Abstract
Analysis of animal models is indispensable to elucidate the molecular mechanism in vascular calcification (VC) as well as to develop new therapies for VC. Various gene-modified mice that show VC have been reported, and considerable progress has been made through the analyses of these animals. Mice o...
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PMID: 21037386
PDF is available here.
Abstract
Autotaxin (ATX) is a catalytic protein, which possesses lysophospholipase D activity, and thus involved in cellular membrane lipid metabolism and remodeling. Primarily, ATX was thought as a culprit protein for cancer, which potently stimulates cancer cell proliferation and tumor cell motility, augme...
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PMID: 20888793
PDF is available here.
Abstract
We have devised a method for the purification of human basophils from umbilical cord blood by FCM. Umbilical cord blood was collected from six healthy, full-term deliveries. After separation of red blood cells, mononuclear cells were isolated by Ficoll-Hypaque. Six samples followed by positive selec...
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PMID: 20715997
PDF is available here.
Abstract
We recently reported that 2,4-thiazolidinediones inhibit ATX activity in the micromolar range. Interestingly, inhibitory potency was dramatically increased by introduction of a boronic acid moiety, designed to target the active site threonine in ATX. Here we report on the discovery and further optim...
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PMID: 20536182
PDF is available here.
Abstract
We investigated intraspecific differences of volatile emissions induced from rosette leaves of 27 accessions of Arabidopsis (Arabidopsis thaliana) upon treatment with coronalon, a jasmonate mimic eliciting responses similar to those caused by insect feeding. Quantitative variation was found for the...
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PMID: 20463089
PDF is available here.
James Gierse,
Atli Thorarensen,
Konstantine Beltey,
Erica Bradshaw-Pierce,
Luz Cortes-Burgos,
Troii Hall,
Amy Johnston,
Michael Murphy,
Olga Nemirovskiy,
Shinji Ogawa,
Lyle Pegg,
Matthew Pelc,
Michael Prinsen,
Mark Schnute,
Jay Wendling,
Steve Wene,
Robin Weinberg,
Arthur Wittwer,
Ben Zweifel and
Jaime Masferrer
Abstract
We report the development of a potent autotaxin inhibitor, PF-8380 [6-(3-(piperazin-1-yl)propanoyl)benzo[d]oxazol-2(3H)-one] with an IC(50) of 2.8 nM in isolated enzyme assay and 101 nM in human whole blood. PF-8380 has adequate oral bioavailability and exposures required for in vivo testing of auto...
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PMID: 20392816
PDF is available here.
Abstract
We show that SaPI derepression is effected by a specific, non-essential phage protein that binds to Stl, disrupting the Stl-DNA complex and thereby initiating the excision-replication-packaging cycle of the island. Because SaPIs require phage proteins to be packaged, this strategy assures that SaPIs...
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PMID: 20473284
PDF is available here.
Abstract
Drug discovery from plants plays an important role in the pharmaceutical therapy field and the alkaloids lycorine and candimine are candidates for this purpose. Trichomonas vaginalis is a parasite that infects the human urogenital tract and causes trichomonosis, the most prevalent non-viral sexually...
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PMID: 20176129
PDF is available here.
Abstract
We will discuss some of the principles for substrate specificity of enzymes in human nucleotide metabolism illustrated by a selected set of enzyme families where a detailed understanding of the structural determinants for specificity is now emerging.
2010. Published by Elsevier Inc....
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PMID: 20494131
PDF is available here.
Abstract
The SOS screen, as originally described by Perkins et al. (1999) [7], was setup with the aim of identifying Arabidopsis functions that might potentially be involved in the DNA metabolism. Such functions, when expressed in bacteria, are prone to disturb replication and thus trigger the SOS response....
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PMID: 20227352
PDF is available here.
Abstract
These results indicate that all three of the human MTH1, MTH2, and NUDT5 proteins act as a defense against the mutagenesis induced by oxidized dGTP.
(c) 2010 Elsevier Inc. All rights reserved....
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PMID: 20144704
PDF is available here.
Abstract
Autotaxin (ATX) is an autocrine motility-stimulating factor and an extracellular enzyme that catalyzes the hydrolysis of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA). Although ATX can also hydrolyze sphingosylphosphorylcholine (SPC) to sphingosine-1-phosphate (S1P), the major source...
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PMID: 20419597
PDF is available here.
Abstract
We investigated the physiological role of Arabidopsis (Arabidopsis thaliana) AtNUDX6, the gene encoding ADP-ribose (Rib)/NADH pyrophosphohydrolase, using its overexpressor (Pro35S:AtNUDX6) or disruptant (KO-nudx6). The level of NADH in Pro35S:AtNUDX6 and KO-nudx6 plants was decreased and increased,...
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PMID: 20181750
PDF is available here.
Abstract
We previously reported that vascular endothelial growth factor (VEGF)-dependent activation of phospholipase Cgamma1 (PLCgamma) regulated tube stability by competing with phosphoinositide 3-kinase (PI3K) for their common substrate. Here we describe an additional mechanism by which PLCgamma promoted r...
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PMID: 20231358
PDF is available here.
Abstract
We still fail to achieve these end points in a large number of our patients. There are many reasons why patients fail to respond or develop toxicity when exposed to drugs used for inflammatory bowel disease, but genetic variation is likely to account for a significant proportion of this. Some exampl...
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PMID: 20235796
PDF is available here.
Abstract
We performed serial analysis of gene expression (SAGE) in HCC, normal liver and cirrhotic liver tissues.
Gene expression profiles of HCC tissues and non-cancerous liver tissues were obtained by SAGE. Suppression of the target gene by RNA interference was used to evaluate its role in...
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PMID: 19968781
PDF is available here.
Abstract
Clear cell adenocarcinoma shows little response to standard therapy. The results of this study suggested that the transcription factor POU6F1 could be a new molecular target for treatment of this cancer....
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PMID: 20134265
PDF is available here.
Abstract
We investigated whether TPMT/ITPA genotypes predicted long-term clinical response in Korean patients with inflammatory bowel diseases (IBDs) undergoing thiopurine treatment. A total of 204 patients with IBD in whom thiopurine treatment was indicated were enrolled and categorized by TPMT and ITPA gen...
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PMID: 19960028
PDF is available here.
Abstract
We report two brothers born to unrelated parents. The elder developed uncomplicated PXE in adolescence and harbored mutations in the ABCC6 gene. The younger child died of a condition strikingly reminiscent of GACI at 15 months of age. This case of GACI was independent of mutations in the ENPP1 gene...
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PMID: 20034067
PDF is available here.
Abstract
We found that lysophosphatidic acid receptor (LPA1) signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination.
In the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG) down-regulati...
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PMID: 21062487
PDF is available here.
Abstract
Our results open new avenues for research into the physiological roles of this family of enzymes and their possible therapeutic potential in bladder cancer.
Copyright (c) 2010 Elsevier Inc. All rights reserved....
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PMID: 19372055
PDF is available here.
Abstract
Adrenaline is known to inhibit the immunological activation of human basophils. The same effect can be obtained with ultra-low doses of histamine.
The present investigation was undertaken to verify the effects of ultra-low doses of adrenaline on the immunological activation of human basophils. For t...
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PMID: 20581771
PDF is available here.
Abstract
This report highlights for the first time the clinical and biological evidence for the involvement of ATX in human HCC. Our observation that links the TNF-alpha/NF-kappaB axis and the ATX-LPA signaling pathway suggests that ATX is likely playing an important role in inflammation related liver tumori...
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PMID: 20356387
PDF is available here.
Jae Hak Kim,
Jae Hee Cheon,
Seong Soo Hong,
Chang Soo Eun,
Jeong-Sik Byeon,
Sung Yi Hong,
Bo-Young Kim,
Soon-Ho Kwon,
Seung Won Kim,
Dong Soo Han,
Suk-Kyun Yang and
Won Ho Kim
Abstract
We retrospectively analyzed 286 Korean patients with IBD who had been treated with AZA/6-MP for at least 6 months between June 1996 and September 2006. Common TPMT mutations, including TPMT*1, *2, *3A, *3B, and *3C, and ITPA mutations, including 94C>A and IVS2+21A>C, were determined using a high-per...
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PMID: 20308917
PDF is available here.
Teruya Nakamura,
Sachiko Meshitsuka,
Seiju Kitagawa,
Nanase Abe,
Junichi Yamada,
Tetsuya Ishino,
Hiroaki Nakano,
Teruhisa Tsuzuki,
Takefumi Doi,
Yuji Kobayashi,
Satoshi Fujii,
Mutsuo Sekiguchi and
Yuriko Yamagata
Abstract
These results indicate that MutT specifically recognizes 8-oxoguanine nucleotides by the ligand-induced conformational change....
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PMID: 19864691
PDF is available here.
Abstract
We discuss the role of relatively infrequent polymorphisms of genes that regulate insulin signaling (including the K121Q polymorphism of ENPP1, the G972R polymorphism of IRS1 and the Q84R polymorphism of TRIB3) in T2DM and other conditions related to insulin resistance. The biological relevance of t...
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PMID: 19924153
PDF is available here.
Abstract
We characterized H+-PPase present in the plasma membrane of L. donovani and investigated its possible role in the survival of promastigote and amastigote. PPase activity was stimulated by K+ and sodium orthovanadate and inhibited by pyrophosphate analogs (imidodiphosphate and alendronate), KF, N,N'-...
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PMID: 19961421
PDF is available here.
Abstract
We recently demonstrated that the ATX-LPA receptor axis plays a causal role in breast tumorigenesis and cancer-related inflammation, further validating the ATX-LPA receptor axis as a rich therapeutic target in cancer....
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PMID: 19855166
PDF is available here.
Abstract
Nudix pyrophosphatases are a well represented protein family in the Deinococcus radiodurans genome. These hydrolases, which are known to be enzymatically active towards nucleoside diphosphate derivatives, play a role in cleansing the cell pool of potentially deleterious damage products. Here, the st...
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PMID: 19923723
PDF is available here.
Abstract
Polar residues play essential roles in the functions of transmembrane helices by mediating and stabilizing their helical interactions. To investigate the structural and functional roles of the conserved polar residues in the N- and C-terminal transmembrane helices of human nucleoside triphosphate di...
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PMID: 19743837
PDF is available here.
Abstract
The study aimed for epidemiology and pathogenesis of ossification of the posterior longitudinal ligament of the cervical spine (OPLL) has been continued by The Investigation Committee of Japanese Ministry of Health, Labour and Welfare till now. As a result, the number of patients and frequency in Ja...
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PMID: 19794248
PDF is available here.
Abstract
Ossification of posterior longitudinal ligament of the spine (OPLL) is a polygenic disease caused by genetic and environmental factors. The genetic factor is composed by multiple susceptibility genes. Studies for the OPLL susceptibility genes mainly using linkage and association analyses are in prog...
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PMID: 19794254
PDF is available here.
Abstract
Diagnosis of drug allergy involves first the recognition of sometimes unusual symptoms as drug allergy and, second, the identification of the eliciting drug. This is an often difficult task, as the clinical picture and underlying pathomechanisms are heterogeneous. In clinical routine, physicians fre...
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PMID: 19563997
PDF is available here.
Abstract
We have evaluated the effect of three different antidepressants in ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP1-3) activities in cultured cells from salivary glands. Rats received imipramine (10mg/ml), fluoxetine (20mg/ml) or moclobemide (30mg/ml) by oral gavage. The drugs were administ...
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PMID: 19473651
PDF is available here.
Shuying Liu,
Makiko Umezu-Goto,
Mandi Murph,
Yiling Lu,
Wenbin Liu,
Fan Zhang,
Shuangxing Yu,
L Clifton Stephens,
Xiaojiang Cui,
George Murrow,
Kevin Coombes,
William Muller,
Mien-Chie Hung,
Charles M Perou,
Adrian V Lee,
Xianjun Fang and
Gordon B Mills
Abstract
We demonstrate that expression of ATX or each edg family LPA receptor in mammary epithelium of transgenic mice is sufficient to induce a high frequency of late-onset, estrogen receptor (ER)-positive, invasive, and metastatic mammary cancer. Thus, ATX and LPA receptors can contribute to the initiatio...
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PMID: 19477432
PDF is available here.
Abstract
Lysophosphatidic acid (LPA) is a lipid growth factor that is produced by an extracellular phospholipase, termed autotaxin (ATX), and acts via G protein-coupled receptors. In this issue of Cancer Cell, Liu et al. show that transgenic overexpression of ATX or LPA receptors leads to inv...
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PMID: 19477423
PDF is available here.
Abstract
Using this anti-NUDT9 antibody, we successfully demonstrated that NUDT9 protein was differentially expressed in endometrial glandular cells at different phases of the menstrual cycle. NUDT9 was also found to be expressed more prominently in the epithelial glandular component than in the stromal comp...
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PMID: 19574167
PDF is available here.
Abstract
Extracellular nucleotides might influence aspects of the biology of reproduction in that ATP affects smooth muscle contraction, participates in steroidogenesis and spermatogenesis, and also regulates transepithelial transport, as in oviducts. Activation of cellular nucleotide purinergic receptors is...
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PMID: 19125273
PDF is available here.
Abstract
Autotaxin (ATX), discovered in human melanoma cells, has been gaining attention because it could be involved in cancer invasion and metastasis as an autocrine motility factor. Recent evidence has indicated that ATX is a key enzyme in the synthesis of lysophosphatidic acid, a lipid mediator with a wi...
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PMID: 19522250
PDF is available here.
Abstract
We have identified and compared the expression of E-NPP family members in two different phenotypes of the mouse hepatic stellate cell line (GRX). In quiescent-like hepatic stellate cells (HSCs), E-NPP activity was significantly higher, NPP2 mRNA expression decreased and NPP3 mRNA increased. The diff...
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PMID: 19194664
PDF is available here.
Abstract
We report that lysophosphatidic acid produced by ATX promotes the secretion of matrix metalloproteinase-3 (MMP3) from the human fibrosarcoma cell line HT-1080. The c-Jun N-terminal kinases (JNKs) and c-Jun of HT-1080 cells were rapidly phosphorylated after ATX treatment. A specific JNK inhibitor als...
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PMID: 19212832
PDF is available here.
Abstract
We previously showed that fibroblast growth factor 2 (FGF2) induces PC-1 and Ank while inhibiting Tnap expression and mineralization in MC3T3E1(C4) calvarial pre-osteoblast cells. In this study, we showed similar FGF2 regulation of these genes in primary pre-osteoblast cultures. In contrast to Ank a...
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PMID: 19049325
PDF is available here.
Abstract
We demonstrate the biochemical and physiological characterization of a pyrophosphatase from Arabidopsis thaliana, called AtCoAse (locus tag At5g45940), cleaving CoA to 4'-phosphopantetheine and 3',5'-adenosine-diphosphate in the presence of Mg2+/Mn2+ ions. The CoA cleaving enzyme isa member of the N...
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PMID: 19340986
PDF is available here.
Abstract
We have performed a screen for ITP-binding proteins because ITP is a deaminated product of ATP, the most abundant nucleotide, and identified RS21-C6 protein, which bound not only ITP but also ATP. Purified, recombinant RS21-C6 hydrolyzed several canonical nucleoside triphosphates to the correspondin...
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PMID: 19220460
PDF is available here.
Abstract
We report on three siblings with GACI and striking phenotypic variability. Two siblings (including the sibling survivor) were compound heterozygotes for mutations in exon 7 (c.783C>G (p.Y261X)) and exon 8 (c. 878_879delAA (p.K293fsX5)) of the ENPP1 gene confirming the diagnosis of GACI. The sibling...
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PMID: 19206175
PDF is available here.
Abstract
We explored genes which are up-regulated by estrogen in the hippocampus using ovariectomized rat models. Microarray analysis revealed that mRNA levels of ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2), insulin like growth factor 2 (Igf2) and insulin-like growth factor binding protein 2 (...
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PMID: 18946176
PDF is available here.
Abstract
We show that the magnesium-dependent ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity of procyclic T. brucei brucei is inhibited by ferrous iron and heme. The inhibition of E-NTPDase activity by ferrous iron, but not by heme, was prevented by pre-incubation of cells with catalase...
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PMID: 19027737
PDF is available here.
Abstract
Recent polymorphism analyses of Mycobacterium tuberculosis strains have identified missense mutations unique to the W-Beijing lineage in genes belonging to the Nudix hydrolase superfamily. This study investigates the structure and function of one of these Nudix hydrolases, MutT2, and examines the ef...
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PMID: 19115962
PDF is available here.
Abstract
We have previously shown that treatment of human monocyte-derived macrophages with EBV-encoded dUTPase induces the expression of proinflammatory cytokines through the activation of NF-kappaB. However, the receptor responsible for EBV-encoded dUTPase-mediated biological effects is not known. In this...
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PMID: 19124728
PDF is available here.
Abstract
Arabidopsis thaliana AtNUDT7, a homodimeric Nudix hydrolase active on ADP-ribose and NADH, exerts negative control on the major signaling complex involved in plant defense activation and programmed cell death. The structural and functional consequences of altering several amino-acid residues of the...
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PMID: 19448856
PDF is available here.
Abstract
We present a case of suspected intrauterine diagnosis at 29 weeks of gestation in a consanguineous couple. The sonographic findings were fetal hydrops (hydrothorax, skin edema, ascites, pericardial effusion and polyhydramnion), echogenic great arteries and pathological Doppler findings. An intrauter...
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PMID: 19521093
PDF is available here.
Abstract
The highest sensitivity and specificity of CD63 were 33.3 and 79.2%, respectively, and of CD203c were 16.7 and 100%, respectively, for ASA. The highest sensitivity and specificity of CD63 were 16.7 and 91.7%, respectively, and of CD203c were 22.2 and 100%, respectively, fordiclofenac. Neither the ad...
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PMID: 19494523
PDF is available here.
Abstract
For several years the incidences of allergic diseases and anaphylactic reactions have been increasing dramatically. Classical method of allergy diagnosis - skin prick test in some situations can provoke life-threatening reactions. Detection of allergen-induced basophil activation by flow cytometry h...
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PMID: 19462349
PDF is available here.
Abstract
We previously showed that FGF2 induces PC-1 expression in preosteoblastic cells and that this induction is differentiation stage dependent. In order to more directly investigate the mechanism by which PC-1 expression is regulated, we have cloned a 2.8-kb region of the PC-1 gene promoter and construc...
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PMID: 18698132
PDF is available here.
Abstract
Thiopurines (such as azathioprine and 6-mercaptopurine) are widely used for the treatment of patients suffering from malignancies, rheumatic disease, inflammatory bowel disease and solid organ transplant rejection. These drugs are activated and eliminated by a number of enzymes in the human body. Th...
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PMID: 20045992
PDF is available here.
Abstract
Combined light- and electron microscopic analysis of immunostained hypothalamic slices revealed that NTPDase3-IR is linked to ribosomes and mitochondria, is predominantly present in excitatory axon terminals and in distinct segments of the perikaryal plasma membrane. Immunohistochemical labeling of...
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PMID: 19383175
PDF is available here.