[LMP1 gene polymorphism in patients with Epstein-Barr virus-negative gastric carcinomas in Russia].

The investigation was undertaken to study the molecular characteristics of Epstein-Barr virus (EBV) LMP1 gene samples amplified from the tumor and intact tissues of patients with EBV-negative forms of gastric carcinoma (GC). The genetic structure of these samples determined by their sequencing was compared with that of the gene samples isolated from the cells of oropharyngeal washing specimens from the same patients with GC, as well as peripheral blood lymphocytes of patients with infectious mononucleosis (IM) and blood donors. The findings suggest that the samples of tumor tissue LMP1 from patients with GC have higher divergence than those from patients with IM and blood donors although no specific variants of the gene for GC were found. Comparison of LMP1 sequences from tumor tissue and cells of oropharyngeal washing specimens from the same patients with EBV-negative GC revealed the common LMP1 variant in 2 cases while they differed in 3 cases. The findings are an initial step in studying the role of EBV in the carcinogenesis of EBV-negative GC that is likely to be established by investigations on representative clinical material, by applying the up-to-date technologies.

[Mutations of the Epstein-Barr virus LMP1 gene mutations in Russian patients with lymphoid pathology and healthy individuals].

Epstein-Barr virus (EBV) is an etiological agent of a number of benign and malignant human diseases, such as infectious mononucleosis (IM), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL). EBV latent membrane protein 1 (LMP1) gene (recognized as a viral oncoprotein) of various clinical and geographical origin was found to have different types of amino acid mutations affecting its biological activity. Since there was no information on the strain differences in LMP1 of EBV persisting in Russia, the authors made a sequence analysis of LMP1 samples amplified from the biological materials of Russian patients with IM, HL, and NHL and healthy individuals. The studies have shown that LMP1 variants of Russian origin are a mixed heterogeneous group containing both the earlier characterized and presumably new genetic variants. Among the point amino avid substitutions, the mutations S366T, F106Y, 185L, and E328Q associated with the enhanced transforming activity of a LMP1 molecule and its reduced cytotoxicity. There was no specific association between the certain Russian variants of LMP1 and the specific forms of the disease (IM, HL, and NHL).

[LMP1 gene variants of Epstein-Barr virus in patients with some lymphoproliferative malignancies].

The samples of tumor biopsy, blood, and saliva from 10 patients with Hodgkin's disease, 10 patients with non-Hodgkin's lymphoma, and the blood samples of 20 donors were tested by polymerase chain reaction (PCR) for standard (wild) B95-8 and Cao-like (deleted) variants of the LMP1 gene. The paraffin sections of most PCR-tested tumors were also investigated by immunohistochemistry using the monoclonal antibodies S12 or 7D7 to detect the expression of the standard or Cao-like variants of LMP1 protein, respectively. It is suggested that Eptein-Barr virus (EBV) that contains the above deletion is not crucial for the development of the study lymphoproliferative malignancies. The fact that in some cases there is the Cao-like variant of LMP1 in the tumor biopsy specimen and its standard variant LMP1-B95-8 in the biological fluids of the same patient is very likely to suggest that the patient is infected with both types of the virus or there is genetic mutation(s) of EBV during viral carcinogenesis preceding or accompanying the development of a tumor.

Humoral antibodies to the capsid antigen of Epstein-Barr virus in Hodgkin's disease.

By the method of indirect immunofluorescence it has been shown in P3HR-I cells that sera from patients with Hodgkin's disease contain high titers of humoral antibodies to the capsid antigen of Epstein-Barr virus (EBV). Higher titers of antibodies of EBV were found in histological variants of Hodgkin's disease with an unfavorable course. The variant of lymphocyte depletion is accomplished by higher titers of the virus and poorer prognosis than the nodular-sclerotic variant having a course with lower titers of antibodies and better prognosis. At the same time, the level of antibodies does not depend on the results of the therapy applied. In the sera of patients with reticulosarcoma or lymphosarcoma no increase in the level of antibodies to EBV has been discovered in comparison with a group of healthy donors; in acute leukemia a certain tendency to decrease in the level of antibodies to this virus can be observed.

A study on the relation between the Epstein-Barr virus and some forms of malignant tumors in children.

The presence of antibodies to the virus capsid antigen of the Epstein-Barr virus was established in the sera of children from different forms of neoplasms with the aid of the indirect method of immunofluorescence according to Henle. 69 sera were studied from children with Wilm's tumor, teratoblastoma, reticulosarcoma, neuroblastoma, sarcoma and also from children with benignant tumors. As control served sera from healthy children of corresponding age. As test cells synthesizing the virus capsid antigen the authors utilized a suspension culture of P3HR-I cells, being one of the clones of Burkitt's lymphoma. The performed investigations have shown that in no one group of children with tumor could there be discovered an increase in the content of antibodies to the Epstein-Barr virus in comparison to controls. It has also been revealed that the spread of the Epstein-Barr virus in different groups of patients and healthy children fluctuated between 83 and 100%.

[Antibodies to the human T-cell leukemia virus in the blood serum of the inhabitants of Sakhalin and Iuzhno-Kuril'sk]. / Antitela k virusu T-kletochnogo leikoza cheloveka v syvorotke krovi u zhitelei Sakhalina i Iuzhno-Kuril'ska.

Two immunological tests were used in testing of 808 blood serum samples from inhabitants of Sakhalin and of the city of Yuzhno-Kurilsk for antibodies against HTLV-1 etiologically associated with human T-cell leukemia. Antibodies to HTLV-1 were detected in 4.2% of Nivkhs, 1.2% of Oroks and 1.5% of Russians. The highest level of virus-carriers reaching 6.0% was detected in Nivkhs from the middle part of Sakhalin. The antibodies were detected more often in persons of old age and in women.

[Serological examination of the population of the Far East for the presence of antibodies to human T cell leukemia virus HTLV-1]. / Serologicheskoe obsledovanie zhitelei Dal'nego Vostoka na nalichie antitel k virusu T-kletochnogo leikoza cheloveka HTLV-1.

Antibodies to HTLV-1 were detected in sera from 1298 healthy adult persons living in the Far East. It is shown that virus infectivity of the Nigidalts was 8%, Nivkhs--2%, Udegeits--2.9%, Oroches--2.4%, Russians--0.9%. However, the incidence of acute leukemia in these regions is low. It is suggested that these regions are not endemic areas for HTLV-1-associated haemoblastoses.

[The level of antibodies to Epstein-Barr virus antigens in the blood serum of the inhabitants of southern Siberia and the Far East]. / Uroven' antitel k antigenam virusa Epshteina--Barr v syvorotke krovi zhitelei iuga Sibiri i Dal'nego Vostoka.

Antibodies to Epstein-Barr virus have been detected in sera from 1538 healthy adult persons living in the south of Siberia and Far East. It has been shown that the virus infectivity varied from 77% in Russians of the Yakutsk ASSR to 100% in Orochi and Russians residing in the territory of the Gorno-Altai Autonomous Province. Antibody levels to the Epstein-Barr virus for inhabitants of the south regions were higher than those for inhabitants of the north regions.

[Human acute lymphoblastic leukemia associated with HTLV-I virus and its infection in healthy populations from various regions of the USSR]. / Ostryi limfoblastnyi leikoz cheloveka, assotsiirovannyi s virusom HTLV-I, i infitsirovannost' im zdorovogo naseleniia nekotorykh regionov SSSR.

Patients with various forms of hemoblastoses (328) and clinically healthy persons (530) were examined for antibodies to HTLV-I. The presence of antibodies was detected in 3 out of 40 patients with acute lymphoblastic leukemia and only in 1 of 70 patients with lymphosarcoma. These data indicate that sporadic cases of T-cell leukemia associated with HTLV-I were detected in the USSR. Out of 530 healthy persons only 4 contained antibodies to HTLV-I antigens.

[Molecular biological and clinical-morphological studies of gastric tumors associated with Epstein-Barr virus]. / Molekuliarno-biologicheskoe i kliniko-morfologicheskoe issledovaniia opukholei zheludka, assotsiirovannykh s virusom Epshteina-Barr.

The paper presents the results of the studies of gastric cancer (GC) associated with Epstein-Barr virus (EBV) among the patients residing in 4 geographical regions. In situ hybridization (ISH) techniques revealed that 49(11.4%) of the 430 examinees were EBV positive (EBV+), the virus-specific marker mRNA-1 of EBV, EBER-1) was found to be present in 80-100) of tumor cells. The proportion of EBV(+)-associated GC cases in different geographic regions ranged from 7.3 to 15%. These tumors were predominant in males (15%) as opposite to females (5.5%). Histological types most common among EBV+ tumors and their location in the stomach are also described. Serological findings indicated that the increased anti-EDV antibody response in 70% of GC cases coincided with the presence of the viral genetic information detected by ISH. In contrast to a humoral response to EBV, a humoral response to Helicobacter pylori was equal both in patients with EBV(+)- and EBV(-)-associated gastric tumors. Further molecular biological analysis of EBV isolates from virus positive and virus negative GC may answer the question whether there are really the so-called tumor and non-tumor variants of EBV.

[Detection of HTLV-I viral antibodies in donor blood samples]. / Obnaruzhenie antitel k virusu HTLV-I v obraztsakh donorskoi krovi.

Sera from 867 donors were tested for antibodies to the virus of T-lymphocyte leukemia of adults (HTLV-I) in parallel by indirect immunofluorescence on acetone-fixed cells of HUT-102 culture producing HTLV-I and by agglutination test using a commercial set ("Serodia-ATLA", Japan). Twelve (1.38%) out of 867 sera were positive in the agglutination test and only 7 of them in immunofluorescence test. The specificity of the results was verified by absorption experiments. The activity of the sera in the agglutination test disappeared completely after their absorption with HUT-102 culture cells but did not change after absorption with LLU cells producing no HTLV-I despite a low percent of virus infection, donor blood control for HTLV-I infection becomes mandatory.

[Humoral antibodies to Epstein-Barr virus in infectious mononucleosis]. / Gumoral'nye antitela k virusu Epshteina-Barr u bol'nykh infektsionnym mononukleozom

A high level of humoral antibody to the capsid antigen of Epstein-Barr virus was found in sera from patients with infectious mononucleosis. For detection of antibody, the method of indirect immunofluorescence in fixed P3HEHR cells of Burkitt's lymphoma was used. Sera from normal subjects were also shown to contain antibody to the capsid antigen of Epstein-Barr virus, but the titers were 5--10 times lower than in the sera from infectious mononucleosis patients. The occurrance of high titers of antibody to EBV in the sera from patients with infectious mononucleosis is diagnostic for IM and may be used for practical purposes.

[Relation of antibody levels to Epstein-Barr virus to histological variant and clinical course of lymphogranulomatosis]. / Zavisimost' urovnia antitel k virusu Epsteina-Barr ot gistologicheskogo varianta i klinicheskogo techeniia limfogranulematoza

The indirect immunofluorescent test in fixed P3HR-1 cells showed the sera from patients with lymphogranulomatosis to contain high titers of humoral antibody to the capsid antigen of Epstein-Barr virus. Higher titers of antibody to EBV were associated with unfavourably running histological variants of lymphogranulomatosis. The lymphoid depletion variant was accompanied by high antibody titers to the virus and had a worse prognosis than the nodular-sclerotic variant with lower antibody titers but better prognosis. The level of antibody in lymphogranulomatosis was stable. No relationship between the antibody level and the stage and results of the therapy given was found. In sera from patients with reticulosarcoma and lymphosarcoma no significant rise of antibody titers to EBV was found as compared with a group of normal donors, while in acute leukosis there was a tend for a decline in antibody titers.

[Antibodies to Epstein-Barr virus in the sera of children with different neoplasms]. / Antitela k virusu Epshteina--Barr v syvorotkakh detei s razlichnymi novoobrazovaniiami

The presence of antibody to virus capsid antigen (VCA) of Epstein-Barr virus (EBV) was determined in sera from children with various forms of neoplasia by the indirect immunofluorescence procedure of Henle. Eighty-one sera from children with Wilms tumor, teratoblastoma, reticulosarcoma, neuroblastoma, soft tissue sarcoma, as well as from children with benign tumors were examined. The controls included sera from normal children of the same ages. The test cells synthesizing VCA were suspension cultures of P3HR-1 cells which are one of the clones of Burkitt lymphoma. The studies showed no increase in the content of antibody to EBV in any of the groups of children with tumors as compared with the controls. It was also found that the percentage of EBV infection in various groups of sick and normal children varied from 82 to 100.

[Screening of sera from the adult populations of some USSR regions for antibodies to the human T-cell leukemia virus type I (HTLV-I)]. / Skrining syvorotok vzroslogo naseleniia nekotorykh regionov SSSR na antitela k virusu T-kletochnogo leikoza cheloveka I tipa (HTLV-I).

The results of serologic survey of 4118 residents of the USSR Far East from 16 to 82 years of age and 1037 blood donors for antibody to HTLV-I by the method of passive agglutination of gelatin particles coated with viral proteins are summarized. The portion of HTLV-1 seropositive subjects in the Khabarovsk Territory was 1.79% (25 out of 1391), in the Maritime Territory 2.2% (18 out of 801), in the Sakhalin Island 1.6% (26 out of 1557), and in Kamchatka 1.6% (6 out of 369). A discrete area of a higher number of positive cases was found among Nivkhi national group in the village of Nogliki in the Sakhalin Island: 6.4% (10 out of 155). In women, antibody to HTLV-1 was found twice as frequently as in men. Seropositives to HTLV-1 among blood donors in Moscow, the town of Komsomol'sk-na-Amure, and the town of Yuzhno-Sakhalinsk comprised 1.4%, 1.6%, and 5.45%, respectively. The occurrence of HTLV-1 infection among the normal population of the Far East and especially among blood donors attests to the expedience of wider seroepidemiological surveys of the population and especially donors for HTLV-I infection in other regions of the USSR as well.

[The human herpesvirus type 6 (HHV-6) and its spread in Russia]. / Virus gerpesa cheloveka tipa 6 (HHV-6) i ego rasprostranenie v strane.

This is the first presentation of information on the circulation of human herpes virus type 6 (HHV-6) in the population of the mid-European part of this country. The results of the study indicate that HHV-6 is widely spread both among apparently normal people and among patients with different pathologies. The studies using immunofluorescence test showed that the percentage of HHV-6-infected subjects was practically similar among blood donors, patients with nasopharyngeal cancer, rheumatoid arthritis, hemophilia, and patients with transplanted kidney, varying from 34% to 49%. A significantly higher per cent (66%) and higher antibody titres to HHV-6 were detected in sera from patients with hemoblastoses. A high level of HHV-6 infection among patients with hemoblastoses was also confirmed by the results of immunoblotting showing a wider spectrum and higher intensity of the detectable proteins. It should be noted that the amounts of virus-specific proteins detectable by some sera showed individual variations indicating different levels of expression of viral proteins in different individuals.

[Serological and molecular-biological study of T-cell leukemia virus in Turkmenistan]. / Serologicheskoe i molekuliarno-biologicheskoe izuchenie virusa T-kletochnogo leikoza (HTLC-1) v Turkmenistane.

Seroepidemiological and molecular-biological screening of 1510 donor blood samples, collected from the residents of the town of Ashgabat (Turkmenistan), for lymphotropic virus of human T-cellular leukemia (HTLV) virus revealed one donor with a high level of immune response to a wide spectrum of viral proteins. Three donors were serologically assessed as dubious, for their sera contained antibodies to gag gene protein but no antibodies to env gene protein. Screening of family members of the donor infected with HTLV-1 revealed four more highly reactive carriers of HTLV-1 virus. The presence of proviral sequences of HTLV-1 in the lymphocyte DNA of infected donor and her relatives was confirmed by polymerase chain reaction and subsequent Southern-blot hybridization of specific amplification products. Proviral sequences of gag, pol, and LTR genes were detected in all the cases. Short-term culturing of peripheral blood lymphocytes of all seropositive subjects was associated with expression of HTLV-1 structural proteins. Analysis of the possible routes of transmission of HTLV-1 isolated in Turkmenistan permits us to hypothesize an Iranian origin of the isolated virus strain.

[The 1st case of adult T-cell leukemia (ATL) with expressed immune response to HTLV in the USSR]. / Pervyi diagnostirovannyi v SSSR sluchai T-kletochnogo leikoza vzrozlykh (ATL) s vyrazhennym immunnym otvetom k HTLV.

The first of case of adult T-cell prolymphocytic lymphosarcoma is reported which according to the natural course, cell composition of tumor, cell surface markers as well as expressed immune response to a wide spectrum of HTLV-1 gag an env encoded proteins can be classified as HTLV-associated adult T-cell leukemia. Diagnosis of the tumor alongside with identification of HTLV-1-infected individuals in the USSR emphasizes the need to stimulate research in HTLV-1-associated carcinogenesis in this country.

[The viral and immunological characteristics of cardiomyopathies and myocarditis]. / Virusoimmunologicheskaia kharakteristika kardiomiopatii i miokarditov.

As many as 97 patients with myocardial lesions: congestive and hypertrophic cardiomyopathy (CMP), postmyocarditis CMP (PM CMP), myocarditis (MC), alcoholic heart injury (AHI), coronary heart disease (CHD), vegetodysovarian myocardiodystrophy were examined by means of a complex of the virological tests (for Coxsackie B, Epstein-Barr and hepatitis B viruses) and immunoassays (for antibodies to different components of the myocardium, leukocyte migration inhibition test, antibody-dependent cellular cytotoxicity test, measurements of T and B lymphocytes and their subpopulations, and so forth). Virus infection was shown to be of a role for the onset of acute MC (usually reversible) and congestive CMP. At the same time the autoimmune mechanisms of the lesions were conclusively ascertained in MC associated with heart failure and in PM CMP. In patients with congestive CMP and AHI coupled with heart failure, antibodies to nerve fibers of the myocardium could be demonstrated in the presence of T-lymphocyte deficiency and high titers of antibodies to Epstein-Barr virus. This does not allow excluding myocardial denervation leading to refractory heart failure. Some immunological parameters made use of in the study provide an opportunity of an objective evaluation of the effect glucocorticoid treatment produces on patients suffering from MC and PM CMP.