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Biomedical subjects

V I Konenkov

Publications and source records attributed to V I Konenkov.

At least 19 recordsLinked to original sources

[Immunogenetic analysis of variants of a clinical course and prognosis of chronic glomerulonephritis in the west Siberia].

AIM: To analyze association of HLA antigens with clinical variants of chronic glomerulonephritis (CGN)in 106 patients. MATERIAL AND METHODS: HLA association with the time of development of terminal chronic renal failure (CRF) from the moment of detection of initial CRF was studied in 80 patients. Determination of HLA of class I was conducted in the lymphocytotoxic test. DRB1 genes specificity was determined with DNA polymerase chain reaction. The control group consisted of 341 healthy citizens of Novosibirsk. Common HLA associations of latent and hypertensive, latent and nephrotic CGN variants were found demonstrating their succession. HLA associations with a mixed CGN variant defining its genetic isolation were established. It is shown that development of terminal CRF at different time since the disease onset is associated with different HLA alleles. The findings allow prognosis of clinical CGN variants, time of development of terminal CRF.

Adult↗

[Immunogenetic prognosis and long-term results of surgery for gastric cancer].

A link between HLA allelic variants and long-term results of surgery for gastric tumors was established on the basis of a 10-years follow-up of 112 cancer patients (stage I-II--37.9, III-IV--62.1%; radical surgery--44.6%). HLA class I was studied in a lymphocytotoxic test; HLA class II--gene DRBI specificity using polymerase chain reaction of peripheral blood cell DNA. The control group included healthy subjects living in the city of Novosibirsk (n = 341). High frequency of antigens HLA-B41, -DR1, -DR7 (p < 0.01) co-occurred with HLA-A2, -B12, -B13 and -B18 presence (p < 0.05) in breast cancer patients. Clinical manifestations of cancer were shown to develop in HLA-A1, -B8, -B15, -DR3 and -DR5 carriers at early stages. Tumor development at later stages (III-IV) was associated with HLA-A2, -B12, -B17, -B35, -B41 and -DR7. A link was registered between lethality rate, on the one hand, and HLA-A3, -B22, and, in particular, DR4, on the other, while remission of more than 7-years--with HLA-A11, -B13, -B21 and -DR5. HLA-B22/DR3 phenotype involved worse prognosis in radically-treated patients whereas that of HLA-B8/DR3--a better one.

Aged↗

Polymorphism of promotor region of the tumor necrosis factor-alpha gene in patients with viral hepatitis C.

Study of the pathogenesis of viral hepatitis C is of primary importance because of persistence of this virus and high incidence of chronic course of this disease, and as a consequence, development of cirrhotic and neoplastic processes in the liver determining high mortality from this condition. Proinflammatory cytokines, in particular, tumor necrosis factor, play an important role in the development of these pathological processes. The content of tumor necrosis factor in the circulating blood plasma and hepatocytes increases in acute and chronic hepatitis C. It seems that the capacity of cells to produce proinflammatory IL in high or low levels spontaneously or after antigenic stimulation largely determines the outcome of infectious process in contact with the virus.

Alleles↗

Genetic differences in immune reactions to radiation exposure in humans and experimental animals.

Examination of populations living in regions of fallout radiation revealed changes in the distribution of HLA genes not only in irradiated individuals, but also in their children and grandchildren. Combined irradiation of inbred mice in comparable doses showed that H-2 genes determine immune reactions in animals and their offspring to radiation. Our results indicate that the immune system in mammals is immunogenetically regulated by low-dose radiation.

Animals↗

Polymorphism of promotor sites of interleukins-4 and -10 and tumor necrosis factor-alpha genes in HIV-infected patients.

The distribution of allele variants of promotor sites of interleukins 4 (C-590T) and 10 (C-597A) and tumor necrosis factor-alpha (G-308A) genes was studied in HIV-infected patients and normal subjects of the Europeoid population in Russia. Some deviations in the distribution of genotypes of the studied polymorphism were revealed in HIV-infected patients compared to the control. The distribution of genotypes in these groups is different for men and women, which is significant for inheritance of allele variants of the cytokine gene.

Adolescent↗

Molecular, genetic, and morphological markers during persistence of RNA-containing hepatitis C virus in the body.

A comparison of 5'-UTR structures in Siberian isolates of hepatitis C virus showed that the majority of genotyped samples had 1b genotype. A correlation was found between HLA antigens and their stable complexes and clinical manifestations of hepatitis C. We revealed immunogenetic criteria of organism's resistance or susceptibility to hepatitis C virus. The presence of hepatitis C virus RNA in the serum determined by the reverse transcription polymerase chain reaction was accompanied by the appearance of pathomorphological signs characteristic of liver tissue infection, but did not correspond to the severity of fibrosis.

5' Untranslated Regions↗

Genetic variability and linkage disequilibrium within the HLA-DP region: analysis of 15 different populations.

In order to understand the forces governing the evolution of the genetic diversity in the HLA-DP molecule, polymerase chain reaction (PCR)-based methods were used to characterize genetic variation at the DPA1 and DPB1 loci encoding this heterodimer on 2,807 chromosomes from 15 different populations including individuals of African, Asian, Amerindian, Indian and European origin. These ethnically diverse samples represent a variety of population substructures and include small, isolated populations as well as larger, presumably admixed populations. Ten DPA1 and 39 DPB1 alleles were identified and observed on 87 distinct DP haplotypes, 34 of which were found to be in significant positive linkage disequilibrium in at least one population. Some haplotypes were found in all ethnic groups while others were confined to a single ethnic group or population. Strong positive global linkage disequilibrium (Wn) between DPA1 and DPB1 was present in all 15 populations. The African populations displayed the lowest values of Wn whereas the Amerindian populations displayed near absolute disequilibrium. Analysis of the distribution of haplotypes using the normalized deviate of the Ewens-Watterson homozygosity statistic, F, suggests that DP haplotypes encoding the functional heterodimer are subject to much lower degrees of balancing selection than other loci within the HLA region. Finally, neighbor joining tree analyses demonstrate the power of haplotype diversity for inferring the relationships between the different populations.

Alleles↗

[Immunogenetic aspects of duodenal ulcer in Helicobacter pylori positive Europeans in Western Siberia].

AIM: To study HLA associations with HP-positive duodenal ulcer (DU). MATERIAL AND METHODS: A total of 47 Europeoid DU and 680 healthy subjects were examined for class I and II HLA antigens. Typing of class I antigens was conducted in the microlymphocytotoxicity test, of class 2 antigens--by polymerase chain reaction. RESULTS: The study has found associations of duodenal ulcer with HLA-A10, -B41 and different combinations of these alleles whereas HLA-A9 was protective. A relative risk of peptic ulcer was 3.03 in HLA-A10 (pcor < 0.05) and 7.78 in HLA-B41 (p < 0.001). The allele A9 occurred more frequently in healthy controls (30.15%) than in Helicobacter pylori-positive patients with DU (10.64%, RR = 3.50, pcor < 0.05). Frequencies of alleles HLA-DR7 and HLA-A1/B12 were higher in HP-positive DU patients with family history of peptic ulcer (RR = 4.00 and RR = 11.92, respectively, p < 0.05). CONCLUSION: These data suggest that HLA may influence duodenal ulcer susceptibility and resistance. The relationships help prognosticate not only development of the disease in HP infection but also the age of the infection manifestation.

Adult↗

Immunogenetic factors of predisposition to duodenal ulcer in Caucasian population of western Siberia.

A total of 47 Caucasian duodenal ulcer patients and 680 healthy persons were investigated for HLA antigens of classes I and II. HLA antigens of the A, B series were sought using the microlymphocytotoxicity test, and HLA-DRBI was analysed by polymerase chain reaction. The study found associations of duodenal ulcer with HLA-A10, -B41 and different combinations of these alleles, whereas HLA-A9 was found to be protective. A relative risk of peptic ulcer was 3.03 in HLA-A10 (pcor < 0.05), and 7.78 in HLA-B41 (p < 0.001). The allele frequency A9 was higher in healthy controls (30.15%) than in Helicobacter pylori-positive patients with duodenal ulcer (10.64%, RR = 3.50, pcor < 0.05). The study showed that frequencies of alleles HLA-DR7 and HLA-A1/B12 were higher in Helicobacter pylori-positive duodenal ulcer patients with family history of peptic ulcer (RR = 4.00 and RR = 11.92, respectively p < 0.05). These data suggest that HLA may influence duodenal ulcer susceptibility and resistance, and according to the high prevalence of Helicobacter pylori (HP) infection in Siberian population (87.5%), this may occur through a non-HP infection pathway.

Adult↗

[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.

Alleles↗

[Association of TAP1/TAP2 gene polymorphism with inflammatory urogenital diseases combined with joint diseases].

AIM: To study association of TAP1/TAP2 gene polymorphism with urogenital infections combined with joint lesions. MATERIALS AND METHODS: Of 139 patients examined 45 ones had inflammation caused by Chlamydia trachomatis (17 had joint disease), 42 had Mycoplasma hominis infection (joint lesions in 17 cases). Method of amplification was used on the basis of specific primers (ARMS). RESULTS: Patients infected with C. trachomatis significantly more frequently had allele TAP1-02011 and TAP2-0201 (RR = 18.5, p < 0.01 and RR = 4.61, p < 0.05, respectively). Joint lesion in patients with chlamydial infection was associated with allele TAP1-02011 (RR = 11.92, p < 0.05). In mycoplasmosis association with joint lesions there is a significant link of joint syndrome with heterogeneous combination threonine/alanine in gene TAP2 position 565 (RR = 4.22, p < 0.05). CONCLUSION: The findings can be used for predicting the joint syndrome development in patients with urogenital infection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Polymorphism of the HLA-DRB1 04 gene in inhabitants of Tuva].

Data on the HLA-DRB1 04 gene typing among Tuvinians from Kyzyl are presented. Experiments were conducted by using the hybridization of allele-specific oligonucleotides with the amplified fragments of high molecular-weight DNA and reverse hybridization. The HLA-DRB1 0401 allele was most frequent among DR4-positive individuals. The HLA-DRB1 0405 and HLA-DRB1 0403 alleles were found at somewhat lower frequencies. In one individual, the rare HLA-DRB1 0410 subtype differing from HLA-DRB1 0405 subtype by the substitution of glycine for valine in codon 86 was detected.

Adolescent↗

[Frequency of the HLA-DP genes and the antigens of the HLA-A, -B, -Cw, and -DR loci in Tuvinians].

The results of DNA typing of the HLA-DPB1 gene among Tuvinians are described. The allele 0201 was found to be the most frequent (26.66%); then, in order of decreasing frequency, followed the alleles 0401 (26.42%), 0402 (13.99%), 0301 (8.55%), 0501 (7.77%), 0901 (5.16%), and 1301 (2.07%). The frequency of the allele 0501 in Tuvinians was significantly lower than that in the published data on allele distributions characteristic of two other Mongoloid populations, the Manchu and Japanese. The results of the serological typing of the loci HLA-A, -B, and -Cw of class I in the Tuva population were compared to the corresponding published data on ten Mongoloid populations of Central and Eastern Asia: Uigurs, Kazakhs, Mongols, Manchu, Tibetans, the Chinese of the northern and southern regions of China, Thais (inhabitants of Northwestern Indochina), Koreans, and Japanese. In Tuvinians, the most frequent antigens were HLA-A2, -A9, -B0, -B35, -B17, -Cw4, and -DR5. In the inhabitants of Tuva, the frequency of the antigens HLA-A1, -A9, -B17, -Cw2, and -Cw4 was significantly higher than in other Mongoloids, while that of the antigens HLA-A26 and -B22 was lower. This difference was greatest in the case of antigen HLA-B40: it a frequency of 43.4% was detected in it, while in individuals of Mongolian origin, the frequency of this antigen did not exceed 22.5%. Indices of genetic similarity (IGSs), calculated from the gene frequencies of the loci HLA-A, -B, and -Cw, suggested that the Tuvinians were most closely related to Kazakhs (IGS = 0.73), and least related to the Japanese and Uigurs (IGS = 0.66). Our data suggest that Tuvinians significantly differ from the compared populations of Central and Eastern Asia.

Asian People↗

[Clinical immunogenetics of stomach cancer in Western Siberia].

An immunogenetic examination of 86 cases of stomach cancer established a correlation between predisposition and resistance, on the one hand, and the distribution of allele sets of HLA-genes (classes I and II), on the other. The relationship was found to vary according to sex and age. The most significant relationships with respect to predisposition were identified for HLA-B51 (RR = 19.82) alleles and allele combinations of HLA-DRI-DR7 (RR = 25.52) and HLA-A9-DRI (RR = 33.67). High relative risk of stomach cancer was attributed to the absence of relevant alleles in 91 patients included into the group of comparison. Also, combinations of allele sets were identified in healthy subjects which never occur in stomach cancer patients. The results provide a substantiation for developing an automated system of interpreting HLA-typing data which are instrumental in evaluating the patient's predisposition, resistance and prognosis.

Adult↗

[The interrelation of the expression of HLA class I and II proteins and of the costimulatory proteins CD11a/CD18 and CD16 with the lytic activity of resting and activated natural killer lymphocytes].

It has been presumed that: 1) rheumatoid arthritis (RA) is a genuine model of activation of the peripheral natural killers (NK); 2) methods of NK separation can cause their activation, and therefore only peripheral mononuclear cells were used. The aim of this research was to study the role of cytolysis of HLA-I, HLA-DR, and costimulatory proteins CD11a and CD16 expressed on resting and activated peripheral NK cells. A total of 74 healthy volunteers (HV) and 74 RA patients were compared before corticosteroid or gold treatment. Two-colour immunofluorescence and cytofluorimetric analysis, cytotoxic test against the target K 562 cells (class I negative) before and after incubation of PMC with monoclonal antibodies (MoAB) to HLA-I (E3D8), HLA-DR (ICO-1), CD11 (ICO-11), PXx63 Ag8.653 as control, and also incubation with recombinant alpha 2-IFN were used. VEP-13 MoAB was used for CD16 determination. Compared with HV PMC, the RA PMC showed a statistically significant increase of activated NK lymphocytes (CD11a+DR+ and CD16+DR+ by 2.03 and 1.96 times, resp.), and increased level of expression of HLA-I, HLA-DR, and CD16 on CD11a+ lymphocytes, resulting in significantly diminished cytolytic activity (CA) by 1.9 times. A short-term incubation with alpha 2-IFN (100 U/ml, 1 h) increased the level of expression of HLA- and costimulatory proteins and the CA of the HV PMC, while the RA PMC did not react. HV peripheral NK are concluded to be mainly resting cells, and the RA peripheral NK are mainly the activated ones. Only using the level of expression of HLA-DR on CD11a lymphocytes, as a ranking criterion, allowed to reveal two types of correlation between the CA and immunocytological parameters of PMC. The first type: in HV, the CA correlated positively (P < 0.025) with the percentage of CD11a+CD16+, and with levels of expression of HLA-I (P < 0.025) and CD16 (P < 0.025) expressed on CD11a lymphocytes (5-9.5 MFI DR--the mean fluorescence intensity of HLA-DR). The second type: the CA positively correlated (P < 0.05) with the percentage of CD11a+CD16-, and with levels of expression of HLA-DR (P < 0.05) and CD11a (P < 0.05) expressed on CD11a lymphocytes (12.4-16 MFI DR). In RA patients with a "normal" density expression of HLA-DR on CD11a lymphocytes (up to 14 MFI) there exists a mixed type: the CA correlated positively (P < 0.05) with the percentage of CD11a+CD16+, and with levels of expression of HLA-DR (P < 0.05) and CD11a (P < 0.05) expressed on CD11a lymphocytes. In RA patients with a very high density expression of HLA-DR on CD11a lymphocytes (VH-DR group, 18-26 MFI) the CA correlated negatively with the percentage of CD11a+CD1 6+ (P < 0.05), and with levels of expression of HLA-DR (P < 0.025) and CD11a (P < 0.025) expressed on CD11a lymphocytes. The anti-HLA-I,-DR, -CD11a MoABs strongly inhibit the Ca in HV- and RA-PMC. However, in the VH-DR group the anti-DR MoAB stimulates the CA from 27.06 +/- 10.25 up to 41.69 +/- 14.23%. Thus, activated peripheral CD11a+CD16+ lymphocytes suppress the CA of other NK.

Adult↗

[Prognostic criteria for the clinical course of systemic lupus erythematosus].

To develop some individual prognostic criteria of SLE clinical course the Wald's analysis of immunogenetic markers (HLA) was used. The obtained summarized diagnostic coefficients allow predicting a subacute or chronic pattern of the disease, the rate of generalization and the most frequent location of the process in certain organs. The constant character of HLA-typing results and the simplicity of the given prognostic tables made the proposed diagnostic method convenient for medical practice.

Acute Disease↗