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E Balint

Publications and source records attributed to E Balint.

18 recordsLinked to original sources

Modulation of the anti-proliferative signal of interferon-alpha by tamoxifen in U937 cells.

Several clinical protocols are attempting to utilize the combined anti-proliferative signal of interferon-alpha (INF-alpha) and tamoxifen on cancer cells. We demonstrated here that the effect of these two agents on the growth of the premacrophage U937 cells is antagonistic. This antagonistic effect is paralleled by the ability of tamoxifen to modulate the INF-alpha-induced hyperpolarization in these cells. INF-alpha-induced hyperpolarization was shown before to be an integral part of the anti-proliferative signal of this agent. Tamoxifen liberates Ca2+ from intracellular stores of U937 cells but this effect of the drug is not the cause of its antagonistic effect with the anti-proliferative signal of IFN-alpha. We suggest therefore, that the combined effect of these two anti-cancer drugs could also be advantageous for macrophage proliferation.

Calcium

Cytoskeletal modulation of plasma membrane events induced by interferon-alpha.

Cytochalasin B, a drug that alters microfilament structure, was found to modulate interferon-alpha (IFN-alpha)-induced changes in ion fluxes, in motional freedom of spin probes, and lateral diffusion of surface antigens. These changes occur in Daudi cells inherently sensitive to the antiproliferative signal of IFN-alpha, but not in insensitive cells, and were associated with the antiproliferative signal previously. The biophysical effects of cytochalasin B were detected by flow cytometric quantitation of membrane potential using an oxonol dye, by electron spin resonance (ESR) spectrometry, and by measurements of fluorescence recovery after photobleaching (FRAP) of surface antigens using a laser-interactive cell imaging system. Cytochalasin B treatment increased an IFN-alpha-induced membrane potential shift by -5 mV. The motional freedom of 5-doxyl-stearic acid changed from 0.67 to 0.63, as expressed by the order parameter, S, with IFN-alpha treatment and was prevented by cytochalasin B. Changes in the lateral diffusion of surface antigens induced by IFN-alpha treatment, D = 5.3 x 10(-10) without treatment and D = 7.8 x 10(-10) cm2/s with treatment, was blocked by cytochalasin B. In contrast, the microtubule stabilizers taxol and D2O and the microtubule depolymerizing colcemid were ineffective at dose levels sufficient to cause the characteristic cell physiological alterations of these agents. These results implicate microfilaments but not the microtubule system in transduction of the antiproliferative signal by IFN-alpha in Daudi cells.

Actin Cytoskeleton

On the mechanism of action of interferons: interaction with nonsteroidal anti-inflammatory agents, pentoxifylline (Trental) and cGMP inducers.

In earlier studies, we showed that when interferon alpha (IFN alpha) binds to cell receptors, it alters membrane potentials. In IFN-sensitive Daudi cells derived from Burkitt's lymphoma patients, IFNs produce dose-dependent hyperpolarization, decreased plasma membrane viscosity, modulation of the microfilament system, and altered synthesis of cAMP, cGMP and prostaglandins. No such changes were seen in IFN alpha-resistant Daudi cells. In this study, we found that indomethacin, pentoxifylline, or the cGMP inducer sodium azide (NaN3) had no significant effect on the IFN alpha induced membrane potential changes, or on membrane viscosity changes as measured by flow cytometry and electron spin resonance spectrometry. In tissue culture, indomethacin did not alter the anti-proliferative effect of IFN alpha on Daudi cells. Indomethacin may influence IFN synthesis, but not it's antiproliferative actions. Relatively high doses of pentoxifylline slightly inhibited proliferation of Daudi cells and synergized with IFN alpha. Measurement of early biophysical changes induced by IFNs may represent a new screening method to rapidly explore certain types of IFN alpha potentiating agents.

Azides

Hepatocellular carcinoma in sub-Saharan (tropical) Africa.

Primary cancer of the parenchymal cells of the liver--hepatocellular carcinoma--is much more common in Africa (and Southeast Asia) than in Europe and North America. The very high incidence of this tumour is one of the outstanding problems of medicine in tropical countries. There is no doubt that it was already widespread in Africa before urbanization and industrialization. In this article the characteristics of hepatocellular cancer in the tropical (sub-Saharan) part of Africa are briefly reviewed.

Africa

Protein kinase C is involved in the early signals of interferon-alpha but not of interferon-gamma in U937 cells.

Increasing interest is being focused on the role of protein kinase C (PKC) in the mode of action of interferons (IFNs). Here we report that IFN-alpha induced a transient translocation of PKC from the cytosol to the particulate fraction of U937 cells. In contrast, after IFN-gamma treatment, no significant change in PKC activity could be observed. IFN-induced changes in membrane potential were also examined by means of a potential sensitive oxonal dye and flow cytometry. Hyperpolarization was induced by both IFN-alpha and IFN-gamma. The protein kinase inhibitor H-7 blocked the hyperpolarization induced by IFN-alpha but not by IFN-gamma. These concordant results suggest that PKC is involved in the early signals of IFN-alpha but not of IFN-gamma in U937 cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Alpha interferon accelerates lateral diffusion of Daudi cell surface differentiation antigens: measurement by fluorescence redistribution after photobleaching.

Lateral diffusion coefficients (D) of two surface differentiation antigens (sIgM and Bp35) were determined on interferon-sensitive (-IFs) or resistant (-IFr) Daudi cells by fluorescence photobleaching, using monospecific FITC-anti-IgM or PE-anti-Leu 16 probes. For untreated Daudi -IFs, mean (D) were 5.8 and 5.3 (x10(-10) cm2/sec). These increased, to 11 and 7.9 x 10(-10) cm2/sec (p less than 0.001) within 30 min after binding of recombinant IFN-a (80 to 800 U/10(6) cells), but decreased by up to 4-fold after Con A Mean (D) of identical surface antigens on Daudi-IFr were 8.2 and 9.4 x 10(-10) cm2/sec; and were not altered by IFN-a. Mean (D) of a lipid analog was up to 40-fold higher than for surface proteins and statistically identical in Daudi-IFs and Daudi-IFr. Rapid acceleration by IFN-a of surface protein lateral diffusion in Daudi-IFs obviously could facilitate anti-proliferative signal transduction; by contrast, a baseline increase of (D) in Daudi-IFr was evidently associated with their refractory state.

Antigens, CD20

Dynamic analyses of lymphoblast membranes exposed to alpha interferon using flow cytometry and fluorescence recovery after photobleaching.

Interferons represent a major group of the biologic response modifiers which exert multipotent effects upon cell growth, cyto-differentiation and immune functions. Previous experimental studies with alpha interferon (IFN-alpha) have suggested that modulation of transmembrane signaling could be a critical determinant in the bioregulatory diversity. To determine whether any initial changes at the plasma membrane would directly correlate with one or more actions of IFN-alpha, we investigated cultures of Daudi lymphoblasts which are uniquely susceptible to growth inhibition. Complementary biophysical techniques were applied. In one approach, changes in plasma membrane ion flux were measured by flow cytometry, using a fluorescent dye indicator of membrane potential: Cells briefly exposed (5-10 min) to a DNA-recombinant IFN-alpha 2 (100 to 800 U/ml) manifested a consistent plasma membrane hyperpolarization (-60 to -90 mV) which could be blocked by ouabain. In a second approach, changes in diffusion coefficients of plasma membrane-associated macromolecules were determined by measuring the fluorescence redistribution after pulse photobleaching (FRAP): Individual plasma membrane proteins (sIgM, Leu 12 or Leu 16) were labelled with FITC conjugated goat antibodies [F(ab')2 or Fab'] or with phycoerythrin-B conjugated monoclonal mouse antibodies. Statistical comparisons of cells exposed to IFN-alpha 2 for 10 to 30 min showed immediate 27 to 88% increases in mean lateral diffusion rates. Mutant Daudi cells, cloned for resistance to growth inhibition showed no plasma membrane hyperpolarization with IFN-alpha 2 (up to 1000 U/ml), and baseline lateral diffusion coefficients matched those of IFN-alpha 2-treated, non-resistant cells. We conclude that biophysical status and responses of the plasma membrane must be closely linked to the molecular mechanisms of anti-proliferative signal transduction.

Cell Membrane

Memory and consciousness.

During the first few years of his analysis Mr Smith had no mental or visual memories. He had body memories in so far as his body both looked like a baby, and behaved in a baby-like way on the couch. There were no words to describe the baby or his environment. He was a baby who could not think or communicate verbally. He made strange noises, but each day was the same as the last. There were no other patterns of behaviour. For the first three years the analysis consisted mainly in the patient coming to sessions and leaving them and starting again the next day; in the analyst trying not to make sense of the content of the words that were spoken, but in trying to catch some sense or feeling from the movements of his body and the sounds that he made. He did not use the words 'I' or 'you' in his sessions. His conscious thoughts were derived from other peoples' consciousness and did not link up with his own perceptions. After about three years of analysis the patient started to remember his sessions. Whereas before he seemed half awake and half asleep, half conscious and half unconscious, he became awake enough to perceive.

Consciousness

Michael Balint.

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History, 20th Century

Psychoanalysis applied to medicine: a personal note.

The psychoanalyst has much to contribute to medicine, more through the teaching of observational skills and an appreciation of relationships than through the teaching of psychoanalytic technique or languate itself. The analyst can promote tolerance in the physician of the unusual, an examination of the impediments of habitual ways of working and seeing, and a facility in the patient to "be himself". Attention to the unusual, as illustrated through experience in training-cum-research seminars, can enhance the doctor's satisfaction with his professional life while offering improved care to his patients. When psychoanalyst, physician and patient interact in their roles as people, there is hope of an improved quality of human existence for all.

Attitude of Health Personnel