Abstract：
:Fabry disease is a lysosomal storage disorder that is due to a deficiency in alpha-galactosidase A (alpha-gal A). Previously we have shown that a recombinant retrovirus synthesized for the transfer of the human alpha-gal A coding sequence was able to engineer enzymatic correction of the hydrolase deficiency in fibroblasts and lymphoblasts from Fabry patients. The corrected cells secreted alpha-gal A that was taken up and utilized by uncorrected bystander cells, thus demonstrating metabolic cooperativity. In separate experiments we used transduced murine bone marrow cells and successfully tested and quantitated this phenomenon in vivo. In the present studies, which were designed to bring this therapeutic approach closer to clinical utility, we establish that cells originating from the bone marrow of numerous Fabry patients and normal volunteers can be effectively transduced and that these target cells demonstrate metabolic cooperativity. Both isolated CD34+-enriched cells and long-term bone marrow culture cells, including nonadherent hematopoietic cells and adherent stromal cells, were transduced. The transferred gene generates increased intracellular alpha-gal A enzyme activity in these cells. Further, it causes functional correction of lipid accumulation and provides for long-term alpha-gal A secretion. Collectively, these results indicate that a multifaceted gene transfer approach to bone marrow cells may be of therapeutic benefit for patients with Fabry disease.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Takenaka T,Hendrickson CS,Tworek DM,Tudor M,Schiffmann R,Brady RO,Medin JAdoi
10.1016/s0301-472x(99)00050-8keywords:
subject
Has Abstractpub_date
1999-07-01 00:00:00pages
1149-59issue
7eissn
0301-472Xissn
1873-2399pii
S0301-472X(99)00050-8journal_volume
27pub_type
杂志文章abstract：OBJECTIVES:Using metaphase cytogenetics (MC), chromosomal defects can be detected in 40% to 60% of patients with myelodysplastic syndromes (MDS); cytogenetic results have a major impact on prognosis. We hypothesize that more precise methods of chromosomal analysis will detect new/additional cryptic lesions in a higher ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.08.009
更新日期：2007-11-01 00:00:00
abstract：:We have studied the effect of cortisone acetate (CA) on two important biological functions: (1) on NK cell-mediated cytotoxicity of B6D2F1 mice to T cell lymphoma, YAC-1 and (2) on hybrid resistance of mice to parental B6 bone marrow grafts. Results of our experiments have shown that 5 mg of CA administered i.p. was e...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1981-08-01 00:00:00
abstract：OBJECTIVE:Generation and expansion of pluripotent unrestricted somatic stem cells (USSCs) and mesenchymal cells (MSCs) from human cord blood as well their functional characterization were assessed. METHODS:USSC generation was initiated from fresh and cryopreserved cord blood (CB). Culture conditions and functional ass...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.07.011
更新日期：2006-11-01 00:00:00
abstract：OBJECTIVE:Our previous study has shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) gene/silica nanoparticles have a leukocytosis effect in normal dogs. Therefore, this study was conducted to determine whether treatment of canine GM-CSF gene/silica nanoparticles has preventive or therapeutic effects i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2008.04.002
更新日期：2008-09-01 00:00:00
abstract：:Pretreatment of mice with 5-fluorouracil (5-FU) depletes total marrow cellularity but leaves a residual population of cells with enhanced regenerative capability. Using the long-term Dexter liquid culture system, we studied the effects of 5-FU on murine marrow cells and their production of pluripotent stem cells (CFU-...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:T(4;11) MLL-AF4 acute leukemia is one of the most aggressive malignancies in infant and pediatric populations. Epidemiological and functional studies have highlighted the influence of an overstimulation of the immune system on leukemia development. This study aimed at assessing if the cell-of-origin of t(4;11) MLL-AF4...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2019.07.004
更新日期：2019-08-01 00:00:00
abstract：:The effects of chronic exposure to graded hypoxia (inspired PO2 = 146, 90, 78, 73 and 60 torr) on the development of hypoxia-induced hemoglobinemia and the rate of hemoglobin degradation in intact and acutely splenectomized rats were studied. Hemoglobin mass increased with hypoxia over the whole range studied. Hemoglo...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1980-03-01 00:00:00
abstract：OBJECTIVE:The aim of this study was to evaluate the effect of CF101, a synthetic agonist to the A3 adenosine receptor (A3AR), on the production of granulocyte colony-stimulating factor (G-CSF). The ability of CF101 to act as a myeloprotective agent in chemotherapy-treated mice was tested. METHODS:CF101 was administere...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(02)00962-1
更新日期：2002-12-01 00:00:00
abstract：OBJECTIVES:GPIIb integrin expression has been found on platelets and megakaryocytes, and more recently on immature hematopoietic progenitors. We set out to investigate expression of GPIIb in other hematopoietic cell lineages and, having detected it on mast cells, aimed to determine what possible role it might perform. ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2005.01.011
更新日期：2005-04-01 00:00:00
abstract：:This study is about enrichment of hemopoietic stem cell concentration in mouse bone marrow by use of a glass wool filtration technique. Maximum stem cell concentration was accomplished when filtration conditions were as follows: (1) support medium supplemented to 15% with fresh serum from syngeneic donors; (2) no incu...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1977-01-01 00:00:00
abstract：OBJECTIVE:Osteoblasts play an important role in regulating hematopoiesis in the bone marrow. Here we show that U2-OS, a widely used osteoblastic cell line derived from an osteosarcoma, has the capacity to support proliferation of human hematopoietic progenitor cells in vitro. In this study, U2-OS cells are characterize...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00127-2
更新日期：2000-04-01 00:00:00
abstract：:Granulocyte colony-stimulating factor (G-CSF) has proven effective in the prophylaxis of chemotherapy-induced neutropenia and as a mobilizer of peripheral blood progenitor cells. The longevity of G-CSF action is limited by its removal from the body by two mechanisms. The first is thought to be mediated via receptors (...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(99)00112-5
更新日期：1999-12-01 00:00:00
abstract：:Marked loss of colony stimulating activity was noted when the highly purified human urinary colony stimulating factor (CSFHU-5) dissolved in 0.1 M Tris-HCl buffer (pH 7) was passed through ethylene oxide sterilized Millipore filters. The addition of 0.5 mg/ml polyethylene glycol (PEG) or 10 mg/ml bovine serum albumin ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
abstract：:The aim of this work was to monitor the functional and phenotypic variations of natural killer (NK) cells in seven children with stage IV neuroblastoma (NB) treated with recurrent 5-day cycles of interleukin-2 (IL-2) at a dose of 18 x 10(6) IU/m2/d by continuous intravenous infusion. All patients who entered the study...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1995-12-01 00:00:00
abstract：:We investigated whether gene transfer into hematopoietic cells could be achieved by direct injection of retroviral vector supernatant into the bone marrow space of newborn sheep. Six sheep (5 weeks old) were injected bilaterally with either 1 mL of G1nBgSvNa8.1 vector supernatant (titer: 1 x 10(7)) in each hip (n = 5)...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/s0301-472x(00)00158-2
更新日期：2000-06-01 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：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:New nonmyeloablative strategies to improve acceptance of mismatched bone marrow (BM) may compensate for the inadequate supply of compatible grafts. Recently we proposed to facilitate engraftment of mismatched BM by selective depletion of activated donor-reactive host cells with cyclophosphamide (CY). Here we ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2004.07.017
更新日期：2004-11-01 00:00:00
abstract：OBJECTIVE:Graft-versus-leukemia effects of donor lymphocytes have been considered to be central to the therapeutic benefit of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for malignant diseases. Surprisingly, some patients who reject donor grafts following nonmyeloablative HCT have sustained rem...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2006.04.022
更新日期：2006-09-01 00:00:00
abstract：:Cells of the murine interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) factor-dependent line, FDC-P1, express the tyrosine kinase receptor, c-kit. The ligand for c-kit, steel factor (SLF), encoded by the steel (Sl) locus, is produced as both membrane-bound and soluble forms by fibroblast...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:Cell surface molecules aberrantly expressed or overexpressed by myeloid leukemic cells represent potential disease-specific therapeutic targets for antibodies. MUC1 is a polymorphic glycoprotein, the cleavage of which yields two unequal chains: a large extracellular α subunit containing a tandem repeat array bound in ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2018.12.002
更新日期：2019-02-01 00:00:00
abstract：OBJECTIVE:The primary objective of this study was to identify and clone the first nonmammalian thrombopoietin (TPO), chicken TPO, and its receptor c-Mpl for the purpose of characterizing their activities both in vitro and in vivo. MATERIALS AND METHODS:Chicken TPO was cloned using the methods of reverse transcriptase ...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：10.1016/j.exphem.2007.12.001
更新日期：2008-04-01 00:00:00
abstract：:Antisera from rabbits immunized with murine macrophage colony-stimulating factor (CSF-1) were evaluated for cross-reactivity with human urine CSF-1. One cross-reactive antiserum was used to purify CSF from human urine. The IgG fractions from normal rabbit serum and the anti-CSF serum were bound to cyanogen bromide-act...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1989-01-01 00:00:00
abstract：:Adherent cells from mouse bone marrow have been shown to promote the in vitro growth of the AVRij-1 tumour cell line. The experiments presented here suggest that the adherent cells involved in this phenomenon are the progeny of bone marrow derived fibroblastoid colony forming units. The latter were characterized by me...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1979-04-01 00:00:00
abstract：:A simple two-step procedure has been developed for the production of human urinary erythropoietin suitable for tissue culture use. Lyophilized human urinary protein was fractionated by phenyl-Sepharose chromatography, the erythropoietin binding in 2 M lithium chloride and being eluted by an ascending linear gradient t...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-09-01 00:00:00
abstract：:The effects of the inhibition of the cyclooxygenase and lipoxygenase metabolic pathways of arachidonic acid on the postirradiation recovery of hematopoietic functions in mice were investigated. Nordihydroguaiaretic acid (NDGA), an inhibitor of prostaglandin (PG) and leukotriene (LT) production, was given to animals in...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1993-01-01 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：:Radiation damage to femoral hemopoietic stroma in mice was measured 6 weeks after irradiation and reconstitution with syngeneic bone marrow by quantitation of fibroblastic progenitor cells (CFUF), and by assaying hemopoietic progenitors and CFUF numbers in regenerated subcutaneous femur implants. A dose-dependent effe...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1983-10-01 00:00:00
abstract：:Peripheral blood lymphocytes obtained at 24-30 months after birth from a male with X-linked severe combined immune deficiency maintained in a gnotobiotic environment were characterized by T and B cell surface markers. A high proportion (55-80 percent) of circulating lymphocytes bore surface IgM as detected by direct i...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1976-01-01 00:00:00
abstract：:Among 75 consecutive allogeneic bone marrow transplant recipients, 24 developed chronic graft-versus-host disease (GVHD), which was diagnosed from day 31 to day 368 after transplantation. Eight (33%) patients had more extensive chronic GVHD, and five patients died. The actuarial incidence of chronic GVHD was 48% at 40...
journal_title：Experimental hematology
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
