M.A. (Biblical Studies) / Please refer to full text to view abstract

La prolifération, la différenciation ainsi que les fonctions des cellules du système immunitaire sont contrôlées en partie par les cytokines. Lors de l’infection par le VIH-1, les défauts observés dans les fonctions, la maintenance, ainsi que la consistance des cellules du système immunitaire sont en large partie attribués à une production altérée des cytokines et à un manque d’efficacité au niveau de leurs effets biologiques. Durant ces études, nous nous sommes intéréssés à la régulation et aux fonctions de deux cytokines qui sont l’IL-18 et l’IL-21. Nous avons observé une corrélation inversée significative entre les concentrations sériques d’IL-18 et le nombre des cellules NK chez les patients infectés par le VIH-1. Nos expériences in vitro ont démontré que cette cytokine induit l’apoptose des cellules NK primaires et que cette mort peut être inhibée par des anticorps neutralisants spécifiques pour FasL et TNF-α. Cette mort cellulaire est due à l’expression de FasL sur les cellules NK et à la production de TNF-α par ces cellules. L’IL-18 augmente aussi la susceptibilité à la mort des cellules NK par un stimulus pro-apoptotique, en diminuant l’expression de la protéine anti-apoptotique Bcl-XL. Nous démontrons aussi que, contrairement à l’IL-18, les niveaux d’IL-18BP sont plus faibles dans les sérum de patients infectés. Ceci résulte sur une production non coordonnée de ces deux facteurs, aboutissant à des niveaux élevés d’IL-18 libre et biologiquement active chez les patients infectés. L’infection de macrophages in vitro induit la production d’IL-18 et réduit celle d’IL-18BP. De plus, l’IL-10 et le TGF-β, dont les concentrations sont élevées chez les patients infectés, réduisent la production d’IL-18BP par les macrophages in vitro. Finalement, nous démontrons que l’IL-18 augmente la réplication du VIH-1 dans les lymphocytes T CD4+ infectés. Les niveaux élevés d’IL-18 libres et biologiquement actives chez les patients infectés contribuent donc à l’immuno-pathogénèse induite par le VIH-1 en perturbant l’homéostasie des cellules NK ainsi qu’en augmentant la réplication du virus chez les patients. Ces études suggèrent donc la neutralisation des effets néfastes de l’IL-18 en utilisant son inhibiteur naturel soit de l’IL-18BP exogène. Ceci permettrait de moduler l’activité de l’IL-18 in vivo à des niveaux souhaitables. L’IL-21 joue un rôle clef dans le contrôle des infections virales chroniques. Lors de ces études, nous avons déterminé la dynamique de la production d’IL-21 lors de l’infection par le VIH-1 et sa conséquence sur la survie des cellules T CD4+ et la fréquence des cellules T CD8+ spécifiques au VIH-1. Nous avons démontré que sa production est compromise tôt au cours de l’infection et que les concentrations d’IL-21 corrèlent avec le compte de cellules T CD4+ chez les personnes infectées. Nos études ont démontré que le traitement antirétroviral restaure partiellement la production d’IL-21. De plus, l’infection par le VIH-1 de cellules T CD4+ humaines inhibe sa production en réduisant l’expression du facteur de transcription c-Maf. Nous avons aussi démontré que la fréquence des cellules T CD4+ spécifiques au VIH-1 qui produisent de l’IL-21 est réduite chez les patients virémiques. Selon nos résultats, l’IL-21 empêche l’apoptose spontanée des cellules T CD4+ de patients infectés et l’absence d’IL-21 réduit la fréquence des cellules T CD8+ spécifiques au VIH-1 chez ces patients. Nos résultats démontrent que l'IL-21R est exprimé de façon égale sur tous les sous-types de cellules NK chez les donneurs sains et chez les patients infectés. L’IL-21 active les protéines STAT-3, MAPK et Akt afin d'augmenter les fonctions effectrices des cellules NK. L'activation de STAT-3 joue un rôle clef dans ces fonctions avec ou sans un traitement avec de l'IL-21. L'IL-21 augmente l'expression des protéines anti-apoptotiques Bcl-2 et Bcl-XL, augmente la viabilité des cellules NK, mais ne possède aucun effet sur leur prolifération. Nous démontrons de plus que l'IL-21 augmente l'ADCC, les fonctions sécrétrices et cytotoxiques ainsi que la viabilité des cellules NK provenant de patients chroniquement infectés par le VIH-1. De plus, cette cytokine semble présenter ces effets sans augmenter en contrepartie la réplication du VIH-1. Elle permet donc d'inhiber la réplication virale lors de co-cultures autologues de cellules NK avec des cellules T CD4+ infectées d'une manière dépendante à l'expression de perforine et à l'utilisation de la protéine LFA-1. Les niveaux d’IL-21 pourraient donc servir de marqueurs biologiques pour accompagner les informations sur le taux de cellules T CD4+ circulantes en nous donnant des informations sur l’état de fonctionnalité de ce compartiment cellulaire. De plus, ces résultats suggèrent l’utilisation de cette cytokine en tant qu’agent immunothérapeutique pour restaurer les niveaux normaux d’IL-21 et augmenter la réponse antivirale chez les patients infectés par le VIH-1. / The proliferation, differentiation, function and maintenance of immune cells is controlled in large part by cytokines. HIV-induced dysfunctions of the antiviral immunity is in part related to defects in the cytokine network, as manifested by altered cytokine secretion and responsiveness to these cytokines. In these studies, we investigated the regulation and the functions of two cytokines, IL-18 and IL-21, during HIV-1 infection. In our studies, we observed an inverse correlation between IL-18 concentrations and absolute numbers of various subsets of NK cells in infected persons. IL-18 caused increased death of a human NK cell line, as well as of primary human NK cells in vitro. The IL-18-mediated cell death was dependent upon Fas-FasL interactions and TNF- secretion. IL-18 induced the expression of TNF-, induced the expression of FasL on NK cells, increased the transcription from the human FasL promoter, reduced the expression of Bcl-XL in NK cells, and increased their sensitivity to FasL-mediated cell death. In contrast to IL-18 levels, IL-18BP levels decreased in the serum of HIV-infected patients. This decrease resulted in enhanced levels of free IL-18 in the serum of such patients. The infection increased production of IL-18 but decreased that of IL-18BP in monocyte-derived macrophages (MDM). Furthermore, IL-10 and TGF-β, two cytokines for which concentrations are increased in HIV-infected persons, also decreased production of IL-18BP by human MDM. Finally, recombinant human IL-18 enhanced HIV-1 replication in human CD4+ T cells. The uncoordinated production of these two cytokines represents an imbalance between these two soluble factors in HIV-infected patients. Our study shows that enhanced IL-18 bioactivity in HIV-infected patients may contribute to the pathogenesis of AIDS by disrupting NK cell homoeostasis and increasing viral replication. This uncoordinated production of IL-18 and IL-18BP contribute to IL-18-induced immunopathology and pathogenesis in HIV-infected AIDS patients. Therefore, these studies suggest that the neutralization of IL-18 may represent an appropriate and useful immunotherapeutic strategy in these patients. It may delay AIDS progression and improve the immune status of infected persons. The best way to achieve this goal may be using exogenous interleukin-18 binding protein. IL-21 is a relatively newly discovered immune enhancing cytokine, which plays an essential role in controlling chronic viral infections. Therefore, we sought to determine the dynamics of the cytokine production and its potential consequences on the viability of CD4+ T cells in HIV-infected persons. We show here that the cytokine production is compromised early in the course of the infection. The serum cytokine concentrations correlated with CD4+ T cell counts in the infected persons. Among different groups of HIV-infected persons, only Elite Controllers maintain normal production of the cytokine. The HAART partially restores production of this cytokine. Interestingly, HIV-1 infection of human PBMC as well as of purified CD4+ T cells inhibits the production of the cytokine by decreasing the expression of c-Maf, a transcription factor involved in the activation of the cytokine gene, in the virus-infected cells but not in uninfected bystander cells. We also show that the frequencies of IL-21 producing HIV-specific antigen experienced CD4+ T cells are decreased in HIV-infected viremic patients. Furthermore, we show that recombinant human IL-21 acts as pro-survival factor and prevents enhanced spontaneous apoptosis of ex vivo cultured CD4+ T cells from HIV-infected patients and that increased serum levels of the cytokine are associated with higher frequencies as well as with better functions of HIV-specific CTL in HIV-infected individuals. We show that the cytokine receptors are expressed equally on all NK cell subsets. We demonstrate that the cytokine activates STAT-3, MAPK and Akt to enhance NK cell functions. IL-21 increases expression of anti-apoptotic proteins Bcl-2 and Bcl-XL, and enhances viability of NK cells, but has no effect on their proliferation. We further show that the cytokine enhances HIV-specific ADCC, secretory and cytotoxic functions as well as viability of NK cells from HIV-infected persons. Furthermore, it exerts its biological effects on NK cells with minimal enhancement of HIV-1 replication, and the cytokine-activated NK cells inhibit viral replication in co-cultured HIV-infected autologous CD4+ T cells in a perforin- and LFA-1-dependent manner. These studies suggest that serum IL-21 concentrations may serve as useful biomarker to accompany CD4+ T cell counts for monitoring HIV-1 disease progression and the fitness of the antiviral immunity. Furthermore, the cytokine may be considered for immunotherapy in HIV-infected patients in order to restore the physiological levels of the cytokine and promote their antiviral immunity.

Zu den bevorzugten Kunstgattungen gehörte in der Klassik auch in der Slowakei die Musik. Der kosmopolitische Charakter der Musikkunst sicherte die Kontinuität beim Übergang des Mäzenatentums vom Adel auf das Bürgertum (bei fortdauernder Mäzenatenrolle der Kirche) auch in jener Zeit, als die Übernahme des Mäzenatentums durch das Bürgertum bei uns Stagnation, sogar den Niedergang anderer Kunstgattungen zur Folge hatte. Zeugnis von der bedeutenden Position der Musik im Leben der zeitgenössischen Gesellschaft in der Slowakei und in ganz Ungarn gibt die Vielzahl an erhaltenen Noten.

Breastfeeding is an important and relatively affordable health promotion and disease prevention activity with positive health outcomes for both the women who breastfeed and the infants who receive human milk as their first source of nutrition. As these benefits are dose dependent, the duration of breastfeeding and exclusivity of breastfeeding are important in the development of these protective effects. The purpose of this study is to understand the process younger mothers, ages 18 to 24 years, undergo to be able to sustain breastfeeding for longer than most women their age breastfeed. Ten women, ages 21 to 24 years, participated in individual, in-depth interviews in this grounded theory study. Following the iterative process of data collection and analysis, focus of the interviews changed as the data analysis guided the data collection process. Data underwent open, focused, axial, and theoretical/selective coding. The analysis process resulted in the development of a middle-range, descriptive theory grounded in the data. Prolonged Breastfeeding Through Fierce Determination succinctly explains the central phenomenon, fierce determination, and the relationship it shares with the other concepts identified as important contributing factors as the women moved through their breastfeeding journeys. Facing and Deciding to Overcome Obstacles, influenced most heavily by fierce determination, exerted its influence upon the outcome of the theory, "Trucking Along", an in vivo code provided by Participant 10, which captured her ongoing breastfeeding even in the face of obstacles. Normalized Infant Feeding Method contributed to the participants' fierce determination. Availability of Support positively impacted the participants' ability to face and overcome their breastfeeding obstacles. Personal Agency had a reciprocal relationship with fierce determination and, like availability of support, also positively impacted their ability to face and overcome obstacles. The concepts within the theory were found to be congruent with a focused review of the literature around long-term goal achievement, healthful behavior adaptation, and breastfeeding. This study contributed to the breastfeeding literature, providing insight into how young mothers engage in prolonged breastfeeding.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

This thesis is devoted to the keyboard concerto in the second half of the 18th century. The main focus is Johann Baptist Vanhal and selection of his keyboard concertos, the analysis should clarify the position in contemporary production. Comparative context consists of works by four composers - G. Ch. Wagenseil, J. G. Lang, J. S. Schröter and L. Kozeluh. The work includes an introduction to the methodological problems of concerto form and theoretical reflection of period opinion on the issue of the concert.

The task is to describe the music activites of ursuline monastery in Kutna Hora in the 18th century. This was achieved using non-music resources of this monastery preserved in the State Regional Archive Praha-Chodovec, and music collection located in the Czech Museum of Music. The music collection was subsequently analyzed according to various criteria. Musical activity of the Ursulines of Kutná Hora was compared with musical activities of the Ursulines of Prague and Bratislava and the Cistercian nuns of Staré Brno. Powered by TCPDF (www.tcpdf.org)

In the first instance the work is concerned with the historical background of Broumov. It also focuses on the operation of both Broumov schools in the 18th century (the monastic school and the municipal schools) with an emphasis on local music education and activities. Further, the work deals with two Broumov collections of music, monastery and church ones. They provide valuable information about local music service in the 18th century, regarding both spiritual figural music and choral practice. Product sheet music of monastic collection from the 17th and 18th centuries, is one of the attachments. A description of the sources, with which study works, is provided. These are five manuscripts by Anthony Celestýna Mentzel (1684? -1740) containing a total of thirteen of his compositions, which are in this work analyzed from the music and text point of view. Their editions are also attached to the work. In conclusion, the study focuses on the rare occurrence of the viola d'amore in some of Mentzel's compositions.

The master thesis deals with the Antonio Salieri's opera Axur, Re d'Ormus and its premiere in 1788 at Nostitz Theatre in Prague. First part of thesis represents source research. On the basis of printed librettos, playbills and periodicals we can observe presence of Salieri's operas in repertory of Prague theaters from 1773 to 1806. Main part of thesis constitute musical and dramatic analysis of Salieri's Axur. This analysis is focused to Prague "version", which represents printed libretto. Musical and textual sources, used in analysis, was furthermore properly investigated. Through mutual comparison was suggested stemma, indicated to relations between these sources and simultaneously to processes, proceeded during transfer of work between particular theaters. I pay attention especially to axis Vienna-Prague-Dresden in period 1788-1789.