Background : Gastric and colon tumors are often associated with eosinophilic infiltration of tumor tissue, the significance of which is still not entirely clear. The recruitment of eosinophils into the tissues can be in part regulated by galectins ― galactose-binding proteins which are expressed by a variety of tissues and are capable of exerting a broad range of effects. Aims : To evaluate the expression of galectin-1 and galec-tin-3 in tumor tissue, and gal-3 gene mRNA expression in blood eosinophils in patients with gastric and colon cancer with or without tissue eosinophilia. Materials and methods : The study included a total of 107 patients (84 males and 23 females, average age 60,9 ± 6,8) with verified gastric cancer (52 persons) and colon cancer (55 persons), who underwent treatment or were registered at the dispensary at the regional medical institution “Tomsk Regional Oncology Center” (Tomsk, Russia). The control group consisted of 15 men and 11 women of comparable age. The materials of the research included samples of gastric and colon tumors obtained during surgery, and eosinophilic granulocytes isolated from whole blood by immunomagnetic separation. Galectin-1 and galectin-3 expression in tumor tissue was evaluated by immunohistochemistry. The expression of gal-3 gene mRNA in eosinophils was determined by real-time reverse transcription polymerase chain reaction. Statistical analysis of the results was carried out using the non-parametric Mann-Whitney U test for independent samples with Benjamini-Hochberg procedure for multiple comparisons, and the Chi-square Pearson criterion with Yates correction. Results : In patients with gastric cancer and colon cancer, regardless of the presence of tissue eosinophilia, low expression of galectin-3 in the tumor tissue and high expression of gal-3 gene mRNA in peripheral blood eosinophils were found. Gastric and colon cancer patients with eosinophilic infiltration of tumor tissue were characterized by low expression of galectin-1 within tumor cells (in 64.0% cases, χ 2 = 4.890, р = 0.029; and in 73.9% cases, χ 2 = 5.981, p = 0.031 respectively). There was a statistically significant connection between the level of galectin-1 expression by tumor cells and the presence of tissue eosinophilia both in gastric (φ = 0.307) and colon cancer (φ = 0.330). Conclusion : Low expression of galectin 1 and 3 by tumor cells in gastric and colon cancer with tissue eosinophilia indicates the lack of a significant effect of these proteins on the process of recruiting eosinophilic granulocytes into tumor tissue. Increased expression of galectin-3 in blood eosinophils in gastric and colon cancer is not associated with the presence of eosinophilic infiltration of tumor tissue.

Обоснование . При раке желудка и толстого кишечника весьма часто обнаруживается эозинофильная инфильтрация опухолевой ткани, значение которой до сих пор неясно. В регуляции рекрутирования эозинофилов в ткань новообразования принимают участие галектины ― белки, экспрессируемые многими клетками и характеризующиеся широким спектром свойств. Цель исследования ― оценить экспрессию галектинов 1 и 3 в опухолевой ткани и м-РНК гена галектина-3 в эозинофилах крови при раке желудка и толстого кишечника с тканевой эозинофилией и без нее. Методы . Обследованы 107 пациентов (84 мужчины и 23 женщины, средний возраст 60,9 ± 6,8 лет) с верифицированным диагнозом рака желудка (52 больных) и рака толстого кишечника (55 больных), которые проходили лечение в ОГАУЗ «Томский областной онкологический диспансер» (Томск). В группу контроля вошли 15 мужчин и 11 женщин сопоставимого возраста. Материал исследования : эозинофильные гранулоциты, выделенные из цельной крови методом иммуномагнитной сепарации, и образцы опухолевой ткани желудка и толстого кишечника, полученные в ходе оперативного вмешательства. Экспрессию галектинов 1 и 3 в опухолевой ткани оценивали методом иммуногистохимии. Исследование экспрессии м-РНК гена галектина-3 в эозинофильных гранулоцитах осуществляли методом полимеразной цепной реакции в режиме реального времени с использованием обратной транскрипции. Для статистической обработки результатов применяли непараметрический U-критерий Манна−Уитни для независимых выборок с поправкой Бенджамини−Хохберга для множественного сравнения и критерий хи-квадрат Пирсона с поправкой Йейтса. Результаты . У пациентов с раком желудка и раком толстого кишечника вне зависимости от наличия тканевой эозинофилии установлена низкая экспрессия галектина-3 в опухолевой ткани и, напротив, высокий уровень экспрессии м-РНК гена галектина-3 в эозинофильных гранулоцитах периферической крови. У больных раком желудка и раком толстого кишечника с тканевой эозинофилией зарегистрирована низкая экспрессия опухолевыми клетками галектина-1 (в 64,0% случаев, χ 2 = 4,890, р = 0,029, и в 73,9% случаев, χ 2 = 5,981, p = 0,031 соответственно). Показана ассоциация гипоэкспрессии галектина-1 с эозинофильной инфильтрацией злокачественных опухолей желудка (φ = 0,307) и толстого кишечника (φ = 0,330). Заключение . Дефицит экспрессии галектинов 1 и 3 в опухолевой ткани при раке желудка и толстого кишечника, сопровождающийся тканевой эозинофилией, свидетельствует об отсутствии значимого влияния данных белков на процесс рекрутирования эозинофильных гранулоцитов в опухолевую ткань. Повышенный уровень экспрессии галектина-3 эозинофилами крови при злокачественных опухолях желудка и толстого кишечника не зависит от наличия эозинофильной инфильтрации опухолевой ткани.

The aim of the investigation was to determine the characteristics of the immune response regulation for pulmonary tuberculosis (TB) and to analyze the role of regulatory T cells in the immunopathogenesis of TB with eosinophilia in the blood, depending on the clinical form of the disease and sensitivity of Micobacterium tuberculosis to anti-TB drugs. Materials and methods. 157 patients who were initially diagnosed with infiltrative and disseminated TB were examined. The material of the study was venous blood and culture of mononuclear leukocytes isolated from venous blood. The content of interleukin (IL) 4, IL-10 and transforming factor beta (TGFβ) in culture suspensions of mononuclear leukocytes in vitro and IL-5 in the blood was determined by enzyme-linked immunosorbent assay (ELISA) test. The expression of surface molecules CD4, CD20, CD25 and intracellular transcription factor Foxp3 by lymphocytes of the blood was evaluated by flow cytometry. The obtained results were analyzed by statistical methods. Results. It is shown that excessive generation of regulatory T cells in patients with TB is associated with eosinophilia of the blood and imbalance of immune response regulation mechanisms. In TB with eosinophilia, an increase in the number of Foxp3-positive regulatory T cells in the blood is combined with in vitro hypersecretion of anti-inflammatory cytokines TGFβ, IL-10, IL-4 and an increase in the content of CD20+ B lymphocytes and IL-5 in the blood. These changes are most pronounced in the disseminated form of TB in combination with drug resistance. Conclusion. Characteristics of immunoregulation at TB with blood eosinophilia are associated with activation of immunosuppression mechanisms and polarization of immune response towards Th2-dependent pathway.

Цель. Оценить соотношение фракций классических, промежуточных, неклассических и переходных моноцитов во взаимосвязи с концентрацией интерлейкинов 4 и 6 в крови у больных ишемической кардиомиопатией. Методы исследования. Обследовано 18 больных ишемической кардиомиопатией (17 мужчин и 1 женщина) в возрасте 47-66 лет с недостаточностью кровообращения II-III функциональных классов по классификации сердечной недостаточности Нью-Йоркской Ассоциации Кардиологов. Группу контроля составили 14 практически здоровых доноров, сопоставимых по полу и возрасту с больными ишемической кардиомиопатией, не имеющих каких-либо заболеваний сердечно-сосудистой системы, а также других систем органов в стадии обострения. У больных ишемической кардиомиопатией в крови оценивали относительное содержание классических (CD14++CD16-), промежуточных (CD14++CD16+), неклассических (CD14+CD16+) и переходных (CD14+CD16-) моноцитов методом проточной цитометрии и концентрацию интерлейкинов 4 и 6 методом иммуноферментного анализа. Результаты. Показано, что численность неклассических моноцитов в крови у больных ишемической кардиомиопатией оказалась в 2 раза ниже нормы (5,05 % [4,08; 6,58] и 10,07 % [9,34; 13,84] соответственно, р < 0,01), как и концентрация интерлейкина-4 (0,02 пг/мл [0; 0,04] и 0,15 пг/мл [0,05; 0,65] соответственно, р < 0,05). Количество классических моноцитов в крови у пациентов проявляло тенденцию к снижению, а доля промежуточных моноцитов и концентрация интерлейкина-6, напротив, были несколько выше, чем у здоровых лиц, и проявляли взаимозависимость (r = 0,61; р < 0,05). Относительное содержание переходных моноцитов в крови оказалось сопоставимым с показателями у здоровых доноров. Выводы. Субпопуляционный состав моноцитов крови у больных ишемической кардиомиопатией характеризуется дефицитом фракции неклассических моноцитов, обладающих протективными свойствами в отношении эндотелия, и интерлейкина-4 в крови при некотором увеличении содержания интерлейкина-6 и численности промежуточных клеток, обладающих способностью к кооперации с Т-лимфоцитами, что предрасполагает к распространенному атероматозу мелких коронарных артерий и диффузному гипоксическому поражению миокарда при ишемической кардиомиопатии.

Subject – polymorphism of genes of estrogen-metabolising enzymes in patients with endometriosis. Objective – to perform analysis of relationship among allelic variants of genes of oestrogen-metabolising enzymes and development of external genital endometriosis (EGE), variants of its clinical progression and multiple-modality treatment efficacy. Methods. Laparoscopy was performed for 417 women with EGE (treatment group) and 112 women without EGE (control group). After laparoscopically verified diagnosis for 358 women from both groups (251 with EGE and 107 without EGE) there were regions of polymorphic genes of estrogen-metabolising enzymes A-4889G CYP1A1, С-734А CYP1A2, G-638А SULT1A1 and С-174T SULT1E1 identified in RFLP-analysis. Main results. It has been established that carriage of not only separate polymorphic genes of estrogen-metabolising enzymes CYP1A1 A-4889G (Allele G and Genotypes GG, АG) and CYP1A2 С-734А (Allele А and Genotypes СА, АА), but also their combinations predisposes to EGE development in women of reproductive age. Carriage of Genotype СA of polymorphism С-734А of CYP1A2 gene predisposes to development of pelvic pains during EGE. The most potent combination of polymorphisms of genes of estrogen-metabolising enzymes which predisposes to EGE development is CYP1A1АА/CYP1A2СА/SULT1A1GG/SULT1E1CC combination, while CYP1A1АА/CYP1A2СС/SULT1A1GА/SULT1E1CC combination predisposes to formation of I-II stages of EGE distribution, as well as CYP1A1АА/CYP1A2СА/SULT1A1GG/SULT1E1CC combination predisposes to development of endometriosis-associated infertility, while CYP1A1АG/CYP1A2CC/SULT1A1GA/SULT1E1CC combination predisposes to efficient treatment of infertility during EGE. Scope of application. The obtained results will allow to form risk groups of EGE development with the purpose of its primary prevention and efficient treatment of endometriosis-associated infertility. Conclusions. Polymorphic variants of estrogen-metabolising enzymes A-4889G CYP1A1, С-734А CYP1A2, G-638А SULT1A1 and С-174T SULT1E1 (separately or in combinations) predispose to EGE development, and are associated with its clinical evidence, distribution stage and treatment efficacy.

Absorption spectra of breath air for 108 healthy persons, 28 patients with pulmonary tuberculosis and 56 patients with many a diseases were recorded using laser photoacoustic technique. It was ascertained that, as the breath air analysis result, pulmonary tuberculosis can be diagnosed.

Subpopulation indices of peripheral blood and pleural exudate lymphocytes have been studied in the patients with various clinical variants of a tuberculous pleurisy. It has been shown that, in patients with both MBT-negative and MBT-positive variants of tubercular pleurisy, decreased quantity of CD3- and CD4-positive lymphocytes was observed, whereas an increase in numbers of CD8+ and CD16+ lymphocytes was more pronounced in the persons with MBT-negative pleurisy. In pleural exudates from the patients with tubercular pleurisy, the numbers of CD3+ lymphocytes proved to be significantly higher than their contents in peripheral blood. It may be assumed that lymphocytosis in pleural exudates results from migration of the cells from peripheral blood into pleural cavity. It is revealed that, during exudative pleurisy of tuberculosis origin, T-cells with CD4+ and CD8+ phenotype are more likely subject to migration into pleural cavity, accomplished by additional migration of CD16+ lymphocytes in MBT-positive cases of pleurisy.

With the help of up-to-date molecular-genetic methods the research of alleles and genotypes of polymorphous variants of genes XRCC1 (G280A, G399A, C194T) and XPD (A751C) distribution was accomplished at 200 females with genital endometriosis and 100 females without endometriosis from Tomsk and Tomsk region. At females with genital endometriosis statistically significant increase of frequency of «pathological» alleles of genes XRCC1 G280A and XPD A751C was registered. It was found that the risk of genital endometriosis is statistically associated with the presence in female genotype of TT genotype of C194T polymorphism of XRCC1 gene and CC genotype of XPD A751C gene.

The work analyzed subpopulation structure of peripheral blood T-regulatory cells (T-reg) and production of cytokines with immunosuppressor activity (IL-10, TGF-b)  in vitro  in patients with disseminated pulmonary tuberculosis, depending on the sensitivity of  Mycobacterium tuberculosis  to anti-tuberculosis drugs. It has been shown that Trn – natural T-regulatory lymphocytes (CD4 + CD25 + Foxр3 + ) and TGF-b cytokine, formed by them, play the leading role in the formation of immunosuppression under disseminated pulmonary tuberculosis. Besides, subpopulation imbalance of Treg-cells in patients with disseminated pulmonary tuberculosis, in case at multi-drug-resistance and drug-susceptible, is shown by the increased content of T-reg-cells with CD4 + CD25 + Foxр3 + phenotypein combination with the deficiency of CD4 + CD25 + Foxр3 –  T-reg lymphocytes in blood. The increase in the amount of CD4 + CD25 + Foxр3 +  T-reg-cells in blood of patients with disseminated multi-drug resistance pulmonary tuberculosis is associated with the increase in basal and BCG-induced production of TGF-b in vitro .

Clinical, molecular and genetic examination of 145 patients with the genital endometriosis, suffering infertility has been conducted. It is registered that distribution of allelic variants of cytokine genes among patients with endometriosis associated infertility is characterized by prevalence of genotypes of TT of a polymorphic site of C511T of a gene of IL1B and the CC polymorphism of G–174C of a gene of IL6. The positive association of endometriosis connected with infertility with allele in T and a genotype of a TT of polymorphism of C511T of a gene of IL1, and also with allele C and a genotype of the CC polymorphism of G–174C of a gene of IL6 is revealed.

The study included patients with ischemic heart disease with moderate (52 patients) and apparent (23 patients) hemolysis after coronary bypass surgery in cardiopulmonary bypass (CB). The concentration of free hemoglobin in blood plasma, mechanical resistance and sorption capacity of red cells as well as the content of TBA-active products, cholesterol and phospholipids in red cells and reticulocytes levels in blood were studied before and after operation. It was shown that among patients with apparent post-perfusion hemolysis (in contrast to the patients with a moderate hemolysis) the sorption capacity of red cells and amount of reticulocytes in blood are increased before operation; level of TBA-active products in erythrocytes is increasing after operation. Development of moderate hemolysis is associated with the decreased mechanical resistance of erythrocytes and increased cholesterol/phospholipid-ratio in membranes before operation. Thus, individually-specified apparent post-perfusion hemolysis is based on free-radical mechanism of erythrocytes damage and moderate hemoglobin level is referred to mechanical trauma of blood cells during CB.

The article presents the results of the research of CD3/CD28-induced production of interleukin-2 by blood lymphocytes in vitro as well as subpopulation composition of peripheral blood T-lymphocytes in patients with drug-sensitive and drug-resistant pulmonary tuberculosis. We detected the decrease in the total amount of CD3-positive cells and suppression of IL-2secretion during CD3/CD28-induction of lymphocytes, which was most expressed in a disseminated form of drug-resistant TB. We also demonstrated the reduction in the percentage value of CD3+CD28+IL-2+ and CD3+CD28+IL-2 cells in patients with pulmonary TB against the background of the increase in the percentage value of CD3+CD28 -IL-2 -. Besides, it was also shown that the detected changes are unidirectional, don't depend on a clinical form of TB and are maximally manifested in patients with a drug resistant variant of the TB process.

Until recent time it has seemed obvious that suppressive function in the immune system is provided by one subpopulation of Tlymphocytes-suppressors. At present it is usually considered that regulatory cells (T-reg) are key cells-suppressors of the immune response. There exist two main mechanisms of T-reg immunosuppression realization: direct (when there is direct contact between cells) and distant (cytokine-dependent). For suppression of the immune response Т-reg cells produce cytokines with suppression activity: TGF-β, IL-10, IFN-γ, IL-35. Meanwhile the increasing number of facts indicates that suppression of the immune response is a multi-component process. A considerable role in suppression of the immune response is assigned to the endocrine system. However, immunosuppression mechanisms under infection, neoplastic processes and the influence of xenobiotics on the organism are not completely clear.