Nakamura H

References (34)

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 : Chemical Synthesis of Triazole-Derived Suppressors of Strigolactone Functions - Ito_2021_Methods.Mol.Biol_2309_25
Author(s) : Ito S , Kikuzato K , Nakamura H , Asami T
Ref : Methods Mol Biol , 2309 :25 , 2021
Abstract : Triazole is a five-membered heteroring consists of two carbon atoms and three nitrogen atoms and exhibits a wide range of biological activities. The basic heterocyclic rings are 1,2,3-triazole and 1,2,4-triazole. Here we describe the chemical synthetic methods for triazole derivatives that can suppress the function of SL by inhibiting SL biosynthesis pathway or SL perception sites such as D14.
ESTHER : Ito_2021_Methods.Mol.Biol_2309_25
PubMedSearch : Ito_2021_Methods.Mol.Biol_2309_25
PubMedID: 34028676

Title : Strigolactone signaling inhibition increases adventitious shoot formation on internodal segments of ipecac - Okazaki_2021_Planta_253_123
Author(s) : Okazaki K , Watanabe S , Koike I , Kawada K , Ito S , Nakamura H , Asami T , Shimomura K , Umehara M
Ref : Planta , 253 :123 , 2021
Abstract : SL inhibited adventitious shoot formation of ipecac, whereas the SL-related inhibitors promoted adventitious shoot formation. SL-related inhibitors might be useful as new plant growth regulators for plant propagation. In most plant species, phytohormones are required to induce adventitious shoots for propagating economically important crops and regenerating transgenic plants. In ipecac (Carapichea ipecacuanha (Brot.) L. Andersson), however, adventitious shoots can be formed without phytohormone treatment. Here we evaluated the effects of GR24 (a synthetic strigolactone, SL), SL biosynthetic inhibitors, and an SL antagonist on adventitious shoot formation during tissue culture of ipecac. We found that exogenously applied GR24 suppressed indole-3-acetic acid transport in internodal segments and decreased the number of adventitious shoots formed; in addition, the distribution of adventitious shoots changed from the apical to middle region of the internodal segments. In contrast, the SL-related inhibitors promoted adventitious shoot formation on both apical and middle regions of the segments. In particular, SL antagonist treatment increased endogenous cytokinin levels and induced multiple shoot development. These results indicate that SL inhibits adventitious shoot formation in ipecac. In ipecac, one of the shoots in each internodal segment becomes dominant and auxin derived from that shoot suppresses the other shoot growth. Here, this dominance was overcome by application of SL-related inhibitors. Therefore, SL-related inhibitors might be useful as new plant growth regulators to improve the efficiency of plant propagation in vitro.
ESTHER : Okazaki_2021_Planta_253_123
PubMedSearch : Okazaki_2021_Planta_253_123
PubMedID: 34014387

Title : Subcutaneous injection of organophosphate (Fenitrothion)-Management of preventing the appearance of toxic symptoms: A case report - Nakamura_2021_Clin.Case.Rep_9_e04424
Author(s) : Nakamura H , Hirayama I , Hiruma T , Doi K
Ref : Clin Case Rep , 9 :e04424 , 2021
Abstract : There is a risk of unnecessary extensive incision because of swelling after the subcutaneous injection; however, removing completely the injected organophosphate by making a skin incision before the appearance of toxic symptoms could reduce sequelae.
ESTHER : Nakamura_2021_Clin.Case.Rep_9_e04424
PubMedSearch : Nakamura_2021_Clin.Case.Rep_9_e04424
PubMedID: 34267910

Title : Triazole Ureas Covalently Bind to Strigolactone Receptor and Antagonize Strigolactone Responses - Nakamura_2019_Mol.Plant_12_44
Author(s) : Nakamura H , Hirabayashi K , Miyakawa T , Kikuzato K , Hu W , Xu Y , Jiang K , Takahashi I , Niiyama R , Dohmae N , Tanokura M , Asami T
Ref : Mol Plant , 12 :44 , 2019
Abstract : Strigolactones, a class of plant hormones with multiple functions, mediate plant-plant and plant-microorganism communications in the rhizosphere. In this study, we developed potent strigolactone antagonists, which covalently bind to the strigolactone receptor D14, by preparing an array of triazole urea compounds. Using yeast two-hybrid and rice-tillering assays, we identified a triazole urea compound KK094 as a potent inhibitor of strigolactone receptors. Liquid chromatography-tandem mass spectrometry analysis and X-ray crystallography revealed that KK094 was hydrolyzed by D14, and that a reaction product of this degradation covalently binds to the Ser residue of the catalytic triad of D14. Furthermore, we identified two triazole urea compounds KK052 and KK073, whose effects on D14-D53/D14-SLR1 complex formation were opposite due to the absence (KK052) or presence (KK073) of a trifluoromethyl group on their phenyl ring. These results demonstrate that triazole urea compounds are potentially powerful tools for agricultural application and may be useful for the elucidation of the complicated mechanism underlying strigolactone perception.
ESTHER : Nakamura_2019_Mol.Plant_12_44
PubMedSearch : Nakamura_2019_Mol.Plant_12_44
PubMedID: 30391752
Gene_locus related to this paper: orysj-Q10QA5

Title : Structural analysis of HTL and D14 proteins reveals the basis for ligand selectivity in Striga - Xu_2018_Nat.Commun_9_3947
Author(s) : Xu Y , Miyakawa T , Nosaki S , Nakamura A , Lyu Y , Nakamura H , Ohto U , Ishida H , Shimizu T , Asami T , Tanokura M
Ref : Nat Commun , 9 :3947 , 2018
Abstract : HYPOSENSITIVE TO LIGHT (HTL) and DWARF14 (D14) mediate the perception of karrikin and strigolactone, which stimulates germination of the parasitic weed Striga. However, their role in parasitic seeds is poorly understood, and the basis for their differing responsiveness remains unclear. Here, we show that Striga hermonthica HTL proteins (ShHTLs) in 'conserved' and 'intermediate' clades are able to bind karrikin. The 'divergent' clade is able to hydrolyze strigolactone. Unexpectedly, we find that ShD14 is also capable of hydrolyzing strigolactone. Through comparative analysis of ShHTLs and ShD14 crystal structures, we provide insights into the basis for their selectivity. Moreover, we show that both ShD14 and divergent clade ShHTLs, but not conserved and intermediate clade ShHTLs, can interact with the putative downstream signaling component ShMAX2 in the presence of the synthetic strigolactone, rac-GR24. These findings provide insight into how strigolactone is perceived and how ligand specificity is determined.
ESTHER : Xu_2018_Nat.Commun_9_3947
PubMedSearch : Xu_2018_Nat.Commun_9_3947
PubMedID: 30258184
Gene_locus related to this paper: strhe-ShD14 , strhe-ShHTL4 , strhe-ShHTL1 , strhe-ShHTL7

Title : Structure function and engineering of multifunctional non-heme iron dependent oxygenases in fungal meroterpenoid biosynthesis - Nakashima_2018_Nat.Commun_9_104
Author(s) : Nakashima Y , Mori T , Nakamura H , Awakawa T , Hoshino S , Senda M , Senda T , Abe I
Ref : Nat Commun , 9 :104 , 2018
Abstract : Non-heme iron and alpha-ketoglutarate (alphaKG) oxygenases catalyze remarkably diverse reactions using a single ferrous ion cofactor. A major challenge in studying this versatile family of enzymes is to understand their structure-function relationship. AusE from Aspergillus nidulans and PrhA from Penicillium brasilianum are two highly homologous Fe(II)/alphaKG oxygenases in fungal meroterpenoid biosynthetic pathways that use preaustinoid A1 as a common substrate to catalyze divergent rearrangement reactions to form the spiro-lactone in austinol and cycloheptadiene moiety in paraherquonin, respectively. Herein, we report the comparative structural study of AusE and PrhA, which led to the identification of three key active site residues that control their reactivity. Structure-guided mutagenesis of these residues results in successful interconversion of AusE and PrhA functions as well as generation of the PrhA double and triple mutants with expanded catalytic repertoire. Manipulation of the multifunctional Fe(II)/alphaKG oxygenases thus provides an excellent platform for the future development of biocatalysts.
ESTHER : Nakashima_2018_Nat.Commun_9_104
PubMedSearch : Nakashima_2018_Nat.Commun_9_104
PubMedID: 29317628
Gene_locus related to this paper: penbi-prhl

Title : Methyl phenlactonoates are efficient strigolactone analogs with simple structure - Jamil_2018_J.Exp.Bot_69_2319
Author(s) : Jamil M , Kountche BA , Haider I , Guo X , Ntui VO , Jia KP , Ali S , Hameed US , Nakamura H , Lyu Y , Jiang K , Hirabayashi K , Tanokura M , Arold ST , Asami T , Al-Babili S
Ref : J Exp Bot , 69 :2319 , 2018
Abstract : Strigolactones (SLs) are a new class of phytohormones that also act as germination stimulants for root parasitic plants, such as Striga spp., and as branching factors for symbiotic arbuscular mycorrhizal fungi. Sources for natural SLs are very limited. Hence, efficient and simple SL analogs are needed for elucidating SL-related biological processes as well as for agricultural applications. Based on the structure of the non-canonical SL methyl carlactonoate, we developed a new, easy to synthesize series of analogs, termed methyl phenlactonoates (MPs), evaluated their efficacy in exerting different SL functions, and determined their affinity for SL receptors from rice and Striga hermonthica. Most of the MPs showed considerable activity in regulating plant architecture, triggering leaf senescence, and inducing parasitic seed germination. Moreover, some MPs outperformed GR24, a widely used SL analog with a complex structure, in exerting particular SL functions, such as modulating Arabidopsis roots architecture and inhibiting rice tillering. Thus, MPs will help in elucidating the functions of SLs and are promising candidates for agricultural applications. Moreover, MPs demonstrate that slight structural modifications clearly impact the efficiency in exerting particular SL functions, indicating that structural diversity of natural SLs may mirror a functional specificity.
ESTHER : Jamil_2018_J.Exp.Bot_69_2319
PubMedSearch : Jamil_2018_J.Exp.Bot_69_2319
PubMedID: 29300919

Title : Rationally Designed Strigolactone Analogs as Antagonists of the D14 Receptor - Takeuchi_2018_Plant.Cell.Physiol_59_1545
Author(s) : Takeuchi J , Jiang K , Hirabayashi K , Imamura Y , Wu Y , Xu Y , Miyakawa T , Nakamura H , Tanokura M , Asami T
Ref : Plant Cell Physiol , 59 :1545 , 2018
Abstract : Strigolactones (SLs) are plant hormones that inhibit shoot branching and act as signals in communications with symbiotic fungi and parasitic weeds in the rhizosphere. SL signaling is mediated by DWARF14 (D14), which is an alpha/beta-hydrolase that cleaves SLs into an ABC tricyclic lactone and a butenolide group (i.e. D-ring). This cleavage reaction (hydrolysis and dissociation) is important for inducing the interaction between D14 and its target proteins, including D3 and D53. In this study, a hydrolysis-resistant SL analog was predicted to inhibit the activation of the D14 receptor, thereby disrupting the SL signaling pathway. To test this prediction, carba-SL compounds, in which the ether oxygen of the D-ring or the phenol ether oxygen of the SL agonist (GR24 or 4-bromo debranone) was replaced with a methylene group, were synthesized as novel D14 antagonists. Subsequent biochemical and physiological studies indicated that carba-SLs blocked the interaction between D14 and D53 by inhibiting D14 hydrolytic activity. They also suppressed the SL-induced inhibition of rice tiller outgrowths. Additionally, carba-SLs antagonized the SL response in a Striga parasitic weed species. Structural analyses revealed that the D-ring of 7'-carba-4BD was hydrolyzed by D14 but did not dissociate from the 4BD skeleton. Thus, 7'-carba-4BD functioned as an antagonist rather than an agonist. Thus, the hydrolysis of the D-ring of SLs may be insufficient for activating the receptor. This study provides data relevant to designing SL receptor antagonists.
ESTHER : Takeuchi_2018_Plant.Cell.Physiol_59_1545
PubMedSearch : Takeuchi_2018_Plant.Cell.Physiol_59_1545
PubMedID: 29727000
Gene_locus related to this paper: arath-AtD14 , arath-KAI2.D14L

Title : Involvement of STH7 in light-adapted development in Arabidopsis thaliana promoted by both strigolactone and karrikin - Thussagunpanit_2017_Biosci.Biotechnol.Biochem_81_292
Author(s) : Thussagunpanit J , Nagai Y , Nagae M , Mashiguchi K , Mitsuda N , Ohme-Takagi M , Nakano T , Nakamura H , Asami T
Ref : Biosci Biotechnol Biochem , 81 :292 , 2017
Abstract : Strigolactones (SLs) and karrikins (KARs) regulate photomorphogenesis. GR24, a synthetic SL and KAR1, a KAR, inhibit the hypocotyl elongation of Arabidopsis thaliana in a weak light. GR24 and KAR1 up-regulate the expression of STH7, encoding a transcription factor belonging to the double B-box zinc finger subfamily. In this study, we used STH7-overexpressing (STH7ox) lines and functionally defective STH7 (STH7-SRDX) mutants to investigate roles of SLs and KARs in photomorphogenesis of Arabidopsis. Hypocotyl elongation of STH7-SRDX mutants was less sensitive to both GR24 and KAR1 treatment than that of wild-type Arabidopsis under weak light conditions. Furthermore, the chlorophyll and anthocyanin content was increased in STH7ox lines when de-etiolated with light and GR24-treated plants had enhanced anthocyanin production. GR24 and KAR1 treatment significantly increased the expression level of photosynthesis-related genes LHCB1 and rbcS. The results strongly suggest that SL and KAR induce photomorphogenesis of Arabidopsis in an STH7-dependent manner.
ESTHER : Thussagunpanit_2017_Biosci.Biotechnol.Biochem_81_292
PubMedSearch : Thussagunpanit_2017_Biosci.Biotechnol.Biochem_81_292
PubMedID: 27858514

Title : Evaluation of the impact of RNA preservation methods of spiders for de novo transcriptome assembly - Kono_2016_Mol.Ecol.Resour_16_662
Author(s) : Kono N , Nakamura H , Ito Y , Tomita M , Arakawa K
Ref : Mol Ecol Resour , 16 :662 , 2016
Abstract : With advances in high-throughput sequencing technologies, de novo transcriptome sequencing and assembly has become a cost-effective method to obtain comprehensive genetic information of a species of interest, especially in nonmodel species with large genomes such as spiders. However, high-quality RNA is essential for successful sequencing, and sample preservation conditions require careful consideration for the effective storage of field-collected samples. To this end, we report a streamlined feasibility study of various storage conditions and their effects on de novo transcriptome assembly results. The storage parameters considered include temperatures ranging from room temperature to -80 degrees C; preservatives, including ethanol, RNAlater, TRIzol and RNAlater-ICE; and sample submersion states. As a result, intact RNA was extracted and assembly was successful when samples were preserved at low temperatures regardless of the type of preservative used. The assemblies as well as the gene expression profiles were shown to be robust to RNA degradation, when 30 million 150-bp paired-end reads are obtained. The parameters for sample storage, RNA extraction, library preparation, sequencing and in silico assembly considered in this work provide a guideline for the study of field-collected samples of spiders.
ESTHER : Kono_2016_Mol.Ecol.Resour_16_662
PubMedSearch : Kono_2016_Mol.Ecol.Resour_16_662
PubMedID: 26561354
Gene_locus related to this paper: partp-a0a2l2yf54 , partp-a0a2l2y331 , partp-a0a2l2y9v9 , partp-a0a2l2ya50

Title : Structural basis of unique ligand specificity of KAI2-like protein from parasitic weed Striga hermonthica - Xu_2016_Sci.Rep_6_31386
Author(s) : Xu Y , Miyakawa T , Nakamura H , Nakamura A , Imamura Y , Asami T , Tanokura M
Ref : Sci Rep , 6 :31386 , 2016
Abstract : The perception of two plant germination inducers, karrikins and strigolactones, are mediated by the proteins KAI2 and D14. Recently, KAI2-type proteins from parasitic weeds, which are possibly related to seed germination induced by strigolactone, have been classified into three clades characterized by different responses to karrikin/strigolactone. Here we characterized a karrikin-binding protein in Striga (ShKAI2iB) that belongs to intermediate-evolving KAI2 and provided the structural bases for its karrikin-binding specificity. Binding assays showed that ShKAI2iB bound karrikins but not strigolactone, differing from other KAI2 and D14. The crystal structures of ShKAI2iB and ShKAI2iB-karrikin complex revealed obvious structural differences in a helix located at the entry of its ligand-binding cavity. This results in a smaller closed pocket, which is also the major cause of ShKAI2iB's specificity of binding karrikin. Our structural study also revealed that a few non-conserved amino acids led to the distinct ligand-binding profile of ShKAI2iB, suggesting that the evolution of KAI2 resulted in its diverse functions.
ESTHER : Xu_2016_Sci.Rep_6_31386
PubMedSearch : Xu_2016_Sci.Rep_6_31386
PubMedID: 27507097
Gene_locus related to this paper: strhe-ShHTL3

Title : Discovery and identification of 2-methoxy-1-naphthaldehyde as a novel strigolactone-signaling inhibitor - Mashita_2016_J.Pestic.Sci_41_71
Author(s) : Mashita O , Koishihara H , Fukui K , Nakamura H , Asami T
Ref : J Pestic Sci , 41 :71 , 2016
Abstract : Knowledge about strigolactone biosynthesis and signaling is increasing and the crystal structure of strigolactone receptor protein D14 has been resolved. Although a variety of strigolactone biosynthesis inhibitors and strigolactone agonists are known, no inhibitors of strigolactone signaling have been reported. Here, we conducted virtual screening in silico to identify chemical regulators that inhibit SL reception. We used LigandScout to analyze a pharmacophore model based on structural information about D14 protein and complex D14-D-OH (a hydrolysis product of strigolactone formed by D14). We identified a candidate compound, XM-47, and confirmed that it inhibits D14-SLR1 and D14-D53 interactions. A possible product of XM-47 hydrolysis, 2-methoxy-1-naphthaldehyde (2-MN), inhibits D14-SLR1 and D14-D53 interactions and restores the growth of rice tillering buds suppressed by strigolactone.
ESTHER : Mashita_2016_J.Pestic.Sci_41_71
PubMedSearch : Mashita_2016_J.Pestic.Sci_41_71
PubMedID: 30363101

Title : A new metabolism-related index correlates with the degree of liver fibrosis in hepatitis C virus-positive patients - Enomoto_2015_Gastroenterol.Res.Pract_2015_926169
Author(s) : Enomoto H , Aizawa N , Nakamura H , Takata R , Sakai Y , Iwata Y , Tanaka H , Ikeda N , Aoki T , Hasegawa K , Yoh K , Hashimoto K , Ishii A , Takashima T , Saito M , Imanishi H , Iijima H , Nishiguchi S
Ref : Gastroenterol Res Pract , 2015 :926169 , 2015
Abstract : Background. Only a few biomarkers based on metabolic parameters for evaluating liver fibrosis have been reported. The aim of this study was to investigate the relevance of an index obtained from three metabolic variables (glycated albumin: GA, glycated hemoglobin: HbA1c, and branched-chain amino acids to tyrosine ratio: BTR) to the degree of liver fibrosis in hepatitis C virus virus- (HCV-) positive patients. Methods. A total of 394 HCV-positive patients were assessed based on the values of a new index (GA/HbA1c/BTR). The index findings were used to investigate the relationship with the degree of liver fibrosis. Results. The new index showed an association with the stage of fibrosis (METAVIR scores: F0-1: 0.42 +/- 0.10, F2: 0.48 +/- 0.15, F3: 0.56 +/- 0.22, and F4: 0.71 +/- 0.30). The index was negatively correlated with three variables of liver function: the prothrombin time percentage (P < 0.0001), albumin level (P < 0.0001), and cholinesterase level (P < 0.0001). The new index showed a higher correlation related to liver function than FIB-4 and the APRI did. In addition, the index showed a higher AUROC value than that of FIB-4 and the APRI for prediction of liver cirrhosis. Conclusion. The new metabolism-related index, GA/HbA1c/BTR value, is shown to relate to the degree of liver fibrosis in HCV-positive patients.
ESTHER : Enomoto_2015_Gastroenterol.Res.Pract_2015_926169
PubMedSearch : Enomoto_2015_Gastroenterol.Res.Pract_2015_926169
PubMedID: 25861264

Title : Development of Inhibitors of Salicylic Acid Signaling - Jiang_2015_J.Agric.Food.Chem_63_7124
Author(s) : Jiang K , Kurimoto T , Seo EK , Miyazaki S , Nakajima M , Nakamura H , Asami T
Ref : Journal of Agricultural and Food Chemistry , 63 :7124 , 2015
Abstract : Salicylic acid (SA) plays important roles in the induction of systemic acquired resistance (SAR) in plants. Determining the mechanism of SAR will extend our understanding of plant defenses against pathogens. We recently reported that PAMD is an inhibitor of SA signaling, which suppresses the expression of the pathogenesis-related PR genes and is expected to facilitate the understanding of SA signaling. However, PAMD strongly inhibits plant growth. To minimize the side effects of PAMD, we synthesized a number of PAMD derivatives, and identified compound 4 that strongly suppresses the expression of the PR genes with fewer adverse effects on plant growth than PAMD. We further showed that the adverse effects on plant growth were partially caused the stabilization of DELLA, which is also related to the pathogen responses. These results indicate that compound 4 would facilitate our understanding of SA signaling and its cross talk with other plant hormones.
ESTHER : Jiang_2015_J.Agric.Food.Chem_63_7124
PubMedSearch : Jiang_2015_J.Agric.Food.Chem_63_7124
PubMedID: 26236918

Title : Effect of different chemical bonds in pegylation of zinc protoporphyrin that affects drug release, intracellular uptake, and therapeutic effect in the tumor - Tsukigawa_2015_Eur.J.Pharm.Biopharm_89_259
Author(s) : Tsukigawa K , Nakamura H , Fang J , Otagiri M , Maeda H
Ref : Eur J Pharm Biopharm , 89 :259 , 2015
Abstract : Pegylated zinc protoporphyrin (PEG-ZnPP) is a water-soluble inhibitor of heme oxygenase-1. In this study, we prepared two types of PEG-ZnPP conjugates with different chemical bonds between PEG and ZnPP, i.e., ester bonds and ether bonds, where both conjugates also contain amide bonds. Cleavability of these bonds in vitro and in vivo, especially cancer tissue, and upon intracellular uptake, was investigated in parallel with biological activities of the conjugates. Each conjugate showed different cleavability by plasma esterases and tumor proteases, as revealed by HPLC analyses. PEG-ZnPP with ester bond (esPEG-ZnPP) was more sensitive than PEG-ZnPP with ether bond (etPEG-ZnPP) for cleavage of PEG chains. etPEG-ZnPP showed no cleavage of PEG chains and had lower intracellular uptake and antitumor activity than did esPEG-ZnPP. The degradation of esPEG-ZnPP appeared to be facilitated by both serine and cysteine proteases in tumor tissues, whereas it was significantly slower in normal organs except the liver. Depegylated products such as free ZnPP had higher intracellular uptake than did intact PEG-ZnPP. We also studied hydrolytic cleavage by blood plasma of different animal species; mouse plasma showed the fastest cleavage whereas human plasma showed the slowest. These results suggest that ester-linked conjugates manifest more efficient cleavage of PEG, and greater yield of the active principle from the conjugates in tumor tissues than in normal tissues. More efficient intracellular uptake and thus an improved therapeutic effect with ester-linked conjugates are thus anticipated with fain stability, particularly in human blood.
ESTHER : Tsukigawa_2015_Eur.J.Pharm.Biopharm_89_259
PubMedSearch : Tsukigawa_2015_Eur.J.Pharm.Biopharm_89_259
PubMedID: 25527214

Title : Target sites for chemical regulation of strigolactone signaling - Nakamura_2014_Front.Plant.Sci_5_623
Author(s) : Nakamura H , Asami T
Ref : Front Plant Sci , 5 :623 , 2014
Abstract : Demands for plant growth regulators (PGRs; chemicals that control plant growth) are increasing globally, especially in developing countries. Both positive and negative PGRs are widely used to enhance crop production and to suppress unwanted shoot growth, respectively. Strigolactones (SLs) are multifunctional molecules that function as phytohormones, inhibiting shoot branching and also functioning in the rhizospheric communication with symbiotic fungi and parasitic weeds. Therefore, it is anticipated that chemicals that regulate the functions of SLs will be widely used in agricultural applications. Although the SL biosynthetic pathway is not fully understood, it has been demonstrated that beta-carotene isomerases, carotenoid cleavage dioxygenases (CCDs), and a cytochrome P450 monooxygenase are involved in strigolactone biosynthesis. A CCD inhibitor, abamine, which is also an inhibitor of abscisic acid biosynthesis, reduces the levels of SL in several plant species and reduces the germination rate of Orobanche minor seeds grown with tobacco. On the basis of the structure of abamine, several chemicals have been designed to specifically inhibit CCDs during SL synthesis. Cytochrome P450 monooxygenase is another target enzyme in the development of SL biosynthesis inhibitors, and the triazole-derived TIS series of chemicals is known to include SL biosynthesis inhibitors, although their target enzyme has not been identified. Recently, DWARF14 (D14) has been shown to be a receptor for SLs, and the D-ring moiety of SL is essential for its recognition by D14. A variety of SL agonists are currently under development and most agonists commonly contain the D-ring or a D-ring-like moiety. Several research groups have also resolved the crystal structure of D14 in the last two years. It is expected that this information on the D14 structure will be invaluable not only for developing SL agonists with novel structures but also in the design of inhibitors of SL receptors.
ESTHER : Nakamura_2014_Front.Plant.Sci_5_623
PubMedSearch : Nakamura_2014_Front.Plant.Sci_5_623
PubMedID: 25414720

Title : Discovery of the lomaiviticin biosynthetic gene cluster in Salinispora pacifica - Janso_2014_Tetrahedron_70_4156
Author(s) : Janso JE , Haltli BA , Eustaquio AS , Kulowski K , Waldman AJ , Zha L , Nakamura H , Bernan VS , He H , Carter GT , Koehn FE , Balskus EP
Ref : Tetrahedron , 70 :4156 , 2014
Abstract : The lomaiviticins are a family of cytotoxic marine natural products that have captured the attention of both synthetic and biological chemists due to their intricate molecular scaffolds and potent biological activities. Here we describe the identification of the gene cluster responsible for lomaiviticin biosynthesis in Salinispora pacifica strains DPJ-0016 and DPJ-0019 using a combination of molecular approaches and genome sequencing. The link between the lom gene cluster and lomaiviticin production was confirmed using bacterial genetics, and subsequent analysis and annotation of this cluster revealed the biosynthetic basis for the core polyketide scaffold. Additionally, we have used comparative genomics to identify candidate enzymes for several unusual tailoring events, including diazo formation and oxidative dimerization. These findings will allow further elucidation of the biosynthetic logic of lomaiviticin assembly and provide useful molecular tools for application in biocatalysis and synthetic biology.
ESTHER : Janso_2014_Tetrahedron_70_4156
PubMedSearch : Janso_2014_Tetrahedron_70_4156
PubMedID: 25045187
Gene_locus related to this paper: 9actn-a0a059uc17

Title : Myasthenia gravis: Predictive factors associated with the synchronized elevation of anti-acetylcholine receptor antibody titer in Kanazawa, Japan - Iwasa_2014_J.Neuroimmunol_267_97
Author(s) : Iwasa K , Yoshikawa H , Samuraki M , Shinohara M , Hamaguchi T , Ono K , Nakamura H , Yamada M
Ref : Journal of Neuroimmunology , 267 :97 , 2014
Abstract : For a brief period, an increased incidence of elevated anti-acetylcholine receptor antibody titer was observed in patients with myasthenia gravis (MG) in Kanazawa, Japan. The purpose of this study was to examine the predictive factors associated with this antibody titer elevation. Decreased odds of titer elevation were seen in patients with early-onset MG than in those with late-onset MG. In patients with non-thymoma-related MG, thymectomy prevented the antibody titer elevation. Our data suggest that late-onset MG may have a different immunogenic response and the thymus might play an immunoregulatory role against extrinsic factors in some types of MG.
ESTHER : Iwasa_2014_J.Neuroimmunol_267_97
PubMedSearch : Iwasa_2014_J.Neuroimmunol_267_97
PubMedID: 24388223

Title : An Increased Ratio of Glycated Albumin to HbA1c Is Associated with the Degree of Liver Fibrosis in Hepatitis B Virus-Positive Patients - Enomoto_2014_Gastroenterol.Res.Pract_2014_351396
Author(s) : Enomoto H , Aizawa N , Nakamura H , Sakai Y , Iwata Y , Tanaka H , Ikeda N , Aoki T , Yuri Y , Yoh K , Hashimoto K , Ishii A , Takashima T , Iwata K , Saito M , Imanishi H , Iijima H , Nishiguchi S
Ref : Gastroenterol Res Pract , 2014 :351396 , 2014
Abstract : Background. In hepatitis B virus- (HBV-) positive patients, the relationship between the metabolic variables and histological degree of liver fibrosis has been poorly investigated. Methods. A total of 176 HBV-positive patients were assessed in whom the ratios of glycated albumin-to-glycated hemoglobin (GA/HbA1c) were calculated in order to investigate the relationship with the degree of liver fibrosis. Results. The GA/HbA1c ratio increased in association with the severity of fibrosis (METAVIR scores: F0-1: 2.61 +/- 0.24, F2: 2.65 +/- 0.24, F3: 2.74 +/- 0.38, and F4: 2.91 +/- 0.63). The GA/HbA1c ratios were inversely correlated with four variables of liver function: the prothrombin time (PT) percentage (P < 0.0001), platelet count (P < 0.0001), albumin value (P < 0.0001), and cholinesterase value (P < 0.0001). The GA/HbA1c ratio was positively correlated with two well-known markers of liver fibrosis, FIB-4 (P < 0.0001) and the AST-to-platelet ratio index (APRI) (P < 0.0001). Furthermore, the GA/HbA1c showed better correlations with two variables of liver function (PT percentage and cholinesterase value) than did FIB-4 and with all four variables than did the APRI. Conclusion. The GA/HbA1c ratio is associated with the degree of liver fibrosis in HBV-positive patients.
ESTHER : Enomoto_2014_Gastroenterol.Res.Pract_2014_351396
PubMedSearch : Enomoto_2014_Gastroenterol.Res.Pract_2014_351396
PubMedID: 24693282

Title : Molecular mechanism of strigolactone perception by DWARF14 - Nakamura_2013_Nat.Commun_4_2613
Author(s) : Nakamura H , Xue YL , Miyakawa T , Hou F , Qin HM , Fukui K , Shi X , Ito E , Ito S , Park SH , Miyauchi Y , Asano A , Totsuka N , Ueda T , Tanokura M , Asami T
Ref : Nat Commun , 4 :2613 , 2013
Abstract : Strigolactones (SLs) are phytohormones that inhibit shoot branching and function in the rhizospheric communication with symbiotic fungi and parasitic weeds. An alpha/beta-hydrolase protein, DWARF14 (D14), has been recognized to be an essential component of plant SL signalling, although its precise function remains unknown. Here we present the SL-dependent interaction of D14 with a gibberellin signalling repressor SLR1 and a possible mechanism of phytohormone perception in D14-mediated SL signalling. D14 functions as a cleavage enzyme of SLs, and the cleavage reaction induces the interaction with SLR1. The crystal structure of D14 shows that 5-hydroxy-3-methylbutenolide (D-OH), which is a reaction product of SLs, is trapped in the catalytic cavity of D14 to form an altered surface. The D14 residues recognizing D-OH are critical for the SL-dependent D14-SLR1 interaction. These results provide new insight into crosstalk between gibberellin and SL signalling pathways.
ESTHER : Nakamura_2013_Nat.Commun_4_2613
PubMedSearch : Nakamura_2013_Nat.Commun_4_2613
PubMedID: 24131983
Gene_locus related to this paper: orysj-Q10QA5

Title : Prevalent LIPH founder mutations lead to loss of P2Y5 activation ability of PA-PLA1alpha in autosomal recessive hypotrichosis - Shinkuma_2010_Hum.Mutat_31_602
Author(s) : Shinkuma S , Akiyama M , Inoue A , Aoki J , Natsuga K , Nomura T , Arita K , Abe R , Ito K , Nakamura H , Ujiie H , Shibaki A , Suga H , Tsunemi Y , Nishie W , Shimizu H
Ref : Hum Mutat , 31 :602 , 2010
Abstract : Autosomal recessive hypotrichosis (ARH) is characterized by sparse hair on the scalp without other abnormalities. Three genes, DSG4, LIPH, and LPAR6 (P2RY5), have been reported to underlie ARH. We performed a mutation search for the three candidate genes in five independent Japanese ARH families and identified two LIPH mutations: c.736T>A (p.Cys246Ser) in all five families, and c.742C>A (p.His248Asn) in four of the five families. Out of 200 unrelated control alleles, we detected c.736T>A in three alleles and c.742C>A in one allele. Haplotype analysis revealed each of the two mutant alleles is derived from a respective founder. These results suggest the LIPH mutations are prevalent founder mutations for ARH in the Japanese population. LIPH encodes PA-PLA(1)alpha (LIPH), a membrane-associated phosphatidic acid-preferring phospholipase A(1)alpha. Two residues, altered by these mutations, are conserved among PA-PLA(1)alpha of diverse species. Cys(246) forms intramolecular disulfide bonds on the lid domain, a crucial structure for substrate recognition, and His(248) is one amino acid of the catalytic triad. Both p.Cys246Ser- and p.His248Asn-PA-PLA(1)alpha mutants showed complete abolition of hydrolytic activity and had no P2Y5 activation ability. These results suggest defective activation of P2Y5 due to reduced 2-acyl lysophosphatidic acid production by the mutant PA-PLA(1)alpha is involved in the pathogenesis of ARH.
ESTHER : Shinkuma_2010_Hum.Mutat_31_602
PubMedSearch : Shinkuma_2010_Hum.Mutat_31_602
PubMedID: 20213768
Gene_locus related to this paper: human-LIPH

Title : Technetium-99m-GSA clearance in mice under long-term dietary restriction - Kouda_2009_Ann.Nucl.Med_23_123
Author(s) : Kouda K , Kohno H , Nakamura H , Ha-Kawa SK , Sonoda Y , Iki M
Ref : Ann Nucl Med , 23 :123 , 2009
Abstract : OBJECTIVE: Dietary restriction (DR) without malnutrition is widely acknowledged to prolong lifespan in laboratory animals. Evidence suggests that DR retards age-related decline in protein turnover of most organs. However, there has been no report about hepatic serum glycoprotein catabolism under DR. In the current study, we evaluate the hepatic uptake of asialoglycoprotein in ICR mice with DR by measuring the plasma clearance of technetium-99m galactosyl human serum albumin (Tc-GSA). METHODS: The amount of food supplied to the restricted mice was 70% of that consumed by the mice fed ad libitum (AL). The regimen was initiated at the age of 7 weeks and terminated after the age of 44 weeks. The plasma clearance of Tc-GSA was measured at the age of 7 weeks, 14 weeks, 28 weeks, and 42 weeks. RESULTS: The restricted animals showed a marked decrease in their body and liver weight, and hepatic uptake of Tc-GSA per liver weight in the restricted mice was greater than that in the mice fed AL. On the other hand, the Tc-GSA plasma clearance in the mice fed AL was stable during the study period, and that in the restricted mice showed no change with age either, and those in the two groups were similar. In addition to the receptor function, there was no difference in the expression of mRNAs of the asialoglycoprotein receptor between the two groups. Serum concentrations of cholinesterase and hepatic mRNAs of glutamine synthetase in the restricted mice were higher than those in the mice fed AL. Serum levels of amino acids in the restricted mice were lower than those in the mice fed AL. CONCLUSIONS: The data presented here show that the DR did not affect the capacity of hepatic serum glycoprotein catabolism, whereas several protein metabolic pathways were affected.
ESTHER : Kouda_2009_Ann.Nucl.Med_23_123
PubMedSearch : Kouda_2009_Ann.Nucl.Med_23_123
PubMedID: 19225934

Title : [Clinical study of porous gelatin sphere (YM 670) in transcatheter arterial embolization] - Yamada_2005_Gan.To.Kagaku.Ryoho_32_1431
Author(s) : Yamada R , Sawada S , Uchida H , Kumazaki T , Hiramatsu K , Ishii H , Nakao N , Nakamura H , Taguchi T
Ref : Japanese Journal of Cancer & Chemotherapy , 32 :1431 , 2005
Abstract : A clinical study on the use of porous gelatin particles(sterile gelatin embolization material, YM 670, Gelpart) in transcatheter arterial embolization (TAE) was performed in patients with hepatocellular carcinoma, and the efficacy (embolization,anti-tumor effect, recanalization and operationality) and safety (tolerability) were studied. An additive agent comprising porous gelatin particles and low osmolarity contrast media was administered peripherally through a catheter into the hepatic artery proper of 63 patients with hepatocellular carcinoma. Good hepatic arterial embolization was confirmed in all cases (embolization: 100%), and a tumor necrosis effect was obtained in most cases (35/62 patients, 56.5%). Moreover, operationality was assessed as "highly easy to use" or "easy to use" in all cases. Frequencies of adverse events in which a relationship to TAE was not excluded and abnormalities of clinical laboratory data were high at 71.4% and 9 8.4%, respectively. The most common adverse reactions were pyrexia, abdominal pain, queasiness and blood pressure increase;abnormalities in clinical laboratory data included hepatic function with increased AST (GOT), increased ALT (GPT), decreased cholinesterase, increased LDH and increased total bilirubin. These adverse reactions and abnormalities in clinical laboratory data, however, were transient and attributed to the TAE procedure itself, and no adverse reactions related to YM 670 as an embolic material were observed. In addition, with regard to tolerability (safety), the treatment was assessed as suitable for use in all the present cases.
ESTHER : Yamada_2005_Gan.To.Kagaku.Ryoho_32_1431
PubMedSearch : Yamada_2005_Gan.To.Kagaku.Ryoho_32_1431
PubMedID: 16227743

Title : In vitro evolution of a polyhydroxybutyrate synthase by intragenic suppression-type mutagenesis - Taguchi_2002_J.Biochem_131_801
Author(s) : Taguchi S , Nakamura H , Hiraishi T , Yamato I , Doi Y
Ref : J Biochem , 131 :801 , 2002
Abstract : In vitro evolution was applied to obtain highly active mutants of Ralstonia eutropha polyester synthase (PhbC(Re)), which is a key enzyme catalyzing the formation of polyhydroxybutyrate (PHB) from (R)-3-hydroxybutyryl-CoA (3HB-CoA). To search for beneficial mutations for activity improvement of this enzyme, we have conducted multi-step mutations, including activity loss and intragenic suppression-type activity reversion. Among 259 revertants, triple mutant E11S12 was obtained as the most active one via PCR-mediated secondary mutagenesis from mutant E11 with a single mutation (Ser to Pro at position 80), which exhibited reduced activity (as low as 27% of the wild-type level) but higher thermostability compared to the wild-type enzyme. Mutant E11S12 exhibited up to 79% of the wild-type enzyme activity. Mutation separation of E11S12 revealed that the replacement of Phe by Ser at position 420 (F420S), located in a highly conserved alpha/beta hydrolase fold region, of the E11S12 mutant contributes to the improvement of the enzyme activity. A purified sample of the genetically engineered mutant, termed E11S12-1, with the F420S mutation alone was found to exhibit a 2.4-fold increase in specific activity toward 3HB-CoA, compared to the wild-type.
ESTHER : Taguchi_2002_J.Biochem_131_801
PubMedSearch : Taguchi_2002_J.Biochem_131_801
PubMedID: 12038975
Gene_locus related to this paper: ralso-PHBC

Title : Analysis of mutational effects of a polyhydroxybutyrate (PHB) polymerase on bacterial PHB accumulation using an in vivo assay system - Taguchi_2001_FEMS.Microbiol.Lett_198_65
Author(s) : Taguchi S , Maehara A , Takase K , Nakahara M , Nakamura H , Doi Y
Ref : FEMS Microbiology Letters , 198 :65 , 2001
Abstract : Polymerase is a central enzyme involved in the biosynthesis of polyhydroxybutyrate (PHB), a well-known bacterial biodegradable polyester. In this study, we have established an in vivo assay system to analyze mutational effects of Ralstonia eutropha polymerase (termed PhbC(Re)) on the level of PHB accumulation in recombinant strains of Escherichia coli. This in vitro evolution system consists of a polymerase chain reaction-mediated random mutagenesis and two assay procedures, a plate assay using a PHB-staining dye and a high-pressure liquid chromatographic assay based on the converting reaction from PHB to crotonic acid. The distribution pattern of the PHB accumulation level of the mutant population using 378 clones arbitrarily selected, suggested that the present level of PhbC(Re) is high and well-optimized. It is noteworthy that many of the amino acid substitutions affecting the PHB accumulation occurred in the conserved positions or regions within an 'alpha/beta hydrolase fold' which is commonly found among hydrolytic enzymes. From a good correlation with the level of PHB accumulation, an activity estimation of the PhbC(Re) would be efficiently achieved by monitoring the level of PHB accumulation using the in vivo assay system established here.
ESTHER : Taguchi_2001_FEMS.Microbiol.Lett_198_65
PubMedSearch : Taguchi_2001_FEMS.Microbiol.Lett_198_65
PubMedID: 11325555

Title : Improvement of enantioselectivity of chiral organophosphate insecticide hydrolysis by bacterial phosphotriesterase - Tsugawa_2000_Appl.Biochem.Biotechnol_84-86_311
Author(s) : Tsugawa W , Nakamura H , Sode K , Ohuchi S
Ref : Appl Biochem Biotechnol , 84-86 :311 , 2000
Abstract : The bacterial phosphotriesterase (PTE) isolated from Flavobacterium sp. can catalyze the cleavage of the P-O bond in a variety of organophosphate triesters and has been shown to be an effective catalyst for the degradation of toxic organophosphate esters. Ethyl 4-nitrophenyl phenylphosphonothioate (EPN) is a chiral organophosphate. Optical isomers of EPN show differences in their toxicity. R-EPN is known to be more toxic to hens and houseflies than S-EPN. We determined the Ki value of each enantiomer toward electric eel acetylcholinesterase. R-EPN (Ki = 6 microM) inhibited acetylcholinesterase much more effectively than S-EPN (Ki = 52 microM) did in vitro. Since PTE has been found to hydrolyze only the S-isomer of EPN, we attempted to alter the enantioselectivity of PTE in order to degrade toxic EPN enantiomer effectively. When PTE hydrolyzed EPN in the presence of dimethyl sulfoxide (DMSO), enzymatic activity toward S-EPN decreased linearly, but enzymatic activity toward R-EPN increased as a function of DMSO concentration. At 20% DMSO, the maximum activity was observed. The kinetic parameters of PTE to EPN isomers clearly indicated that in the presence of 20% DMSO, the enantioselectivity of PTE changed. The Km value for R-EPN decreased from 0.24 to 0.03 mM, and the Vmax value increased from 0.25 to 0.60 U/mg of protein. Vmax/Km values indicated that PTE preferred R-EPN over S-EPN in the presence of DMSO by a factor of 2.
ESTHER : Tsugawa_2000_Appl.Biochem.Biotechnol_84-86_311
PubMedSearch : Tsugawa_2000_Appl.Biochem.Biotechnol_84-86_311
PubMedID: 10849798

Title : Platelet-activating factor acetylhydrolase gene mutation in Japanese children with Escherichia coli O157-associated hemolytic uremic syndrome - Xu_2000_Am.J.Kidney.Dis_36_42
Author(s) : Xu H , Iijima K , Shirakawa T , Shiozawa S , Miwa M , Yamaoka K , Kawamura N , Nakamura H , Yoshikawa N
Ref : Am J Kidney Dis , 36 :42 , 2000
Abstract : Platelet-activating factor (PAF) may be involved in the pathogenesis of Escherichia coli O157-associated hemolytic uremic syndrome (HUS). PAF is degraded to inactive products by PAF acetylhydrolase. In this study, we investigated whether a PAF acetylhydrolase gene mutation (G-->T transversion at position 994) is involved in HUS in Japanese children. A point mutation in the PAF acetylhydrolase gene (G994T) was identified using polymerase chain reaction in 50 Japanese children with E coli O157-associated HUS and 100 healthy Japanese. We then determined the relationship between the PAF acetylhydrolase G994T gene mutation and clinical features of HUS. There was no difference in genotype and allele frequencies between patients with HUS and healthy controls. The mean duration of oligoanuria was significantly longer in patients with the GT genotype than in those with the GG genotype (P = 0.012). Although 11 of 15 patients (73%) heterozygous for the mutant allele (GT) required dialysis, only 13 of the 35 wild-type homozygotes (GG; 37%) required dialysis (P = 0. 030). Mean plasma PAF acetylhydrolase activity was significantly less in patients with the GT genotype than in those with the GG genotype (P < 0.0001). In conclusion, we have shown an association between the G994T PAF acetylhydrolase gene mutation and the severity of renal damage in E coli O157-associated HUS. Our study suggests that analysis of the PAF acetylhydrolase gene mutation in Japanese children with E coli O157-associated HUS may allow the prediction of the severity of HUS.
ESTHER : Xu_2000_Am.J.Kidney.Dis_36_42
PubMedSearch : Xu_2000_Am.J.Kidney.Dis_36_42
PubMedID: 10873870
Gene_locus related to this paper: human-PLA2G7

Title : Current status of liver function tests in Japan - Tatsumi_1999_Southeast.Asian.J.Trop.Med.Public.Health_30 Suppl 3_99
Author(s) : Tatsumi N , Hino M , Nakamura H , Tsuda I , Kondo H
Ref : Southeast Asian J Trop Med Public Health , 30 Suppl 3 :99 , 1999
Abstract : Inter-laboratory variations in data obtained from surveillance in Japan were studied. The items evaluated were related to liver function and were as follows: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (gamma-GT), cholinesterase (CHE), lactate dehydrogenase (LD), alkaline phosphatase (ALP) and hepatitis markers. Inter-laboratory coefficients of variations for bilirubin, AST and ALT were acceptable, being less than 10%. but higher variations were found for thle other enzyme assays. Detection of hepatitis markers was acceptable. However. even for parameters with lower inter-laboratory variation, differences in obtained values among different reagents or methods still existed. Thus, standardization will be needed for laboratory data in Japan, and this will contribute to international standardization in laboratory medicine in the future.
ESTHER : Tatsumi_1999_Southeast.Asian.J.Trop.Med.Public.Health_30 Suppl 3_99
PubMedSearch : Tatsumi_1999_Southeast.Asian.J.Trop.Med.Public.Health_30 Suppl 3_99
PubMedID: 10926268

Title : Role of platelet-activating factor acetylhydrolase gene mutation in Japanese childhood IgA nephropathy - Tanaka_1999_Am.J.Kidney.Dis_34_289
Author(s) : Tanaka R , Iijima K , Xu H , Inoue Y , Murakami R , Shirakawa T , Nishiyama K , Miwa M , Shiozawa S , Nakamura H , Yoshikawa N
Ref : Am J Kidney Dis , 34 :289 , 1999
Abstract : Platelet-activating factor (PAF) is a potent mediator of inflammatory injury in renal diseases. PAF is degraded to inactive products by PAF acetylhydrolase. Recently, a point mutation (G to T transversion) of the PAF acetylhydrolase gene was observed at position 994, and this mutation was found to contribute to the variability in plasma PAF levels, with undetectable plasma PAF acetylhydrolase activity occurring in homozygous patients (TT genotype) and reduced levels of activity in heterozygous patients (GT genotype). Therefore, we investigated the effect of the PAF acetylhydrolase gene mutation on the pathogenesis and progression of immunoglobulin A (IgA) nephropathy. Genomic DNA was obtained from 89 children with IgA nephropathy and 100 controls. We identified the PAF acetylhydrolase gene mutation (G994T) by polymerase chain reaction. There was no significant difference in genotypic frequency between patients and controls. However, urinary protein excretion at the time of biopsy was significantly greater in patients with the GT/TT genotypes than in those with the GG genotype. The percentage of glomeruli with mesangial cell proliferation was significantly greater in patients with the GT/TT genotypes than in those with the GG genotype. These results indicate the PAF acetylhydrolase gene mutation may influence the degree of proteinuria and the extent of mesangial proliferation in the early stage of childhood IgA nephropathy.
ESTHER : Tanaka_1999_Am.J.Kidney.Dis_34_289
PubMedSearch : Tanaka_1999_Am.J.Kidney.Dis_34_289
PubMedID: 10430976
Gene_locus related to this paper: human-PLA2G7

Title : [Evaluation of transcatheter hepatic segmental or subsegmental infusion of SMANCS for treatment of hepatocellular carcinoma] - Inoue_1998_Gan.To.Kagaku.Ryoho_1_56
Author(s) : Inoue Y , Tomoda K , Oi H , Nakamura H
Ref : Japanese Journal of Cancer & Chemotherapy , 1 :56 , 1998
Abstract : A total of seventeen patients with hepatocellular carcinoma (HCC), nineteen HCCs, who underwent as an initial treatment transcatheter hepatic segmental or subsegmental arterial administration of SMANCS alone for hepatocellular carcinoma (HCC), were studied to evaluate the efficacy and complication of that treatment. The initial treatments provided CR in eight patients (47%), and repeat administrations of SMANCS achieved CR in an additional four patients (24%). The initial treatment provided a dense deposit of Lipiodol in the twelve tumors (63%), in five of which Lipiodol was thereafter washed out in some portions of the tumor. Complete necrosis was obtained in nine (75%) of fourteen hypervascular tumors, and in two (40%) of five intermediately vascular or hypovascular tumors. Segmental or subsegmental administration of SMANCS was well tolerated with self-controlled abdominal pain or fever well responding to medication. Ascites was seen in three cases, and atrophy of the segment infused occurred in five patients. Cholinesterase significantly reduced at one week and one month, then recovered to baseline two to three months after initial treatment. The cumulative survival rates were 77% at 1 year, 66% at 2 years, and 53% at 5 years in the whole patients. The survival rate was 100% at 5 years in the Child A group. In the patients who obtained CR using SMANCS alone, the survival rates were 89% at 1 year, 74% at 2 years and 56% at 5 years. Although this method may transiently deteriorate hepatic function, segmental or subsegmental administration of SMANCS may be an excellent therapeutic method for treatment of HCC and promising for use in properly selected patients.
ESTHER : Inoue_1998_Gan.To.Kagaku.Ryoho_1_56
PubMedSearch : Inoue_1998_Gan.To.Kagaku.Ryoho_1_56
PubMedID: 9512689

Title : Platelet-activating factor acetylhydrolase gene mutation in Japanese nephrotic children - Xu_1998_Kidney.Int_54_1867
Author(s) : Xu H , Iijima K , Shiozawa S , Tanaka SS , Inoue Y , Shirakawa T , Nishiyama K , Miwa M , Nakamura H , Yoshikawa N
Ref : Kidney Int , 54 :1867 , 1998
Abstract : BACKGROUND: Platelet-activating factor (PAF) may be involved in the pathogenesis of steroid-responsive nephrotic syndrome (SRNS). PAF is degraded to inactive products by PAF acetylhydrolase. We have investigated whether PAF acetylhydrolase gene mutation is involved in SRNS in Japanese children.
METHODS: We identified a point mutation in the PAF acetylhydrolase gene (G994T) using the polymerase chain reaction in 101 Japanese children with SRNS and 100 healthy Japanese.
RESULTS: There was no difference in the genotype and allele frequencies between patients with SRNS and normal controls. The mean number of relapses during the first year after onset was significantly higher in the 26 patients who were heterozygous for the mutant allele (GT) than in 75 wild-type homozygotes (GG) (2.61 +/- 1.98 vs. 1.33 +/- 1.35; P = 0.0019).
CONCLUSIONS: We conclude that analysis of the PAF acetylhydrolase gene mutation at position 994 in Japanese children with SRNS allows the identification of patients who are more likely to have a disease relapse.
ESTHER : Xu_1998_Kidney.Int_54_1867
PubMedSearch : Xu_1998_Kidney.Int_54_1867
PubMedID: 9853251
Gene_locus related to this paper: human-PLA2G7

Title : Valilactone, an inhibitor of esterase, produced by actinomycetes -
Author(s) : Kitahara M , Asano M , Naganawa H , Maeda K , Hamada M , Aoyagi T , Umezawa H , Iitaka Y , Nakamura H
Ref : J Antibiot (Tokyo) , 40 :1647 , 1987
PubMedID: 3693135

Title : Luteolin-7-glucosid-sesquihydrat. -
Author(s) : Nakamura H , Ohta T , Hukuti G
Ref : J. Pharm. Soc. Japan , 56 :107 , 1936