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Biomedical subjects

A L Pawlak

Publications and source records attributed to A L Pawlak.

At least 19 recordsLinked to original sources
PubMed1991

Ah locus-associated differences in induction of sister-chromatid exchanges and in DNA adducts by benzo[a]pyrene in mice.

The effect of alleles of the Ah locus on the induction of sister-chromatid exchanges (SCE) was studied in C57Bl/6 and in DBA/2 mice treated twice intragastrically with benzo[a]pyrene (BP, 100 or 10 mg/kg b.w.). To measure the changes in the frequency of SCE, 2 protocols were used: in vivo in bone marrow cells after implantation of 5-bromodeoxyuridine (BrdU) tablets and in vivo/in vitro in spleen lymphocytes cultured with BrdU. On day 5 mice were killed and SCEs estimated in bone marrow cells. BP-DNA adducts in bone marrow and spleen were analyzed on day 5 after the same exposure to BP. In the spleen lymphocytes SCE frequencies were analyzed after an additional 48 h of culture. We found that at both doses of BP, the number of SCEs and BP-DNA adducts in bone marrow and in spleen cells was significantly higher in aryl hydrocarbon hydroxylase (AHH)-non-inducible (DBA/2) mice than in AHH-inducible (C57BL/6) mice. Only marginal induction of SCE was noted after the high dose of BP in C57BL/6 mice in bone marrow in vivo, whereas a highly significant increase in the frequency of SCEs was found in splenocytes in the in vivo/in vitro test. The spleen cells contained larger amounts of BP-DNA adducts and demonstrated higher absolute levels of SCEs than bone marrow cells. The sensitivity of both the in vivo/in vitro and the in vivo SCE test is high enough for assessment of Ah locus-linked differences in BP genotoxicity in mice at the prolonged time between treatment and cell preparation. The present data confirm the influence of inducibility of AHH in the intestine on the genotoxicity of BP to distal tissues after oral exposure to BP.

Animals↗
PubMed1991

Unaltered cell proliferation rate of the ataxia telangiectasia lymphocytes dividing in vitro.

Lower cell density was found in cultures of ataxia telangiectasia lymphocytes as compared to control lymphocyte cultures. This fits with the earlier observations of decreased incorporation of 3H-Thymidine into lymphocytes of ataxia telangiectasia (AT) patients. However, the finding that there was no significant difference in proliferation rate index between AT and control cultures was unexpected. This may indicate that both cell count and measurements of thymidine incorporation in lymphocyte cultures characterize cell populations distinct from that of proliferating cells.

Ataxia Telangiectasia↗
PubMed1990

Carriers of ataxia-telangiectasia gene display additional protein fraction and changes in the environment of SH groups in erythrocyte membrane.

Additional protein fraction migrating slower than spectrin has been detected in erythrocyte membranes from an ataxia-telangiectasia (A-T) patient and from his mother (A-T heterozygote). In erythrocyte membranes labelled with maleimide spin label changes in signal of the weakly immobilized spin label as related to that of strongly immobilized one (w/s) were noted. In comparison to age-matched control groups the values of w/s were lower in A-T heterozygotes (ten persons) and higher in A-T homozygotes (four persons). In control persons the values of w/s increased with age, whereas in families with A-T no significant differences in this parameter were noted between children and parents. The presence of additional protein fraction in erythrocytes membranes of A-T patient and A-T heterozygote indicates that these phenotypes can be differentiated from the healthy control persons for the first time on the basis of changes detected in the erythrocytes. This change in erythrocyte membrane may explain the decrease in the w/s parameter of electron spin resonance in A-T heterozygotes. On the other hand increased values of w/s in A-T patients may be caused by disease process.

Adult↗
PubMed1990

Increased frequency of chromatid breaks in lymphocytes of heterozygotes of ataxia telangiectasia after in vitro treatment with caffeine.

The frequencies of caffeine-induced chromosomal aberrations (CA), mainly chromatid (CdB) and chromosome (CB) breaks, were studied in lymphocyte cultures derived from 6 obligatory heterozygotes and 1 homozygote of ataxia telangiectasia (AT), and from 4 control adult healthy persons. Caffeine (CF, 1 mM) was added at the beginning of the culture. In control cultures exposed to CF the frequency of CB was 1.9% and of CdB 1.3%. In cells of the AT homozygote, the frequency of CdB was 6.8% in the absence and 8.7% in the presence of caffeine, the frequencies of CB being 3.4 and 10.9%, respectively. In AT heterozygous cells treated with CF, CdB increased 13-fold as compared to a less than 3-fold increase in control cells. Comparing the frequencies of CF-induced chromosomal lesions in control and AT heterozygous cells, potentiation factors (Pf) for the effect of 1 AT gene on cell sensitivity to CF (Pf [AT]) were 3.5 for CB, 6.6 for CdB and 5.5 for CA. These data demonstrate that lymphocytes of AT heterozygotes are significantly more sensitive to caffeine treatment in vitro in terms of increased frequency of CdB than normal cells, which may be useful for the diagnosis of carriers of this defective gene.

Ataxia Telangiectasia↗
PubMed1990

[Use of monoclonal antibodies for studying cytochrome P-450 forms. Use of interspecies homology of amino acid sequence].

The current research on utilization of monoclonal antibodies for isolation of cytochrome P-450 forms, substrate specificity determination, localization in tissues and contribution in DNA adduct formation is reviewed in this paper. Usefulness of monoclonal antibodies directed against rodent cytochrome P-450 isoenzymes to human investigations is emphasized.

Amino Acid Sequence↗
PubMed1990

Increase in cooperativity of oxygen binding as a factor related to high maximal oxygen uptake during physical effort.

In a group of trained, nonsmoking men, apparent haemoglobin oxygen affinity was assessed in vitro in the whole blood collected immediately before and after maximal physical effort. Measurements were performed using standard laboratory equipment. Maximal oxygen uptake (V O2 max) has been monitored during maximal physical effort. Increase in app Hb-oxygen affinity after exercise was found by measurements of p25 and by differences between plots of correlations between V O2 max and resting and post-exercise parameters of Hb-oxygen binding. Significant correlations were found between preexercise n50 and VO2 max (r = -0.59) and between post-exercise log P50 and V O2 max (r = 0.6). Exercise-induced increase in Hb-oxygen affinity and in cooperativity of Hb-O2 binding were found to be higher in persons with higher values of VO2 max.

Adolescent↗
PubMed1989

The inhibitory effect of theophylline on cell cycle kinetics of human lymphocytes in vitro.

The effect of theophylline (TF) on proliferation of lymphocytes in phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) freshly stimulated 3-4 days cultures or of 14-days cultured lymphoblasts was studied. Proliferation was estimated by measurement of incorporation of tritiated thymidine (3H-TdR), and by microscopic analysis of cellular divisions progression up to the 4th generation of cells cultured in presence of 5-bromodeoxyuridine (BrdUrd). The strongest inhibition of proliferation was observed when TF was added at the beginning of the cultures. However, when TF was added for the last 20 h of the cultures, a significant decrease in number of the third (M3) and fourth (M4) generation cells was noted and M3/M4 ratio increased from 6.4 up to 19.1. TF inhibited also incorporation of 3H-TdR into cultured lymphoblasts. The obtained data indicate an inhibitory effect of TF both an activation and cell cycle progression of lymphocytes.

Aminophylline↗
PubMed1988

Kinetics of benzo(a)pyrene hydroxylation at varying concentrations of NADPH and NADH in liver microsomes of nontreated and beta-naphthoflavone-treated C57BL/2 and DBA/2 mice.

The biphasic kinetics of hydroxylation of benzo(a)pyrene (B(a)P) dependent on the concentration of either NADPH or NADH has been observed in DBA/2 (AhdAhd) but not in C57BL/6 (AhbAhb) beta-naphthoflavone-treated mice. On the other hand, in nontreated mice, this biphasic kinetics has been observed in both strains of mice. This shows that characteristics of biphasic kinetics differentiate Ahb from Ahd mice only after treatment with methylcholanthrene-type of inducers. The discussed biphasic kinetics was more regular and distinct in the NADH-dependent reaction as compared with NADPH-dependent hydroxylation of B(a)P. It is suggested that the NADH-specific pathway of electron transport to cytochrome P-450 is necessary for the occurrence of this effect both in NADH- and NADPH supported reaction.

Animals↗
PubMed1987

Physical effort-induced decrease in apparent whole blood Hb-oxygen affinity normalized for intraerythrocytic pH (pHe) at low initial values of pHe.

Effect of physical effort on haemoglobin-oxygen affinity was studied in whole blood of 28 healthy males. In persons showing decrease in pH gradient between plasma and erythrocytes after physical effort, a parallel decrease in apparent, normalized for intraerythrocytic pH (pHe), Hb-oxygen affinity was noted. An increase in pH gradient after exercise was accompanied by increase in apparent, corrected for pHe, Hb-oxygen affinity and in blood Hb content. Correlation between exercise-induced changes in Hb-oxygen affinity and in pH gradient (-0.66) was highly significant (p less than 0.001). It is suggested that both parameters may be increased by recruitment into circulation of old erythrocytes from spleen. Decrease in both parameters may be related to low values of intraerythrocytic pH before effort. Groups of persons differing in exercise-induced changes of Hb-oxygen affinity did not differ in maximal oxygen utilization.

2,3-Diphosphoglycerate↗
PubMed1977

Parallel occurrence of oxidant-sensitivity and decreased inhibition by NADPH in G-6-PD Lublin and G-6-PD Poxnań.

In two studied variants of G-6-PD without chronic hemolysis in probands, sensitivity of enzymes to inhibition by NADPH was decreased. Ki for NADPH was 28 micronM in Gd Lublin and 19 micronM in Gd Poznań. Susceptibility to the oxidant-induced hemolysis was described in probands, as well as in patients hemizygous for two other variants of G-6-PD with increased Ki for NADPH. It is suggested that in these cases, the oxidant-induced hemolysis is aggravated by their inability to counteract the drop in NADPH concentration with an increase in G-6-PD activity.

Adolescent↗
PubMed1977

Effect of ligands of ferric hemes on interaction between ferric and ferrous chains in partially oxidized hemoglobin A.

Normal values of Bohr effect of oxygenation of partially oxidized hemoglobin A with ferrihemes liganded either with H2O and OH or with CN have been found in the range of pH values from 6.8 to 7.6 in 45 micrometer (Fe)-hemoglobin containing 36--38% of ferrihemes. As the changes of oxygen affinity of Hb A induced by changes of pH are due to the modifications of R state, this quaternary conformation is thought to be unchanged in the studied of R state, this quaternary conformation is thought to be unchanged in the studied forms of partially oxidized hemoglobin. It is suggested that interactions between ferric and ferrous hemes leading to the increased affinity of ferrous hemes to oxygen occur in deoxygenated form of partially oxidized hemoglobin. In partially oxidized hemoglobin with ferric hemes liganded with H2O asymmetry of oxygen binding curves has been noted, which is not observed in forms with ferric hemes liganded with OH ot CN. This shows the effect of ligands of ferric hemes on interactions between chains containing ferric and ferrous hemes.

Ferric Compounds↗
PubMed1975

G-6-PD Poznań, variant with severe enzyme deficiency.

A new variant of G-6-PD with severe enzyme dificiency without chronic hemolysis is characterized. The biochemical properties of the variant closely resemble those of the G-6-PD Ramat-Gan described in a case of chronic non-spherocytic hemolytic anemia. As the family data on linking of chronic hemolysis with Ramat-Gan variant are lacking, the differentiation of the variants on the basis of clinical manifestations is not well-founded.

Child, Preschool↗