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Biomedical subjects

H D Preisler

Publications and source records attributed to H D Preisler.

At least 199 records · Page 11Linked to original sources
PubMed1983

Separation of leukemic and nonleukemic subpopulations of spleen cells from mice with myeloid leukemia.

Centrifugal elutriation has been adapted for use in obtaining highly enriched populations of leukemic myeloblasts and normal appearing lymphocytes from RFM/UN mice with myeloid leukemia. The myeloblasts were functionally intact as evidenced by their high cloning efficiency in vitro and malignant potential in vivo. The lymphocyte-enriched subpopulation had a low thymidine labeling index, and cloning efficiency in vitro, and was only marginally malignant in vivo indicating minimal contamination by leukemic myeloblasts. In preterminal leukemic mice the proportion of cycling leukemic cells remained high with a labeling index of 30-50%.

Animals↗
PubMed1983

Effects of S-phase-specific agents on granulocyte-macrophage and erythroid progenitor cells obtained from normal individuals and from patients with chronic myelogenous leukemia.

The effects of three S-phase-specific agents, [3H]thymidine, hydroxyurea, and 1-beta-D-arabinofuranosylcytosine, on granulocyte-macrophage colony-forming units (CFU-C) and erythroid progenitor cells (erythroid burst-forming units) (BFU-E) from the bone marrow or peripheral blood obtained from 23 normal individuals and 12 patients with chronic myelogenous leukemia were investigated. CFU-C, regardless of their source, showed comparable degrees of sensitivity to each of the S-phase-specific agents, with perhaps a slightly greater level of sensitivity to [3H]thymidine. In contrast, the sensitivities of chronic myelogenous leukemia and normal marrow BFU-E to the 3 agents were quite different, with essentially all BFU-E being killed by [3H]thymidine, 50 to 70% being killed by 1-beta-D-arabinofuranosylcytosine, and only 15 to 20% being killed by hydroxyurea. BFU-E present in normal peripheral blood were insensitive to [3H]thymidine or hydroxyurea but were sensitive to 1-beta-D-arabinofuranosylcytosine. These studies demonstrated similarities between the CFU-C and BFU-E of CML patients and the CFU-C and BFU-E present in normal bone marrow. On the other hand, the sensitivities of normal peripheral blood progenitor cells to "S-phase-specific" agents differed from that of CML progenitor cells or the progenitor cells present in normal bone marrow. Additionally, these studies have demonstrated the limitations inherent in suicide techniques as methods for estimating the cell cycle characteristics of clonogenic cells.

Adult↗
PubMed1983

In vitro drug sensitivity studies of CFUc in chronic myelocytic leukemia: I. Suicide indices and busulfan sensitivity determinations during the chronic phase.

Serial clonogenicity studies employing an agar CFUc culture assay are being performed on cells from CML patients to determine if clonal growth, 3HTdR suicide indices (SI) and in vitro busulfan sensitivity are of prognostic significance in predicting blastic transformation. Initial studies performed on specimens obtained from 20 chronic phase patients were directed at determining whether blood and marrow cells differed in growth pattern, SI, and busulfan sensitivity and whether the cells giving rise to clusters differed from those forming colonies. In comparing marrow to blood cells, there was a correlation between the two with respect to the number of colonies produced and the sensitivity of the clonogenic cells to busulfan. By contrast the SI of blood and marrow clonogenic cells were not correlated. In both blood and marrow, colony forming cells had a higher SI and were more sensitive to busulfan than were cluster forming cells.

Adolescent↗
PubMed1983

In vitro busulfan sensitivity of granulocyte-macrophage and erythroid progenitor cells in patients with chronic myelogenous leukemia.

As part of an attempt to develop and test potential in vitro measures of busulfan sensitivity of patients with chronic myelogenous leukemia (CML) in chronic phase, we compared the busulfan sensitivity of granulocyte-macrophage (CFU-C) and early erythroid progenitor cells (BFU-E) in the bone marrow (BM) and peripheral blood (PB) specimens obtained from ten normal individuals and from 13 patients with CML. CFU-C in the normal BM and in both the BM and PB of CML patients showed comparable degrees of sensitivity to busulfan. BFU-E, regardless of source, showed similar degrees of sensitivity to busulfan, except that normal PB BFU-E were less sensitive than were PB BFU-E of CML patients. CFU-C were more resistant to busulfan than BFU-E. The sensitivity of BM CFU-C and BFU-E of CML patients reflected that of PB CFU-C and BFU-E, respectively, and the sensitivity of BM and PB CFU-C of CML patients reflected that of BM and PB BFU-E, respectively. When the CML patients were ranked according to sensitivity to busulfan, the order of sensitivity of BM CFU-C and BFU-E paralleled that of PB CFU-C and BFU-E, respectively, and the order of sensitivity of BM and PB CFU-C paralleled that of BM and PB BFU-E, respectively. These results suggest that any of the four progenitor cells, BM CFU-C, BM BFU-E, PB CFU-C, and PB BFU-E, can be used to investigate the relative busulfan sensitivity of the hemopoietic progenitor cells of different CML patients.

Busulfan↗
PubMed1983

In vitro drug sensitivity studies of colony-forming units in culture in chronic myelocytic leukemia: lack of specificity between chronic-phase patients and normal donors.

Attempts to eliminate Philadelphia chromosome-positive cells during the treatment of chronic-phase chronic myelocytic leukemia (CML) have been largely unsuccessful, probably due to the lack of specificity of drugs which have been used. In an attempt to develop more specific therapy for CML, an assay for colony-forming units in culture was used to test for differences between CML blood and normal marrow progenitor cells. The following drugs, which have activity in acute nonlymphocytic leukemia, were tested over a range of concentrations achievable in vivo: Adriamycin; 1-beta-D-arabinofuranosylcytosine; aclacinomycin; m(4-acridinylamino)-3-methoxyphenyl methansulfamide; methylglyoxalbis(guanylhydrazone), and 5-azacytidine. [3H]Thymidine suicide indices were also determined. Normal marrow colony-forming units in culture tended to be more sensitive to all the drugs which were tested, although not of statistical significance. There was no difference in the suicide index between CML and normal colony-forming units in culture. It is concluded that the drugs which were tested are not likely to selectively kill CML progenitor cells while permitting normal hematopoietic elements to survive.

Antineoplastic Agents↗
PubMed1982

The treatment of acute myelocytic leukemia in patients 30 years of age and younger.

The treatment of acute myelocytic leukemia in childhood and young adults has lagged behind that for acute lymphocytic leukemia. The studies described here were directed towards evaluating the role of intensive chemotherapy in the treatment of this illness. Intensive remission induction therapy combining cytosine arabinoside with an anthracycline antibiotic produced a complete remission rate comparable to that achieved in acute lymphocytic leukemia (45 of 49 patients or 92%). Intensive consolidation chemotherapy produced a median duration of complete remission of 160 weeks with 40% of patients projected to be in remission at 4 years. By contrast, the median duration of remission for patients treated with moderate consolidation/maintenance therapy was 23 weeks with only 10% of patients in remission at 4 years. These studies demonstrate that intensive chemotherapy can be administered to pediatric patients and young adults and that this approach to therapy produces a high remission rate with a 3 year median duration of remission.

Adolescent↗
PubMed1982

The effects of exposure to cytosine arabinoside upon the proliferation of leukemia colony forming units in vitro.

The sensitivity of leukemic colony forming units to exposure to cytosine arabinoside in vitro was measured for both acute myelocytic leukemia cells and for chronic myelocytic leukemia cells. There was significant variability in the sensitivity of the leukemic cells of different patients. By simultaneous measurement of the sensitivity of leukemic clonogenic cells to 3H-TdR one can distinguish between metabolic and cell cycle kinetic resistance to cytosine arabinoside.

Bone Marrow↗
PubMed1982

Treatment failure in AML.

Emphasis on the reasons for successful therapy in the treatment of acute myelocytic leukemia (AML) has generally obscured the problem of treatment failures. This paper discusses failures in remission induction and relapse of leukemia. The contribution of patient-related factors as well as the heterogeneous characteristics of the leukemic cells are considered.

Antineoplastic Agents↗
PubMed1982

A pilot study of high-dose 1-beta-D-arabinofuranosylcytosine for acute leukemia and refractory lymphoma: clinical response and pharmacology.

1-beta-D-Arabinofuranosylcytosine (ara-C), 2 or 3 g/sq m, was administered as a 1-hr i.v. infusion every 12 hr for 10 or 12 doses to patients with acute leukemia and refractory lymphoma. Four of seven patients with relapsed or refractory acute myelocytic leukemia and two of four patients with previously untreated acute myelocytic leukemia achieved complete remission. Of five treatment failures, two patients had leukemia which was clearly resistant to high-dose ara-C, and three patients died of infections or hemorrhagic complications during periods of pancytopenia. Three patients with acute myelocytic leukemia in remission received high-dose ara-C as consolidation therapy following previous courses of intensive, multiagent consolidation chemotherapy. Two of these three patients had prolonged thrombocytopenia following high-dose ara-C. Five patients with refractory acute lymphocytic leukemia were treated. Three patients achieved partial remission, and two patients had drug-resistant disease. Complete or partial disappearance of measurable disease parameters was seen in three of three patients with refractory lymphoma. Response was seen in five of five patients with meningeal leukemia, including complete response in one patient with extensive meningeal infiltration. Toxicity of this regimen was generally moderate and limited to pancytopenia and mild nausea. Patients who had received prior multiagent consolidation chemotherapy appeared to be at greater risk for hematopoietic toxicity. Patients who had received prior cranial irradiation or intrathecal chemotherapy appeared to be at greater risk for neurological toxicity. Plasma levels of ara-C immediately after completion of the infusion were 17.96 +/- 8.02 (S.D.) and 35.0 +/- 2.8 micrograms/ml for doses of 2 and 3 g/sq m, respectively. From 160 to 720 min following completion of the infusion, the plasma levels of drug were comparable to steady-state levels achieved with a continuous infusion of ara-C at 100 mg/sq m over 24 hr. A high degree of penetration into the central nervous system was demonstrated. High-dose ara-C has substantial activity against leukemic and lymphomatous cell populations, including cell populations resistant to conventional doses of the drug, and is an effective treatment modality for patients with these diseases. The high degree of penetration into the central nervous system suggests that this drug regimen may be useful as consolidation therapy for patients at high risk for central nervous system disease.

Adolescent↗
PubMed1982

Macrophage differentiation of human precursor B-cell line by phorbol ester and colony-stimulating factor.

A human round cell line, KLM-2, is considered to be precursor B-cell by immunologic surface marker analysis and histochemical studies. The effect of 12-O-tetradecanoyl phorbol-13-acetate (TPA) and/or colony-stimulating factor (CSF) on KLM-2 cells was investigated. KLM-2 cells became adherent to the bottom of the flask on day 2 after liquid culture with TPA, and the number of macrophage-like adherent cells (mAC) with pseudopodia showed a TPA dose-dependent increase to the peak level on day 3 or 4. The mAC had a phagocytic activity. The suspending cells were positive for alpha-naphthyl acetate esterase (NAE) up to about 50% in culture with TPA. A TPA concentration of 100 ng/ml was optimal to provide a maximum number of mAC and NAE-positive suspending cells. Particularly, such effects of TPA on KLM-2 cells were markedly accelerated in the presence of CSF. These findings indicate macrophage differentiation of KLM-2 cells in the presence of TPA and CSF. KLM-2 cells may be a bipotential stem cell line differentiating into B-cell and monocyte-macrophage lineages.

B-Lymphocytes↗
PubMed1982

Effects of partially thiolated polycytidylic acid and liposomes on in vitro colony-forming cells of leukemic mice.

Partially thiolated polycytidylic acid (MPC), an antileukemic agent, when administered to leukemic RF/UN mice inhibited the clonogenicity of bone marrow progenitor cells in a time- and dose-dependent manner. The effect of a single dose of MPC disappeared within 40 hr due to the rapid degradation of this compound in mice. When MPC was encapsulated in liposomes before injection, its activity at 19 hr after inoculation was similar to that of free MPC. The inhibitory effect of this liposome-MPC complex, however, persisted for at least 40 hr, indicating that the MPC was protected from hydrolysis by the nucleases present in blood. Drug-free liposomes increased the number of clonogenic progenitor cells, whereas a mixture of plain liposomes and MPC decreased the number of clonogenic cells to a greater extent than did MPC alone or MPC within liposomes. A possible explantation for these observations is that the liposomes per se altered the clearance function of the reticuloendothelial system and completed with MPC for uptake by the reticuloendothelial system cells, thereby resulting in increased plasma levels of MPC which in turn resulted in greater killing of the target cells.

Animals↗
PubMed1982

Comparison of agar and methylcellulose culture methods for human erythroid colony formation.

An agar culture method to permit human erythroid colony growth was described and was compared with the standard methylcellulose culture method. Although the cloning efficiency was greater and the colonies were larger in size in methylcellulose, the relative number of colonies was indistinguishable in the two culture systems after short-term exposure to cytosine arabinoside, adriamycin, tritiated thymidine, or busulfan. Thus, the agar culture system permits the growth of erythroid progenitor cells, which are at the same stage of differentiation as erythroid progenitor cells which can grow in methylcellulose. Since cultures in which agar is used as the semisolid matrix can be fixed and counted at the convenience of the investigator, the cloning of erythroid progenitor cells in agar will greatly facilitate investigation of the proliferative properties and drug sensitivity of erythroid progenitor cells obtained from normal individuals as well as from patients with hematologic neoplasms.

Agar↗
PubMed1981

Prevention of infection and bleeding in leukemic patients receiving intensive remission maintenance therapy.

Leukemic patients were treated with intensive chemotherapy to reduce the number of leukemic cells remaining after complete remission was induced. This therapy resulted in periods of severe granulocytopenia and thrombocytopenia. Considering 13 patients who did not receive antibacterial prophylaxis, documented infection was quite common including four episodes of bacteremia and three urinary tract infections. By contrast, patients who received co-trimoxazole as antibacterial prophylaxis experienced one half as many febrile episodes and no serious infections. Prophylactic co-trimoxazole is beneficial for patients with marrow remission in this study. Similar benefit in patients with leukemic marrows remains to be established. All patients received prophylactic platelet transfusion three times a week when their platelet counts were less than 20,000/microliter. There were no episodes of bleeding other than petechiae.

Adult↗