当前位置： SCI文献检索 > BLOOD期刊下所有文献 > Hyperantithrombotic, noncytoprotective Glu149Ala-activated protein C mutant.

Hyperantithrombotic, noncytoprotective Glu149Ala-activated protein C mutant.

Abstract：

:Activated protein C (APC) reduces mortality in severe sepsis patients. APC exerts anticoagulant activities via inactivation of factors Va and VIIIa and cytoprotective activities via endothelial protein C receptor and protease-activated receptor-1. APC mutants with selectively altered and opposite activity profiles, that is, greatly reduced anticoagulant activity or greatly reduced cytoprotective activities, are compared here. Glu149Ala-APC exhibited enhanced in vitro anticoagulant and in vivo antithrombotic activity, but greatly diminished in vitro cytoprotective effects and in vivo reduction of endotoxin-induced murine mortality. Thus, residue Glu149 and the C-terminal region of APC's light chain are identified as functionally important for expression of multiple APC activities. In contrast to Glu149Ala-APC, 5A-APC (Lys191-193Ala + Arg229/230Ala) with protease domain mutations lacked in vivo antithrombotic activity, although it was potent in reducing endotoxin-induced mortality, as previously shown. These data imply that APC molecular species with potent antithrombotic activity, but without robust cytoprotective activity, are not sufficient to reduce mortality in endotoxemia, emphasizing the need for APC's cytoprotective actions, but not anticoagulant actions, to reduce endotoxin-induced mortality. Protein engineering can provide APC mutants that permit definitive mechanism of action studies for APC's multiple activities, and may also provide safer and more effective second-generation APC mutants with reduced bleeding risk.

journal_name

Blood

journal_title

Blood

authors

Mosnier LO,Zampolli A,Kerschen EJ,Schuepbach RA,Banerjee Y,Fernández JA,Yang XV,Riewald M,Weiler H,Ruggeri ZM,Griffin JH

doi

10.1182/blood-2008-10-183327

subject

Has Abstract

pub_date

2009-06-04 00:00:00

pages

5970-8

issue

23

eissn

0006-4971

issn

1528-0020

pii

blood-2008-10-183327

journal_volume

113

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes.

    abstract：:A cohort of MDS patients was examined for mutations affecting 4 splice genes (SF3B1, SRSF2, ZRSR2, and U2AF35) and evaluated in the context of clinical and molecular markers. Splice gene mutations were detected in 95 of 221 patients. These mutations were mutually exclusive and less likely to occur in patients with com...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2011-12-400994

    authors： Damm F,Kosmider O,Gelsi-Boyer V,Renneville A,Carbuccia N,Hidalgo-Curtis C,Della Valle V,Couronné L,Scourzic L,Chesnais V,Guerci-Bresler A,Slama B,Beyne-Rauzy O,Schmidt-Tanguy A,Stamatoullas-Bastard A,Dreyfus F,Prébet T,

    更新日期：2012-04-05 00:00:00

  • Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP.

    abstract：:Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caus...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Packham MA,Perry DW,Kinlough-Rathbone RL,Rand ML,Guccione MA,Evans RM,Mustard JF

    更新日期：1985-03-01 00:00:00

  • Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism?

    abstract：:Despite many studies on the pathophysiology of antiphospholipid antibodies (aPL), the mechanism by which aPL causes thrombosis has not been established. We have tried to elucidate the paradox between the prolongation of the clotting time of phospholipid-dependent coagulation tests in vitro and the occurrence of thromb...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Oosting JD,Derksen RH,Bobbink IW,Hackeng TM,Bouma BN,de Groot PG

    更新日期：1993-05-15 00:00:00

  • The tumor marker Fascin is strongly induced by the Tax oncoprotein of HTLV-1 through NF-kappaB signals.

    abstract：:Oncogenic transformation of CD4(+) T cells by human T-cell lymphotropic virus type 1 (HTLV-1) is understood as the initial step to adult T-cell leukemia/lymphoma, a process that is mainly initiated by perturbation of cellular signaling by the viral Tax oncoprotein, a potent transcriptional regulator. In search of nove...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2010-09-305805

    authors： Kress AK,Kalmer M,Rowan AG,Grassmann R,Fleckenstein B

    更新日期：2011-03-31 00:00:00

  • IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells.

    abstract：:Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against preleukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2015-01-621631

    authors： Schinke C,Giricz O,Li W,Shastri A,Gordon S,Barreyro L,Bhagat T,Bhattacharyya S,Ramachandra N,Bartenstein M,Pellagatti A,Boultwood J,Wickrema A,Yu Y,Will B,Wei S,Steidl U,Verma A

    更新日期：2015-05-14 00:00:00

  • Transcriptional and posttranscriptional modulation of human neutrophil elastase gene expression.

    abstract：:Human neutrophil elastase (NE), a 29-Kd potent serine protease stored in azurophilic granules of mature neutrophils, is coded for by the NE gene, a single copy gene with 5 exons spanning a 6-kb segment of chromosome 11 at q14. With the knowledge that the NE gene expression is limited to early myeloid cell differentiat...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Yoshimura K,Crystal RG

    更新日期：1992-05-15 00:00:00

  • A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma.

    abstract：:The serine/threonine Pim kinases are up-regulated in specific hematologic neoplasms, and play an important role in key signal transduction pathways, including those regulated by MYC, MYCN, FLT3-ITD, BCR-ABL, HOXA9, and EWS fusions. We demonstrate that SMI-4a, a novel benzylidene-thiazolidine-2, 4-dione small molecule ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2009-07-233445

    authors： Lin YW,Beharry ZM,Hill EG,Song JH,Wang W,Xia Z,Zhang Z,Aplan PD,Aster JC,Smith CD,Kraft AS

    更新日期：2010-01-28 00:00:00

  • Sickle cell acute chest syndrome: pathogenesis and rationale for treatment.

    abstract：:Acute chest syndrome (ACS) is a leading cause of death in sickle cell disease (SCD). Our previous work showed that hypoxia enhances the ability of sickle erythrocytes to adhere to human microvessel endothelium via interaction between very late activation antigen-4 (VLA4) expressed on sickle erythrocytes and the endoth...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Stuart MJ,Setty BN

    更新日期：1999-09-01 00:00:00

  • Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump.

    abstract：:Imatinib mesylate (STI571), a potent tyrosine kinase inhibitor, is successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. However, the intended chronic oral administration of imatinib may lead to development of cellular resistance and subsequent treatment failure. Indee...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2004-04-1398

    authors： Burger H,van Tol H,Boersma AW,Brok M,Wiemer EA,Stoter G,Nooter K

    更新日期：2004-11-01 00:00:00

  • In vivo stem cell function of interleukin-3-induced blast cells.

    abstract：:The treatment of mice with high doses of 5-fluorouracil (5-FU) results in an enrichment of primitive hematopoietic progenitors. Using this procedure, we obtained a new class of murine hematopoietic colonies that had very high secondary plating efficiencies in vitro and could differentiate into not only myeloid cells b...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Tsunoda J,Okada S,Suda J,Nagayoshi K,Nakauchi H,Hatake K,Miura Y,Suda T

    更新日期：1991-07-15 00:00:00

  • Direct correlation between the load of Epstein-Barr virus-infected lymphocytes in the peripheral blood of pediatric transplant patients and risk of lymphoproliferative disease.

    abstract：:The Epstein-Barr virus (EBV) is known to cause posttransplant lymphoproliferative disease (PTLD) in immunosuppressed transplant patients. The results of this pilot study showed that all EBV- patients pretransplant experienced primary EBV infection within the first 3 months after transplant surgery. Virtually all of th...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Savoie A,Perpête C,Carpentier L,Joncas J,Alfieri C

    更新日期：1994-05-01 00:00:00

  • Prion protein expression in human leukocyte differentiation.

    abstract：:The cellular isoform of the prion protein (PrPC) is a small glycoprotein attached to the outer leaflet of the plasma membrane by a glycosylphosphatidylinositol anchor. This molecule is involved in the pathogenesis of prion diseases in both humans and animals. We have characterized the expression patterns of PrPC durin...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Dodelet VC,Cashman NR

    更新日期：1998-03-01 00:00:00

  • Telomerase functions beyond telomere maintenance in primary cutaneous T-cell lymphoma.

    abstract：:Telomere erosion may be counteracted by telomerase. Here we explored telomere length (TL) and telomerase activity (TA) in primary cutaneous T-cell lymphoma (CTCL) by using quantitative polymerase chain reaction and interphase quantitative fluorescence in situ hybridization assays. Samples from patients with Sézary syn...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2013-05-500686

    authors： Chevret E,Andrique L,Prochazkova-Carlotti M,Ferrer J,Cappellen D,Laharanne E,Idrissi Y,Boettiger A,Sahraoui W,Ruiz F,Pham-Ledard A,Vergier B,Belloc F,Dubus P,Beylot-Barry M,Merlio JP

    更新日期：2014-03-20 00:00:00

  • Identification of base substitutions in the promoter regions of the A gamma- and G gamma-globin genes in A gamma- (or G gamma-) beta+-HPFH heterozygotes using the DNA-amplification-synthetic oligonucleotide procedure.

    abstract：:DNA amplification combined with hybridization with 32P-labeled synthetic oligonucleotide probes has been used to identify base substitutions in the 5' promoter region of the A gamma globin gene in members of eleven families from China, Sardinia, Canada, and the United States who had a heterozygosity for the A gamma-be...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Yang KG,Stoming TA,Fei YJ,Liang S,Wong SC,Masala B,Huang RB,Wei ZP,Huisman TH

    更新日期：1988-05-01 00:00:00

  • Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes.

    abstract：:To determine the risk factors and outcomes associated with rising cytomegalovirus (CMV) antigenemia levels during preemptive therapy among stem cell allograft recipients, 119 patients with CMV antigenemia were studied. Patients were prospectively monitored for CMV antigenemia weekly; those with positive findings on an...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood.v97.4.867

    authors： Nichols WG,Corey L,Gooley T,Drew WL,Miner R,Huang M,Davis C,Boeckh M

    更新日期：2001-02-15 00:00:00

  • Indoles derived from intestinal microbiota act via type I interferon signaling to limit graft-versus-host disease.

    abstract：:The intestinal microbiota in allogeneic bone marrow transplant (allo-BMT) recipients modulates graft-versus-host disease (GVHD), a systemic inflammatory state initiated by donor T cells that leads to colitis, a key determinant of GVHD severity. Indole or indole derivatives produced by tryptophan metabolism in the inte...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2018-03-838193

    authors： Swimm A,Giver CR,DeFilipp Z,Rangaraju S,Sharma A,Ulezko Antonova A,Sonowal R,Capaldo C,Powell D,Qayed M,Kalman D,Waller EK

    更新日期：2018-12-06 00:00:00

  • Infants with acute lymphoblastic leukemia and a germline MLL gene are highly curable with use of chemotherapy alone: results from the Japan Infant Leukemia Study Group.

    abstract：:Although infants with acute lymphoblastic leukemia (ALL) and a germline MLL gene have a better prognosis than comparable infants with a rearranged MLL gene, their optimal therapy is controversial. In 2 consecutive studies, conducted between 1996 and 2002, we treated 22 cases of infant ALL with germline MLL using chemo...

    journal_title：Blood

    pub_type： 临床试验,杂志文章,多中心研究

    doi：10.1182/blood-2005-11-4728

    authors： Nagayama J,Tomizawa D,Koh K,Nagatoshi Y,Hotta N,Kishimoto T,Takahashi Y,Kuno T,Sugita K,Sato T,Kato K,Ogawa A,Nakahata T,Mizutani S,Horibe K,Ishii E,Japan Infant Leukemia Study Group.

    更新日期：2006-06-15 00:00:00

  • Endothelial cells undergoing apoptosis become proadhesive for nonactivated platelets.

    abstract：:Under normal conditions, platelets do not adhere to endothelium. However, when platelets or endothelial cells are stimulated by thrombin or cytokines, respectively, platelets bind avidly to endothelium. Because there is accumulating evidence that endothelial cells may become apoptotic under certain proinflammatory or ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Bombeli T,Schwartz BR,Harlan JM

    更新日期：1999-06-01 00:00:00

  • Inhibition of IL-32 activation by α-1 antitrypsin suppresses alloreactivity and increases survival in an allogeneic murine marrow transplantation model.

    abstract：:Interleukin (IL)-32 was originally identified in natural killer cells and IL-2-activated human T lymphocytes. As T cells are activated in allogeneic transplantation, we determined the role of IL-32 in human mixed lymphocyte cultures (MLCs) and GVHD. In allogeneic MLCs, IL-32 increased two-fold in responding T cells, a...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2011-07-365247

    authors： Marcondes AM,Li X,Tabellini L,Bartenstein M,Kabacka J,Sale GE,Hansen JA,Dinarello CA,Deeg HJ

    更新日期：2011-11-03 00:00:00

  • Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia.

    abstract：:The clinical and prognostic relevance of many recently identified driver gene mutations in adult acute myeloid leukemia (AML) is poorly defined. We sequenced the coding regions or hotspot areas of 68 recurrently mutated genes in a cohort of 664 patients aged 18 to 86 years treated on 2 phase 3 trials of the German AML...

    journal_title：Blood

    pub_type： 杂志文章,多中心研究,随机对照试验

    doi：10.1182/blood-2016-01-693879

    authors： Metzeler KH,Herold T,Rothenberg-Thurley M,Amler S,Sauerland MC,Görlich D,Schneider S,Konstandin NP,Dufour A,Bräundl K,Ksienzyk B,Zellmeier E,Hartmann L,Greif PA,Fiegl M,Subklewe M,Bohlander SK,Krug U,Faldum A,Berdel

    更新日期：2016-08-04 00:00:00

  • Excellent T-cell reconstitution and survival depend on low ATG exposure after pediatric cord blood transplantation.

    abstract：:Successful immune reconstitution (IR) is associated with improved outcomes following pediatric cord blood transplantation (CBT). Usage and timing of anti-thymocyte globulin (ATG), introduced to the conditioning to prevent graft-versus-host disease and graft failure, negatively influences T-cell IR. We studied the rela...

    journal_title：Blood

    pub_type： 临床试验,杂志文章

    doi：10.1182/blood-2016-06-721936

    authors： Admiraal R,Lindemans CA,van Kesteren C,Bierings MB,Versluijs AB,Nierkens S,Boelens JJ

    更新日期：2016-12-08 00:00:00

  • Imprinting of insulin-like growth factor 2 is modulated during hematopoiesis.

    abstract：:The transcription of insulin-like growth factor 2 (IGF-2) is affected by genomic imprinting, a multistep process through which the parental origin of a gene influences its transcription. The maternal copy of IGF-2 is silenced in most human tissues, but in the choroid plexus and the adult liver both alleles of IGF-2 ar...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Morison IM,Eccles MR,Reeve AE

    更新日期：2000-11-01 00:00:00

  • Hematologic effects of stem cell factor in vivo and in vitro in rodents.

    abstract：:Recombinant rat stem cell factor (rrSCF) administered to rats as a single intravenous injection causes a dose-dependent neutrophilia and lymphocytosis as well as the appearance of immature myeloid cells and occasional blast cells in the circulation. Neutrophilia begins at 2 hours, peaks at 4 to 6 hours, and subsides b...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Ulich TR,del Castillo J,Yi ES,Yin S,McNiece I,Yung YP,Zsebo KM

    更新日期：1991-08-01 00:00:00

  • Timing of neutrophil tissue repopulation predicts restoration of innate immune protection in a murine bone marrow transplantation model.

    abstract：:It has been suggested that neutrophil tissue repopulation following bone marrow transplantation (BMT) serves as an earlier and more relevant marker of susceptibility to infection than circulating neutrophil counts. In a previous study using an oral rinse protocol, we found that oral neutrophil recovery always preceded...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2006-04-018184

    authors： Cheretakis C,Leung R,Sun CX,Dror Y,Glogauer M

    更新日期：2006-10-15 00:00:00

  • Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes.

    abstract：:Pregnancy can precipitate thrombotic thrombocytopenic purpura (TTP). We present a prospective study of TTP cases from the United Kingdom Thrombotic Thrombocytopenic Purpura (UK TTP) Registry with clinical and laboratory data from the largest cohort of pregnancy-associated TTP and describe management through pregnancy,...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood-2014-02-553131

    authors： Scully M,Thomas M,Underwood M,Watson H,Langley K,Camilleri RS,Clark A,Creagh D,Rayment R,Mcdonald V,Roy A,Evans G,McGuckin S,Ni Ainle F,Maclean R,Lester W,Nash M,Scott R,O Brien P,collaborators of the UK TTP Registr

    更新日期：2014-07-10 00:00:00

  • In vitro and in vivo effects of a farnesyltransferase inhibitor on Nf1-deficient hematopoietic cells.

    abstract：:Oncogenic RAS alleles encode proteins that accumulate in the guanosine triphosphate (GTP)-bound state. Because post-translational processing of Ras by farnesyltransferase is essential for biologic function, inhibitors of this enzyme have been developed as rational cancer therapeutics. We have investigated farnesyltran...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Mahgoub N,Taylor BR,Gratiot M,Kohl NE,Gibbs JB,Jacks T,Shannon KM

    更新日期：1999-10-01 00:00:00

  • Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG).

    abstract：:The Children's Cancer Group (CCG) and the Pediatric Oncology Group (POG) joined to form the Children's Oncology Group (COG) in 2000. This merger allowed analysis of clinical, biologic, and early response data predictive of event-free survival (EFS) in acute lymphoblastic leukemia (ALL) to develop a new classification ...

    journal_title：Blood

    pub_type： 杂志文章,多中心研究

    doi：10.1182/blood-2006-01-024729

    authors： Schultz KR,Pullen DJ,Sather HN,Shuster JJ,Devidas M,Borowitz MJ,Carroll AJ,Heerema NA,Rubnitz JE,Loh ML,Raetz EA,Winick NJ,Hunger SP,Carroll WL,Gaynon PS,Camitta BM

    更新日期：2007-02-01 00:00:00

  • Two distinct categories of warm autoantibody reactivity with age-fractionated red cells.

    abstract：:Using age-fractionated erythrocytes, warm autoantibodies can be classified into two distinct categories, depending on their reactivity with reticulocyte-enriched (younger) or reticulocyte-poor (older) red cell fractions. The strength of the direct antiglobulin test (DAT) on the age-fractionated red cells of 24 patient...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Branch DR,Shulman IA,Sy Siok Hian AL,Petz LD

    更新日期：1984-01-01 00:00:00

  • The Mpl-ligand or thrombopoietin or megakaryocyte growth and differentiative factor has both direct proliferative and differentiative activities on human megakaryocyte progenitors.

    abstract：:Previously, it was believed that megakaryocytopoiesis was regulated by two types of humoral factors: megakaryocyte colony-stimulating factor (MK-CSF), which acts on progenitors inducing their proliferation, and thrombopoietin (TPO), a megakaryocyte(s) (MK) maturational factor that induces platelet formation. The recen...

    journal_title：Blood

    pub_type： 杂志文章

    doi：

    authors： Debili N,Wendling F,Katz A,Guichard J,Breton-Gorius J,Hunt P,Vainchenker W

    更新日期：1995-10-01 00:00:00

  • Contribution of clonal hematopoiesis to adult-onset hemophagocytic lymphohistiocytosis.

    abstract：:Adult-onset hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation. Unlike pediatric HLH, adult HLH is rarely driven by germline genetic variants. Although numerous precipitating etiologies have been identified, the reason that HLH occurs in only a subset of individuals ...

    journal_title：Blood

    pub_type： 杂志文章

    doi：10.1182/blood.2020008206

    authors： Miller PG,Sperling AS,Gibson CJ,Viswanathan K,Castellano C,McConkey M,Ceremsak J,Taylor MS,Birndt S,Perner F,Arnason J,Agrawal M,Schram AM,Nikiforow S,Pihan G,Hasserjian RP,Aster JC,La Rosée P,Morgan EA,Berliner N,

    更新日期：2020-12-24 00:00:00