Abstract:
:The proteolytic cleavage and subsequent inactivation of recombinant human factor VIII (rhFVIII) and human factor VIIIa (rhFVIIIa) by recombinant human activated protein C (rAPC) was analyzed in the presence and absence of human protein S and human factor V (FV). Membrane-bound rhFVIIIa spontaneously looses most of its initial cofactor activity after 15 minutes of incubation at pH 7.4. The remaining activity can be eliminated after incubation with rAPC. Complete inactivation of the membrane-bound rhFVIII and rhFVIIIa by APC correlates with cleavage at Arg336. The inactivation of rhFVIII and human plasma FV by rAPC were also compared. Under similar experimental conditions, complete inactivation of membrane-bound FVIII (60 nmol/L) by rAPC (10 nmol/L) requires 4 hours of incubation, in contrast to 5 minutes for FV (60 nmol/L). The presence of protein S (100 nmol/L) enhances rhFVIII inactivation by rAPC by 6.4-fold and FVa inactivation by twofold, whereas membrane-bound FV showed no protein S dependence during inactivation. The addition of human FV to the APC/protein S inactivation mixture increases by approximately twofold the rate of inactivation of rhFVIII. The effect of FV on the rhFVIII inactivation by APC is protein S-dependent, because FV alone has no effect on the inactivation rate of rhFVIII by APC. Western blotting using a monoclonal antibody that recognizes an epitope between amino acid residues 307 and 506 of human FV showed that FV was completely cleaved by APC at the beginning of the rhFVIII inactivation process. These data suggest that FV fragments derived from the B region of the procofactor after incubation of the membrane-bound procofactor with APC, but not intact single-chain FV, stimulate APC activity in the presence of protein S. rhFVIII, FV, and rhFVIIIa were not inactivated by Glu20-->Ala-substituted rAPC (rAPCgamma20A), and membrane-bound factor Va was only partially inactivated. Our data suggest that (1) FV and FVa are the physiologically significant substrates for APC inactivation and (2) membranes-bound APC-treated FV is a cofactor for the APC inactivation of rhFVIII only in the presence of the intact form of protein S.
journal_name
Bloodjournal_title
Bloodauthors
Lu D,Kalafatis M,Mann KG,Long GLsubject
Has Abstractpub_date
1996-06-01 00:00:00pages
4708-17issue
11eissn
0006-4971issn
1528-0020journal_volume
87pub_type
杂志文章相关文献
BLOOD文献大全abstract::A recent clinical trial for adrenoleukodystrophy (ALD) showed the efficacy and safety of lentiviral vector (LV) gene transfer in hematopoietic stem progenitor cells. However, several common insertion sites (CIS) were found in patients' cells, suggesting that LV integrations conferred a selective advantage. We performe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-09-306761
更新日期:2011-05-19 00:00:00
abstract::Hematopoietic stem cells purified from mouse bone marrow are quiescent with less than 2% of Lin- Hoechst(low)/Rhodamine(low) (Lin- Ho(low)/Rho(low)) and 10% to 15% of Lin-/Sca+ cells in S phase. These cells enter proliferative cycle and progress through G1 and into S phase in the presence of cytokines and 5% heat-inac...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-09-15 00:00:00
abstract::Daratumumab targets CD38-expressing myeloma cells through a variety of immune-mediated mechanisms (complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and antibody-dependent cellular phagocytosis) and direct apoptosis with crosslinking. These mechanisms may also target nonplasma cells tha...
journal_title:Blood
pub_type: 杂志文章,多中心研究
doi:10.1182/blood-2015-12-687749
更新日期:2016-07-21 00:00:00
abstract::Although well characterized in the mouse, the role of Notch signaling in the human T-cell receptor alphabeta (TCR-alphabeta) versus TCR-gammadelta lineage decision is still unclear. Although it is clear in the mouse that TCR-gammadelta development is less Notch dependent compared with TCR-alphabeta differentiation, re...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-06-164871
更新日期:2009-03-26 00:00:00
abstract::Neutrophil dysfunction consequent to influenza A virus infection has been described in vivo and in vitro and may contribute to the serious bacterial sequelae which occur in influenza-infected hosts. On the premise that such dysfunction may represent a form of "deactivation," we sought to characterize neutrophil activa...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-01-01 00:00:00
abstract::Platelet endothelial cell adhesion molecule 1 (PECAM-1) is involved in leukocyte migration and angiogenesis, which are key components of venous thrombus resolution. This study investigated the effect of PECAM-1 deficiency on thrombus resolution in FVB/n mice and the extent to which levels of soluble PECAM-1 (sPECAM-1)...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-04-499558
更新日期:2013-11-07 00:00:00
abstract::The Wrb antigen is a high-frequency human erythrocyte antigen invariably absent from En (a-) erythrocytes, which lack glycophorin A. However, glycophorin A from En (a+) Wr (a+b-) red cells has an amino acid sequence identical to that of glycophorin A from Wr (b+) erythrocytes. Evidence has suggested that the Wrb antig...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-08-15 00:00:00
abstract::Children with constitutional trisomy 21 (Down syndrome) have an approximately 500-fold increased risk of developing acute megakaryoblastic leukemia (AMKL), a form of acute myeloid leukemia. Unique to newborn infants with Down syndrome is a transient leukemia (TL), also referred to as transient myeloproliferative syndr...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-01-0013
更新日期:2003-06-01 00:00:00
abstract::Human granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances numerous functions of mature neutrophils (PMN) including phagocytosis, superoxide responses to chemotaxins, antibody-dependent cellular cytotoxicity, and expression of complement receptors. A central question concerns whether the mechanism of enh...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-03-01 00:00:00
abstract::Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor of the extrinsic coagulation system, synthesized in endothelial cells, which has recently been shown to play an important role in the regulation of activated coagulation factors at the endothelial cell surface. In the present study we investigated t...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-11-01 00:00:00
abstract::The nuclear receptors (NR) retinoid X receptors (RXRs) exert immunomodulatory functions to control inflammation and metabolism via homodimers and heterodimers with several other NRs including retinoic acid receptors. IRX4204 is a novel, highly specific RXR agonist in clinical trials that potently and selectively activ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2020005628
更新日期:2020-09-24 00:00:00
abstract::We have designed two subfamilies of lipophilic iron (III) chelators previously termed reversed siderophores (RSFs). The agents display physicochemical properties that favor extraction of iron beyond membrane barriers of Plasmodium falciparum-infected red blood cells. We studied the in vitro antimalarial potency of RSF...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increas...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-03-15 00:00:00
abstract::Active immunization with the idiotype of follicular lymphoma induces tumor-specific immunity. T cells induced in vivo by idiotype vaccination recognize human leukocyte antigen (HLA)--restricted hypervariable but not conserved idiotype peptides. We hypothesized that idiotype-directed T-cell immunity occurs naturally an...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-02-270199
更新日期:2010-09-09 00:00:00
abstract::This study describes a simple and relatively rapid method of purifying Reed-Sternberg (R-S) cells and their morphologic variants from the lymph nodes of patients affected by Hodgkin's disease. Our initial studies defined the optimal procedure for a quantitative disaggregation of Hodgkin's lymph nodes and the densities...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::Osteoporosis is a frequent problem in disorders characterized by iron overload, such as the thalassemias and hereditary hemochromatosis. The exact role of iron in the development of osteoporosis in these disorders is not established. To define the effect of iron excess in bone, we generated an iron-overloaded mouse by...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-12-260083
更新日期:2010-10-07 00:00:00
abstract::Cord plasma contains colony-stimulating activity (CSA) which stimulates the in vitro clonal growth of neutrophils, eosinophils, macrophages, erythrocytes, and persisting mast cells in semisolid cultures. Analysis of day 35 colonies in agar cultures was found to be a suitable means of demonstrating this activity and di...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
abstract::Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, IL-11, and ciliary neurotrophic factor constitute the IL-6 family of cytokines and play important roles in hematopoiesis, immune response, and nervous system. The receptors for the IL-6 family of cytokines share gp130 through which signals are generated, ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1995-02-01 00:00:00
abstract::Congenital erythropoietic porphyria (Günther's disease) is a rare disorder of heme biosynthesis inherited in an autosomal recessive fashion. The molecular abnormality responsible for the characteristic defect in uroporphyrinogen III synthase activity was investigated in two patients. For the first patient, complementa...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::The regenerative capacity of hematopoietic stem cells (HSCs) is limited by the accumulation of DNA damage. Conditional mutagenesis of the histone 3 lysine 4 (H3K4) methyltransferase, Setd1a, revealed that it is required for the expression of DNA damage recognition and repair pathways in HSCs. Specific deletion of Setd...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-09-806844
更新日期:2018-03-22 00:00:00
abstract::The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or...
journal_title:Blood
pub_type: 临床试验,杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Identification of receptor activator of nuclear factor-kappaB (RANK) and RANK-ligand (RANKL) has provided new insights into the osteoclast differentiation pathway. Osteoclast precursor cells were isolated using monoclonal antibodies against c-Fms and RANK, and the effect of adherence on the in vitro differentiation an...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-12-15 00:00:00
abstract::Three patients developed blastic transformation of essential thrombocythemia (tET). Morphological studies in all patients showed that the majority of blasts had either myeloblastic or myelomonoblastic differentiation. Immunologic assays of hematopoietic cells were performed in two patients. In patient 1, 86% of periph...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1984-04-01 00:00:00
abstract::It has been shown previously that multilineage human hematopoiesis is maintained within human fetal bone marrow (BM) fragments implanted into severe combined immunodeficient (SCID) mice. We describe here an application of this animal model, the SCID-hu mouse, to the study of human myeloid leukemias. BM cells from 8 pa...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-10-15 00:00:00
abstract::Therapeutic gene delivery to hematopoietic stem cells (HSCs) holds great potential as a life-saving treatment of monogenic, oncologic, and infectious diseases. However, clinical gene therapy is severely limited by intrinsic HSC resistance to modification with lentiviral vectors (LVs), thus requiring high doses or repe...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019000040
更新日期:2019-10-17 00:00:00
abstract::Acute myeloid leukemia (AML) is an aggressive malignancy with a relapse rate approaching 50%, despite aggressive chemotherapy. New therapies for AML are targeted at signal transduction pathways known to support blast survival, such as the Stat3 pathway. Aberrant activation of Stat3 has been demonstrated in many differ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2010-04-280123
更新日期:2011-05-26 00:00:00
abstract::Interleukin-2 (IL-2) induces differential secretion of lymphokines by IL-2 receptor (IL-2R)-positive and IL-2R-negative T cells. We studied T cell IL-2R-specific modulation of adult bone marrow erythropoiesis by recombinant IL-2 (rIL-2). I3-2R were induced by CD3 T cell surface determinant-triggering and analyzed by c...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract::This study reassesses the occurrence of Epstein-Barr virus (EBV) diversity and coinfection versus dominance of a single viral strain within immunocompetent normal carriers. Polymerase chain reaction analysis of several different polymorphic loci of the EBV genome was performed on collections of peripheral blood mononu...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:2000-04-01 00:00:00
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:
更新日期:1994-05-01 00:00:00
abstract::Quantitative studies of bone marrow neutrophil pool sizes and production rates and of blood neutrophil kinetics were performed in 16 patients with chronic neutropenia without splenomegaly. Marrow netrophil cellularity was determined from a ferrokinetic estimate of marrow normoblasts and from neutrophil-erythroid ratio...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1979-09-01 00:00:00