Zymodeme conversion of isolates of Entamoeba histolytica.

A non-cloned and a cloned isolate of non-pathogenic (zymodeme I) Entamoeba histolytica derived from homosexual males were incubated in Diamonds' TP-S-1 medium in the presence of Crithidia for 52 d. A single addition of Escherichia coli irradiated at 1000 Gy rendered the culture axenic. Analysis of zymodeme patterns established that both isolates had transformed to zymodeme II. The re-establishment of cultures in the presence of microflora from the original cultures resulted in a return to zymodeme I, whereas incubation with microflora from an amoebic isolate exhibiting a zymodeme II pattern maintained the pathogenic pattern.

Effects of vascular endothelial growth factor on acute myelogenous leukemia blasts.

Vascular endothelial growth factor (VEGF) and its specific receptors are expressed by various malignant cells, including acute myelogenous leukemia (AML) blasts. In this study we performed a detailed characterization of VEGF effects on native human AML blasts derived from a large group of consecutive AML patients with high blast counts in peripheral blood. Exogenous VEGF had divergent effects on spontaneous proliferation and cytokine-dependent (GM-CSF, G-CSF, IL-3) proliferation. Increased, decreased, or unaltered proliferation was observed in the presence of VEGF for various patients, and the VEGF effect differed even in the same patient depending on which exogenous cytokine being present together with VEGF. Similarly, increased, decreased or unaltered interleukin-1beta (IL-1beta) and IL-6 secretion was detected when VEGF was added, and for certain patients the effect of VEGF differed between IL-1beta and IL-6. Exogenous VEGF could also modulate proliferation and differentiation of clonogenic AML progenitors. Constitutive AML blast secretion of VEGF was detected for 40% of patients. Leptin, Flt3-L, IL-4, IL-10, and IL-13 had divergent effects on VEGF release by AML blasts. These results suggest that VEGF can modulate AML blast functions in vivo for a subset of patients. Furthermore, the detection of VEGF in peripheral blood stem cell (PBSC) autografts suggests that VEGF may influence the proliferation and possibly also the survival of contaminating AML cells in PBSC autografts. We conclude that VEGF may influence the functional characteristics of AML cells. Our results suggest that VEGF is important in leukemic hematopoiesis, and the detection of VEGF in PBSC autografts indicates that VEGF may influence the functional phenotype of contaminating AML cells in these grafts.

Effects of hematopoietic growth factors on interleukin 6 secretion by blast cells derived from acute myelogenous leukemia patients.

Interleukin 6 (IL6) secretion by blast cells derived from peripheral blood of patients with acute myelogenous leukemia (AML) was characterized. IL6 secretion showed a wide variation both when AML blasts were cultured in medium alone and in the presence of exogenous cytokines. The level of IL6 secretion was significantly correlated to secretion of other cytokines (IL1 alpha, IL1 beta, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha). IL1 beta, granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor and stem cell factor increased IL6 secretion, whereas IL4 caused decreased IL6 secretion together with increased release of IL1 receptor antagonist.

Human T lymphocyte activation in the presence of acute myelogenous leukaemia blasts: studies of allostimulated interferon-gamma secretion.

Normal peripheral blood mononuclear cells (PBMC responders) were cultured together with non-irradiated allogeneic PBMC (more than 95% leukaemia blasts) derived from patients with acute leukaemia (referred to as leukaemic PBMC stimulators). Cytokine secretion was determined as cytokine concentrations in supernatants. Both normal PBMC and enriched CD4+ and CD8+ T cells responded to allostimulation with interferon (IFN gamma) secretion. Interleukin-I (IL-1) receptor antagonist and IL-2-neutralizing antibodies decreased IFN gamma secretion. Exogenous IL-1 beta, IL-2 and IL-7 increased allostimulated IFN gamma secretion, whereas decreased levels were seen in the presence of IL-6, IL-10 and granulocyte-colony-stimulating factor (G-CSF). During allorecognition IFN gamma-neutralizing antibodies decreased acute myelogenous leukaemia (AML) blast secretion of G-CSF. We conclude that (i) both CD4+ and CD8+ T cells show allostimulated cytokine secretion in response to allogeneic stimulator cells containing a dominating population of native, cytokine-secreting leukaemia blasts, and (ii) IFN gamma released during this response can modulate the function of allogeneic AML blasts.