMedID: 23209830

Title : Whole-genome analysis of Salmonella enterica serovar Typhimurium T000240 reveals the acquisition of a genomic island involved in multidrug resistance via IS1 derivatives on the chromosome - Izumiya_2011_Antimicrob.Agents.Chemother_55_623
Author(s) : Izumiya H , Sekizuka T , Nakaya H , Taguchi M , Oguchi A , Ichikawa N , Nishiko R , Yamazaki S , Fujita N , Watanabe H , Ohnishi M , Kuroda M
Ref : Antimicrobial Agents & Chemotherapy , 55 :623 , 2011
Abstract : Salmonella enterica serovar Typhimurium is frequently associated with life-threatening systemic infections, and the recent global emergence of multidrug resistance in S. enterica isolates from agricultural and clinical settings has raised concerns. In this study, we determined the whole-genome sequence of fluoroquinolone-resistant S. enterica serovar Typhimurium T000240 strain (DT12) isolated from human gastroenteritis in 2000. Comparative genome analysis revealed that T000240 displays high sequence similarity to strain LT2, which was originally isolated in 1940, indicating that progeny of LT2 might be reemerging. T000240 possesses a unique 82-kb genomic island, designated as GI-DT12, which is composed of multidrug resistance determinants, including a Tn2670-like composite transposon (class 1 integron [intI1, bla(oxa-30), aadA1, qacEDelta1, and sul1], mercury resistance proteins, and chloramphenicol acetyltransferase), a Tn10-like tetracycline resistance protein (tetA), the aerobactin iron-acquisition siderophore system (lutA and lucABC), and an iron transporter (sitABCD). Since GI-DT12 is flanked by IS1 derivatives, IS1-mediated recombination likely played a role in the acquisition of this genomic island through horizontal gene transfer. The aminoglycoside-(3)-N-acetyltransferase (aac(3)) gene and a class 1 integron harboring the dfrA1 gene cassette responsible for gentamicin and trimethoprim resistance, respectively, were identified on plasmid pSTMDT12_L and appeared to have been acquired through homologous recombination with IS26. This study represents the first characterization of the unique genomic island GI-DT12 that appears to be associated with possible IS1-mediated recombination in S. enterica serovar Typhimurium. It is expected that future whole-genome studies will aid in the characterization of the horizontal gene transfer events for the emerging S. enterica serovar Typhimurium strains.
ESTHER : Izumiya_2011_Antimicrob.Agents.Chemother_55_623
PubMedSearch : Izumiya_2011_Antimicrob.Agents.Chemother_55_623
PubMedID: 21098248
Gene_locus related to this paper: salty-ycfp

Title : [Acute respiratory failure associated with cholinergic crisis: report of five cases and review of the literature] - Takahashi_2011_Nihon.Kokyuki.Gakkai.Zasshi_49_877
Author(s) : Takahashi M , Ubukata S , Sato E , Shoji M , Morikawa N , Watanabe H , Takahashi H
Ref : Nihon Kokyuki Gakkai Zasshi , 49 :877 , 2011
Abstract : Distigmine bromide is a cholinesterase inhibitor widely used for the treatment of hypotonic neurogenic bladder. However, this drug is also known to cause cholinergic crisis, a rare but serious adverse reaction. Cholinergic crisis is an excessive amount of acetylcholine due to the systemic inhibition of cholinesterase activity, characterized by parasympathetic symptoms such as sweating, salivation, miosis, bradycardia, diarrhea and circulatory and respiratory failure. The incidence of cholinergic crisis has been estimated at approximately 0.2%, and the majority of the patients are elderly with underlying conditions such as cerebrovascular disease. Since 2004, we have encountered 5 cases of acute respiratory failure associated with cholinergic crisis induced by the administration of a normal oral dose of distigmine. We present these cases here and review an additional 23 cases from the literature in Japan. In these 28 cases, mechanical ventilation was required for 57%, with a mean duration of 5.1 days and a mortality rate of 11%. Pneumonia was observed in half of the cases in the acute phase, and relapse due to the readministration of distigmine was reported in 20% of cases. It is important to remember that cholinergic crisis in the elderly is often misdiagnosed and is occasionally treated as simple aspiration pneumonia.
ESTHER : Takahashi_2011_Nihon.Kokyuki.Gakkai.Zasshi_49_877
PubMedSearch : Takahashi_2011_Nihon.Kokyuki.Gakkai.Zasshi_49_877
PubMedID: 22352046

Title : The dynamic genome of Hydra - Chapman_2010_Nature_464_592
Author(s) : Chapman JA , Kirkness EF , Simakov O , Hampson SE , Mitros T , Weinmaier T , Rattei T , Balasubramanian PG , Borman J , Busam D , Disbennett K , Pfannkoch C , Sumin N , Sutton GG , Viswanathan LD , Walenz B , Goodstein DM , Hellsten U , Kawashima T , Prochnik SE , Putnam NH , Shu S , Blumberg B , Dana CE , Gee L , Kibler DF , Law L , Lindgens D , Martinez DE , Peng J , Wigge PA , Bertulat B , Guder C , Nakamura Y , Ozbek S , Watanabe H , Khalturin K , Hemmrich G , Franke A , Augustin R , Fraune S , Hayakawa E , Hayakawa S , Hirose M , Hwang JS , Ikeo K , Nishimiya-Fujisawa C , Ogura A , Takahashi T , Steinmetz PR , Zhang X , Aufschnaiter R , Eder MK , Gorny AK , Salvenmoser W , Heimberg AM , Wheeler BM , Peterson KJ , Bottger A , Tischler P , Wolf A , Gojobori T , Remington KA , Strausberg RL , Venter JC , Technau U , Hobmayer B , Bosch TC , Holstein TW , Fujisawa T , Bode HR , David CN , Rokhsar DS , Steele RE
Ref : Nature , 464 :592 , 2010
Abstract : The freshwater cnidarian Hydra was first described in 1702 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals. Today, Hydra is an important model for studies of axial patterning, stem cell biology and regeneration. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann-Mangold organizer, pluripotency genes and the neuromuscular junction.
ESTHER : Chapman_2010_Nature_464_592
PubMedSearch : Chapman_2010_Nature_464_592
PubMedID: 20228792
Gene_locus related to this paper: 9burk-c9y6c0 , 9burk-c9y8q9 , 9burk-c9y9d4 , 9burk-c9ya28 , 9burk-c9yb37 , 9burk-c9ycr9 , 9burk-c9ydq0 , 9burk-c9ydr2 , 9burk-c9yew1 , 9burk-c9yf78 , 9burk-c9ygh2 , 9burk-c9y7j2

Title : Serum immunosuppressive acidic protein reflects systemic deterioration of colorectal cancer patient condition - Toiyama_2008_J.Surg.Oncol_97_404
Author(s) : Toiyama Y , Miki C , Inoue Y , Okugawa Y , Koike Y , Watanabe H , Yokoe T , Hiro J , Ojima E , Tanaka K , Kusunoki M
Ref : J Surg Oncol , 97 :404 , 2008
Abstract : AIMS: Immunosuppressive acidic protein (IAP) is a potent biological marker for immunological surveillance in patients with malignant tumors. This study aimed to investigate the significance of serum IAP as an index of disease status, clinicopathological findings and prognosis in colorectal cancer. METHODS: A total of 101 patients with colorectal cancer and 80 normal volunteers were included in this retrospective trial. Preoperative serum IAP was assayed using a commercially available enzyme-linked immunosorbent assay kit. RESULTS: The serum IAP level in the patients, which was not associated with clinicopathological features except for tumor size, was significantly higher than that in controls. The serum IAP level was closely correlated with percent body weight loss, serum albumin and cholinesterase, and percentage of circulating lymphocytes reflecting the host's nutritional and immunological conditions. Interestingly, these parameters were not associated with factors reflecting disease progression except for tumor size. The prognosis of patients with higher IAP levels was significantly worse than that of patients with lower IAP levels. Furthermore, an elevated serum IAP level was an independent prognostic marker in all patients. CONCLUSION: The preoperative serum IAP level may reflect the general condition of colorectal cancer patients, and thus may predict long-term survival independently of stage progression.
ESTHER : Toiyama_2008_J.Surg.Oncol_97_404
PubMedSearch : Toiyama_2008_J.Surg.Oncol_97_404
PubMedID: 18181167

Title : Effect of metformin on serum lipoprotein lipase mass levels and LDL particle size in type 2 diabetes mellitus patients - Ohira_2007_Diabetes.Res.Clin.Pract_78_34
Author(s) : Ohira M , Miyashita Y , Ebisuno M , Saiki A , Endo K , Koide N , Oyama T , Murano T , Watanabe H , Shirai K
Ref : Diabetes Res Clin Pract , 78 :34 , 2007
Abstract : We previously reported that lipoprotein lipase mass levels in preheparin serum (preheparin LPL mass) was significantly lower in type 2 diabetes mellitus compared to healthy subjects and that low preheparin LPL mass may be a high-risk factor of coronary atherosclerosis. The aim of this study was to clarify the effects of metformin on serum lipoprotein lipase mass levels (preheparin LPL mass), adiponectin and lipid metabolism in patients with type 2 diabetes mellitus. Twenty-eight patients with type 2 diabetes mellitus (HbAlc>7.0%), who were already receiving sulfonylurea agents, took metformin 500 mg orally twice daily for 3 months. Fasting blood glucose (FBG), immunoreactive insulin (basal IRI) and HbAlc decreased significantly after metformin treatment. LDL-Rm ratio decreased significantly (from 0.3521+/-0.046 to 0.3339+/-0.030, P<0.05) and preheparin LPL mass increased significantly (from 42.5+/-3.2 to 50.6+/-3.5 ng/ml, P<0.0005), but adiponectin was unchanged. The correlation of a change of LDL-Rm ratio and a change of preheparin LPL mass showed a negative correlation tendency. The changes in LDL-Rm ratio and preheparin LPL mass were independent of the hypoglycemic effect of metformin. These results suggest that metformin may increase LPL production, thereby increasing LDL particle size. These effects might be independent of the hypoglycemic effect of metformin.
ESTHER : Ohira_2007_Diabetes.Res.Clin.Pract_78_34
PubMedSearch : Ohira_2007_Diabetes.Res.Clin.Pract_78_34
PubMedID: 17374417

Title : Involvement of up-regulation of hepatic breast cancer resistance protein in decreased plasma concentration of 7-ethyl-10-hydroxycamptothecin (SN-38) by coadministration of S-1 in rats - Yokoo_2007_Drug.Metab.Dispos_35_1511
Author(s) : Yokoo K , Hamada A , Watanabe H , Matsuzaki T , Imai T , Fujimoto H , Masa K , Saito H
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 35 :1511 , 2007
Abstract : The safety and efficacy of combination therapy with 7-ethyl-10-[4-[1-piperidino]-1-piperidino]carbonyloxycamptothecin (CPT-11, irinotecan) and S-1 composed of tegafur, a prodrug of 5-fluorouracil, gimeracil, and potassium oxonate, have been confirmed in patients with colorectal cancer. Previously, we showed that p.o. coadministration of S-1 decreased the plasma concentration of both CPT-11 and its metabolites in a patient with advanced colorectal cancer. The aim of this study was to clarify the mechanism of drug interaction using both in vivo and in vitro methods. Rats were administered S-1 p.o. (10 mg/kg) once a day for 7 consecutive days. On day 7, CPT-11 (10 mg/kg) was administered by i.v. injection. Coadministration of S-1 affected the pharmacokinetic behavior of CPT-11 and its metabolites, with a decrease in the C(max) and area under the plasma concentration curve (AUC) of the active metabolite 7-ethyl-10-hydroxycampothecin (SN-38) lactone form. Furthermore, the rate of biliary excretion of the SN-38 carboxylate form increased on coadministration of S-1. In the liver, the level of breast cancer resistance protein (BCRP), but not P-glycoprotein and multidrug resistance-associated protein 2, was elevated after administration of S-1. Enzymatic conversion of CPT-11 to SN-38 by carboxylesterase (CES) was unaffected by the liver microsomes of rats treated with S-1. In addition, components of S-1 did not inhibit the hydrolysis of p-nitrophenylacetate, a substrate of CES, in the S9 fraction of HepG2 cells. Therefore, the mechanism of drug interaction between CPT-11 and S-1 appears to involve up-regulation of BCRP in the liver, resulting in an increased rate of biliary excretion of SN-38 accompanied by a decrease in the C(max) and AUC of SN-38.
ESTHER : Yokoo_2007_Drug.Metab.Dispos_35_1511
PubMedSearch : Yokoo_2007_Drug.Metab.Dispos_35_1511
PubMedID: 17537871

Title : Schedule-dependent cytotoxicity of 5-fluorouracil and irinotecan in a colon cancer cell line - Inoue_2006_J.Gastroenterol_41_1149
Author(s) : Inoue Y , Miki C , Watanabe H , Hiro J , Toiyama Y , Ojima E , Yanagi H , Kusunoki M
Ref : J Gastroenterol , 41 :1149 , 2006
Abstract : BACKGROUND: Our aim was to clarify the significance of widely accepted irinotecan (CPT-11)/5-fluorouracil (5-FU) combinations in colon cancer by investigating their sequential effect. METHODS: The sequential effect of CPT-11/5-FU in two colon cancer cell lines, LoVo and SW480, was evaluated by WST-8 colorimetric assay. The cell cycle distributions of each drug were analyzed by flow cytometry, and then the chemoresistant mechanisms and expression of a drug transporter (MDR1), the bcl-2 apoptotic pathway, metabolizing enzymes [carboxylesterase (CE), dihydropyrimidine dehydrogenase], and target enzymes (topoisomerase I, thymidine synthase) associated with sequence-dependent cytotoxicity were examined. RESULTS: The cytotoxicity of 5-FU (10, 100, 1000 microM) followed by CPT-11 (1 microM) was significantly greater than that of CPT-11 (1 microM) followed by 5-FU (10, 100, 1000 microM) (P < 0.05). Reverse transcription-polymerase chain reaction analysis revealed that exposure to 5-FU downregulated both MDR1 and bcl-2 mRNA and simultaneously upregulated CE2 mRNA expression, suggesting enhancement of subsequent CPT-11 cytotoxicity. CONCLUSIONS: The cytotoxic effects of the CPT-11/5-FU combinations were shown to be schedule-dependent in human colon cancer cells. The findings suggest that 5-FU followed by CPT-11 administration might be the optimal sequence for CPT-11/5-FU treatment of advanced colon cancer.
ESTHER : Inoue_2006_J.Gastroenterol_41_1149
PubMedSearch : Inoue_2006_J.Gastroenterol_41_1149
PubMedID: 17287894

Title : Effects of diacylglycerol administration on serum triacylglycerol in a patient homozygous for complete lipoprotein lipase deletion - Yamamoto_2005_Metabolism_54_67
Author(s) : Yamamoto K , Asakawa H , Tokunaga K , Meguro S , Watanabe H , Tokimitsu I , Yagi N
Ref : Metabolism , 54 :67 , 2005
Abstract : We investigated postprandial and long-term effects of dietary diacylglycerol (DAG) on serum triacylglycerol (TAG) levels in a 34-year-old man homozygous for complete lipoprotein lipase deletion (LPL deletion). In study 1, Three different oils (DAG, TAG, or medium-chain fatty acid TAG [MCT]) were ingested to examine differences in the postprandial serum TAG response. Postprandial serum TAG levels after DAG oil ingestion were lower than those after TAG oil ingestion and similar to those after MCT oil ingestion. In study 2, the patient was allowed to ingest ordinary cooking oil for 2 months and then DAG oil (containing 80% DAG; target, 20 g/d) for the next 3 months. During the test period, serum TAG levels were measured and dietary evaluations were performed every month. The patient was provided with dietary instruction and consultation at each clinical visit. Serum TAG levels were 1939 to 2525 mg/dL when he used ordinary cooking oil, 1926 to 1173 mg/dL when he used ordinary cooking oil together with DAG oil, and 749 mg/dL when he used DAG oil alone. The TAG intake decreased from 86.9 to 43.0 g and the DAG intake increased from 0.9 to 12.4 g during the study period. Subsequently, 45 g DAG oil (equivalent to 36 g DAG) per day was consumed, and the serum TAG level increased to 2195 mg/dL. Although there was a positive correlation between the TAG intake and serum TAG levels during the period of DAG oil use (P < .01, y = 33.7x - 583.1), there was no such correlation between DAG oil intake and serum TAG levels. These results suggested that substitution of 12.0 g/d DAG (equivalent to 15 g DAG oil) for TAG oil had the same effect as reducing TAG oil consumption for controlling the serum TAG levels in an LPL-depleted patient with hypertriglyceridemia. In conclusion, the results of study 1 and study 2 demonstrate that DAG oil might be replaced by MCT oil as cooking oil for those with LPL deletion.
ESTHER : Yamamoto_2005_Metabolism_54_67
PubMedSearch : Yamamoto_2005_Metabolism_54_67
PubMedID: 15562382

Title : Esterase-like activity of serum albumin: characterization of its structural chemistry using p-nitrophenyl esters as substrates - Sakurai_2004_Pharm.Res_21_285
Author(s) : Sakurai Y , Ma SF , Watanabe H , Yamaotsu N , Hirono S , Kurono Y , Kragh-Hansen U , Otagiri M
Ref : Pharm Res , 21 :285 , 2004
Abstract : PURPOSE: To elucidate the catalytic mechanism of the esterase-like activity of serum albumin (SA), the reactivity of SA from six species was investigated using p-nitrophenyl esters as model substrates.
METHODS: The effect of pH and the energetic and thermodynamic profiles of SA were determined for all species for p-nitrophenyl acetate (PNPA). Then, kinetic and thermodynamic studies using a series of p- and o-nitrophenyl esters with different side chains and human SA (HSA) were carried out. The influence of deuterium oxide was also evaluated. Finally, the information gained was used to construct a computer model of the structural chemistry of the reaction.
RESULTS: The pH profiles suggest that the nucleophilic character of the catalytic residue (Tyr-411 in the case of HSA) is essential for activity. This kcat-dependent activity was found to increase with a decrease in the activation free energy change (deltaG). Hence, the magnitude of deltaG, which is dependent on activation entropy change (deltaS), as calculated from the thermodynamic analysis, can be regarded as an indicator of hydrolytic activity. It indicates that p-nitrophenyl propionate (PNPP) is the best substrate by evaluating the reactions of nitrophenyl esters with HSA. The findings here indicate that deuterium oxide has no significant effect on the rate of hydrolysis of PNPA by HSA.
CONCLUSIONS: The results are consistent with a scenario in which HSA becomes acylated due to a nucleophilic attack by Tyr-411 on the substrate and then is deacylated by general acid or base catalysis with the participation of water.
ESTHER : Sakurai_2004_Pharm.Res_21_285
PubMedSearch : Sakurai_2004_Pharm.Res_21_285
PubMedID: 15032310

Title : DNA sequence and comparative analysis of chimpanzee chromosome 22 - Watanabe_2004_Nature_429_382
Author(s) : Watanabe H , Fujiyama A , Hattori M , Taylor TD , Toyoda A , Kuroki Y , Noguchi H , BenKahla A , Lehrach H , Sudbrak R , Kube M , Taenzer S , Galgoczy P , Platzer M , Scharfe M , Nordsiek G , Blocker H , Hellmann I , Khaitovich P , Paabo S , Reinhardt R , Zheng HJ , Zhang XL , Zhu GF , Wang BF , Fu G , Ren SX , Zhao GP , Chen Z , Lee YS , Cheong JE , Choi SH , Wu KM , Liu TT , Hsiao KJ , Tsai SF , Kim CG , S OO , Kitano T , Kohara Y , Saitou N , Park HS , Wang SY , Yaspo ML , Sakaki Y
Ref : Nature , 429 :382 , 2004
Abstract : Human-chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized.
ESTHER : Watanabe_2004_Nature_429_382
PubMedSearch : Watanabe_2004_Nature_429_382
PubMedID: 15164055
Gene_locus related to this paper: pantr-a0a2j8lmv7

Title : Effects of acute nicotine on hemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain - Cumming_2003_Neuroimage_19_1127
Author(s) : Cumming P , Rosa-Neto P , Watanabe H , Smith D , Bender D , Clarke PB , Gjedde A
Ref : Neuroimage , 19 :1127 , 2003
Abstract : Positive reinforcing properties of nicotine and the psychostimulants have been attributed to elevated dopamine release in the basal ganglia. It is well known that the specific binding of [(11)C]raclopride to dopamine D(2,3) receptors in living striatum is reduced by cocaine and amphetamines, revealing increased competition between endogenous dopamine and [(11)C]raclopride for dopamine D(2,3) receptors. However, the sensitivity of [(11)C]raclopride binding to nicotine-induced dopamine release is less well documented. In order to provide the basis for mapping effects of nicotine, we first optimized reference tissue methods for quantifying [(11)C]raclopride binding sites in striatum of living pigs (n = 16). In the same animals, the rate of cerebral blood flow (CBF) was mapped using [(15)O]water. Neither a low dose of nicotine (50 mu kg(-1), iv) nor a high dose of nicotine (500 microg kg(-1), iv) altered CBF in the pig brain, an important condition for calculating the binding of radioligands when using a reference tissue to estimate the free ligand concentration. The methods of Logan and of Lammertsma were compared using the cerebellum or the occipital cortex as reference tissues for calculating the binding potential (pB) of [(11)C]raclolpride in brain. Irrespective of the method used, the mean undrugged baseline pB in striatum (ca. 2.0) was significantly asymmetric, with highest binding in the left caudate and right putamen. Test-retest estimates of pB were stable. Subtraction of Logan pB maps revealed that the low dose of nicotine reduced the pB of [(11)C]raclopride by 10% in a cluster of voxels in the left anteroventral striatum, but this effect did not persist after correction for multiple comparisons. The high dose of nicotine (n = 9) acutely reduced pB by 10% bilaterally in the ventral striatum; 3 h after the high nicotine dose, the reductions had shifted dorsally and caudally into the caudate and putamen. Evidently, nicotine challenge enhances the competition between endogenous dopamine for [(11)C]raclopride binding sites with a complex temporal and spacial pattern in pig brain, initially presenting in the left ventral striatum.
ESTHER : Cumming_2003_Neuroimage_19_1127
PubMedSearch : Cumming_2003_Neuroimage_19_1127
PubMedID: 12880838

Title : Genome sequence of the endocellular obligate symbiont of tsetse flies, Wigglesworthia glossinidia - Akman_2002_Nat.Genet_32_402
Author(s) : Akman L , Yamashita A , Watanabe H , Oshima K , Shiba T , Hattori M , Aksoy S
Ref : Nat Genet , 32 :402 , 2002
Abstract : Many insects that rely on a single food source throughout their developmental cycle harbor beneficial microbes that provide nutrients absent from their restricted diet. Tsetse flies, the vectors of African trypanosomes, feed exclusively on blood and rely on one such intracellular microbe for nutritional provisioning and fecundity. As a result of co-evolution with hosts over millions of years, these mutualists have lost the ability to survive outside the sheltered environment of their host insect cells. We present the complete annotated genome of Wigglesworthia glossinidia brevipalpis, which is composed of one chromosome of 697,724 base pairs (bp) and one small plasmid, called pWig1, of 5,200 bp. Genes involved in the biosynthesis of vitamin metabolites, apparently essential for host nutrition and fecundity, have been retained. Unexpectedly, this obligate's genome bears hallmarks of both parasitic and free-living microbes, and the gene encoding the important regulatory protein DnaA is absent.
ESTHER : Akman_2002_Nat.Genet_32_402
PubMedSearch : Akman_2002_Nat.Genet_32_402
PubMedID: 12219091
Gene_locus related to this paper: wigbr-BIOH

Title : The DNA sequence of human chromosome 21 - Hattori_2000_Nature_405_311
Author(s) : Hattori M , Fujiyama A , Taylor TD , Watanabe H , Yada T , Park HS , Toyoda A , Ishii K , Totoki Y , Choi DK , Groner Y , Soeda E , Ohki M , Takagi T , Sakaki Y , Taudien S , Blechschmidt K , Polley A , Menzel U , Delabar J , Kumpf K , Lehmann R , Patterson D , Reichwald K , Rump A , Schillhabel M , Schudy A , Zimmermann W , Rosenthal A , Kudoh J , Schibuya K , Kawasaki K , Asakawa S , Shintani A , Sasaki T , Nagamine K , Mitsuyama S , Antonarakis SE , Minoshima S , Shimizu N , Nordsiek G , Hornischer K , Brant P , Scharfe M , Schon O , Desario A , Reichelt J , Kauer G , Blocker H , Ramser J , Beck A , Klages S , Hennig S , Riesselmann L , Dagand E , Haaf T , Wehrmeyer S , Borzym K , Gardiner K , Nizetic D , Francis F , Lehrach H , Reinhardt R , Yaspo ML
Ref : Nature , 405 :311 , 2000
Abstract : Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.
ESTHER : Hattori_2000_Nature_405_311
PubMedSearch : Hattori_2000_Nature_405_311
PubMedID: 10830953
Gene_locus related to this paper: human-LIPI

Title : Genome sequence of the endocellular bacterial symbiont of aphids Buchnera sp. APS - Shigenobu_2000_Nature_407_81
Author(s) : Shigenobu S , Watanabe H , Hattori M , Sakaki Y , Ishikawa H
Ref : Nature , 407 :81 , 2000
Abstract : Almost all aphid species (Homoptera, Insecta) have 60-80 huge cells called bacteriocytes, within which are round-shaped bacteria that are designated Buchnera. These bacteria are maternally transmitted to eggs and embryos through host generations, and the mutualism between the host and the bacteria is so obligate that neither can reproduce independently. Buchnera is a close relative of Escherichia coli, but it contains more than 100 genomic copies per cell, and its genome size is only a seventh of that of E. coli. Here we report the complete genome sequence of Buchnera sp. strain APS, which is composed of one 640,681-base-pair chromosome and two small plasmids. There are genes for the biosyntheses of amino acids essential for the hosts in the genome, but those for non-essential amino acids are missing, indicating complementarity and syntrophy between the host and the symbiont. In addition, Buchnera lacks genes for the biosynthesis of cell-surface components, including lipopolysaccharides and phospholipids, regulator genes and genes involved in defence of the cell. These results indicate that Buchnera is completely symbiotic and viable only in its limited niche, the bacteriocyte.
ESTHER : Shigenobu_2000_Nature_407_81
PubMedSearch : Shigenobu_2000_Nature_407_81
PubMedID: 10993077

Title : Ameliorative effect of tacrine on spatial memory deficit in chronic two-vessel occluded rats is reversible and mediated by muscarinic M1 receptor stimulation - Murakami_2000_Behav.Brain.Res_109_83
Author(s) : Murakami Y , Ikenoya M , Matsumoto K , Li H , Watanabe H
Ref : Behavioural Brain Research , 109 :83 , 2000
Abstract : Our previous study demonstrated that permanent two-vessel occlusion (2VO)-induced working memory deficit was improved by daily administration of tacrine, a cholinesterase inhibitor. In this study, we investigated the mechanism underlying the effects of tacrine in 2VO rats using the eight-arm radial maze task. Daily administration of tacrine (0.1 or 0.3 mg/kg i.p.) started 5 weeks after the 2VO operation significantly improved the maze performance. In the delay-interposition task, a significant impairment of maze performance was observed in the tacrine (0.3 mg/kg, i.p.)-treated rats at a delay of 90 min but not delays of 5 or 30 min. Sham-operated rats were not affected by delay. After leaving animals with no further treatment for 4 weeks, the tacrine-pretreated 2VO rats showed significantly impaired performance compared to the sham-operated control animals. However, the performance of the tacrine-pretreated 2VO rats was significantly improved by restarting the daily administration of tacrine (0.3 mg/kg, i.p.). The effect of tacrine was reversed by the muscarinic antagonist scopolamine and the selective M1 antagonist pirenzepine. Moreover, a microdialysis study revealed that tacrine (1 or 3 mg/kg, i.p.) increased the extracellular acetylcholine (ACh) level for a period of over 3 h in the cerebral cortex of 2VO rats. These findings suggest that the ameliorative effect of tacrine on the spatial memory deficit in 2VO rats is reversible and may be mediated by stimulating the muscarinic M1 receptor via elevation of the extracellular ACh level in the brain.
ESTHER : Murakami_2000_Behav.Brain.Res_109_83
PubMedSearch : Murakami_2000_Behav.Brain.Res_109_83
PubMedID: 10699660

Title : Preheparin serum lipoprotein lipase mass level: the effects of age, gender, and types of hyperlipidemias - Watanabe_1999_Atherosclerosis_145_45
Author(s) : Watanabe H , Miyashita Y , Murano T , Hiroh Y , Itoh Y , Shirai K
Ref : Atherosclerosis , 145 :45 , 1999
Abstract : To clarify the factors regulating preheparin serum lipoprotein lipase mass (preheparin LPL mass), the correlations between preheparin LPL mass and age, gender and types of hyperlipidemias were investigated in 377 persons who underwent annual health examinations. Preheparin LPL mass level did not significantly differ in individuals from 19 to 70 years old, for both men and women. Preheparin LPL mass level correlated negatively with triglyceride (TG), positively with high density lipoprotein-cholesterol (HDL-C), and not at all with total cholesterol (TC) or low density lipoprotein-cholesterol (LDL-C). Preheparin LPL mass levels were apparently higher in women than in men, but when serum lipid levels were adjusted, preheparin LPL mass levels were identical. In type IV and IIb hyperlipidemia, preheparin LPL mass levels were lower than in type IIa patients and in normals. Remnant positive individuals had lower levels of preheparin LPL mass than the negative individuals. In conclusion, preheparin LPL mass levels were not affected by aging and gender, but were lower in the conditions in which TG catabolism was disturbed, indicating that preheparin LPL mass might reflect somewhat the amount of LPL working in the body.
ESTHER : Watanabe_1999_Atherosclerosis_145_45
PubMedSearch : Watanabe_1999_Atherosclerosis_145_45
PubMedID: 10428294

Title : Protective effect of GTS-21, a novel nicotinic receptor agonist, on delayed neuronal death induced by ischemia in gerbils - Nanri_1998_Jpn.J.Pharmacol_76_23
Author(s) : Nanri M , Yamamoto J , Miyake H , Watanabe H
Ref : Japanese Journal of Pharmacology , 76 :23 , 1998
Abstract : The neuroprotective effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride] were studied and compared with those of nicotine, 9-amino-1,2,3,4-tetrahydroacridine hydrochloride hydrate (THA) and pentobarbital-Na (PB) using a cerebral ischemia model in Mongolian gerbils. The learning performance and memory retention were elucidated by a step-through passive avoidance task at 2 and 3 days after ischemia-reperfusion. In this task, the ischemia-operated gerbils showed impairment of learning performance and memory retention. Neuronal cell death in the hippocampal CA1 area was observed at 7 days after ischemia. When administered i.p. 30 min before ischemia, GTS-21 (5 mg/kg), (-)-nicotine (1.5 mg/kg), THA (5 mg/kg) and PB (50 mg/kg) significantly attenuated the impairment of passive avoidance performance and the neuronal cell death induced by the ischemia. When administered orally twice daily for 2 weeks prior to the ischemia, GTS-21 (10 mg/kg) significantly suppressed both amnesia and neuronal cell death, while (-)-nicotine (10 mg/kg) and THA (10 mg/kg) suppressed only the amnesia. These results suggest that GTS-21 exerts a protective activity on not only impairment of learning and memory but also delayed neuronal death and that the underlying mechanism of GTS-21 differs from that of nicotine or THA.
ESTHER : Nanri_1998_Jpn.J.Pharmacol_76_23
PubMedSearch : Nanri_1998_Jpn.J.Pharmacol_76_23
PubMedID: 9517401

Title : Tacrine improves working memory deficit caused by permanent occlusion of bilateral common carotid arteries in rats - Murakami_1997_Jpn.J.Pharmacol_75_443
Author(s) : Murakami Y , Tanaka E , Sakai Y , Matsumoto K , Li HB , Watanabe H
Ref : Japanese Journal of Pharmacology , 75 :443 , 1997
Abstract : Effect of tacrine, a cholinesterase inhibitor, on spatial acquisition deficit caused by permanent occlusion of bilateral common carotid arteries (2VO) was examined by using the conventional 8-arm and the 4-arm baited radial maze tasks in rats. Daily administration of tacrine (0.1 and 0.3 mg/kg, i.p.) 1 month after 2VO operation significantly improved the impaired spatial acquisition in the conventional maze task. This treatment also ameliorated the 2VO-induced working but not reference memory deficit in the 4-arm baited radial maze task. These results suggest that tacrine improvement of working memory deficit in the 2VO rats is due to stimulation of central cholinergic systems.
ESTHER : Murakami_1997_Jpn.J.Pharmacol_75_443
PubMedSearch : Murakami_1997_Jpn.J.Pharmacol_75_443
PubMedID: 9469652

Title : Paeoniflorin attenuates learning impairment of aged rats in operant brightness discrimination task - Ohta_1994_Pharmacol.Biochem.Behav_49_213
Author(s) : Ohta H , Matsumoto K , Shimizu M , Watanabe H
Ref : Pharmacol Biochem Behav , 49 :213 , 1994
Abstract : The effects of paeoniflorin isolated from peony were examined on an aging-induced learning deficit in an operant brightness discrimination task in Fischer 344 rats. Learning in aged (25 months) rats was significantly impaired compared with young (5 months) rats. Daily administration of paeoniflorin (0.01 mg/kg, PO) significantly attenuated the learning impairment in aged rats, whereas it did not affect the learning in young rats. Although tacrine (0.3 and 1 mg/kg, IP), a cholinesterase inhibitor, also did not affect the learning in young rats, it slightly augmented the aging-induced learning deficit in the present task. These data indicate the therapeutic potential of paeoniflorin in the treatment of senile dementia and aging-induced cognitive dysfunction.
ESTHER : Ohta_1994_Pharmacol.Biochem.Behav_49_213
PubMedSearch : Ohta_1994_Pharmacol.Biochem.Behav_49_213
PubMedID: 7816876