Abstract:
:It has been hypothesized that some of the irreversible microrheologic abnormalities of sickle red blood cell (RBC) membranes could result from autoxidative perturbation. To model this possibility, we used micromechanical manipulation to examine the static extensional rigidity and inelastic or plastic behavior of normal RBCs exposed to phenazine methosulfate (PMS), an agent that generates superoxide from within the cell. In response to this stress, RBC membranes became stiff as evidenced by increasing extensional rigidity. At 50 mumol/L PMS they were as stiff as the membranes of most dense, dehydrated sickle RBCs; and at 25 mumols/L PMS the membranes were similar to somewhat less dense sickle RBCs. When examined for inelastic behavior, RBCs exposed to PMS even at 10 mumols/L showed hysteresis in loading and unloading phases of the curve relating aspiration length to suction pressure, and they developed membrane bumps that persisted after RBC release from the pipette. Examination of single cells in both isotonic and hypotonic buffers showed that the effect of PMS on RBC microheology is not mediated by cellular dehydration. Independent confirmation of the membrane stiffening effect of PMS was obtained by ektacytometric analysis of resealed RBC ghosts, with sickle-like increases in membrane rigidity observed between 50 and 100 mumol/L PMS. The rigidity of these ghosts was partially ameliorated by exposure to a thiol reductant. In terms of biochemical abnormalities, treated RBCs became significantly different from control RBCs at 25 mumol/L PMS, at which point they just began to enter the sickle range for amounts of membrane thiol oxidation and membrane-associated heme. The sickle average was achieved at 50 mumol/L PMS (for thiol oxidation) to 100 mumol/L PMS (for membrane heme). Thus, micromolar concentrations of PMS induce abnormalities of membrane microrheology that closely mimic those of unmanipulated sickle RBCs while reproducing similar degrees of oxidative biochemical change. We conclude that membrane protein oxidation could explain existence of an irreversible component to the abnormal rheology of the sickle membrane.
journal_name
Bloodjournal_title
Bloodauthors
Hebbel RP,Leung A,Mohandas Nsubject
Has Abstractpub_date
1990-09-01 00:00:00pages
1015-20issue
5eissn
0006-4971issn
1528-0020journal_volume
76pub_type
杂志文章相关文献
BLOOD文献大全abstract::The c-myb proto-oncogene has been implicated in leukemogenesis, but possible mechanisms remain ill defined. To gain further insight to this process, we used transcript profiling in K562 cells expressing a dominant-negative Myb (MERT) protein. A total of 105 potential Myb gene targets were identified. Neuromedin U (NmU...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2003-10-3577
更新日期:2004-09-15 00:00:00
abstract::Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with a complex pathogenesis, which includes both antibody- and T-cell-mediated effector mechanisms. Rituximab (an anti-human CD20 monoclonal antibody [mAb]) is one of the treatments for ITP and is known to deplete B cells but may also work by affecting t...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2015-06-655126
更新日期:2016-02-11 00:00:00
abstract::Ectopic expression of fibroblast growth factor receptor 3 (FGFR3) associated with t(4;14) has been implicated in the pathogenesis of human multiple myeloma. Some t(4;14) patients have activating mutations of FGFR3, of which a minority are K650E (thanatophoric dysplasia type II [TDII]). To investigate the role of autop...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2004-09-3686
更新日期:2005-07-01 00:00:00
abstract::The phenotypes of early stages of T cell maturation are reflected by precursor T (lymphoblastic) neoplasms. In the present study, a series of such neoplasms was analyzed to reveal the developmental association of the expression of stage-related cell surface markers and T cell receptor gene rearrangement. Rearrangement...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
abstract::Although the role of systemic activation of the nuclear factor kappaB (NF-kappaB) pathway in septic coagulation has been well documented, little is known about the contribution of endothelial-specific NF-kappaB signaling in this pathologic process. Here, we used transgenic mice that conditionally overexpress a mutant ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-205914
更新日期:2009-09-17 00:00:00
abstract::In the present study, Epstein-Barr virus (EBV) isolates from 18 malignant tumors (angioimmunoblastic lymphadenopathy [AILD], n = 4; Hodgkin's disease [HD], n = 3; pleomorphic T-cell non-Hodgkin's lymphoma [T-NHL], n = 1; B-cell non-Hodgkin's lymphoma [B-NHL], n = 8; gastric carcinoma, n = 2) as well as from 10 tonsils...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1996-02-15 00:00:00
abstract::We investigated whether the stem cell that reconstitutes total erythropoiesis of a WBB6F1-W/Wv mouse differentiates into lymphoid lineage. The electrophoretic pattern of hemoglobin was used as a marker of the reconstitution; 3-phosphoglycerate kinase (PGK), an X chromosome-linked enzyme was used as a tool for estimati...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1989-04-01 00:00:00
abstract::Recent studies with long-term mouse marrow cultures have indicated the importance of the adherent layer as a primary reservoir of the most primitive stem cells, from which derivative stem cells and more differentiated progenitors are continuously generated. We have now examined the role of the adherent cell layer in l...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1983-08-01 00:00:00
abstract::Pediatric-type follicular lymphoma (PTFL) is a variant of follicular lymphoma (FL) with distinctive clinicopathological features. Patients are predominantly young males presenting with localized lymphadenopathy; the tumor shows high-grade cytology and lacks both BCL2 expression and t(14;18) translocation. The genetic ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2016-03-703819
更新日期:2016-08-25 00:00:00
abstract::Hematopoiesis is a tightly regulated process resulting in the production of blood cells. Self-renewal and differentiation of hematopoietic stem cells (HSCs) are key processes in hematopoietic development. Disruption of these steps can lead to altered cell distribution and disease. To investigate the role of the nuclea...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2013-02-486142
更新日期:2013-06-20 00:00:00
abstract::Alkylureas are capable of inhibiting sickling in vitro and the gelation of solutions of hemoglobin S at concentrations between 0.05 and 0.1 M with increasing effectiveness that is directly proportional to the length of the alkyl chain (butyl greater than propyl greater than ethyl greater than methyl). 6The inhibitory ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1976-08-01 00:00:00
abstract::A nonanemic chronic lymphocytic leukemia patient with nearly 500,000 lymphocytes/microL underwent leukapheresis when she presented with CNS symptoms and retinal vascular engorgement. Respiratory distress developed during the cell separator run, which led us to ask whether the procedure could have changed the adhesive ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::The production and deployment of phagocytes are central functions of the hematopoietic system. In the 1950s, radioisotopic studies demonstrated the high production rate and short lifespan of neutrophils and allowed researchers to follow the monocytes as they moved from the marrow through the blood to become tissue mac...
journal_title:Blood
pub_type: 杂志文章,评审
doi:10.1182/blood-2007-12-077917
更新日期:2008-08-15 00:00:00
abstract::This study includes 47 normal subjects and 25 hemophilia B patients without inhibitor(s), showing different factor IX coagulant activity and antigen levels. Genomic DNA, digested with various restriction endonucleases, was hybridized with two different factor IX probes, ie, the cDNA and the subgenomic probe for the in...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Dendritic cell (DC) development is efficiently supported by Flt3-ligand or GM-CSF in vitro, and lymphoid-organ DC maintenance in vivo is critically dependent on Flt3-ligand. However, the relevance of GM-CSF for lymphoid-tissue DC maintenance and the importance of both cytokines for nonlymphoid organ DC homeostasis are...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2009-02-206318
更新日期:2009-07-23 00:00:00
abstract::The rates of endocytosis, intracellular degradation, and cell-surface shedding of 125I-labeled monoclonal antibodies (MoAbs) HD-37 (anti-CD19), B1 (anti-CD20), MB-1 (anti-CD37), BC8 (anti-CD45), and DA4-4 (anti-mu) by B-lymphoma cells were compared by cellular radioimmunoassay, ultrastructural autoradiography, sodium ...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract::Granulocyte colony-stimulating factor (G-CSF) is the major regulator of granulopoiesis and acts through binding to its specific receptor (G-CSF-R) on neutrophilic granulocytes. Previous studies of signaling from the 4 G-CSF-R cytoplasmic tyrosine residues used model cell lines that may have idiosyncratic, nonphysiolog...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.v99.3.879
更新日期:2002-02-01 00:00:00
abstract::ADAMTS13 proteolytically regulates the platelet-tethering function of von Willebrand factor (VWF). ADAMTS13 function is dependent upon multiple exosites that specifically bind the unraveled VWF A2 domain and enable proteolysis. We carried out a comprehensive functional analysis of the ADAMTS13 cysteine-rich (Cys-rich)...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-08-594556
更新日期:2015-03-19 00:00:00
abstract::Toll-like receptors (TLRs) and complement are 2 components of innate immunity that are critical for first-line host defense and elicitation of adaptive immune responses. Many pathogen-associated molecular patterns activate both TLR and complement, but whether and how these 2 systems, when coactivated in vivo, interact...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2006-12-063636
更新日期:2007-07-01 00:00:00
abstract::Hematologic engraftment and immune reconstitution were examined in patients who received cyclophosphamide and total body irradiation therapy followed by infusion of autologous bone marrow purged with anti-B1 monoclonal antibody (MoAb) and complement as therapy for non-Hodgkin's lymphoma. Hematologic engraftment was pr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-02-01 00:00:00
abstract::Different forms of interleukin-15 (IL-15) have been identified and shown to elicit different transduction pathways whose impact on hematopoiesis is poorly understood. We demonstrated herein that hematopoietic CD34+ cells constitutively produced endogenous secreted IL-15 (ES-IL-15) that activated different transcriptio...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-09-2760
更新日期:2003-07-01 00:00:00
abstract::Daratumumab, a monoclonal CD38 antibody, is approved in the treatment of myeloma, but its efficacy and safety in light-chain (AL) amyloidosis has not been formally studied. This prospective phase 2 trial of daratumumab monotherapy for the treatment of AL amyloidosis was designed to determine the safety, tolerability, ...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood.2019004436
更新日期:2020-04-30 00:00:00
abstract::We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock protein (HSP)H1/105 in function of their aggressiveness. Here, we now clarify its role as a functional B-NHL target by testing the hypothesis that it promotes the stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2014-07-590034
更新日期:2015-03-12 00:00:00
abstract::The FOXP1 forkhead transcription factor is targeted by recurrent chromosome translocations in several subtypes of B-cell non-Hodgkin lymphomas, where high-level FOXP1 protein expression has been linked to a poor prognosis. Western blotting studies of diffuse large B-cell lymphoma (DLBCL) cell lines unexpectedly identi...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2007-09-115113
更新日期:2008-03-01 00:00:00
abstract::We have recently shown that proteasome inhibitor PS-341 induces apoptosis in drug-resistant multiple myeloma (MM) cells, inhibits binding of MM cells in the bone marrow microenvironment, and inhibits cytokines mediating MM cell growth, survival, drug resistance, and migration in vitro. PS-341 also inhibits human MM ce...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2002-08-2543
更新日期:2003-02-15 00:00:00
abstract::CD4(+) T helper 1 (Th1) cells and Th2 cells are distinguished based on the pattern of cytokines they are able to produce. Selectin ligands and chemokine receptors are differentially expressed in Th1 and Th2 cells, providing a basis for tissue-specific recruitment of helper T-cell subsets. However, the modes and mechan...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1999-11-01 00:00:00
abstract::Cytotoxic T lymphocytes (CTLs) kill target cells through the polarized release of lytic molecules from secretory lysosomes. Loss of munc13-4 function inhibits this process and causes familial hemophagocytic lymphohistiocytosis type 3 (FHL3). munc13-4 binds rab27a, but the necessity of the complex remains enigmatic, be...
journal_title:Blood
pub_type: 杂志文章
doi:10.1182/blood-2011-02-339523
更新日期:2011-08-11 00:00:00
abstract::We have examined the effects of administration of stem cell-factor (SCF) on the number and distribution of pluripotent hematopoietic stem cells (PHSC) in normal mice. Using the competitive repopulation assay we found that in vivo administration of SCF increases the absolute number of PHSC per mouse threefold. The incr...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1993-07-15 00:00:00
abstract::The formation and functioning of the factor X activating complex on the surface of cultured human venous endothelial cells (HVEC) were investigated. To the HVEC monolayer human factors IXa, VIII, X, CaCl2, and S-2222 were added, and a gradually increasing activation of factor X was observed. The maximum activity of 88...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1987-02-01 00:00:00
abstract::Varying doses of 5-azacytidine (5-aza) were given to four sickle cell individuals for 500, 200, 100, and 30 days. The percentage of fetal hemoglobin (HbF) containing reticulocytes (F reticulocytes) increased two- to five-fold within five days of 5-aza therapy in all patients, with a two- to three-fold rapid response (...
journal_title:Blood
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00