Brucella causes undulant fever in humans and uterine and systemic infection leading to abortions in domestic animals and wild life. For the acquisition of iron in mammalian hosts, species of Brucella are known to produce two siderophores, 2, 3-dihydroxy benzoic acid (2, 3-DHBA) and brucebactin. Inability to synthesize of 2, 3-DHBA affects the ability of pathogen to metabolize erythritol, replicate in trophoblast cells and cause abortion in pregnant ruminant host. The entF gene has been implicated in the unresolved pathway allowing brucebactin biosynthesis in Brucella. The research effort presented in this thesis tries to relate the role of entF in iron acquisition and potential relation with erythritol metabolism by wild type B. abortus 2308. An entF deletion mutant (BAN1) of B. abortus 2308, generated using cre-lox methodology was found to be growth inhibited in iron minimal media compared to wild type strain. Growth inhibition was further enhanced with the addition of an iron chelator or 0.1% erythritol. Compared to wild type strain, no growth inhibition of BAN1 mutant was found in murine J774A.1 macrophages, which suggests that Brucella could acquire iron inside mammalian cells. The entF gene complemented mutant strains of BAN1 (BAN2A and BAN2B) were found to be intermediate in their ability to grow in iron minimal media supplemented with 0.0.05% erythritol, when compared to wild type and BAN1 strain. The results from the present thesis demonstrate that entF gene plays an important role in iron acquisition and erythritol metabolism by B. abortus 2308 under iron limiting conditions. / Master of Science

Yes / In the study of microbial keratitis, in vivo animal models often require a large number of animals, and in vitro monolayer cell culture does not maintain the three-dimensional structure of the tissues or cell-to-cell communication of in vivo models. Here, we propose reproducible ex vivo models of single- and dual-infection keratitis as an alternative to in vivo and in vitro models. / Wellcome Trust

Suite à une lésion, la réparation d’un tissu à l’identique est l’objectif clinique recherché. Ainsi un hémostatique, au-delà de sa capacité à arrêter un saignement, se doit au minimum de ne pas être délétère pour la réparation tissulaire. Or, malgré une efficacité hémostatique démontrée Tachosil® et Surgicel®, couramment utilisés en chirurgie, peuvent générer en raison de leur persistance in situ associée à une résorption incomplète, des évènements indésirables graves (nécrose, hypersensibilité, allergie, sténose, complication thromboembolique, sepsis…). Dans ce contexte, nous avons étudié les effets d’un nouvel hémostatique non implantable, HÉMO-IONIC®, sur toutes les étapes de la réparation tissulaire : de l’hémostase à la phase de maturation. HÉMO-IONIC®, Tachosil® et Surgicel® ont été évalués in vitro sur la fonctionnalité des Endothelial Colony Forming Cells (ECFCs) ; et in vivo dans deux modèles murins, un modèle d’hémostase et un de réparation tissulaire. Grâce à ces travaux, constituant une approche originale de l’évaluation des hémostatiques, nous avons démontré que seul HÉMO-IONIC®, en plus d’être un hémostatique efficace, maintient l’ensemble des propriétés fonctionnelles des cellules endothéliales et agit, à plus long terme, positivement sur l’ensemble des étapes de la réparation tissulaire. Ces données ouvrent des perspectives particulièrement intéressantes, notamment dans la prise en charge des brûlures nécessitant la restitution d’un tissu cutané de qualité (souple et élastique). Ainsi, l’association d’HÉMO-IONIC® à l’expertise du Service de Santé des Armées (SSA) dans l’utilisation des cellules stromales mésenchymateuses comme Médicament de Thérapie Innovante (MTI) pourrait représenter, dans la prise en charge des brûlures, une avancée thérapeutique en améliorant les résultats fonctionnels et esthétiques. / After an injury, the clinical objective is to faithfully repair tissues. Thus, a hemostatic agent, beyond its ability to stop bleeding, must at least not be deleterious for tissue repair. However, despite proven hemostatic efficacy, Tachosil® and Surgicel®, which are commonly used in surgery, can lead to serious adverse events (necrosis, hypersensitivity, allergy, stenosis, thromboembolic complication, sepsis…) due to their in situ persistence associated with their incomplete resorption. In this context, we studied the effects of a new non-implantable hemostatic agent, HÉMO-IONIC®, on all stages of tissue repair : from hemostasis to maturation phase. The effects of HÉMO-IONIC®, Tachosil® and Surgicel® were assessed in vitro on Endothelial Colony Forming Cell function (ECFCs) and in vivo in two mouse models of hemostasis and tissue repair. Using an original approach to the assessment of hemostatic agents, we showed that only HÉMO-IONIC®, in addition to being effective, maintained all the functional properties of endothelial cells and acted positively on all stages of tissue repair in the longer term. These data open up very interesting perspectives, in particular in the management of burns where restoring a quality cutaneous tissue (supple and elastic) is required. Thus, in burn management, combining HÉMO-IONIC® with the French Defence Health service expertise in the use of mesenchymatous stromal cells as an advanced therapy medicinal product could be a therapeutic advance by improving the functional and esthetic outcomes.

The non-receptor tyrosine kinase Src has been found to be overexpressed and activated in many human cancers, where it has been implicated in changes in cellular proliferation, adhesion, migration, apoptosis, angiogenesis, and tumour growth. In addition, several other members of the Src family have also been implicated in various cancer phenotypes. Our examination of a wide panel of colon, breast, and lung cancer cell lines revealed that not only Src, but also Yes, Fyn, Lyn, and Lck, were expressed at both the mRNA and protein levels in different combinations, and at varying levels, between cell lines. When examined for kinase activity, it was discovered that only a subset of the expressed Src family members had detectable kinase activity within a given cell line. To investigate the involvement of the Src family members in the proliferation, adhesion, migration, and colony forming ability of four selected cancer cell lines, both Src family kinase inhibitors, which inhibit the kinase activity of multiple Src family members, and RNA interference, which selectively decreases the expression of individual proteins, were used. It was found that the involvement of these proteins in all of the cellular processes investigated was cell line-specific, with the greatest effects observed in HT29 cells, which have relatively high Src protein levels and kinase activity. Furthermore, the consequences of Src family member inhibition were also inhibitor specific, as treatment with PP2 and SKI I generally had greater effects on the cellular processes examined than did treatment with SU6656 or SKI II. It was also found that the inhibition of multiple Src family kinases by at least one of the inhibitors generally resulted in greater effects on the cancer cell phenotypes investigated than were observed when the expression of Src, Fyn, or Yes was decreased using RNA interference. This suggests that multiple Src family members may need to be targeted in order to inhibit the increased proliferation, cell-matrix adhesion, migration, and colony forming ability exhibited by cancer cells. The identification of the cancer cell phenotypes in which particular Src family members are involved is of interest, as these proteins are attractive targets for cancer therapy.

The non-receptor tyrosine kinase Src has been found to be overexpressed and activated in many human cancers, where it has been implicated in changes in cellular proliferation, adhesion, migration, apoptosis, angiogenesis, and tumour growth. In addition, several other members of the Src family have also been implicated in various cancer phenotypes. Our examination of a wide panel of colon, breast, and lung cancer cell lines revealed that not only Src, but also Yes, Fyn, Lyn, and Lck, were expressed at both the mRNA and protein levels in different combinations, and at varying levels, between cell lines. When examined for kinase activity, it was discovered that only a subset of the expressed Src family members had detectable kinase activity within a given cell line. To investigate the involvement of the Src family members in the proliferation, adhesion, migration, and colony forming ability of four selected cancer cell lines, both Src family kinase inhibitors, which inhibit the kinase activity of multiple Src family members, and RNA interference, which selectively decreases the expression of individual proteins, were used. It was found that the involvement of these proteins in all of the cellular processes investigated was cell line-specific, with the greatest effects observed in HT29 cells, which have relatively high Src protein levels and kinase activity. Furthermore, the consequences of Src family member inhibition were also inhibitor specific, as treatment with PP2 and SKI I generally had greater effects on the cellular processes examined than did treatment with SU6656 or SKI II. It was also found that the inhibition of multiple Src family kinases by at least one of the inhibitors generally resulted in greater effects on the cancer cell phenotypes investigated than were observed when the expression of Src, Fyn, or Yes was decreased using RNA interference. This suggests that multiple Src family members may need to be targeted in order to inhibit the increased proliferation, cell-matrix adhesion, migration, and colony forming ability exhibited by cancer cells. The identification of the cancer cell phenotypes in which particular Src family members are involved is of interest, as these proteins are attractive targets for cancer therapy.

No description available.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Thesis (Ph.D. in Pharmaceutical Sciences) -- University of Colorado, 2006. / Typescript. Includes bibliographical references (leaves 191-216). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

This thesis examines the influence of packaging on the microbial condition of beef for sale. The beef - Muscullus semimembranosus - was studied in an unpackaged state, and in the packaging of stretchable plastic wrap, in multilayer polyamide - polyethylene (PA / PE) wrap using a protective atmosphere and using 80% of vacuum into a bag from a multi-layered PA / PE wrap. The beef was stored at refrigerated temperature of +5 ° C. The total number of microorganisms (the number of colony forming units) were examined for 27 days. The compared samples show that the speed of increasing number of microorganisms is dependent on the type of packaging. According to the observed averages the best results are showed at meat packaged into a modified atmosphere and vacuum packaging, where there were no significant differences between these two types. Statistically there were no sigificant differences between the observed types of packaging. Packing in plastic wrap reduced microbial contamination of meat compared to unpackaged meat, but with vacuum packaging and modified atmosphere it could not be compared.