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Biomedical subjects

H D Preisler

Publications and source records attributed to H D Preisler.

At least 163 records · Page 9Linked to original sources
PubMed1985

Treatment of dysmyelopoietic/leukemic syndromes with myelofibrosis and megakaryocytic hyperplasia with large doses of cytosine arabinoside.

Eight patients with inaspiratable bone marrows due to significant degrees of fibrosis were treated with high dose cytosine arabinoside because of either documented or suspected coexistent acute leukemia. The peripheral blood counts returned to normal in 7 patients. Remissions were short lived and bone marrow abnormalities persisted suggesting that consolidation therapy should be administered to these patients as soon as their peripheral blood counts are normalized.

Acute Disease↗
PubMed1985

Comparison of autoradiography and DNA histograms in assessing S-phase cells from patients with myeloid leukemias.

The studies reported here were designed to determine whether DNA histogram analysis provided the same estimate for the percentage of cells in S-phase as does 3H-TdR labeling index (LI). For DNA histogram analysis high resolution flow cytometry was employed together with 3 different computer based methods for histogram analysis. When tissue culture cells were employed there was a good correlation (r = 0.89) between the estimates for the percentage of cells in S-phase by the LI and DNA histogram techniques. In contrast, when 1138 bone marrow or peripheral blood specimens obtained from leukemic patients were studied the correlation was poor. For example when 243 pretherapy bone marrow aspirate cells were studied by both methods the correlation was only 0.46. A direct comparison of the clinical relevance of the two methods for measuring S-phase cells when high dose cytosine arabinoside therapy was used to treat patients demonstrated that only LI measurements provided clinically useful information. In conclusion, DNA histogram analysis provides an inaccurate estimate of the percentage of cells in S-phase.

Animals↗
PubMed1985

Changes in the characteristics of the bone marrow during therapy for acute non-lymphocytic leukemia: relationship to response to remission induction therapy.

The bone marrows of patients with acute non-lymphocytic leukemia being treated with 'high dose' cytosine arabinoside remission induction therapy were sampled prior to the initiation of chemotherapy, after 6 days of therapy and again 7 days after the conclusion of therapy. These studies demonstrated that the marrows of patients who would enter remission (CR patients) contained less leukemic cells prior to therapy than patients who would fail to enter remission because of persistent leukemia (resistant disease, or RD patients). A comparison of the day 6 and 7-day post-therapy marrows with the pretherapy marrow demonstrated that while the % reduction in leukemic cells was greater for CR patients than for RD patients, the absolute reduction in leukemic cell mass was the same for both groups. While there was no relationship between the percentage of cells in S phase and the pretherapy leukemic cell mass, the greater the pretherapy leukemic cell mass the greater the likelihood that the leukemic cells would be resistant to the metabolic effects of cytosine arabinoside in vitro.

Aged↗
PubMed1985

Relationship between leukemic cell retention of cytosine arabinoside triphosphate and the duration of remission in patients with acute non-lymphocytic leukemia.

Bone marrow cells were obtained from patients with acute non-lymphocytic leukemia immediately prior to the administration of cytosine arabinoside/anthracycline antibiotic remission induction therapy. The ability of the leukemic cells to take up and phosphorylate cytosine arabinoside (araC) and to retain cytosine arabinoside triphosphate (araCTP) was measured and compared to the outcome of remission induction therapy and the duration of remission. While the outcome of remission induction therapy was unrelated to cellular metabolism of araC, the duration of remission was highly correlated with araCTP retention. A comparison of the remission durations of patients treated on successive chemotherapeutic protocols suggests that the benefits of intensive remission consolidation therapy may be limited to patients whose leukemic cell retention of araCTP is low and that aggressive consolidation chemotherapy may reduce the prognostic significance of araCTP retention.

Acute Disease↗
PubMed1985

Peer review.

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Peer Review↗
PubMed1985

Double labeling of human leukemic cells using 3H-cytarabine and monoclonal antibody against bromodeoxyuridine.

A new technique using immunofluorescence and autoradiography is described, in which the DNA of cells in S phase are labeled with two different probes. This method makes it possible to study the relationship between DNA synthesis and the uptake and/or incorporation of chemotherapeutic agents into normal or neoplastic cells. An example is provided in which the incorporation of 3H-cytarabine into DNA is demonstrated to occur only in cells which were synthesizing DNA during exposure to 3H-cytarabine. Other radioactively labeled probes can be used as well.

Antibodies, Monoclonal↗
PubMed1985

Double labeling of S-phase murine cells with bromodeoxyuridine and a second DNA-specific probe.

A rapid method has been developed which combines immunofluorescence and autoradiography and permits the double labeling of DNA. P388 murine leukemic cells were incubated with bromodeoxyuridine and tritiated thymidine simultaneously. After fixation, the sample was first processed with a monoclonal antibody to bromodeoxyuridine (RPMB I) so that any cell in S-phase was brightly fluorescent (RPMB technique). Next, tritiated thymidine grains were developed by autoradiography, and the result demonstrated fluorescence as well as black grains in each S-phase cell. P388 cells sensitive (P388S) and resistant (P388R) to 1-beta-D-arabinofuranosylcytosine (ara-C) were incubated with bromodeoxyuridine and [3H]ara-C simultaneously. Processing by autoradiography and RPMB techniques revealed that all S-phase cells in the P388S sample demonstrated vivid "double labeling," whereas P388R cells only revealed bright green fluorescence in S-phase cells, but no grains, confirming a lack of ara-C incorporation into the DNA by this line. Finally, a computerized digital analysis system attached to a microphotometer was used to quantitate fluorescence and grains per cell, and the data demonstrated that the number of [3H]ara-C grains in each P388S cell was inversely proportional to the degree of fluorescence in that cell, indicating that DNA synthesis was inhibited by ara-C. In conclusion, a simple, easy-to-use double-labeling method has been introduced which will be useful to a wide variety of researchers, because this technique together with the digital analysis system offers the possibility of measuring drug sensitivities in individual cells.

Animals↗
PubMed1984

Relationship between plasma adriamycin levels and the outcome of remission induction therapy for acute nonlymphocytic leukemia.

Plasma adriamycin and adriamycinol levels were measured in 45 patients with acute nonlymphocytic leukemia 3 h after the drug was administered. A wide range of levels as found. Plasma levels increased after the administration of each of the three daily doses of the drug. High plasma levels were associated with both death during remission induction therapy and, for patients who entered remission, long remissions.

Acute Disease↗
PubMed1984

Potential limitations of in vitro clonogenic drug sensitivity assays.

P388 murine leukemic cells lines which were resistant (P388R) or sensitive (P388S) to adriamycin (adr) were used to evaluate the potential utility of in vitro clonogenic assays for detecting and quantitating the number of adr-resistant cells present in a cell mixture. The progeny of P388S cells that had been exposed for 1 h or continuously to adr were as sensitive to the drug as the original P388S cells. Serial passages in the presence of adr, however, resulted in the selection of adr-resistant cells, but even these cells varied in their level of resistance. When P388S and P388R cells were mixed together and exposed to adr, the clonogenic assay consistently overestimated the proportion of P388S cells present. These studies demonstrate some of the inherent limitations of clonogenic drug sensitivity assays and may provide an explanation for the reported discrepancies between in vitro drug sensitivity and clinical responses to therapy reported in the literature.

Animals↗
PubMed1984

Uptake of adriamycin by human leukemic cells as measured by flow cytometry.

Leukemic cells were obtained from 12 patients with acute nonlymphocytic leukemia and 2 patients with acute lymphocytic leukemia. The specimens were incubated with a range of concentrations of adriamycin (Adr) for different periods of time and then analyzed by flow cytometry. For incubations of up to 5 h, only cells exposed to 5 or more micrograms of Adr ml-1 became fluorescent while cells incubated with 1 microgram ml-1 for 24 h became fluorescent. Fluorescence decreased when the cells were washed and further decreased when the cells were incubated in Adr-free media. The cells from different patients exhibited a wide range of Adr uptakes and retentions. Simultaneous analysis of right angle light scatter and fluorescence intensity demonstrated that there may be subpopulations of cells whose Adr uptake and/or retention differ from the weighted mean population values. With this method rare cells which fail to take up Adr can be recognized.

Bone Marrow↗