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Biomedical subjects

J Malec

Publications and source records attributed to J Malec.

At least 37 records · Page 2Linked to original sources
PubMed1987

Modification by caffeine of acute cytotoxic response of cultured L5178Y cells to hydroxyurea treatment.

The effect of caffeine (CAF) on acute cytotoxic response of L5178Y lymphoblasts to hydroxyurea (HU) treatment was studied. The following events were examined: abnormal cell enlargement (giant cell formation), the rate of recovery of cell reproduction and DNA synthesis after releasing the cells from the HU blockage, parental DNA breakage and cell death. The presence of CAF at nontoxic concentration prevented giant cell formation, enhanced cell growth inhibition and cell killing. The effect of CAF was variable, dependent on the duration of exposure to HU and the time of exposure to CAF. To obtain maximal effect, the continuous presence of CAF during HU treatment and posttreatment time was necessary. Hydroxyapatite chromatography assay of single strand (ss) and double strand (ds) fractions in parental DNA and the measurement of the rate of post-treatment recovery of DNA synthesis indicated that CAF enhanced HU-induced DNA lesions. It is concluded that the results give further evidence that even short HU treatment can damage not only newly formed but also parental DNA. The lesions are normally, at least partly repaired and can be expressed under the conditions of DNA repair inhibition.

Animals↗
PubMed1986

Mechanism of unbalanced growth-induced cell damage. II. A probable relationship between unbalanced growth, DNA breakage and cell death.

This study examines the relationship between unbalanced growth, DNase II activity, DNA breakage and cell survival during the exposure of L5178Y cells to hydroxyurea (HU), excess thymidine (dThR) or HU with excess of four deoxyribonucleosides (dNR). It has been found that in the cells arrested by HU or dThR, but still appearing viable with the trypan blue exclusion test, Protein/DNA imbalance and abnormal cell volume are correlated with enhancement of DNase II activity in the cells and in the medium and with moderate increase in parental DNA breakage. The incidence of DNA breaks was markedly potentiated in the presence of non-toxic concentration of caffeine (CAF), used to inhibit DNA repair. In HU+dNR arrested cells, in which unbalanced growth was abolished, enhancement of DNase II activity and of DNA breakage in the presence or absence of CAF was substantially prevented. Comparison of posttreatment cell survival in the presence or absence of CAF confirmed the differential effect of CAF: while in HU or dThR arrested cells the presence of CAF induced marked cell killing, in HU+dNR arrested cells the influence of CAF was negligible. Only a slight effect of CAF was observed in cells in which dThR-induced arrest and unbalanced growth were reversed by deoxycytidine (dCR) addition. It is suggested that the involvement of DNA nucleases in the unbalanced growth-induced overproduction of numerous hydrolytic enzymes, with their progressive leakage through the cell membranes, can lead to progressive DNA digestion. DNA breaks produced in this way are normally, at least partly, repaired. Concomitant exposure of such cells to DNA repair inhibitor can markedly enhance the level of breaks, leading to potentiation of unbalanced growth-induced cell killing.

Animals↗
PubMed1986

Mechanism of unbalanced growth-induced cell damage. I. A probable role for hydrolytic enzymes synthesis.

This study examines the relationship between cell progress into the state of unbalanced growth, hydrolytic enzyme activities and cell survival during the exposure of L5178Y cells to hydroxyurea (HU), excess thymidine (dThR), hydroxyurea with excess of four deoxyribonucleosides (dNR) or excess dTHR with deoxycytidine (dCR). Cell progress into the state of unbalanced growth was measured as cell size, protein/DNA ratio and protein content per cell. Activities of two lysosomal (acid phosphatase, beta-N-acetylglucosaminidase) and one cytoplasmic non-lysosomal (LDH) enzymes were determined. It has been found that in cells arrested by HU or excess dThR, a progressive cell volume increase with protein/DNA imbalance is correlated with a progressive increase in lysosomal and non-lysosomal hydrolase activities in the cells and in the medium and with a marked lethal effect. Cell volume increase, enhancement of enzyme activities and cell killing could be prevented in HU-arrested cells by concomitant addition of excess dNR (deoxyadenosine, deoxyguanosine, thymidine, deoxycytidine) leading to equal inhibition of DNA and protein synthesis. Control-like values of all parameters were achieved also in cells in which the dThR-inhibiting effect was reversed by dCR addition. It is suggested that a common pathway in the mode of action of the chemotherapeutic agents inducing cell killing through the state of unbalanced growth can be the over-production, abnormal accumulation and progressive leakage of numerous hydrolytic enzymes through the cell membranes, leading in consequence to 'lytic' cell death.

Acetylglucosaminidase↗
PubMed1986

Effect of hydroxyurea treatment on lysosomal membrane stability and enzyme latency in L5178Y cells in culture.

The stability of lysosomes prepared from hydroxyurea (HU) treated or untreated L5178Y cells and exposed to an HU-free iso- or hypoosmotic solution was compared. The data revealed that exposure of the cells to 1-10 mM HU for few hours tends to stabilize lysosomes. Partial protection against this effect could be afforded by catalase and superoxide dismutase. Under the same conditions of HU treatment lysosomal enzyme latency remained similar in HU treated and untreated cells.

Acid Phosphatase↗
PubMed1985

Amelioration of hydroxyurea-induced suppression of phagocytosis in human granulocytes by free radical scavengers.

The exposure of human circulatory white cells in vitro to 0.1-1-10 mol/l hydroxyurea (HU) for 20 h induced a progressive dose-dependent suppression of the phagocytic activity of granulocytes. The suppressing effect of 20 h exposure to 1 mol/l HU was used to examine the protection afforded by free radical scavengers against HU-induced cytotoxicity. It has been found that, in the suitable concentration of the protecting agent, a substantial protective effect of sodium benzoate, acetylosalicylic acid, alpha-tocopherol, ascorbic acid, catalase, peroxidase or superoxide dismutase can be achieved.

Antioxidants↗
PubMed1985

Giant cell formation in cultured L5178Y lymphoblasts induced by hydroxyurea treatment.

The conditions leading to hydroxyurea-induced abnormal cell enlargement (giant cell formation) were studied in L5178Y lymphoblasts in the culture. Exposure for only 1 hour to a concentration of 1 mM hydroxyurea (HU) was sufficient to produce an abnormal enlargement of about 25 percent of the cells. The maximal proportion of giant cells reached the value of about 50 percent after treatment with 1 mM HU for 5 hours and was not changed by a further prolongation of exposure time and/or by increasing the concentration of HU to 10 mM. Comparison of cell populations with various proportions of giant cells as regards their ability to reproduce, DNA synthesis and persistence in the culture suggested that at least some part of giant cells lost the ability to divide, their DNA synthesis was markedly suppressed or retarded and more than 50 percent of them disappeared earlier than 48 hours after the termination of HU exposure. It is concluded that at least at certain HU concentrations and in suitable stage of target cells the response of cells to short HU treatment can resemble that produced by X-rays or other DNA damaging agents.

Cells, Cultured↗
PubMed1984

Hydroxyurea has the capacity to induce damage to human erythrocytes which can be modified by radical scavengers.

The treatment of human erythrocytes with hydroxyurea [HU] results in the azide-dependent changes in osmotic fragility and in increased methemoglobin formation. Similar changes were induced by H2O2 treatment. However when H2O2 in the presence of azide stimulated malondialdehyde production, in the HU-treated cells no malondialdehyde was detectable. When subjected to an oxidant stress [sodium ascorbate] HU-treated erythrocytes were more fragile and revealed changes in the absorption spectrum of the TBA-reactive material in comparison with the cells treated with ascorbate alone. Partial protection by radical scavengers against certain HU-induced changes can be achieved. The results indicate that HU can damage erythrocytes and suggest the radical origin of these effects.

Ascorbic Acid↗
PubMed1983

Alteration in lysosome supravital staining as a marker of hydroxyurea-induced cytotoxicity and its modification by radical scavengers in L5178Y cells in culture.

Supravital staining of lysosomal membranes with euchrysine was employed to study hydroxyurea (HU)-induced side toxic effects in L5178Y lymphoblasts in culture. Exposure of cells to 0.1-1.0-10.0 mM HU-induced progressive increase in the proportion of cells without detectable lysosomal fluorescence. This effect preceded the occurrence of non-viable cells, determined by trypan-blue exclusion test. Addition of alpha-tocopherol, acetylsalicylic acid, sodium benzoate or ascorbic acid to the culture medium afforded a concentration-dependent modification of lysosomal response to HU treatment. It is suggested that the fluorescence technique of supravital lysosome staining can be a useful test in studies on the side toxic effects of free radical-forming drugs and their amelioration by radical scavengers.

Animals↗
PubMed1983

Rehabilitation of memory after craniocerebral trauma: case report.

A memory rehabilitation procedure is illustrated by a case study of a man with craniocerebral injury whose memory improved through practice of systematic approaches to remembering. The single-subject description involved tracking measures of several different cognitive abilities and demonstrated significant improvement in the patient's memory independent of changes in other nontreated cognitive abilities.

Adult↗
PubMed1983

Psychologic prediction of duration of inpatient spinal cord injury rehabilitation and performance of self-care.

The Beck Depression Inventory (BDI), the Derogatis Symptom Check List (SCL-90) and a short form of the Minnesota Multiphasic Personality Inventory (MMPI-168) were administered to 28 spinal cord injury (SCI) patients on admission to an inpatient rehabilitation program. Of the several psychologic measures derived from this battery of tests, measures of distress/depression predicted both duration of inpatient rehabilitation and performance of self-care of bladder and skin at discharge. Based on follow-up an average of 7 months post-discharge, the best predictor of future self-care behavior seems to be past self-care behavior, augmented by knowledge of personality tendencies. Results emphasize the importance of minimizing patient distress during SCI inpatient rehabilitation and suggest that, for some patients, psychologic intervention following discharge directed at modifying certain personality features may facilitate continued performance of critical self-care behaviors.

Adolescent↗
PubMed1982

Cannabis effect on spasticity in spinal cord injury.

A study was done to examine the perceived effects of cannabis on spasticity of spinal cord injured persons. Data compiled from 43 questionnaires of spinal cord injured persons suggested the following: 1) spinal cord injured persons reported decreased spasticity with marijuana use; 2) present use of marijuana correlated positively with past use; and 3) the person's reference or peer group contributed significantly to current use. The study suggests the need to examine the relationship between measurable and reported changes in spasticity.

Adult↗
PubMed1981

Pain management: long-term follow-up of an inpatient program.

To determine maintenance of lifestyle changes following completion of an inpatient behavioral pain management program, 40 patients were followed up by questionnaire 6 months to 3 years after program completion, with the majority contacted at least 18 months postdischarge. Thirty-two patients completed some portion of the questionnaire. Responders were similar to nonresponders in age, sex, chronicity of pain on admission, and time since discharge. Responses to specific items indicated that patients had increased activity level and employment and had decreased use of pain-related medications. A global measure of success was based on 3 criteria: (1) reported nonuse of narcotic analgesics, muscle relaxants and tranquilizers; (2) status as employed, in training, or running a household or continuation of 50% to 100% of exercises and reported increased recreational activities; and (3) no reported increase in pain. Of the patients providing adequate data for application of these criteria, 37% met all 3 standards at follow-up. Such a multivariate criterion is recommended for assessment of multidisciplinary pain programs. More frequently practices behaviors (ie, nonuse of medications, exercises) appeared better maintained. Thus, increased behavioral practice, particularly in vocational and recreational activities, is recommended.

Activities of Daily Living↗
PubMed1980

The use of Ficoll gradient centrifugation to obtain synchronously growing L5178Y cells.

Linear Ficoll gradient centrifugation has been used to separate exponentially growing cells according to their position in the cell cycle and to obtain synchronously growing cells. Analysis of the distribution of 3H-thymidine prelabeled cells revealed the optimal separation of the cells in the G1 phase in the gradient prepared from 3--9% solutions. Such G1-rich cell fraction collected from the gradient has proved useful to obtain fairly good synchronization of cell growth as evaluated by the measurement of cell number, 3H-thymidine incorporation and mitotic index.

Animals↗