Abstract：
:Diaspirin cross-linked hemoglobin (DCLHb) is an intramolecularly cross-linked hemoglobin-based oxygen carrier being developed as a therapy for acute blood loss. We report here the absence of immunogenicity of DCLHb in patients enrolled in phase II and III clinical trials of DCLHb. Two very sensitive immunoassays, an enzyme-linked immunosorbent assay (ELISA) and a Western blot assay, were developed and validated for this assessment. The DCLHb-antibodies used in these assays were raised in monkeys, had similar affinities for DCLHb and native human hemoglobin (SFHb), and showed cross-reactivity for subunits of DCLHb and SFHb on the Western blot, suggesting that these antibodies were elicited as a xenogenic response to the protein. In the ELISA, the optical density of a patient sample exposed to DCLHb-coated wells was compared with that of the patient sample exposed to carbonate buffer-coated wells; an optical density ratio of 1.4 was established for discriminating between a positive (reactive) or negative DCLHb antibody response. To date, all of the more than 300 patient specimens (preinfusion and postinfusion) from clinical trials have exhibited a ratio of less than 1.4, confirming the lack of preexisting antibodies to DCLHb and clearly showing the absence of DCLHb antibodies after exposure to this new biologic entity. There has been no requirement for use of the confirmatory Western blot assay. Taken together, the results from this study indicate DCLHb is not immunogenic in humans at doses evaluated clinically.
journal_name
Bloodjournal_title
Bloodauthors
Patel MJ,Webb EJ,Shelbourn TE,Mattia-Goldberg C,George AJ,Zhang F,Moore EG,Nelson DJsubject
Has Abstractpub_date
1998-01-15 00:00:00pages
710-6issue
2eissn
0006-4971issn
1528-0020journal_volume
91pub_type
杂志文章相关文献
BLOOD文献大全abstract：:Human ADAMTS13 is a multidomain protein with metalloprotease (M), disintegrin-like (D), thrombospondin-1 (T), Cys-rich (C), and spacer (S) domains, followed by 7 additional T domains and 2 CUB (complement components C1r and C1s, sea urchin protein Uegf, and bone morphogenetic protein-1) domains. ADAMTS13 inhibits the ...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2018-11-886309
更新日期：2019-04-25 00:00:00
abstract：:The transforming growth factor-beta (TGF-beta) family of cytokines regulates vascular development and inflammatory responses. We have recently shown that exposure of human umbilical vein endothelial cells (HUVECs) to hypoxia (1% O(2)) increases gene expression and bioactivation of TGF-beta2 and induces its downstream ...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2002-02-0629
更新日期：2003-03-15 00:00:00
abstract：:Donor lymphocyte infusions (DLIs) induce potent graft versus tumor (GVT) effects for relapsed chronic myelogenous leukemia (CML) after allogeneic stem cell transplantation (SCT) but are disappointing for other diseases. Disease resistance can occur if donor T cells are not appropriately activated in vivo. Ex vivo T-ce...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2005-08-3373
更新日期：2006-02-15 00:00:00
abstract：:The engraftment of donor bone marrow (BM) cells in nonablated mice is inefficient. Niche availability has been thought to be the reason, and cytoablation with irradiation or cytotoxic agents is routinely used with the belief that this frees the preoccupied niches in recipients. In this study, donor cell redistribution...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2002-04-1256
更新日期：2002-11-15 00:00:00
abstract：:Blockade of the CD40/CD154 signal is a potential immunomodulatory strategy for T-cell-mediated diseases. As a part of a phase 1, multicenter, dose-escalating trial of humanized monoclonal antibody to CD154 (IDEC-131/E6040) in patients with refractory immune thrombocytopenic purpura (ITP), the autoimmune response to gl...
journal_title：Blood
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1182/blood-2003-06-2167
更新日期：2004-02-15 00:00:00
abstract：:Thymosin beta 4 (T beta 4) was originally isolated as a thymic hormone. Its functional properties remain obscure; however, the N-terminal peptidic sequence could have a regulatory function on hematopoietic stem cell proliferation. To investigate the mechanism of T beta 4 expression, we studied T beta 4 gene expression...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1990-09-01 00:00:00
abstract：:The genetic diversity of the human immunodeficiency virus (HIV) isolated from transfusion-associated AIDS patients has been examined. Restriction enzyme mapping studies of integrated proviral DNA of donor and recipient origin demonstrated genomic variation between isolates. Analysis of the molecularly cloned viral gen...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1987-06-01 00:00:00
abstract：:Indolent systemic mastocytosis (SM) patients have a varied clinical presentation, ranging from predominantly cutaneous symptoms to recurrent systemic symptoms (eg, flushing, palpitations, dyspepsia, diarrhea, bone pain) that can be severe and potentially life threatening (anaphylaxis). Mastocytosis patients without sk...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2013-01-453183
更新日期：2013-04-18 00:00:00
abstract：:Gemtuzumab ozogamicin (GO) contains an anti-CD33 antibody to facilitate uptake of a toxic calicheamicin-gamma(1) derivative. While recent in vitro data demonstrated a quantitative relationship between CD33 expression and GO cytotoxicity, previous correlative studies failed to identify a significant association between...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2006-09-047399
更新日期：2007-05-15 00:00:00
abstract：:Treatment outcome of acute myeloid leukemia (AML) in elderly patients remains unsatisfactory. It has been shown that the infusion of granulocyte colony-stimulating factor-mobilized donor peripheral blood stem cells (G-PBSCs) can enhance graft-versus-leukemia effects and speed hematopoietic recovery. Fifty-eight AML pa...
journal_title：Blood
pub_type： 杂志文章,随机对照试验
doi：10.1182/blood-2010-06-288506
更新日期：2011-01-20 00:00:00
abstract：:Recent evidence suggests chronic myeloid leukemia (CML) stem cells are insensitive to kinase inhibitors and responsible for minimal residual disease in treated patients. We investigated whether CML stem cells, in a transgenic mouse model of CML-like disease or derived from patients, are dependent on Bcr-Abl. In the tr...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2010-12-326843
更新日期：2012-02-09 00:00:00
abstract：:Interleukin-3 (IL-3) is involved in proliferation and differentiation of hematopoietic progenitor cells. Its expression is subject to precise, tissue-specific regulation, and has been studied extensively in the gibbon T-cell line MLA 144 by a combination of functional assays and DNA binding experiments. To extend thes...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1994-05-15 00:00:00
abstract：:The TEL-JAK2 gene fusion, which has been identified in human leukemia, encodes a chimeric protein endowed with constitutive tyrosine kinase activity. TEL-JAK2 transgenic expression in the mouse lymphoid lineage results in fatal and rapid T-cell leukemia/lymphoma. In the present report we show that T-cell leukemic cell...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2006-09-048801
更新日期：2007-05-01 00:00:00
abstract：:The human peripheral B-cell compartment displays a large population of immunoglobulin M-positive, immunoglobulin D-positive CD27(+) (IgM(+)IgD(+)CD27(+)) "memory" B cells carrying a mutated immunoglobulin receptor. By means of phenotypic analysis, complementarity-determining region 3 (CDR3) spectratyping during a T-in...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2004-01-0346
更新日期：2004-12-01 00:00:00
abstract：:Interleukin-3 (IL-3) has been shown to be a promising agent in the stimulation of bone marrow regeneration following myeloablative therapy. The biologic half-life of this agent is very short (5 to 15 minutes), which limits the effectiveness of low-dose therapy. Here we show that the biologic effects of low-dose IL-3 i...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1993-08-15 00:00:00
abstract：:A new human leukemia cell line, KT-1, was established from a patient in the blastic crisis phase of chronic myelogenous leukemia (CML). This cell line had a positive reaction for intracytoplasmic myeloperoxidase and two Philadelphia chromosomes (Ph1) [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22....
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1998-01-15 00:00:00
abstract：:Hematide is an investigational pegylated synthetic peptide that stimulates erythropoiesis in animal models and is being developed for the treatment of anemia associated with chronic renal failure and cancer. This study evaluated the safety and pharmacodynamics of single, intravenous doses (0.025, 0.05, and 0.1 mg/kg) ...
journal_title：Blood
pub_type： 杂志文章,随机对照试验
doi：10.1182/blood-2006-04-015818
更新日期：2006-09-15 00:00:00
abstract：:Fibronectin (FN) plays a role in several adhesion mediated functions including the interaction of platelets with subendothelium. We investigated the role of plasma FN in platelet adhesion and platelet thrombus formation under flow conditions. We used two different perfusion models: the annular chamber with alpha-chymo...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1987-11-01 00:00:00
abstract：:In this issue of Blood, Smith and colleagues report on the functional role of the interaction between these 2 proteins by studying the involved binding sites responsible for clot stabilization.(1) ...
journal_title：Blood
pub_type： 评论,杂志文章
doi：10.1182/blood-2013-01-479055
更新日期：2013-03-14 00:00:00
abstract：:The plasminogen activator inhibitor PAI-1 is markedly elevated in vivo and in vitro upon exposure to the inflammatory mediators tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and bacterial lipopolysaccharide. Here we report that the isoflavone compound genistein prevents the increase in synthesis of PA...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:The interaction of thrombin with plasminogen activator inhibitor 1 (PAI-1) is shown to result in the simultaneous formation of both cleaved PAI-1 and a sodium dodecyl sulfate-stable thrombin-PAI-1 complex. The kinetics of this reaction can be described by a "suicide substrate" mechanism that includes a branched reacti...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1997-09-01 00:00:00
abstract：:Patients aged ≥60 years with treatment-naive Hodgkin lymphoma (HL) have few treatment options and inferior survival due to treatment-related toxicities and comorbidities. This phase 2, nonrandomized, open-label study evaluated brentuximab vedotin (BV) monotherapy (results previously reported), BV plus dacarbazine (DTI...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2017-06-787200
更新日期：2017-12-28 00:00:00
abstract：:IL-12 exerts several regulatory effects on natural killer (NK) cells by activating IL-12 signaling. IL-12 signaling is tightly auto-regulated to control its onset and termination, with prolonged IL-12 treatment resulting in IL-12 hyporesponsiveness. However, the mechanisms underlying IL-12 auto-regulation are still un...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2011-05-356162
更新日期：2011-12-22 00:00:00
abstract：:High molecular weight (HMW) kininogen, the cofactor for activation of the contact system of plasma proteolysis, transports and optimally positions prekallikrein and factor XI on a negatively charged surface, allowing those zymogens to be activated by surface-bound factor XIIa. HMW kininogen circulates in plasma as a p...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:Biologic responses to cytokines are mediated by intracellular pathways involving induction of signaling and metabolic cascades. Interferon (IFN) regulatory factor-1 (IRF-1) is a major transcription factor induced not only by IFN-gamma but also by other cytokines including tumor necrosis factor-alpha (TNF-alpha). Possi...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:Chronic lymphocytic leukemia of B-cell origin (B-CLL) is generally thought to arise by neoplastic transformation of B lymphocytes, which express CD5 and have features of an early stage of B-cell differentiation. To study isotype-switched B-CLL as a potentially more differentiated variant, we performed genetic and func...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1992-11-01 00:00:00
abstract：:Monocytes/macrophages exert a series of important functions in vivo. To facilitate detailed investigation of their functional capacity and the mechanism leading to their differentiation, several cell lines have been established from primary material. We present here a new human monoblastic cell line, designated UG3. U...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1998-06-15 00:00:00
abstract：:The anemia of chronic disease (ACD) results from 3 major processes: slightly shortened red cell survival, impaired reticuloendothelial system iron mobilization, and impaired erythropoiesis. Hepcidin is an acute-phase protein with specific iron regulatory properties, which, along with the anemia seen with increased hep...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2005-07-2854
更新日期：2006-04-01 00:00:00
abstract：:We investigated the correlation between the detection of clonal rearrangement of the T-cell antigen receptor gene (TCRR) in lymph node tissue with histopathologic lymph node classification in 33 patients with mycosis fungoides with and without the Sezary Syndrome. We analyzed DNA extracted from lymph nodes that were h...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1992-06-15 00:00:00
abstract：:A plethora of myeloma growth factors (MGFs) has been identified, but their relative importance and cooperation have not been determined. We investigated 5 MGFs (interleukin-6 [IL-6], insulin-like growth factor type 1 [IGF-1], hepatocyte growth factor [HGF], HB-epidermal growth factor [HB-EGF], and a proliferation-indu...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2008-07-170464
更新日期：2009-05-07 00:00:00
