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Biomedical subjects

M Beran

Publications and source records attributed to M Beran.

At least 199 records · Page 11Linked to original sources
PubMed1981

Aspects on treatment principles of tongue carcinomas.

The present investigation of a retrospective series of patients with tongue cancers aimed at assessing the results of various treatment principles. We suggest that surgery must be taken into account particularly when large primary tumors as well as palpable regional nodes are found. Because of the unpredictable metastasis behavior, even in cases of small primary tumors without clinical evidence of regional spread, the potential risk of regional microdeposits must always be suspected. Therefore, irradiation of the neck field with fractionated doses of 5,000 rad, alone or in combination with surgery should be considered in all patients with tongue cancers.

Aged↗
PubMed1981

Differences in the plasma kinetics of daunorubicin in normal and leukemic rats.

The plasma pharmacokinetics of the anthracycline drug daunorubicin in doses of 1 and 10 mg/kg body weight were compared in normal and leukemic inbred Sutton-August rats (50-70 x 10(9) leukemic cells/1 blood). The area under the plasma concentration versus time curve was about 25 times larger in the leukemic rats at both dose levels. The data indicate that daunorubicin has a lower volume of distribution in leukemic rats as compared with normals. The large reduction in plasma clearance of daunorubicin in the leukemic rats can to some extent be explained by impairment of hepatic and renal functions but the results indicate that the leukemic state per se was of importance for the observed pharmacokinetic differences. This finding may be of importance for the treatment of patients with a high leukemic cell load, since higher retention of the drug in the central compartment leads to lower concentrations in poorly vascularized tissues, which favours the development of resistant leukemic cell clones.

Animals↗
PubMed1981

Adherent cell inhibition of human leukemic in vitro agar clonal growth by short-term cell-to-cell contact.

The effects of peripheral blood adherent cells from normal donors on human myeloid leukemic cluster growth in agar were studied. A prior co-incubation of nonadherent leukemic cells with adherent cell monolayers from 9 out of 10 donors in liquid cultures over a 4-hr period was sufficient to reduce subsequent leukemic growth in semisolid agar cultures. Inhibition was seen with adherent to leukemic cell ratios of as low as 0.5:1. Conversely, identical numbers of adherent cells in agar cultures but separated from the leukemic cells enhanced growth more than the cultures containing human placental conditioned media alone. Because leukemic cell exposure to adherent cells was brief, a cytotoxic mechanism appeared likely; however, this could not be detected by 51Cr release. Human peripheral blood adherent cells not activated by any in vitro mechanism suppress clonal growth of human myeloid leukemic cells by a mechanism requiring cell to cell contact. Examination of the inhibition of clonal growth appears to be more sensitive than 51Cr release as an indicator of adherent cell effects on myeloid leukemia.

Agar↗
PubMed1980

Leukemic cell versus plasma levels of daunorubicin and daunorubicinol after infusion of daunorubicin as free drug or the DNA complex.

In two patients with acute non-lymphocytic leukemia, leukemic cell as well as plasma concentrations of Daunorubicin (D) and Daunorubicinol (DOH) were studied after administration of D as free drug or as a complex with DNA. The peak plasma concentration of D was slightly higher after infusion of the D-DNA complex than after free drug while the intracellular pattern was the opposite. The intracellulr peak concentrations were found to be 50-100 fold higher and displayed a kinetic pattern which was completely different from that of D in plasma. We therefore suggest that assays of the concentrations of the drug and its toxic metabolite in leukemic cells are more relevant than the monitoring of plasma concentrations in the evaluation of the clinical effect of this drug's action.

Adult↗
PubMed1980

Response to treatment in acute non-lymphatic leukaemia: prognostic value of colony forming and colony stimulating capacities of bone marrow and blood cells compared to other parameters.

Growth of bone marrow and mononuclear white blood cells (MWBC) in soft-agar cultures was studied in 26 patients with untreated acute non-lymphocytic leukaemia (ANLL). Marrow and MWBC from 30 healthy volunteers served as controls. All ANLL patients revealed an abnormal growth in vitro. Patients with an increased number of clones in marrow cultures and large cluster predominance ('excessive growth') responded poorly to therapy with only one of 10 patients entering remission. On the contrary, only two of the 15 patients with a decreased clone number ('low growth') failed to achieve remission. The number of colonies and clusters in both bone marrow and blood cultures was significantly lower at presentation in patients who later entered remission than in those who did not. The correlations between the number of colonies and clusters in the blood and the marrow cultures were statistically significant. No significant correlations were found between prognosis or colony formation, on one hand, and the production of colony stimulating activity (CS)bA), by bone marrow and blood cells of ANLL patients, on the other. Nor could such correlations be found between prognosis, blood cell counts, and age. It is concluded that the growth pattero cytostatic drugs and particularly in selecting patients with a high probability to respond poorly to current cytostatic regimes.

Acute Disease↗
PubMed1980

Colony stimulating factor augmentation in human placental conditioned medium.

Because of the variability of different placentas to condition culture medium for colony-stimulating factor (CSF), we have attempted to augment CSF elaboration using endotoxin and bacillus Calmette Guerin (BCG) during the incubation period. Of 14 batches of human placental conditioned media (HPCM) prepared from different placentas, six were found to be inactive (no colony formation at concentrations of 5% to 40% vol/vol), five were found to be a weak stimulator of colony formation (producing < 10 colonies/10(5) human marrow cells plated at a HPCM concentration of 30%) and three were found to be active (producing 30 or more colonies/10(5) cells plated at HPCM concentration of 30%). In six cases augmentation of CSF elaboration was attempted using endotoxin or BCG and in all a marked increase in CSF was achieved. The increased colony formation was found to be due to greater increase in neutrophil and macrophage colonies than eosinophil colonies. The method of augmenting CSF elaboration in HPCM could have important implications for producing large quantities of potent and standardized source of CSF for the use in clinical laboratories and for increasing the yield of colony-stimulating factor(s) for further purification.

Cells, Cultured↗
PubMed1980

Adherent cell-mediated inhibition of human leukemic myelopoiesis.

We investigated the possibility that the control of leukemic growth by autologous adherent marrow cells may explain the indolent behavior of oligoleukemia. Leukemic cluster growth was measured by in vitro agar culture. The following marrow fractions (Fr) were examined from 13 patients for leukemic growth: Fr I: ficollisopaque interface cells (density less than 1.077 g/ml); Fr II: adherent-cell depleted Fr I (4.8% +/- 2.1 (SE) monocytes); Fr III: adherent and phagocytic cell depleted Fr I (0.3% +/- 0.2 monocytes); and Fr IV: adherent cells removed from plastic surfaces by lidocaine plus EDTA (74% +/- 10.9 monocytes). Two patient groups were recognized: Group A showed cluster growth in Fr IV with no absolute increase in Fr III and no suppression of Fr III cluster growth with addition of Fr IV. In Group B, Fr III showed an absolute increase in cluster growth. Fr IV did not show cluster growth and addition of Fr IV to Fr III suppressed growth. This suggested that in Group B, monocytes may suppress leukemic growth, the failure to observe this in Group A indicated the possible leukemic nature of the adherent cell fraction and the absence of residual normal monocytes. Other possible explanations are discussed.

Bone Marrow↗
PubMed1980

One-step procedure for human T-lymphocyte colony growth and its regulation by T and B cells, and monocytes.

Previous systems for cloning human T-cells have been either one step procedures with small colony size (40 less than 40 cells) or two-step procedures with agglutination problems. These systems also require erythrocytes, thiols and human serum. We have regularly grown more than 10(3) colonies (more than 40 cells)/5 X 10(5) cells from purified T-cells or phagocytic and adherent cell depleted mononuclear cells in agar using phytohemagglutinin (PHA) as the mitogenic stimulus. The reason for the poor colony size in other single step procedures using agar may be related to cell-to-cell interaction. We found that both adherent (Ad) and phagocytic cells were suppressive of T-cell colony growth (TCCG) in donors with low or absent TCCG from whole mononuclear cells. This effect was reproduced by adding Ad cells to T-cell concentrated fractions. Both irradiated T and unirradiated enriched B-cells increased TCCG of T fractions. TCCG is possible in simple in vitro systems from both adherent and phagocytic cell depleted fractions and concentrated T-cell fractions. This allows for the examination of factor regulation of TCCG and has enabled the identification of a possible B-cell released T-cell growth factor. Previously described complex growth requirements may be related to cell interactions.

B-Lymphocytes↗
PubMed1980

Enhancement of hemopoietic recovery after bone marrow transplantation with the addition of nucleated blood cells in mice.

Recovery of bone marrow cellularity, CFU-C, and CFU-S were studied sequentially over 90 days time after syngeneic bone marrow transplantation in mice. A minimal cell dose of 2 X 10(5) bone marrow cells was given. At day 28 after transplantation, CFU-C reached more than 50% of the normal range whereas the CFU-S concentration was less than 15%. Normalization of CFU-S occurred at day 90. The effect of the addition of peripheral blood nucleated cells on bone marrow hemopoietic recovery was studied at day 28. The augmentation of CFU-C and CFU-S recoverey were dose dependent. Optimal enhancement was seen with bone marrow to blood ratios of 1:1 and 1:2.5. This enhancement effect was lost when nucleated blood cells in a ratio of 1:10 were administered.

Animals↗
PubMed1980

Effect of pyran copolymer on murine hemopoiesis.

Pyran Copolymer (NSC-46015), a divinyl-ether maleic anhydride leads to a significant shift in distribution of nucleated cells and CFUs in the bone marrow and spleen. The bone marrow cellularity and the CFUs content reach a nadir 4 to 6 days after Pyran injection, simultaneous rise in spleen cellularity and CFUs concentration of circulating pluripotent stem cells by a factor of 10 to 45 and a concomitant rise of CFUc is seen. the origin of the mobilized pluripotent stem cells is likely to be the bone marrow, not athe spleen.

Animals↗
PubMed1979

Liquid chromatographic monitoring of daunorubicin and daunorubicinol in plasma from leukemic patients treated with daunorubicin or the daunorubicin-DNA complex.

Fifteen patients with acute nonlymphocytic leukemia have been randomized for treatment with daunorubicin (1.0--1.5 mg/kg) either as the free drug (for 45 min or 4 h) or as the drug bound to a DNA carrier (for 5--6 h). The correlation between plasma kinetics of daunorubicin and its main metabolite daunorubicinol and the different administration schedules of daunorubicin has been studied by reversed-phase liquid chromatography. Plasma concentration kinetics of daunorubicin as well as the daunorubicin-DNA complex was biphasic in character. Maximum plasma level of daunorubicin was found during the infusion period. Its concentration decreased rapidly when the infusion stopped and was below the detection limit of the analytical method 2--4 h later. The data suggests a slower disposition of the duanorubicin-DNA complex compared with the free drug.

Animals↗
PubMed1979

Uptake and distribution of daunorubicin and daunorubicin-DNA complex in mice as studied by whole-body autoradiography and liquid chromatography.

The tissue distribution of daunorubicin (D) and daunorubicin-DNA complex (D-DNA) was studied in mice by means of whole-body autoradiography (WBA) and high-performance liquid chromatography (HPLC). A higher accumulation of radioactivity in the blood after 1 min and a lower initial accumulation in the cardiac muscle were found after administration of 3H-D-DNA than after the infection of free drug. Comparative studies of plasma levels of daunorubicin and daunorubicinol (DOH) in D- and D-DNA-treated animals by HPLC showed that the initial differences were negligible from 2 h onward. A rapid accumulation of D in bone marrow occurred in both D- and D-DNA-treated mice. D reached its maximum level after 1 h and was almost constant for 12 h. A new WBA finding was a rapid and specific accumulation of radioactivity in the pituitary gland, in the thyroid, and in the pancreatic islets, which might be of some interest in consideration of possible late endocrine side effects of anthraquinone glycoside therapy.

Animals↗