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Biomedical subjects

J Hradec

Publications and source records attributed to J Hradec.

At least 55 records · Page 3Linked to original sources
PubMed1990

[Is it possible to treat cardiac hypertrophy?].

Cardiac hypertrophy in heart disease is associated with a deterioration of the patient's prognosis. From experimental work it is known that hypertrophy can recede, sometimes it is, however, associated with an undesirable increase of fibrous tissue in the heart muscle. In clinical practice we can reduce cardiac hypertrophy (assessed mainly by echocardiography), at least in some patients, by reducing or eliminating the evoking cause (e.g. in sportsmen terminate training, in aortic valve disease by replacement of the valve, in hypertonic patients we reduce the pressure by drugs). After regression of hypertrophy later also the amount of fibrous tissue recedes and as a rule the function does not deteriorate. Lately we are trying to influence factors which directly participate in the hypertrophy of the myocytes, in particular in hypertonic subjects by preferential action on the adrenergic system and the renin angiotensin system.

Cardiomegaly↗
PubMed1990

Peroxidase-mediated reaction of the carcinogenic non-aminoazo dye 1-phenylazo-2-hydroxynaphthalene with transfer ribonucleic acid.

Horseradish peroxidase in the presence of hydrogen peroxide has the ability to mediate the activation of carcinogenic 1-phenylazo-2-hydroxynaphthalene (Sudan I) to DNA- and transfer RNA (tRNA)-bound products in vitro. tRNA is more accessible for modification by the activated carcinogen studied. tRNA modified by activated Sudan I becomes colored and has an absorption maximum of approximately 480 nm. Binding of metabolite(s) to tRNA is inhibited by ascorbate, glutathione, Mg2+ ions and nitrosobenzene. The mechanism of these protections was shown to be different for the different agents. tRNA modified by activated Sudan I exhibits a significantly increased acceptance for L-methionine. Enzymatic hydrolysis of modified tRNA with subsequent separation of nucleosides by HPLC suggests that the covalent modification of tRNA originating from the formation of more than one adduct with the nucleosides in tRNA is the predominant interaction of the activated Sudan I with tRNA.

Animals↗
PubMed1990

Mechanism of formation and 32P-postlabeling of DNA adducts derived from peroxidative activation of carcinogenic non-aminoazo dye 1-phenylazo-2-hydroxynaphthalene (Sudan I).

Horseradish peroxidase in the presence of hydrogen peroxide mediates the activation of carcinogenic 1-phenylazo-2-hydroxynaphthalene (Sudan I) to DNA-bound products in vitro. The peroxidase activating system is greater than 10 times more effective with respect to DNA modification by Sudan I than the microsomal enzymes containing cytochrome P450. The DNA-binding reaction of the Sudan I metabolite(s) formed by the peroxidase system is dependent on Sudan I and H2O2 concentration and pH. Reactive intermediate(s) or product(s) of the Sudan I oxidation by peroxidase with a short half-life are responsible for the DNA modification. DNA modified by peroxidase-activated Sudan I becomes colored and has an absorption maximum at approximately 480 nm. The modification of DNA by Sudan I metabolites(s) formed by the peroxidase system is inhibited by some compounds of physiological importance (ascorbate, glutathione, Mg2+ ions) and by radical trapping agents (nitrosobenzene, methyl viologen). 32P-Postlabeling assay of the DNA modified by Sudan I activated by the peroxidase system indicates that the covalent DNA adduct formation is the principal type of the DNA modification. Four major and several minor adducts of deoxyribonucleotide 3',5'-bisphosphate from DNA with Sudan I metabolite(s) were detected by the classical Randerath 32P-postlabelling assay as well as by the nuclease P1 version of the same method.

Animals↗
PubMed1990

The initiator tRNA acceptance assay as a short-term test for carcinogens. 6. Results with 78 polycyclic aromatic compounds.

A total of 78 polycyclic aromatic compounds (PAH), including pure hydrocarbons, PAH metabolites, aromatic amines and nitroarenes, were tested in the initiator tRNA acceptance assay (tR assay) for carcinogens. Among the pure hydrocarbons, all strong carcinogens were highly active in the tR assay. Some weak carcinogens showed moderate positive responses, others as well as all possible non-carcinogens were inactive. Various PAH metabolites, including phenols, dihydrodiols, arene oxides, dihydrodiol epoxides, quinones and benzylic sulfate esters, were positive as well. Strikingly, however, their effects rarely reached the levels observed with the strong carcinogens among the pure hydrocarbons. Moreover, the correlation with carcinogenicity was less clear, partially due to limitations in the available carcinogenicity data. The activities in the tR assay were also compared with the mutagenicity in Salmonella typhimurium. No appreciable correlation was observed. For example, trans-9,10-dihydroxy-9,10-dihydrobenzo[c]chrysene, in the absence of a mammalian metabolic system, was highly active in the tR assay, but non-mutagenic. Upon addition of rat liver enzymes, the reverse result was obtained. syn-Benzo[c]chrysene-9,10-dihydrodiol-11,12-oxide, on the other hand, was a potent direct mutagen, but required the presence of liver microsomes for a positive response in the tR assay. Thus, the metabolic basis for these two activities is different, and not yet understood for the tR assay. The partial correlations in the tR assay and in the Salmonella mutagenicity assay with carcinogenicity, and the pronounced discrepancies between these in vitro tests, may suggest that they detect different mechanisms involved in carcinogenicity. However, the tR assay was less predictive for the carcinogenicity of PAHs as compared to the previously investigated N-nitroso compounds and mycotoxins.

Carcinogenicity Tests↗
PubMed1990

Stimulating effect of blood serums from tumor-bearing rats on cholesteryl ester synthesis in normal rat liver cytosol in vitro.

Addition of diluted blood serum from tumor-bearing rats stimulated significantly the synthesis of cholesteryl esters from labeled cholesterol and endogenous fatty acids in the cytosol derived from normal rat liver. With both Zajdela and Walker transplantable tumors this effect was found to be associated with the most intensive period of tumor growth. During chemical carcinogenesis induced by a single subcutaneous administration of benzo(a)pyrene the stimulating effect of sera was found to precede several weeks the appearance of palpable tumors and persisted during the period of progressive tumor growth. With all tumors used, sera in ultimate stages of tumor growth failed to show a stimulating effect. The stimulating effect was due to the presence of a yet unidentified lipid. Higher quantities of this substance may appear in the serum of tumor-bearing animals to meet higher requirements for cholesteryl esters during tumor growth. The stimulating effect of the blood serum on cholesteryl esters may be a useful marker of malignant tumors in humans.

Animals↗
PubMed1989

[The relation of flow velocity in the carotid vessels to age].

Using continual Doppler sonography, the authors measured the highest systolic blood flow rate in the extracranial carotid bloodstream in 3 groups of non-cardiac patients of an average age of 22, 76 and 93 years. In each group, the arteria carotis communis showed, with increasing age, a decrease in the highest systolic rate: 0.692 +/- 0.084 - 0.414 +/- 0.073 - 0.297 +/- 0.031 m/s (p less than 0.01 in all the three groups). Equally, a decrease in the highest systolic rate was found in the arteria carotis interna: 0.506 +/- 0.071 - 0.298 +/- 0.064 - 0.211 +/- 0.10 m/s (p less than 0.01 in all 3 groups). The paper shows a statistically significant decrease in the systolic blood rate in the carotid bloodstream related to aging (p less than 0.01) and discusses causes of this phenomenon.

Adolescent↗
PubMed1989

Micropreparative separation of transfer ribonucleic acids by high-performance liquid chromatography.

A method was developed for the micropreparative separation of individual species of tRNA using reversed-phase high-performance liquid chromatography on large pore spherical silica bonded with C3 alkyl chains. Columns were eluted with linear gradients of decreasing sodium chloride and increasing methanol concentrations. The decreasing salt gradient gradually abolished hydrophobic interactions and a significantly higher selectivity was thus obtained when compared with increasing gradients of salts usually employed in reversed-phase separations of tRNA. The acceptance of tRNA fractions was tested by charging them with fifteen different amino acids. Significantly different separations were obtained with tRNA from Escherichia coli and from rat liver. tRNAGlu and tRNATyr from E. coli were obtained in a pure form, all other tRNAs were more or less contaminated by adjoining tRNAs for other amino acids. Rechromatography under suitable isocratic conditions was required to obtain pure tRNA species from rat liver. Isoaccepting tRNAs for several amino acids were separated from rat liver. The method described seems suitable for preliminary fractionations of complex mixtures of tRNA and for a simple purification of isoaccepting species if the presence of tRNAs for other amino acids is not an hindrance.

Animals↗
PubMed1989

The initiator tRNA acceptance assay as a short-term test for carcinogens. 4. Results with 20 mycotoxins.

The activity of 20 mycotoxins was tested by the recently developed initiator tRNA acceptance assay for carcinogens. With the exception of citrinin, all compounds carcinogenic for rodents stimulated the charging of tRNA with L-methionine. In three out of four non-carcinogenic mycotoxins the test was negative. Five carcinogenic mycotoxins were negative in mutagenicity tests but positive in the acceptance assay indicating that also non-mutagenic carcinogens may be detected by the latter procedure.

Carcinogenicity Tests↗
PubMed1989

The initiator tRNA acceptance assay as a short-term test for carcinogens. 5. Results with 42 cytostatic drugs.

The activity of 42 cytostatic drugs used for the treatment of human cancer was tested by the initiator tRNA acceptance assay for carcinogens. Of 17 drugs carcinogenic for rodents, 16 (94.1%) gave a positive response in the assay and six (85.7%) out of seven non-carcinogens showed no activity. The predictive value of the test for cytostatics was 91.7%. Treatment of tRNA with several cytostatics resulted in an inhibition of its acceptance for L-methionine. Cyclophosphamide, dibromdulcitol, 5-deoxy-5-fluorouridine and vincristine also inhibited, in addition to this, the charging of unfractionated tRNA from rat liver with L-alanine, L-lysine, L-phenylalanine and L-valine. Some drugs apparently react with the same target nucleoside which is common for all species of tRNA (probably the terminal adenosine residue that is esterified with amino acids). Such compounds do not yield reliable results in the initiator tRNA acceptance assay since this inhibitory effect interferes with the stimulating effect characteristic for carcinogens. However, results of the present study agree well with those obtained earlier with different classes of compounds (N-nitroso compounds, mycotoxins, etc.) and indicate that this newly developed assay may be a useful alternative also for the testing of carcinogenicity of cytostatic drugs.

Amino Acids↗
PubMed1989

Valvular regurgitations in healthy young people.

Using colour Doppler flow imaging technique (CDFI) 153 young healthy volunteers (80 M, 73 W) aged 23.9 +/- 1.4 years were studied for the prevalence and characteristics of regurgitations in morphologically normal valves. Regurgitation in normal pulmonary valve was found in 67.4%. Mid- to end-diastolic pulmonary regurgitation prevailed with the jet of predominantly central type, with the mean maximal jet length (DJmax) = 1.1 cm and the mean proximal jet width = 0.3 cm. "Physiological" mitral regurgitation was registered in 39.3%, with DJmax = 1.3 cm, mean maximal left atrial systolic dimension at the moment of maximal regurgitation (DLAmax) = 4.2 cm and with LJmax/DLAmax ratio of 0.3. Tricuspid regurgitation was present in 54%, with DJmax = 2.1 cm. Aortic regurgitation was found in 1.3% only. Authors propose diagnostic criteria to differentiate regurgitations in normal valves ("physiological" regurgitations) from pathological ones.

Adult↗
PubMed1988

The initiator tRNA acceptance assay as a short-term test for carcinogens. 1. A standardized procedure.

A short-term test for carcinogens has been developed based on the interaction of chemical carcinogens with tRNA(FMet) in vitro. Transfer RNA from rat or rabbit liver is pre-treated with compounds to be tested in the presence of microsomal enzymes and NADPH. Re-isolated tRNA is then charged with L-methionine by aminoacyl-tRNA synthetases from E. coli B. Carcinogens induce a stimulation of tRNA charging whereas chemically similar non-carcinogenic compounds do not show this effect. Experiments with model substances N-methyl-N'-nitro-N-nitrosoguanidine (strong carcinogen) and aflatoxin G1 (weak carcinogen) revealed some differences in dose effect relationships. It is advisable to test unknown compounds at three different concentrations (10(-5), 10(-7) and 10(-9) mg/ml) with at least two different quantities of microsomal enzymes. Tests on greater than 150 different compounds performed so far indicate that the evaluation of results as % of stimulation (when compared with the control value obtained with the charging of tRNA treated with the solvent only) may allow a quantitative discrimination between weak and intermediate, and strong carcinogens. The procedure is rapid, well reproducible and relatively inexpensive and may be used to complement the other short-term tests for carcinogenicity.

Animals↗
PubMed1988

The initiator tRNA acceptance assay as a short-term test for carcinogens. 2. Results with ten compounds selected by the International Programme on Chemical Safety for the evaluation of short-term tests for carcinogens.

Eight carcinogenic and two non-carcinogenic compounds that are difficult to detect by short-term tests (acrylonitrile, benzene, benzoin, caprolactam, diethylhexylphtalate, diethylstilbestrol, hexamethylphosphoramide, phenobarbital, safrole and o-toluidine) were tested independently in Prague and in Heidelberg by the newly developed initiator tRNA acceptance assay. Seven out of eight tested carcinogens gave a positive response in this assay, only safrole showed a false negativity in both laboratories. Both non-carcinogenic compounds, benzoin and caprolactam, exhibited no activity. An absolute qualitative agreement was found with all compounds tested between the results of both laboratories. With the exception only of phenobarbital (intermediate activity in Prague and low in Heidelberg) the quantitative results obtained in both laboratories were comparable. The initiator tRNA acceptance assay thus appears to be a reliable short-term test for carcinogenicity with good reproducibility.

Carcinogens↗
PubMed1988

The initiator tRNA acceptance assay as a short-term test for carcinogens. 3. Results with 69 N-nitroso compounds.

The activity of 69 carcinogenic and non-carcinogenic N-nitroso compounds was tested by the recently developed initiator tRNA acceptance assay for carcinogens. Of 51 carcinogens tested, 50 were active in the assay. Only N-nitrosopropylpropanolamine showed a false negativity. Eleven out of 14 tested non-carcinogenic compounds were not active in the assay, nitrosoethyl-tert-butylamine and nitrosoprolineethylester were positive. As calculated from these data, the sensitivity of the assay was 98.0%, specificity 84.6%, accuracy 95.4% and predictive value 94.4%. Comparison of relative carcinogenicities in animal bioassays with quantitative results (% stimulation of initiator tRNA charging) of the short-term test showed a good correlation for non-carcinogenic compounds and strong carcinogens. However, carcinogens of low and median potency could not be easily distinguished. A good correlation was obtained for three isomer N-nitrosomethylaminopyridines between the TD50-value and activity in the tRNA acceptance assay. The initiator tRNA acceptance assay thus seems preferable for recognizing and classifying carcinogenic and non-carcinogenic N-nitroso compounds than any other individual short-term test for carcinogenicity.

Animals↗