1982 |
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Hume, D. A.; Gordon, S. Regulation of bone-marrow macrophage proliferation. (Journal Article) In: Advances in experimental medicine and biology, vol. 155, pp. 261–266, 1982, ISSN: 00652598. @article{hume_regulation_1982, | |
1981 |
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Hume, D. A.; Wrogemann, K.; Ferber, E.; Kolbuch-Braddon, M. E.; Taylor, R. M.; Fischer, H.; Weidemann, M. J. Concanavalin A-induced chemiluminescence in rat thymus lymphocytes. Its origin and role in mitogenesis (Journal Article) In: Biochemical Journal, vol. 198, no. 3, pp. 661–667, 1981, ISSN: 02646021. @article{hume_concanavalin_1981, | |
1979 |
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Hume, D. A.; Weidemann, M. J.; Ferber, E. Preferential inhibition by quercetin of mitogen-stimulated thymocyte glucose transport (Journal Article) In: Journal of the National Cancer Institute, vol. 62, no. 5, pp. 1243–1249, 1979, ISSN: 00278874. @article{hume_preferential_1979,The ATPase Inhibitor quercetin, which inhibits tumor glycolysis, was shown to be a glucose transport inhibitor like the chemically related compound phloretin. Rat thymocyte glucose transport stimulated by the mitogens concanavalin A or ionophore A 23187 was more sensitive than unstimulated transport to quercetin Inhibition. The partial inhibition of Na+-, K+-ATPase activity by quercetin observed in tumor cells was confirmed In thymocyte plasma membranes. The specific Na+-, K+-ATPase inhibitor ouabain did not mimic the effect of quercetin on mitogen-stimulated glucose transport but did reduce the effectiveness of concanavalin A as a stimulator of mitochondrial pyruvate oxidation. The results support the idea that glycolytic flux and the activity of plasma membrane ATPase are related but suggest that glucose transport, rather than the Na+-, K+-ATPase, is the rate-limiting reaction in lymphocytes. © 1979 Oxford University Press. All rights reserved. | |
Hume, D. A.; Thornton, M. R.; Weidemann, M. J.; Speth, V. Rapid alterations in cellular morphology and plasma membrane structure induced in rat thymocytes by mitogenic stimuli (Journal Article) In: Journal of Cellular Physiology, vol. 101, no. 3, pp. 523–528, 1979, ISSN: 00219541. @article{hume_rapid_1979,Under conditions where a maximum stimulation of 3‐O‐methyl‐glucose transport is observed, three thymocyte mitogens (concanavalin A, ionophore A23187 and hydrogen peroxide) cause cell rounding and a decrease in the density of intra‐membrane particles on the plasma membrane. The early effects of mitogens on the thymocyte plasma membrane are similar to those of osmotic shock. Copyright © 1979 Wiley‐Liss, Inc. | |
Hume, D. A.; Weidemann, M. J. Role and regulation of glucose metabolism in proliferating cells (Journal Article) In: Journal of the National Cancer Institute, vol. 62, no. 1, pp. 3–8, 1979, ISSN: 00278874. @article{hume_role_1979,The history of the interest in glucose metabolism in malignantly transformed cells dates back to the pioneering studies of Warburg. These studies led to the statement, in 1956: “The era in which the fermentation of cancer cells, or its importance, could be debated is over and no-one today can doubt that we understand the origin of cancer cells if we know how their large fermentation originates, or to express it more fully, if we know how the damaged respiration and the excessive fermentation of cancer cells originates.” Even at this time, doubts were expressed about the respiratory deficiency of tumor cells. © 1979 Oxford University Press. All rights reserved. | |
1978 |
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Hume, D. A.; Hansen, K.; Weidemann, M. J.; Ferber, E. Cytochalasin B inhibits lymphocyte transformation through its effects on glucose transport (Journal Article) In: Nature, vol. 272, no. 5651, pp. 359, 1978, ISSN: 00280836. @article{hume_cytochalasin_1978,THE effects of the fungal metabolite, cytochalasin B, on lymphocyte transformation induced by mitogenic plant Jectins have been much studied 1-7. Results have generally been interpreted in terms of the known effects of cytochalasin B on the microfilaments of the cellular cytoskeleton. A potential site of action which has been largely ignored lies in the inhibitory effects of cytochalasin B on metabolite transport. Cytochalasin B is a potent, competitive inhibitor of erythrocyte glucose transport8, and we have shown that it also inhibits thymocyte glucose transport, and that concanavalin A-stimulated glucose transport is more sensitive to this inhibition9. Glucose transport has been shown to be rate-limiting for thymocyte glycolysis10. Also, glucose has been found to be essential for mitogen-stimulated DNA synthesis in lymphocytes11, and we show here that cytochalasin B can exert its inhibitory effect on DNA synthesis by inhibiting glucose transport. © 1978 Nature Publishing Group. | |
Hume, D. A.; Weidemann, M. J. On the stimulation of rat thymocyte 3‐0‐methyl‐glucose transport by mitogenic stimuli (Journal Article) In: Journal of Cellular Physiology, vol. 96, no. 3, pp. 303–308, 1978, ISSN: 00219541. @article{hume_stimulation_1978,Pretreatment of rat thymus lymphocytes with N‐ethyl‐maleimide prevents the stimulation of 3‐0‐methyl‐glucose transport by concanavalin A or ionophore A23187 but does not affect the ability of concanavalin A to induce a rapid increase in cellular Ca2+ uptake. N‐ethyl‐maleimide added after concanavalin A amplifies rather than prevents the subsequent stimulation of 3‐0‐methyl‐glucose transport. Incubation of thymocytes with concanavalin A produces a decrease of 43% in the apparent Ki for phloretin, a competitive inhibitor of 3‐0‐methyl‐glucose transport, without affecting the apparent Km for the substrate. Similarly, very low concentrations of cytochalasin B inhibit concanavalin A‐stimulated glucose transport preferentially, without markedly affecting the unstimulated transport rates. The similarity between concanavalin A‐stimulated 3‐0‐methyl‐glucose transport in thymocytes and insulin‐stimulated glucose transport in adipose tissue, with particular emphasis on the effects of the modifying agents described in this paper, is discussed. Copyright © 1978 Wiley‐Liss, Inc. | |
Hume, D. A.; Weidemann, M. J. Effect of NH4 and Ca2+ on gluconeogenesis from lactate by isolated rat hepatocytes (Journal Article) In: Hormone and Metabolic Research, vol. 10, no. 5, pp. 449–450, 1978, ISSN: 00185043. @article{hume_effect_1978, | |
Hume, D. A.; Vijayakumar, E. K.; Schweinberger, F.; Russell, L. M.; Weidemann, M. J. The role of calcium ions in the regulation of rat thymocyte pyruvate oxidation by mitogens (Journal Article) In: Biochemical Journal, vol. 174, no. 3, pp. 711–716, 1978, ISSN: 02646021. @article{hume_role_1978,Calcium concentrations in the nanomolar range cause a specific stimulation of the oxidation of pyruvate by isolated mitochondria from rat thymus that is sufficient to account precisely for the stimulation of pyruvate oxidation observed when rat thymocytes are incubated with the mitogens concanavalin A or ionophore A23187. Higher concentrations of Ca2+ (more than 50 nM) inhibit the oxidation of NAD+ linked substrates by rat thymus mitochondria without affecting the oxidation of succinate or ascorbate + NNN'N'-tetramethyl-p-phenylenediamine. The addition of Ni2+ or Co2+ (2 mM) to rat thymocytes prevents the response to concanavalin A at the level of pyruvate oxidation without affecting the stimulation of glycolysis induced by this mitogen. In contrast, the complete metabolic response to the ionophore A23187 is abolished by these lesions. Ni2+ and Co2+ interfere with the ability of the ionophore to transport Ca2+ across the plasma membrane. Concanavalin A, but not ionophore A23187, increases the respiratory inhibition induced by Ni2+ and Co2+. These results support the view that mitogens stimulate lymphocyte pyruvate oxidation through an increase in cellular Ca2+ uptake. | |
Hume, D. A.; Radik, J. L.; Ferber, E.; Weidemann, M. J. Aerobic glycolysis and lymphocyte transformation (Journal Article) In: Biochemical Journal, vol. 174, no. 3, pp. 703–709, 1978, ISSN: 02646021. @article{hume_aerobic_1978,The role of enhanced aerobic glycolysis in the transformation of rat thymocytes by concanavalin A has been investigated. Concanavalin A addition doubled [U-14C]glucose uptake by rat thymocytes over 3h and caused an equivalent increased incorporation into protein, lipids and RNA. A disproportionately large percentage of the extra glucose taken up was converted into lactate, but concanavalin A also caused a specific increase in pyruvate oxidation, leading to an increase in the percentage contribution of glucose to the respiratory fuel. Acetoacetate metabolism, which was not affected by concanavalin A, strongly suppressed pyruvate oxidation in the presence of [U-14C]glucose, but did not prevent the concanavalin A-induced stimulation of this process. Glucose uptake was not affected by acetoacetate in the presence or absence of concanavalin A, but in each case acetoacetate increased the percentage of glucose uptake accounted for by lactate production. [3H]Thymidine incorporation into DNA in concanavalin A-treated thymocyte cultures was sensitive to the glucose concentration in the medium in a biphasic manner. Very low concentrations of glucose (25 μM) stimulated DNA synthesis half-maximally, but maximum [3H]thymidine incorporation was observed only when the glucose concentration was raised to 1mM. Lactate addition did not alter the sensitivity of [3H]-thymidine uptake to glucose, but inosine blocked the effect of added glucose and strongly inhibited DNA synthesis. It is suggested that the major function of enhanced aerobic glycolysis in transforming lymphocytes is to maintain higher steady-state amounts of glycolytic intermediates to act as precursors for macromolecule synthesis. | |
1977 |
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Yasmeen, D.; Laird, A. J.; Hume, D. A.; Weidemann, M. J. In: BBA - General Subjects, vol. 500, no. 1, pp. 89–102, 1977, ISSN: 03044165. @article{yasmeen_activation_1977,1. 1. A method is described for the determination of the rate of 3-O-methyl-D-[U-14C]glucose transport into rat thymuse lymphocytes. Some kinetic properties of this facilitated diffusion transport process have been determined, both before and after stimulation with concanavalin A, and the effects of Ca2+, puromycin and cycloheximide have been investigated. 2. 2. The initial rate of 3-O-methyl-D-glucose transport into rat thymus lymphocytes is significantly stimulated within 5 min of concanavalin A addition and is approximately doubled after 30 min. 3. 3. Maximun stimulation of sugar transport by concanavalin A requires at least 30 μM free Ca2+ in the extracellular medium, and is sigmoidally dependent on free Ca2+ up to this concentration; in contrast, the unstimulated transport process appears to be Ca2+-independent. 4. 4. In both the presence and absence of concanavalin A, 3-O-methyl-D-glucose transport is a saturable process with a Km of approx. 4.5 mM; the stimulation by concanavalin A can be attributed solely to a two-fold increase in the value of V, as the Km value remains essentially unaltered. 5. 5. Concanavalin A alters the temperature-dependence of 3-O-methyl-D-glucose transport so that the activation energy at 37°C is substantially increased. 6. 6. The enhancement of sugar transport by concanavalin A is independent of de novo protein synthesis, as it is not prevented by cycloheximide, which blocks the incorporation of [14C]leucine into trichloroacetic acid-precipitation protein. 7. 7. On the other hand, the stimulation of 3-0-methyl-D-glucose transport by concanavalin A, as well as the enhanced utilization of D-glucose, is suppressed by puromycin, which also blocks [14C]leucine incorporation into protein. This suppression appears to be due to a hitherto unreported inhibitory effect of puromycin on glucose transport. © 1977. | |
1976 |
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hume, D. A.; weidemann, M. J. Hormonal regulation of gluconeogenesis in isolated rat hepatocytes: An undergraduate experiment (Journal Article) In: Biochemical Education, vol. 4, no. 1, pp. 13–14, 1976, ISSN: 03074412. @article{hume_hormonal_1976, | |
1982 |
|
Regulation of bone-marrow macrophage proliferation. (Journal Article) In: Advances in experimental medicine and biology, vol. 155, pp. 261–266, 1982, ISSN: 00652598. | |
1981 |
|
Concanavalin A-induced chemiluminescence in rat thymus lymphocytes. Its origin and role in mitogenesis (Journal Article) In: Biochemical Journal, vol. 198, no. 3, pp. 661–667, 1981, ISSN: 02646021. | |
1979 |
|
Preferential inhibition by quercetin of mitogen-stimulated thymocyte glucose transport (Journal Article) In: Journal of the National Cancer Institute, vol. 62, no. 5, pp. 1243–1249, 1979, ISSN: 00278874. | |
Rapid alterations in cellular morphology and plasma membrane structure induced in rat thymocytes by mitogenic stimuli (Journal Article) In: Journal of Cellular Physiology, vol. 101, no. 3, pp. 523–528, 1979, ISSN: 00219541. | |
Role and regulation of glucose metabolism in proliferating cells (Journal Article) In: Journal of the National Cancer Institute, vol. 62, no. 1, pp. 3–8, 1979, ISSN: 00278874. | |
1978 |
|
Cytochalasin B inhibits lymphocyte transformation through its effects on glucose transport (Journal Article) In: Nature, vol. 272, no. 5651, pp. 359, 1978, ISSN: 00280836. | |
On the stimulation of rat thymocyte 3‐0‐methyl‐glucose transport by mitogenic stimuli (Journal Article) In: Journal of Cellular Physiology, vol. 96, no. 3, pp. 303–308, 1978, ISSN: 00219541. | |
Effect of NH4 and Ca2+ on gluconeogenesis from lactate by isolated rat hepatocytes (Journal Article) In: Hormone and Metabolic Research, vol. 10, no. 5, pp. 449–450, 1978, ISSN: 00185043. | |
The role of calcium ions in the regulation of rat thymocyte pyruvate oxidation by mitogens (Journal Article) In: Biochemical Journal, vol. 174, no. 3, pp. 711–716, 1978, ISSN: 02646021. | |
Aerobic glycolysis and lymphocyte transformation (Journal Article) In: Biochemical Journal, vol. 174, no. 3, pp. 703–709, 1978, ISSN: 02646021. | |
1977 |
|
In: BBA - General Subjects, vol. 500, no. 1, pp. 89–102, 1977, ISSN: 03044165. | |
1976 |
|
Hormonal regulation of gluconeogenesis in isolated rat hepatocytes: An undergraduate experiment (Journal Article) In: Biochemical Education, vol. 4, no. 1, pp. 13–14, 1976, ISSN: 03074412. | |