Rebuilding Babel: On Fragility and The Palimpsest in Jakob Ullmann’s voice, books and FIRE

This article serves as an overview of Jakob Ullmann's voice, books and FIRE series, providing an examination of the cycle's scores, and the fragmented memories contained within. voice, books and FIRE stands monolithically in the composer's catalogue. The music – Ullmann refers to it as an ‘imaginary folklore’ – is presented through an elaborate notational system: partly effaced by layers of religious iconography, abstract imagery and fragments of religious texts and lists of names. The series (currently unfinished) serves as an elaborate memorial to the victims of Stalinist persecution as well as the demise of religious and cultural traditions across European history. In Ullmann's most ambitious and striking body of work to date, the score is encountered as a palimpsest – an overlaying and effacement of memory. The notion of the palimpsest is also traced through the music's performance and subsequent recording, assessing Ullmann's use of extreme quietness – a partial erasure – as a destabilising force for the performers, which ultimately renders the work fragile

Chronic tubulointerstitial nephritis in children: New approaches to diagnosis and treatment

A survey of 120 children with HTIN, aged from 4 to 15 years, was conducted. Taking into account the clinical variant of HTIN, all patients were divided into 2 groups: group 1 –52 (43%) children with recurrent form of HTIN and group 2 -68 (57%) patients with latent HTIN. Among them, there were 65 boys (54%), 55 girls (46%). The conducted studies have shown that with the development of rHTIN and lHTIN, an important mechanism of damage to interstitial kidney tissue, the development of clinical symptoms and the course of the disease is both a metabolic disorder leading to structural shifts at the level of various elements of the nephron and changes in the functional state of the kidneys, and instability of the cytomembranes of tubular cells. The analysis of the results of the study showed that the method of treatment proposed by the authors is the most effective way of treating HTIN, due to accelerated recovery, both clinical and laboratory parameters of the disease and indicators of protein metabolism, as well as in relation to the restoration of the functional state of the kidneys, which leads to a reduction in the length of hospital stay, a reduction in the number of relapses of exacerbation, prevention complications of the chronic process. All this contributes to preventing the development of disability and reducing the number of child deaths from CRF

The Impact of Adjuvanted and Non-Adjuvanted Influenza Vaccines on the Innate and Adaptive Immunity Effectors

To date, the advantage of adjuvanted over non-adjuvanted vaccines in the specific antibodies formation is proved. However, cellular mechanisms, including parameters of the innate immunity, involved in the vaccine-induced immune response are not well studied. The human study of inactivated vaccines showed that both subunit vaccine and split vaccine induced cellular immune response, but adjuvanted vaccine containing Polyoxidonium had the greatest potential. Despite the fact that influenza vaccines must activate endosomal receptors, they cause non-specific activation of the surface TLRs. They can trigger intracellular signals leading to the induction of antiviral mechanisms and to the activation of the body’s protective resources against microbial infections. To assess the immunological efficacy of adjuvanted vaccines and humoral reactions to vaccination it is necessary to evaluate activation of cellular mechanisms of innate and adaptive immunity

Effect of virulent and vaccine variants of influenza virus on the immunophenotype of dendritic cells generated from murine bone marrow

The aim of this study was to generate dendritic cells from the bone marrow of mice (DC) in vitro and to assess the effect of virulent and attenuated variants of influenza virus on the maturation of DCs. Granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) were used in combination, to induce differentiation of mouse bone marrow (BM) mononucleocytes into DCs. On the 5th day, distinct variants of influenza virus were added to the cell culture, and the cells were additionally incubated for 2 days. The morphological characteristics of DCs, immunophenotype of DCs and expression of some Toll-like receptors were evaluated. On the 5th day of incubation. the DCs acquired typical morphological characteristics. DCs were large in size with an eccentrically located nucleous, often irregular in shape, with numerous processes. On the 7th day of incubation with influenza virus variants, their cytoplasm was somewhat denser. DCs acquired more processes, necessary for intercellular contacts. Expression levels of CD11c, a specific marker of BM-derived DCs, and of co-stimulatory molecules such as CD40, CD80, CD86, and MHC-II were elevated in mature DCs. Virulent versus attenuated strains of the influenza virus induced special variants of DCs differentiation, with respect to expression rates of differentiation markers, as well as expression of Toll-like receptors and costimulatory molecules. Conclusions. The in vitro cultured murine mononucleocytes derived from bone marrow can produce a large number of n-DCs, that can mature in the presence of different variants.During evolution of the DC immunophenotype treated with variant influenza viruses, we have found distinct signs of immunosuppression.The attenuated U-2 and M-26 influenza variants obtained by site-specific mutagenesis upon development of DCs immunophenotype, exhibited a decreased immunosuppressive activity and were not inferior to the cold-adapted (CA) reassortant for the most positions, but exceeded it in some instances. These studies can help to assess the criteria for evaluation the efficiency of in vitro developed influenza vaccines

The Efficacy of Immunoadjuvant-Containing Influenza Vaccines in Pregnancy

The aim of the work was to determine the clinical safety and immunogenicity of immunoadjuvant vaccines against influenza (MonoGripol Plus and Grippol® Plus) in 182 pregnant women in the II and III trimesters of gestation, and further assessment of fetal conditions and infants of the first 6 months of life. Results: It was shown that immunoadjuvant vaccines do not have a negative effect on the physiological course of pregnancy and the functional state of the fetoplacental complex. In the early postpartum period, the rates of physical and neuro-psychological development and the nature of feeding of children did not differ from the control group. In pregnant women vaccinated with Grippol® plus, the levels of seroprotection to strains of A/H1N1/v are 82.0%, A/H3N2/—88.0%, B—88.3% that measure the CPMP criteria and last more than a year . After birth, transplacental antibodies in children in protective values were observed in 52.3–68.9% of cases, did not differ from the control group, and disappear after 6 months. Respiratory infections during the first 6 months of life of infants born from mothers vaccinated against influenza registered in 1.8 times less frequently

Examining immune arms in mice immunized with site-specific influenza virus mutants

Site-specific mutants as candidates for live influenza vaccines were resulted from directly introducing into the genome of the pathogenic influenza virus A/WSN/33 (H1N1) strain ts mutations derived from the genes encoding the polymerase complex proteins from some cold-adapted strains serving as attenuation donor. Here we present the data of a comparative study examining immune system arms in mice immunized intranasally with influenza virus mutants and classical cold-adapted reassortant obtained by crossing cold-adapted strain Donor A/Krasnodar/101/35/59 (H2N2) with strain A/WSN/33 (H1N1) bearing surface antigens (hemagglutinin and neuraminidase) similar to mutants. Immunophenotyping mononuclear leukocytes from immunized mice indicated at moderate suppressive effect after using site-specific mutant and the HA reassortant viruses on some immune cell subsets. All viruses in immunized mice resulted in activation of certain lymphocyte subsets including MHC II-positive cells, CD45+/CD19+ B lymphocytes and natural killer cells (CD16/32+/CD3–). Timescale and magnitude of activation markedly differed for each cell subsets. Mice immunized with mutants M26 and U2 peaked with count of CD16/32+/CD3– expressing cells on day 2 after the second immunization compared with control (p < 0.05) that may suggest about an important role for NK cells in activating immune response. In contrast, no significant changes were observed during the study in percentage of CD4+/CD25+/Fox P3 regulatory T cells, CD4+ T helpers and CD8+ cytotoxic cells, except for a sharply decreased count of activated CD4+/CD25+ cells (4-fold) on day 7 after immunization with mutant virus M26. Moreover, mutants U2 and M26 more moderately increased percentage of TLR2- and TLR4-positive cells. The viruses studied ambiguously affected count of TLR9-expressing cells in immunized animals. All viruses increased phagocytic activity in monocytes, but not neutrophils. Despite the moderate activation of innate and adaptive immunity arms, site-specific mutants more profoundly affected humoral reactions inducing increased antibody titers, so that immunogenicity of mutant viruses was higher than that of the cold-adapted reassortant. Thus, the findings hold a promise of using site-specific mutants as live influenza vaccines

MICE SERUM CYTOKINE LEVEL UNDER MUCOSAL IMMUNIZATION WITH OPPORTUNISTIC MICROBIAL ANTIGENS

An important parameter of immunotropic preparation effect is the influence on the production of cytokines that provide the interaction between the effectors of both congenital and adaptive immunity. Cytokine level was determined in the work while using the methods of mucosal immunization with Immunovac-VP-4 and compared with the subcutaneous introduction of this preparation. In case of intranasal and peroral methods of antigen application IL-5, IL-6, and IL-12 expression was found to be elevated, the same was true for IL-1β, IL-5, IL-6, IL-12, and IFN-γ under the subcutaneous immunization. Resulting mice cytokine profile confirmed that irrespective of the method of Immunovac introduction, the activation of immune effectors occurred that was manifested in the increase in proinflammatory and regulatory cytokine levels. It was concluded that the introduction of opportunistic microbial antigens initiated the activation of the cascade of immunologic reactions and under the influence of synthesized cytokines the polarization of immune response was involved that was predominantly of Th1 type

MORPHOFUNCTIONAL PECULIARITIES OF MUCOSAL IMMUNITY DEPENDING ON METHODS OF OPPORTUNISTIC MICROBIAL INTRODUCTION

Immunophenotypic and morphological peculiarities of immune reactions under intranasal, peroral and subcutaneous introduction of multicomponent vaccine Immunovac VP-4 containing a group of opportunistic bacterial antigens were investigated. The investigated preparation was found to cause marked activation of congenital immunity effectors both in parenteral and mucosal immunization. It is manifested in the expression of differential, costimulatory, adhesive molecules on the surface of mononuclear leukocytes in proliferation of key mucosal immunity effectors (γδТ, В1, NK cells), and changes in structure, cellular composition of immunocompetent organs both regional and distant as to the site of introduction. Currently existing data on effects and mechanisms of vaccine and immunomodulator mucosal introduction allows considering the development of mucosal mono- and associated vaccines as the priority direction in modern vaccinology