[Alveolar rhabdomyosarcoma: novel surrogate markers associated with oncogenic translocation]. / Al'veolyarnaya rabdomiosarkoma: novye vspomogatel'nye surrogatnye markery onkogennykh translokatsii.

BACKGROUND: Anomalies of the FOXO1 gene in alveolar rhabdomyosarcoma are associated with a worse clinical prognosis, which determines the high value of studying the status of this gene when choosing a therapy strategy. The «gold standard¼ for determining FOXO1 gene rearrangements is currently the fluorescent in situ hybridization (FISH) technique. OBJECTIVE: Study of the relationship between canonical FOXO1 translocation and immunohistochemical expression of new surrogate markers in alveolar rhabdomyosarcoma to determine their predictive value. MATERIAL AND METHODS: 139 cases of rhabdomyosarcoma were retrospectively studied. The study used tissue matrix technology (TMA). On sections obtained from TMA blocks, the FISH technique was implemented using the locus-specific probe MetaSystems XL FOXO1 Break Apart (Metasystems, Germany). Immunohistochemical studies were performed on similar sections from TMA blocks with OLIG2 (Cell Marque Antibodies, clone 211F1.1) and MUC4 (Cell Marque Antibodies, clone 8G7) antibodies. RESULTS: The final expression analysis and statistical processing using a 2x2 contingency table and Fisher's exact test passed 111 cases (76 without FOXO1 rearrangement and 35 with rearrangement). The specificity of OLIG2 and MUC4 expression for FOXO1-rearranged alveolar rhabdomyosarcoma was 85.53% and 80.26%, respectively (p<0.01). CONCLUSION: The present study confirms the high predictive value of the expression of surrogate markers OLIG2 and MUC4 in determining the genetic status of alveolar rhabdomyosarcoma, which makes it possible to predict with high specificity the detection of the FOXO1 gene rearrangement.

[Ligands of the AMPA-subtype glutamate receptors: mechanisms of action and novel chemotypes]. / Ligandy glutamatnykh AMPA-retseptorov: mekhanizmy deistviia i novye khemotipy.

Ionotropic glutamate receptors of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype play a key role in synaptic plasticity representing one of the mechanisms for learning and memory formation. They can also serve as targets for the development of novel classes of pharmaceuticals for the treatment or substantive correction of many serious neurodegenerative and psychoneurological disorders. The search and studies of various types of AMPA receptor ligands attract considerable attention from academic organizations and pharmaceutical companies all over the world. This review mainly focuses on recent advances in this field. The architecture and operational mechanism of the receptor as well as its major binding sites and ligand types are considered. Special attention is paid to the studies of mechanisms of action and novel chemotypes of AMPA receptor agonists and competitive antagonists, positive and negative allosteric modulators, auxiliary protein-dependent allosteric modulators, and ion channel blockers.

Coarse-grained model of tropoelastin self-assembly into nascent fibrils.

Elastin is the dominant building block of elastic fibers that impart structural integrity and elasticity to a range of important tissues, including the lungs, blood vessels, and skin. The elastic fiber assembly process begins with a coacervation stage where tropoelastin monomers reversibly self-assemble into coacervate aggregates that consist of multiple molecules. In this paper, an atomistically based coarse-grained model of tropoelastin assembly is developed. Using the previously determined atomistic structure of tropoelastin, the precursor molecule to elastic fibers, as the basis for coarse-graining, the atomistic model is mapped to a MARTINI-based coarse-grained framework to account for chemical details of protein-protein interactions, coupled to an elastic network model to stabilize the structure. We find that self-assembly of monomers generates up to ∼70 â€‹nm of dense aggregates that are distinct at different temperatures, displaying high temperature sensitivity. Resulting assembled structures exhibit a combination of fibrillar and globular substructures within the bulk aggregates. The results suggest that the coalescence of tropoelastin assemblies into higher order structures may be reinforced in the initial stages of coacervation by directed assembly, supporting the experimentally observed presence of heterogeneous cross-linking. Self-assembly of tropoelastin is driven by interactions of specific hydrophobic domains and the reordering of water molecules in the system. Domain pair orientation analysis throughout the self-assembly process at different temperatures suggests coacervation is a driving force to orient domains for heterogeneous downstream cross-linking. The model provides a framework to characterize macromolecular self-assembly for elastin, and the formulation could easily be adapted to similar assembly systems.

[Treatment of chronic tonsillitis: prognostic criteria of efficacy].

An original method of wedge dehydration of biological fluids assessing the ability for separation of organic and mineral constituents was for the first time used in patients with different forms of chronic tonsillitis (CT). The method was used in 102 patients aged 8-68 years with chronic inflammation of the palatine tonsils out of exacerbation. A dehydrated drop of tonsillar lacuna discharge (TLD), facia, was studied morphologically under microscope at small magnification (x10--x50). Three types of TLD facia were identified in CT patients. These types characterized severity of the pathological process in the palatine tonsils. Changes of facia type in patients with different CT forms were compared. Basic regularities in the disease progress were determined. This enabled prognosis of a further course of CT in an individual patient and, therefore, planning treatment policy for each case.

The influence of pluronics and their conjugates with proteins on the rate of oxygen consumption by liver mitochondria and thymus lymphocytes.

The membranotropic properties of block co-polymers and their protein conjugates were studied by their effect on the rate of oxygen consumption by isolated liver mitochondria and on thymus-derived lymphocytes. The block co-polymers consisted of poly(ethylene oxide) (PoE) [poly(ethylene glycol)] and poly(propylene oxide) (PoP) to give either PoE-PoP or PoE-PoP-PoE. Both types inhibited uncoupled respiration of liver mitochondria in a medium containing glutamate and malate and also of lymphocytes. They also uncoupled respiration in the presence of succinate in K(+)-containing medium and of lymphocytes. A method is described for linking protein to the block polymers to form conjugates. Such conjugates were formed from alpha-chymotrypsin, BSA and cytochrome c, all of which produced similar effects on the respiration of the isolated mitochondria and lymphocytes. The data suggest that both the block co-polymers and their protein conjugates inhibit the NADH dehydrogenase complex and induce a K(+)-conductivity of the mitochondrial inner membrane; the surface activity of the conjugates allows them to pass through the plasma membrane and interact with the mitochondrial inner membrane.

The abnormal-shaped mitochondria in thymus lymphocytes treated with inhibitors of mitochondrial energetics.

The effects of uncouplers (DNP, FCCP), oligomycin, and rotenone on the energetics and mitochondrial ultrastructure in lymphocytes have been studied. We confirmed the previous observations done on Ehrlich ascites and cardiomyocyte culture cells that uncouplers and respiratory inhibitors cause the appearance of ringlike and dumbbell-like mitochondria. It is shown that this effect does not correlate with decrease in ATP concentration, changes in oxygen consumption, or condensation of the mitochondrial matrix. FCCP (2 microM) is more effective in the induction of abnormal-form mitochondria than 240 microM DNP, oligomycin, or rotenone. Combined treatment with DNP, oligomycin, and rotenone or with DNP and rotenone produces an effect as strong as 2 microns FCCP. DNP (240 microM) and FCCP (2 microM) have a similar effect on respiration and intracellular ATP, but only the latter induces condensation of the mitochondrial matrix.

[Effect of biologically active substances on lymphocyte energetics studied by using a simple luminometer-ATP meter]. / Izuchenie deistviia biologicheski aktivnykh veshchestv na énergetiku limfotsitov s pomoshch'iu prostogo liuminometra-ATF-metra.

A method of lymphocyte energetics investigation according to the ATP concentration in cell suspension has been described. A simple easily reproducible luminometer was applied for ATP measurement by luminescence of luciferin/luciferase system. The conditions of cell incubation were found when the changes in mitochondrial metabolic state reflected on ATP concentration. For all this rotenone (5 nM) decreases the ATP concentration heavily than inhibits the rate of oxygen consumption. Ecto-ATPases hydrolyze quickly the low concentrations of exogenous ATP. The examples given show the possibilities of this method for studying the effect of biologically active substances on cell energetics.

[Study of the host glycosyl component of the influenza virus using monoclonal antibodies]. / Izuchenie glikozil'nogo khoziaiskogo komponenta virusa grippa s ispol'zovaniem monoklonal'nykh antitel.

The crossreacting glycosylated host component (COHC) of influenza virus propagated in chick embryo has been studied using the monoclonal antibodies (MA). The specificity of MA to COHC has been demonstrated by different methods. Both MA of clones A9 and B7 react with the spatially overlapping antigenic sites of oligosaccharide chain, but only MA of B7 are active in hemagglutination inhibition test. The COHC is shown to be associated with both surface glycoprotein adsorbing on the surface of the virion. The study of the components from the allantonic fluid has shown the COHC to be associated with the sole embryo glycoprotein with the mol. mass around 150 kD and p1 9.0-9.5. Thus, the glycoprotein is possibly identical with the glycoprotein adsorbing on the virion surface. The content of COHC in various preparations of influenza virions has been also studied. The relative content of COHC is shown to increase during the purification of viral preparation. The COHC effect on the characteristics of vaccine preparations is discussed.