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Biomedical subjects

V A Kuznetsov

Publications and source records attributed to V A Kuznetsov.

At least 37 records · Page 2Linked to original sources

[Prevalence and intensity of smoking among adult urban population of Tiumen': data of population mail questionnaire survey].

AIM: To estimate prevalence and intensity of smoking among adult Tyumen citizens by mail questionnaire survey. MATERIALS AND METHODS: A representative sample of adult population of Tyumen (central district) was randomly selected using the list of the electors. The questioning covered a total of 3200 citizens (8 groups per 400 age- and sex-matched subjects). The response reached 71.5%. Smoking in the population was studied in three aspects: prevalence, intensity and passive smoking. RESULTS: Overall prevalence of smoking was not great (28.8%), but smoking was frequent in women, especially young, was intensive in males of all the age groups. The number of smokers who had quit smoking was small. Passive smoking at jobs was prevalent. CONCLUSION: The data of the survey indicate difficulties of social adaptation for the studied population who fall under risk to develop cardiovascular diseases.

Adult↗

[Data of one-stage screening trial of an open Tumen population].

AIM: To evaluate epidemiological situation by cardiovascular diseases and their risk factors in Tyumen. MATERIALS AND METHODS: An open population of the Central Tyumen district was studied (1608 patients) for prevalence of obesity, arterial hypertension, systolic and diastolic arterial pressure. RESULTS: It was found: high incidence of arterial hypertension both in males and females (25.6 and 24.6%, respectively) with predominance of isolated systolic arterial hypertension in younger patients, high incidence of borderline hypertension in young men, higher predisposition to obesity in males vs females. Body mass index was higher in 25-34-year-old males but increased with age in females. CONCLUSION: It is necessary to perform a cohort study of epidemiological parameters to detect persons with cardiovascular disease risk.

Adult↗

Kinetic analysis of high affinity forms of interleukin (IL)-13 receptors: suppression of IL-13 binding by IL-2 receptor gamma chain.

Interleukin-13 (IL-13) is a pleiotropic cytokine that controls growth, differentiation, and apoptosis of immune and tumor cells. To understand the mechanisms of interaction between IL-13 and IL-13 receptors (IL-13R), and the role of the IL-2 receptor common gamma chain (gammac) in IL-13 binding and processing, we have examined IL-13 binding kinetics, dissociation/shedding, and internalization in renal cell carcinoma (RCC) cell lines. We observed a new phenomena in that the apparent rate of association, but not the dissociation, was strongly related to IL-13 concentration. We also observed cooperativity phenomena in IL-13 and IL-13R interaction in control RCC (MLneo) cells, but not in cells transfected with gammac chain (MLgammac). The number of IL-13 binding sites, the effective rate of ligand association, and the dissociation rate constants were reduced in gammac-transfected cells compared to control RCC cells. Two forms of IL-13R were detected in these cell lines, which differed in the kinetics of endocytosis and dissociation/exocytosis. Only a small fraction of bound receptors (14-24%) was rapidly internalized and the same fraction of the ligand-receptor complexes was shed and/or dissociated. The expression of gammac chain did not change any of these processes. A two independent high-affinity and moderate-affinity receptor model fit the kinetic observations in gammac-transfected cells. However, in control cells, the binding kinetics were more complicated. A mathematical model that fit a set of kinetic and steady state data in control cells was selected from a set of possible models. This best-fit model predicts that 1) two different IL-13R are expressed on the cell membrane, 2) a minor fraction of IL-13R exist as microclusters (homodimers and/or heterodimers) without exogenous IL-13, 3) high morphological complexity of the gammac-negative control cell membrane affects the cooperativity phenomena of IL-13 binding, and 4) a large number of co-receptor molecules is present, which helps keep the ligand on the cell surface for a long period of time after fast IL-13 binding and provides a negative control for ligand binding via production of the high affinity inhibitor bound to IL-13. Our data demonstrate that gammac exerts dramatic changes in the kinetic mechanisms of IL-13 binding.

Binding, Competitive↗

[Attitude of urban population to health and knowledge about risk factors of cardiovascular diseases according to postal questionnaire].

AIM: To elucidate attitude of urban population of Tyumen city to own health and compare the knowledge of cardiovascular disease risk factors in different population groups using postal questionnaire. MATERIALS AND METHODS: 3200 men and women were included into the lists of population selection, 400 subjects in each group according to the age and sex. 71.5% of those on the lists agreed to take part in the survey. RESULTS: The population knew about the risk factors in the following order: hypercholesterolemia (44.6%), arterial hypertension (74.8%), low physical activity (75.2%), smoking (75.7%), obesity (83.7%), stress (93.7%). The knowledge of the risk factors among persons with higher education was greater than among less educated individuals. CONCLUSION: Most respondents worried about their health, especially males, understand the importance of preventive approach to cardiovascular diseases, are aware of the major risk factors but they have low trust in public health service.

Adult↗

Individual prognoses of long-term responses to antiretroviral treatment based on virological, immunological and pharmacological parameters measured during the first week under therapy.

OBJECTIVE: To predict long-term (12 weeks or longer) virological responses to antiretroviral treatment from measurements made during the first few days on therapy. METHODS: Forty-one HIV-1-infected children were treated with ritonavir for 12 weeks followed by triple drug combination treatment, and the kinetics of virus decay in plasma, ritonavir concentration and CD4 cell counts were measured. A robust multivariate pattern recognition method was used for prediction of the longterm virological responses. RESULTS: The virus decay rate constants calculated from measurements of plasma viral RNA concentrations on the first, second, third, fourth and seventh day on therapy, the drug concentrations in the plasma on day seven, and the pretreatment levels of viral RNA and CD4 cell counts, correlated with long-term levels of plasma HIV-1 RNA. The combination of these parameters contained sufficient information for correct and robust prediction of the long-term response in 88% of the treated children. The predictions of individual responses were stable as demonstrated by a cross-validation analysis, which was highly statistically significant (r=0.87) and specific. CONCLUSION: These results demonstrate that multiple parameters determine the response to antiretroviral therapy and offer a very early measure of individual long-term responses, suggesting that treatment could be optimized after few days of therapy.

Adolescent↗

Prognosis of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer by immunological urinary measurements: statistically weighted syndrome analysis.

PURPOSE: The goal of this research was to discover new biological indicators in urine which could be used for short-term prognosis of local Bacillus Calmette-Guerin (BCG) therapy outcome in patients with superficial bladder cancer. PATIENTS AND METHODS: We measured and statistically evaluated soluble immunological molecules in urine from bladder cancer patients (n = 34) receiving BCG intravesically. Urine was collected following each of 6 weekly treatments, processed and assayed. The data base included measurements of interleukin-1 (IL-2, IL-4, IL-6, IL-10, IL-12, soluble intercellular adhesion molecule-1 (sICAM-1), tumour necrosis factor-alpha (TNF alpha), soluble CD14 (sCD14), interferon-gamma (IFN gamma), GM-CSF, volume of urine and its pH. The clinical response was evaluated by urine histology and random quadrant biopsy 3 months after the start of therapy. Patients were divided into 2 groups, with good and poor therapeutic effect. The initial complete response rate was 62% (21/34). The data base was analyzed using traditional multivariate statistical methods and a pattern recognition method which deals with combinatorial-statistical analysis (statistically weighted syndromes (SWS) method) of the gradated features. The SWS method is capable of identifying robust patterns in small "fuzzy" sets with high dimensional objects and some missing values. RESULTS: Only one parameter gave significant differences at p < 0.05, GM-CSF at instillation 6. Repeated measurement analysis of variance, backward stepwise multiple logistic regression and linear discriminant analysis failed to show any significance. However, significant differences in the structure of correlation between features in the groups with and without therapeutic effect were observed and four highly informative variables (the masses of sICAM-1, TNF alpha, sCD14 and pH) relating to 5th-6th installations were selected by SWS. These features provided accurate individual prediction of therapeutic outcome for all our patients. Cross-validation analysis and computer simulation showed the statistically significant stability of the prediction. CONCLUSION: We have selected a set of urinary variables that could be considered as a perspective combination of indicators (syndromes) of outcome of pre-operation BCG therapy of patients with superficial bladder cancer. A larger patient database will provide testing and evaluation of the biological and clinical significance of selected features. The computational syndrome-disease approach should be applicable for the solution of decision-making problems for management of cancer.

Adjuvants, Immunologic↗

Kinetics of T cell proliferation: a mathematical model and data analysis.

A mathematical model of in vitro T cell proliferation controlled by IL-2 internalization is presented. The model describes the T cell transition from G1 to S+G2+M stages of the cell cycle and introduces "molecular" equations for the G1-S phase control. These equations consider current knowledge of the biochemical mechanisms of receptor synthesis, ligand-receptor binding, and internalization of ligand-receptor complexes. The model describes the kinetic data for in vitro T cell proliferation at various IL-2 concentrations (50-500 pM) for various exposure time (6-26 h). The kinetic parameters were calculated based on the model. The results obtained suggest that increase in the IL-2 concentration and exposures decrease the critical ligand-receptor concentration in the cells which control proliferation. The time tau, which characterizes the delay in the G1-S transition, was constant at various IL-2 concentrations.

Animals↗

[Development of monoclonal antibody-based immunoenzyme kit for detection of human thyrotropin hormone].

An enzyme immunoassay kit based on monoclonal antibodies (Mab) has been developed for measuring thyroid-stimulating hormone in human serum and plasma. Laboratory trials demonstrated its high sensitivity (3.1 microIU/ml), specificity, reliability, and accuracy. The analysis is simple and rapid (2.5 h), which is convenient for clinical use. The kit permits differentiation between normal subjects and patients with primary hypo- or hyperthyroidism and helps monitor the treatment efficacy. Comparison with the Amerlite TSH-60 kit, carried out on 357 sera, showed a high correlation coefficient (0.96) between the two kits.

Antibodies, Monoclonal↗

[Disputable aspects of surgical treatment of acute disseminated purulent peritonitis].

The comparative clinical analysis of effectiveness of two methods of treatment of acute purulent disseminated peritonitis was performed. In the 1st group (63 patients) the semiopen method was used, in the 2nd group (45 patients)--open method was used. The rate of mortality in the 1st group was 68.3%, in the 2nd group--71.1%. The duration of in-hospital period was 53.4 +/- 3.9 days and 52.1 +/- 4.4 days, respectively. A great number of postoperative complications was noted in both groups. In contrast to other authors, no advantages of the open method over the semiopen method were found.

Acute Disease↗

A mathematical model of T lymphocyte proliferation controlled by interleukin-2 internalization.

A mathematical model of the first in vitro IL-2-controlled division cycle of T lymphocytes is presented. The model describes the population dynamics of T cells at different stages of the cell cycle and introduces "molecular" equations for the G1-S phase control. These equations are based on the current knowledge of the biochemical mechanisms of ligand-receptor binding, ligand and receptor synthesis, and internalization of the ligand-receptor complexes. The temporal order in the biosynthesis of IL-2 and IL-2R during the G1a and G1b phases is investigated. We show numerically that the maximum number of cells in the S-phase depends on the reversibility of the G1a-G1b transitions, on the rates of ligand-receptor binding, ligand and receptor synthesis, and internalization of the ligand-receptor complexes. The phase portraits for different hypotheses on the temporal order of the IL-2 and high affinity receptor synthesis at the G1 phase of the cell cycle are qualitatively different. On this basis, simple kinetic experiments to distinguish between these alternatives are proposed.

Animals↗

"Harpoon" model for cell-cell adhesion and recognition of target cells by the natural killer cells.

The mechanism of recognition by natural killer (NK) cells is still unknown. A dynamic model is formulated describing recognition of NK-sensitive target cells (TCs) by NK cells or NK-like cells. This model does not assume the presence of the specific NK-receptor(s) on the membrane of NK cells and corresponding specific ligands on the NK-sensitive TCs. We suggest: (1) the expression of various kinds of "non-NK receptors" and corresponding ligands (counter-receptors) on the plasma membrane of the same NK cell and, possibly, of TCs (e.g. LFA-1 and ICAM-1-ICAM3, CD2 and LFA-3; receptors for TNF and corresponding ligand etc.0; (2) the presence of multiple disorders in the organization of "extracellular matrix-surface membrane-submembrane cytoskeleton" assembly of the NK-sensitive TCs; (3) non-specific primary linking of NK cell with TCs, which induces a transfer of vesicles or membrane fragments from the NK surface to the target cell surface (and perhaps vice versa). These processes may also permit the transfer of many types of receptor and counter-receptor molecules from the surface of one conjugated cell to another by vesicles or membrane fragments. After transferral through the intercellular cleft, the free receptors and counter-receptors will be localized on both cell surfaces at the contact region between conjugated cells. By this model the NK cell can "harpoon" the TC and enhance the binding forces between cells up to the critical level and then switch on killing mechanisms for the TC. By means of this "harpoon" model of cell recognition, it seems possible to explain the nature of the wide polymorphism of TCs which are sensitive to the effect of NK and NK-like cells. A mathematical model of the NK cell cytotoxic reaction is described. The model describes many nonlinear peculiarities of the cytotoxic process and predicts some new phenomena. We suggest new approaches of manipulation of cell membranes which can transform NK-resistant target cells in NK sensitive cells and vice versa.

Animals↗

Nonlinear dynamics of immunogenic tumors: parameter estimation and global bifurcation analysis.

We present a mathematical model of the cytotoxic T lymphocyte response to the growth of an immunogenic tumor. The model exhibits a number of phenomena that are seen in vivo, including immunostimulation of tumor growth, "sneaking through" of the tumor, and formation of a tumor "dormant state". The model is used to describe the kinetics of growth and regression of the B-lymphoma BCL1 in the spleen of mice. By comparing the model with experimental data, numerical estimates of parameters describing processes that cannot be measured in vivo are derived. Local and global bifurcations are calculated for realistic values of the parameters. For a large set of parameters we predict that the course of tumor growth and its clinical manifestation have a recurrent profile with a 3- to 4-month cycle, similar to patterns seen in certain leukemias.

Animals↗

Kinetic approach and estimation of the parameters of cellular interaction between the immunity system and a tumor.

A method is suggested to estimate multi component dynamic systems, which permits, with the help of the computer-calculated kinetic curves, to obtain information about the possible mechanisms of the system component interaction. The method is based on the structural and parametrical identification of mathematical models presented in the form of a system of nonlinear differential equations, using a multi-criterial approach. Using experimental data of studies on growth kinetics and regression of multicellular tumor EMT6 line spheroids in the mouse allogenic system and the immune system cell accumulation in spheroids a mathematical model has been developed of the cellular interaction process in a spheroid. It has been stated that the rate of macrophage and neutrophil accumulation in a spheroid depends on the amount of tumor cells and is determined by the hyperbolic law (as analogous to the Michaelis-Menthen kinetics), while the accumulation of immune lymphocytes in a tumor is determined besides that by the three-cellular cooperation of lymphocytes, macrophages and tumor cells. According to the model, the inhibition of the process of neutrophil and lymphocyte (but not of macrophages) accumulation is realized through the auto-suppression mechanism. The numerical values of the process parameters, which characterise the rates of accumulation, cellular death in a tumor and of local cellular interactions intensity are obtained.

Cell Communication↗

[Middle weight molecules before and after detoxification in patients with peritonitis].

The dynamics of changes of the middle mass molecule (MMM) content in blood serum and peritoneal exudate was studied in 193 patients before and after different methods of detoxification: intraoperative cleansing of the abdominal cavity in closed treatment, planned stage cleansing in open treatment of peritonitis, hemosorption, therapeutic plasmapheresis, sorption through a pig spleen. The control group was made up of 88 donors and 16 patients with an urgent abdominal disease without signs of peritonitis. The diagnostic value of MMM and the expediency of combining surgical methods for cleansing of the abdominal cavity with methods of extracorporeal detoxification are shown.

Adolescent↗

Relationship between ventricular arrhythmias and left ventricular false tendons in acute myocardial infarction.

To evaluate the association between left ventricular false tendon (LVFT) and ventricular arrhythmias in acute myocardial infarction (MI) on the 1-st day of acute MI 71 patients were examined by 24-hour ECG-monitoring and M-mode, two-dimensional, Doppler echocardiography. LVFT was detected in 30 patients (42.3%). The frequency of left ventricular fibrillation, the number of patients with multiform ectopic ventricular beats (EVB), the number of single and pair EVB and runs of ventricular tachycardia were greater in group of patients with LVFT. 37 patients had Lown grades 1-2 (A) of arrhythmias, 34 patients had grades 3-5 (B). LVFT was revealed in four patients in group A (10.8%) and in 27 patients in group B (76.5%, p < 0.001). There were no significant differences between groups in left ventricular asynergy area and wall motion score, left and right ventricular, left atrium dimensions, left ventricular contractility indices, left ventricular walls thickness, frequency of mitral regurgitation. Multifactor analysis has shown significant relationship between Lown's class value and LVFT (p < 0.0001), Lown's class and arterial hypertension (p = 0.0376). Other 17 clinical factors were not connected with Lown's class value. Thus, LVFT was associated with severe ventricular arrhythmias in patients with AMI. This fact can be used as a predictor of these disturbances.

Arrhythmias, Cardiac↗