Clinical significance of sensitization to house dust mite allergens using flow cytometry-based basophil activation test

Respiratory allergy takes a significant place among allergic diseases. Similar clinical manifestations occur in sensitized patients in response to various airborne allergens. Accordingly, the allergen testing by means of in vivo and in vitro techniques is necessary to identify a causally significant allergen. The main laboratory assay to estimate sensitization to the airborne allergens is based on detection of specific immunoglobulin E (sIgE). However, clinical manifestations cannot be always confirmed by this test. The aim of this work was to evaluate the potential of basophil activation test (BAT) using flow cytometry, in order to confirm sensitization to house dust mite allergens. The BAT was carried out with allergens from Dermatofagoides in 34 volunteers, 130 patients were examined at the Russian Centre of Emergency and Radiation Medicine (33 people with household and 97 people with polysensitization), and 10 patients with allergy to house dust mites confirmed by skin testing. The sensitization was assessed using two laboratory kits (Allergenicity and BD FastImmune). The total IgE and sIgE to house dust mites, as well as concentrations of eosinophilic cationic protein, were determined. Specificity of the BAT with Allergenicity kit for the house dust mites was 94%. The sensitivity was 88% in the patients with household sensitization, thus being comparable with skin testing results available from the literature. An absolute correlation was found between positive results of skin testing and the BAT. In patients with household sensitization, sIgE levels > 0.35 UA/mL were detected in 39% of cases. A positive correlation was shown between the indices of basophil activation in response to testing allergens, and total immunoglobulin E and sIgE concentrations. High degree of correlation was found between the results of Dermatofagoides sensitization testing with both BAT kits. It was shown that the use of H1 histamine receptor blockers had no effect on BAT results. A decrease in sensitivity assay for airborne allergens was revealed upon therapy with glucocorticosteroids. Due to the proven clinical significance of the basophil activation test for diagnosing sensitization to inhaled allergens, one may require to supplement the range of approved assays in Russian Clinical Guidelines with BAT testing to prove sensitization in patients with allergic rhinitis and bronchial asthma, thus contributing to better diagnosis of causally significant allergens and, accordingly, administration of proper therapy

Monitoring of respiratory viral infections in Moscow during 2011–2022

Introduction. Respiratory viruses (RV) circulate throughout the world and in all seasons of the year. Long-term monitoring of the distribution of respiratory pathogens is necessary to analyze the relevance of diagnostic systems to current viral isolates, to assess the risks of infection and the need for vaccine development and use, as well as to investigate the interdependence of RV reproduction in mixed infections. Objective — to study the causative agents of acute respiratory viral infections (ARVI) in Moscow during 2011–2022 by reverse transcription with subsequent polymerase chain reaction with fluorescent hydrolysis probes detection in real-time (RT2-PCR). Materials and Methods. Nasopharyngeal swabs from 3908 patients with acute respiratory infections were examined by the RT2-PCR. Results. Monitoring of RV spread in Moscow showed cyclical changes in frequencies with three dominant species: influenza A virus (up to 31.3%), respiratory syncytial virus (up to 24.8%) and human rhinoviruses (up to 21.3%) in 2011–2020. The increase in the portion of unidentified clinical specimens from 1.2 to 28.5% in 2022 indicated incomplete accordance of diagnostic systems to modern RV isolates or the emergence of new species or strains of pathogens. Unidirectional changes in dynamics were registered for 5 out of 9 studied RVs with correlation coefficients of 0.43–0.79. High frequencies of mixed acute respiratory viral infections (up to 33.4%) along with unidentified samples do not allow us to accurately assess the risks of infection with various RV in Moscow, but prove the necessity of preventing infectious diseases with the most common RV. Conclusion. Analysis of the dynamics of RV frequencies in Moscow showed the preservation of the dominant species: influenza A virus, respiratory syncytial virus and human rhinoviruses. During the period of vaccination against COVID-19, the proportion of seasonal coronaviruses increased

LONG-LIVED BONE MARROW PLASMA CELLS DURING IMMUNE RESPONSE TO ALPHA (1→3) DEXTRAN

Production kinetics and some functional properties of long-lived marrow plasma cells were studied in mice immunized with T-independent type 2 antigens. Alpha (1→3) dextran was used as an antigen for immunization. The mice were immunized by dextran, and the numbers of IgM antibody producing cells were determined by ELISPOT method. The cell phenotype was determined by cytofluorimetric technique. In the area of normal bone marrow lymphocytes ~4% of T and ~85% of B cells were detected. About 35% of the cells expressed a plasmocyte marker (CD138); 3% were CD138+IgM+, and about 6% of the lymphocytes were double-positive for CD138+IgA+. Among spleen lymphocytes, 50% of T and 47% of B cells were detected. About 1.5% lymphocytes were CD138+, and 0.5% were positive for CD138 and IgM. Time kinetics of antibody-producing cells in bone marrow and spleen was different. In spleen populations, the peak amounts of antibody-secreting cells have been shown on the day 4; the process abated by the day 28. Vice versa, the numbers of the antibody-producing cells in bone marrow started to increase on the day 4. The process reached its maximum on day 14, and after 28th day became stationary. The in vitro experiments have shown that supplementation of bone marrow cells from immune mice with dextran did not influence their functional activity. It was previously shown for cells responding to T-dependent antigens only. A specific marker for the long-lived plasma cells is still unknown. However, these cells possess a common CD138 marker specific for all plasma cells. A method for isolation of bone marrow CD138+ cells was developed. The CD138+ cells were of 87-97% purity, being enriched in long-lived bone marrow cells, and produced monospecific antibodies

Full Multiple Scattering Analysis of XANES at the Cd L 3- and O K- Edges in CdO Films Combined with a Soft-X-Ray Emission Investigation

X-ray absorption near edge structure (XANES) at the cadmium L3 and oxygen K edges for CdO thin films grown by pulsed laser deposition method, is interpreted within the real-space multiple scattering formalism, FEFF code. The features in the experimental spectra are well reproduced by calculations for a cluster of about six and ten coordination shells around the absorber for L3 edge of Cd and K edge of O, respectively. The calculated projected electronic density of states is found to be in good agreement with unoccupied electronic states in experimental data and allows to conclude that the orbital character of the lowest energy of the conductive band is Cd 5s-O 2p[sigma]*. The charge transfer has been quantified and not purely ionic bonding has been found. Combined XANES and resonant inelastic x-ray scattering measurements allow us to determine the direct and indirect band gap of investigated CdO films to be ~2.4 eV and ~0.9 eV, respectively

The use of {99m}Tc-Al[2]O[3] for detection of sentinel lymph nodes in cervical cancer patients

The purpose of the study was to evaluate the feasibility of using {99m}Tc-Al[2]O[3]- based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (TlaNxMx- T[2]bNxMx) treated at the Tomsk Cancer Research Institute. At 18 hours before surgery, 80 MBq of the {99m}Tc-Al[2]O[3] were injected peritumorally, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3(the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac, obturator, presacral and retrosacral regions (they amounted to 14%, respectively),and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image

Comparison between optical and electrical data on hole concentration in zinc-doped p-GaAs

The optical and electrical properties of zinc-doped Cz p-GaAs have been studied. Reflection spectra of ten p-GaAs specimens have been taken in the mid-IR region. Van der Pau galvanomagnetic, electrical resistivity and Hall coefficient measurements have been carried out for the same specimens (all the measurements were carried out at room temperature). The reflection spectra have been processed using the Kramers–Kronig relations, spectral dependences of the real and imaginary parts of the complex dielectric permeability have been calculated and loss function curves have been plotted. The loss function maximum position has been used to calculate the characteristic wavenumber corresponding to the high-frequency plasmon-phonon mode frequency. Theoretical calculations have been conducted and a calibration curve has been built up for determining heavy hole concentration in p-GaAs at T = 295 K based on known characteristic wavenumber. Further matching of the optical and Hall data has been used for determining the light to heavy hole mobility ratio. This ratio proves to be in the 1.9–2.8 range which is far lower as compared with theoretical predictions in the assumption of the same scattering mechanism for light and heavy holes (at optical phonons). It has been hypothesized that the scattering mechanisms for light and heavy holes differ

БЕЛКИ КЛЕТОЧНОЙ ПОДВИЖНОСТИ В КАРЦИНОМЕ ЭНДОМЕТРИЯ И ЭНДОМЕТРИАЛЬНОЙ ГИПЕРПЛАЗИИ: СВЯЗЬ С РИСКОМ РАЗВИТИЯ РАКА

Introduction. Proteins associated with cellular motility are known to play an important role in invasion and metastasis of cancer, however there is no evidence of their association with the development of malignant tumors including endometrial cancer (EC).The aim of the present study was to investigate the levels of actin-binding proteins, p45-Ser-β-catenin, and calpain activity in endometrial hyperplasia and in EC.Material and Methods. Total calpain activity, p45-Ser β-catenin, Arp3, gelsolin, cofillin and thymosin β-4 levels were evaluated in 43 postmenopausal patients with stage I–II endometrioid EC and 40 endometrial hyperplasia patients. Flow cytometry and Western blotting were used for expression determination of p45 Ser β-catenin and actin-biding proteins. Total calpain activity was estimated by fluorimetric method.Results. Levels of cofilin-1, thymosin β-4 and calpain activity were higher in cancer tissues than in endometrial hyperplasia. Cofilin-1 and thymosin β-4 levels were associated with the depth of myometrial invasion. The thymosin β-4 expression was correlated with the presence of tumor cervical invasion. Revealed correlations between the actin-binding proteins, p45-Ser-β-catenin and total calpain activity in endometrial hyperplasia tissue, but not in the tissue of cancer, is evidence of the involvement of these proteases in regulation of cell migration in endometrial hyperplasia. Levels of thymosin β-4, cofilin and total calpain activity are independent cancer risk factors in patients with endometrial hyperplasia.Conclusion. The level of actin-binding proteins as well as the total calpain activity were enhanced in endometrium carcinoma tissues compared to endometrial hyperplasia. The levels of thymosinβ-4, cofilin and total calpain activity in endometrial hyperplasia tissues are associated with a hyperplasia transition to cancer and may be considered as predictive biomarkers. Введение. Известно, что белки, связанные с клеточной подвижностью, играют важную роль в инвазии и метастазировании злокачественных опухолей, тем не менее нет данных об их связи с развитием новообразований, в том числе рака эндометрия (РЭ).Целью исследования было изучение уровня актин-связывающих белков, p45-Ser-β-катенина и активности кальпаинов при гиперплазии эндометрия и при РЭ.Материал и методы. Общая активность кальпаинов, уровни p45-Ser β-катенина, Arp3, гельзолина, кофиллина и тимозина β-4 были оценены у 43 больных раком эндометрия I–II стадии в постменопаузе и у 40 пациенток с гиперплазией эндометрия. Проточную цитометрию и вестерн-блоттинг использовали для определения экспрессии p45 Ser β-катенина и актин-связывающих белков. Общая активность кальпаинов оценивалась флуориметрическим методом.Результаты. Уровни кофилина-1, тимозина β-4 и активность кальпаинов были выше в тканях злокачественных опухолей, чем при гиперплазии эндометрия. Уровни кофилина-1 и тимозина β-4 были связаны с глубиной инвазии рака эндометрия в миометрий. Содержание тимозина β-4 коррелировало с наличием инвазии опухоли в шейку матки. Выявленные корреляции между актин-связывающими белками, р45-Ser-β-катенином и общей активностью кальпаинов в ткани гиперплазии эндометрия, но не в ткани рака свидетельствуют об участии этих протеаз в регуляции клеточной миграции при гиперплазии эндометрия. Уровни тимозина-4, кофилина и общая активность кальпаинов являются независимыми факторами риска развития рака у пациентов с гиперплазией эндометрия.Заключение. Уровень актин-связывающих белков, а также общая активность кальпаинов были повышены в тканях карциномы эндометрия по сравнению с гиперплазией эндометрия. Уровни тимозина-4, кофилина и общая активность кальпаинов в тканях гиперплазии эндометрия могут быть независимыми факторами риска развития рака.

РЕЦЕПТОРЫ РОСТОВЫХ ФАКТОРОВ И АДИПОКИНОВ В ПАТОГЕНЕЗЕ И ПРОГНОЗЕ РАКА ЭНДОМЕТРИЯ НА ФОНЕ МЕТАБОЛИЧЕСКОГО СИНДРОМА

The role of growth factor receptors (insulin-like growth factor and transforming growth factor-beta) and adipokine receptors (leptin and adiponectin) in pathogenesis of endometrial cancer under conditions of metabolic syndrome is discussed. Cyclooxygenase-2 is an effector of signaling pathways activated by growth factors and cytokines. The detailed study of the mechanisms involving these proteins in pathogenesis of endometrial cancer in patients with metabolic syndrome and search for new biological prognostic markers appear to be promising.В обзоре обсуждается роль рецепторов ростовых факторов (инсулиноподобного фактора роста и трансформирующего фактора роста beta) и адипокинов (лептина и адипонектина) в патогенезе рака эндометрия на фоне метаболического синдрома. Нижележащим эффектором активируемых ростовыми факторами и данными цитокинами сигнальных путей является циклооксигеназа-2. Представляется весьма перспективным изучение более детальных механизмов вовлеченности этих протеинов в патогенез рака эндометрия на фоне метаболического синдрома с поиском новых биологических прогностических биомаркеров у этой категории больных

Сравнение результатов оптических и электрофизических измерений концентрации дырок в образцах p-GaAs, легированных цинком

Optical and electrophysical properties of Cz-grown zinc doped p-GaAs samples have been investigated. Middle-infrared reflection spectra of ten p-GaAs samples have been obtained. Galvanomagnetic Van der Pau measurements have been made on these samples also, and the values of resistivity and Hall coefficient have been calculated. All experiments have been carried out at room temperature.Reflection spectra have been processed by Kramers–Kronig relations. The spectral dependences of real and imaginary parts of complex dielectric permittivity have been obtained and loss function has been calculated. The value of characteristic wave number corresponding to high-frequency plasmon-phonon mode has been determined by loss function maximum position.The theoretical calculations have been made, and the dependence has been obtained which gave the possibility to determine heavy hole concentration value at T = 295K by the value of characteristic wave number. Then by comparison of optical and Hall data the values of light hole mobility to heavy hole mobility ratio have been determined. This mobility ratio has been shown to be equal to (1.9–2.8) which is considerably less, than predicted theoretical value based on assumption that both light and heavy holes are scattered by optical phonons. It has been suggested that scattering mechanisms of light and heavy holes might be quite different.Исследованы оптические и электрофизические свойства образцов p-GaAs, выращенных методом Чохральского и легированных цинком. Измерены спектры отражения десяти образцов p-GaAs в средней ИК-области. На этих же образцах проведены гальваномагнитные измерения по методу Ван-дер-Пау и определены значения удельного электрического сопротивления и коэффициента Холла (все измерения проведены при комнатной температуре). Спектры отражения обработаны с использованием соотношений Крамерса—Кронига; вычислены спектральные зависимости действительной и мнимой частей комплексной диэлектрической проницаемости и построены функции потерь. По положению максимума функции потерь определено значение характеристического волнового числа, отвечающего частоте высокочастотной плазмон-фононной моды. Проведены теоретические расчеты и построена градуировочная зависимость, позволяющая по известному значению характеристического волнового числа определить концентрацию тяжелых дырок в p-GaAs при Т = 295 К. Далее путем сопоставления оптических и холловских данных определены значения отношения подвижностей легких и тяжелых дырок. Показано, что оно лежит в пределах 1,9—2,8, что значительно меньше значений, предсказываемых теорией в предположении, что и легкие, и тяжелые дырки рассеиваются одинаково (на оптических фононах). Высказано предположение, что механизмы рассеяния легких и тяжелых дырок различны