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Biomedical subjects

E Bruno

Publications and source records attributed to E Bruno.

At least 91 records · Page 5Linked to original sources

Effect of interleukin 6 on in vitro human megakaryocytopoiesis: its interaction with other cytokines.

The effects of human recombinant interleukin 6 (rIL-6) on in vitro human megakaryocytopoiesis were studied utilizing a serum-depleted culture system. Recombinant IL-6 increased both the number of megakaryocyte (MK) colonies formed and the number of cells comprising individual MK colonies cloned from normal low-density bone marrow (LDBM) cells. This stimulation of MK colony number and size was significantly less than that observed following the addition of recombinant interleukin 3 (rIL-3) or granulocyte-macrophage colony-stimulating factor (rGM-CSF). The addition of either rIL-3 or rGM-CSF, but not rIL-6 promoted MK colony formation by nonadherent, low-density, T-cell-depleted (NALDT-) marrow cells. Recombinant interleukin 1 alpha (rIL-1 alpha) and interleukin 4 (rIL-4) failed either to promote LDBM MK colony formation when added alone or to significantly increase rIL-6-promoted MK colony formation. MK colony formation promoted by optimal doses of rIL-6 was, in fact, significantly inhibited by rIL-1 alpha at all concentrations tested. Addition of either recombinant erythropoietin (rEpo) or purified thrombocytopoiesis-stimulating factor (TSF) to assays containing rIL-6 also resulted in significant inhibition of MK colony formation. The effect of suboptimal concentrations of rIL-6 on MK colony formation was additive to that of rIL-3 but not rGM-CSF. The addition of transforming growth factor beta (TGF-beta) resulted in a 58% reduction of rIL-6-promoted MK colony formation by LDBM. These data suggest that rIL-6 can promote in vitro megakaryocytopoiesis and that this effect can be either augmented or inhibited by the addition of several other cytokines. Recombinant IL-6, however, might affect the MK colony-forming unit (CFU-MK) by acting through bone marrow accessory cells or requiring the presence of as yet unidentified additional cytokines.

Biological Factors↗

Influence of T lymphocytes on hematopoiesis in a patient with T cell hypoplasia.

In this communication, we describe an unusual patient with a reported lifelong history of anemia. Investigation of the pathogenesis of this patient's bone marrow failure provided an interesting opportunity to determine the role of T cells in the regulation of human blood cell production. Phenotyping of the patient's mononuclear cells revealed severe T cell hypoplasia in both the peripheral blood and bone marrow. The patient's bone marrow was capable of producing 50-60% of the normal numbers of burst-forming units--erythroid (BFU-E) in the presence of optimal concentrations of erythropoietin, suggesting that marrow BFU-E formation is in part independent of T cells. Addition of small numbers of class I identical donor T cells enhanced BFU-E cloning efficiency to a level observed in normal controls. This enhancing effect was supplied by a T4+ (CD4) population of donor cells. The addition of donor T cells partially corrected the inability of patient marrow cells to produce megakaryocyte and mixed colonies. These studies suggest that prolonged T cell hypoplasia might deprive marrow progenitor and stem cells of a necessary enhancing effect that is required for sustained normal hematopoiesis. Such a T cell defect in rare instances may result in bone marrow failure.

Aged↗

Incidence of jaw lesions in 193 patients with multiple myeloma.

The incidence of alterations of the maxilla and mandible at radiographic screening was evaluated in 193 patients with multiple myeloma, both at the time of diagnosis and after the start of chemotherapy during the course of the disease. Although the study confirms that osteolytic lesions are more frequent in the mandible than in the maxilla, it showed that their incidence was lower than reported in the past. Furthermore, these lesions were mostly asymptomatic and were observed in patients who had extensive skeletal involvement, particularly at the skull level. These findings indicate that systematic radiologic monitoring of the stomatognathic system should be performed, particularly in patients with multiple myeloma at an advanced stage.

Adult↗

Effect of recombinant and purified human haematopoietic growth factors on in vitro colony formation by enriched populations of human megakaryocyte progenitor cells.

Nonadherent low density T-lymphocyte depleted (NALT-) marrow cells from normal donors were sorted on a Coulter Epics 753 Dye Laser System using Texas Red labelled My10 and phycoerythrin conjugated anti HLA-DR monoclonal antibodies in order to obtain enriched populations of colony forming unit-megakaryocyte (CFU-MK). The CFU-MK cloning efficiency (CE) was 1.1 +/- 0.5% for cells expressing both high densities of My10 and low densities of HLA-DR (My10 DR+). This procedure resulted in an 18-fold increase in CE over NALT- cells. The effect of purified or recombinant human haematopoietic growth factors including erythropoietin (Epo), thrombocytopoiesis stimulating factor (TSF), interleukin 1 alpha (IL-1 alpha), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF or CSF-1) and interleukin MK colony formation by My10 DR+ cells was determined utilizing a serum depleted assay system. Neither Epo, TSF, CSF-1, IL-1 alpha nor G-CSF alone augmented MK colony formation above baseline (2.5 +/- 0.8/5 x 10(3) My10 DR+ cells plated). In contrast, the addition of GM-CSF and IL-3 each increased both CFU-MK colony formation and the size of colonies with maximal stimulation occurring following the addition of 200 units/ml of IL-3 and 25 units/ml of GM-CSF. At maximal concentration, IL-3 had a greater ability to promote megakaryocyte colony formation than GM-CSF. The stimulatory effects of GM-CSF and IL-3 were also additive in that the effects of a combination of the two factors approximated the sum of colony formation in the presence of each factor alone. The CFU-MK appears, therefore, to express HPCA-1 and HLA-DR antigens. These studies also indicate that GM-CSF and IL-3 are important in vitro regulators of megakaryocytopoiesis, and that these growth factors are not dependent on the presence of large numbers of macrophages or T cells for their activity since the My10 DR+ cells are largely devoid of these accessory cells.

Colony-Forming Units Assay↗

Effect of recombinant and purified hematopoietic growth factors on human megakaryocyte colony formation.

The effect of a number of purified or recombinant hematopoietic growth factors, including recombinant erythropoietin (rEpo), thrombocytopoiesis stimulating factor (TSF), recombinant interleukin 1 alpha (rIL-1 alpha), recombinant granulocyte colony-stimulating factor (rG-CSF), macrophage colony-stimulating factor (CSF-1), recombinant interleukin 3 (rIL-3), and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), on megakaryocyte (MK) colony formation by normal human marrow cells in a serum-depleted assay system was determined. Neither rEpo, TSF, CSF-1, rIL-1 alpha, nor rG-CSF alone augmented MK colony formation. Both rGM-CSF and rIL-3 at optimal doses increased MK colony formation eightfold and tenfold, respectively, above baseline values. Addition of increasing amounts of either rGM-CSF or rIL-3 led to progressively greater numbers of MK colonies formed until plateau levels were reached. Both rGM-CSF and rIL-3 also led to a dose-related increase in the number of cells per MK colony formed in culture. These molecules were equivalent stimulators of MK colony formation when their effects at optimal concentrations were compared. The effects of rGM-CSF and rIL-3 were additive at suboptimal concentrations of rIL-3 in that colony formation by a combination of the two growth factors approximated the sum of colony formation by each growth factor alone. These data suggest that rGM-CSF and rIL-3 alone and in combination are important regulators of in vitro megakaryocytopoiesis at the progenitor cell level.

Cell Division↗

Effects of hematopoietic growth factors on in vitro colony formation by human megakaryocyte progenitor cells.

In order to study the effects of recombinant and purified hematopoietic growth factors on megakaryocyte (MK) progenitor cells (CFU-MK), enriched populations of human CFU-MK were isolated utilizing fluorescence activated cell sorting after labelling of cells with monoclonal antibodies exhibiting specificity to the My10 (HPCA-1) antigen and the major histocompatibility (MHC) class II (HLA-DR) locus. The CFU-MK cloning efficiency (CE) was 1.1 +/- 0.5% for cells expressing both high densities of My10 and low densities of HLA-DR (My10 DR+). This procedure resulted in an 18 fold increase in CE over NALT- cells. The effects of natural or recombinant human hematopoietic growth factors including erythropoietin (Epo), thrombocytopoiesis stimulating factor (TSF), interleukin 1 alpha (IL-1 alpha), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (CSF-1), and interleukin 3 (IL-3) on MK colony formation by My10 DR+ cells were determined utilizing a defined medium assay system. Neither Epo, TSF, CSF-1, IL-1 alpha nor G-CSF alone augmented MK colony formation above baseline (2.5 +/- 0.8 per 5 x 10(3) My10 DR+ cells plated). By contrast, the addition of GM-CSF and IL-3 each increased CFU-MK colony formation with maximal stimulation occurring following the addition of 200 units/ml of IL-3 and 100 units/ml of GM-CSF. At maximal concentration, IL-3 had a greater ability to promote megakaryocyte colony formation than GM-CSF.

Cell Division↗