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Biomedical subjects

M Beran

Publications and source records attributed to M Beran.

At least 181 records · Page 10Linked to original sources
PubMed1985

A characteristic pattern of leukemic cell differentiation without cytoreduction during remission induction in acute promyelocytic leukemia.

While differentiation of leukemic cells in vitro is well established, the role of differentiation in vivo is not defined and is generally attributed to differentiation inducers. In five patients with acute promyelocytic leukemia (APL) an unusual pattern of a slow and progressive decrease of immature blasts with a concomitant increase in mature cellular elements was observed following intensive combination chemotherapy. All patients eventually achieved complete remission, four of them without an intermediate phase of marrow hypoplasia. This morphologic pattern of response suggests that leukemic cellular differentiation rather than cytotoxicity was one mechanism involved in remission induction. Cytogenetic studies of remission revealed disappearance of the cytogenetic marker, the balanced translocation between the long arms of chromosomes 15 and 17. This remission induction process appears to be due to the cellular biologic characteristic rather than the therapy used as it occurs in a substantial proportion of patients with APL. It should be considered for optimal diagnostic and therapeutic decisions.

Acute Disease↗
PubMed1983

Busulfan kinetics.

Busulfan kinetics were studied in patients with chronic myelocytic leukemia after oral doses of 2, 4, and 6 mg. The plasma concentration-time data could be fitted to a zero-order absorption one-compartment open model. The elimination rate constant averaged 0.27 +/- 0.05 hr-1 (SD). The plasma AUC was linearly related to the dose. The lag time for the start of absorption, the time absorption ends, and the absorption rate constant showed some interindividual variations. About 1% of busulfan is excreted unchanged in urine over 24 hr.

Adult↗
PubMed1983

Human natural killer cells can inhibit clonogenic growth of fresh leukemic cells.

The effect of allogenic human natural killer (NK) cells on fresh leukemic cells from three patients was investigated. The low levels of leukemic target cell lysis in the conventional 51Cr-release assay contrasted with a pronounced inhibitory effect on the colony growth of the clonogeneic leukemic target cells (L-CFC). The ability of allogeneic lymphocytes to inhibit L-CFC increased if they were pretreated with interferon (IFN), which also increased their NK activity, monitored in parallel cytotoxicity assay, against K562. Furthermore, cell separation procedures, based on differences in density among nonadherent lymphocytes, revealed that only NK cell containing fractions were inhibitory. We have also compared the susceptibility to NK-mediated L-CFC inhibition of IFN pretreated leukemic target cells with that of nontreated target cells. As in the case of NK lysis in general, this pretreatment of target cells abolished the presumably NK-mediated L-CFC inhibition. In conclusion, these data provide the first indication that NK cells can inhibit the in vitro growth of fresh clonogenic leukemia cells from patients with nonlymphocytic leukemia. The identity of NK cells as effector is strongly suggested by Percoll separation and responsiveness to interferon; the final proof awaits more sophisticated purification of these cells.

Clone Cells↗
PubMed1982

Human leukocyte interferon-mediated granulopoietic differentiation arrest and its abrogation by lithium carbonate.

Interferon has been shown to inhibit erythropoietic and granulopoietic differentiation. Since lithium carbonate (Li) elevates granulocyte levels in a variety of neutropenic disorders, we investigated the effect of Li on human leukocyte interferon (HLIF)-mediated inhibition of granulopoietic differentiation. Using an agar culture technique for cloning granulocyte-macrophage progenitor cells (GM-CFC), we demonstrated that Li blocks HLIF-induced granulopoietic differentiation arrest in a dose-dependent manner. Results of removal of T lymphocytes from marrow cells suggest that this Li effect is not mediated through marrow T lymphocytes.

Cell Differentiation↗
PubMed1982

DR antigen positive monocyte-macrophages control granulocyte-macrophage colony-stimulating activity and burst promoting activity elaboration in man.

To investigate the mechanisms that modulate granulocyte-macrophage colony-stimulating activity (GM-CSA) and burst promoting activity (BPA) elaboration, we studied human peripheral blood-derived monocyte-macrophage (M0) and T-lymphocyte (TL) interaction. Coincubation of live M0 with autologous TL at a 1:3 ratio in the presence of 1% phytohemagglutinin synergistically increased GM-CSA (6 of 6 experiments) and BPA (4 of 6 experiments) (P less than 0.002). Prior treatment of M0 with cycloheximide or actinomycin D significantly (P less than 0.002) diminished this M0's capacity to collaborate with TL. Mitomycin C treatment did not. Live M0 also enhanced TL-derived GM-CSA (P less than 0.002) and BPA (P less than 0.001). This enhancement was again compromised by prior cycloheximide or actinomycin D treatment, but not by mitomycin C treatment. Further experiments in which we blocked DR antigen on M0 membrane with monoclonal anti-DR antibodies suggested that M0 required their membrane DR antigen to collaborate with TL in elaborating GM-CSA and BPA.

Bone Marrow Cells↗
PubMed1982

Possible mechanisms of immunotherapy action in acute nonlymphocytic leukemia: macrophage production of colony-stimulating activity.

Earlier studies show that immunotherapy (IT) improves prognosis in acute nonlymphatic leukemia (ANLL), and that ANLL cells probably have tumor-associated antigens, for autologous lymphocytes can react to them. Also, IT seems to immunize against allogeneic ANLL cells, but there is no cross-immunity to autologous ones. Moreover, patients immunized against their ANLL cells have no better prognosis than patients not having lymphocytes reacting to their ANLL cells. It has also been suggested that IT causes nonspecific immunostimulation, but IT patient's lymphocytes actually react less than those of patients not given IT. The current hypothesis is macrophage activation: Lymphocyte suppression in IT could be explained by suppressor macrophages. Colony-stimulating activity, produced by bone marrow macrophages, decreases during remission in patients not given IT, but not in IT patients. Numerically, blood cells from patients given IT form more colonies than those from patients not given IT. Three of eight patients given IT had more colonies than the upper normal limit.

Acute Disease↗
PubMed1982

Monocyte-macrophage modulation of T-lymphocyte-derived colony-stimulating activity elaboration in man.

To investigate the source and the mechanisms of synergistically enhanced colony-stimulating activity elaboration by the coincubated monocyte-macrophages and T lymphocytes, we simultaneously prepared conditioned media both from the coincubated monocyte-macrophages and T lymphocytes (ratio 1:3) in the presence of phytohemagglutinin (1%) or methanol extraction residue of bacillus Calmette-Guerin (50 micrograms/ml) and from the isolated T lymphocytes that had been primed with monocyte-macrophages in the presence or absence of phytohemagglutinin or methanol extraction residue of bacillus Calmette-Guerin. Subsequently, colony-simulating activity in various conditioned media was assayed using light-density (less than 1.070 g/ml), nonadherent normal human marrow cells. Live monocyte-macrophages synergized with and significantly (P less than 0.01) agumented the T lymphocyte-derived colony-stimulating activity elaboration; while killed monocytes-macrophages had no such effect. Similarly, actinomycin D and cycloheximide not only diminished monocyte-macrophage colony-stimulating activity elaboration but also reduced their synergistic interaction with T lymphocytes and their ability to augment the T lymphocyte-derived colony-stimulating activity elaboration. In contrast, mitomycin C failed to diminish both - monocyte-macrophages' ability to synergise with T lymphocytes and also to augment T lymphocyte-derived colony-stimulating activity. These data suggest that monocyte-macrophages require an intact transcriptional and translational processes, but not DNA synthesis for synergising with T lymphocytes or for augmenting T lymphocyte colony-stimulating activity elaboration.

Cell Adhesion↗
PubMed1982

Inhibition of in vitro granulopoiesis by autologous allogeneic human NK cells.

This study demonstrates the ability of human NK cells to inhibit in vitro granulopoiesis of autologous and allogeneic BM cells. NK lytic activity and GM-CFC inhibition was present among nonstimulated lymphocytes from healthy donors and could be increased by treatment of PBL with IFN. Both the cytotoxic NK cells and the GM-CFC inhibitory cells could be enriched for among nonadherent, low-density cells. High-density cells were not cytotoxic, only inhibitory to a small extent, and could become neither cytotoxic nor more inhibitory after IFN treatment. In contrast, low-density cells showed an increased cytotoxic and GM-CFC inhibitory capacity after IFN treatment. The NK mediated GM-CFC inhibition was dependent on cell contact with BM cells, increased with longer preincubation times, and was most efficient against 7-day GM-CFC as compared with 14 day GM-CFC progenitors. In conclusion, these data provide new information about the human NK cell as a potent inhibitor of in vitro granulopoiesis and also as a possible regulator of hematopoiesis in vivo.

Binding, Competitive↗
PubMed1982

Human adherent cell contact-mediated modulation of normal myeloid colony formation.

The effects of coincubation of normal nonadherent bone marrow cells on adherent monolayers created from human peripheral blood mononuclear cells or marrow cells were investigated. Nonadherent marrow cells were coincubated for 4 hours with peripheral blood adherent cells at ratios of adherent cells to marrow cells of 2:1 to 5:1. This coincubation suppressed subsequent neutrophilic agar colony growth but not eosinophilic growth. Further studies suggested that this suppression was a cell-cell-mediated process and not secondary to soluble factors. However, coincubation on marrow adherent cells caused increased neutrophilic colony recovery. The possible in vivo relevance is discussed.

Agar↗
PubMed1982

High-dose AMSA and bone marrow rescue in patients with solid tumors.

The feasibility of high-dose AMSA followed by autologous bone marrow rescue was studied in seven patients with solid tumors. They received a total of 12 courses of treatment. Total doses ranged from 600 to 1000 mg/m2/course. Major toxic effects were myelosuppression, fever of unknown origin, and stomatitis. One patient with malignant melanoma had stable disease lasting 2 months; the other six had progressive disease.

Aminoacridines↗
PubMed1982

Significance of cellular pharmacokinetics for the cytotoxic effects of daunorubicin.

The effect of free and DNA-linked daunorubicin on the colony-forming ability of granulocyte-macrophage committed stem cells and spleen colony-forming cells (i.e., multipotent stem cells) from normal mice has been studied in vitro and in vivo. After incubation of bone marrow cells in short-term suspension cultures, both committed and multipotent stem cells were more sensitive to the free drug than to the DNA complex, whereas the reverse was found in vivo after i.v. injection. However, when the in vitro cell-killing effect was related to the cellular retention of daunorubicin, no difference in activity was found between free and DNA-linked drug. Incubation of the bone marrow cells with a higher drug concentration for a shorter time resulted in a considerably lower cell survival than incubation with a lower concentration for a longer time, the intracellular exposure dose being the same. When the in vivo cell survival was related to the cellular retention of daunorubicin, the DNA complex was slightly more toxic than free drug, which can be explained by the higher peak concentration obtained. The results obtained with committed granulocytic stem cells and multipotent stem cells were comparable. Thus, the observed discrepancy between the in vitro and in vivo toxicity of free and DNA-linked daunorubicin can be explained by the differences in cellular retention of daunorubicin under these two conditions; i.e., the DNA complex probably acts as a slow-release preparation of daunorubicin. The results also demonstrated for the first time the importance of the peak concentration of daunorubicin in the target cells and indicate an important role of dose scheduling for the cytostatic effect of the drug.

Animals↗
PubMed1982

Testosterone and synthetic and androgens improve the in vitro survival of human marrow progenitor cells in serum-free suspension cultures.

The direct effect of testosterone and its synthetic analogs on the maintenance of human erythroid progenitor cells (BFU-E) and GM-CFC was studied in suspension cultures. To avoid interference by serum components, the experiments were conducted in serum-free media containing insulin, transferrin, selenium, BSA, and alpha-thioglycerol. When added at concentrations between 10(-7)M and 10(-9)M, testosterone improved survival of BFU-E and GM-CFC. Of the nine analogs tested, eight improved BFU-E maintenance in vitro: nandrolone norethandrolone, and oxymetholone were most active, whereas etiocholanolone had only marginal effects. The influence of these compounds on GM-CFC was less pronounced, with testosterone showing the highest activity. It is concluded that testosterone and some of the synthetic analogs tested exert their hemopoietic effect, at least partly, by affecting the maintenance of erythroid and granulocytic stem cells, directly by increasing their survival or proliferation or indirectly by increasing the input from multipotent stem cell pool, or by both mechanisms.

Cell Count↗
PubMed1981

Bell's palsy and herpes simplex virus.

The possible association of some viral infections with the onset of Bell's palsy was examined in a study of 142 patients. The number of probable recent viral infections, as judged by increase in antibody titers or presence of IgM antibodies, did not differ statistically from that found in a sex- and age-matched control group. However, a higher prevalence of herpes simplex virus (HSV) antibodies was found in the patient group with both a complement-fixation (CF) test and a radioimmunoassay (RIA). Moreover, titers of HSV CF antibodies and antibodies against HSV envelope antigens (RIA) were higher in the patient group. The possibility of reactivated HSV infection and transient demyelination of the facial nerve being causatively associated with Bell's palsy is discussed.

Adult↗
PubMed1981

Pharmacokinetics of daunorubicin after administration as free drug or as DNA complex in leukemic patients.

An earlier whole-body autoradiographic study in mice revealed large differences between the tissue distribution of daunorubicin (D) after administration as free drug as as DNA-linked D. Therefore, the pharmacokinetics of D administered as free drug or linked to DNA was studied in 15 adult patients with acute non-lymphoblastic leukemia. The data obtained following infusion of free drug over either 45 or 240 min could be fitted to a two-compartment open-body model. With the D-DNA infusion considerably higher plasma concentrations were achieved, with a slower distribution and elimination from plasma than seen after the administration of free drug. this confirmed earlier animal data indicating a different pharmacokinetic behavior of D when it was administered linked to DNA. Furthermore, different pharmacokinetic parameters were obtained for D during infusion and in the post-infusion phase after administration of DNA-linked D (P less than 0.005). This finding strongly indicates that the D-DNA acts as a slow-release preparation in humans, which might modify tissue distribution and toxic side-effects of the drug.

DNA↗
PubMed1981

Human myeloid leukaemic cell interactions in vitro with normal myeloid colonies.

To determine whether myeloid leukaemic cells could inhibit normal myeloid colony formation, leukaemic cells at concentrations ranging from 0.5 to 8 X 10(6)/ml were co-cultured in agar but separated by a 1 ml underlayer from 10(5) low-density (less than 1.077 g/ml) nonadherent normal marrow cells. Inhibition of normal-marrow myeloid colony formation occurred regularly at high cell concentrations (8 X 10(6)) at a leukaemic:normal cell ratio of 80:1. This suppression persisted with addition of indomethacin (10(-6)M). On the other hand, both low leukaemic cell numbers and irradiated leukaemic cells frequently stimulated normal colony growth. No inhibitor of colony growth could be detected in leukaemic-conditioned media, and absorption of colony-stimulating activity (CSA) with leukaemic cells improved CSA activity. These experiments point to the difficulty in unravelling the effect of leukaemic cells on normal haemopoiesis (both inhibitory and stimulatory) by in vitro agar culture.

Cell Count↗
PubMed1981

Secondary hematological changes mimicking the preleukemic syndrome. Report of two cases.

Two women with hematological and clinical features typical of the preleukemic syndrome, including low marrow myeloid colony and cluster formation in vitro, showed unexplained spontaneous improvement with normalization of both peripheral blood values and in vitro cloning efficiency after 2-4 years. One patient had and the other developed later an autoimmune disorder. It is therefore suggested that secondary hematopoietic changes might have mimicked the preleukemic syndrome.

Aged↗