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Biomedical subjects

V Brabec

Publications and source records attributed to V Brabec.

At least 91 records · Page 5Linked to original sources

[The importance of determination of ferritin levels in erythrocytes].

The basic ferritin level in red cells was examined in 60 healthy volunteers and in 110 patients with various diseases of the red cell series. From samples of heparinized whole blood first leucocytes were removed and then they were haemolyzed. After subsequent centrifuging in the supernatant the basic ferritin content was assessed by means of an Amersham Ferritin RIA kit (Amersham, Great Britain). Normal values in healthy volunteers varied between 3.2 and 30.2 ag/ery. In patients with iron deficiency the values were significantly reduced, in patients with pernicious anaemia, beta-thalassemia minor, hereditary spherocytosis and glucose-6-phosphate dehydrogenase deficiency or pyruvate kinase deficiency the levels of red cell ferritin were significantly elevated, as compared with the control group. The red cell ferritin level depends on the iron supply to cells of the red cell series and the amount needed for erythropoiesis. A reduced supply in sideropenia leads to a reduced level of red cell ferritin, in haemolytic anaemia its level depends on the generally elevated iron supply in the organism and possibly impaired haemoglobin synthesis, on the one hand, and concurrent elevated iron requirements in case of hyperplasia of red cell formation, on the other hand. Assessment of red cell ferritin is important not only for accurate estimation of the amount of iron available in the cell for haeme formation but also to elucidate the pathogenesis of some changes of iron metabolism in diseases of the red cell series.

Anemia, Hemolytic↗

[Elution of sensitized erythrocytes with chloroquine].

The results of erythrocyte elutions sensitized either in vitro or in vivo with a 15% solution of Chloroquine indicate that at a low degree of sensitization it is possible in more than half of the tested cases to release incomplete antibodies from the red cell surface without causing damage of the group receptors. This makes it possible to assess the phenotypes of the majority of erythrocyte characteristics, although some may be weakened by elution.

Antigen-Antibody Reactions↗

Biophysical studies of the modification of DNA by antitumour platinum coordination complexes.

Cisplatin (cis-diamminedichloroplatinum(II] is widely used in the treatment of various human tumours. A large body of experimental evidence indicates that the reaction of cisplatin with DNA is responsible for the cytostatic action of this drug. Several platinum-DNA adducts have been identified and their effect on the conformation of DNA has been investigated. Structural studies of platinum-DNA adducts now permit a reasonably good explanation of the biophysical properties of platinated DNA. Antitumouractive platinum compounds induce in DNA, at low levels of binding, local conformational alterations which have the character of non-denaturing distortions. It is likely that these changes occur in DNA due to the formation of intrastrand cross-links between two adjacent purine residues. On the other hand, the modification of DNA by antitumour-inactive complexes results in the formation of more severe local denaturation changes. Conformational alterations induced in DNA by antitumour-active platinum compounds may be reparable with greater difficulty than those induced by the inactive complexes. Alternatively, non-denaturation change induced in DNA by antitumour platinum drugs could represent more significant steric hindrance against DNA replication as compared with inactive complexes.

Animals↗

Serum ferritin in patients with various haemolytic disorders.

174 serum ferritin assays in 121 patients with various haemolytic disorders have been performed. The mean serum ferritin levels were significantly increased in all these disorders in contrast to healthy controls. The highest serum ferritin levels were found in pyruvate kinase (PK) deficiency, moderate increase was observed in hereditary sphaerocytosis (HS) and in autoimmune haemolytic anaemia (AIHA) with massive haemolysis and in glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Mild elevation of serum ferritin levels was depicted in paroxysmal nocturnal haemoglobinuria (PNH), in beta thalassaemia minor and in other types of haemoglobinopathies. The range of values was associated with a degree of haemolysis and its relation to duration of the disease was not apparent in most cases. Highly significant differences between serum ferritin levels in splenectomized and non-splenectomized patients with HS and between serum ferritin levels in patients with AIHA with massive haemolysis or in remission were found. As compared to normal controls, significant increase of serum ferritin levels was observed even in patients with AIHA in remission or in splenectomized patients with HS. In two patients with PK deficiency the levels exceeding 2,000 micrograms/l indicated manifest iron overload. A reliability of serum ferritin assay as an index of iron stores in haemolytic disorders has been discussed.

Adult↗

Acidified glycerol lysis test in various haemolytic anaemias.

Acidified glycerol lysis test (AGLT) was found to be an appropriate technique for detection of sphaerocytes in blood particularly in hereditary sphaerocytosis. The incubation of blood for 5 hours at 37 degrees C prior to measurement exerts positive effect on the reliability of the test and may further suggest the type of haemolytic disorder.

Anemia, Hemolytic↗

[Beta thalassemia in pediatric practice. A group of 22 pediatric patients].

The authors describe 22 cases of beta-thalassaemia minor in 11 boys and 11 girls from Czech families. The children suffer as a rule mild hypochromic anaemia with marked microcytosis and rather elevated red cell values. The serum ferritin values are normal, serum iron is normal or slightly elevated. In all children the ratio of haemoglobin A2 is raised (to 4-7%) and in 40% the ratio of haemoglobin F is raised (to 1.5 to 5.9%). There are no differences between boys and girls in the investigated parameters. The boy have, as compared with adult men with beta-thalassaemia minor, significantly lower values of red blood cells and serum ferritin. There are no significant differences between girls and adult women suffering from this disease.

Adolescent↗

Heterogeneity of glucose-6-phosphate dehydrogenase enzymopathies in the CSSR.

GdB- variants of 7 patients from the CSSR have been isolated and characterized kinetically. The properties of these G6PD variants differ phenotypically. Among them we found both a variant with a very high Km G6P and a severe chronic hemolytic anemia and one patient with a low Km G6P variant and only intermittent hemolytic crises and moderate hyperbilirubinemia. The low-Km enzyme corresponds to GdMediterranean like variants with a high utilization of substrate analoga and a biphasic pH profile. A third GdB- variant exhibits a low NADP affinity and high inhibition by ATP. A noticeable low utilization of the analogon dNADP was detectable for two enzymes of heterozygotes.

Czechoslovakia↗

Rheological evaluation of pathological, perturbed normal and reconstituted red cell membranes.

Whole red cell deformability was studied by ektacytometry. Reduced shear induced red cell elongation was observed in some hemolytic disorders, chiefly in those where spherocytes occur. With the same technique, red cell membrane deformability and stability were studied following mild proteolytic digestion with trypsin. Reconstitution with spectrin restored in part the membrane elasticity while band 4.1-protein exerted stabilizing effect on the perturbed membrane.

Anemia, Hemolytic↗

Reinterpretation of fluorescence of terbium ion-DNA complexes.

Terbium (Tb3+) fluorescence was used to investigate local non-denaturation perturbations of double-helical DNA structure induced in this nucleic acid by various physical and chemical agents. It has been shown that the interaction of Tb3+ with DNA into which single-strand or double-strand breaks have been introduced by DNase I or by low doses of ionizing radiation does not influence the fluorescence of the lanthanide cation. On the other hand, interaction of terbium with DNA modified by the antitumour drug cis-diamminedichloroplatinum(II) at low levels of binding and by low doses of ultraviolet radiation (wavelength 254 nm) has been shown to result in substantial enhancement of the fluorescence of this cation. It has been proposed that the terbium fluorescent probe can also be exploited successfully for the purpose of analysing the guanine bases present in distorted double-stranded regions of DNA, in which only the vertical stacking of the base-pairs is altered.

Antineoplastic Agents↗

[Clinico-biochemical characteristics of patients with congenital glucose-6-phosphate dehydrogenase deficiency in erythrocytes].

The authors submit a clinical and biochemical investigation of five families with a congenital glucose-6-phosphate dehydrogenase red cell deficiency. Congenital nonspherocytic haemolytic anaemia was detected only in one hemizygous carrier, in four there was latent haemolysis with intermittent haemolytic crises and hyperbilirubinaemia. In 14 relatives carriership was revealed without clinical manifestations. The authors give a biochemical characteristic of kinetic properties of enzymatic variants according to WHO instructions (enzyme activity, thermal stability, pH stability and other kinetic constant) and emphasize the need to improve the diagnosis.

Adolescent↗

Evaluation of cytotoxic and antitumor effects of a tetravalent analog of carboplatin.

The cytostatic and cytocidal effects of a newly synthesized tetravalent platinum drug (CBDCA-ox) on two experimental ascites tumors as well as on normal tissues of the mouse were investigated. It was found that CBDCA-ox exhibited only negligible acute toxicity in comparison with its reduced analog. Also hemotoxicity of this tetravalent drug was markedly lower than that of CBDCA. The comparison of antitumor activity of CBDCA and CBDCA-ox tested against LS/BL lymphosarcoma and EAT tumor cells strongly supports the view that CBDCA-ox deserves further preclinical testing.

Animals↗

Adsorption of human beta 2-microglobulin at a water/mercury interface.

Adsorption of human beta 2-microglobulin from a neutral solution of 0.15 M NaCl on a mercury surface was studied at 25 degrees C by measurement of the differential capacity of the electrical double layer. From the diffusion-controlled adsorption kinetics, the surface concentration and hence the area occupied by the adsorbed beta 2-microglobulin molecule were determined at various potentials of the mercury surface. The results indicate unfolding or flattening of beta 2-microglobulin molecules adsorbed in particular on the electrically uncharged surface. The extent of this interfacial conformational rearrangement was reduced with growing positive or negative surface charge density.

Adsorption↗

Pyruvate kinase-deficiency anemia: membrane approach.

Low ionic strength extraction (37 degrees C, 30 min) of ghosts from PK-deficient erythrocytes provided crude spectrin extract. No significant differences in the extract composition compared to normal donors were observed. The reticulocyte-dependent spectrin extractability was found among the subjects with PK-deficiency anemia. Likewise ATP-depletion affects spectrin extractability and also leads to the adsorption of cytoplasmic protein MW 50,000 to the reticulocyte membrane. The measurement of membrane fluidity using the fluorescence probe DPH did not reveal significant alterations in the moiety of integral membrane constituents.

Adenosine Triphosphate↗

The effect of platinum derivatives on interfacial properties of DNA.

The interaction of DNA modified by the binding of various platinum compounds with an electrically charged mercury surface was studied by means of linear sweep voltammetry. It was found that DNA and its adducts with antitumour active cis-diammine-dichloroplatinum(II) (cis-DDP) on the one hand and antitumour inactive trans-diamminedichloroplatinum(II) (trans-DDP) and diethylenetriaminechloroplatinum(II) chloride (dien-Pt) on the other were unwound due to their adsorption on the negatively charged mercury surface polarized to the potentials of a narrow region around -1.2 V (vs. saturated calomel electrode). The modification of DNA by bifunctional platinum compounds (cis- and trans-DDP) resulted in a substantial lowering of the extent of this interfacial conformational rearrangement, the modification by trans-DDP being more effective. The modification of DNA by monofunctional dien-Pt influenced the unwinding of DNA on the mercury surface only negligibly. It has been concluded that in particular interstrand cross-links induced by platinum compounds in DNA are responsible for the effect of these drugs on the extent of the interfacial unwinding of DNA. This conclusion is in good agreement with the view that among the lesions induced in DNA by platinum compounds, the interstrand cross-links are of less significance from the point of view of the antitumour efficacy of these inorganic drugs.

Antineoplastic Agents↗

Reticulocyte-dependent labeling alterations of red cell membrane in pyruvate kinase deficiency anemia.

The radioactive labeling of spectrin using the pentavalent complex of molybdenum-99 was applied to the study of membrane protein in pyruvate kinase deficient red cells. Compared to the control, the labeling profile of the enzymopathic red cell membrane proteins remained generally unchanged but the molybdenum uptake was found to depend largely on the reticulocyte count. This finding may reflect changes during the cell maturation.

Anemia, Hemolytic↗