Manifestations of angina morbidity as a reflection of the self-regulation of the epidemic process in streptococcal infection

The data on the application of the principles of the self regulation of the epidemic process for understanding the annual dynamics of angina morbidity in organized groups of adults are presented. In this case the reservation of group A streptococci occurs in chronic (resident) carriers, whose proportion was found to be 15.8 +/- 2.6%. The epidemic manifestations of morbidity are regulated mainly by the concentration of newly arrived members in the groups, i. e. by the size of the stratum providing the optimum conditions for the parasitization of the streptococcal population. The annual morbidity levels depend essentially not only on the heterogeneity of the group members with respect to their susceptibility to streptococcal infection, but also on the conditions of their accommodation, affecting the transmission of droplet infection. The role of individual risk factors in the variation of the quantitative characteristics of the angina morbidity manifestations under study is calculated.     

Phase changes in the population of group A streptococci and their influence on the course of the epidemic process of tonsillitis

This work presents the data on the complex evaluation of the population of group A streptococci, studied at each of four phases (reservation, epidemic transformation, epidemic spread, reservational transformation) of the course of the epidemic process of streptococcal infection of the respiratory tracts (tonsillitis) in an organized group of adults. The characterization of the phases of the infective agent in accordance with the level of the carrier state, the size of streptococcal foci and the virulence of streptococci is given. Thus, the study shows that the heterogeneity of group A streptococci with respect to their virulence reaches its maximum level at the phases of reservation and epidemic spread and its minimum level at the phases of epidemic and reservational transformation. The size of streptococcal foci in carriers and the virulence of streptococci isolated from them are the inter-related unidirectional signs of the population of the infective agent and, at the same time, the main factors responsible for the phase character of the epidemic process and the morbidity level in tonsillitis.     

Sensitivity of beta-hemolytic streptococci to antibiotics]

Susceptibility of 64 beta-hemolytic streptococcal strains isolated from the patients with sore throat was studied by the method of serial dilutions in fluid nutrient medium (Konikov broth). Heterogenecity with respect to the sensitivity was investigated in 34 strains among separate populations of the microbes (10 to 15 in every strain). The MIC of benzylpenicillin, oxacillin and erythromycin ranged within 0.007--0.24 U/ml, 0.02--0.36 gamma/ml and 0.005--0.1 gamma/ml respectively. The MIC of benzylpenicillin with respect to separate populations most sensitive to it was 0.007--0.015 U/ml, while that with respect to the lease sensitive populations ranged from 0.015 to 0.24 U/ml. The respective values for oxacillin were 0.02--0.12 and 0.18--0.36 gamma/ml and those for erythromycin were 0.005--0.025 and 0.05--0.1 gamma/ml. Therefore, the beta-hemolytic streptococci isolated from the patients with sore throat were characterized by a rather high sensitivity to the antibiotics which was important precondition for their efficiency in treatment of the patients with the above disease.     

A Group of Hypermethylated miRNA Genes in Breast Cancer and Their Diagnostic Potential

Molecular Biology - miRNA genes play an important role in cancer pathogenesis, while they may be suppressed by hypermethylation. Here, we assess the diagnostic potential of a group of...     

Determination of <Emphasis Type="Italic">EGFR</Emphasis> gene somatic mutations in tissues and plasma of patients with non-small cell lung cancer

Activating mutations in the EGFR gene influence cell proliferation, angiogenesis, and increases metastatic ability of non-small cell lung cancer (NSCLC) cells; they have a significant impact on the choice of medical therapy of NSCLC. The use of targeted therapy with tyrosine kinase inhibitors requires performance of appropriate genetic tests in NSCLC patients. The aim of this study was to develop a real-time PCRbased diagnostic test-system for rapid and cost-effective analysis of EGFR mutations in paraffin blocks and plasma and to perform comparative estimation of diagnostic characteristics features of real-time wild type blocking PCR and digital PCR. The study included 156 patients with different degrees of lung adenocarcinoma differentiation. A simple and efficient real-time PCR-based method for detection of L858R activating mutation and del19 deletion in the EGFR gene in DNA isolated from paraffin blocks or blood has been developed. The test system for EGFR mutations has been validated using 411 samples of paraffin blocks. The proposed system demonstrated high efficiency for DNA testing from paraffin blocks: a concordance with results of testing by means a Therascreen® EGFR RGQ PCR Kit (Qiagen, Germany) was 100%. Applicability of this test system has been also demonstrated for detection of mutations in plasma.     

Human chromosome 3P regions of putative tumor-suppressor genes in renal, breast, and ovarian carcinomas

Allelic imbalances (AI) of polymorphic markers at the short arm of chromosome 3 (3p) were mapped using DNA samples of renal cell carcinoma (RCC, 80 cases), breast carcinoma (BC, 95 cases), and epithelial ovarian cancer (EOC, 50 cases) at the same dense panel of markers (up to 24 loci). Six regions with the increased AI frequency (versus the average values determined for all the analyzed 3p markers) at RCC, BC or EOC were found in 3p chromosome. Four 3p regions presumably contain suppressor genes of tumor growth (TSG) observed in the epithelial tumors of various types. Region between D3S2409 and D3S3667 markers in the 3q21.31 region was identified in this study for the first time. The AI peak in D3S2409-D3S3667 region was statistically significant (P < 0.001, according to Fisher) when representative sample of 95 BC patients was analyzed. The data on increased frequency of polymorphic marker allele amplification suggest that the D3S2409-D3S3667 region contains both putative TSG and protooncogenes.     

Methylation of the <Emphasis Type="Italic">RASSF1A</Emphasis> promoter region and the allelic imbalance frequencies in chromosome 3 critical regions correlate with progression of clear cell renal carcinoma

The short arm of chromosome 3 (3p) contains several critical regions that have increased frequencies of allelic deletions and harbor a set of tumor suppressor genes. In particular, the range of functions performed by RASSF1A (LUCA region, 3p21.31) includes those potentially associated with carcinogenesis. Among 3p genes, RASSF1A has the highest methylation frequency in epithelial tumors of various locations. For the first time, two different methods (methylation-specific PCR and methylation-sensitive restriction analysis) independently showed that the methylation level of the CpG island in the RASSF1A promoter region significantly correlated with grade and clinical stage of clear cell renal cell carcinoma (RCC). An analysis of 23 3p polymorphic markers in a representative set of 80 RCC cases characterized clinically and histologically revealed that RCC progression significantly correlated with the frequency of allelic imbalances in some critical regions of 3p (LUCA and AP20), but not in 3p as a whole. These data suggest that RCC progression is associated with the methylation of the RASSF1A promoter and, possibly, with structural and functional alterations in other 3p genes. In addition, significant correlation between RASSF1A methylation and allelic losses at the nearby polymorphic marker locus suggests the “two hit” model for the inactivation of this tumor suppressor gene in RCC.     

Two CpG islands in the <Emphasis Type="Italic">SEMA3B</Emphasis> gene: Methylation in clear cell renal cell carcinoma

Earlier, methylation of a CpG island in the SEMA3B gene (3p21.31) was observed in cell lines of small-cell and non-small-cell lung carcinoma. According to NCBI (Build 36), that island belonged to intron 1 of the gene. Our study concerns the methylation of two CpG islands, promoter and intronic, in the SEMA3B gene in patients with clear cell renal cell carcinoma (RCC). Methylation-specific PCR and bisulfite sequencing revealed a high frequency of methylation in the promoter CpG island (34/61, 56%) and somewhat lower, in the intronic (17/48, 35%). A significant inverse correlation was found between the SEMA3B mRNA level and methylation of the promoter CpG island in RCC (P < 0.05 according to Fisher’s exact test). The intronic island showed no such correlation. Thus, we suggest that the methylation of the promoter CpG island contributes to the inactivation of the SEMA3B suppressor gene in RCC tissue.