Abstract:
:Thrombocytopenia is an important clinical problem for many acquired immunodeficiency syndrome (AIDS) patients. Recently, the utility of recombinant cytokines in alleviating the hematopoietic complications of AIDS and AIDS therapy has been evaluated. The newly cloned cytokine stem cell factor (SCF) has been demonstrated to be a potent regulator of hematopoietic progenitor cell proliferation. Therefore, we evaluated the ability of SCF to alleviate thrombocytopenia caused by infection with LP-BM5 murine leukemia virus (mLV) in a murine model of AIDS (MAIDS). In addition, we evaluated the effects of SCF on previously demonstrated azidothymidine (AZT)-induced elevations of platelet counts. SCF was administered to normal or LP-BMS-infected C57BL/6 mice in combination with oral AZT for up to 1 month and effects on platelet, megakaryocyte (MK), and megakaryocyte colony-forming cell (CFU-MK) numbers were evaluated. SCF alone significantly increased the number of circulating platelets in thrombocytopenic MAIDS mice by 53%. SCF also significantly elevated platelet levels by 29% in normal mice. AZT elevated platelet counts 100% in normal and 50% in MAIDS mice. AZT and SCF increased platelet counts in an additive manner. SCF alone was a potent inducer of splenic CFU-MK in both MAIDS and normal mice, increasing splenic CFU-MK 13- to 15-fold at day 15 as compared with untreated controls. By day 30, however, the numbers of splenic CFU-MK had returned to control levels. In infected mice, AZT alone increased the number of splenic CFU-MK. SCF administered to AZT-treated MAIDS mice did not further enhance these increases. In contrast, in normal mice, AZT decreased splenic CFU-MK numbers. In AZT-treated mice, SCF enhanced the numbers of splenic CFU-MK 90-fold at day 8. In MAIDS mice, the number of bone marrow CFU-MK was significantly increased by SCF treatment at all time points. SCF significantly affected the total number of femoral CFU-MK in AZT-treated mice only at day 15. In normal mice, SCF or SCF and AZT in combination increased the total number of bone marrow CFU-MK five-fold at day 8, but failed to induce changes in the total number of femoral CFU-MK after that. These results indicate that SCF elevates platelet levels in both thrombocytopenic MAIDS and normal mice and profoundly affects CFU-MK proliferation. Combinations of SCF and AZT may be further explored to enhance the therapeutic effectiveness of these two drugs in alleviating thrombocytopenia.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Chow FP,Zsebo K,Hamburger AWsubject
Has Abstractpub_date
1993-08-01 00:00:00pages
1255-62issue
9eissn
0301-472Xissn
1873-2399journal_volume
21pub_type
杂志文章abstract::Previously, recombinant erythropoietin (rEpo) was shown to increase the number and size of megakaryocytic colonies in vitro, and in vivo it elevates the number of megakaryocytes in mouse spleens. To test the hypothesis that rEpo would stimulate platelet production in mice, both normal mice and mice in rebound-thromboc...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-07-01 00:00:00
abstract::Merocyanine 540 (MC 540) is a photosensitizing dye with antineoplastic and antiviral properties. Because photoexcited MC 540 generates singlet molecular oxygen and possibly other reactive oxygen species there is concern that MC 540-mediated photosensitization may be mutagenic. In this paper, we report on the induction...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1989-02-01 00:00:00
abstract:OBJECTIVE:The function of neutrophils as primary mediators of innate immunity depends on the activity of granule proteins and critical components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Expression of their cognate genes is regulated during neutrophil differentiation by a complex netw...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.02.009
更新日期:2008-07-01 00:00:00
abstract:OBJECTIVE:Activating mutations in FLT3 are known to be a frequent transforming event in acute myeloid leukemia. Small molecule-inhibitor therapy targeting the FLT3 kinase is, therefore, an attractive strategy. FLT3 kinase inhibitors, such as PKC412, have already entered clinical trials. Even though results are encourag...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.07.008
更新日期:2007-10-01 00:00:00
abstract:OBJECTIVE:Peripheral blood progenitor cells (PBPC) have been established as an alternative source of hematopoietic stem cells for allogeneic transplantation, but an increased incidence of both acute and chronic graft-vs-host disease (GVHD) has become apparent. We performed a prospective randomized trial comparing bone ...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0301-472x(03)00195-4
更新日期:2003-10-01 00:00:00
abstract::It has been demonstrated that genomic alterations of cells in the hematopoietic microenvironment could induce myelodysplastic syndromes (MDS) with ineffective hematopoiesis and dysmorphic hematopoietic cells, and subsequent transformation to acute myeloid leukemia. This investigation is the first attempt to correlate ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2012.10.009
更新日期:2013-02-01 00:00:00
abstract::Transcription factors are essential to govern differentiation along the lymphoid lineage from uncommitted hematopoietic stem cells. Although many of these transcription factors have putative roles based on murine knockout experiments, their function in human lymphoid development is less known and was studied further. ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00680-9
更新日期:2001-04-01 00:00:00
abstract::The presence of multilineage dysplasia (MLD) by morphology at diagnosis in acute myeloid leukemia (AML) defines a separate subset in the World Health Organization classification with still-debated prognostic value. A major controversy concerns MLD's role in NPM1-mutated (NPM1⁺) AML, which correlates with good prognosi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.06.003
更新日期:2015-10-01 00:00:00
abstract::We examined the effect of vesnarinone, an oral cardiotonic, on the growth and differentiation of human myeloid leukemia cells. Vesnarinone alone markedly induced erythroid differentiation of HEL cells. All-trans-retinoic acid also induced erythroid differentiation of the cells, and the differentiation was greatly enha...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-01-01 00:00:00
abstract::Erythropoiesis requires large amounts of iron for hemoglobin synthesis. There are two sources of iron for erythropoiesis, dietary and stored iron; however, their relative contributions to erythropoiesis remain unknown. In this study, we used the stable iron isotope (57)Fe to quantify synthesis of hemoglobin derived fr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2016.02.005
更新日期:2016-06-01 00:00:00
abstract::A functional method for estimation of plasminogen activator (PA) activity is described. The end-point method follows the PA-dependent conversion of the inactive plasminogen to the potent protease plasmin. The formation of plasmin is monitored by its activity on 14C-globin to form acid-soluble radioactive products. The...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1986-05-01 00:00:00
abstract::Serum levels of monokines, including macrophage colony-stimulating factor (M-CSF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and IL-1 beta (IL-1 beta), were measured in patients with chronic renal failure in an attempt to clarify the kinetics of these cytokines in the course of renal an...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract:OBJECTIVE:Strategies to expand hematopoietic stem cells (HSCs) ex vivo are of key interest. The objective of this study was to resolve if ability of HOXB4, previously documented to induce a significant expansion of HSCs in culture, may extend to other HOX genes and also to further analyze the HOX sequence requirements ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.02.012
更新日期:2007-05-01 00:00:00
abstract:OBJECTIVE:The Hedgehog family of intercellular proteins has a crucial role in embryonic development. Recent experimental data suggests that the Hedgehog pathway may play a role in early hematopoiesis and angiogenesis. Stem cell leukemia (SCL), a basic helix-loop-helix (bHLH) transcription factor, is essential for the s...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.07.019
更新日期:2006-12-01 00:00:00
abstract:OBJECTIVE:Patients with myelodysplasia (MDS) show a disturbed production of ROS in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) in granulocyte-macrophage colony-stimulating factor (GM-CSF)-primed neutrophils. Because generation of ROS is mediated by the NADPH oxidase complex, a component of which is...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(03)00188-7
更新日期:2003-09-01 00:00:00
abstract::Studies were undertaken to produce monoclonal antibodies directed against the murine receptor for macrophage colony-stimulating factor (M-CSF or CSF-1). Sprague-Dawley rats were injected with lysates prepared from a murine myelomonocytic cell line (RAW cell line) that has high levels of M-CSF receptors. Spleen cells f...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-04-01 00:00:00
abstract::A novel polypeptide with a molecular weight of 17 kd (17k protein) was identified in bone marrow cell cultures. The synthesis of 17k protein is elevated in cell cultures maintained under Dexter conditions, which support myelopoiesis. The predominance of macrophages in the stromal layer of these cultures and the observ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::We performed the present study to define the in vitro hemopoietic activity of murine recombinant (r) granulocyte colony-stimulating factor (G-CSF) using murine hemopoietic culture systems of normal bone marrow cells, fetal liver cells, and spleen cells of 5-fluorouracil (FU)-treated mice. Recombinant G-CSF supported o...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::Epitopes on the CD34 molecule detected by some CD34 antibodies can be cleaved by a unique glycoprotease from Pasteurella haemolytica, which cleaves only glycoproteins rich in O-linked glycans. A method to isolate CD34+ cells from adult bone marrow was developed subsequently, in which CD34+ cells were isolated in high ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
abstract::We evaluated the expansion capacity of untreated and 5-fluorouracil (5-FU)-resistant peripheral blood stem cells (PBSC) after 7-day incubation with interleukin-1 (IL-1) plus IL-3 plus stem cell factor (SCF) or with medium alone. We found a significant increase in the proportion of CD34+ cells in the PBSC fraction resi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-04-01 00:00:00
abstract::Different human hematopoietic cell lines were analyzed for the presence of interleukin 6 (IL-6) and IL-6 receptor (IL-6-R). Both IL-6 mRNA and secreted active IL-6 protein were detectable in untreated cell lines with erythroid or megakaryoblastic features (K562, HEL, KU 812, MEG-01, and Dami), but they were not expres...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::We compared the kinetic recovery of lymphocytes and their subsets in two groups of patients submitted to allogeneic peripheral blood progenitor cell transplantation (allo-PBT): those receiving lymphocyte-depleted leukaphereses by positive selection of CD34+ cells (group 1, n = 18) and those receiving unmanipulated leu...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00029-0
更新日期:1999-03-01 00:00:00
abstract:OBJECTIVE:CD34(+) cells, present within the bone marrow, have previously been shown to possess pancreatic endocrine potential. Based on this observation, we explored the capacity of CD34(+) cells derived in culture from the differentiation of human embryonic stem cells (hESC), for their in vivo pancreatic endocrine cap...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2010.03.002
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVE:A complete process for mass generation of megakaryocytes from hematopoietic stem cells under serum-free conditions has great clinical potential for rapid platelet reconstruction in thrombocytopenia patients. We have previously reported on the generation of an optimized serum-free medium (serum-free hematopoie...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.07.012
更新日期:2009-11-01 00:00:00
abstract::The course of development of graft-versus-host reactions (GVHR) following lethal irradiation was compared in two mouse donor-host combinations disparate at non H-2 loci alone or associated to H-2 complex. The pathogenesis of these reactions was very different (mortality rates faster in the second situation for example...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-05-01 00:00:00
abstract::Overexpression of immune-related genes is widely reported in myelodysplastic syndromes (MDSs), and chronic immune stimulation increases the risk for developing MDS. Aberrant innate immune activation, such as that caused by increased toll-like receptor (TLR) signaling, in MDS can contribute to systemic effects on hemat...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2015.05.016
更新日期:2015-08-01 00:00:00
abstract::Exosomes are virus-size membrane-bound vesicles of endocytic origin present in all body fluids. Plasma of AML patients is significantly enriched in exosomes, which carry a cargo of immunosuppressive molecules and deliver them to recipient immune cells, suppressing their functions. However, whether these exosomes origi...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2019.07.005
更新日期:2019-08-01 00:00:00
abstract::The granulocyte defects of Chediak-Higashi syndrome (CHS) include neutropenia, characteristic giant lysosomal granule morphology, and functionally abnormal cell motility, degranulation, and bacterial killing. Findings of elevated levels of adenosine 3', 5' cyclic monophosphate nucleotide (cAMP) and of concanavalin A (...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::We analyzed the accessory function of malignant B cells from non-Hodgkin's lymphomas (NHLs). Among the 70 samples of malignant B cells included, four patterns of expression of the costimulatory molecules CD80 and CD86 were distinguished (+/+, +/-, -/+ and -/-). In two-thirds of the cases, CD80, CD86, or both were expr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00059-9
更新日期:1999-03-01 00:00:00
abstract::After a single pharmacologic dose of estriol (E3) treatment, an increase in number of focal areas of hepatic hemopoiesis was observed in adult mice. When syngeneic bone marrow cells were transfused into E3-treated mice, focal hepatic hemopoiesis was increased further. In a single experiment, using a single cell suspen...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1983-08-01 00:00:00