[Proteomics as a fundamental tool for subclinical screening, tests verification and assessment of applied therapy].

Proteomics is a science which studies proteins of the body, interactions of proteins and their biological functions. Today, it is an essential partner in establishing preclinical diagnosis protocols. In conjunction with other sciences such as genomics and bioinformatics it will be possible to diagnose diseases on the earliest stages before its clinical onset or to gain the dynamics of pathological processes in the body and response to drug therapy. This article discusses general aspects of proteomics as well as special ones on the basis of models of cardiac diseases and cancer.

[Neuroimmunoendocrine mechanisms of regulation of reproductive function].

Modern molecular biological studies have significantly improved understanding of structural and functional organization of the female reproductive system. The paper gives a brief overview of the literature and own research on verification and expression in the endometrium and placenta of many peptides, biogenic amines, steroids, cytokines and other signalling molecules, which, acting as hormones, enzymes, inhibitors, receptors, growth factors, immunoregulatory agents, transport's and binding proteins, provide the local regulation of intercellular neuroimmunoendocrine relationships that play a key role in the mechanisms of human embryogenesis and reproduction.

[Regulation of human dendrite cells' physiological functions with the recombinant heat shock protein Hsp70].

Reference literature review. The dendrite cells (DC) are the most important antigen-representing cells of the organism. They are the target for various vaccines, and on the basis of the DC cellular anti-tumour and anti-viral vaccines (DC vaccines) have been developed. At the same time, the DC can be a convenient model for studying activity and action mechanisms of different immune-therapeutic preparations. One of the aspects of the DC use optimization for induction of antigen-specific immune response might involve use of the heat shock proteins (Hsp), the Hsp70 in particular. This protein can be used for administration of protein antigens into the DC and for regulation of the DC activity. Knowledge of the DC physiology and specifics of interrelationship among the Hsp70 and its complexes with the DC antigens of different differentiation degree is an important aspect for implementation of these ideas. Human Hsp70 has been shown both to bring antigens to the DC and to regulate activity of the DC as well as to optimize induction of antigen-specific cellular immune response.

[Antithyroid antibodies of varying specificity in the pathogenesis and diagnosis of autoimmune thyroid diseases].

AIM: To compare the possible pathogenetic and clinicodiagnostic value of antithyroid autoantibodies (autoAB) different in specificity, such as monospecific ones to thyroglobulin and thyroid peroxidase (anti-TG and anti-TPO autoAB) and bispecific ones to thyroglobulin and thyroid peroxidase simultaneously (anti-TGPO autoAB), in patients with autoimmune thyroid diseases. MATERIALS AND METHODS: The sera from 240 patients with autoimmune thyroiditis (AIT) and from 124 with diffuse toxic goiter (DTG) were examined. The sera from 40 healthy donors served as a control. The sera were screened for anti-TG and anti-TPO autoAB, anti-TGPO autoAB, by employing enzyme immunoassay and/or radioimmunoassay. The results were statistically processed using the variation statistics-based programs. RESULTS: The specific features of an autoantigenic component to thyroid tissues were found in the sera of patients with AIT and DTG. An association was established between the progression of disease and the phasic change of autoAB populations or their combinations. CONCLUSION: The procedure for evaluating seropositivity for antithyroid autoAB, which is referred to as non-invasive studies, can be considered as a criterion test in the diagnosis and prediction of the course of AIT and DTG.

[Modern technologies in diagnosis and treatment of patients with late stages of hydronephrosis].

To evaluate the role of modern ultrasonic, x-ray and radionuclide methods in staging hydronephrosis; that of stimulators of stem cells of the bone marrow in combined therapy of patients with late hydronephrosis, we examined and treated 18 patients with late-stage hydro- and ureterohydronephrosis. All the patients were operated. Preoperative preparation included drainage of the upper urinary tract and stimulation of bone marrow stem cells. Organ-saving surgery was conducted with a satisfactory functional result in 14 of 18 patients. Modern methods of investigation provide an objective assessment of structural-functional condition of the kidneys and upper urinary tract in patients with late hydro- and ureterohydronephrosis, may evidence for possible reversibility of registered uro- and hemodynamic alterations. Preoperative use of stimulators of bone marrow stem cells promotes activation of repair processes in renal parenchyma which is essential for efficacy of a further reconstructive operation.

[Architectonics of cell subpopulations of peripheral blood in patients with autoimmune myocarditis: clinical and pathogenetic aspects].

AIM: To compare the most significant architectonic parameters of peripheral blood cell subpopulations in patients with different variants of an autoimmune myocarditis (AIM) course and their clinical value in therapeutic practice. MATERIAL AND METHODS: Blood cell subpopulations were studied with flow cytometry in 99 blood samples from patients having different AIM variants and myocardiosclerosis as well as in 40 healthy donors. RESULTS: Severe (malignant) AIM was characterized by growing indices of T-/B lymphocyte activation, expression of activation markers on the cells of both differentiation lines, disproportions in composition of subpopulations of the immunoregulatory cells, parallel rise in specific weight of dendritic cells, reduced intensity of apoptosis of autoreactive T-lymphocytes. In benign AIM marked immunopathology was not found. This group can be considered as a separate variant of AIM course necessitating an individual approach to planning pathogenetically sound therapeutic and rehabilitation measures. CONCLUSION: The study of activation markers expression on peripheral blood cells is superior to the study of endomyocardial biopsies providing a non-invasive method of immunodiagnosis.

[The current concept of immunological disorders in the case of basal-cell carcinoma].

Imbalance in the interaction of mechanisms of innate and adaptive immunity rather than selective defect of each of the links is a determinant of the development of basal-cell carcinoma of this or that form of immunopathology or that of transformation of one to another form. The lecture gives notions on immunological phenotypes and the parameters of innate and adaptive immunity and on the association of two links of immunity. The major tumor-associated immunological phenotypes are pathogenetically and clinically different, but have signs of two-link immunodeficiency in each case. Tumor-associated secondary immunodeficiency is characterized by defects encompassing both the innate and adaptive links of immunity. Predominant are autoimmune disorders involving mainly the adaptive link of immunological responsiveness in case of tumor-associated autoimmune syndrome concurrent with immunodeficiency.

[Extracellular and cell-matrix interaction in pathology].

A lot of physiological processes including cell proliferation, cell migration, and differentiation are regulated by intercellular and cell-matrix interaction. The misbalance of intercellular and stroma-epithelial interaction is one of main factor of initiation of different pathological processes. Nonhealing wounds (chronic inflammation) and adenocarcinomas, despite the different external features, have many general inner features: cell proliferation, survival, cell migration, differentiation induced by cocktail of different growth factors and cytokines which promote inflammation and angiogenesis. Various stroma components including extracellular matrix are active participants of wound healing and cancer growth. The changes of pl-integrins distribution and cytokine expression, TGFbeta in particular, influence the development of pathological processes. It is possible to consider these factors as potential pharmacological targets.

[Independent postmortem examination: contents of its concept, organizational aspects of its performance].

The paper discloses the contents of the concept of independent postmortem examination and describes the organizational aspects of postmortem examination according to the materials of primary postmortem studies of autopsy and biopsy of surgically removed organs.

[Role of a transforming growth factor beta-1 in regulation of invasive growth of prostatic adenocarcinoma]. / Rol' transformiruiushchego faktora rosta beta 1 v reguliatsii invazivnogo rosta adenocartsinomy predstal'noi zhelezy.

Immunohistochemical study of histological sections and immunochemical study in supernatants of primary cultures demonstrated a marked increase of the factor production in the regions of the background changes outside foci of carcinoma invasive growth. There was no difference in the type of expression of TGFbeta-I and TGFbeta-II receptors in morphologically different regions of the tumour. TGFbeta-I is considered as a principal factor that mediates hyperplastic reaction of the stroma in prostatic adenocarcinoma outside the zones of invasive growth. Formation of reactive stroma, in the authors' opinion, plays the role of a defensive mechanism hindering invasion of tumour cells into the connective tissue and its progression.

[The role of Fas/FasL system in induction of hepatocyte apoptosis in chronic viral hepatitides]. / Rol' sistemy Fas/FasL v induktsii apoptoza gepatotsitov pri khronicheskikh virusnykh gepatitakh.

The aim of the study was assessment of hepatocyte apoptosis depending on expression of Fas and FasL proteins by various liver cells in patients with chronic viral hepatitis B (CVHB) or chronic viral hepatitis C (CVHC). The symptoms of hepatocyte apoptosis were observed in 3 of 12 patients with CVHB and in 9 of 14 patients with CVHC, the proportion of apoptotic cells being 12-65%. Hepatocytes of healthy people and patients with hepatitis B or C express Fas protein in the cytoplasm diffusely, as granules or on cell membrane. In health, hepatocytes do not express FasL, but in CVH they do. The highest apoptosis was observed in Fas protein location as granules in cytoplasm or in their preferable location on the cell membrane. The severity of hepatocyte apoptosis in CVH directly correlated with FasL expression by the cells of the lymphoid-histiocytic infiltrate in the liver and inversely correlated with FasL expression by hepatocytes. Thus, a great part of hepatocytes in CVH are killed by the virus; Fas/FasL interaction is leading in damage to hepatocytes in CVH.

[Histological and molecular-biological markers of malignancy in different variants of thyroid papillary carcinoma]. / Gistologicheskie i molekuliarno-biologicheskie markery zlokachestvennosti v razlichnykh variantakh papilliarnogo raka shchitovidnoi zhelezy.

Material for this study from 61 patients (thyroid papillary carcinoma) is shown to represent a heterogenic group of tumors differing from each other morphologically, molecular-biologically and histogenetically. The most malignant were long-cell and B-cell variants and the least malignant--a follicular variant. 81% of the tumors had neuro-endocrine differentiation and their malignant potential was higher compared to tumors without this differentiation.

[Primary culture of prostatic adenocarcinoma: a model for studies of stromal-epithelial interactions]. / Pervichnaia kul'tura adenokartsinomy prostaty: model' dlia izucheniia stromal'no-épitelial'nykh vzaimodeistvii.

Primary culture of prostatic adenocarcinoma is obtained from surgical material after radical prostatectomy. Typing of the obtained culture with antibodies to vimentin and cytokeratins has shown that the proportion of basic cell components--stromal and epithelial--in vitro correlates with such in the initial tumor tissue. In cultivation in different media active migration and proliferation of all cell types in the presence of embryonal serum and suppression of the stromal component in the medium where the serum was replaced for bovine hypophysis extract were observed. A comparative immunohistochemical analysis registered a release into culture of alpha SMA-positive myofibroblasts and active expression of TGF beta-1 in the medium containing serum. Design of dynamic mixed cell systems may serve a convenient model for investigation of stromal-epithelial interactions and their changes in cancer progression.

[Small cell carcinoma and carcinoids of the lung: morphology of apoptosis and expression of biomolecular markers of tumor growth]. / Melkokletochnyii rak i kartsinoidy legkikh: morfologiia apoptoza i ékspressiia biomolekuliarnykh markerov opukholevogo rosta.

Neuroendocrine lung tumors (NELT) from 50 patients were studied immunohistochemically. Malignant carcinoid and small-cell lung carcinoma (SCC) have a higher level of apoptosis than ordinary carcinoid. An increase of apoptosis index in NELT coincides with an increase in NELT proliferative activity (Ki-67, Bcl-2, c-myc, p-53) as compared to a typical carcinoid. Phagocytosis of apoptotic bodies was absent in SCC. Classic SCC differs from combined SCC by a higher apoptosis index and lower expression of p-53 and Bcl-2. Metastatic SCC differs from SCC without metastases by lower apoptosis level and higher level of proliferative indices (Ki-67, Bcl-2) of tumor cells. Development of unbalance between apoptosis and proliferation may result from mitosis and apoptosis pathology.

Role of Bcl-2, Bax, and Bak in spontaneous apoptosis and proliferation in neuroendocrine lung tumors: immunohistochemical study.

Fifty-six primary neuroendocrine lung tumors were examined morphologically and histologically and their apoptosis level was determined. Malignant carcinomas were characterized by increased apoptotic index and enhanced expression ofBcl-2, Bak, p53, and Ki-67 compared to typical carcinoid. However, apoptosis in these tumors was not completed. Proteins of the Bcl family play an important role in the regulation of spontaneous apoptosis in neuroendocrine lung tumors. Bcl-2 accumulating in the nucleus is a morphological analogue of phosphorylated inactive form of this protein, which does not inhibit apoptosis. Expression of Bcl-2 and Bax decreases in small-cell lung carcinoma (SCLC) with metastases indicating attenuation of apoptosis and development of metastatic clones resistant to apoptosis induces.

[Comparative study of Hashimoto thyroiditis and "focal thyroiditis"]. / Sravnitel'noe izuchenie tireoidita Khashimoto i "ochagovogo tireoidita".

As shown by a semiquantitative analysis of histological changes in the thyroid tissue, there is a correlation between some characteristic features of autoimmune thyroiditis (Hashimoto's thyroiditis). Formation of lymphoid nodules in the thyroid in autoimmune thyroiditis was followed up and its three stages were distinguished. Autoimmune thyroiditis has three degrees of activity by diffuse lymphoid-plasmocytic infiltration, thyroid tissue destruction and lymphoid nodules formation. Differences between autoimmune thyroiditis and focal thyroiditis are revealed. The above differences include spread and cellular composition, content of the lymphoid-plasmocytic infiltrate, the degree of the destructive changes, B-cell hyperplasia, expression of CD-4 on T-helpers and CD-19 on B-lymphocytes, cytological picture. These differences allow differential diagnosis between these diseases.