MONOCLONAL ANTIBODIES AGAINST MAN'S IMMUNOGLOBULINES

On base of the new strain of the mice myeloma cells and immunic lymphocytes of the SJL/J line mice the monoclonal antibodies (MCAB) against the types, basic isotypes and subisotypes lg of the man have been created. As a result of studying epitopic specifity and serological activity of MCAB and separation of the reagents answering to a number of the criteria the panel providing the quantitative determination of the free light chains, lg cappa- and lambda-types, basic isotypes and sub-isotypes and also investigation of the isotypical spectra in the antibodies directed against the infections agents, allergens and autoantigens has been formed. A possibility to apply MCAB in the test-systems for diagnosis of the infectious, allergic, autoimmunic diseases, malignant and benign gammapathies has been determined.Available from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

Effect of exercise on specific indicators of physical fitness and physical development of military student artilleryman

<p>The features of professional roles ground artillery ground forces in peacetime. Presented educational experiment on the application of special physical exercises to improve performance standards for the combat work of students. In the experiment were involved 52 students. Students also performed the test - bringing gun D - 30 from traveling to combat. Found that special training exercise significant influence on the performance of physical fitness of students. It is noted that the physical exercises for strength and power endurance develop gunners in precisely those physical qualities that are necessary for the performance of their direct duties. It is noted that the exercises for strength and strength endurance is necessary to give priority to the preparation of artillery of the Army.</p

Предварительная обработка информации с датчиков для контроля надежности мобильного робота

Головко Владимир Адамович, Климович А. Н., Гладыщук В. Б. Предварительная обработка информации датчиков для контроля надежности мобильного роботаThe neural system for orientation of the robot on unfamliar district in this article is considered. In basis it lays several of the neural networks, which are united in the uniform system The primal problem o f the system is, that with an inexact іnfonration from sensor devices should to supply correct control of the robot

A Principal Approach to the Detection of Radiation-Induced DNA Damage by Circular Dichroism Spectroscopy and Its Dosimetric Application

Using cholesteric liquid-crystalline dispersion (CLCD) of DNA, we demonstrate that the molecularly organized systems may be used both for qualitative assessment of the degree of radiation-induced DNA damage, as well as for detection of radiation doses in a very wide range. The doses up to 500 Gy do not cause any significant changes in optical signals of DNA in solution. However, when irradiated molecules are used to prepare the CLCD by addition of crowding polymer, a clear correlation of its optical signals with an absorbed dose is observed. For example, at a dose of 500 Gy, a maximum drop in the circular dichroism (CD) signal for DNA solution and for CLCD formed from preliminary irradiated molecules is &asymp;20% and &asymp;700%, respectively. This approach can also be used to expand the dosimetric capabilities of DNA CLCD. Compared to the case of irradiation of ready-made DNA CLCD, formation of the dispersed system from irradiated DNA allows to increase its sensitivity by more than 2 orders of magnitude. A similar decrease in the CD signal (&asymp;1.45-fold) is observed in these systems at the doses of 100 kGy and 200 Gy, respectively. This principal approach seems to be relevant for other biomolecules and molecularly organized systems

A Principal Approach to the Detection of Radiation-Induced DNA Damage by Circular Dichroism Spectroscopy and Its Dosimetric Application

Using cholesteric liquid-crystalline dispersion (CLCD) of DNA, we demonstrate that the molecularly organized systems may be used both for qualitative assessment of the degree of radiation-induced DNA damage, as well as for detection of radiation doses in a very wide range. The doses up to 500 Gy do not cause any significant changes in optical signals of DNA in solution. However, when irradiated molecules are used to prepare the CLCD by addition of crowding polymer, a clear correlation of its optical signals with an absorbed dose is observed. For example, at a dose of 500 Gy, a maximum drop in the circular dichroism (CD) signal for DNA solution and for CLCD formed from preliminary irradiated molecules is ≈20% and ≈700%, respectively. This approach can also be used to expand the dosimetric capabilities of DNA CLCD. Compared to the case of irradiation of ready-made DNA CLCD, formation of the dispersed system from irradiated DNA allows to increase its sensitivity by more than 2 orders of magnitude. A similar decrease in the CD signal (≈1.45-fold) is observed in these systems at the doses of 100 kGy and 200 Gy, respectively. This principal approach seems to be relevant for other biomolecules and molecularly organized systems

Chemical Dosimetry Using Bisbenzimidazoles: Solvent-Dependent Fluorescence Response of Hoechst 33258 to Radiation Exposure

Bisbenzimidazoles have a broad spectrum of potential applications: radioprotectors, drug delivery vectors, antiviral agents, etc. At the same time, they seem to be promising fluorescent probes for radiation measurements. Therefore, in the present work, a fluorescent response to X-ray irradiation of Hoechst 33258, one of the most widely known representatives of the bisbenzimidazole family, was studied for the first time. Irradiation of the dye was performed in aqueous and organic solutions (DMSO and glycerol), as well as in their mixtures. It is shown that the reaction of the dye to radiation exposure is very versatile and may be controlled by the solvent properties, which makes it possible to build relationships between the absorbed dose and a wide variety of parameters of its fluorescence signal. For example, irradiation may induce fluorescence quenching caused by the degradation of the dye, a change in the position of the fluorescence band maximum due to the modification of the dye molecules or to the radiation-induced changes in the properties of the medium, as well as a fluorescence flare-up mediated by the changes in pH

Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk

Objectives. Considering growing evidence of mucosal involvement in RA induction, this study investigated circulating free secretory component (SC) in patients with either recent-onset RA or with ACPA and musculoskeletal pain. Methods. Two prospective cohorts were studied: TIRA-2 comprising 452 recent-onset RA patients with 3 years of clinical and radiological follow-up, and TIRx patients (n = 104) with ACPA IgG and musculoskeletal pain followed for 290 weeks (median). Blood donors and three different chronic inflammatory diseases served as controls. Free SC was analysed by sandwich ELISA. Results. Serum levels of free SC were significantly higher in TIRA-2 patients compared with TIRx and all control groups (P &amp;lt; 0.01). Among TIRx patients who subsequently developed arthritis, free SC levels were higher compared with all control groups (P &amp;lt; 0.05) except ankylosing spondylitis (P = 0.74). In TIRA-2, patients with ACPA had higher baseline levels of free SC compared with ACPA negative patients (P &amp;lt; 0.001). Free SC status at baseline did not predict radiographic joint damage or disease activity over time. In TIRx, elevated free SC at baseline trendwise associated with arthritis development during follow-up (P = 0.066) but this disappeared when adjusting for confounders (P = 0.72). Cigarette smoking was associated with higher levels of free SC in both cohorts. Conclusion. Serum free SC levels are increased in recent-onset RA compared with other inflammatory diseases, and associate with ACPA and smoking. Free SC is elevated before arthritis development among ACPA positive patients with musculoskeletal pain, but does not predict arthritis development. These findings support mucosal engagement in RA development.Funding Agencies|Swedish Society of Medicine [SLS-682741]; Swedish Research CouncilSwedish Research Council [2011-02532]; Medical Research Council of Southeast Sweden [FORSS-37631]; King Gustaf Vs 80-year foundation [FAI-2017-0420]; Swedish Rheumatism association [R-754141]; Ostergotland County Council [LIO700501]</p

Probable Mechanisms of Doxorubicin Antitumor Activity Enhancement by Ginsenoside Rh2

Ginsenoside Rh2 increases the efficacy of doxorubicin (DOX) treatment in murine models of solid and ascites Ehrlich&rsquo;s adenocarcinoma. In a solid tumor model (treatment commencing 7 days after inoculation), DOX + Rh2 co-treatment was significantly more efficacious than DOX alone. If treatment was started 24 h after inoculation, the inhibition of tumor growth of a solid tumor for the DOX + Rh2 co-treatment group was complete. Furthermore, survival in the ascites model was dramatically higher for the DOX + Rh2 co-treatment group than for DOX alone. Mechanisms underlying the combined DOX and Rh2 effects were studied in primary Ehrlich&rsquo;s adenocarcinoma-derived cells and healthy mice&rsquo;s splenocytes. Despite the previously established Rh2 pro-oxidant activity, DOX + Rh2 co-treatment revealed no increase in ROS compared to DOX treatment alone. However, DOX + Rh2 treatment was more effective in suppressing Ehrlich adenocarcinoma cell adhesion than either treatment alone. We hypothesize that the benefits of DOX + Rh2 combination treatment are due to the suppression of tumor cell attachment/invasion that might be effective in preventing metastatic spread of tumor cells. Ginsenoside Rh2 was found to be a modest activator in a Neh2-luc reporter assay, suggesting that Rh2 can activate the Nrf2-driven antioxidant program. Rh2-induced direct activation of Nrf2 might provide additional benefits by minimizing DOX toxicity towards non-cancerous cells

Urokinase Receptor uPAR Downregulation in Neuroblastoma Leads to Dormancy, Chemoresistance and Metastasis

uPAR is a membrane receptor that binds extracellular protease urokinase, contributes to matrix remodeling and plays a crucial role in cellular adhesion, proliferation, survival, and migration. uPAR overexpression in tumor cells promotes mitogenesis, opening a prospective avenue for targeted therapy. However, uPAR targeting in cancer has potential risks. We have recently shown that uPAR downregulation in neuroblastoma promotes epithelial-mesenchymal transition (EMT), potentially associated with metastasis and chemoresistance. We used data mining to evaluate the role of uPAR expression in primary and relapsed human neuroblastomas. To model the decreased uPAR expression, we targeted uPAR using CRISPR/Cas9 and shRNA in neuroblastoma Neuro2a cells and evaluated their chemosensitivity in vitro as well as tumor growth and metastasis in vivo. We demonstrate that the initially high PLAUR expression predicts poor survival in human neuroblastoma. However, relapsed neuroblastomas have a significantly decreased PLAUR expression. uPAR targeting in neuroblastoma Neuro2a cells leads to p38 activation and an increased p21 expression (suggesting a dormant phenotype). The dormancy in neuroblastoma cells can be triggered by the disruption of uPAR-integrin interaction. uPAR-deficient cells are less sensitive to cisplatin and doxorubicin treatment and exhibit lower p53 activation. Finally, low uPAR-expressing Neuro2a cells formed smaller primary tumors, but more frequent metastasis in mice. To the best of our knowledge, this is the first study revealing the pathological role of dormant uPAR-deficient cancer cells having a chemoresistant and motile phenotype

Urokinase System in Pathogenesis of Pulmonary Fibrosis: A Hidden Threat of COVID-19

Pulmonary fibrosis is a common and threatening post-COVID-19 complication with poorly resolved molecular mechanisms and no established treatment. The plasminogen activator system, including urokinase (uPA) and urokinase receptor (uPAR), is involved in the pathogenesis of COVID-19 and contributes to the development of lung injury and post-COVID-19 pulmonary fibrosis, although their cellular and molecular underpinnings still remain obscure. The aim of the current study was to assess the role of uPA and uPAR in the pathogenesis of pulmonary fibrosis. We analyzed uPA and uPAR expression in human lung tissues from COVID-19 patients with pulmonary fibrosis using single-cell RNA-seq and immunohistochemistry. We modeled lung fibrosis in Plau-/- and Plaur-/- mice upon bleomycin instillation and explored the effect of uPAR downregulation in A549 and BEAS-2B lung epithelial cells. We found that uPAR expression drastically decreased in the epithelial airway basal cells and monocyte/macrophage cells, whereas uPA accumulation significantly increased in tissue samples of COVID-19 patients. Lung injury and fibrosis in Plaur-/- vs. WT mice upon bleomycin instillation revealed that uPAR deficiency resulted in pro-fibrogenic uPA accumulation, IL-6 and ACE2 upregulation in lung tissues and was associated with severe fibrosis, weight loss and poor survival. uPAR downregulation in A549 and BEAS-2B was linked to an increased N-cadherin expression, indicating the onset of epithelial–mesenchymal transition and potentially contributing to pulmonary fibrosis. Here for the first time, we demonstrate that plasminogen treatment reversed lung fibrosis in Plaur-/- mice: the intravenous injection of 1 mg of plasminogen on the 21st day of bleomycin-induced fibrosis resulted in a more than a two-fold decrease in the area of lung fibrosis as compared to non-treated mice as evaluated by the 42nd day. The expression and function of the plasminogen activator system are dysregulated upon COVID-19 infection, leading to excessive pulmonary fibrosis and worsening the prognosis. The potential of plasminogen as a life-saving treatment for non-resolving post-COVID-19 pulmonary fibrosis warrants further investigation