S G Khaspekova

Center for Theoretical Problems of Physicochemical Pharmacology, Moskva, Moscow, Russia

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Publications (27)23.12 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Quantity of platelet adhesion molecules significantly varies in normal donors and cardiovascular patients and might be affected by platelet size and genetic variations. In this study, we assessed relationships of the content of glycoprotein (GP) IIb-IIIa and GPIb with mean platelet volume (MPV) and their genetic polymorphisms. MPV and GPIIb-IIIa and GPIb numbers were measured in 116 patients with acute coronary syndrome (ACS) at days 1, 3-5 and 8-12 after disease onset and in 32 healthy volunteers. GPIIb-IIIa and GPIb allelic variants were determined in ACS patients. Strong interactions of GPIIb-IIIa and GPIb numbers and MPV were observed in ACS patients and healthy volunteers. In patients, coefficients of correlation (r) were 0.642 and 0.510 (analysis of individual mean values) and in volunteers - 0.594 and 0.508 for GPIIb-IIIa and GPIb, respectively (everywhere P < 0.005). In ACS patients, correlations were highly significant at each tested time point. GPIIb-IIIa and GPIb genetic polymorphisms [GPIIIa Leu33Pro, GPIbα Thr145Met and GPIbα (-5)T/C (Kozak)] determined in ACS patients had no significant impact on their expression. Modest correlation was revealed between MPV and plasma thrombopoietin (TPO) measured at the first day of ACS (r = 0.279, P = 0.005). The data obtained indicated that GPIIb-IIIa and GPIb levels are mainly affected by platelet size (MPV) but not by their genetic variations. In some ACS patients, production of large platelets with high GPIIb-IIIa and GPIb contents might be stimulated by elevated TPO.
    Blood coagulation & fibrinolysis: an international journal in haemostasis and thrombosis 08/2013; · 1.25 Impact Factor
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    ABSTRACT: Spontaneous platelet aggregation was evaluated in patients with acute coronary syndrome on days 1, 3-5, and 8-12 of the disease. On day 1, aggregation was analyzed after aspirin, but before clopidogrel administration; during other periods after both antiaggregants. The mean levels of spontaneous aggregation after antithrombotic therapy did not change during different periods after the onset of acute coronary syndrome, in contrast to ADP-induced aggregation that decreased after the development of clopidogrel effects (days 3-5 and 8-12). Spontaneous aggregation during different periods directly correlated (r>0.4, p<0.01) with spontaneous and ADP-induced aggregation during different periods (r=0.372, r=0.447, and r=0.543 on days 1, 3-5, and 8-12, respectively; p<0.01). No relationship between spontaneous aggregation and plasma concentration of von Willebrand's factor was detected. Spontaneous aggregation was completely suppressed after in vitro addition of prostaglandin E1 (platelet activation inhibitor), slightly (by ≈20%) decreased in the presence of antibodies to glycoprotein Ib, blocking its reactions with von Willebrand's factor, and did not change in the presence of aptamer inhibiting thrombin activity.
    Bulletin of Experimental Biology and Medicine 04/2013; 155(1):89-91. · 0.34 Impact Factor
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    ABSTRACT: Characteristics of a new antithrombin DNA-aptamer RE31 were studied. This aptamer inhibited thrombin formation in human plasma catalyzed by exogenous (lengthening of thrombin time) and endogenous thrombin (lengthening of partial prothrombin time and activated partial thromboplastin time). In addition, the aptamer completely suppressed thrombin-induced aggregation of human platelets. On the other hand, RE31 did not reduce amidolytic activity of thrombin towards the short peptide substrate, in other words, did not modify the state of enzyme active center. By the capacity to inhibit clotting reactions, RE31 was superior to the previously described highly effective 31-component antithrombin aptamer 31TBA (thrombin binding aptamer, TBA). The effect of RE31 was species-specific: it inhibited human thrombin activity more effectively than activities of rat and rabbit thrombins.
    Bulletin of Experimental Biology and Medicine 02/2011; 150(4):422-5. · 0.34 Impact Factor
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    ABSTRACT: Glycoprotein (GP) IIb-IIIa (αIIbβ3-integrin) is the central receptor of platelet aggregation. Activated GP IIb-IIIa binds fibrinogen or von Willebrand factor, which forms molecular bridges between aggregating platelets. This review summarizes data on the relationship between GP IIb-IIIa expression on the platelet surface and platelet aggregating activity. GP IIb-IIIa number, measured as maximal binding of complex-specific monoclonal antibody, varied by approximately two fold in both healthy volunteers (n = 35) and patients with acute coronary syndrome (ACS) (n = 65). In healthy volunteers positive associations were observed between GP IIb-IIIa number and the level of ADP-induced aggregation when this relationship was analysed in untreated platelet-rich plasma (PRP) as well as upon in vitro addition of aspirin or non-saturating concentrations of GP IIb-IIIa blockers. In the same group of volunteers almost no differences in aggregating activity were detected between donors carrying the GP IIIa Pro33 allele (n = 15) and those with the GP IIIa Leu33Leu33 genotype (n = 20). No significant relationships were revealed between platelet aggregability and variations of plasma fibrinogen concentration. Positive correlation of the level of ADP-induced aggregation and GP IIb-IIIa content was detected in patients with ACS within the first hour upon admission to the hospital when they had already received aspirin, but not clopidogrel. However, there were no correlations between these parameters at days 3-5 and days 8-12 (before discharge). At these time points patients were treated not only with aspirin but were saturated with clopidogrel as well. In ACS patients we also evaluated the expression of another platelet adhesive receptor, GP Ib, and found a significant positive correlation between GP IIb-IIIa and GP Ib content. A strong association was also revealed between the number of both receptors and mean platelet volume. The latter observation indicated that individual variations of the number of glycoprotein molecules are mainly affected by platelet size but not the density of their expression on the platelet membrane. Possible usefulness of measuring GP IIb-IIIa content as a marker of increased platelet reactivity is discussed.
    Platelets 02/2011; 22(4):243-51. · 2.24 Impact Factor
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    ABSTRACT: Interaction between aggregating activity of platelets and glycoprotein (GP) IIb/IIIa (fibrinogen receptor) content on their surface was investigated in patients with acute coronary syndrome (ACS). Eighty nine ACS patients were included into the study - 69 with and 20 without elevation of ST segment. Blood was collected within the first hour of admission to the clinic (1 day), and then at 3-5 and 8-12 days. All patients received standard antiaggregant therapy - acetylsalicylic acid - ASA (thromboxane A2 synthesis inhibitor) and clopidogrel (ADP receptor antagonist). Platelet aggregation was analyzed at the first time point when patients had already taken ASA but not clopidogrel, and then (3-5 and 8- 12 days) upon combined therapy with both preparations. Aggregation was induced by 5 and 20 uM ADP and measured by turbidimetric method. In comparison with the initial level (1 day, ASA) at days 3-5, i.e. after development of clopidogrel effect, platelet aggregation was decreased by 54 and 40% upon its stimulation with 5 and 20 uM ADP, and was not further changed at days 8-12. GP IIb/IIIa content on platelet surface was determined by binding of 125I-labelled monoclonal antibody CRC64. GP IIb/IIIa number varied from 31100 to 73000 per platelet with the mean level of 48500 +/- 8400 (mean +/- standard deviation). No differences were detected between mean GP IIb/IIIa number at 1, 3-5 and 8-12 days after ACS onset. Upon repeat GP IIb/IIIa measurement coefficient of variation was 6.1% demonstrating the stability of this parameter in each patient. Positive correlation between platelet aggregation and GP IIb/IIIa content was detected at the first day - correlation coefficients (r) 0.425 and 0.470 for 5 and 20 uM ADP (n=57, p<0.001). However positive association between these parameters was not revealed at 3-5 and 8-12 days, when patients received not only ASA but clopidogrel as well (r from -0.054 to -0.237, p>0.05). These results indicates that variations of GP IIb/IIIa content affect platelet aggregating activity within first hours of ACS upon ASA treatment. However after saturation with clopidogrel this factor has no significant influence on platelet aggregation, at least on aggregation induced by ADP which receptor is the target of this antiaggregant. Under such conditions aggregation parameters are presumably influenced first of all by individual characteristics of clopidogrel pharmacokinetics.
    Kardiologiia 01/2011; 51(7):4-7. · 0.25 Impact Factor
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    ABSTRACT: The effects of two DNA aptamers (oligonucleotides) 15TBA and 31TBA (15- and 31-mer thrombin-binding aptamers, respectively) on thrombin activity were studied. Both aptamers added to human plasma dose-dependently increased thrombin time (fibrin formation upon exposure to exogenous thrombin), prothrombin time (clotting activation by the extrinsic pathway), and activated partial thromboplastin time (clotting activation by the intrinsic pathway). At the same time, these aptamers did not modify amidolytic activity of thrombin evaluated by cleavage of synthetic chromogenic substrate. Aptamers also inhibited thrombin-induced human platelet aggregation. The inhibitory effects of 31TBA manifested at lower concentrations than those of 15TBA in all tests. These data indicate that the studied antithrombin DNA aptamers effectively suppress its two key reactions, fibrin formation and stimulation of platelet aggregation, without modifying active center of the thrombin molecule.
    Bulletin of Experimental Biology and Medicine 07/2009; 148(1):33-6. · 0.34 Impact Factor
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    ABSTRACT: The effects of content of a fibrinogen receptor, glycoprotein (GP) IIb–IIIa (αIIb/β3-integrin), GP IIIa genetic polymorphism (substitution Leu33Pro), and fibrinogen concentration in blood plasma on platelet aggregation activity have been investigated in a group of healthy volunteers. In 35 examined donors the GP IIb–IIIa content on platelet surface varied from 40 to 71 × 103 per platelet. Repeated measurements revealed that the GP IIb–IIIa content coefficient of variation was 9.5%, and deviations from mean levels did not exceed 20%. The level and the rate of platelet aggregation induced by ADP (1.25–20 μM) correlated with GP IIb–IIIa number (r from 0.315 to 0.591) and were higher in the group of donors with high in comparison with low GP IIb–IIIa content (>60 and (40–50) × 10−3 per platelet, respectively). Aspirin, the inhibitor of thromboxane A2 synthesis, partially suppressed ADP-induced platelet aggregation. The level of residual aggregation in the presence of aspirin also correlated with GP IIb–IIIa content and increased in subjects with high receptor content. Parameters of ADP-induced aggregation did not differ in donors with genotypes GP IIIa Pro33(−) (Leu33Leu33, n = 20) and Pro33(+) (Leu33Pro33, n = 13, and Pro33Pro33, n = 2) genotype. GP IIb–IIIa content was also not affected by GP IIIa polymorphism. No significant correlations were found between the level and rate of platelet aggregation and fibrinogen concentration in blood plasma. The data obtained indicate that the effects of variations of GP IIb–IIIa content on platelet aggregation are higher than GP IIIa Leu33Pro polymorphism and variations of fibrinogen concentration. High GP IIb–IIIa content is associated with increased platelet aggregation activity and decreased efficacy of aggregation inhibition by aspirin.
    Biochemistry (Moscow) Supplement Series B Biomedical Chemistry 01/2008; 3(1):92-98.
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    ABSTRACT: We investigated the influence of glycoprotein (GP) IIIa Leu33Pro polymorphism, platelet GP IIb-IIIa number, and plasma fibrinogen concentration on platelet aggregation and antiaggregatory action of GP IIb-IIIa antagonists. Healthy volunteers with GP IIIa Pro33(-) (Leu33Leu33, n = 20) and Pro33(+) (Leu33Pro33, n = 13, and Pro33Pro33, n = 2) genotypes were included into the study. GP IIIa Leu33Pro substitution was associated with the increase of the level and rate of platelet microaggregate formation induced by GP IIb-IIIa activating antibody CRC54 (100, 200, 400 microg/ml) against the epitope within 1-100 residues of GP IIIa N-terminal part (p from 0.001 to 0.047). No significant differences were detected between parameters of platelet aggregation induced by ADP (1.25, 2.5, 5.0, 20 microM) in GP IIIa Pro33(+) and Pro33(-) donors. GP IIb-IIIa antagonist Monafram (F(ab')(2) fragment of GP-IIb-IIIa blocking antibody CRC64) (1, 2, 3 microg/ml), but not eptifibatide (50, 100, 150 ng/ml) inhibited ADP-induced aggregation slightly less efficiently in GP IIIa Pro33(+) group (p < 0.05 at 1 and 2 microg/ml Monafram). GP IIb-IIIa number (evaluated as maximal binding of (125)I-labelled antibody CRC64) varied from 40.5 to 80.8 x 10(3) per platelet with no significant influence of GP IIIa genotype. Consistent correlations were revealed between GP IIb-IIIa quantity and the level and rate of ADP-induced aggregation (r from 0.353 to 0.583, p from <0.001 to 0.037) as well as resistance (level of residual aggregation) to both GP IIb-IIIa antagonists (r from 0.345 to 0.602, p from <0.001 to 0.042). ADP-induced aggregation was considerably increased and efficiency of GP IIb-IIIa antagonists decreased in donors with high in comparison with low GP IIb-IIIa quantity (>60 and 40-50 x 10(3) per platelet respectively, p < 0.01 for most tests). No correlations were observed between all tested parameters and plasma fibrinogen concentration. Our results indicate that inter-individual variability of platelet GP IIb-IIIa number significantly affects platelet aggregation and antiaggregatory effects of GP IIb-IIIa antagonists. Contribution of this factor is higher than that of GP IIIa Leu33Pro polymorphism and variations of fibrinogen concentration.
    Platelets 11/2007; 18(7):506-14. · 2.24 Impact Factor
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    ABSTRACT: In some patients with stable and unstable angina pectoris and in some donors without clinical manifestations of cardiovascular diseases and other pathologies, spontaneous platelet aggregation was completely suppressed by glycoprotein IIb-IIIa antagonists blocking the interaction of this glycoprotein with fibrinogen. Antibodies inhibiting binding of glycoprotein Ib with von Willebrand factor had no effect on the level and rate of spontaneous platelet aggregation. In the donor group, the level of spontaneous aggregation was almost 1.5-fold higher in persons with a certain genetic polymorphism (Leu-->Pro substitution in position 33 of glycoprotein IIIa). The level of spontaneous aggregation correlated with the amount of glycoprotein IIb-IIIa on the platelet surface (r = 0.41).
    Bulletin of Experimental Biology and Medicine 05/2007; 143(4):422-5. · 0.34 Impact Factor
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    ABSTRACT: Soluble P-selectin (marker of activation of platelets) and von Willebrand factor (marker of activation of endothelium) were measured in 44 patients with non ST-Elevation acute coronary syndrome (NSTEACS) 21 of whom received glycoprotein IIb/IIIa antagonist eptifibatide (two 180 mg/kg boluses with 10 min interval followed by infusion of 2 mcg/kg/min during first 24 hours and 1.3 mcg/kg/min during subsequent 48 hours). Measurements were made within first 2 hours, in 2--3 and 10--14 days after development of NSTEACS. During first 2 hours P-selectin content was 1.6 times higher than in healthy donors, but in 2--3 and 10--14 days after onset of NSTEACS it did not differ from normal values. Contrary to P-selectin value of von Willebrand factor was elevated both during first 2 hours (1.3 times) and in 2--3 days (2 times) compared with healthy donors. Some elevation of von Willebrand factor (1.2 times) persisted after 10--14 days after development of NSTEACS. The results obtained have shownd that elevated activity of endothelium persists at least for 2--3 days after onset of NSTEACS, while activity of platelets during this period decreases. In none of temporal points there have been revealed differences in contents of P-selectin and von Willebrand factor between groups of patients receiving and not receiving glycoprotein IIb/IIIa antagonists. No differences were also found between these parameters in groups of patients favorable and unfavorable outcomes (myocardial infarction, angina recurrence) of the disease during 30 days of follow-up.
    Kardiologiia 02/2007; 47(6):4-9. · 0.25 Impact Factor
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    ABSTRACT: The purpose of the study was to evaluate safety, effects on platelet aggregation and pharmacokinetics of F(ab')(2) fragments of anti-glycoprotein (GP) IIb-IIIa murine monoclonal antibody FRaMon (F(ab')(2) FRaMon) upon its intravenous administration in patients undergoing high-risk coronary angioplasty. Patients were treated before angioplasty with F(ab')(2) FRaMon at 0.2 mg/kg (n = 17) and 0.25 mg/kg (n = 12) bolus or with abciximab at 0.25 mg/kg bolus + 12 h infusion at 0.125 microg/kg per min (n = 29). F(ab')(2) FRaMon at both doses decreased platelet aggregation induced by 20 microM ADP to <10, <20, <40 and <70% of the predrug level at 1, 12, 24 and 72 h after injection, respectively. No significant differences were observed between F(ab')(2) FRaMon and abciximab antiaggregatory effects. In none of the patients did F(ab')(2) FRaMon cause allergic reactions, major bleedings or deep thrombocytopenia. Antibodies against F(ab')(2) FRaMon were detected in one patient. Free F(ab')(2) FRaMon was cleared from plasma within 12 h, while platelet-bound preparation occupied >95, 70-80 and 40-50% of GP IIb-IIIa at 1 and 12-24 h and 3 days after injection, respectively. Thrombotic complications within the first month after angioplasty in groups treated with F(ab')(2) FRaMon and abciximab were observed in one and two patients, respectively. The data obtained have shown that F(ab')(2) FRaMon at bolus administration to patients undergoing coronary angioplasty caused no serious side effects and at comparative dosage inhibited platelet aggregation with the same efficacy as abciximab at bolus + infusion administration.
    Platelets 01/2003; 13(8):465-77. · 2.24 Impact Factor
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    ABSTRACT: Preparation framon [F(ab')2 fragments of the anti-glycoprotein (GP) IIb/IIIa monoclonal antibody (FRaMon)] blocks fibrinogen binding to GP IIb/IIIa and platelet aggregation. Dynamics of platelet aggregation inhibition, safety, and clinical effects of framon were studied in high-risk coronary angioplasty. Twenty seven patients underwent angioplasty with framon, 29 - with abciximab and 28 - with no GP IIb/IIIa antagonists. Framon at 0.2 mg/kg (n=16) and 0.25 mg/kg (n=11) bolus administration inhibited platelet aggregation induced by 20 mcM ADP by more than 90%, 80%, 60% and 30% in comparison with the predrug level 1, 12, 24 and 72 h after injection, respectively. Almost the same dynamics of aggregation inhibition was observed upon abciximab administration at 0.25 mg/kg bolus + 0.125 mcg/kg/min infusion for 12 h. No signs of individual intolerance and side effects including allergic reactions and bleedings were detected in patients treated with framon. Slight decrease of platelet count (15-20%) was observed on the first day after framon administration. Antibodies against framon were detected in 1 out of 22 tested patients. Free (nonbound to platelets) framon was completely removed from the circulation 12 h after injection. The number of endpoints (death, myocardial infarction and indications for repeat revascularization) within 1 year after angioplasty was approximately the same in the groups with framon and abciximab - 7 of 25 (28%) and 7 of 28 (25%), respectively, and more than 1.5 fold higher in the group without GP IIb/IIIa blockers - 12 of 27 (44,4%).
    Kardiologiia 02/2002; 42(6):8-17. · 0.25 Impact Factor
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    ABSTRACT: To study the effects of F(ab')2 fragments of the monoclonal antibody (monAB) FRaMon against glycoproteins (GP) IIb-IIIa on platelet aggregating activity in vitro and after injection to healthy volunteers. In vitro experiments were performed to study effects of F(ab')2 and Fab fragments of FRaMon on platelet aggregation (PA) and 14C-serotonin secretion and characteristics of 125I-labelled F(ab')2 and Fab FRaMon binding to platelets. In vivo effects of F(ab')2 FRaMon (preparation FRAMON) were studied upon its bolus i.v. injection to 10 healthy volunteers at the doses of 0.025-0.2 mg/kg. PA was registered before and 1, 6, 12, 24 hours and 3 and 12-15 days after FRAMON injection. FRAMON binding to platelets in the vascular bed was evaluated by inhibition of 125I-FRAMON in vitro binding to platelets obtained from volunteers. Development of antibodies against FRAMON was evaluated by ELISA two weeks after FRAMON injection. In vitro F(ab')2 FRaMon completely blocked PA induced by ADP and thrombin at the concentrations < 4 and < 7.5 mcg/ml, respectively, and revealed higher inhibitory capacity than Fab FRaMon. F(ab')2 FRamon also inhibited 14C-serotonin secretion from ADP-activated platelets. F(ab')2 FRamon interacted with two GP IIb-IIIa molecules on one platelet and bound to platelets more tightly than Fab FRaMon. F(ab')2 FRaMon (preparation FRAMON) bolus i.v. injection to healthy volunteers at the doses of 0.025-0.2 mg/kg did not induce any signs of individual intolerance, including allergic reactions, bleeding and thrombocytopenia. FRAMON at 0.2 mg/kg almost completely inhibited ADP-induced PA of volunteer's platelets 1 h after injection and by more than 70% at 12 h and by more than 50% at 24 h after injection. PA ability recovered to normal 3 days after injection. Antibodies against FRAMON were detected in 1 out of 10 volunteers. F(ab')2 fragments of monAB FRaMon effectively inhibited aggregating ability both in vitro and after injection to healthy volunteers and could be suggested as a basis for development of a new GP IIb-IIIa antagonist.
    Terapevticheskii arkhiv 01/2001; 73(9):66-73. · 0.15 Impact Factor
  • Biulleten' eksperimental'noĭ biologii i meditsiny 11/1999; 128(10):476-9.
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    ABSTRACT: We propose a method for measurement of plasma glycocalicin, a fragment of platelet membrane glycoprotein Ib. The concentration of glycocalicin is elevated in thrombocythemia and reduced in thrombocytopenia caused by insufficient platelet production, but not in immune thrombocytopenia due to enhanced platelet degradation. Thus, plasma content of glycocalicin is an indicator of platelet turnover. The proposed assay can be used for differential diagnostics of thrombocytopenia.
    Bulletin of Experimental Biology and Medicine - BULL EXP BIOL MED-ENGL TR. 01/1999; 128(4):1070-1073.
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    ABSTRACT: Effects of two lectins, wheat germ agglutinin (WGA) and concanavalin A (Con A), on platelet functional reactions and interaction of lectins with the platelet membrane glycoproteins (GPs) have been studied. Both lectins stimulated platelet aggregation and secretion of serotonin from platelet dense granules. The effects of WGA and Con A were blocked by specific sugars, N-acetyl-D-glucosamine and alpha-methyl-D-mannopyranoside, respectively, by adenylate cyclase activator prostaglandin E1, and by anti-GP IIb-IIIa monoclonal antibody (monAB), CRC64, that inhibits platelet interaction with fibrinogen. The data indicate that both lectins interacting with the carbohydrate moiety on the platelet surface stimulated not passive agglutination but fibrinogen--GP IIb-IIIa-dependent platelet aggregation which is coupled with the secretion from granules and activation of the intracellular systems of signal transduction. However, there were significant differences between the stimulatory effects of WGA and Con A. WGA induced more pronounced and quick platelet aggregation and stimulated several times higher serotonin secretion than Con A. In addition, adhesion studies showed that plastic-adsorbed WGA appeared to be a nonadhesive substrate, whereas Con A effectively stimulated platelet adhesion. Unlike Con A-induced platelet aggregation, adhesion to Con A substrate was not inhibited by monAB CRC64, i.e., was not dependent on GP IIb-IIIa--fibrinogen interaction. Binding of lectins with major platelet GPs was studied using immobilized WGA and Con A and platelet lysate as a source of GPs. Platelet lysate was incubated with immobilized lectins and then binding of individual GPs was evaluated using specific mono- and polyclonal antibodies. WGA binds with GP Ib and P-selectin but not with other GPs tested. Interaction of Con A with platelet GPs was less specific. This lectin binds with GP IIb-IIIa, GP Ib, GP IV, and P-selectin. Although GP Ib appeared to be the main protein which bound WGA on platelet surface, anti-GP Ib antibodies failed to affect WGA-induced platelet aggregation, but inhibited WGA-induced agglutination of fixed platelets. Thus, interaction of the WGA with GP Ib could not be considered as a major stimulus initiating WGA-dependent platelet activation and aggregation.
    Biochemistry (Moscow) 07/1998; 63(6):710-8. · 1.15 Impact Factor
  • Biulleten' eksperimental'noĭ biologii i meditsiny 06/1998; 125(5):596-600.
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    ABSTRACT: Sandwich enzyme-linked immunosorbent assay was developed for evaluation of target antigens reacting with antiplatelet auto- and alloantibodies. The method based on specific immobilization of platelet antigens via monoclonal antibodies was applied to identify antigens of platelet-associated and serum autoantibodies in patients with different thrombocytopenias and to determine platelet HPA-1 alloantigens.
    Bulletin of Experimental Biology and Medicine 04/1998; 125(5):528-531. · 0.34 Impact Factor
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    ABSTRACT: Platelet glycoprotein (GP) IIb-IIIa complex (alpha IIb beta 3-integrin) changes its conformation upon platelet activation that results in binding of RGD-containing ligands and expression of ligand-induced binding site (LIBS) neoepitopes. Anti-GIIb-IIIa monoclonal antibody (monAB) CRC54 bound to < or = 10% of GPIIb-IIIa on resting platelets but binding was enhanced by the occupation of GPIIb-IIIa with RGDS peptide and by platelet activation indicating that CRC54 is directed against LIBS epitope. The epitope was located within the first 100 N-terminal residues of GPIIIa and differed from other LIBS epitopes. CRC54 as well as its Fab fragments were able to induce platelet aggregation. CRC54 also stimulated interaction of GPIIb-IIIa with its ligands (fibrinogen and fibronectin) and conformation-dependent antibodies. The results indicated that changes of GPIIb-IIIa conformation, binding of ligands and platelet aggregation could be stimulated via interaction of anti-LIBS antibody with the N-terminal part of GPIIIa.
    FEBS Letters 09/1996; 391(1-2):84-8. · 3.58 Impact Factor
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    ABSTRACT: Patient B.G. is a 29-yr-old female with a lifelong bleeding disorder characterized clinically by a highly increased bleeding time, menorrhagias, long-lasting bleeding after cuts and tooth extractions and large post-traumatic haematomas. Her coagulation tests were within normal range, platelet count was 140,000-160,000 per microliters, but platelet function was impaired as demonstrated by the absence of collagen-induced aggregation, although no abnormalities were detected in aggregation response to ADP and ristocetin. Morphologically her platelets were characterized by gigantic size-average profile area was about 2.5 times higher than that of control donors, and severe deficiency of alpha-granules-only 16% of their number in control donors. These features taken together indicated the diagnosis of grey platelet syndrome. As has been shown by quantitative immunoblotting, patient's platelets contained small amounts of alpha-granule membrane protein P-selectin-about 15% of that in control donors. The content of plasma membrane glycoproteins IIb-IIIa and Ib was not reduced, suggesting the specific deficiency of alpha-granule membrane protein. Thus, B.G. is the second patient described in the literature (see also Lages et al, J Clin Invest 1991: 87: 919-929) with combined deficiency of alpha-granules and P-selectin.
    European Journal Of Haematology 08/1996; 57(1):38-41. · 2.55 Impact Factor

Publication Stats

65 Citations
23.12 Total Impact Points

Institutions

  • 2013
    • Center for Theoretical Problems of Physicochemical Pharmacology
      Moskva, Moscow, Russia
  • 2007–2011
    • Russian Cardiology Research and Production Complex
      Moskva, Moscow, Russia
    • Petersburg Nuclear Physics Institute
      Krasnogwardeisk, Leningrad, Russia
  • 2009
    • Lomonosov Moscow State University
      Moskva, Moscow, Russia
  • 1998
    • Institute of Biochemistry and Physiology of Microorganisms
      Pushchino-na-Oke, Moskovskaya, Russia
  • 1995
    • Russian Academy of Medical Sciences
      Moskva, Moscow, Russia
  • 1993
    • Kemerovo Cardiology Centre
      Shcheglovsk, Kemerovo, Russia