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Biomedical subjects

G W Bazill

Publications and source records attributed to G W Bazill.

At least 19 recordsLinked to original sources
PubMed1990

Role of endocytosis in the action of ether lipids on WEHI-3B, HL60, and FDCP-mix A4 cells.

We investigated the effect of a number of platelet activating factor antagonists on cell killing by 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphoryl choline (ET-18-OCH3). Of six platelet activating factor antagonists tested, four were found to protect WEHI-3B leukemic cells against cell death induced by ET-18-OCH3. Certain other compounds, not platelet activating factor antagonists, had similar protective effects. The protective compounds were all lipophilic weak bases. We describe experiments that indicate that these compounds protect by inhibition of endocytic uptake of ET-18-OCH3. Sensitive cells showed rapid endocytic uptake, whereas in resistant cells, uptake was slow. Uptake of ET-18-OCH3 could be suppressed by inhibitors of endocytosis such as chloroquine, monensin, and vinblastine. We conclude that one of the principal determinants of sensitivity or resistance to ether lipids may be the rate at which cells take them up by endocytosis.

Animals↗
PubMed1985

Stimulation of hexose uptake by haemopoietic cell growth factor occurs in WEHI-3B myelomonocytic leukaemia cells: a possible mechanism for loss of growth control.

WEHI-3B myelomonocytic leukaemia cells secrete a haemopoietic cell growth factor (HCGF) which facilitates the proliferation and development of multipotential stem cells and committed progenitor cells. Several cloned, nonleukaemic cell lines (FDC-P cells) are absolutely dependent on HCGF and die in the absence of it. In these cell lines, factor dependence is associated with the ability of HCGF to increase glucose uptake, thereby controlling glycolytic flux and intracellular ATP levels. We have now investigated the effects of HCGF on glucose uptake in WEHI-3B cells. At 20 degrees C 2-deoxyglucose uptake could be stimulated by the addition of HCGF to the extracellular medium. L-glucose uptake was markedly lower than 2-deoxyglucose uptake and did not respond to the addition of HCGF. At 37 degrees C no HCGF stimulation of 2-deoxyglucose uptake was found. However, at this temperature HCGF release from WEHI-3B cells was markedly higher than at 20 degrees C. Our experiments indicate that HCGF stimulates the glucose transport system in both WEHI-3 cells and FDC-P cells. The similarities between the WEHI-3B cell and FDC-P2 cell polypeptide phenotype were investigated using two-dimensional isoelectric focussing/poly-acrylamide gel electrophoresis. This revealed a high degree of correlation between the two cell types in their protein constituents, indicating a close relationship between the normal and leukaemic cells. These similarities between WEHI-3B cells and FDC-P2 cells are considered and their relevance to haemopoiesis and leukaemogenesis is discussed.

Animals↗
PubMed1984

Haemopoietic cell growth factor mediates cell survival via its action on glucose transport.

A number of haematopoietic precursor cell lines have been established which exhibit an absolute dependence on haematopoietic cell growth factor (HCGF) which is secreted by WEHI-3 myelomonocytic leukaemia cells. In the presence of HCGF, ATP levels are maintained in these factor-dependent cells (FDC-P cells); in the absence of HCGF, intracellular ATP levels undergo a steady depletion. The cell death that follows this ATP depletion can be prevented by supplying exogenous ATP suggesting that HCGF maintains these cells via its effects on energy metabolism. We have investigated the effect of HCGF on FDC-P cells further and found that: (i) HCGF markedly and rapidly increases lactate production; (ii) high extracellular glucose or glycolytic intermediate concentrations can maintain FDC-P cell viability to some extent whilst stimulating lactate production; (iii) the uptake of 2-deoxyglucose by FDC-P2 cells is stimulated by HCGF in a dose-dependent fashion. This uptake is inhibited by cytochalasin B; (iv) HCGF does not stimulate L-glucose uptake by FDC-P cells. These results suggest that HCGF acts to maintain FDC-P cells via its action on glucose transport. The significance of these results to haemopoiesis and leukaemogenesis is discussed.

Adenosine Triphosphate↗
PubMed1984

Membrane-mediated responses to 12-O-tetradecanoylphorbol-13-acetate in human skin fibroblasts.

The effects on primary human skin fibroblasts of the structurally unrelated tumour promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin B were compared with those of epidermal growth factor and the non-promoting derivative 4-O-methyl TPA by means of two-dimensional gel electrophoresis. Both TPA and teleocidin B caused a marked increase in the synthesis of two polypeptides of molecular weights 44 kilodaltons (P44) and 55 kilodaltons (P55). P55 was complexed in cell lysates by antiactin antibody and was shown to be a component of the cytoskeleton. P44 migrated very near to actin, but it was shown not to be a variant form of actin. No such specific increase in polypeptide synthesis was observed following treatment with either epidermal growth factor or 4-O-methyl TPA. TPA inhibited the beta-adrenergic hormone response in the same human skin fibroblasts.

Carcinogens↗
PubMed1983

Characterization and partial purification of a haemopoietic cell growth factor in WEHI-3 cell conditioned medium.

A myelomonocytic leukaemia cell line, WEHI-3, releases into its growth medium factors which stimulate the development of pluripotential cells, granulocyte/macrophage progenitor cells, megakaryocytic and erythroid progenitor cells. Also present is a factor which is essential for the continued proliferation in vitro of a variety of haemopoietic precursor cell lines of a granulocytic nature (FDC-P cells). Characterization of this growth factor has demonstrated that it is a glycoprotein of apparent Mr 25 800, in which the carbohydrate component appears to be important for activity. After several purification steps, there is an increase in specific activity of approx. 4000-fold over the starting material. At each stage of purification, the factor necessary for the proliferation of FDC-P cells 'co-purifies' with activity which stimulates the proliferation and development of normal multipotential haemopoietic cells as well as megakaryocytic, erythroid and granulocytic committed progenitor cells. This 'co-purification' occurs to the extent that the multilineage stimulating factor and the FDC-P growth factor can be eluted from the same region of sodium dodecyl sulphate/polyacrylamide gels. Thus, evidence so far, using different starting methods and purification regimes, suggests that one molecule may have multiple activities on diverse cell types.

Animals↗
PubMed1981

The effects of fibronectin on the migration of human foreskin fibroblasts and Syrian hamster melanoma cells into three-dimensional gels of native collagen fibres.

The effects of fibronectin on the migration of human skin fibroblasts and Syrian hamster melanoma cells into 3-dimensional gels of native collagen fibres have been examined. Cell migration into the 3-dimensional gel was measured by plating cells on the gel surface and then determining the percentage of cells within the gel at various times thereafter by direct microscopic examination. We find that fibronectin bound to collagen inhibits the migration of human skin fibroblasts and stimulates the migration of melanoma cells into the gel matrix. Fibronectin had no apparent effect on cell adhesion to the collagen gels, proliferation or morphology under the conditions studied.

Animals↗
PubMed1981

The effects of fibronectin on the adhesion and migration of chinese hamster ovary cells on collagen substrata.

Data are presented indicating that the adhesion of Chinese hamster ovary cells (CHO) to films of denatured type I collagen occurs by a fibronectin-dependent mechanism, whereas the adhesion of these cells to 3-dimensional gels of native type I collagen fibres may occur by either a rapid, fibronectin-dependent mechanism or by a slower, fibronectin-independent mechanism, whereas the adhesion of these cells to 3-dimensional gels of native type I collagen fibres may occur by either a rapid, fibronectin-dependent mechanism or by a slower, fibronectin-independent mechanism. Data are also presented indicating that fibronectin promotes the migration of CHO cells on native type I collagen fibres.

Animals↗
PubMed1976

Extracellular cyclic AMP-phosphodiesterase accelerates differentiation in Dictyostelium discoideum.

Extracellular cyclic AMP-phosphodiesterase accelerates the development of aggregation competence in Dictyostelium discoideum when present during the preaggregation stage. The effect on development appears to depend only on hydrolysis of extracellular cyclic AMP and not on other properties of the phosphodiesterase molecule. Extracellular cyclic AMP-phosphodiesterase, as a promoter of differentiation, acts mainly throughout the first half of interphase. Our evidence supports the proposal that cyclic AMP oscillations control the rate and possibly the initiation of development. Since extracellular cyclic AMP-phosphodiesterase acts from the beginning of interphase cyclic AMP oscillations may also occur from early interphase, at least in the presence of this enzyme. This would imply that the cyclic AMP oscillator is a determinant, but not a product, of the developmental programme.

3',5'-Cyclic-AMP Phosphodiesterases↗