The clinical immunogenetics of viral hepatitis C in a Caucasoid population of western Siberia

The analysis of the immunogenetic studies on hepatitis C patients among the Caucasoid population of western Siberia has revealed a significant increase in the detection rate of antigens HLA-A10 and HLA-DR5, the combinations of DR2-DR5, DR5-DR7, DR1-B27 and the complete absence of antigen HLA-DR4, which is indicative of the fact that susceptibility and resistance to the development of the disease is associated with the genes of the main histocompatibility complex. In hepatitis of mixed etiology, B and C, a significant increase in the occurrence of HLA antigens: -A1, -B8, -DR1 and -DR3, as well as the combinations of A1-DR1, A1-DR3, A3-DR3, A9-A10, DR1-DR3, B8-DR3 is noted; at the same time a decrease in the occurrence of antigen DR4 and its combination with antigen HLA-A2 is observed.     

Target cells for lithium in different forms within a heterogeneous hepatocarcinoma-29 population

Liver cancer is an aggressive and heterogeneous human tumor. Lithium compounds block proliferation and induce apoptosis of hepatocarcinoma cells, but cannot cause the death of an entire population of tumor cells. The aim of this study was to reveal morphological types of target cells for different lithium preparations on the basis of their action on hepatocarcinoma-29 cells. The viability of hepatocarcinoma-29 cells was assessed by the MTT test. A dose-dependent decrease in viability was revealed upon addition of native and nanosized lithium carbonate and citrate. Target cells for lithium salts were revealed based on the morphological criteria for five differentiation stages of hepatocarcinoma-29 cells. It was shown that hepatocarcinoma- 29 proliferating cells of differentiation stages I and II are the target cells for native and nanosized lithium citrate, while differentiated cells of differentiation stages III and IV are the target cells for nanosized lithium carbonate. It was revealed that hepatocarcinoma-29 cells are more sensitive to nanosized lithium salts rather than to their native forms. This makes it possible to affect tumor growth more effectively.     

Alleles distribution of polymorphic promoter region C-590T in interleukin-4 genes and Q-576r and Ile-50Val regions in IL-4 receptor gene IL-4RA in patients with HCV-infection

81 patients with confirmed HCV-infection and 48 healthy volunteers were examined. In healthy Caucasian participants living in Siberian region significant predominance of C/T genotype in promoter region C-590T of interleukin-4 (IL-4) gene and Q/Q and Ile/Val genotypes in points -50 and -576 of IL-4RA gene that codes alpha-chains of IL-4 receptor were revealed. In patients with HCV-infection predominance of C/T genotype in C-590T region in IL-4 gene (OR = 1.86), R/R genotype in Q-576R region of IL-4RA gene (OR=7.86), and Val/Val genotype in point Ile-50Val (OR = 2.6) of the same gene. Summary predictive coefficient of hepatitis C development in carriers of these genotypes approached to 95%. During analysis of role of allelic polymorphism of IL-4 genes in predisposition to hepatitis C development it is necessary to consider not only presence of allelic variants of promoter regions of the IL-4 genes, but also the polymorphism of genes coding molecules binding with this cytokine on target cells membranes and in its soluble form.     

Analysis of polymorphism of the interleukin-4 gene of healthy and HIV-infected persons

The distribution of the allel variants of the promoter area (C = 590T) of the interleukin-4 (IL-4) gene in HIV-infected and relatively healthy representatives of the Caucasoid population has been studied. The relationship between the genotypes of this polymorphism and the production of IL-4 by mononuclear cells of peripheral blood as well as distribution of IL-4 genotypes among males and females is analyzed. The occurrence of the homozygous combination of the allel variant C/C of the promoter of IL-4 has been shown to prevail almost twofold over the occurrence of the variant C/T among healthy donors and HIV-infected patients. Sexual differences play an essential role in the character of inheriting the allel variants of the genes of IL-4, the presence of the homozygous variant C/C or T/T being a risk factor of HIV infection in males. As revealed in this study, in the peripheral blood of healthy donors mononuclear cells having genotype C/C differ from cells with the heterozygous variant C/T in higher spontaneous production of IL-4 and, simultaneously, in lower capacity for the activation of its production in response to stimulation with mitogen. In HIV-infected patients mononuclear cells differ in higher spontaneous production of IL-4 in comparison with controls. We may thus infer that the human genotype controlling the initial level of the production of IL-4 by lymphocytes Th2 may influence the intensity of antibody production in the process of infection.     

Frequencies of the <Emphasis Type="Italic">DRB1</Emphasis>, <Emphasis Type="Italic">DQA1</Emphasis>, <Emphasis Type="Italic">DQB1</Emphasis> and <Emphasis Type="Italic">TNFA</Emphasis> alleles in immigrant population of west Siberia

Based on population analysis of the DRB1, DQA1, DQB1 and TNFA allele frequency distribution patterns, regional features of immunogenetic structure of the population of West Siberia were investigated. Statistically significant linkage disequilibrium within the HLA class II region, as well as between the TNFA and DRB1, DQA1, and DQB1 was demonstrated. Population frequency distribution patterns of two- and multilocus haplotypes were examined.     

Changes in a late positive component of evoked potentials in the <Emphasis Type="Italic">GO/NOGO</Emphasis> test after cryocingulotomy

The influence of cingulotomy on the components of brain evoked potentials detected by a modified GO/NOGO paradigm was investigated. Patients with a diagnosis of heroin dependence (13 subjects) participated in the study. For medical indications, patients were treated with stereotaxic anterior cryocingulotomy in order to reduce the compulsive need that makes the drug dependence intractable. A two-stimulus modification of the GO/NOGO paradigm developed in our laboratory was used in this study. Cingulotomy did not change significantly the early (in the 100-to 200-ms range) components evoked by visual or auditory stimuli. The positive component evoked by the GO stimuli also did not change. This component corresponds to the P3b component observed in the ODD BALL paradigm. The only component that changed after the anterior cingulotomy was a late component generated by the NOGO stimuli in the 400-ms range, which was distributed in the medial frontocentral area. Thus, we have obtained a direct confirmation of the relationship between this component and the activity of the anterior cingulate gyrus. Analysis of the individual evoked potentials allows us to conclude that the suggested modification of the GO/NOGO test and methods for correcting artifacts in the statistical analysis of differences may be regarded as a reliable approach to the assessment of the functional activity of the anterior cingulate gyrus in humans.     

Apoptosis and autophagy in hepatocarcinoma cells induced by different forms of lithium salts

Hepatocellular carcinoma (HCC) is an aggressive cancer that is resistant to drug therapy. It is believed that the development of HCC is correlated with misregulation of programmed cell death. Discovery of effective inducers of HCC cell death is very important for HCC therapy. The aim of this work was to identify structural changes leading to the death of HCC cells exposed to nanosized and original forms of lithium salts. Structural features of autophagy and apoptosis were revealed in HCC cells after their incubation with various forms of lithium salts by light, electron microscopy, and flow cytometry. It was shown that nanosized forms of lithium carbonate and lithium citrate had a pronounced effect on HCC-29 cells. Of these forms, the nanosized lithium citrate induced mainly apoptosis, while the nanosized form of lithium carbonate, along with apoptosis, induced autophagic death of HCC cells.     

Study of the most often encountered allele of the HLA-B27 gene in Tuvinian and Russian inhabitants of Western Siberia

HLA-B27 gene frequencies and allelic polymorphism were studied in two Siberian ethnic groups: Russians from Novosibirsk (western Siberia) and Tuvinians from Kyzyl (southern Siberia). The HLA-B27 frequencies were determined by means of serologic typing of HLA antigens in 198 Tuvinians and 288 Russians. Molecular typing was performed via hybridization of oligonucleotide probes with amplified DNAs obtained from 30 HLA-B27-positive Russians and 11 HLA-B27-positive Tuvinians. The HLA-B27 gene frequencies in Tuvinians and Russians were 5.5 and 10.4%, respectively. Molecular variants of the HLA-B27 gene were studied in Tuvinians for the first time. The proportions of the HLA-B2705 and HLA-B2704 alleles were found to be 64 and 36%, respectively, in the population studied. The presence of the HLA-B2704 allele indicates a Mongoloid origin of Tuvinians. In the Russian population of Novosibirsk, the HLA-B2704 allele was not found, whereas the proportions of the HLA-B2705 and HLA-B2702 alleles were 76.2 and 23.8%, respectively, which is characteristic of Caucasoid populations.     

Time dependence of the shedding of class I and II HLA antigens. Interrelation of the fluctuations of HLA-antigen shedding and 51Cr-labeled macromolecules

Soluble HLA-A, -B and -DR antigens were determined every 10 min with a rate nephelometry method in supernatants of human mononuclear cells cultured for 3 hrs. The time-dependent oscillations in the quantity of soluble HLA antigens with ultradian (circadian) rhythm characteristics were found. Quantity oscillations of HLA-A antigens were synphase to HLA-B ones and antiphase to HLA-DR antigens. Amplitude characteristics were found to depend on the temperature and cytoskeleton activity.