Abstract:
:Bleeding problems are associated with defects in platelet alpha-granules, yet little is known about how these granules are formed and released. Mutations affecting VPS33B, a novel Sec1/Munc18 protein, have recently been linked to arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome. We have characterized platelets from patients with ARC syndrome and observed reduced aggregation with arachidonate and adenosine diphosphate (ADP). Structural abnormalities seen in ARC platelets included increased platelet size, a pale appearance in blood films, elevated numbers of delta-granules, and completely absent alpha-granules. Soluble and membrane-bound alpha-granule proteins were significantly decreased or undetectable in ARC platelets, suggesting that both the releasable protein pools and membrane components of alpha-granules were absent. The role of VPS33B in platelet granule biogenesis was evaluated by immunofluorescence microscopy in normal human megakaryocytes. VPS33B colocalized appreciably with markers of alpha-granules, moderately with late endosomes/lysosomes, minimally with delta-granules/lysosomes, and not with cis-Golgi complexes. VPS33B protein expression determined by immunoblotting confirmed the presence of VPS33B in control fibroblasts but not in ARC fibroblasts, and in normal megakaryocytes but not in platelets. We conclude that like other Sec1/Munc18 proteins, VPS33B is involved in intracellular vesicle trafficking, being essential for the development of platelet alpha-granules but not for granule secretion.
journal_name
Bloodjournal_title
Bloodauthors
Lo B,Li L,Gissen P,Christensen H,McKiernan PJ,Ye C,Abdelhaleem M,Hayes JA,Williams MD,Chitayat D,Kahr WHdoi
10.1182/blood-2005-04-1356subject
Has Abstractpub_date
2005-12-15 00:00:00pages
4159-66issue
13eissn
0006-4971issn
1528-0020pii
2005-04-1356journal_volume
106pub_type
杂志文章相关文献
BLOOD文献大全abstract::Somatic hypermutation and class-switch recombination of the immunoglobulin (Ig) genes occur in germinal center (GC) B cells and are initiated through deamination of cytidine to uracil by activation-induced cytidine deaminase (AID). Resulting uracil-guanine mismatches are processed by uracil DNA glycosylase (UNG)-media...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-02-628164
更新日期:2016-01-07 00:00:00
abstract::The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) is the most problematic and costly complication of FVIII replacement therapy that affects up to 30% of previously untreated patients with severe hemophilia A. The development of inhibitors is a multifactorial complication i...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-12-685735
更新日期:2016-06-09 00:00:00
abstract::The balanced manifestation of effector functions and the generation of long-living memory cells is a hallmark of efficient CD8(+) T-cell response. Accumulating data pinpoint CD4(+) CD25(high) regulatory T (Treg) cells as a key factor for the inefficiency of CD8(+) T-cell responses in viral persistence. Little is known...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2008-04-151407
更新日期:2009-05-07 00:00:00
abstract::We investigated the in vivo effects of erythropoietin (EPO) on granulopoiesis and, conversely, the effect of granulocyte colony-stimulating factor (G-CSF) treatment on erythropoiesis. Recombinant human EPO at four different doses in combination with recombinant human G-CSF also at four different doses was simultaneous...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-12-15 00:00:00
abstract::Inversion of chromosome 16 is a consistent finding in patients with acute myeloid leukemia subtype M4 with eosinophilia, which generates a CBFB-MYH11 fusion gene. Previous studies showed that the interaction between CBFβ-smooth muscle myosin heavy chain (SMMHC; encoded by CBFB-MYH11) and RUNX1 plays a critical role in...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2017-04-780106
更新日期:2017-11-30 00:00:00
abstract::Bacterial DNA and synthetic oligodeoxynucleotides containing the CpG motif (CpG ODN) can activate various immune cell subsets, including natural killer cells and macrophages. We evaluated whether the combination of CpG ODN and antitumor monoclonal antibody is effective at preventing tumor growth in an immunocompetent ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1997-04-15 00:00:00
abstract::In search of a possible involvement of the human herpesvirus type 6 (HHV-6) in human Hodgkin's and non-Hodgkin's lymphomas, we studied the levels of anti-HHV-6 antibodies in the sera of 94 cases by an immunofluorescence assay, as well as the presence of HHV-6 sequences in the affected tissues of 66 cases by polymerase...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1991-05-15 00:00:00
abstract::Pulmonary complication in severe Plasmodium falciparum malaria is manifested as a prolonged impairment of gas transfer or the more severe acute respiratory distress syndrome (ARDS). In either clinical presentation, vascular permeability is a major component of the pathologic process. In this report, we examined the ef...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-04-084582
更新日期:2007-11-01 00:00:00
abstract::Erythropoietin (EPO) is the hormone necessary for development of erythrocytes from immature erythroid cells. EPO activates Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family in the EPO-dependent murine erythroid HCD57 cells. Therefore, we tested if JNK activity supported prolif...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-05-1754
更新日期:2004-08-01 00:00:00
abstract::We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) stimulate the differentiation of human monocytes into two phenotypically distinct types of macrophages. However, in vivo, not only CSF but also many other cytokines are produced under va...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-11-15 00:00:00
abstract::The mouse Pim-1 gene encodes two cytoplasmic serine-threonine-specific protein kinases. The gene has been found to be activated (overexpressed) by retroviral insertion in hematopoietic tumors in mice. Transgenic mice that overexpress Pim-1 (E mu-Pim-1) have a low incidence of spontaneous T-cell lymphomas and an increa...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::Pluripotent hematopoietic progenitor cells (CFU-GEMM), myeloid progenitor cells (CFU-GM), and erythroid progenitors (BFU-E) were studied in midtrimester human fetuses using the mixed colony assay. All three progenitor cell populations were detected at high levels in the fetal liver from 12 to 23 wk of gestation. Stem ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1983-07-01 00:00:00
abstract::Transplantation of ex vivo expanded human umbilical cord blood cells (hCB) only partially enhances the hematopoietic recovery after myelosuppressive therapy. Incubation of hCB with optimal combinations of cytokines and niche cells, such as endothelial cells (ECs), could augment the efficiency of hCB expansion. We have...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-12-398115
更新日期:2012-08-09 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::Since the introduction of replacement therapy in the early 1960s by the infusion of plasma-derived factor VIII and IX preparations, important changes have occurred for hemophilia patients. We studied the medical and social developments over 30 years of hemophilia treatment. Since 1972, 5 cross-sectional national posta...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-05-2008
更新日期:2004-12-01 00:00:00
abstract::We have investigated the interaction of fibroblast growth factor (FGF) with megakaryocytopoiesis. Acidic FGF (aFGF) stimulated the proliferation of murine megakaryocytes and human erythroleukemia (HEL) cells in a concentration-dependent manner. The concentrations of aFGF required to elicit half-maximum and maximum eff...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1992-10-15 00:00:00
abstract::Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. H...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-01-01 00:00:00
abstract::Growing evidence supports a pathophysiological role for platelets during the manifestation of postischemic reperfusion injury; in the current study, we investigated the nature and the molecular determinants of platelet-endothelial cell interactions induced by ischemia/reperfusion (I/R). Platelet-endothelium and leukoc...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1998-07-15 00:00:00
abstract::Leukemia in infants is rare but generates tremendous interest due to its aggressive clinical presentation in a uniquely vulnerable host, its poor response to current therapies, and its fascinating biology. Increasingly, these biological insights are pointing the way toward novel therapeutic approaches. Using represent...
journal_title:Blood
pub_type: 杂志文章,随机对照试验
doi:10.1182/blood-2018-04-785980
更新日期:2019-01-17 00:00:00
abstract::T-cell depletion (TCD) of the donor marrow graft has been shown to reduce the severity of graft-versus-host disease (GVHD) in patients with chronic-phase (CP) chronic myelogenous leukemia (CML) undergoing HLA-identical sibling allogeneic marrow transplantation. However, there has been a corresponding reduction in the ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-07-15 00:00:00
abstract::Juvenile chronic myelogenous leukemia (JCML), a myeloproliferative disorder of childhood, is distinct from adult-type chronic myelogenous leukemia (CML) and bears resemblance to chronic myelomonocytic leukemia (CMMoL). Since mutations in the N-ras gene have been found at high frequencies in CMMoL, but only rarely in C...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-04-15 00:00:00
abstract::The spread of multiple myeloma (MM) involves (re)circulation into the peripheral blood and (re)entrance or homing of MM cells into new sites of the BM. Hypoxia in solid tumors was shown to promote metastasis through activation of proteins involved in the epithelial-mesenchymal transition (EMT) process. We hypothesized...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-09-380410
更新日期:2012-06-14 00:00:00
abstract::Interleukin-1 (IL-1) has been shown to ameliorate the hematopoietic toxicities of antitumor chemotherapeutic agents in both mice and humans. However, IL-1 toxicity in humans is considerable and is similar to the systemic inflammatory toxicities induced by IL-3, IL-6, and other cytokines with pleiotropic biologic activ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::Hematopoietic stem cells (HSCs) undergo dramatic expansion during fetal liver development, but attempts to expand their numbers ex vivo have failed. We hypothesized that unidentified fetal liver cells produce growth factors that support HSC proliferation. Here we describe a novel population of CD3+ and Ter119- day-15 ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-08-2955
更新日期:2004-04-01 00:00:00
abstract::Aberrant regulation of endogenous survival pathways plays a major role in progression of chronic lymphocytic leukemia (CLL). Signaling via conjugation of surface receptors within the tumor environmental niche activates survival and proliferation pathways in CLL. Of these, the phosphoinositide 3-kinase (PI3K)/protein k...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-06-583518
更新日期:2015-01-08 00:00:00
abstract::Mammals express thousands of long noncoding (lnc) RNAs, a few of which are known to function in tissue development. However, the entire repertoire of lncRNAs in most tissues and species is not defined. Indeed, most lncRNAs are not conserved, raising questions about function. We used RNA sequencing to identify 1109 pol...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-12-544494
更新日期:2014-03-20 00:00:00
abstract::Epinephrine causes platelet aggregation and secretion by interacting with alpha 2-adrenergic receptors on the platelet surface. Platelet aggregation requires the binding of fibrinogen to a specific receptor on the membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of r...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-12-01 00:00:00
abstract::The expression of a number of blood coagulation factors (F) (FX, FIX, FVIII, FVII, alpha-, beta-, gamma-fibrinogen chains, protein C, and antithrombin III [AT III]) was analyzed at RNA and protein level in 5- to 10-week-old human embryos and fetuses. FX, FIX, and FVII were also analyzed at protein level. Total and pol...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1990-09-15 00:00:00
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
更新日期:2001-02-15 00:00:00
abstract::Measurement of plasma levels of two secreted platelet proteins (beta-thromboglobulin and platelet factor 4) has been suggested as a means for detecting increased platelet activation in vivo. A crucial question in the measurement is the distinction between in vivo and in vitro secretion of the proteins. One approach to...
journal_title:Blood
pub_type: 杂志文章,评审
doi:
更新日期:1981-02-01 00:00:00