In Vivo Effects of Human Bone Marrow Mesenchymal Stromal Cells on the Development of Experimental B16 Melanoma in Mice.

Experiments on F1(CBA×C57BL/6) mice with experimental metastatic melanoma B16 F10 showed that single intravenous injection of xenogeneic bone marrow mesenchymal stromal cells (BM-MSC) in a dose of 106 cells/mouse significantly increased 100-day survival rate of tumor-bearing animals. In contrast, administration of BM-MSC in a dose of 2×106 cells/ mouse reduced survival rates in comparison with the biocontrol (injection of B16 cells alone, 5×105 cells/mouse). This phenomenon can be related to in vivo participation of BM-MSC in reprogramming of resident tissue macrophages, including tumor microenvironment, towards pro- (M1) or anti-inflammatory (M2) phenotype. This is indirectly confirmed by the data on switching from activation to inhibition of ROS-producing activity of blood mononuclears and peritoneal macrophages in tumor-bearing mice in the test of luminol-dependent zymosaninduced chemiluminescence.

Performance of photoelectron spin polarimeters with continuous and pulsed sources: from storage rings to free electron lasers.

In this work the experimental uncertainties concerning electron spin polarization (SP) under various realistic measurement conditions are theoretically derived. The accuracy of the evaluation of the SP of the photoelectron current is analysed as a function of the detector parameters and specifications, as well as of the characteristics of the photoexcitation sources. In particular, the different behaviour of single counter or twin counter detectors when the intensity fluctuations of the source are considered have been addressed, leading to a new definition of the SP detector performance. The widely used parameter called the figure of merit is shown to be inadequate for describing the efficiency of SP polarimeters, especially when they are operated with time-structured excitation sources such as free-electron lasers. Numerical simulations have been performed and yield strong implications in the choice of the detecting instruments in spin-polarization experiments, that are constrained in a limited measurement time. Our results are therefore applied to the characteristics of a wide set of state-of-the-art spectroscopy facilities all over the world, and an efficiency diagram for SP experiments is derived. These results also define new mathematical instruments for handling the correct statistics of SP measurements in the presence of source intensity fluctuations.

Syngeneic and Xenogeneic Transplantations of Mesenchymal Stromal Cells Modify the Production of Reactive Oxygen Species by Blood Mononuclears of Mice.

In vivo modifying effects of bone marrow mesenchymal stromal cells of humans and laboratory mice on ROS production by mouse blood mononuclears are studied by luminol-dependent zymosan-induced chemiluminescence after syngeneic and xenogeneic transplantation into systemic blood flow. The chemiluminescent activity of mouse blood mononuclears has increased early (1 day) after syngeneic (mouse mesenchymal stromal cells) and xenogeneic (human mesenchymal stromal cells) transplantation. Later, 7-21 days after syngeneic and xenogeneic transplantation, the chemiluminescent activity of mouse mononuclears is suppressed. The probable mechanisms of involvement of the transplanted mesenchymal stromal cells in reprogramming of the blood mononuclear phagocytes from proinflammatory (M1) to anti-inflammatory (M2) phenotype under conditions of their in vivo interactions are discussed; a frequent manifestation of this reprogramming is transition of the phase of activation into inhibition of ROS-producing activity of macrophages.

Modifying Effect of Autotransfusion of Mesenchymal Stromal Cells on the Production of Reactive Oxygen Species and Cytokines by Mononuclear Cells in Patients with Chronic Heart Failure.

We studied in vivo modifying effect of autotransfusion of human bone marrow mesenchymal stromal cells on ROS generation and production of cytokines (TNFα,TNFß, IL-1α, IL-10, IFNγ, and GM-CSF) and PGE2 by mononuclear cells of patients (N=21) with chronic heart failure. These parameters were evaluated prior to (control) and after (immediately and on day 14) intravenous administration of stromal cells in doses of 100-200×106. Immediately after autotransfusion, significant increase of in vitro zymosan-induced chemiluminescence of blood mononuclear cells from 10 patients was observed. At later terms after autotransfusion (day 14), inhibition of chemiluminescent activity of blood mononuclear cells was revealed in 50% patients. We discuss possible mechanisms of involvement of transplanted autologous bone marrow mesenchymal stromal cells in reprogramming of blood mononuclear phagocytes from the pro- to anti-inflammatory phenotype under conditions of their in vivo interaction manifesting in transition from activation to inhibition of ROS-producing activity of macrophages and significant suppression of in vitro LPS-induced production of TNFα and GM-CSF by blood mononuclears against the background of significantly elevated TNFß, IL-10, and IL-1α concentrations.

Positron re-emission, reflection, and diffraction from W(100) surface at very low energies.

The energy distributions of scattered and re-emitted low-energy positrons from a W(100) surface were measured as a function of incident positron energy from 0 to 25 eV. Given that tungsten has a negative work function of about -3 eV for positrons, one can envisage three scenarios of very low-energy positron scattering from such a surface. First, a positron approaching the sample surface with energy say 1 eV above the vacuum level will see a potential barrier of about 2 eV height and will be reflected back to the vacuum. Second, when the energy of incident positrons increases up to the top of the surface potential barrier (positron work function), they start entering the solid and, therefore, the reflectivity of positrons from the surface reduces. Positrons entering the solid are thermalised within few picoseconds and have a chance to escape back to the vacuum with kinetic energy about 3 eV above the vacuum level undergoing so-calledre-emission. Third, coherent scattering of low-energy positrons may occur on the crystal surface, i.e. positron diffraction. All the three scenarios of low-energy positrons scattering are studied here experimentally. Measured spectra are very sensitive to the surface conditions of the sample: they change dramatically after surface oxidation or thin film deposition.

Ecology of influenza virus in wild bird populations in Central Asia.

The study provides the results of avian influenza virus surveillance in Central Asia during 2003-2009. We have analyzed 2604 samples from wild birds. These samples were collected in Kazakhstan (279), Mongolia (650), and Russia (1675). Isolated viruses from samples collected in Mongolia (13 isolates) and in Russia (4 isolates) were described. Virological analysis has shown that six isolates belong to the H3N6 subtype and five isolates belong to the H4N6 subtype. Two H1N1 influenza viruses, one H10N7 virus, two H3N8 viruses, and an H13N8 virus that is new for Central Asia have been also isolated. Samples were taken from birds of six orders, including several species preferring water and semiaquatic biotopes, one species preferring dry plain regions, and one more species that can inhabit both dry and water biotopes.

Ultrafast compact classical Mott polarimeter.

An ultrafast compact classical Mott detector is described. The efficiency of the polarimeter is epsilon = 6 x 10(-4) and the maximum counting rate approximately 2000 kcps. The Mott polarimeter employs photomultipliers with scintillators as electron energy sensitive detectors with low dark noise. The photomultipliers and scintillators are placed in vacuum. With this choice of technology, it will be possible to build a classical Mott detector with a bulk size of cubic decimeter in the future.

Design and optimization of a modular setup for measurements of three-dimensional spin polarization with ultrafast pulsed sources.

ULTRASPIN is an apparatus devoted to the measurement of the spin polarization (SP) of electrons ejected from solid surfaces in a UHV environment. It is designed to exploit ultrafast light sources (free electron laser or laser high harmonic generation) and to perform (photo)electron spin analysis by an arrangement of Mott scattering polarimeters that measure the full SP vector. The system consists of two interconnected UHV vessels: one for surface science sample cleaning treatments, e-beam deposition of ultrathin films, and low energy electron diffraction/AES characterization. The sample environment in the polarimeter allows for cryogenic cooling and in-operando application of electric and magnetic fields. The photoelectrons are collected by an electrostatic accelerator and transport lens that form a periaxial beam that is subsequently directed by a Y-shaped electrostatic deflector to either one of the two orthogonal Mott polarimeters. The apparatus has been designed to operate in the extreme conditions of ultraintense single-X-ray pulses as originated by free electron lasers (up to 1 kHz), but it allows also for the single electron counting mode suitable when using statistical sources such as synchrotron radiation, cw-laser, or e-gun beams (up to 150 kcps).

[Multiplicity of affinity modification of RNAse during its alkylation with a reactive analog of 5-deoxyribonucleotide]. / Mnozhestvennost' affinnoi modifikatsii RNKazy pri alkilirovanii ee reaktsionnosposobnym analogom 5'-dezoksiribonukleotida.

The interaction of pancreatic RNase with 5'-deoxyribodinucleotide alkylating derivative, 4-(N-2-chloroethyl-N-methylamino)benzylamide of d(pTpA) d[(ClRCH2NH)pTpA], was studied. The unreactive oxyanalogue d[(HORCH2NH)pTpA] was shown to act as competitive inhibitor of cCMP hydrolysis by RNase. d[(ClRCH2NH)pTpA] irreversibly inactivated RNase. A protective effect was exerted by d(pTpA) and d[(HORCH2NH)pTpA]. The modification, although having an affinity character, was not accompanied by total inactivation of the enzyme. It was supposed that covalent bonding between the reagent and enzyme induced the dinucleotide displacement from the recognition site. The formation of four RNase monolabeled forms retaining the activity in the hydrolysis of cCMP and poly(U) was demonstrated.

[Synthesis and immunogenic properties of peptides--fragments of the immunodominant regions of the VP1 protein of the Asia-1 type of foot- and-mouth disease virus]. / Sintez i immunogennye svoistva peptidov--fragmentov immunodominantnykh raionov belka VP1 virusa iashchura tipa Aziia-1.

Potential immunodominant epitopes were predicted on the basis of a theoretical analysis of the antigenic structure of the VP1 protein of the type Asia-1 foot-and-mouth disease virus. Peptides corresponding to the 140-153, 136-153, 132-153, 143-157, 137-157, and 193-208 fragments of the VP1 protein sequence were synthesized by the solid phase method, and the immunogenic properties of the peptides were studied on guinea pigs. The shortest peptide exhibiting the protective effect was found to correspond to the, 140-153 fragment of the VP1 sequence. The Plm-(Gly)3-(140-153)-(Gly)2-Lys(Plm)-Leu and [Ac-(140-153)-(Gly)3]8-(Lys)7-Gly synthetic constructions in combination with adjuvants provided up to 80% protection of immunized animals against infection with the foot-and-mouth disease virus.

[Protection of naturally susceptible animals against foot-and-mouth disease with a peptide, synthesized on a lysine matrix]. / Zashchita estestvenno-vospriimchivykh zhivotnykh ot iashchura peptidom, sintezirovannym na lizinovoi matritse.

A peptide VP1-(142-158)-MAP (Multiple antigen peptide system) consisting of two parts: a lysine matrix made up of three levels of lysine residues coupled with each other and amino acid sequence 142-158 of VP1 of FMD virus strain A(22)550--has been synthesized. Guinea-pigs inoculated with 20 mkg of the peptide incorporated with Freund's complete adjuvant were protected against challenge with 500 ID50 of homologous FMD virus. Sheep were immunized with a single inoculation of the peptide in a dose of 1.0 mg. Cattle inoculated twice with 1.5 mg of the peptide with incomplete adjuvant on the basis of synthetic oil developed high virus-specific antibody titres both after the first (5.3-7.6 log2 ND50/0.1 ml) and the second inoculation (10.2-11.0 log2 ND50/0.1 ml). The peptide-immunized animals were resistant to challenge with homologous virulent virus in a dose of 10(4) ID50. The immunogenic and protective capacities of the peptide VP1-(142-158)-MAP were shown to be greater as compared with those of its linear analogue-peptide VP1-(141-160).

[Protection from foot-and-mouth disease virus in naturally-susceptible animals by a linear polymer of a synthetic peptide]. / Zashchita ot iashchura estestvenno-vospriimchivykh zhivotnykh lineinym polimerom sinteticheskogo peptida.

Linear polymer of a peptide corresponding to the fragment 142-155 of the foot-and-mouth disease virus A22(550) protein (VP1) was synthesized. Whereas the monomeric peptide was only slightly immunogenic, the polymer induced virus-neutralizing antibodies in rabbits and protected 100% guinea pigs. Sheep vaccinated once and cattle vaccinated twice were stable against infection with the homologous virulent foot-and-mouth disease virus.

[The use of synthetic peptides for detection of antibodies against foot-and-mouth disease virus in the blood from convalescent animals]. / Ispol'zovanie sinteticheskikh peptidov dlia vyiavleniia antitel k virusu iashchura v syvorotkakh krovi perebolevshikh zhivotnykh.

Peptides were synthesized, which, according to theoretical analysis of the antigenic structure of protein VP1 of foot-and-mouth disease (FMD) virus types A, 0, and Asia 1, corresponded to potential immunodominant protein sites. Activities of the peptides were studied by solid-phase indirect radioimmunoassay on polyethylene film with purified immunoglobulins against intact FMD virus. Virtually no cross reactions were observed. Blood sera of cattle convalescent after FMD were tested with the FMD virus and peptides containing VP1 fragments 141-160 (A22 No. 550), 140-160 (O1 No. 194), and 140-153 (Asia 1 No. 48). The specificity of interactions between the sera and peptides and the virus was uniform, this permitting the identification of the virus type which caused the disease.

[Changes in the activity level of tumor necrosis factor in the blood serum after irradiation and a combined radiation-thermal lesion]. / Izmeneniia urovnia aktivnosti tumornekroticheskogo faktora v syvorotke krovi posle oblucheniia i kombinirovannogo radiatsionno-termicheskogo porazheniia.

To elucidate the role of the tumor-necrosis factor (TNF) in the pathogenesis of an additional aggravating effect of a thermal burn on the development and outcome of a radiation disease, the changes in the activity of cytokine in the blood serum of irradiated mice were studied. The mice were exposed to radiation at a dose of 7 Gy and subjected to a combined radiation-thermal injury (CRTI). The level of endogenous and LPS-induced TNF was determined in a cytotoxic test on a mice fibroblast L-929 culture. It was found that the activity of TNF in the blood circulation of mice subjected to irradiation and CRTI did not increase much. As a result of an intravenous injection of a provoking stimulus (LPS from E. coli), an increase in the TNF activity in the early period after irradiation was higher than with CRTI. There is no correlation between the increase in the death rate for mice with a combined injury and the changes in the LPS-induced TNF activity.

[Study of the possibility of hyperparathyroidism development in rats exposed to internal irradiation by iodine radioisotope]. / Issledovanie vozmozhnosti razvitiia giperparatireoza u krys, perenesshikh vnutrennee obluchenie ot radioizotopa ioda.

The possibility of hyperparathyroidism development secondary to earlier internal irradiation with radioactive iodine was studied experimentally in Wistar rats. This report describes the parathyroid morphology and biochemical findings for animals irradiated with 131I at the doses of 4.5, 40, or 80 Gy. The interval between the radiation exposure of two-month-old rats and their examination for thyroid and parathyroid pathology was 14 months. Neither hypercalcemia nor hypophosphatemia was found. Moreover, the level of calcium in serum slightly decreased following 40 and 80 Gy irradiation. The increased incidence of parathyroid fibrosis and hypofunctional structure transformation were revealed.

[Decrease in the concentration of leukocyte acetylation coenzyme associated with vitamin precursor deficiency in patients with alcoholic delirium]. / Umen'shenie soderzhaniia kofermenta atsetilirovaniia leikotsitov v sviazi s nedostatochnost'iu vitaminnogo predshestvennika u bol'nykh alkogol'nym deliriem.

Sixty-three patients with the typical variant of delirium tremens were examined. The results showed a marked reduction (by 8.7 times) in levels of coenzyme A (CoA) in leukocytes, which was indicative of deficiency of the coenzymic form of pantothenic acid (PA). Changes in CoA concentrations in leukocytes observed at the height of psychosis in patients with alcoholic delirium as compared to other parameters of PA metabolism have great significance for the assessment of vitamin metabolism. PA deficiency was more expressed in cases of long-standing and massive alcoholization which induces an earlier development of psychosis. CoA levels in leukocytes may be used as a parameter of detoxication processes in patients with delirium tremens. The data obtained are considered as indication for administration of PA drugs in combined detoxifying therapy of alcoholic psychoses.

[Treatment of alcoholism by affective counterattribution]. / Lechenie alkogolizma s pomoshch'iu affektivnoi kontratributsii.

A new narcopsychotherapeutic technique termed "affective counterattribution" (ACA) is offered to treat alcohol addiction. The use of ACA increased the effectiveness of alcoholism treatment that was ensured by association of strong pharmacogenic negative emotional experience coupled with bright hallucinatory images to notions of alcohol and alcohol-related stimuli. Alcoholic attitude was destroyed and the patients' pathological personality traits were corrected.

[Study of toxin from burned skin]. / Izuchenie toksina obozhzhennoi kozhi

By means of gel filtration, ion exchange chromatography and polyacrylamide gel disc electrophoresis the toxin from burned rat skin was characterized as a protein with molecular weight 300,000 containing 3-5 subunits. Dissociation of the initial complex was caused by ion exchange chromatography, electrophoresis in fine pore gels and under storage. The dissociation was shown to become irreversible in presence of detergents.

[Study of gamma-aminobutyric acid (GABA) concentration in blood plasma of alcoholism patients]. / Issledovanie kontsentratsii gamma-aminomaslianoi kisloty (GAMK) v plazme bol'nykh alkogolizmom.

Concentration of gamma-aminobutyric acid (GABA) was estimated in the plasma of 104 patients with alcoholism during 2 month treatment course in addiction hospital and in 29 healthy volunteers. Highly distinct differences in content of GABA were detected in the plasma of the volunteers and patients with alcoholism, which remained within 60 days of alcohol withdrawal.

[Effect of adrenalectomy and anti-adrenergic preparations on the development of hyperenzymic and biochemical changes in the blood in burns]. / Vliianie adrenaléktomii i antiadrenergicheskikh preparatov na razvitie giperfermentamii i biokhimicheskie izmeneniia v krovi pri termicheskom ozhoge.

Activities of alpha-hydroxybutyrate- and lactate dehydrogenases (HBDH, LDH), aspartate- and alanine aminotransferases (AST, ALT), alkaline phosphatase, alpha-amylase as well as content of total proteins, glucose, cholesterol, triglycerides and Ca2+ were estimated sprectrophotometrically in blood serum of rat males within 2 hrs after thermic burns of the III degree involving 15% the body surface. The burns caused about 2-fold increase in activities of LDH, HBDH and AST and in content of triglycerides in blood serum but did not affect the other biochemical patterns. Adrenalectomy, carried out within 3 days before the burns, accelerated and pseudoadrenalectomy decreased the early postburn enzymatic activation. Preadministration of reserpine, phentolamine and obsidane (propranolol) decreased distinctly the hyperenzymic reaction observed after the burn stress.