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Biomedical subjects

S A Killmann

Publications and source records attributed to S A Killmann.

At least 37 records · Page 2Linked to original sources
PubMed1976

Cell proliferation and protein synthesis in human leukaemic myeloblasts after cytosine arabinoside therapy.

The effect of a single intravenous bolus injection of cytosine arabinoside (ARA-C) on the cytokinetics and 3H-leucine uptake of leukaemic myeloblasts in bone marrow and blood was studied at intervals up to 96 h after ARA-C in five patients with previously untreated acute myelogenous leukaemia. An early decrease in mitotic index and in 3H-thymidine labelling was observed in four of five patients and pretreatment values were reached again within the observation period. Changes suggesting synchronization were not observed. ARA-C induced a marked decrease in protein synthesis in the leukaemic myeloblasts as estimated from either a decrease in the 3H-leucine labelling index or the mean grain count of 3H-leucine labelled cells. It is suggested that ARA-C is incorporated also by cell which are not in S-phase and has a prolonged biochemical effect on the leukaemic cells.

Adult↗
PubMed1976

Nuclear DNA-polymerase estimation in human leukaemic myeloblasts.

A technique which detects the presence of DNA-polymerase in cell nuclei by measuring the incorporation of 3H-thymidine-5-triphosphate (3H-TTP) has been used to estimate the proportion of leukaemic myeloblasts which contains DNA-polymerase and DNA capable of acting as primer-template. In six cases of previously untreated acute myeloid leukaemia the 3H-TTP labelling index (3H-TTP LI) was much larger than the fraction in DNA synthesis. After a single 'flash' injection of cytosine arabinoside a pronounced decline was observed in the 3H-TTP LI, which can be explained by a direct inhibition of NDA-polymerase. No change was observed in the fraction of cells labelled with 3H-thymidine. A decrease in 3H-TTP LI was also observed after a single i.v. dose of methotrexate.

Bone Marrow↗
PubMed1976

Arabinosyl cytosine in chronic myeloid leukaemia: evidence for high cytokinetic sensitivity of myeloblasts.

The effect of a single and of repeated i.v. push dose(s) of Arabinosyl Cytosine (ARA-C) has been investigated in 9 chronic myeloid leukaemia (CML) patients in non-blastic phase. This was done by determining separately the relative compartment size, the mitotic index (IM), and the in vitro 3H-TdR labelling index (IL) of marrow and blood myeloblasts (MB) and promyelocytes plus myelocytes (PMC + MC), before and at intervals after the drug. After a single dose of ARA-C, the IL of marrow MB declines rapidly, and recovers thereafter, often with an overshoot at 15 h. After 2 to 4 doses of ARA-C, the IL of marrow and blood MB rises by a factor of 2 to 3, and is maintained at a plateau during further treatment. The behaviour of the IL of blood MB is not always the same as that of marrow MB. The IM of marrow MB does not rise proportionally to the IL, and sometimes is even found to be decreased. It is suggested that these kinetic perturbations reflect an accumulation of MB in S-phase where many but not all of them are trapped and sooner or later die off. With a few exceptions, ARA-C induces only milder kinetic perturbations in marrow and blood PMC+MC. The overall results of this study are in agreement with the generally accepted mechanism of action of ARA-C (S-phase specific effector agent), and with studies that indicate that the effect of ARA-C depends on the growth pattern and on the degree of maturation of the target cells. It is suggested that a proper evaluation of ARA-C on a cell population should take into account the existence of different cell pools, provided with different proliferative activity and potential, and with variable degrees of maturation.

Adult↗