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Biomedical subjects

V Vladimirov

Publications and source records attributed to V Vladimirov.

16 recordsLinked to original sources

Alcohol dependence is associated with the ZNF699 gene, a human locus related to Drosophila hangover, in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD) sample.

Because tolerance is an important aspect of alcohol dependence (AD) in humans, recent evidence showing that the Drosophila gene hang is critically involved in the development of alcohol tolerance in the fly suggests that variation in related human loci might be important in the etiology of alcohol-related disorders. The orthology of hang in mammals is complex, but a number of human gene products (including ZNF699) with similar levels of amino-acid identity (18-26%) and similarity (30-41%), are consistently identified as the best matches with the translated hang sequence. We tested for association between the dichotomous clinical phenotype of alcohol dependence and seven single nucleotide polymorphisms (SNPs) in ZNF699 in our sample of 565 genetically independent cases and 496 siblings diagnosed with AD, and 609 controls. In analyses of genetically independent cases and controls, four of the seven single markers show strong evidence for association with AD (0.00003<Fisher's exact P<0.001), and the most significant single marker, rs7254880, tags an associated haplotype with frequency 0.071 in cases compared to 0.034 in controls (chi2 15.563, P<0.00008, 5000 permutation P<0.001, OR 2.17); inclusion of affected siblings gives similar results. Expression analyses conducted in independent postmortem brain samples show that expression of ZNF699 mRNA is significantly reduced in the dorsolateral prefrontal cortex of individuals carrying this haplotype compared with other observed haplotype combinations.

Alcohol-Related Disorders↗

Genetics of susceptibility to leishmaniasis in mice: four novel loci and functional heterogeneity of gene effects.

Symptoms of human leishmaniasis range from subclinical to extensive systemic disease with splenomegaly, hepatomegaly, skin lesions, anemia and hyperglobulinemia, but the basis of this variation is unknown. Association of progression of the disease with Th2 lymphocyte response was reported in mice but not in humans. As most genetic studies in Leishmania major (L. major)-infected mice were restricted to skin lesions, we analyzed the symptomatology of leishmaniasis in mice by monitoring skin lesions, hepatomegaly, splenomegaly and seven immunological parameters. We detected and mapped 17 Leishmania major response (Lmr) gene loci that control the symptoms of infection. Surprisingly, the individual Lmr loci control 13 different combinations of pathological and immunological symptoms. Seven loci control both pathological and immunological parameters, 10 influence immunological parameters only. Moreover, the genetics of clinical symptoms is also very heterogeneous: loci Lmr13 and Lmr4 determine skin lesions only, Lmr5 and Lmr10 skin lesions and splenomegaly, Lmr14 and Lmr3 splenomegaly and hepatomegaly, Lmr3 (weakly) skin lesions, and Lmr15 hepatomegaly only. Only two immunological parameters, IgE and interferon-gamma serum levels, correlate partly with clinical manifestations. These findings extend the paradigm for the genetics of host response to infection to include numerous genes, each controlling a different set of organ-specific and systemic effects.

Animals↗

Safety investigation of team performance in accidents.

The paper presents the capacities of the performance evaluation of teamwork (PET) method. Its practicability and efficiency are illustrated by retrospective human reliability analyse of the famous nuclear and maritime accidents. A quantitative assessment of operators' performance on the base of thermo-hydraulic (T/H) calculations and full-scope simulator data for set of NPP design basic accidents with WWER is demonstrated. The last data are obtained on the 'WWER-1000' full-scope simulator of Kozloduy NPP during the regular practical training of the operators' teams. An outlook on the "evaluation system of main control room (MCR) operators' reliability" project, based on simulator data of operators' training is given.

Disaster Planning↗

Separation and mapping of multiple genes that control IgE level in Leishmania major infected mice.

The strain BALB/cHeA (BALB/c) is a high producer, and STS/A (STS) a low producer of IgE after Leishmania major infection. We analyzed this strain difference using 20 recombinant congenic (RC) BALB/c-c-STS/Dem (CcS/Dem) strains that carry different random subsets of 12.5% of genes of the strain STS on the BALB/c background. Strains CcS-16 and -20 exhibit a high and a low IgE level, respectively. In their F(2) hybrids with BALB/c we mapped nine Leishmania major response (Lmr) loci. Two of them we previously found to influence IgE level in CcS-5. IgE production in CcS-16 is controlled by loci on chromosomes 2, 10, 16 and 18 and in CcS-20 by loci on chromosomes 1, 3, 4, 5 and 8. The STS alleles of loci on chromosomes 1, 4, 5, 8 and 10 were associated with a low, whereas the STS alleles on chromosomes 16 and 18 with a high IgE production. The loci on chromosomes 2 and 3 have no apparent individual effect, but interact with the loci on chromosomes 10 and 1, respectively. The loci on chromosomes 10 and 18 were mapped in the regions homologous with the human regions containing genes that control total serum IgE and intensity of infection by Schistosoma mansoni, suggesting that some Lmr loci may participate in the pathways influencing atopic reactions and responses to several parasites. The definition of genes controlling anti-parasite responses will permit a better understanding of pathways and genetic diversity underlying the disease phenotypes.

Animals↗

Optimization of single-strand conformation polymorphism analysis in the presence of polyethylene glycol.

We report optimization of single-strand conformation polymorphism (SSCP) analysis in the presence of polyethylene glycol. The protocol developed separates single-strand conformers in a much shorter time (1-3 h) than conventional SSCP protocols and broadens the applicability of SSCP analysis from 150 to as much as 500 bp of DNA by different percentages of GC content present. We conclude that addition of polyethylene glycol helps improve the differential separation of conformers and, in combination with high-resolution polyacrylamide gel electrophoresis, offers an alternative to previous SSCP analysis protocols. This protocol should be very useful for clinical applications in routine detection of mutations as well as for research purposes.

Cystic Fibrosis Transmembrane Conductance Regulato↗

[Left heart ventricle in chronic cor pulmonale patients. Etiological, pathomorphological and organ weight measurement studies].

The histories and the results of the postmortem examinations of 507 patients with chronic pulmonary heart disease were studied. In 62.6% of them left ventricular hypertrophy was found. As probable causes for this left ventricular hypertrophy are suggested: arterial hypertension, ischemic heart disease, hypoxemia, hypercapnia, heart failure, diabetes mellitus. The weight measurement correlations between the left and the right heart ventricles were studied in: "normal hearts", hearts with right ventricular, hypertrophy only, hypertrophy of both ventricles, left ventricular hypertrophy only. A correlation between the mass increase and the wall thickness of the ventricles was established. In the patients with chronic pulmonary heart disease and hypertrophy of both ventricles the mass and the wall thickness of the ventricles increase simultaneously. The possible pathogenetic mechanisms of the left ventricular involvement in patients with chronic pulmonary heart disease are discussed.

Cardiomegaly↗

[Carcinoembryonic antigen, its clinical and prognostic significance in malignant tumors of the gastrointestinal system].

A radioimmunoassay to determine the CEA level in 100 patients with GIT malignant tumors was performed. The test was shown to be of particular value for making a preoperative prognosis of the disease. In operated on patients it could be used for early diagnosis of recurrences and metastases. The dynamic performance of the test made it possible to evaluate therapeutic efficacy.

Adult↗

[Clinical and prognostic significance of determining the carcinoembryonic antigen in patients with gastrointestinal cancer].

The paper discusses the results of a radioimmunologic assay of carcinoembryonic antigen (CEA) levels in 100 cases of gastrointestinal cancer. CEA--PRIST kits (Phadebas, Sweden) and NGR-603 automatic gamma-unit (Tesla, Czechoslovakia) were employed. The test proved to be highly instrumental in the preoperative evaluation of prognosis and early detection of recurrence and metastasis. CEA concentrations within 30-50 ng/ml are highly suggestive of recurrence or metastases, whereas 50-100 ng/ml should serve an indicator of organ dissemination. The test is useful in assessing the effectiveness of treatment in the course of follow-up.

Adult↗

[Risk factors in ischemic heart disease patients].

Four hundred sixty patients with ischemic heart disease (IHD) were examined: 226 of them--with myocardial infarction; 38--stenocardia, 196--myocardiosclerosis. With age advancing all forms of IHD increase. The incidence of the followed up risk factors progessively increases. Hypertension has the greatest share--56.30 per cent out of all the subjects examined. Second place as regards incidence is occupied by the emotional stress--46.52 per cent. Further they are as follows: heredity--38.91 per cent; tobacco smoking--34.57 per cent, sedentary life--32,83 per cent, obesity--31.52 per cent, overfeeding--30 per cent, hypercholesterinemia--30 per cent, diabetes--17.61 per cent. The significance of the indicated risk factors alarmingly grows, consideration given to their combined effect. An average of 3.18 risk factors fall on patient. In patients with myocardial infarction they are more frequent and appear at an earlier age. Such an accumulation of the noxae upon the contemporary man requires the complex effors of the whole society.

Adult↗

[Deviation of the electrical cardiac axis to the left between -30 degrees and -90 degrees as an index of left ventricular hypertrophy].

The index of left ventricular hypertrophy A between --30 degrees and --90 degrees was established to be with low sensitivity (23 per cent) and high false positiveness (13 per cent) with the analysis of 448 electrocardiograms of 269 deceased, to 60 of them being applied the pathologoanatomical separating-gravimetric method of Fulton and to the rest--the classical methods. The disturbances of the intraventricular conductivity and especially the left anterior hemiblock contribute considerably. The left axial deviation in left ventricular hypertrophy was established not to be due mainly to the increased muscular mass but also to the accompanying or conditioned by it processes (coronary insufficeincy, sclerosis) leading to disturbances of the left ventricular conductivity.

Adult↗

[Experience with the electrocardiographic diagnosis of cardiac ventricular hypertrophy by the methods of mathematical statistical analysis].

A new index in the diagnostics of right ventricular hypertrophy: AQRS + 52 less than or equal to 235 is derived by means of the discriminant multifactorial analysis and processing the elements of 488 electrocardiograms in the 12 routine leads in 269 deceased. AQRS is the electric heart axis in the frontal plane, determined by Pis'menji tables; Z is the transitory zome in precordial leads, expressed with tenfold increased number of the lead, e.g. V1-10, V2-20 etc. In case of transitory zone between two leads, e.g. V4-V5-the interpolated value between 40 and 50 is indicated-i.e. 45. The new index as compared with selected 18 basic indices for right ventricular hypertrophy is with considerably better diagnostic qualities: sensitivity--84%, false positiveness 13% and diagnostic accuracy 86%.

Cardiomegaly↗