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Biomedical subjects

V A Tkachuk

Publications and source records attributed to V A Tkachuk.

At least 19 recordsLinked to original sources
PubMed2006

[Participation of the DNA-binding cytokine amphoterine in triggering the processes of tissue reparation].

Author's studies and literature references indicate that the DNA-binding cytokine: amphoterine, being a non-histone component of chromatin, acts in extracellular milieu as cytokine regulating gene expression in target cells. The amphoterine effects are mediated by its interaction with the cell surface receptors including those of the final glucosiding product (RAGE), which leads to activation of the ERK and p38 MAP-kinases as well as NF-kappaB. Amphoterine prompts inflammatory response by means of activating synthesis of interleukins-1, -6 and -8 as well as tumour necrosis factors (TNF-alpha) and activates tissue regeneration by means of involvement of the precursor cells into the damage foci and induction of the cells' differentiation. These properties of amphoterine suggest that appearance of this protein in extracellular space signals of a tissue damaging.

Animals↗
PubMed2006

[Adipose stromal cells--plastic type of cells with high therapeutic potential].

Much effort has been made in searching for multipotent cell types with high therapeutic potentials for repair of damaged tissue. Through enzymatic digestion of fat tissue, it is possible to obtain a large number of stromal cells. Isolated cells show a high proliferate capacity in culture. All this makes adipose stromal cells (ASC) promising candidates for their use in cell therapy. This review is focused on analyzing the surface antigen profile of isolated population of ASC, expression of angiogenic factors by these cells, as well as on their differentiation potential. A high percentage of ASC population initially express the progenitor cell marker CD34, but during culturing, cells exhibit a mesenchymal cell phenotype and express CD29, CD105, CD106, CD166. Culturing ASC in specific differentiation media induces expression of early markers of differentiated mesenchymal cells, such as adipocytes, chondrocytes and osteoblasts, as well as myoblasts, cardiomyocytes and neural cells. It has been also shown that ASC have a strong pro-angiogenic potential, they are able to secret growth factors, such as VEGF, HGF, bFGF and others, which stimulate survival and proliferation of endothelial cells. In addition, systemic or local delivery of ASC to mice with hindlimb ischemia stimulates recovery of injured tissue and blood flow. Potential clinical uses of ASCs are discussed in the review.

Adipocytes↗
PubMed2006

[Adipose tissue stromal cells -- multipotent cells with therapeutic potential for stimulation of angiogenesis in tissue ischemia].

Results of studies of properties of adipose tissue stromal cells are summarized in this review. It contains data on separation and cultivation of these cells as well as description of their antigenic characteristics, ability to differentiate into cells of mesenchymal and nonmesenchymal origin, angiogenic potential, and potential for transfection and transfer of therapeutic genes. Analysis of perspectives of clinical use of adipose tissue stromal cells in therapy of cardiovascular and other diseases is also presented.

Adipose Tissue↗
PubMed2005

Urokinase increases the content and activity of matrix metalloproteinases 2 and 9 during in vivo constrictive arterial remodeling.

Perivascular application of urokinase to ballooned artery stimulating the formation of neointima and constrictive arterial remodeling increased the content and activity of matrix metalloproteinases 2 and 9 in vivo. Application of recombinant tissue plasminogen produced no such changes. It was demonstrated that urokinase stimulates expression of matrix metalloproteinases in vivo.

Angioplasty, Balloon↗
PubMed2005

[The effect of lipoproteins on signal transduction in thrombocytes and vascular wall cells].

In recent decades, studies have shown that lipoproteid physiological role goes beyond just their part in lipid transport. Database is accumulating on connection of lipoproteid pathological effects upon cardiovascular system with their ability to interfere in the signal transmission processes necessary for normal control of the vascular homeostasis. There is some evidence that lipoproteids are capable of affecting vascular tonus, coagulation balance, and inflammatory processes in the vascular wall. These effects will be realized through activation of the blood cell and vascular wall signal systems and can accelerate development of atherosclerosis and prompt hypertension and arterial thrombophilia.

Animals↗
PubMed2005

[The role of mutation in cardiac beta-myosin heavy chain gene in population of patients].

One of most widely spread causes of hypertrophic cardiomyopathy (HCMP) is mutation in cardiac beta-myosin heavy chain gene. Data on contribution of this mutation to development of HCMP in Russian patients are very limited. We conducted screening of beta-myosin heavy chain gene for the presence of mutations in 116 patients with confirmed HCMP (probands). DHPLC was used with subsequent sequencing of DNA fragments. Genetic defects of beta-myosin heavy chain were found more than in every 10-th patient. These defects were represented by 13 mutations (Ala729Pro mutation was found twice). Phenotypes of majority of known mutations in Russian population did not differ substantially from their phenotypes in other populations. Six mutations had not been previously described; most of them were associated with especially severe clinical and hemodynamic signs and relatively unfavorable course of the disease. Thus beta-myosin heavy chain gene mutation play important role in etiology of HCMP in patients in Russia.

Adolescent↗
PubMed2005

[Genetic factors of risk of ischemic heart disease development in patients with familial hypercholesterolemia].

UNLABELLED: Ischemic heart disease (IHD) develops in patients with familial hypercholesterolemia (FHC) 15-20 years earlier than in general population. However age of onset of the disease, its clinical manifestations are variable and not completely determined by cholesterol level and class of low density lipoprotein receptor mutations. AIM: To elucidate associations of some auxiliary genetic factors -- such as C151565T, C677T, R353Q polymorphisms of glycoprotein IIIa (GPIIIa), methylenetetrahydrofolate reductase (MTHFR) and coagulation factor VII genes, respectively, -- with the presence of IHD in patients with FHC. MATERIAL: Patients with clinical diagnosis of heterozygous FHC (n=198) with (n=106) and without (n=92) IHD. RESULTS: Patients with compared with those without IHD had similar frequency of T-allele of MTHFR gene (p=0.519), more often had T-allele of GPIIIa gene (23 and 12.5%, respectively, p=0.009), and less often -- Q-allele of factor VII gene (13 and 21%, respectively, p=0.048). Multifactorial analysis showed that risk of IHD was higher in patients with TT compared with CC genotype of the GPIIIa gene (OR 1.53, 95%CI 1.12-2.3), and lower in patients with RQ and QQ compared with RR genotype of factor VII gene (OR 0.41, 95%CI 0.19-0.75). CONCLUSION: In patients with FHC polymorphisms in factor VII and GPIIIa genes but not C677T polymorphism of MTHFR gene were associated with the presence of IHD.

Adult↗
PubMed2004

[Plasminogen activator of urokinase-type: mechanisms of involvement in vessel remodeling and angiogenesis, gene therapy approaches to ischemia].

The review summarizes data obtained by the authors and other laboratories concerning the role of urokinase plasminogen activator in vessel remodeling and angiogenesis. The data have shown that urokinase is involved in unfavorable vascular remodeling during the development of restenosis, atherosclerosis and also in the regulation of angiogenesis. Urokinase is a promising target for therapeutic interventions aimed at restenosis prevention. Urokinase gene therapy may be a perspective strategy for the treatment of tissue ischemia.

Animals↗
PubMed2004

[Antiadhesive molecule T-cadherin is an atypical low-density lipoprotein receptor in vascular cells].

Elevated serum LDL level, which results in cholesterol accumulation in vascular wall, is widely accepted as a risk factor in atherosclerosis development. Additionally to metabolic effects, LDL can produce hormone-like effects in a number of cells: activate second messenger systems, regulate gene expression and activate platelets and stimulate cell proliferation. The responses elicited by LDL are rapid, dose-dependent and capable of being saturated, indicating the involvement of specific receptor/binding sites in LDI-stimulated signal transduction. This LDL-binding protein was isolated from human aorta media and identified as T-cadherin. Cadherins are a superfamily of adhesion molecules that mediate Ca2+ -dependent cell-cell adhesion in embryogenesis and in adult organism's solid tissues. Intercellular junctions are formed as a result of interactions between extracellular domains of the neighboring cells' cadherins. Binding of the intercellular domain to the acting cytoskeleton ensures stability of cadherin-mediated adhesive junctions. T-cadherin is a unique member of calcium-dependent adherent proteins; in contrast to classical cadherins T-cadherin is anchored to the cell surface membranes via a glycosyl phosphatidyl inositol (GPI) moiety. Subcellular distribution of T-cadherin is restricted to lipid rafts on the cell membranes where it co-localizes with signal-transducing molecules. The function of T-cadherin has not yet been revealed. It was originally cloned from chicken embryo brain where the spatial-temporally restricted pattern of T-cadherin suggests its role as a negative guidance cue in tegulating the segmental organization of trunk neural crest migration and motor axon projections. Comparative study of the T-cadherin expression in human organs and tissues revealed that T-cadherin content was maximal in cardiovascular system. Its expression in VSMC depends on the cell phenotype and proliferate activity and increases in atherosclerotic lesion and restenosis. T-cadherin seems to play a key role in the regulation of the vascular cell phenotype, migration and growth. We hypothesize that T-cadherin is an anti-adhesive molecule which participates in intercellular interactions informing cells about their environment and regulating migration and proliferation of cells in vascular wall, while LDL interfere with the normal function of T-cadherin.

Animals↗
PubMed2003

[Psychological basis for self-regulation of behavior in sailors drafted into military service].

Valuable-and-semantic spheres of Navy servicemen called-up for military service were investigated. For the servicemen with "psychical discomfort" the behavior "disadaptation" strategy is characteristic: the unrealistic orientation towards the freedom and material security; the problem of difficult choice between the interest in unofficial contact and the necessity to defer to rank; the "internal vacuum" state connected with little value of cognitive orientations and their relative accessibility, and on the contrary, the "internal conflict" state conditioned by the inaccessibility of vital and social values. The most of investigated persons are not oriented towards the highest levels of behavior self-regulation that are connected with the search for sense and choice freedom. They are characterized by the regulation lowest levels connected with stereotype and comfort in observing the social standards (the group of "relative" psychical comfort) or by the non-adequate ways of behavior self-regulation that aggravate the disadaptation, morbidity and person's deformation (the group of "psychical discomfort").

Adaptation, Psychological↗
PubMed2003

[Molecular mechanisms of G-proteins coupling with membrane receptors and second messenger systems].

G-proteins transmit the signals from hormone receptors onto intracellular effector systems which take part in production of the second messengers such as cAMP, IP3, DAG and Ca2+. Molecular mechanisms of G-protein participation in the coupling of the seven-domain receptors to adenylate cyclase, phospholipase C and channels for Ca2+ and K+ ions are discussed in this paper. G-protein is a heterotrimers built of alpha-, beta- and gamma-subunits, which dissociate onto alpha- and beta gamma-subunits during interaction with hormone-receptor complex. alpha-subunit as well as beta gamma-dimmer may interact with effector system that leads to acceleration or slowing down of second messengers formation. Molecular mechanisms of such regulatory signal diversification are described. Seven-domain receptors possess very high recognition specificity of G-proteins. It is defined by combination of both alpha- and beta gamma-subunits in the G-protein structure. There is well-defined interaction specificity of G-protein alpha-subunit with effector systems. Combinations of different beta- and gamma-subunits involved in complex formation define interaction specificity of G-protein beta gamma-complex with effector systems. The highest interaction specificity of receptors with G-proteins and G-proteins with effector systems is found during triple complex formations: receptor--G-protein--effector. Such specificity is stronger in living cells than in membrane preparations. It can be an evidence of intracellular factors influence on the processes of interaction of the proteins involved in transmembrane regulatory signal transduction.

Animals↗
PubMed2002

Urokinase as a multidomain protein and polyfunctional cell regulator.

The urokinase type plasminogen activator (urokinase) plays a pivotal role in the regulation of cell adhesion and migration during tissue remodeling. Urokinase not only specifically cleaves plasminogen and converts it into plasmin but also activates intracellular signaling upon binding to certain receptors on the cell surface. The polyfunctional properties of this protein are associated with its three-domain structure as follows: the C-terminal proteolytic domain containing the serine protease active center, the central kringle domain, and the N-terminal domain homologous to epidermal growth factor. This review considers functional properties of urokinase and of its fragments generated on the cell surface as a result of proteolytic processing. This review will discuss the mechanisms of urokinase-mediated regulation of cellular function upon binding to membrane receptors.

Animals↗
PubMed2002

Plasminogen activators in vascular remodeling and angiogenesis.

This review considers cellular and molecular mechanisms of the involvement of plasminogen activators in extracellular proteolysis and cell migration and proliferation. The role of plasminogen activators in vascular remodeling in atherosclerosis, restenosis, and angiogenesis is discussed.

Animals↗
PubMed2002

[Acute phase proteins and recurrence of angina after effective coronary angioplasty].

AIM: Analysis of relationships between clinical characteristics of the patients, high concentration of acute phase proteins--fibrinogen, C-reactive protein (CRP), activity of the inhibitor of type 1 plasminogen activator (PAI-1)--and frequency of angina recurrence after successful coronary angioplasty (CA). MATERIAL AND METHODS: The trial included 53 patients after successful CA for a single hemodynamically significant stenosis. Peripheral blood was examined for plasm fibrinogen, CRP, activity of PAI-1 one day before and 2 days, 3 and 6 months after CA. After 12-month follow-up the patients were divided into two groups: angina-free patients (n = 37) and with recurrent angina (n = 16). RESULTS: Significant differences between the above groups were in PAI-1 activity 3 and 6 months after CA, in CRP initially, on day 2, after 6 months after CA (p < 0.05) but multifactor analysis has found that only CRP level both initial and on day 2 after CA is an independent predictor of recurrent angina pectoris after successful CA. CONCLUSION: An anginal recurrence after successful CA can be predicted by the initial and postoperative day 2 levels of CRP.

Acute-Phase Proteins↗
PubMed2001

Structure and functions of classical cadherins.

Cadherins are a family of membrane receptors that mediate calcium-dependent homophilic cell-cell adhesion. Cadherins play a key role in the regulation of organ and tissue development during embryogenesis. In adult organisms, these proteins are responsible for formation of stable cell-cell junctions and maintenance of normal tissue structure. Disruption in expression or function of cadherins may cause uncontrolled cell migration and proliferation during tumor development. This review focuses on the structure and physiological functions of classical cadherins.

Actins↗
PubMed2001

Monocyte integrin expression and monocyte-platelet complex formation in humans with coronary restenosis.

1. In the present study, we sought to determine whether patients with restenosis after coronary stenting possess increased monocyte reactivity, as manifested by a higher level of adhesion molecule expression and an enhanced propensity to form monocyte-platelet aggregates after activation in vitro. 2. Anti-coagulated peripheral venous blood from 24 patients, 10 with and 14 without angiographically verified restenosis, was obtained. Leucocyte antigen expression and the number of leucocyte-platelet complexes were measured by flow cytometry after activation in whole blood. 3. Surface integrin Mac-1 (CD11b/CD18) and VLA-4 (CD49d/ CD29) expression on monocytes and the relative number of monocyte-platelet complexes after in vitro activation were significantly elevated in patients with restenosis compared with patients without restenosis (fluorescence intensities of 1425 +/- 76 vs 1195 +/- 71, 87 +/- 7 vs 65 +/- 6 and 47 +/- 4 vs 29 +/- 3% for for Mac-1, VLA-4 and monocyte-platelet complexes, respectively; P < 0.05 for each parameter). 4. The results suggest that restenosis is associated with increased monocyte VLA-4 and Mac-1 integrin expression and monocyte-platelet complex formation, which can be revealed after activation in vitro.

Blood Platelets↗
PubMed2001

[Urokinase stimulates whereas tissue plasminogen activator attenuates blood vessel stenosis].

Periadventitial application of the urokinase-plasminogen activator (uPA) in pluronic gel to an injured artery stimulated the neointima and neoadventitia formation as well as cell migration and proliferation in vivo. In contrast, the tissue-type plasminogen activator (tPA) reduced the number of neointimal smooth muscle cells and neointimal area and attenuated the lumen stenosis after a balloon catheter injury of the rat carotid artery. This ability to stimulate the neointima and neoadbentitia formation was found to be quite specific for the uPA. The findings suggest that this uPA property provides a specific functional target for attenuating growth of the damage.

Angioplasty, Balloon↗