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Biomedical subjects

H D Preisler

Publications and source records attributed to H D Preisler.

At least 253 records · Page 14Linked to original sources

Separation of leukemic cells into proliferative and quiescent subpopulations by centrifugal elutriation.

Centrifugal elutriation was used to separate human acute leukemia cells into proliferative and quiescent subpopulations. Ten bone marrow specimens and 5 peripheral blood specimens were subjected to centrifugal elutriations. From each patient, leukemic cell subpopulations were obtained for which the [3H]thymidine labeling index differed by 10- to 30-fold. In 6 of the marrow specimens and in 2 of the peripheral blood specimens, cell subpopulations were obtained for which the labeling index exceeded 20%. In 5 marrow specimens, subpopulations were obtained for which the labeling index exceeded 40%. Preliminary studies of the uptake of 1-beta-D-arabinofuranosylcytosine and 5-azacytidine failed to show any correlation between drug uptake and the proliferative characteristics of the leukemic subpopulations.

Azacitidine↗

Phospholipid membrane stabilization by dimethylsulfoxide and other inducers of Friend leukemic cell differentiation.

A large number of low molecular weight polar cryoprotective agents have recently been found to induce erythroid differentiation of Friend leukemic cells in vitro. The effect of these agents on membrane fluidity in phospholipid vesicles was studied by determining the solid-to-liquid crystalline phase transition using differential scanning calorimetry. Some of the inducing agents studies were found to raise the normal transition temperature (Tc) by a few degrees. All of these agents were found to produce a separate transition at a much higher temperature. Changes in the head group of the phospholipid, the pH, the presence of divalent cations, and the addition of other membrane-active compounds were found to significantly influence the inducing agent's effects on the Tc of phospholipid membranes. The ability of the different agents to produce a new transition at a high temperature was found to correlate well with their ability to induce Friend leukemic cell differentiation. The possible mechansims of action of the chemical inducers, and the significance of the observed membrane effects on differentiation and malignancy are discussed. It is concluded that inducing agents decrease the fluidity and stabilize phospholipid membranes, and that their effects in cell differentiation might be initiated by a similar change in the properties of cell membranes.

Animals↗

Membrane action of DMSO and other chemical inducers of Friend leukaemic cell differentiation.

DMSO and other cryoprotective agents produce a pronounced increase on the phase transition temperature of phospholipid membranes, indicating an increased stability. The effects of DMSO and other cryoprotective agents, divalent cations, and local anaesthetics on the transition temperature of phospholipid membranes seem to correlate with their effects on the differentiation of Friend leukaemic cells in vitro. These studies suggest that the induction of differentiation by cryoprotective agents may be the result of the interaction of these agents with cell membranes.

Anesthetics, Local↗

Clones of Friend leukemia cells: differences in karyotypes and responsiveness to inducers of differentiation.

Several clones of Friend leukemia cells have been established which differ in their chromosome composition. These cells also vary with regard to their responsiveness to DMSO, whereas all are responsive to butyric acid. Hence, there appears to be independent assortment of the ability of a cell line to respond to DMSO and to butyric acid, suggesting a different mechanism of action for each agent. Further, individual Friend cells possess the ability to simultaneously contain chloroacetate esterase and heme--two biochemical properties which have previously been believed to be mutually exclusive.

Acetamides↗

Inducers of Friend leukaemic cell differentiation in vitro--effects of in vivo administration.

Studies were conducted of the in vivo therapeutic potential of compounds which induce the differentiation of Friend leukaemia cells (FLC) in vitro. DBA2/J mice were inoculated with Friend leukaemia cells grown in tissue culture and at various times thereafter were treated with either N-methylacetamide, dimethylacetamide, or tetramethylurea. While survival was only occasionally prolonged, in every study these agents significantly inhibited leukaemia cell proliferation in the spleen and to a lesser extent in the marrow. These agents had no effect on the rate of proliferation of FLC growing subcutaneously nor on the proliferation of myeloid leukaemia in RFMS mice. These studies indicate that the administration of inducing agents to mice bearing Friend leukaemia can alter the proliferation characteristics of the leukaemia cells and hence suggest that these agents may have therapeutic potential.

Acetamides↗

Cryoprotective agents as inducers of erythroleukemic cell differentiation in vitro.

The ability of families of compounds with known and potential cryoprotective properties to induce the differentiation of Friend leukemia cells in vitro was studied. For each agent, both the proportion of differentiated cells in the culture and the total amount of heme/10(7) cells were determined. Within each family of compounds there was a direct correlation between a compound's cryoprotective ability, its ability to donate electron pairs for hydrogen bonding (basicity), and its ability to induce differentiation. While individual agents differed with respect to the proportion of cells which were induced to differentiate, the biology of the process of differentiation appeared to be similar, regardless of the agent used. A cell line which was unresponsive to DMSO was responsive to other inducers, suggesting that this DMSO-resistant cell line differed from its parent DMSO-responsive cell line either in its metabolism of the inducers or in the ability of the inducers to enter the cell. Alternatively, there may be more than one mechanism involved in the chemical induction of differentiation.

Acetamides↗

Differentiation of erythroleukemic cells in vitro: irreversible induction by dimethyl sulfoxide (DMSO).

The inclusion of DMSO in the media of suspension cultures of Friend erythroleukemia cells results in the erythroid differentiation of these cells. The studies reported here were directed towards answering two questions. (1) How long an exposure to DMSO is necessary to induce the differentiation of these cells; and (2) What is the fate of the differentiating cells when DMSO is removed from the medium. Exposure to DMSO for less than 24 hours failed to produce any detectable evidence of erythroid differentiation. On the other hand, culture in the presence of DMSO for 24 hours followed by culture in DMSO-free medium for four additional days produced a small but detectable increment in the proportion of benzidine positive cells in the culture. Once the differentiation of an individual cell was initiated, the process continued after removal of DMSO from the medium. The cell became progressively more differentiated as evidenced by increases in the intensity of benzidine staining as well as the rate of heme synthesis and heme content. However, when cells which had been induced to differentiate by DMSO were cultured in DMSO-free medium for more than 3--4 days, they became vacuolated and apparently died. This latter phenomenon, as well as the more rapid proliferation of the undifferentiated cells in the culture, accounts for the observation that when new cultures are established from cultures which have been grown in the presence of DMSO for several days, the culture which results ultimately contains only differentiated cells.

Benzidines↗

Granulocyte differentiation by Friend leukemia cells.

Friend leukemia cells growing in suspension culture are thought to represent a population of primitive erythroid cells which have undergone malignant transformation. We have found that when growing in vivo or in plasma clots in vitro, these suspension culture cells can exhibit morphologic and enzymatic properties which are characteristic of primitive granulocytic cells. The microenvironment in which the tumor cells grow plays a major role in determining the direction of differentiation of these leukemia cells. Hence it appears likely that the Friend cell is in fact a neoplastic pluripotent hematopoietic stem cell.

Animals↗

Differentiation of erythroleukemia cells in vitro: properties of chemical inducers.

Murine erythroleukemia cells growing in vitro can be induced to differentiate. The physical properties of chemical inducers has been defined and has permitted the recognition of a variety of potent inducers. The compounds can be linear, branched, or aromatic molecules. Some are methylated. All are low molecular weight basic compounds which are hydrophylic and are potent cryoprotective agents. The inducing effects of combinations of some agents are synergistic while others are additive. These observations will permit a rational search for inducing agents with increased potency and decreased toxicity.

Acetamides↗