[Long-term results of HBV and HCV infection in patients with blood system diseases].

AIM: To specify trends in clinical and laboratory manifestations of virus hepatitis B and C (HBV and HCV) in patients with blood diseases from the moment of the first positive specific tests for HBV and HCV markers; to assess effects of HBV and HCV infection on efficacy of treatment of blood disease treatment, i.e. lifespan of patients with hematological diseases. MATERIAL AND METHODS: The study enrolled 257 patients: 205 with acute leukemia - AL, 40 with lymphoproliferative diseases, 4 - with CML and 8 - others; 8 healthy bone marrow donors. The patients were admitted to Russian Hematological Research Center in 2004-2006 Follow-up median was 253 days. A total of 7800 biological samples were studied, among them about 4000 tests for HBV DNA and HCV RNA. RESULTS: Positive tests for specific markers of HBV and HCV were absent only in 78 (29.4%) patients. Positive markers of coinfection were detected in 57 (32.8%) of 174 patients with HBV infection and in 81.4% of 70 patients with HCV infection. Probability of detection of HCV markers after positive tests for HBV markers and vice versa is about 3 times higher than probability of their isolated detection. Among patients infected with HBVsymptoms of hepatitis B are likely to appear in 56% patients to day 500 of follow-up from the date of the first positive specific test. Median of the interval between the first positive test for HBV markers and probable clinical signs of hepatitis was 30 days. Among patients with HCV infection, 85% develop hepatitis to follow-up day 300 since the date of the first specific positive test. Almost 100% patients infected with two viruses develop hepatitis to follow-up day 600. Median of the interval between the first positive test for HBV and HCV markers and probable hepatitis picture was 47 days. Overall 3-year survival of AL patients was 40%, of patients with lymphoproliferative diseases - 58%. Overall 7-month survival was 75% in AA patients. HBV infection in patients with blood disease is associated with high risk of death, especially in AA and AL. Association between HCV infection and survival is not proved. CONCLUSION: A high rate of clinical realization of viral hepatitis B and C, especially in coinfection, calls for virological and clinical monitoring of patients with any positive test for HBV and HCV markers.

[Laboratory diagnosis of herpesvirus infections in patients with acute leukemias].

The paper presents the results of monitoring the markers of herpes simplex viruses types 1 and 2, cytomegalovirus, Epstein-Barr virus, and human herpesvirus type 6 in the blood and bone marrow of patients with acute leukemias during induction multidrug therapy. Whether it is expedient to diagnose herpesvirus markers in patients with acute leukemias in the period of remission induction is discussed.

[Serotypical profile of HIV infection in Moscow]. / Serotipicheskii profil' VICh-infektsii v Moskve.

A total of 310 sera from HIV-1 infected patients detected in Moscow were serologically typed using 10 V3-imitating synthetic peptides. Subtype B virus is the most prevalent in Moscow (66.7%), serotype A/C ranks second (21.3%).

[Increase in the serotypical heterogeneity in HIV-1 in Svetlogorsk focus 1 year after the start of an epidemic]. / Narastanie serotipicheskoi geterogennosti VICh-1 v svetlogorskom ochage cherez 1 god posle nachala épidemii.

Serotypical heterogeneity of HIV-1 variants in the Svetiogorsk focus of HIV-1 epidemic (Gomel region, Belarus) increased in the cohort of intravenous drug addicts in comparison with the situation one year before. A more complex serotypical profile of the epidemic can reflect the routes of virus transmission.

[The molecular epidemiological characteristics of the HIV-1 variants circulating among injection drug addicts on the territory of the CIS Nations]. / Molekuliarno-épidemiologicheskie osobennosti variantov VICh-1, tsirkuliruiushchikh sredi shpritsevykh narkomanov na territorii SNG.

Different strains of HIV-1, circulating among drug addicts introducing drugs intravenously and detected on the territories of Russia, Ukraine and Belarus, have been characterized by the methods of the comparative analysis of genetic sequences of different variants of HIV (gene typing) and the study of the immunological properties of autoimmune sera (serotyping).

[New approaches to the chemotherapy of HIV infection]. / Novye podkhody k khimioterapii VICh-infektsii.

The preclinical analysis of the effectiveness of AZT and new compounds (sulphatized derivate of chitosan (Sch) and adamantileted Sch, contents 10 and 18% of adamantine) prepared on the basis of chitosan (Ch), carried out with the use of the experimental clinical test system (the in vitro model of peripheral blood mononuclears of a concrete patient) developed in laboratory, is presented. Both combinations in concentration 0.01 mkg/ml are decreased HIV antigens till 6.4 and 8.6% accordingly, while whilst initial Sch hare caused less effect in 4-5 fold.

[Serological properties of HIV-1 isolates from the focus of an epidemic in the Gomel region of the Belarus Republic (1996)]. / Serologicheskie svoistva izoliatov VICh-1 iz ochaga épidemii v Gomel'skoi oblasti Respubliki Belarus' (1996 g.).

Immunoreactivity of sera obtained in 1996 from HIV-1-infected intravenous narcomaniacs from an epidemic focus in Gomel region, Belarus, is studied with a panel of 10-16-component synthetic peptides simulating apical epitope of surface glycoprotein gp120 V3 loop of HIV-1 variants. Comparative analysis of resultant spectra with representative immunoreactivity spectra of sera from a sampling of HIV-1-positive sera collected in 1986-1997 in different regions of the former USSR demonstrated a high homogeneity of immunoreactivity spectra of sera from Gomel region. Serotypes of HIV-1 A/C variants circulating in populations of intravenous narcomaniacs in the focus in Gomel region in 1996 and in Southern and South-Eastern Ukraine in 1995-1996 are similar. This confirms a previous conclusion about the prevalence of A/C serotype among intravenous narcomaniacs in the former USSR.

[Serotypical stratification of HIV-1 in populations of intravenous drug users in the south/southwestern Ukraine]. / Serotipicheskaia stratifikatsiia VICh-1 v populiatsii vnutrivennykh narkomanov na iuge/iogo-vostoke Ukrainy.

A total of 101 HIV-1 positive sera from intravenous drug users (IVDU) in Southern and South-Eastern Ukraine were serotyped using V3-mimicking peptides. Serotype B circulates in Nikolaev and type A/C in Odessa and Donetsk. Prevalence of A/C serotype in the population of IVDU is a characteristic feature of the epidemic situation in this region, in contrast to the USA and Western Europe, where subtype B circulates. Serotypical stratification indicates that routes of HIV-1 dissemination in the Ukraine differ from those in the USA and Western Europe, which should be borne in mind when planning the strategy of epidemic control.

[Biological properties of primary HIV-1 isolates with varying serotype]. / Biologicheskie svoistva pervichnykh izoliatov VICh-1 razlichnykh serotipov.

Russian HIV variants with common (rapid/high SI and slow/low NSI) and rare (slow/low SI and rapid/high NSI) phenotypes are described. SI variants demonstrate a higher p24 concentration level than serotype-independent NSI. The majority of SI variants belonging to A, B, and C serotypes were isolated from patients with mainly stage B3. At stages B2 and C2, when the majority of viruses are characterized by NSI phenotype, serotype D isolates are characterized only by SI phenotype. The spectrum of cell tropism was wide for all rapid/high strains and narrow for all slow/low ones.

[Identification of immunoreactive epitopes in proteins coded by gag, env, and pol genes of the type I human T-lymphotropic virus (HTLV-I) using synthetic peptides]. / Identifikatsiia immunoreaktivnykh épitopov v belkakah, kodiruemykh genami gag, env i pol T-limfotropnogo virusa cheloveka tipa I (HTLV-I) s ispol'zovaniem sinteticheskikh peptidov.

Reactivity of 26 synthetic peptides that comprise 12 to 26 amino acid residues corresponding to segments of the gag p19, env gp46, and pol proteins of human T-lymphotropic virus type I toward 31 positive sera was studied using enzyme-linked immunosorbent assay. Specific reactivity with high titers of antibodies (presented in reciprocal dilution values) was detected for the synthetic peptides corresponding to fragments 110-130 and 100-130 (titers up to 4050) of p19, 174-197 (up to 800), 186-201 (up to 4050), 191-215 (up to 1350), 242-257 (up to 800), and 272-292 (up to 450) of gp46. Immunoreactivity of seven peptides, fragments of pol-proteins, was weak. New linear epitopes in the regions 145-158, 272-277, and 292-300 of gp46 were detected. In addition, location of the known linear epitopes in p19 and gp46 was refined on the basis of comparative study of overlapping peptides from these proteins.

[Cytomorphological and cultural characteristics of tylosin-producing strains with different antibiotic activity]. / Tsitomorfologicheskie i kul'tural'nye kharakteristiki shtammov-produtsentov tilozina s razlichnoi antibioticheskoi aktivnost'iu.

Cytomorphological and cultural characteristics of highly and low active collection strains of Streptomyces fradiae producing tylosin were studied. The strains were grown on agarized and liquid media. It was shown that unlike the low active strain, the highly active one was less sporogenic, the difference being more pronounced when tylosin was added to the agarized medium. When the strains were grown in the fermentation medium there were detected differences between them in the growth type and microcolony structure at the early stages of the fermentation process. During intensive synthesis of tylosin spheric structures were found to form near the hyphal surfaces. The phenomenon was previously observed in cultures producing other antibiotics. In the low active strain the structures were single while in the highly active strain they formed in large numbers.

[Effect of the matrix protein of the influenza virus on oxidative phosphorylation in preparations of isolated liver mitochondria from white mice]. / Vliianie matriksnogo belka virusa grippa na okislitel'noe fosforilirovanie v preparatakh izolirovannykh mitokhondrii pecheni belykh myshei.

The effect of matrix proteins (M proteins) of influenza A/MRC-11 and B/Lee viruses on oxidative phosphorylation in preparations of isolated mitochondria of white mice liver was studied. M proteins were shown to cause disorders in the system of oxidative phosphorylation leading to reduction of the coefficient of respiratory control and amplification coefficient recorded by the polarographic method. It was also shown that an anti-influenza compound 2-(1'-aminoethyl)-bicyclo(2.2.1)heptane hydrochloride reduced the damaging effect of influenza virus A/MRC-11 M protein but had no influence on the effect on mitochondrial respiration of influenza B/Lee virus M protein.

[Detection of the human immunodeficiency virus in a lymphocyte culture from a patient from Central Africa with acquired immunodeficiency syndrome and Kaposi's sarcoma]. / Obnaruzhenie virusa immunodefitstita cheloveka v kul'ture limfotsitov ot bol'nogo iz Tsentral'noi Afriki s sindromom priobretennogo immunodefitsita i sarkomoi Kaposhi.

The results of HIV virus isolation from patient A. T., resident of Central Africa, are discussed, in whom Kaposi sarcoma was diagnosed clinically and histologically, and immunological examinations revealed the acquired immunodeficiency syndrome (AIDS). Cocultivation of the peripheral blood leukocytes of the patient with normal donor leukocytes yielded a leukocyte culture in which HIV virus expression was demonstrated. The HIV antigen was detected in the ultracentrifugate of the cultures by means of indirect enzyme-immunoassay using sera to the virus from the standard kits of Organon (Netherlands) and Abbot (USA). HIV antigen was also detected on the surface of lymphocytes in the culture by indirect immunofluorescence using the same sera. Besides, reverse transcriptase activity was demonstrated in ultracentrifugates of the culture fluid by exogenous reverse transcription test using poly(zA)-oligo(dT) matrix.

[Determination of antibodies to the AIDS virus and the viral antigen by an immunoenzyme method using peroxidase and beta-lactamase]. / Opredelenie antitel k virusu SPID i virusnogo antigena immunofermentnym metodom na osnove ispol'zovaniia peroksidazy i beta-laktamazy.

The ELISA test using beta-lactamase for the detection of anti-AIDS virus antibodies and virus antigen in serum is described. The properties of this test system are compared with those of the system based on horseradish peroxidase conjugates.

[Enhanced immunogenicity of influenza virus surface proteins when incorporated into liposomes]. / Povyshenie immunogennosti poverkhnostnykh belkov virusa grippa pri ikh vkliuchenii v liposomy.

A method for incorporation of influenza virus surface proteins into monolayer liposomes has been developed on the basis of removal of dialysed non-ionic detergent (beta-octyl glucoside) from a mixture of viral proteins and lipids. The resulting lipid-protein complexes (virosomes) are similar to intact virus particles by their morphological parameters. The immunogenicity of hemagglutinin incorporated into virosomes was significantly higher than that in the preparation of surface proteins isolated from virions which was inoculated into mice with or without complete Freund's adjuvant. The high immunogenicity of hemagglutinin incorporated into liposomes correlated with their high hemagglutinating activity. The possibility of using virosomes as subunit influenza vaccines is discussed.

[Fusion of Bacillus subtilis and Bacillus licheniformis protoplasts. The mapping of the mutations leading to the supersynthesis of riboflavin in interspecies hybrids]. / Sliianie protoplastov Bacillus subtilis i Bacillus licheniformis. Kartirovanie mutatsii, privodiashchikh k sverkhsintezu riboflavina u mezhvidovykh gibridov.

As a result of fusion of the protoplasts of B. subtilis and B. licheniformis the majority of the prototrophic hybrids, as well as the auxotrophs with the Thi-Hom-phenotype or the Thi-phenotype acquired capacity for over-production of riboflavin lacking in the initial parent strains. When grown on the minimal Spizizen medium with aeration at 37 degrees C the auxotrophic recombinants accumulated 10-60 micrograms/ml of riboflavin for 2 days, while the prototrophic recombinants accumulated up to 90 micrograms/ml of riboflavin. The respective figures for their cultivation in the sucrose fermentation medium were 100-330 and 600 micrograms/ml. For mapping 3 random variants of them with different phenotypes, i.e. SL-7 (prototroph), SL-15 Thi-and SL-52 Thi-Hom-were used. Localization of the mutation on the chromosome of B. subtilis was based on transformation experiments with three marker crossing, where hybrid strains SL-7, S1-15 and SL-52 were used as the DNA donor and strain lys-rib-of B. subtilis was used as the recipient. The analysis showed that the required mutation designated as R1 was localized on the chromosome of B. subtilis in the regulatory region rib0 of the riboflavin operon.