Abstract:
:Activated platelets release their granule content in a concentrated fashion at sites of injury. We examined whether ectopically expressed factor VIII in developing megakaryocytes would be stored in alpha-granules and whether its release from circulating platelets would effectively ameliorate bleeding in a factor VIIInull mice model. Using the proximal glycoprotein 1b alpha promoter to drive expression of a human factor VIII cDNA construct, transgenic lines were established. One line had detectable human factor VIII that colocalizes with von Willebrand factor in platelets. These animals had platelet factor VIII levels equivalent to 3% to 9% plasma levels, although there was no concurrent plasma human factor VIII detectable. When crossed onto a factor VIIInull background, whole blood clotting time was partially corrected, equivalent to a 3% correction level. In a cuticular bleeding time study, these animals also had only a partial correction, but in an FeCl3 carotid artery, thrombosis assay correction was equivalent to a 50% to 100% level. These studies show that factor VIII can be expressed and stored in platelet alpha-granules. Our studies also suggest that platelet-released factor VIII is at least as potent as an equivalent plasma level and perhaps even more potent in an arterial thrombosis model.
journal_name
Bloodjournal_title
Bloodauthors
Yarovoi HV,Kufrin D,Eslin DE,Thornton MA,Haberichter SL,Shi Q,Zhu H,Camire R,Fakharzadeh SS,Kowalska MA,Wilcox DA,Sachais BS,Montgomery RR,Poncz Mdoi
10.1182/blood-2003-05-1519subject
Has Abstractpub_date
2003-12-01 00:00:00pages
4006-13issue
12eissn
0006-4971issn
1528-0020pii
2003-05-1519journal_volume
102pub_type
杂志文章相关文献
BLOOD文献大全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:
更新日期:1995-10-01 00:00:00
abstract::Before the contemporary development of rationally designed antineoplastic therapies, cladribine was identified as a lymphocyte-specific agent. Its profound impact on the natural history of hairy cell leukemia, with responses approaching 100% and a median duration of response of nearly a decade after only a single 7-da...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2010-02-246140
更新日期:2010-10-21 00:00:00
abstract::Fanconi anemia (FA) is an autosomal recessive syndrome featuring diverse symptoms including progressive bone marrow failure and early occurrence of acute myeloid leukemia. Nine genetic subtypes have been described for FA (A, B, C, D1, D2, E, F, G, and L), all of which have been connected to distinct disease genes, exc...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-08-2915
更新日期:2004-04-01 00:00:00
abstract::Immune function has been restored in 9 of 10 children with X-linked severe combined immunodeficiency by gamma c gene transfer in CD34+ cells. The distribution of both T-cell receptor (TCR) V beta family usage and TCR V beta complementarity-determining region 3 (CDR3) length revealed a broadly diversified T-cell repert...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:10.1182/blood-2004-07-2648
更新日期:2005-04-01 00:00:00
abstract::Recombinant human macrophage colony-stimulating factor (rhM-CSF) was given to cynomolgus monkeys by continuous intravenous infusion or subcutaneous injection, at a dose of 50 to 100 micrograms/kg/d in repetitive 14-day cycles. Starting within 24 to 48 hours of initiation of rhM-CSF, there was a progressive increase in...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-05-15 00:00:00
abstract::In vitro agar culture patterns of bone marrow cells in acute myeloid leukemia may show several growth patterns, including cultures where no colonies or clusters develop, cultures with varying numbers of clusters and no colonies, or colony and cluster formation with an extremely high ratio of clusters to colonies. Twel...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1979-08-01 00:00:00
abstract::In this issue of Blood, Kochenderfer et al show that engineered CD19–chimeric antigen receptor (CAR) and donor-derived allogeneic T cells can safely treat CD19-positive B-cell malignancies, which have relapsed after allogeneic stem cell transplantation. ...
journal_title:Blood
pub_type: 评论,杂志文章
doi:10.1182/blood-2013-10-528984
更新日期:2013-12-12 00:00:00
abstract::Stem cell localization, conservation, and differentiation is believed to occur in niches in the marrow stromal microenvironment. Our recent observation that long-term in vitro human hematopoiesis requires a stromal heparan sulfate proteoglycan (HSPG) led us to hypothesize that such HSPG may orchestrate the formation o...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-12-15 00:00:00
abstract::Primary myelofibrosis (PMF) is the most serious myeloproliferative disorder, characterized by clonal myeloproliferation associated with cytokine-mediated bone marrow stromal reaction including fibrosis and osteosclerosis. Current drug therapy remains mainly palliative. Because the NF-kappaB pathway is implicated in th...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-10-054502
更新日期:2007-07-01 00:00:00
abstract::Mantle cell lymphoma (MCL) is a mature B-cell neoplasm initially driven by CCND1 rearrangement with 2 molecular subtypes, conventional MCL (cMCL) and leukemic non-nodal MCL (nnMCL), that differ in their clinicobiological behavior. To identify the genetic and epigenetic alterations determining this diversity, we used w...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2020005289
更新日期:2020-09-17 00:00:00
abstract::Adeno-associated virus (AAV)-based gene therapies can restore endogenous factor VIII (FVIII) expression in hemophilia A (HA). AAV vectors typically use a B-domain-deleted FVIII transgene, such as human FVIII-SQ in valoctocogene roxaparvovec (AAV5-FVIII-SQ). Surprisingly, the activity of transgene-produced FVIII-SQ was...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2020005683
更新日期:2020-11-26 00:00:00
abstract::Somatic mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) were recently demonstrated in acute myeloid leukemia (AML), but their prevalence and prognostic impact remain to be explored in large extensively characterized AML series, and also in various other hematologic malignancies. Here, we demonstrate in 8...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-11-250878
更新日期:2010-09-23 00:00:00
abstract::CREB-binding protein (CBP) and the closely related adenovirus E1A-associated 300-kD protein (p300) function as coactivators of transcription factors such as CREB, c-Fos, c-Jun, c-Myb, and several nuclear receptors. To study the roles of CBP in embryonic development, we generated CBP homozygous mutant mouse embryos tha...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::Hematopoietic function of some aplastic anemia (AA) patients is dependent on the administration of cyclosporine (CyA). To investigate whether certain HLA class II genes are associated with susceptibility to such CyA-dependent AA, we determined the HLA class II alleles of 59 AA patients treated with CyA. Among 26 patie...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-12-15 00:00:00
abstract::Bruton tyrosine kinase (Btk) has a well-defined role in B-cell development, whereas its expression in osteoclasts (OCs) further suggests a role in osteoclastogenesis. Here we investigated effects of PCI-32765, an oral and selective Btk inhibitor, on osteoclastogenesis as well as on multiple myeloma (MM) growth within ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-12-396853
更新日期:2012-08-30 00:00:00
abstract::Three populations of erythrocytes have been shown by flow cytometric analysis on complement regulatory proteins: CD59 and decay-accelerating factor (DAF) on erythrocytes in paroxysmal nocturnal hemoglobinuria (PNH). CD59 and DAF in PNH may be completely deficient in CD59- and DAF-negative erythrocytes, they may be dec...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::We assessed primary cutaneous large B-cell lymphoma, leg type (PCLBCL, leg type; n = 13), and primary cutaneous follicle center lymphoma (PCFCL; n = 19) for somatic hypermutation (SHM) of BCL6, and aberrant SHM of MYC, RhoH/TTF, and PAX5. We demonstrate SHM of BCL6 in 8 PCLBCLs (62%), leg type, and 7 PCFCL patients (3...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-08-3443
更新日期:2006-06-15 00:00:00
abstract::The presence of minimal amounts of fibrinogen-fibrin intermediates in human plasma was visualized by an agglutination reaction of glutaraldehyde-treated human erythrocytes coated with purified fibrin monomers. A degree of monomer coating was established which produced erythrocytes not agglutinated by normal plasma but...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1976-06-01 00:00:00
abstract::Plasmodium vivax merozoites only invade reticulocytes, a minor though heterogeneous population of red blood cell precursors that can be graded by levels of transferrin receptor (CD71) expression. The development of a protocol that allows sorting reticulocytes into defined developmental stages and a robust ex vivo P vi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-08-596015
更新日期:2015-02-19 00:00:00
abstract::IL-17 and its receptor are founding members of a novel family of inflammatory cytokines. IL-17 plays a pathogenic role in rheumatoid arthritis (RA)-associated bone destruction. However, IL-17 is also an important regulator of host defense through granulopoiesis and neutrophil trafficking. Therefore, the role of IL-17 ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2005-09-010116
更新日期:2007-05-01 00:00:00
abstract::Current approaches for treatment of late-stage breast cancer rarely result in a long-term cure. In part this is due to tumor stroma that prevents access of systemically or intratumorally applied therapeutics. We propose a stem cell gene therapy approach for controlled tumor stroma degradation that uses the pathophysio...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-10-187237
更新日期:2009-05-28 00:00:00
abstract::Two families of Epstein-Barr virus (EBV), type A and type B, have been defined on the basis of sequence divergence in the EBNA-2 gene. Type A EBV immortalizes B cells more efficiently in vitro and infects immunocompetent individuals more commonly than type B EBV. However, increased rates of infection by type B EBV are...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-03-01 00:00:00
abstract::Bone morphogenetic proteins (BMPs), members of the transforming growth factor (TGF)-beta superfamily, are a group of related proteins that are capable of inducing the formation of cartilage and bone but are now regarded as multifunctional cytokines. We show in this report a novel function of BMPs in hematopoietic cell...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-09-15 00:00:00
abstract::Fibrinogen was isolated from the plasma of a 25-year-old female with a history of mild bleeding and several recent moderate to severe hemorrhagic episodes. Coagulability with thrombin approached 100% and varied directly with the time of incubation with the enzyme. High-performance liquid chromatography analysis of thr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::To understand the etiology of bone modulation and hypercalcemia observed in granulocytosis of a tumor-bearing animal model and to gain insight into the implication of sustained hematopoietic stimulation on the bone tissue, in vivo responses of normal mouse hematopoietic and bone tissues to long-term injections of reco...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-05-15 00:00:00
abstract::Histone deacetylases (HDACs) are epigenetic erasers of lysine-acetyl marks. Inhibition of HDACs using small molecule inhibitors (HDACi) is a potential strategy in the treatment of various diseases and is approved for treating hematological malignancies. Harnessing the therapeutic potential of HDACi requires knowledge ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-08-450916
更新日期:2013-03-14 00:00:00
abstract::Previous results, presented in abstract form, indicate that replacement of thromboplastin with a mixture of phospholipid and truncated soluble tissue factor apoprotein results in a coagulation assay that can directly measure plasma factor VIIa levels without interference from zymogen factor VII (Atherosclerosis Thromb...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::The evolutionarily conserved immune system of the zebrafish (Danio rerio), in combination with its genetic tractability, position it as an excellent model system in which to elucidate the origin and function of vertebrate immune cells. We recently reported the existence of antigen-presenting mononuclear phagocytes in ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-11-321448
更新日期:2011-06-30 00:00:00
abstract::Immunoaffinity chromatography using conformation-specific antibodies yields pure factor IX from human plasma in a single rapid, facile purification step. We evaluated this technique to determine whether factor IX can be separated from human T cell leukemia virus-I (HTLV-I) and human immunodeficiency virus (HIV) in pla...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-11-01 00:00:00
abstract::The immunoreceptors NKG2D and NKp46 are known for their capacity to activate natural killer (NK) cell cytotoxicity and secretory responses in the contexts of tumors and infections, yet their roles in NK cell education remain unclear. Here, we provide the first characterization of mice deficient for both NKG2D and NKp4...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2012-12-471607
更新日期:2013-06-20 00:00:00