[Little-studied human viral hepatitides].
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Biomedical subjects
Publications and source records attributed to M S Balaian.
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The hepatitis A virus (HAV) capsid protein VP1, VP2 and VP3 are exposed at the virion surface and should therefore contain antigenic determinants. Algorithms for hydrophilicity, antigenicity and flexibility were used to predict probable antigenic sites. Synthesis of 7- to 23-membered overlapping peptides from seven sites, viz., 1-11, 1-17, 2-33, 11-25, 73-82, 76-86, 98-109, 98-112, 102-107, 102-108, 108-127, 113-123, 118-140, 276-298 from VP1, 42-62 from VP2, 76-85 from VP3, and 1-23 from VP4, was performed by various solid-phase methods. Free peptides and their conjugates with different carriers were used for immunization and study of antigenicity. The peptides did not interact with antibodies to the hepatitis A virus, whereas their conjugates did not induce the formation of anti-HAV-antibodies.
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The diagnostic value of the first experimental production batches of assay kit "DIAGN-A-HEP", produced at the Institute of Poliomyelitis and Viral Encephalitides (USSR Acad. Med. Sci.) and intended for the determination of IgM to hepatitis A virus (HAV) in the enzyme immunoassay (EIA), has been studied in comparison with that of the internationally known and widely approved commercial EIA system "HAVAB-MEIA" for the determination of antibodies to HAV (the product of Abbott, USA). The study has revealed that the EIA kit "DIAGN-A-HEP" is highly sensitive and specific, and the diagnostic value of this kit is not inferior to that of the commercial assay system "HAVAB-MEIA". On the basis of this study the use of the EIA kits "DIAGN-A-HEP" in medical practice has been allowed by the decree of the Ministry of Health of the USSR.
Additional observation on the formation of humoral immunity to hepatitis A virus has been carried out in 2,375 adolescents aged 15-17 years and belonging to 12 groups at 3 areas of the USSR. This observation has shown that in the presence of a high level of the immune stratum the spread of infection occurs, as a rule, outside the group under observation. Besides, as revealed in this study, the risk of seroconversion and the loss of specific antibodies are, respectively, directly and inversely related to the level of the immune stratum in the group. The level of the immune stratum in a given age group supposedly reflects the intensity of the development of the epidemic process at a definite area.
The results of study of the clinical picture and outcomes of type A viral hepatitis (HA) in 80 male adolescents aged 15-18 years are presented. The diagnosis was confirmed serologically. A greater incidence of the protracted forms of HA has been found in adolescents which in most cases had a favourable outcome. Protracted hepatitis was marked by long-term persistence of anti-HVA IgM. The chronic form of viral hepatitis had a course of a mixed A and B viral infection.
The authors have studied the effectiveness of the first Soviet test system for the diagnosis of hepatitis A by means of the enzyme immunoassay (Diagn-A-Hep), developed at the Institute of Poliomyelitis and Viral Encephalitides, Moscow, under the conditions of different epidemic situations. In the process of this trial the high specificity and sensitivity of this test system, established earlier in the certification and commission trials, have been confirmed. Diagn-A-Hep has proved to be highly effective in the diagnosis of acute forms of hepatitis A and permitted its detection in patients during the incubation period, as well as in patients with anicteric and asymptomatic subclinical forms. Besides clinical diagnosis, the kit Diagn-A-Hep may be used in large-scale seroepidemiological surveys of the immune structure of the population, as well as in detection of HAV in different material under test.
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The results of adaptation of hepatitis A viral strain JaM-55 to the culture of embryo kidney cells FRhk-4 from macaque Rhesus are presented. The viral strain was isolated from a M. fascicularis suffering from spontaneous hepatitis. Before inoculating the cell culture the virus was passaged twice in the M. arctoides capable of reproducing hepatitis. FRhk-4 cell line inoculation by the monkey liver extract, containing the strain HAV-YaM-55, resulted in isolation of single viral particles of hepatitis A in the preparations obtained at the first 3 passages by the 28-31 day of cultivation. Beginning from the fourth passage the abrupt increase in the number of viral particles and hepatitis A antigen was registered. There were no traces of cytopathogenic effect at any level of viral passages in the inoculated cell culture. The adapted virus contains hepatitis A viral RNA identified by spot hybridization with the cloned cDNA of hepatitis A virus.
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Antibodies to hepatitis A virus were determined in the sera of healthy population by enzyme immunoassay techniques. The distribution of antibodies in different age groups was compared, taking into account the proportion of persons with high, moderate and low titers. Among the surveyed regions, the highest proportion of nonimmune persons was detected in Moscow (45 %) and the lowest proportion, in Aralsk (7%) and Mongolia (3%). In some regions (Moscow, Vilnius) the characteristic feature of the immune structure of the population was the gradual increase of the occurrence of antibodies and their levels with age, while in other regions (Aralsk, Mongolia) the intensive acquisition of antibodies occurred at younger ages with a subsequent decline in antibody levels. Some of the possible mechanisms of the formation of population immunity to hepatitis A are discussed.
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