The genotypic characteristics and drug susceptibility profiles of clinical isolates of Mycobacterium tuberculosis recovered from prison hospital patients in the Tula region (central Russia) during 2001 and 2002 are reported. The emergence of multi-drug-resistant tuberculosis (TB) poses a major health risk to the population, with economic implications for TB control. Prisons serve as a continuous source of TB transmission. The results showed that members of the LAM and Beijing families are major contributors to the epidemiological picture of TB in the population studied. The two families of strains accounted for most of the drug-resistant TB in the population. The genotypic characteristics of the M. tuberculosis predominant LAM strain that was responsible for 31 % of TB cases in this setting are presented.

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The cytotoxicity of DNA-specific autoantibodies from sera of patients with systemic lupus erythematosis (SLE) and with lymphoproliferative diseases, and from blood of healthy donors was examined on tumor-cell lines L929 and HL-60. DNA-binding IgG fractions from SLE and chronic lymphocytic leukemia (CLL) sera were cytotoxic at concentrations of up to 10(-10) M. No detectable changes in cell viability were observed after incubation with antibodies devoid of DNA-binding activity and DNA-specific antibodies isolated from blood of healthy donors and patients with T-cell lymphoma, B-cell lymphosarcoma, and acute B-cell leukemia. There was good correlation between the cytotoxic activity and DNA-hydrolyzing activity of anti-DNA antibodies. The cytotoxic effect of DNA-binding antibodies presumably was complement-independent, because it was attributed only to the Fab fragment. The cytotoxic effect was completely inhibited by preincubation with double-stranded DNA (dsDNA). Both the cytotoxic effect and the DNA-hydrolyzing activity of anti-DNA antibodies were significantly increased in the antibody fraction that displayed cross-reactivity with nuclear matrix proteins. Possible mechanisms for the formation and pathogenicity of cytotoxic anti-DNA antibodies are discussed in this article.

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We analyzed IS6110-associated polymorphisms in the phospholipase C genes of 107 isolates of Mycobacterium tuberculosis selected to be representative of isolates circulating in central Russia. We found that the majority of Latin American-Mediterranean family strains contained an insertion in a unique position in the plcA gene, suggesting a common ancestor. This insertion can serve as a specific genetic marker for this group, which we designate the LAM-RUS family.

Tuberculosis remains a major public health concern in Russia and worldwide. Given the great geographical, ethnic, and socio-economic heterogeneities between Russian regions, epidemiological data cannot be generalized from a regional to a country-wide level. We present data on the epidemiology of tuberculosis in Central Russia. We report a high level of resistance to major antitubercular drugs in both new and previously treated patients in the region. The level of drug resistance in new cases was almost twice as high as the estimated average national level. The Mycobacterium tuberculosis strains that circulated in the region were predominantly represented by LAM-RUS and Beijing genotypes. These two lineages were strongly associated with drug resistance and clustering. Using molecular epidemiology techniques, we showed a high interpenetration by M. tuberculosis strains between the prison and civilian populations. A limited number of identical strains were responsible for the majority of drug-resistant tuberculosis cases in both settings.

BNP immunoassays. We found better agreement between the results obtained with the IRMA and ADVIA methods ( Fig. 1D; see also Fig. 1D in the online Data Supplement). We also observed a significant difference between the results obtained with these two methods (P ϭ 0.0032); the mean (SD) difference was 2.1 (140.8) ng/L.All immunoassay methods could differentiate between healthy individuals and patients with different degrees of heart failure as well as between patients with mild (NYHA classes I and II) and severe (NYHA classes III and IV) heart failure ( Table 1B).We tested the diagnostic accuracy of immunoassay methods for BNP and NT-proBNP by ROC curve analysis. All immunoassay methods clearly differentiated between the group of healthy individuals and the two groups of cardiac patients with mild (NYHA classes I and II) or severe (NYHA classes III and IV) heart failure [areas under the curves (AUC), 0.865-0.999]. The electrochemiluminescence immunoassay for NT-proBNP (AUC ϭ 0.954; 95% confidence interval, 0.920 -0.978) showed the best power, compared with the other immunoassays (AUC values ranging from 0.865 for the ADVIA to 0.902 for the IRMA; P Ͻ0.01), for separating healthy individuals from patients with mild symptoms of heart failure. The MEIA method showed different diagnostic characteristics compared with other the BNP immunoassays (McNemar 2 test, P ϭ 0.0036 vs ADVIA, 0.0083 vs IRMA, and 0.0153 vs POCT TRIAGE) in this group of patients, whereas there were no significant differences in performance among the other immunoassays. All immunoassay methods performed well (AUC values, 0.982-0.999) in differentiating between healthy individuals and patients with severe heart failure.The main goal of this study was to evaluate the analytical performance of several BNP and NT-proBNP immunoassays in samples subjected to the same preanalytical conditions. This protocol was chosen to better focus on performance differences among the tested methods to reduce as much as possible the other confounding causes of variability typical of multicenter studies or metaanalysis of published data. However, the clinical results of this study cannot be extrapolated to other clinical settings. Comparison of our results with those of other recent studies (7)(8)(9)(10)(11)(12)(13)(14) suggests that diagnostic accuracy can strongly depend on patient selection and on the cardiac natriuretic peptide assayed (BNP, N-terminal pro-A-type natriuretic peptide, or NT-proBNP), as well as on the analytical performance and diagnostic accuracy of the immunoassay chosen.

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