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Biomedical subjects

A Dvilansky

Publications and source records attributed to A Dvilansky.

At least 19 recordsLinked to original sources
PubMed1998

Alterations in membrane lipid dynamics of leukemic cells undergoing growth arrest and differentiation: dependency on the inducing agent.

The effect of various differentiation inducers on membrane cell dynamics was studied using HL-60 and K562 leukemic cell lines. Membrane lipid dynamics was measured by the steady-state fluorescence polarization (P) method utilizing either 1,6-diphenyl-1,3,5-hexatriene (DPH) or the trimethyl ammonium derivative of DPH (TMA-DPH), which ascertains anchorage of the label to the membrane-water-lipid interface. Decrease in membrane microfluidity was observed in HL-60 cells undergoing differentiation into macrophages by 1,25-dihydroxyvitamin D3 and by K562 cells induced to differentiate by DMSO. Sodium butyrate caused an increase in membrane fluidity in K562 cells undergoing differentiation into erythroid-like cells while in HL-60 cells a dual effect was observed. At 0.4 mM concentration, in which the cells were induced to differentiate along the monocyte pathway, a decrease in membrane fluidity was observed, while at 1 mM concentration an increase in membrane fluidity occurred. Interferon-gamma (IFN-gamma) induced an increase in membrane fluidity in both cell lines. Using HL-60 cells fluorescently labeled by TMA-DPH, similar results indicating fluidization of the membrane following IFN-gamma treatment were obtained. Advanced fluorescence lifetime measurements, evaluated either by phase modulation spectrofluorometry or by single photon correlation fluorometry confirmed that the decrease in fluorescence polarization by IFN-gamma resulted from membrane fluidization and not from elongation of the probe's excited state lifetime. It is suggested that the inducer mode of action, and not the differentiation route, determine the outcome of changes in membrane microviscosity.

Butyrates↗
PubMed1997

Distamycin-A derivatives potentiate tumor-necrosis-factor activity via the modulation of tyrosine phosphorylation.

The cytotoxic activities of 2 novel distamycin-A derivatives, FCE 24517 and FCE 25450A, alone and in combination with tumor-necrosis factor-alpha (TNF), were studied. Both drugs, especially FCE 25450A, analyzed extensively here, inhibited the growth of HL60 promyelocytic cells, and human SV80 and murine L929 transformed fibroblasts in a dose-dependent manner. The growth-inhibitory potential of sequential exposure to the distamycin-A analogs and TNF was determined. A 4-hr treatment of L929 fibroblasts with 100-1,000 ng/ml FCE 25450A, followed by 2 ng/ml TNF, resulted in a synergistic anti-proliferative effect. The synergism of FCE 24517 with TNF was less profound. Experiments to elucidate the mechanism underlying the cooperation revealed that FCE 25450A pre-treatment almost completely abolished the elevated tyrosine phosphorylation of a 137-kDa and other membranal proteins and prevented the de-phosphorylation of another protein band observed in L929 cells in the presence of TNF. FCE 25450A alone induced no changes in the phosphotyrosine profile of the cells. The effect of FCE 25450A was counteracted by the tyrosine-phosphatase inhibitor orthovanadate. In parallel, the inhibitor also diminished the antiproliferative action of the FCE 25450A/TNF combination. These findings suggest that, beyond their cytotoxic effects as single agents, the distamycin derivatives increase the sensitivity of cells to TNF. This effect is governed via the inhibition of TNF-induced tyrosine phosphorylation of specific proteins which are probably involved in the development of TNF resistance. Thus, protein de-phosphorylation might provide an additional mechanism of action of these novel distamycin-A-derived drugs.

Animals↗
PubMed1996

The roles of protein phosphorylation/dephosphorylation in tumor necrosis factor antitumor effects.

The roles of protein phosphorylation and dephosphorylation in the tumor necrosis factor (TNF) cytotoxic and antiproliferative effects on L-929-transformed fibroblasts were explored. Genistein and erbstatin, specific inhibitors of tyrosine kinase, had antiproliferative but not cytotoxic effects on the cells by themselves and synergistically enhanced the cytotoxic and antiproliferative effects of TNF-alpha. Immunoblot analysis with a monoclonal antiphosphotyrosine antibody revealed that TNF, administered for 5-180 min, induced tyrosine dephosphorylation of two pairs of membranal proteins, 34-36 kDa and 50-52 kDa, and potentiated tyrosine phosphorylation of a 115-kDa protein in both the cytosolic and membranal fractions of the cells. A very brief exposure (30 sec) to TNF induced rapid phosphorylation of several proteins, whereas genistein, but not inhibitors of other protein kinases, enhanced this effect of TNF. The results suggest that TNF activity could be potentiated by the inhibition of tyrosine phosphorylation and point to specific proteins that are dephosphorylated on tyrosine in response to TNF.

Animals↗
PubMed1996

Effect of radiation on red cell membrane and intracellular oxidative defense systems.

Ionizing radiation is currently used for prevention of transfusion associated graft versus host disease (TAGVHD). As radiation damage is associated with the production of activated oxygen species, the aim of this study was to observe the immediate effect of ionizing radiation on red cell membrane and intracellular oxidative defense systems. Neonatal and iron deficiency (IDA) cells, known for their increased sensitivity to oxidative stress, were chosen and compared with normal cells. Irradiation was performed in doses of 1500 cGy, 3000 cGy and 5000 cGy. GSH and methemoglobin levels and the activity of different antioxidant enzymes, measured under optimal in vitro conditions, were preserved in all cells after irradiation. Only radiation at the highest does of 5000 cGy, caused significant potassium leakage in neonatal cells and insignificant increase in IDA cells. Thus, cells with increased sensitivity to oxidative stress are more susceptible to damage by ionizing radiation than normal cells.

Catalase↗
PubMed1996

Protein C and protein S in pediatric nephrotic patients.

Nephrotic syndrome (NS) is associated with an increased incidence of various thromboembolic complications in adult patients. It was found to be due to elevated factor IX (FIX) F.VII, F.VIII, F.V, fibrinogen, thrombocytosis and increased platelet reactivity. Acquired AT-III deficiency, reduced functional levels of protein S and reduced activity of protein C were also reported. We evaluated 15 children aged 1 to 13 years. Thirteen of these children suffered from nephrotic syndrome and two others had non-nephrotic proteinuria. All patients but one were normotensive. Two patients were not steroid responsive. Serum creatinine was normal for age in 14 patients. Kidney biopsy was carried out only in three children. Haemostatic parameters included protein C and S antigenicity in plasma and urine. Plasma levels of protein C and protein S were within the normal range. Protein C antigenicity in urine was increased in five children out of 14 examined. Protein S in urine was increased in seven out of 12 children examined. No thromboembolic phenomena were documented even though protein C and protein S antigenicity were identified in the urine.

Adolescent↗
PubMed1994

Rapid interferon-gamma-stimulated tyrosine phosphorylation of cytosolic and membranal proteins in HL-60 promyelocytic cells.

The involvement of tyrosine phosphorylation in the early stages of interferon-gamma (IFN gamma)-induced monocytic differentiation of HL-60 cells was studied. Immunoblotting analysis demonstrated that IFN gamma induced rapid changes in the tyrosine phosphorylation of several endogenous cytosolic and membranal proteins. The most prominent of these polypeptides was a 84 kDa protein. In membranes, the IFN gamma-induced phosphorylation of this protein was detectable in 5 min, remained elevated for 3 h and declined thereafter, while a gradual decrease in the phosphotyrosine content was observed in cytosols. In parallel, a 40% increase in the phosphotyrosine phosphatase activity was detected in the later stages of IFN gamma treatment. Rapid changes in tyrosine phosphorylation were detected also in a 64 kDa protein. In contrast, 2-day exposure to IFN gamma was needed to potentiate significantly the tyrosine phosphorylation of a 36 kDa membranal polypeptide. These data support the involvement of tyrosine phosphorylation in the early stages of IFN gamma-induced monocytic differentiation of HL-60 cells.

Cell Differentiation↗
PubMed1994

Prolonged storage of red cells: the effect of pH, adenine and phosphate.

Prolonged storage of red blood cells (RBCs) at 4 degrees C results in decreased intracellular ATP levels with diminished posttransfusion survival. Meryman described a preservative medium, exceptional in its capacity to increase these intracellular levels during the first weeks of storage and later in maintaining adequate levels, for extended storage periods. We modified this medium, investigated its constituents, and found that its ATP-preserving effect was unrelated to its tonicity or to the presence of mannitol. Throughout storage, RBC potassium leakage and lactate production were moderate. No evidence of osmotic swelling was detected. In spite of high ATP levels, the cells became echinocytes, thus discounting a direct correlation between shape and metabolic status. The most striking finding in this study was that the prestorage pH of the blood unit (pH 7.0), has a crucial contribution in elevating nucleotide levels in a medium containing high levels of phosphate (18-40 mM) and adenine. We suggest that a combined effect of optimal pH, adenine, glucose and phosphate in the medium contributes to the ability of the RBCs to synthesize the necessary purine nucleotides by the 'salvage pathway'.

Adenine↗
PubMed1994

Radiation damage to the erythrocyte membrane: the effects of medium and cell concentrations.

Human erythrocytes suspended in plasma, or in phosphate buffered saline (PBS), were exposed to ionizing radiation. Potassium leakage from irradiated erythrocytes is significantly higher in PBS than in plasma. The potassium leakage decreases when PBS is gradually replaced by plasma. These findings suggest that some of the plasma constituents have radioprotective properties. The potassium leakage per cell is independent of the hematocrit, Hct. The potassium leakage is attributed to the formation of radiation defects in the membrane. Analysis of the effect of radiation dose, plasma and cell concentrations on the product of the number and surface area of the radiation defects indicates that the radiation damage is mainly due to the direct formation of free radicals in the cell membrane. The radioprotective effect of plasma is attributed to surface reactions of these free radicals with plasma constituents adsorbed on the membrane.

Blood Banks↗
PubMed1993

Increased platelet thromboxane A2/prostaglandin H2 receptors in patients with pregnancy induced hypertension.

Pregnancy induced hypertension (PIH) is associated with a variety of disturbances in the hemostatic system including alterations in platelet function, thrombocytopenia, and an increase in platelet turnover. The density of platelet Thromboxane A2 (TXA2)/Prostaglandin H2 (PGH2) receptors was determined in patients with PIH and normal pregnant women, using [125I]-PTA-OH, a TXA2/PGH2 receptor antagonist. The number of platelet TXA2/PGH2 receptors significantly increased (p < 0.008) from 1734 +/- 370 sites/platelet (n = 8) in normal pregnant women to 3703 +/- 846 sites/platelet (n = 9) in patients with severe PIH. The sensitivity of platelets to the TXA2 mimetic U46619 was significantly (p < 0.0005) increased in platelets obtained from severe PIH patients (EC50 = 150 +/- 10nM, n = 3) compared to controls (EC50 = 290 +/- 60 nM, n = 5). These results indicate that an increased number of TXA2/PGH2 receptors as well as increased sensitivity to TXA2/PGH2 mimetics occurs in PIH. Collectively, these results provide further support for the notion that TXA2 and its receptor may play an important role in the pathophysiology of PIH.

Blood Platelets↗
PubMed1993

Synergistic effect of interferon-gamma and phorbol myristate acetate on superoxide production by human monocytes.

This study demonstrates a synergistic effect of IFN gamma and PMA on superoxide generation by human monocytes. A strict correlation was observed between the induction of superoxide production and PK-C activation by PMA alone. No such correlation was evident for IFN gamma. However, exposure of the cells to IFN gamma for 10 to 15 hr prior to PMA treatment enhanced both superoxide production and PK-C activation. Using protein kinase inhibitors, we noticed that while PMA exerted its effect by activating PK-C, IFN gamma operated via activation of calcium/calmodulin-dependent or some other calcium-dependent protein kinases. These kinases appeared to be involved in the effect of IFN gamma on superoxide production, as well as in its potentiation of PMA activity.

Cells, Cultured↗
PubMed1993

Iron deficiency anemia: recovery from in vitro oxidative stress.

Red blood cells in iron deficiency anemia (IDA) have a decreased activity of essential antioxidant enzymes. The present study examined the effect of in vitro exposure to oxidative agents in IDA cells and their recovery capacity. Red cells of 26 IDA patients and 10 healthy subjects were examined. Cells of IDA patients had higher levels of reduced glutathione (GSH), and normal methemoglobin and malonyldialdehyde (MDA) levels. Exposure to butyl hydroperoxide revealed a dose-dependent sensitivity in IDA cells, with extensive GSH depletion and increased MDA levels. These changes were partially reversible by incubation with dithiothreitol. Exposure to phenazine methosulfate, to produce intracellular superoxide ions, resulted in moderate GSH depletion and methemoglobin production. IDA cells were more sensitive than control cells to high concentrations of this substance. This effect was further augmented by preincubation with a superoxide dismutase inhibitor. Our data demonstrate that IDA cells are more susceptible to oxidation but have good capacity for recovery.

Adolescent↗
PubMed1992

Effect of synthetic enantiomeric cannabinoids on platelet aggregation.

The effect of a synthetic pair of enantiomeric cannabinoids on platelet function was evaluated. The nonpsychotropic enantiomer, the 1,1-dimethylheptyl homolog of (+)-(3S,4S)-7-hydroxy-delta-6-tetrahydrocannabinol (HU-211), was found to be more active in inhibiting ADP-induced platelet aggregation than the highly psychotropic (-)-enantiomer (HU-210). The related (+)-(3R,4R) cannabinoid, HU-213, which lacks the 7-hydroxy moiety, exerted its inhibitory effect within a wider range of concentrations. The results indicate a differentiation between psychotropic activity and inhibition of platelet aggregation in the cannabinoid group of compounds.

Adenosine Diphosphate↗
PubMed1992

A novel agarose acrobeads protein A column for selective immunoadsorbance of whole blood: performance, specificity and safety.

The present study describes the performance and safety parameters of a novel column composed of protein A linked to acrobeads. Hemoperfusion of anticoagulated whole human blood was carried out in a closed system. Specific adsorption of IgG was documented in whole blood, plasma and IgG diluted in saline. Specific activity of the column was 3.52 mg/ml beads. These studies revealed slight changes in platelet counts and minor hemolysis. The relatively short period needed for maximal hemoperfusion effect and safety may enable the use of this novel therapeutic approach in clinical practice.

Biocompatible Materials↗
PubMed1992

Familial thrombotic thrombocytopenic purpura in a Bedouin family.

A 24-year-old Beduin pregnant woman in her 22nd week of gestation was treated successfully by plasmaphereses and steroids as soon as the diagnosis of TTP was confirmed by the clinical and laboratory criteria needed. Her sister died due to complications of TTP in pregnancy five years earlier while her other sister recuperated from TTP during pregnancy. However, fetal loss ensued. Thus, family history in pregnant women presenting with toxemia of pregnancy--like--syndrome may be the first clue to familial TTP.

Adrenal Cortex Hormones↗
PubMed1991

Acquired auto-anti D in a patient with myelodysplastic syndrome.

Modification of blood group in the course of malignant haemopathy in an aged patients is described. To our knowledge, this is the first published case describing the appearance of autoantibody due to anti-D in a patient with Rh typing DCcee who has myelodysplastic syndrome in transition to acute leukaemia. We present a patient who developed acquired autoantibody to Rh locus as co-phenomenon of myelodysplastic syndrome in transition to acute leukaemia.

Aged↗