Vol 68, No 9 (2013)

MOLECULAR MEDICINE AND GENETICS: CURRENT ISSUES
STRUCTURAL AND FUNCTIONAL ANALYSIS OF TUMOR GENOMES AND THE DEVELOPMENT OF TEST SYSTEMS FOR EARLY DIAGNOSIS, PROGNOSIS AND CANCER THERAPY OPTIMIZATION
Zaletaev D.V., Strel'nikov V.V., Nemtsova M.V., Babenko O.V., Kuznetsova E.B., Zemlyakova V.V., Kekeeva T.V., Mikhailenko D.S., Tanas A.S., Rudenko V.V., Babayan A.Y., Alekseeva E.A., Simonova O.A.

Abstract

The article discusses results of the structural and functional analysis of molecular genetic abnormalities in various malignant tumors. Investigations have discovered more than 20 new markers for sporadic breast cancer. Several of them formed the test system, allowing the diagnosis with a specificity of 100%. Appearance of TMPRSS2/ERG4 chimeric gene is a frequent tumor-specific event, its expression is correlated with more aggressive forms of prostate cancer, may serve as a molecular marker for tumor cells and androgen assessment of tumor response to hormonal therapy. The effective systems for the early diagnosis of cervix and endometrium cancer were developed as well. Mutations in the VHL, deletions of chromosome 3 and methylation of several genes can predict the course and selection of effective therapy of clear cell kidney cancer. a number of molecular markers were identified for early diagnosis and prognosis of recurrence of bladder cancer. For diagnosis, prognosis and treatment of brain tumors we developed an effective complex system of markers. Protocol of molecular genetics investigation reveals the cause of the disease by more than 90% of patients with retinoblastoma. In order to study abnormal methylation in tumor genomes an innovative technology AFLOAT has been developed that allows to efficiently identify new markers with diagnostic value. Test systems of molecular genetic and epigenetic markers for early diagnosis and prognosis as well as for cancer therapy optimization have shown to be effective, have been approved for use in clinical practice and are being introduced into practical healthcare.

Annals of the Russian academy of medical sciences. 2013;68(9):7-14
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AGE AND SEXUAL CHANGES STRUCTURE OF GENES CYTOKINES NETWORKS IN RUSSIAN POPULATION
Konenkov V.I., Prokof'ev V.F., Shevchenko A.V., Chernyavskii A.M., Karas'kov A.M.

Abstract

Objective: to study frequencies of occurrence of the combined genetic attributes including different variants of cytokines genotypes (TNFA, IL1B, IL4, IL6, IL10, VEGF), in different on sexual  and age groups in population of Siberia Caucasoid. Material and methods. Frequencies of distribution of variants of structure genes cytokines networks  among 500 representatives of Siberia  Caucasian population, men and women  of  two age groups - more younger than 35 years ("young") and 55 and more years ("elderly") are  investigated. In structure of  investigated genes cytokines net  has come 10 variants of polymorphic sites of cytokines genes and  vascular endothelial growth factor gene: TNFА-863 C→A, TNFА-308 G→A, TNFА-238 G→A, IL1B-31 С→T, IL4-590 С→T, IL6-174 G→C, IL10-1082 G → A, IL10-592 А→С, VEGF-2578 C→A and VEGF+936 С→T. Genotyping are carried out by  restriction fragment length polymorphism method. Processing of results carried out on the basis of the original methodological approach including the complex connected computer analysis of genic circuits of various dimension. Results and conclusions. It is shown, that the significant part of variants genes cytokines networks, which   widely distributed among young people is completely absent in the "elderly" age group. Such variants disappearing with age separately for men and women are established. At the program mathematical analysis it is established, that parameters of the odds ratio  achieve two-place sizes (OR =27, p =0,0004), that testifies to high specificity of complex genetic attributes. Presence in genome such variants of genes cytokines networks  , found out in the childhood or young age, as supposed, is unfavorable personalized prognostic factors of life span of the individual.

 

Annals of the Russian academy of medical sciences. 2013;68(9):15-21
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CARDIOLOGY: CURRENT ISSUES
APOPTOSIS CELLS OF CORONARY ARTERY WALL AS DEVELOPING AND PROGRESSING FACTOR OF CORONARY SCLEROSIS
Vladimirskaya T.E., Shved I.A., Krivorot S.G.

Abstract

Objective: to study apoptosis of individual cellular components of the vascular wall of coronary arteries at different morphological stages of atherosclerosis. Material and methods. The study was performed on coronary arteries taken from 52 deceased patients with atherosclerosis and coronary heart disease at different stages of atherogenesis. For morphological study prepared paraffin sections, which were stained for morphological studies were prepared paraffin sections, which were stained with hematoxylin and eosin, by Van Gieson, Masson, on lipids with Sudan black B, according to Van Cossu. .To determine apoptosis, TUNEL method used in paraffin sections. Apoptotic index (AI) was calculated by TUNEL-positive cells and the average inner shell coronary artery around the perimeter each with increasing microscopic 1000. Results. Investigation showed significant apoptosis (p <0.05) increase in AI smooth muscle, endothelial cells, macrophages in the coronary arteries affected by atherosclerosis compared to intact control group vascular segments significant reduction AI endothelial, smooth muscle cells and macrophages (p 0,05) traced from the early stages of atherogenic disorders to atheromatosis. Conclusions. It is established that apoptosis of smooth muscle cells, macrophages and endothelial cells is the most intensive on early stages of atherosclerotic process. In process of progressing of atherosclerosis intensity and prevalence of apoptosis of coronary artery wall cells decreases, and processes of necrosis becomes predominant. Apoptosis of coronary artery wall cells is valuable in increasing the zones of atheromatosis, plaque destabilizations, and also increases the risk of thrombosis and ulcerations.

 

Annals of the Russian academy of medical sciences. 2013;68(9):22-26
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PARAMETERS ASSOCIATED WITH ABSENCE OF SIGNIFICANT CORONARY ATHEROSCLEROSIS BY DATA OF REGISTER OF PROVIDED CORONARY ANGIOGRAPHY
Kuznetsov V.A., Yaroslavskaya E.I., Gorbatenko E.A., Varshavchik M.V., Krinochkin D.V., Kolunin G.V., Karpov R.S.

Abstract

Aim of the study: the study aimed to reveal the sign of coronary atherosclerosis absence using the factor analysis in patients referred for the coronary angiography. Patients and methods: 9409 patients suspected stable coronary artery disease (CAD) or with confirmed diagnosis of CAD from the «Registry of provided coronary angiography» were included in the study. Results of the study: principal factor described about 59% of the variation and included the burdens of 4 parameters (gender, smoking, significant coronary atherosclerosis and hypothyroidism) and was interpreted as factor of coronary atherosclerosis. Conclusions: it was found that the absence of coronary stenosis was associated with female gender, non-smoking status and hypothyroidism.

 

Annals of the Russian academy of medical sciences. 2013;68(9):27-31
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WORK-RELATED DISEASES: CURRENT ISSUES
WORKING CONDITIONS АND MORTALITY AMONG MEN OF WORKING AGE IN RUSSIA (EXPERIENCE OF MURMANSK REGION)
Izmerov N.F., Tikhonova G.I., Gorchakova T.Y.

Abstract

Objective: To study the mortality of the male population of working age in the industrial cities depending on the specifics of the town-forming enterprises. Materials and methods.  In three cities in the Murmansk region, where the town -forming enterprises of non-ferrous metallurgy (Monchegorsk, Kandalaksha) and the mining industry (Kirovsk) are located, the capital of the region (Murmansk), and in the country as a whole has been studied of mortality on average for 6-year period  (2000-2005) age-standardized death rates (direct method). Results. Comparative analysis of the causes and death rates in males of working age has shown that in all the studied cities of Murmansk region there were higher death rates in men of working age from diseases of the circulatory system (in 1,3–2,0 times) and diseases of the respiratory system (in 1,1–1,8 times) in comparison with Russia. In industrial cities, compared with Murmansk,  higher death rates of male population of working age from causes which etiologically are connected with harmful factors of manufacture have been registered: from cardiovascular diseases — in 1,1–1,5 times and respiratory diseases — in 1,2–1,6 times. In cities where non-ferrous metallurgy enterprises are located, concerning to cancerogenic, death rates from malignant neoplasms have been raised in 1,2–1,4 times. This happens, in particular, in Monchegorsk where Open Joint-Stock Company «Severonickel Combine» enterprise is located. Mortality from lip, oral cavity and pharynx cancer raised in 1,8 times: the localization specific at influence of nickel.

Annals of the Russian academy of medical sciences. 2013;68(9):32-36
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IMPORTANCE OF OCCUPATIONAL SELECTION IN PREVALENCE OF HYPERTENSION: EFFECTS OF HEALTHY AND UNHEALTHY WORKER
Maksimov S.A., Artamonova G.V.

Abstract

The importance of occupational selection in prevalence of arterial hypertension in researches of professional cohorts is considered in the article. Because arterial hypertension represents not only the independent disease, but also one of the most important indexes of the functional status of a human body, prevalence of arterial hypertension in professional groups can be substantially caused by occupational selection. As an epidemiological phenomenon of occupational selection "healthy worker effect", known of scientific literature from the middle of last century is considered. Besides, it is offered to consider the regularities of professional selection opposite to "healthy worker effect", as "unhealthy worker effect". The professional conditionality of arterial hypertension considered from epidemiological line items can be distorted by occupational selection. Thus existence of "healthy worker effect" makes impression of absence of direct link between level of occupational influence and frequency of arterial hypertension. At the same time, the increase in prevalence of arterial hypertension not always testifies to its professional conditionality, and can be connected to "unhealthy worker effect". Possible solutions of problems associated with identification of relationships between occupational factors and prevalence of hypertension in the presence of «effects of the healthy» and «unhealthy worker» are discussed. The challenge of considered problem in occupational medicine despite the numerous offered methodological approaches of elimination or decrease in influence of occupational selection is noted.

 

Annals of the Russian academy of medical sciences. 2013;68(9):37-41
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SHORT MESSAGES
PLATELET ACTIVITY IN THE CHRONIC SCHIZOPHRENIC PATIENTS DURING ATTACKS OUTCOME AND REMISSION DEVELOPMENT
Brusov O.S., Zlobina G.P.

Abstract

The purpose of this work was to evaluate the degree of activation of platelets chronically schizophrenic patients with paroxysmal course of the disease during outcome from the attack of disease or in process of forming of the remission. Platelets in platelet-rich-plasma (PRP) and after PRP gel-filtration through the column with Sepharose CL-2B taken from the ulnar vein of males with chronic schizophrenia during outcome from the attack of disease or in process of forming of the remission were measured. Patients were investigated on the peak of the disease attack (visit 1), at the stage of significant improvement of clinical state (visit 2), and at the stage of stable drug-induced remission (visit 3). Platelet quantities in PRP prepared by centrifugation are equal in patients in visits 1, 2 or 3. These platelets quantities are much less than similar platelet quantities in healthy individuals matched in age. The additional decreases of platelet quantities were found after the elution of PRP platelets from the column with Sepharose CL-2B. These additional platelet quantity losses are increased from visit 1 to visit 3. Such losses of cells indicate decrease in their resistance to various influences, their activation in spite of remission development in this group of patients.

 

Annals of the Russian academy of medical sciences. 2013;68(9):42-45
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RECENT ADVANCES IN THE STUDY OF THE STEM CELLS MIGRATION METHODS
Poveshchenko A.F., Poveshchenko O.V., Konenkov V.I.

Abstract

Review is devoted to a comparative analysis of stem cells migration methods for studying in experimental conditions and clinics, assessing their strengths and weaknesses. It is impossible to single out any one preferred method for studying the migration of stem cells. Each method has its own set of advantages and disadvantages. X-ray methods " suffer" from non-specific binding of contrast marks, followed by rapid degradation and the release of the body. If it is necessary to study the migration of the transplanted stem cells for a long time interval, the visualization of the reporter gene is the best available techniques, since it can provide a non-invasive real time monitoring of the location in the tissue and stem cells isolated help assess their viability and proliferation. The most attractive of the agents for monitoring - endogenous, i.e. natural constituents stem cells, for example, genetic markers. Criteria for the application of methods to study migration in clinical and experimental results have significant differences. The main criteria for the methods of the study of cell migration in clinical settings, it must be biocompatible, safe, non-toxic, non-invasive. Accordingly, the main criteria for the experimental methods for studying the migration will be accuracy, the ability to quantify the long-term migration of cells and stability of the "label".
Annals of the Russian academy of medical sciences. 2013;68(9):46-51
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DEVELOPMENT OF THE QUANTITATIVE IMMUNOCHROMATOGRAPHY TESTS FOR SOMATIC DEASEASE MARKERS DETECTION
Tret'yakov S.I., Basharova L.A., Yarkov S.P., Titov A.A., Khramov E.N.

Abstract

The purpose of work was creation of quantative immunochromatographic tests (ICT)   for measuring concentrations of the marker substance associated with somatic diseases: immunoglobulin Е (IgE), C-reactive protein (CRP) and fibrin D-dimer  in blood serum (plasma),  which is carried out with the help of videodigital analyzers of domestic development "Reflecom" and "Zondaj". ICT were designed in "sandwich» format, using colloid gold and monoclonal antibodies. It is shown, that calibration curves received with the help of ICT and devices of videodigital registration, are well approximated by exponential dependence Y=Aexp(-x/B)+y0, where Y- device readings , х- analytes concentration, А, В, у0– constants. Samples of blood serum (plasma), under investigation received in conditions of a hospital from patients. Correlation with electrochemiluminescent immunoassay, enzyme linked immunoassay, latex-agglutinations assay and immunochromatographic method was observed.  Sensitivity of the developed tests was- 7,5 IU/ML for IgE, 5,7 ng/ml for CRP, 500 ng/ml for fibrin D-dimer. The developed analytical complex- videodigital analyzer "Zondaj" and ICT for quantitative measure of concentration IgE, fibrin D-dimer and CRP- can be successfully applied in  laboratory practice and clinical laboratory researches alongside with actual immunochemistry methods.

 

Annals of the Russian academy of medical sciences. 2013;68(9):52-57
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