Although Cyclosporin A (CyA) is an effective immunosuppressive agent following liver transplantat... more Although Cyclosporin A (CyA) is an effective immunosuppressive agent following liver transplantation and is associated with increased survival, its use in some cases may be limited by nephrotoxicity. The long term, consequences have not been reported. We have ...
The application of mechanical loads to bone cells in vitro has been found to generate variable re... more The application of mechanical loads to bone cells in vitro has been found to generate variable responses, which may in part be due to the source of the cell used and the characteristics of the strain applied. The aim of this study was to establish a system for applying well-defined physiological levels of mechanical strain to a well-defined population of human osteoblast-like cells. Human bone-derived cells obtained from the greater trochanter of the femur during total hip arthroplasty for osteoarthritis were cultured in the presence of 10 nmol/L dexamethasone and 100 mumol/L L-ascorbate-2-phosphate. Replicates of cells from each patient were loaded on separate occasions using controlled cyclical strains of 4000 microstrain (mu epsilon) or less. Strain gauges recorded reliable, reproducible strains between 1000 and 6000 mu epsilon. To establish reproducibility, sequential explant cultures derived from two patients were studied. A consistent increase (p < 0.05) in proliferation between replicates and explants derived from one patient subjected to 1600 mu epsilon on separate occasions was observed. Cells derived from sequential explants of the second patient showed no consistent increase in proliferation between replicates and explants. Three of six patients showed a significant increase (p < 0.05) in PGE2 production after 5 h in response to stretch (4000 mu epsilon) in all replicates on separate occasions, whereas, in the other three populations of cells, no increase in PGE2 was measured in any of the replicates. These results show that the application of highly controlled strains causes a significant effect on human bone cells, but only in a proportion of subjects. The response is consistent between sequential explants derived from the same patient. The implications of this study are that human osteoblast-like cells do respond to physiological strain in vitro, although some cells are more strain sensitive than others.
ABSTRACT Hematopoietic stem cell transplantation is used for treatment of lymphoma. In an attempt... more ABSTRACT Hematopoietic stem cell transplantation is used for treatment of lymphoma. In an attempt to design an efficacious and safe prehematopoietic stem cell transplantation conditioning regimen, we investigated the cytotoxicity of the combination of busulfan (B), melphalan (M), and gemcitabine (G) in lymphoma cell lines in the absence or presence of drugs that induce epigenetic changes. Cells were exposed to drugs individually or in combination and analyzed by the MTT proliferation assay, flow cytometry, and Western blotting. We used ∼IC(10) drug concentrations (57 μM B, 1 μM M and 0.02 μM G), which individually did not have major effects on cell proliferation. Their combination resulted in 50% inhibition of proliferation. Reduction to almost half concentration (20 μM B, 0.7 μM M and 0.01 μM G) did not have significant effects, but addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (0.6 μM) to this combination resulted in a marked (∼65%) growth inhibition. The cytotoxicity of these combinations correlates with the activation of the ataxia telangiectasia mutated-CHK2 pathway, phosphorylation of KRAB-associated protein-1, epigenetic changes such as methylation and acetylation of histone 3, and activation of apoptosis. The relevance of epigenetic changes is further shown by the induction of DNA methyltransferases in tumor cells with low constitutive levels of DNMT3A and DNMT3B. The addition of 5-aza-2'-deoxycytidine to (BMG+suberoylanilide hydroxamic acid) further enhances cell killing. Overall, BMG combinations are synergistically cytotoxic to lymphoma cells. Epigenetic changes induced by suberoylanilide hydroxamic acid and 5-aza-2'-deoxycytidine further enhance the cytotoxicity. This study provides a rationale for an ongoing clinical trial in our institution using (BMG+suberoylanilide hydroxamic acid) as pre-hematopoietic stem cell transplantation conditioning for lymphoma.
Australian Journal of Experimental Agriculture, 2008
ABSTRACT The authors overview integrated pest management (IPM) in grain crops in north-eastern Au... more ABSTRACT The authors overview integrated pest management (IPM) in grain crops in north-eastern Australia, which is defined as the area north of latitude 32°S. Major grain crops in this region include the coarse grains (winter and summer cereals), oilseeds and pulses. IPM in these systems is complicated by the diversity of crops, pests, market requirements and cropping environments. In general, the pulse crops are at greatest risk, followed by oilseeds and then by cereal grains. Insecticides remain a key grain pest management tool in north-eastern Australia. IPM in grain crops has benefited considerably through the increased adoption of new, more selective insecticides and biopesticides for many caterpillar pests, in particular Helicoverpa spp. and loopers, and the identification of pest-crop scenarios where spraying is unnecessary (e.g. for most Creontiades spp. populations in soybeans). This has favoured the conservation of natural enemies in north-eastern Australia grain crops, and has arguably assisted in the management of silverleaf whitefly in soybeans in coastal Queensland. However, control of sucking pests and podborers such as Maruca vitrata remains a major challenge for IPM in summer pulses. Because these crops have very low pest-damage tolerances and thresholds, intervention with disruptive insecticides is frequently required, particularly during podfill. The threat posed by silverleaf whitefly demands ongoing multi-pest IPM research, development and extension as this pest can flare under favourable seasonal conditions, especially where disruptive insecticides are used injudiciously. The strong links between researchers and industry have facilitated the adoption of IPM practices in north-eastern Australia and augers well for future pest challenges and for the development and promotion of new and improved IPM tactics.
Wilson, L., Mensah, R., Dillon, M., Wade, MR, Scholz, B., Murray, D., Heimoana, V. and Lloyd, R. ... more Wilson, L., Mensah, R., Dillon, M., Wade, MR, Scholz, B., Murray, D., Heimoana, V. and Lloyd, R. (2002) Impact of insecticides and miticides on predators in cotton. Australian Cotton Research, 1 : 1-2. ... Wilson, L. Mensah, R. Dillon, M. Wade, MR Scholz, B. Murray, D. ...
Although Cyclosporin A (CyA) is an effective immunosuppressive agent following liver transplantat... more Although Cyclosporin A (CyA) is an effective immunosuppressive agent following liver transplantation and is associated with increased survival, its use in some cases may be limited by nephrotoxicity. The long term, consequences have not been reported. We have ...
The application of mechanical loads to bone cells in vitro has been found to generate variable re... more The application of mechanical loads to bone cells in vitro has been found to generate variable responses, which may in part be due to the source of the cell used and the characteristics of the strain applied. The aim of this study was to establish a system for applying well-defined physiological levels of mechanical strain to a well-defined population of human osteoblast-like cells. Human bone-derived cells obtained from the greater trochanter of the femur during total hip arthroplasty for osteoarthritis were cultured in the presence of 10 nmol/L dexamethasone and 100 mumol/L L-ascorbate-2-phosphate. Replicates of cells from each patient were loaded on separate occasions using controlled cyclical strains of 4000 microstrain (mu epsilon) or less. Strain gauges recorded reliable, reproducible strains between 1000 and 6000 mu epsilon. To establish reproducibility, sequential explant cultures derived from two patients were studied. A consistent increase (p < 0.05) in proliferation between replicates and explants derived from one patient subjected to 1600 mu epsilon on separate occasions was observed. Cells derived from sequential explants of the second patient showed no consistent increase in proliferation between replicates and explants. Three of six patients showed a significant increase (p < 0.05) in PGE2 production after 5 h in response to stretch (4000 mu epsilon) in all replicates on separate occasions, whereas, in the other three populations of cells, no increase in PGE2 was measured in any of the replicates. These results show that the application of highly controlled strains causes a significant effect on human bone cells, but only in a proportion of subjects. The response is consistent between sequential explants derived from the same patient. The implications of this study are that human osteoblast-like cells do respond to physiological strain in vitro, although some cells are more strain sensitive than others.
ABSTRACT Hematopoietic stem cell transplantation is used for treatment of lymphoma. In an attempt... more ABSTRACT Hematopoietic stem cell transplantation is used for treatment of lymphoma. In an attempt to design an efficacious and safe prehematopoietic stem cell transplantation conditioning regimen, we investigated the cytotoxicity of the combination of busulfan (B), melphalan (M), and gemcitabine (G) in lymphoma cell lines in the absence or presence of drugs that induce epigenetic changes. Cells were exposed to drugs individually or in combination and analyzed by the MTT proliferation assay, flow cytometry, and Western blotting. We used ∼IC(10) drug concentrations (57 μM B, 1 μM M and 0.02 μM G), which individually did not have major effects on cell proliferation. Their combination resulted in 50% inhibition of proliferation. Reduction to almost half concentration (20 μM B, 0.7 μM M and 0.01 μM G) did not have significant effects, but addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (0.6 μM) to this combination resulted in a marked (∼65%) growth inhibition. The cytotoxicity of these combinations correlates with the activation of the ataxia telangiectasia mutated-CHK2 pathway, phosphorylation of KRAB-associated protein-1, epigenetic changes such as methylation and acetylation of histone 3, and activation of apoptosis. The relevance of epigenetic changes is further shown by the induction of DNA methyltransferases in tumor cells with low constitutive levels of DNMT3A and DNMT3B. The addition of 5-aza-2'-deoxycytidine to (BMG+suberoylanilide hydroxamic acid) further enhances cell killing. Overall, BMG combinations are synergistically cytotoxic to lymphoma cells. Epigenetic changes induced by suberoylanilide hydroxamic acid and 5-aza-2'-deoxycytidine further enhance the cytotoxicity. This study provides a rationale for an ongoing clinical trial in our institution using (BMG+suberoylanilide hydroxamic acid) as pre-hematopoietic stem cell transplantation conditioning for lymphoma.
Australian Journal of Experimental Agriculture, 2008
ABSTRACT The authors overview integrated pest management (IPM) in grain crops in north-eastern Au... more ABSTRACT The authors overview integrated pest management (IPM) in grain crops in north-eastern Australia, which is defined as the area north of latitude 32°S. Major grain crops in this region include the coarse grains (winter and summer cereals), oilseeds and pulses. IPM in these systems is complicated by the diversity of crops, pests, market requirements and cropping environments. In general, the pulse crops are at greatest risk, followed by oilseeds and then by cereal grains. Insecticides remain a key grain pest management tool in north-eastern Australia. IPM in grain crops has benefited considerably through the increased adoption of new, more selective insecticides and biopesticides for many caterpillar pests, in particular Helicoverpa spp. and loopers, and the identification of pest-crop scenarios where spraying is unnecessary (e.g. for most Creontiades spp. populations in soybeans). This has favoured the conservation of natural enemies in north-eastern Australia grain crops, and has arguably assisted in the management of silverleaf whitefly in soybeans in coastal Queensland. However, control of sucking pests and podborers such as Maruca vitrata remains a major challenge for IPM in summer pulses. Because these crops have very low pest-damage tolerances and thresholds, intervention with disruptive insecticides is frequently required, particularly during podfill. The threat posed by silverleaf whitefly demands ongoing multi-pest IPM research, development and extension as this pest can flare under favourable seasonal conditions, especially where disruptive insecticides are used injudiciously. The strong links between researchers and industry have facilitated the adoption of IPM practices in north-eastern Australia and augers well for future pest challenges and for the development and promotion of new and improved IPM tactics.
Wilson, L., Mensah, R., Dillon, M., Wade, MR, Scholz, B., Murray, D., Heimoana, V. and Lloyd, R. ... more Wilson, L., Mensah, R., Dillon, M., Wade, MR, Scholz, B., Murray, D., Heimoana, V. and Lloyd, R. (2002) Impact of insecticides and miticides on predators in cotton. Australian Cotton Research, 1 : 1-2. ... Wilson, L. Mensah, R. Dillon, M. Wade, MR Scholz, B. Murray, D. ...
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Papers by D. Murray