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Biomedical subjects

K Lenhart

Publications and source records attributed to K Lenhart.

At least 19 recordsLinked to original sources

Mutants of dermatophytes resistant to ketoconazole.

Authors describe the frequency and properties of mutants resistant to ketoconazole, obtained from the dermatophytes Microsporum gypseum and Trichophyton mentagrophytes. Spontaneous mutants occurred with the frequency of 10(-9) to spore and nucleus. Ultraviolet radiation increased the frequency of mutants by two numeric orders. The resistance level was relatively small in both types of mutants (RL within the range of 2-5).

Drug Resistance, Microbial↗

Effect of ketoconazole on potassium pool, c-AMP-release and ergosterol synthesis in resistant mutants of Microsporum gypseum.

The effect of ketoconazole (KK) on chosen biochemical indexes was studied in three mutants of dermatophyte Microsporum gypseum (MG-155 wild strain) resistant to KK. Fungistatic concentration of KK added to liquid cultivate medium increases significantly ergosterol pool and nonsignificantly demethylation activity, potassium content, cAMP release in three days old mycelium of mutants when compared to the cultivation without KK. On the contrary, there is a significant suppression of ergosterol level and demethylation activity followed by highly significant increasing of potassium content and cAMP release in the case of wild strain MG-155.

Cyclic AMP↗

[HLA antigens in patients with celiac disease].

In 104 non-related children with coeliac disease, all from northern Moravia, the authors assessed the distribution of HLA antigens class I and II and compared the findings with a control group. They revealed a positive association between HLA A1 (62% sick subjects as compared 27% healthy ones), B8 (68% as compared with 18%), DR3 (66% as compared with 14%) and DQw2 (79% as compared with 23%). In HLA antigens class II there is a higher relative risk of the disease for subjects with antigens DR3 and DQw2 and a higher aetiological fraction for the investigated antigens.

Adolescent↗

Genetics of dermatophytes.

By the end of 60s a team of scientists has started at Medical Faculty of Olomouc the research of micromycetes pathogenic for both the humans and animals. In this study, the appropriate results are summarized as concerned with the genetics of dermatophytes. Among these results, those significant in deeper assessing the biology of dermatophytes and etiopathogenesis of dermatophytoses have been selected. In our opinion, they may be of interest for the successors in the direction mentioned. Here are also formulated certain open problems and the applicative outputs are traced, for example, those concerning with vaccines. The approaches used, even unusual in the medical mycology from a traditional scope, are believed to prove the convenience of genetic methods when researching mycopathogens. We regret to miss at the edition of this publication the late founder of the team, RNDr. Nora Hejtmánková, CSc. which had the greatest contribution to the Chapters on the karyology and variability of dermatophytes as well as to the hybridization analysis of Trichophyton mentagrophytes complex.

Arthrodermataceae↗

Quantitative indices in paternity cases.

The study discusses the basic quantitative indices used as a standard method in foreign professional literature dealing with paternity cases. They are as follows: 1. mean probability of exclusion (PE) which characterizes the informative value of the experts opinions and is the same in all the disputes evaluated by this expert. 2. relative frequency of men chosen at random from the population and excluded at given phenotype of mother and child (RME). 3. probability of paternity (PP) for particular trio: mother-child-the accused man. Hereinafter the results of our studies in the HLA laboratory in Olomouc from 1976-1991 are introduced.

Blood Group Antigens↗

HLA antibodies in renal transplant candidates.

The level of anti-HLA antibodies was followed in 155 patients of the chronic dialyzed program: against antigens HLA Class I and antigens HLA-DR representing HLA Class II. Correlation between the titre of these antibodies and additional factors were analyzed. The effect of pregnancy and consequently of sex was proved. Of significance were the number of dialyses undergone and the time of inclusion into the dialyses program. Positive correlation between the titre of both types of anti-HLA antibodies is so significant that it makes possible to concentrate on the more simple anti HLA I antibodies determination. The result of crossmatch test is of crucial importance when making decisions on suitable recipient of the kidney from the set of patients of dialyzed program (DP). The presence of anti-HLA alloantibodies can cause hyperacute rejection. The anti-HLA alloantibodies titre is regularly followed in DP patients. Several significant hypotheses can be verified in a large enough set of patients (hypotheses marked with ordinal numbers 1-5): 1. Only the titre of anti-HLA Class I antibodies is usually followed in DP patients. Some workplaces abroad consider it useful to follow even the anti-HLA Class II antibodies. Is anti-HLA I and HLA II antibodies titre in such a significant correlation that it is sufficient to follow only anti-HLA Class I? 2. Mechanisms of HLA antigen sensitization in DP patients are well known. We can verify the influence of transfusion number, allograft rejections and number of previous pregnancies on the anti-HLA antibodies titre.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

HLA-A and HLA-B typing: classification of errors.

The authors followed the frequency of errors in serologic identification of HLA-A and HLA-B antigens. They analyzed 205 paternity cases evaluated independently by two judicial experts (a revision of expert opinions). The specification of revealed discrepancies is demonstrated in the study and possible causes of their origin are analyzed. In the conclusions the authors recommend useful steps leading to the decrease of error frequency in HLA antigen typing. The HLA system--the major histocompatibility system of a man, has a broad utilization in the field of practical medicine. HLA compatibility should be respected in the choice of the couple donor-recipient for transplant therapy. HLA, as a highly polymorphic system, is successfully applied in forensic medicine. A strong association with some diseases makes it possible to utilize HLA as a supporting diagnostic sign. The commission for nomenclature of WHO at XI. International Histocompatibility Workshop (1991) recognized the following numbers of HLA specificities: 25 A, 55 B, 10 C, 21 DR, 9 PQ, 6 DP. At present HLA laboratories used mostly serological methods. The need to mutually differentiate HLA antigens which are similar due to their molecular structure puts an extraordinary demand on HLA laboratories. On one hand, a great number of HLA phenotypes exist in the population, which ensures the identification of every individual and the distinguishing of self-nonself components. On the other hand there appear the limited possibilities of HLA laboratories with relatively low numbers of diagnostic sera. We inquired how often errors occurred in HLA antigens determination. We chose a set of 205 auditing experts opinions of paternity cases for analyzing the problem.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Sensitivity of Trichophyton mentagrophytes strains to three imidazole drugs.

A total of 84 strains of the dermatophyte Trichophyton mentagrophytes were studied for their sensitivity to ketoconazole, miconazole, and clotrimazole. Minimal inhibitory concentration was used for determination of sensitivity. Variability in the sensitivity of strains to the tested imidazole drugs ranged within one to two orders (10(-2)-10(0) micrograms/ml). By means of UV radiation ketoconazole-resistant mutants were prepared: their frequency was 1.3 x 10(-7) mutants per spore and nucleus. A repeated exposition to the mutagen lead to increased resistance. Correlation was also studied between inhibitory effect of ketoconazole on mycelial growth and that on ergosterol biosynthesis but no significant results were obtained.

Clotrimazole↗

Study of lipids in dermatophytes. II. The effect of ketoconazole in the exponential stage of growth.

There was studied the effect of ketoconazole on the growth, the amount of ergosterol and the relative distribution of fatty acids in the sensitive strain MG-155 of M. gypseum and its two ketoconazole-resistant mutants UV-1 and UV-2 (induction by UV radiation) in the exponential stage growth. After three-day cultivation in the medium with ketoconazole (0.64 microgram.ml-1) there appeared 40% inhibition of growth in MG-155, 10% inhibition in UV-2 and only 4% inhibition UV-1. The amount of ergosterol decreased in MG-155, in both mutants the amount of ergosterol increased by the effect of ketoconazole (by more than 50%). The main saturate fatty acids are palmitic acid (10% and stearic acid (4%). The major fraction of unsaturate fatty acids is formed by linoleic acid (50%) and by oleic acid (4%). Ketoconazole does not affect the quality of fatty acids spectre, it changes only the size of the relative distribution of individual fatty acids. In this point of view, the mutant UV-2, and namely the mutant UV-1 (the higher degree of resistance) differ from the initial sensitive strain MG-155. Ketoconazole provokes in mutants a higher reduction of stearic acid fraction, of saturate fatty acids C greater than 18 and of triunsaturate fatty acids and it causes only minimum (4% for UV-1) decrease of oleic acid. The results of cultivations with postponed application of ketoconazole to the medium (on the 2nd the 1st day before the mycelium harvest) show in a decisive way that effect of ketoconazole is fully developed only on condition that ketoconazole is added to the medium simultaneously with the inoculum. There are discussed several conclusions with regard to the findings in the identical strains in stationary stage of growth.

Animals↗

Genetic component of growth rate and ovicidal activity in Penicillium lanosum.

The growth rate and ovicidal activity of 10 complementary biauxotrophic mutants (haploid constitution) obtained from strain No 45 of the ovicidal fungus Penicillium lanosum was studied. The quantitative characters were further evaluated in 17 diploid strains prepared from pairs of mutants. By means of correspondence analysis "LINDA" was determined the share of parent haploid strains in the variability of diploids. This share is interpreted as the estimate of the genetic component. In the case of the growth rate the size of this component fluctuates from 70% to 90%; in the case of ovicidal activity it achieves the value of 75%.

Animals↗

Diploids of ovicidal fungus Penicillium lanosum.

By use of auxotrophic mutants of Penicillium lanosum were prepared the heterokaryonts. From more rapidly growing sectors from heterokaryotic mycelium on minimal medium were isolated 17 diploid strains. They were prototrophic and on the whole they did not differ from the wild strain in their morphology and their growth rate. All diploids had considerably larger spores than the wild strain. Ovicidity of one half of the diploids, as well as ovicidity of the wild strain was inconspicuous and low. Ovicidity of the second half of diploids was either medium or higher, the 2nd and 3rd type. The set of these diploid mutants will serve for another study of genetic determination of ovicidity.

Animals↗

Study of lipids in dermatophytes. I. The effect of ketoconazole on fatty acids of Microsporum gypseum and its mutants.

There was studied the spectre of fatty acids and its changes induced by ketoconazole in the strain M. gypseum and its two mutants (UV-1, UV-2). The main saturate fatty acid in MG-155 and in both mutants is palmitic acid, the main unsaturate fatty acid is linoleic acid. In comparison with MG-155, UV-1 and UV-2 manifest a lower amount of stearic and oleic acids and a higher amount of stearic acid) in MG-155 and UV-1, an increase of saturate fatty acids is observed in UV-2. The unsaturate fatty acids affected by ketoconazole increase in MG-155 and UV-1, they decrease in UV-2 (the changes are most marked in linoleic acid). Oleic acid, as the main representant of monounsaturate fatty acids, decreases in MG-155 and in both mutants. There is discussed the relationship of these changes in fatty acids distribution to the eventual damage of membrane function, to the growth characteristics and to the metabolism of ergosterol.

Fatty Acids↗

Ketoconazole-resistant mutants of Microsporum gypseum. I. Isolation of mutants, biochemical methods.

The ketoconazole-resistant mutants were isolated from four strains of the dermatophyte Microsporum gypseum. The frequency of spontaneous mutants ranged within 10(-8) to 10(-9) (per spore and nucleus). The method was established for obtaining the spontaneous mutants manifested as the faster growing sectors. By means of mutagenic effect of UV radiation, the frequency of mutants increased by one order. The method used for determination of ergosterol the biosynthesis of which could be associated with the mechanism of resistance to ketoconazole is described and evaluated.

Drug Resistance, Microbial↗

Ketoconazole-resistant mutants of Microsporum gypseum. II. Characteristics of mutants.

The presented study deals with the properties of two wild strains of dermatophyte Microsporum gypseum and of eleven mutants resistant to ketoconazole. The growth rate of spontaneous mutants is greater than that of the wild strain, the group of UV-induced mutants manifests in general lower growth rate. The resistance level varies in the interval 1.1-1.6 (spontaneous mutants), resp. 2.7-5.5 (UV-induced mutants). The phenomenon of cross-resistance to other imidazole drugs (miconazole, clotrimazole) has been observed in mutants. There is further given the characteristic of ergosterol synthesis influence by the three used antifungal drugs. The data obtained are discussed from the point of view of possible biochemical processes resulting in the formation of resistance to ketoconazole.

Clotrimazole↗

Adaptation of Microsporum gypseum to ketoconazole.

The mycelium of the strain MG-155 of the dermatophyte Microsporum gypseum was repeatedly cultivated in three subinhibitory concentrations of ketoconazole: 1, 2, and 6 micrograms/ml. The adaptability of the fungus to this antifungal drug was estimated on the basis of the sensitivity of spores and the sensitivity of the mycelium. In the first phase, the mycelium grew on the medium with ketoconazole in consequence to the physiological adaptation (without the change of genome). In the following phase of the adaptation training, there occurred a manifestation of resistant mutants. After twenty-eight transfers, only a slight increase of resistance was found (resistance level = 2), however, this resistance was of a constant character. Basing on the data of ergosterol amount, there is discussed the biochemical mechanism of the described changes in the sensitivity of the fungus to ketoconazole.

Antifungal Agents↗