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Biomedical subjects

V P Chernyshov

Publications and source records attributed to V P Chernyshov.

At least 19 recordsLinked to original sources

[Anti-idiotypic antibodies as a physiological mechanism of inhibition of cofactor-independent antiphospolipid antibody formation].

Antiphospholipid antibodies (APA) and anti-idiotypic antiphospholipid antibodies (AiAPA) were studied in 148 women subjected to IVF. APA (IgG aCL, aPS,) levels in serum have been defined. Sera IgG fraction was also examined for the presence of AiAPA by three different methods: 1) binding of AiAPA with mouse monoclonal cofactor-independent APA (mAPA) immobilized on plate; 2) AiAPA neutralization of human affinity isolated APA and 3) mAPA binding with phospholipids. Significant difference in AiAPA levels between APA+ and APA- women subjected to IVF have been found. The mean level of AiAPA was lower in APA women subjected to IVF than in APA- women from the same group (p < 0.05). IV infusion of Ig decreased the APA level significantly as well as increased the AiAPA level in APA+ women subjected to IVF. Ig application to incubation in vitro results in decrease of APA levels in serum. Results of this study confirmed possibility of AiAPA participation in down regulation of cofactor-independent APA production in women undergoing to IVF.

Antibodies, Anti-Idiotypic↗

[Immunopathophysiologic characteristics of early pregnancy in women with recurrent miscarriage].

UNLABELLED: The lymphocyte subsets, activation marker expression and activity of ConA-treated lymphocytes have been studied in 58 patients with a history of unexplainable pregnancy loss (UPL) and 22 normal pregnant women (control) in 4-7 weeks of pregnancy. The increase of CD16/56+ cell level and CD4+/ CD8+ ratio and decrease of CD19+ cell level have been found in peripheral blood of UPL patients in comparison with control. The expression of HLA-DR was upregulated on CD3+ and CD8+ cells and the expression of CD25 was downregulated on CD3+, CD4+, CD8+, and CD16/56+ cells in UPL women. According to correlation analysis results, low expression of CD25 was related to a low expression of CD8 on NK, high expression of CD45RA on CD4+ helper cells, high expression of HLA-DR on CD8+ cytotoxic cells. High frequency of ConA-induced activation, low frequency of ConA-induced suppression and low suppressive activity of ConA-induced lymphocyte were found in UPL patients compared to control. CONCLUSION: women with UPL have disorders in feto-maternal recognition in early pregnancy that led to a development of the inadequate immune response to fetus realized as a defect of NK activation, deficiency of T-cytotoxic cell limitation and memory helper cell generation, downregulation of TR cells and suppressor function.

Abortion, Habitual↗

[Cofactor-antiphospholipid antibodies relationship in patients with systemic lupus erythematosus and infertility women].

High frequency of detecting antiphospholipid antibodies (APA) is typical for patients with systemic autoimmune diseases as well as infertility women irresponsive to IVF treatment. Antiphospholipid antibodies cause thrombotic complications in patients with systemic autoimmune diseases contrary to antiphospholipid antibodies with in-vitro fertilization taken place. The authors have compared specificity and cofactor-antiphospholipid antibodies relationship in patient with systemic lupus erythematosus, infertility women irresponsive to IVF treatment and patients with chronic virus hepatitis. It has been shown that 80% of patients with systemic lupus erythematosus are mostly beta2-glycoprotein- and cofactor dependant. Patients with chronic virus hepatitis and women with in-vitro fertilization (IVF) have been found to have pretty low beta2-glycoprotein dependant antiphospholipid antibodies. Antiphospholipid antibodies in in-vitro fertilization women were cofactor dependant only in 28%. of the cases. These data can explain absence of thrombotic complication in APA positive IVF patient, because its complications have been associated with cofactor-dependent APA. It also can explain a lot of controversial results about significance of APA on IVF result.

Annexins↗

[Effect of progesterone and 17beta-estradiol on proinflammatory cytokine costimulatory proliferative activity].

The lymphocyte proliferation is multicomponent mechanism of immune system reactivity. Many costimulatory factors take part in this process. Proinflammatory cytokines (TNF, IL-1 alpha and beta) enhance proliferation of activated lymphocytes. Female steroid hormones inhibit proliferation of mitogen and alloantigen-activated lymphocytes. The aim of this study was to investigate the effect of progesterone and 17 beta-estradiol on the costimulatory proliferative activity of proinflammatory cytokines in vitro. Female steroid hormones inhibit lymphocyte response to antiCD3 antibody. Progesterone had a stronger effect than 17 beta-estradiol (64 and 13% of inhibition respectively). 17 beta-estradiol enhanced the TNF costimulatory effect on the lymphocyte proliferation. Progesterone neutralized this TNF-induced effect and reverted it (inhibition of lymphocyte proliferation was enhanced in the presence of TNF). We found dominant inhibitory effect of progesterone on the TNF costimulatory activity when progesterone and estrogen were added simultaneously. Progesterone and 17 beta-estradiol downregulated costimulatory proliferative activity of IL-1 alpha or beta. Thus female steroid hormones had suppressive effect on the antiCD3-stimulated lymphocyte proliferation. They downregulated costimulatory proliferative activity of IL-1 alpha/beta and had opposite effect on TNF costimulatory activity. Our results suggest possible roles female steroid hormones as regulators on activity of proinflammatory cytokines and their functions in lymphocyte proliferation.

Cells, Cultured↗

[Effect of female steroid hormones on expression of adhesion molecules by peripheral blood leukocytes].

The specific adhesion of cells to other cells or to extracellular matrices is a basic component of cell migration and recognition, and it underlies a lot of biologic processes including embryogenesis, tissue repair, and both immune and inflammatory responses. The aim of this study was to investigate the influence of female steroid hormones on expression of the adhesion molecules on the leukocytes. The whole blood from healthy people was incubated in a presence or an absence of progesterone (2 micrograms/ml) or 17 beta-estradiol (0.2 microgram/ml) for 4 h., and then with TNF for 18 h. The phenotype of the leukocytes was investigated by flow cytometry. Progesterone inhibited an expression of CD54 on monocytes and lymphocytes due to reducing density of these molecules on the cellular surface; 17 beta-estradiol inhibited an expression of CD54 on monocytes and CD69 molecules on monocytes and lymphocytes due to reducing density of these molecules on the cellular surface. Progesterone inhibited TNF-stimulated CD54 and CD11b expression on the granulocytes and CD69 expression on lymphocytes by reducing partly the density of these molecules on the surface of cells, and in such way it partly blocked the proinflammatory activity of this cytokine. Progesterone also reduced CD62L expression on the granulocytes by reducing an amount of a marker, positive to those cells but enhanced the effect of TNF. The data obtained evidence that female steroid hormones take part in the regulation of an expression of adhesion molecules by the leukocytes and are likely to be important in the circulation and activation of the leucocytes.

Antigens, CD↗

Immune disorders in women with premature ovarian failure in initial period.

PROBLEM: Premature ovarian failure (POF) may be considered as an autoimmune endocrine disease. Autoantibodies and lymphocyte subset changes are associated with premature ovarian failure. Immune cell parameters were studied in relation with anticardiolipin antibodies (ACAB) classes M and G in the initial period of POF. METHODS: Two-color flow cytometry was used to determine lymphocyte subsets and enzyme-linked immunosorbent assay (ELISA) was used to detect ACAB and hormones in the peripheral blood of 68 POF patients, 32 women with normal menopause (NM) and 13 healthy women as a normal control (NC). RESULTS: Patients in the initial period of POF had decreased levels of CD3+, CD19+, CD3+8+, and CD8+57+ lymphocytes and a high percentage of CD5 positive in CD19+ cell population compared to the control; frequencies of IgM ACAB in POF patients were significantly higher than both IgG ACAB and IgM ACAB in NC; correlation between lymphocyte subsets and hormone levels was absent. Women with early NM showed a low number of CD3+, CD3+4+, and CD3+8+ lymphocytes, a high number of CD3 + DR, and elevation of the percentage of CD5 positive in CD19+ lymphocytes compared with the control. The frequencies of both IgM and IgG ACAB were high; the levels of lymphocyte subsets had correlations with progesterone and estradiol concentrations. CONCLUSIONS: An increase of autoantibody producing B cells (CD5+19+) and a low number of effector suppressor/cytotoxic lymphocytes (CD8+57+) with active production of anticardiolipin autoantibodies class M were found. This suggested a primary autoimmune process in the initial period of POF. Autoimmune defeat of the ovary could be the primary cause of POF, whereas in NM autoimmunity is a result of hormone dysfunction.

Adult↗

[Functional properties of cooperative monoclonal antibodies against human tumor necrosis factor].

The panel of 23 newly produced monoclonal antibodies (mAbs) against human tumor necrosis factor (TNF) was examined for enhanced or cooperative TNF binding. Epitopic mapping revealed a preferential mAb generation against two epitopes designed as A1 and C1. Both A1 and C1 mAbs have neutralizing activity and display remarkable property to bind TNF synergistically comprising a pair of cooperative mAbs. C1 epitope resides within the TNF receptor-binding site (RBS) and responsible for generation of competitive neutralizing mAbs that block TNF activity by direct RBS masking. RBS-distal A1 epitope represents allosteric neutralizing mAbs that block TNF activity by conformational RBS changes. Combination of A1 and C1 mAbs resulted in synergistic TNF neutralization through complementary effect of competitive and allosteric TNF blocking mechanisms. Generation of cooperative Abs may have significance to achieve the most efficient neutralization of protein antigens with an intolerable functional activity in vivo.

Allosteric Regulation↗

Immunomodulatory and clinical effects of Viscum album (Iscador M and Iscador P) in children with recurrent respiratory infections as a result of the Chernobyl nuclear accident.

Ninety-two children 5 to 14 years of age living in areas exposed to the radioactive fallout from Chernobyl with recurrent respiratory infections (RRIs) were treated after randomization with either Viscum album praeparatum mali or pini (Iscador M or P). The dosage was two subcutaneous injections a week for 5 weeks with individual doses of 0.001 mg to 1.0 mg. Both Viscum album preparations were effective in significantly reducing clinical symptoms. One year after a single treatment course, the frequency of RRI relapses decreased by 78% and 73%, respectively. Immunomodulatory effects were assessed by investigation of lymphocyte subsets, natural killer (NK) cell activity, phagocytic and oxidative activity of polymorphonuclear leukocytes, and antiviral activity of serum before and 1 week after treatment. Viscum album therapy resulted in normalization of initial immune indices either below or above the normal ranges. High levels of antiviral activity before treatment were significantly decreased by Viscum album mali. Viscum album treatment should be studied further in children with RRI.

Adolescent↗

Analysis of blood lymphocyte subsets in children living around Chernobyl exposed long-term to low doses of cesium-137 and various doses of iodine-131.

Epidemiological studies have found that children living around Chernobyl have rates of respiratory tract illness that are higher than those seen in the area before the Chernobyl accident. The present study investigates the possible effects of radiation exposure on the composition of peripheral blood lymphocyte subsets in children living around Chernobyl. Two hundred nineteen healthy children and children suffering from recurrent respiratory diseases aged 6-14 years who received both low doses of radiation to the whole body from (137)Cs and various doses of radiation to the thyroid from (131)I as fallout from the accident were assessed 5 (1991) and 8-10 years (1994-1996) after the accident. A total of 148 healthy children and children suffering from recurrent respiratory diseases living in noncontaminated areas were also evaluated as controls. Children with recurrent respiratory diseases who lived around Chernobyl had a significantly lower percentage of T cells and a higher percentage of NK cells compared to control children with recurrent respiratory diseases during the study period. In contrast to the findings in 1991, a significant decrease in the percentage of helper-inducer cells was observed in children with recurrent respiratory diseases in 1994-1996. In contrast to 1991, there is a positive correlation between the percentage of helper-inducer cells, the helper-inducer/cytotoxic-suppressor cell ratio, and the dose of radiation to the thyroid of healthy children from (131)I in 1994-1996. There was a positive correlation between the dose of radiation to the thyroid from (131)I and the percentage of helper-inducer cells in children with recurrent respiratory diseases 5 years (1991) after the accident. Further, the dose of radiation to the thyroid from (131)I correlated negatively with the percentage of T and B cells and positively with the percentage of NK cells in children with recurrent respiratory diseases 8-10 years (1994-1996) after the accident. These results raise the possibility that long-term exposure to low doses of (137)Cs may have altered the composition of the T-cell subsets and NK cells in children with recurrent respiratory diseases. The differences in the composition of the peripheral blood lymphocyte subsets between healthy children and those with recurrent respiratory diseases may be attributed to long-term low-dose exposure of the whole body to radiation from (137)Cs and exposure of the thyroid to radiation from (131)I subsequent to the Chernobyl accident.

Adolescent↗

Analysis of blood lymphocyte subsets in children living on territory that received high amounts of fallout from Chernobyl accident.

The major lymphocyte subsets in the peripheral blood were assessed in 120 children 6-13 years old living on areas that received high levels of radioactivity as fallout after the Chernobyl nuclear power plant accident. Seventy-one of the children were suffering from recurrent respiratory disease (RRDC) and 49 were not (non-RRDC). As controls, a total of 87 RRDC and non-RRDC living on noncontaminated areas were evaluated. We did not find significant differences in major lymphocyte subsets between the values in non-RRDC living on radionuclide-contaminated areas and noncontaminated areas. However, RRDC living on radionuclide-contaminated areas had a significantly lower percentage of CD3+ T and CD3+CD4+ T-helper/ inducer cells compared to control RRDC. Furthermore, the decrease in percentage of CD3+CD4+ cells was more profound in RRDC living in radiation-contaminated settlements with an average summary dose (ASD) Cs-137(134) and Sr-90 for the population > 1.0 mSv than in RRDC living in contaminated settlements with an ASD Cs-137(134) and Sr-90 < 1.0 mSv. These data indicated that long-time exposure to small doses of radiation could affect the immune system in children living around Chernobyl.

CD3 Complex↗

131I dose-dependent thyroid autoimmune disorders in children living around Chernobyl.

We assessed the major lymphocyte subsets in the peripheral blood, thyroid ultrasonography, levels of serum autoantibodies to thyroglobulin (AbTg), thyroid hormones, and thyroid-stimulating hormone (TSH) in 53 children without any chronic diseases living continuously around Chernobyl. The subjects ranged in age from 7 to 14 years and had different doses of 131I to their thyroid. Healthy children living on noncontaminated areas were assessed as controls. The majority of children with doses of 131I had normal levels of thyroid hormones. However, the percentages of positive sera for AbTg, TSH levels, ultrasonographic thyroid abnormalities, and abnormal echogenicity were significantly higher in children with doses of 131I than in controls. The dose of 131I to thyroid correlated positively with serum AbTg levels, percentage of CD3+CD4+ cells, and CD3+CD4+/CD3+CD8+ cell ratio and negatively with number of CD3+CD8+ and CD3-/CD16, CD56+ cells. Thus, our study demonstrates an association between dose of 131I and autoimmune thyroid disorders in this population of children.

Adolescent↗

[Functional activity of blood and biliary neutrophils in patients with purulent cholangitis].

Study of the functional activity of blood and biliary neutrophils in patients with purulent cholangitis revealed different patterns of blood neutrophil reaction in the NBT test. The share of type 1 cells (with diffuse staining of the cytoplasm) in spontaneous and stimulated NBT test is a constant value in the studied patient population. The count of active blood neutrophils (type 2, with formasane granules) depends on the antigen dose in the test. A more grave form (with strictures of the bile duct) is associated with a decreased count of formasane-positive type 2 cells in comparison with that in patients with choledocholithiasis. An accurate and rapid method for the diagnosis of purulent cholangitis has been developed, based on measuring the functional activity of A bile neutrophils collected during surgery. The C bile neutrophils differ from blood neutrophils of patients with purulent cholangitis by morphology and function. Biliary neutrophils reduce the NBT after the diffuse punctuate type. The detected differences are presumably due to specific features of the environment.

Bile↗

Differential expression of CD45RA and CD45RO molecules on human decidual and peripheral blood lymphocytes at early stage of pregnancy.

PROBLEM: The use of monoclonal antibodies for CD45RA and CD45RO antigens is important in defining maturational and functional stages on lymphocytes. METHOD: To characterize distribution of two isoforms of CD45 antigen CD45RA and CD45RO on CD3+, CD4+, CD8+ and CD56+ lymphocyte subsets from first trimester human decidua, two-color flow cytometry were used. RESULTS: In decidua, there were much higher levels of CD45RO+ and much lower levels of CD45RA+ cells among CD3+, CD4+, and CD8+ cells as compared with peripheral blood samples of the same pregnant women. Only approximately 40% of CD56+ cells in decidua expressed CD45RA. Unlike peripheral blood, approximately 30% of decidual natural killer (NK) cells weakly stained with anti-CD45RO antibodies. Double-negative CD45RA- CD45RO- NK cells were also present in decidua. CONCLUSIONS: The significantly raised percentage of intradecidual T cells expressing CD45RO suggest decidual accumulation of antigen-committed memory cells. The patterns of CD45 isoforms expression on decidual CD56+ cells are consistent with hypothesis that uterine CD56+ lymphocytes are terminally differentiated cells of NK lineage.

Cell Differentiation↗

Differential expression of adhesion and homing molecules by human decidual and peripheral blood lymphocytes in early pregnancy.

Decidual and peripheral blood lymphocyte subsets were studied for their expression of CD44, L-selectin (Leu-8), CD54, and CD11b cell adhesion molecules (CAM). Most CD3+, CD4+, CD8+, and CD56+ cells in decidua were L-selectin- and CD44+, i.e., had a phenotype consistent with mucosa-homing preference of decidual lymphocytes (DL). We observed trimodal staining of decidual and peripheral blood CD56+ and CD8+ cells with anti-CD44 monoclonal antibody; negative, weakly positive, and brightly positive subpopulations were evident. Relatively high levels of CD44-negative CD56+ and CD8+ cells were found in decidua. Most decidual T and natural killer (NK) cells expressed high amounts of the CD54 molecule. Substantially higher numbers of CD3+, CD4+, and CD8+ cells in decidua bore CD11b, whereas the percentage of CD11b-positive NK cells was significantly lower in decidua, compared with that seen in peripheral blood. As opposed to peripheral blood lymphocytes (PBL), phorbol 12-myristate 13-acetate (PMA) stimulation of decidual NK cells elicited a rapid increase in the numbers of CD11b-positive cells but not increased fluorescence intensity of CD11b on the stained cells. The CD54 molecule was also up-regulated on decidual and peripheral blood NK cells but only after 15 hr of stimulation with PMA. In contrast to peripheral blood cells, activation of decidual mononuclear cells by K562 did not lead to an augmentation of the CD11b and CD54 expression on NK lymphocytes. These findings suggest that expression of CAM on DL is regulated in a manner different from that of PBL, and CAM expression may be adapted to accommodate placentation in human beings. The interaction of lymphocytes by means of antigen-independent cell-cell adhesion could be essential for the development of the placenta and the regulation of the local maternal immune response to the genetically foreign fetus.

Antigens, CD↗

Phenotypic characterization of CD7+, CD3+, and CD8+ lymphocytes from first trimester human decidua using two-color flow cytometry.

PROBLEM: There is increasing evidence that decidual lymphocytes play a major role in local interactions at the fetomaternal interface. METHOD: In this paper we use two-color flow cytometry to delineate the phenotype of lymphocytes obtained from human early decidua by mechanical dispersal technique. RESULTS: The most abundant decidual lymphocytes expressed CD7, CD38, CD56, and CD2 markers, relatively small proportions of CD3+, CD8+, CD4+, CD16+, CD45RA+, CD11b+, and Leu8+ cells were also present. The vast majority of decidual CD7+ lymphocytes expressed CD38, CD2, and CD56 markers and were CD3-, CD8-, CD16-, and CD57-. Decidual CD3+ lymphocytes were weakly staining for TCR alpha/beta, lacked T-cell receptor (TCR) gamma/delta molecules, and approximately 40% of them expressed HLA-DR. All decidual CD8+ lymphocytes were CD2+ and the majority of them expressed CD38, CD56, and CD7 markers and were CD3- at the same time CD8+CD7- lymphocytes were found in decidua. According to the expression of the CD45RA marker, decidual CD8+ lymphocytes could be divided into two subsets: CD8+CD45RA+CD56+ and CD8+CD45RA-. CONCLUSIONS: These data clearly demonstrate that decidual lymphocytes display phenotypical features different from those of their counterparts in peripheral blood.

Antigens, CD↗