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R M Khaitov

Publications and source records attributed to R M Khaitov.

At least 19 recordsLinked to original sources

[Peptides from the principal neutralizing and CD4-binding domain: similar immunoreactive properties and structure pattern].

The human immunodeficiency virus (HIV) proteins gp120 and gp41 are the principal immune target in HIV infection. One of the most important trends in the study of AIDS is linked to the mapping of sites involving in the binding to the cell receptor CD4 and in the induction of virus-neutralizing antibodies (VNA). Recent studies have revealed that gp120 as the major domain contains inducing type-specific BNA (PND) and a binding region with CD4 (CD4-BR). PND is located in the hypervariable loop of gp120 (residues 301-336 for a BRU strain), and CD4-BR is in the conservation area (residues 410-450). By using the synthetic fragments from these areas (BRU and MN strains) and HIV-infected persons' sera, the authors established that the immune response to PND and CD4-BR is somewhat interrelated: there is a synchronized response of HIV antibodies to peptides from the two regions in ELISA (r = 0.82). For analysis of this phenomenon, experiments with cross-linked immunoreactivity of rabbit antisera to peptides from PND and CD4-BR with homologous and heterologous peptides were performed by applying three control peptides from HIV and hepatitis B virus. It has been found that there is a cross reactivity between rabbit anti-PND (MN, BRU) and anti-CD4-BR abs. Peptide homological analysis revealed common structural elements for PND and CD4-BR despite significant differences in their proposed functions. There is a large amount of positively charged aa within both PND and CD4-BR which may be involved in gp120-CD4 interaction. Acetylation of Lys residues resulted in complete loss of peptide reactivity.

Acquired Immunodeficiency Syndrome

[Persistent viruses in serological diagnosis of HIV infection].

Specific antibodies to persistent viruses (CMV, EBV, HBV) were detected by ELISA in groups of HIV-infected patients and persons showing indefinite results of the immunoblotting test for HIV-1 antigens, on the one hand, and in HIV-seronegative donors and patients with clinical manifestations of viral infection (CMVI) on the other. The findings indicate that the persons with indefinite immunoblotting test results show elevated blood CMV and HBV antigen levels than in the matched group of seronegative donors. This fact suggests that persistent viral infections might involve in the formation of an indefinite pattern when the sera were tested for HIV. The patients whose sera behaved in such a way represent a clinical risk group for HIV infection and call for further follow-up.

AIDS Serodiagnosis

Analysis of the fine structure of the antigenic determinants of the transmembrane protein in the HIV coat with chemically modified synthetic peptides.

The amino acids involved in IgG reactivity to four HIV-1 gp41 overlapping synthetic peptides from the sequence 584-624 have been determined by a method based on the chemical modification of trifunctional amino acids, especially the acetylation of the amino groups of the lysine residues at pH 8-9. The reactivities of the sera from HIV-infected individuals and gp41-specific human Mab were studied with the overlapping peptides and their modified forms in indirect and competitive ELISA. Peptides 584-602 and 609-624 (CN-185) reacted with 88% of HIV-positive sera; the highest diagnostic significance (100%) was found with peptides 584-611 (AS-551) and 603-624 (CN-191). Acetylation resulted in a 10%-15% decrease in peptide reactivity. Moreover the concentration at which 50% inhibition occurred was 1.5 x 10(-6) M for unmodified AS-551 compared with 1.5 x 10(-5) M for the modified peptide. Circular dichroism spectra showed that acetylation did not alter the conformation of these peptides. Coupling of peptide AS-551 to a protein carrier at pH 6.5-7.0 did not affect the immunoreactivity of this peptide. Mab against human gp41 reacted with peptide 603-624 (CN-191). The concentration of this peptide necessary for 50% inhibition of Mab binding was 5.2 x 10(-6) M. It is concluded from the epitope mapping of the Mab that the antigenic determinant lies within the 603-609 fragment. Lys-608 appears to play a crucial role in the interaction with human HIVc-Mab.

Amino Acid Sequence

[Cellular immunity function in HIV-1-infected persons].

The data on the state of cell-mediated immunity in patients with AIDS-related complex are presented. The synthetic peptide of membrane protein gp120 of HIV-1 was shown to inhibit leukocyte adhesion in persons under examination, as well as to have the tendency towards inhibiting the chemotaxis of migratory cells. The maximum effect was achieved at a peptide concentration of 10(-6) M. The data obtained in this investigation suggest the presence of specific cell-mediated sensitization to the fragment of protein gp120, detected by the adhesion inhibition test with the use of spectrophotometric techniques and the capillary evaluation of the chemotaxis of migrating cells, in patients with AIDS-related complex.

AIDS-Related Complex

[Inhibitor factors in the serum of patients with the AIDS-related complex].

The data on the presence of factors blocking the reaction of E-rosette formation and leukocyte chemotaxis in the blood sera of patients with AIDS-related complex (ARC) and HIV-positive donors are presented. Most frequently the blocking of E-rosette formation coincided with the presence of a inhibiting effect on the migration capacity of leukocytes. This blocking activity was not linked with the presence of C-reactive protein in the circulation stream. The treatment of ARC patients with plasmapheresis and/or travolol was accompanied either by the disappearance of blocking activity or by the appearance of activity stimulating E-rosette formation.

AIDS-Related Complex

Prospects for the use of synthetic antigens in immunodiagnosis.

Methods for the localization and prediction of protein antigenic determinants are described, and the diagnostic potential of synthetic peptide antigens in cases of HIV, hepatitis B, and influenza is demonstrated. Attention is concentrated on the principles governing the creation and application of artificial diagnostic preparations.

Amino Acid Sequence

Molecular bases for the construction of artificial immunogens.

The molecular and cellular mechanisms of action of synthetic polyions on immunogenesis are reviewed. The results of studies of the principal properties of polyionic immunostimulators and of the cell responses to the action of these stimulants have been used to construct artificial antigen-polyion complexes with enhanced immunogenic properties. The vaccinating properties of such macromolecular complexes, constructed with the use of bacterial or viral antigens, are analysed.

Amino Acid Sequence

The use of synthetic peptides in the diagnosis of HIV infections.

The antigenic structure of HIV proteins was analyzed semiempirically. Peptides mimicking fragments of the main structural HIV-1 proteins (p17, p24, gp41, and gp120) were selected and synthesized, with account taken of the level of conservation of various HIV genome fragments. The synthesized peptides were then subjected to immunological study with human sera in an enzyme-linked immunosorbent assay (ELISA). Peptides from two regions were found to be particularly immunoreactive with sera from HIV-1 infected persons: the C-terminal end of gp120 and a sequence approximately sixty to eighty amino acids in from the N-terminus of gp41. In fact, more than 96% of HIV-1 positive sera reacted with peptide 495-516 of gp120 (SP-III), peptide 584-602 of gp41 (LS-19), and peptide 601-616 of gp41 (SP-15). Additionally, twelve out of twelve serum samples from Ugandans infected with HIV-1 reacted with both SP-III (from HTLV-III) and SP-29 (gp41, 598-609; from the LAV-ELI isolate), suggesting that these immunodominant sites are useful diagnostically irrespective of the infecting isolates. HIV-2 peptides were also synthesized, and immunoreactivity and cross-reactivity examined. Only two peptides (581-603 of gp32 and 592-605 of gp32) reacted with all of the six HIV-2 positive sera tested. These peptides did not react with HIV-1 positive sera or control sera from healthy blood donors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence

[The HLA system antigens in patients with cardiovascular diseases].

Tissue typing applied to the Russian population was used to study distribution of HLA antigens, classes I and II, in patients with essential hypertension (EH), coronary heart disease (CHD), hypertrophic cardiomyopathy (HCMP), dilated cardiomyopathy (DCMP) and virus myocarditis (VM). As control use was made of the data on HLA antigen distribution in 267 healthy persons (donors) of the Russian nationality. The genetic markers of the predisposition to the indicated diseases were revealed: in EH, DR 1 (RR-3.56), DR 4 (RR-2.17); in CHD, B 12 (RR-2.91), DR 1 (RR-3.41), DR 4 (RR-3.14); in HCMP, DR 1 (RR-2.25), DR 4 (RR-3.29); in DCMP, DR 4 (RR-3.90); in VM, DR 3 (RR-5.26), DR 4 (RR-3.51). DR 4 turned out to be the common marker of the predisposition to cardiac diseases. Besides, DR 1 was discovered to be the marker of the predisposition to EH and DR 3 to VM. The data obtained may be of importance for the clinical practice in forming risk groups.

Adult

[The protective effect of preparations made from plant seedlings in experimental Pseudomonas aeruginosa infection].

The influence of preparations obtained from oat and wheat seedlings (immunostimulating factors IF-1 and IF-2, respectively) on the natural resistance of mice to P. aeruginosa infection was studied. IF-1 and IF-2 were introduced intraperitoneally in a single injection in doses of 100 micrograms and 1000 micrograms per mouse 2 and 7 days prior to the inoculation of P. aeruginosa strain 8 in doses of 1 and 10 LD50. The presence of substances capable of stimulating the immunobiological reserves of the body in actively growing plants (seedlings) was shown.

Adjuvants, Immunologic

[Immunogenic activity of synthetic brucellosis antigens].

Experimental data obtained in this investigation indicate that the conjugation of Brucella protective antigen with a polymer carrier essentially increase the immunogenic properties of the antigen. Synthesized vaccinal preparations can be of interest for practical use, as these preparations, while inducing the development of intense immunity, do not impede the diagnosis of brucellosis by serological reactions. The comparative study of the conjugates of Brucella antigen with different carriers shows that the conjugated preparation obtained on the basis of modified dextran possesses high protective potency, which makes it possible to regard this carrier as very promising for further use.

Animals

[Rapid immunoenzyme diagnosis of influenza in patients with various allergoses and bronchial asthma].

In an investigation carried out in the allergological clinic of the Tbilisi State Medical Institute in the period between two outbreaks of influenza, the presence of influenza antigen was determined in nasal washings taken from 127 patients with different allergoses and bronchial asthma by means of the enzyme immuno-assay with the use of the type-specific virion antigen of M1-protein. This method was found to be highly sensitive and to have some advantages over traditional methods used for the diagnosis of influenza. In patients with preasthma and different forms of bronchial asthma elevated susceptibility to influenza infection and its unfavorable influence on the clinical course of these pathological conditions were established.

Asthma

[Immunobiological aspects of AIDS].

The growing pandemia of AIDS, which resulted in about 40,000 AIDS patients and about 3 million infected persons by the end of 1986, demands for the urgent creation of methods for diagnosis, prevention and treatment of the disease. The present paper analyzes the main aspects of AIDS immunobiology, i. e. the molecular genetics of the virus, production of the viral components, construction of kits for immunoenzyme detection of antibodies to the virus, development of confirmatory immunoenzyme assays. The authors discuss the prospects of creating the synthetic antigens of the AIDS virus or producing them on the basis of genetic engineering both for the diagnosis and prophylaxis of the infection.

Acquired Immunodeficiency Syndrome

Immunology of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. An update.

Recent advances in the understanding of the pathogenesis of infection with human immunodeficiency virus (HIV) stems from the demonstration that the membrane glycoprotein, CD4, is the cellular receptor for HIV. This glycoprotein is found mainly on the surface of a major subpopulation of T lymphocytes and also on macrophages, natural killer cells, some B lymphocytes, and neuronal cells. Cells infected with HIV may be destroyed or have their normal function impaired. Host immune responses to HIV are poor and are not sustained. Neutralizing antibody often is not produced, or HIV may escape from normal immunosuppressive mechanisms through the process of rapid antigenic variation. Factors and markers that may be important in the outcome or that may predict progression of HIV infection are genetic (Gc type), environmental (nutritional status or intercurrent sexually transmitted diseases sustained by the host), and immunologic (rate of decline in number and impairment of function of CD4 lymphocytes and of decline in antibody titers to HIV core protein, p24). A recombinant vaccine will probably be developed for testing in future clinical trials.

Acquired Immunodeficiency Syndrome