Abstract:
:The expression of exogenous genes in long-lived primary T cells is potentially beneficial for the treatment of various diseases including cancer, AIDS, genetic defects of the lymphoid compartment, and systemic enzyme deficiencies such as hemophilia. One approach for genetic modification of T cells is to introduce therapeutic genes into hematopoietic stem cells that would give rise to cells of the lymphoid lineage. Efficient gene transfer and expression in stem cells is often problematic, however. A more direct approach is to introduce the genes into mature primary T lymphocytes since the transferred genes can be maintained and expressed for long periods by long-lived peripheral T cells. In this report, we describe the adoptive transfer into SCID mice of both murine and human primary T cells that have been efficiently transduced with exogenous genes. Primary murine T cells transduced with a retroviral vector containing the human adenosine deaminase (ADA) gene persisted for at least 5 months in lymphoid organs of SCID mice, continuously expressing the exogenous gene. Primary human T cells were also used as target cells for transfer of the beta-galactosidase (lacZ) gene. Expression of the lacZ gene could be detected in over 20% of the transduced primary T cells before adoptive transfer into SCID mice. Transduced human T cells were injected into SCID mice intraperitoneally (ip), and the beta-galactosidase activity could be detected in cells collected from peritoneal exudate washes of recipient mice 6 weeks post-injection. These results demonstrate the availability of a murine model in which the long-term effects of expression of exogenous genes in both murine and human T cells can be tested.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Gu J,Kuo ML,Rivera A,Sutkowski N,Ron Y,Dougherty JPsubject
Has Abstractpub_date
1996-10-01 00:00:00pages
1432-40issue
12eissn
0301-472Xissn
1873-2399journal_volume
24pub_type
杂志文章abstract:OBJECTIVE:Potent immunosuppressants, such as rapamycin, FK506, and ascomycin, are known to regulate the phosphorylation of proteins. The purpose of this study was to investigate the effects of these immunosuppressants on differentiation of several human myeloid leukemic cell lines. MATERIALS AND METHODS:Human myeloid ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00626-9
更新日期:2001-05-01 00:00:00
abstract::The effects of intraperitoneal Ehrlich ascites tumor (ET) growth on the kinetics of hemopoietic stem cells in the host bone marrow were studied using the spleen colony and the soft agar culture techniques. There is a decrease in spleen colony forming capacity of bone marrow of ET bearing mice, whereas in vitro assays ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-05-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to evaluate the occurrence of T-cell spontaneous apoptosis (A(spont)) and its modulation in vitro by the interleukin-2 receptor (IL-2R) gamma-chain (gammac)-signaling cytokine IL-15 in patients transplanted with autologous peripheral blood progenitor cells (PBPC) for hematologic mali...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00747-0
更新日期:2001-12-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to investigate the effects of interleukin-2 (IL-2) gene-transduced hematopoietic progenitor cells or cytotoxic function and systemic toxicity following syngeneic bone marrow transplantation. MATERIAL AND METHODS:Marrow of 5-fluorouracil pretreated donor mice were transfected wit...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00487-2
更新日期:2000-08-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to develop novel markers for enrichment of hematopoietic progenitors from bone marrow of swine. MATERIALS AND METHODS:We previously showed that pig bone marrow contains a "side population" (SP) of Hoechst dye-effluxing cells that resembles the hematopoietic stem cell (HSC)-containin...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(02)00835-4
更新日期:2002-07-01 00:00:00
abstract::Purified normal murine bone marrow-derived fibroblasts were shown to produce a factor that stimulates the in vitro growth of fibroblastic colony-forming unit (CFU-F) colonies. Conditioned medium from the purified fibroblasts (F-CM) also stimulated pure marrow fibroblasts themselves. Analysis of the F-CM detected the p...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::The long-term effects of a maximum tolerated dose of doxorubicin (ADR) (10 mg/kg, LD10/60) on the recovery of the hematopoietic compartments of the femoral marrow from radiation (450 rad) were investigated over a 32-week interval using a mouse model. Comparative radiation response curves, estimating hematopoietic prol...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract:OBJECTIVE:Recruitment of endothelial progenitor cells to the sites of ischemia has recently been suggested as a mechanism of tissue repair. Here we address the hypothesis that the hypoxia-inducible full-length endothelial-monocyte-activating polypeptide II (EMAP II) provides a mechanism to recruit late outgrowth highly...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2006.05.021
更新日期:2006-08-01 00:00:00
abstract:OBJECTIVE:Haplotype-mismatched CD34(+) selected allogeneic stem cell transplantation (HASCT) has been described as a therapeutic option for patients with acute myeloid leukemia. The success of this regimen is based mainly on natural killer (NK) cell-mediated antileukemia effects. MATERIALS AND METHODS:We prospectively...
journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
doi:10.1016/j.exphem.2007.12.006
更新日期:2008-04-01 00:00:00
abstract::The cycle specific drug, hydroxyurea (HU), has previously been used to study the proliferative kinetics of various hemopoietic precursor cells such as granulocyte-macrophage precursors (CFUc) and multipotential stem cells (CFUs). We have investigated the kinetics of another hemopoietic precursor, a T-cell colony (CFUT...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-05-01 00:00:00
abstract:OBJECTIVE:We previously showed that the organotellurium compound, ammonium trichloro (dioxyethylene-0-0') tellurate (AS101), has antitumoral activity in multiple myeloma (MM) cell lines. Here, we evaluated the antimyeloma activity of AS101 combined with low-dose melphalan, and also examined the activity of AS101 in the...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2009.01.006
更新日期:2009-05-01 00:00:00
abstract::It is known that inadequate erythropoietin (EPO) production contributes to the pathogenesis of anemia of inflammation, although the exact molecular mechanism is unknown. Aryl hydrocarbon receptor (AhR) may compete with hypoxia-inducible factor 2α (HIF-2α), the master regulator of EPO production, for binding with HIF-1...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.08.010
更新日期:2016-01-01 00:00:00
abstract::Cells for study were obtained from mouse bone marrow by three methods: 1) Mechanical dissociation; 2) Trypsin release; and 3) Passage through a syringe and needle. The ratio of the fibroblast colony-forming cells in these suspensions was, respectively, 1:13:1. Of the colonies formed by cells obtained by trypsin releas...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1982-02-01 00:00:00
abstract:OBJECTIVE:Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed by the malignant cells of about 30% of cases of Hodgkin's lymphoma (HL) and is therefore a potential target for immune attack. Given the predominantly immunosuppressive nature of HL infiltrating lymphocytes (HLILs) and the ability ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.01.030
更新日期:2007-04-01 00:00:00
abstract::The history of clonal hematopoiesis (CH) research is punctuated by several seminal discoveries that have forged our understanding of cancer development. The clever application of the principle of random X-chromosome inactivation (XCI) in females led to the development of the first test to identify clonal derivation of...
journal_title:Experimental hematology
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.exphem.2020.01.008
更新日期:2020-03-01 00:00:00
abstract::Inoculation of human bone marrow with hepatitis A virus (HAV) resulted in a dose- and duration-of-incubation-dependent suppression of hematopoietic progenitor (CFU-GM, BFU-E, CFU-Mix) growth in vitro. Monocytic progenitors appeared to be least affected. While HAV inactivation by heat or beta-propiolactone and neutrali...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-10-01 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::The effect of indomethacin (6 mg/kg daily orally for 2, 3 or 4 days) on myelopoiesis was studied in mice by estimating 1) differential cell counts of bone marrow, 2) proliferation of the CFUC in presence of GM-CSF, 3) proliferative state of CFUC after tritiated thymidine suicide. After 4 days of treatment, a rise in t...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-10-01 00:00:00
abstract::Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) is an autosomal dominant disease associated with a germline mutation in the RUNX1 gene and is characterized by thrombocytopenia and an increased risk of developing myeloid malignancies. We generated induced pluripotent stem cells (iPSCs) fr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2015.05.004
更新日期:2015-10-01 00:00:00
abstract::In the present study we investigated the absolute numbers of granulocytic progenitor cells (CFUc) in the spleens of adult normal dogs, their differentiation pattern and also their proliferative state. Between 10 and 40 times as many CFUc were found in the spleens of individual dogs as were present in the total blood v...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1980-09-01 00:00:00
abstract::Specific changes taking place in the erythroid tissue following depletion or replacement of androgens were studied in rats. The reduction of testosterone levels in blood of orchiectomized animals did occur in conjunction with a decline of erythrocyte glucose-6-phosphate (G6P) and lactate levels. No evidence of anemia ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1976-09-01 00:00:00
abstract::Protein kinase activities are involved in cellular proliferation and differentiation, and inhibitors of these activities are useful for studying the mechanisms of induction of differentiation. We found that staurosporine, an inhibitor of protein kinase activities, induced morphological differentiation of human myelobl...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::A reliable dose-response curve has been established by exposing normal mice to graded doses of exogenous erythropoietin (ESF). In CF1 femal mice, made polycythemic by exposure to reduced air pressure , 59 Fe incorporation in RBC following injections of ESF (ranging from 0.05 to 3.2 IRP-units) varied according to the...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1976-03-01 00:00:00
abstract:OBJECTIVE:The mechanism for anagrelide's potent platelet lowering activity in human subjects is not well defined. Studies related to anagrelide function have been hampered by its lack of activity in nonhuman primates and water insolubility. In an effort to define the mechanism whereby anagrelide exerts its therapeutic ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(01)00742-1
更新日期:2001-12-01 00:00:00
abstract:OBJECTIVE:B-cell chronic lymphocytic leukemia is a heterogeneous disease with a pronounced variation in the clinical course. With the purpose of identifying genes that could be related to disease progression, we have performed gene expression profiling on B-CLL patients with an indolent disease and patients with a prog...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.05.007
更新日期:2005-08-01 00:00:00
abstract:UNLABELLED:In this paper we describe an experimental model for ex vivo purging of contaminating tumor cells from peripheral blood stem cell (PBSC) collections obtained from patients with acute myeloblastic leukemia (AML). We studied the combination of the alkylating agent nitrogen mustard (NM; concentrations ranging fr...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1997-11-01 00:00:00
abstract::Tumor necrosis factor alpha (TNFalpha) is thought to contribute to the blunted erythropoietin (Epo) production in inflammatory diseases. The present study was carried out to find out as to whether the 55 kD (TNF-RI) or the 75 kD (TNF-RII) receptor is responsible for the TNFalpha-induced inhibition of hepatic Epo synth...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(98)00054-x
更新日期:1999-02-01 00:00:00
abstract::Leukemia associated inhibitor, LAI, reversibly inhibits DNA synthesis in normal human granulocyte-macrophage colony-forming units (CFU-GM). LAI is produced by myeloid leukemia cells, a subpopulation of normal nonadherent low-density mononuclear cells in peripheral blood and bone marrow, as well as by the human promyel...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Human umbilical cord blood (CB) appears to be an exciting new source of transplantable stem cells for a variety of clinical conditions. In this study, we have attempted to further characterize the primitive progenitors in CB. First we analyzed the effects of early-acting growth factors on blast cell colony formation f...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Stem cell maintenance in continuous bone marrow culture has been shown to be associated with close range interaction between hematopoietic cells and marrow derived adherent cells (MDAC). The extent to which the culture system is dependent upon this type of interaction has not been ascertained. Explants of non-adherent...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1981-03-01 00:00:00