• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 219
  • 192
  • 36
  • 27
  • 19
  • 14
  • 10
  • 8
  • 8
  • 5
  • 4
  • 4
  • 4
  • 4
  • 3
  • Tagged with
  • 572
  • 572
  • 73
  • 58
  • 39
  • 38
  • 38
  • 33
  • 29
  • 28
  • 27
  • 26
  • 26
  • 26
  • 25
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
351

Effekten av probiotika på eradikering av Helicobacter pylori-infektion

Najjar, Rasha January 2024 (has links)
Bakgrund: Helicobacter pylori är en viktig bakterie som kan leda till magcancerutveckling, då den ökar risken för magcancer med 4–6 gånger. År 2020 rapporterades över en miljon Helicobacter pylori-relaterade magcancer och runt 800 000 dödsfall. Från 2014 har världshälsoorganisationen rekommenderat att Helicobacter pylori ska utrotas för att minska antal dödsfall av magcancer över hela världen. Behandling av Helicobacter pylori består oftast av två olika antibiotika och protonpumpshämmare. Flera kliniska studier visade att probiotika som komplement till standard eradikeringsbehandling av Helicobacter pylori ökar eradikeringsfrekvens och minskar biverkningar till följd av antibiotikabehandling. Syfte: Studien syftar till att granska och analysera publicerade kliniska prövningar för att studera effekten av probiotika som komplement till standardterapi på eradikering av Helicobacter pylori.Metod: Fem randomiserade, placebo-kontrollerade kliniska prövningar granskades. Sökningen av studier gjordes i januari 2024 med hjälp av PubMed och Google Scholar databaser. Resultat: Fyra av fem studier visade statistiskt signifikant skillnad i Helicobacterpylori eradikeringsfrekvens hos patienter som behandlades med probiotika, som komplement till eradikeringsbehandling, jämfört med placebo. Två av fem studier visade statistiskt signifikant skillnad i antibiotikaassocierade biverkningar hos interventiongruppen jämfört med placebo.Slutsats: Probiotika som komplement till standarderadikeringsbehandling är effektiv på att öka Helicobacter pylori eliminering och utrotningshastigheten.
352

Etude de petits ARN régulateurs chez Helicobacter pylori / Search for small regulatory RNA in Helicobacter pylori

Reignier, Jérémy 14 December 2010 (has links)
Ces dernières années de nombreuses recherches ont montré l’importance des petits ARN dans la régulation de l’expression des gènes, chez tous les organismes vivants, des bactéries aux mammifères. Le projet de cette thèse était de recherche et d’identifier des petits ARN chez une bactérie pathogène pour l’homme, Helicobacter pylori (Hp). Cette bactérie colonise exclusivement l’estomac humain, un organe qui pendant longtemps a été considéré comme étant stérile, en raison du pH parfois très acide qui y règne. L’infection persistante de l’estomac humain causée par Hp est associée avec plusieurs pathologies gastriques tels que les gastrites, les ulcères peptiques, les cancers gastriques et les lymphomes du MALT. La moitié de la population est infectée par Hp, qui est responsable d’environ 1 million de décès par an à travers le monde, et de 6000 nouveaux cas de cancers gastrique par an en France. Au cours de ma thèse, j’ai travaillé en étroite collaboration avec le groupe du Pr. Jörg Vogel (RNA Biology, MPI, Berlin, Allemagne) pour développer une méthode rapide et efficace d’analyse du transcriptome complet d’Hp, en s’appuyant sur une nouvelle sur une technologie émergente de pyroséquençage haut-débit (HTPS 454 technology, Life Science, USA). Notre méthode de séquençage du transcriptome d’Hp à partir de banques enrichies en transcrits primaires (dRNA-seq), nous a permis d’identifier les sites d’initiation de la transcription (TSS) de milliers de d’ARN. Plus de la moitié de ces TSS ont été associés à des petits ARN non codants, de courte taille (de 50 à 250 nucléotides en moyenne), qui n’avaient jamais été découverts jusqu’alors, et dont les gènes sont localisés dans des régions intergéniques (sRNA) ou en antisens (asRNA) par rapport aux ORF précédemment annotées dans le génome d’Hp. Nos travaux ont également permis de mettre en évidence une forte activité de transcription antisens sur l’ensemble du génome de la bactérie, un phénomène déjà observé chez E. coli et les eucaryotes. Ainsi, au moins un TSS est localisé sur le brin opposé à 46 % des ORF et à 28% des régions « leaders » des précurseurs des ARNr 23S et 16S, et des ARNt. Enfin, l’approche dRNA-seq a permis l’identification de la première famille de toxines de type I (AapA) identifiée à ce jour chez Hp. Dans ces conditions normales de culture, la traduction de ces toxines est constitutivement réprimée par des petits ARN antisens (IsoA) qui ciblent les ARNm aapA par complémentarité de base. Malgré leur homologie avec des modules toxine-antitoxine identifiés chez d’autres bactéries, pour certaines impliquées dans la réponse aux stress, nous n’avons pas encore découvert les conditions dans lesquelles ces peptides aapA seraient exprimées chez Hp, et leur rôle biologique reste à élucider. / In the past few years, small regulatory RNAs have emerged as an important class of post-transcriptional regulators of gene expression. Indeed they have been identified and/or predicted to exist in all species ranging from bacteria to mammals. The project of this thesis was to search for small non coding RNAs in a human pathogen: Helicobacter pylori (Hp). This bacterium exclusively colonizes the human stomach, an organ that until recently was thought to be sterile due to its extreme acidity. It is now established that persistent colonization by Hp is associated with various gastric pathologies including gastritis, peptic ulcer, gastric cancer and MALT lymphoma. Half of the human population is infected by Hp that is responsible for about 1 million deaths per year and around 6000 cases of gastric cancer in France. During my thesis we , in a close collaboration with the group of Joerg Vogel (RNA biology, MPI, Berlin, Germany) developed a rapid and efficient method to reveal the whole transcriptome of Hp based on recent advances in high-throughput pyrosequencing technologies (HTPS 454 technology, Life Science, USA). By using specifically enriched libraries in primary transcripts, our strategy allowed us to map thousand (1907) of transcription start sites (TSS) on the Hp genome. More than half of these TSS correspond to new short transcripts (non coding RNAs, between 50 and 250 nucleotides in length) that have never been annotated in this genome and that are localized both in intergenic regions (sRNA) and in regions antisense to annotated ORFs (asRNA). Analysis of associations between primary transcription start sites (pTSS) revealed more complexity in the Hp transcriptome than previously anticipated: around one third (27%) of pTSS belong to antisense transcripts (aTSS). The strikingly high degree of antisense transcription occurs, similar to E. coli and higher eukaryotes, across the entire Hp genome. Overall, at least one aTSS is linked to ~46% of all ORFs, ~28% of tRNAs, and the 5’ leaders of 23S and 16S rRNA precursors. Finally our dRNA-seq approach led us to identify the first family of putative type I toxins (AapA) in the Hp genome. Under normal growth conditions these toxins are constitutively repressed by a sophisticated antisense RNA-mediated (IsoA) mechanism. Despite their homology to other toxin-antitoxin modules previously described in other bacteria, we have not found physiological conditions under which these peptides are expressed and have yet to determine the biological significance (if any ?) of these suicide genes.
353

Development of nanodispersions based on polyoxylglycerides to protect unstable molecules : Application to Helicobacter pylori treatment / Développement de nanodispersions à base de polyoxylglycerides pour la protection de molécules instables : Application au traitement d'Helicobacter pylori

Tran, Le Tuyet Chau 25 November 2014 (has links)
L’utilisation des nanoparticules Janus pour la délivrance de médicaments suscite un grand intérêt depuis quelques années. Cependant, beaucoup d’aspects sont encore à comprendre dans la préparation de tels systèmes, notamment en présence de principes actifs.Le but de cette thèse était d’étudier des nanoparticules compartimentées Janus (JNP) constituées d’excipients lipidiques, et principalement de glycérides polyoxyéthylénés. Les objectifs étaient, d’une part, une meilleure compréhension de la structure et de la physico-chimie de ces objets puis, d’autre part, leur utilisation contre Helicobacter pylori (H. pylori).Ces JNP sont produites facilement par un procédé d’homogénéisation haute pression qui a permis de fabriquer des lots allant de 10 mL à 1 L. Elles ont été caractérisées par cryo-microscopie, calorimétrie, diffraction des rayons X, diffusion quasi-élastique de la lumière notamment et ont montrées une très grande stabilité physique sur plus d’un an. Les résultats les plus intéressants ont été obtenus avec une formulation contenant 20% de phase lipidique (Labrafil® M1944CS ou Labrafil® M2125CS) et 3% d’un mélange de tensioactifs (Gelucire® 50/13 – Phospholipon® 90G 2:1 en masse). Diverses expériences autour de la formulation et du procédé ont permis d’identifier certains paramètres critiques, notamment la nature de la phase lipidique, l’ordre d’incorporation des excipients ou le taux de diesters de PEG 1500.Des essais d’encapsulation dans ces JNP et de protection d’un principe actif instable en milieu acide, l’érythromycine, ont également été menés. Les nanodispersions formées, physiquement stable pendant au moins 6 mois, avaient une taille de l’ordre de 150 nm et une distribution de taille unimodale. Des tests in vitro ont montré que l’érythromycine encapsulé gardait son efficacité anti-microbienne et était plus stable en milieu acide. Par contre, les nanoparticules ont perdu leur compartimentation en présence d’érythromycineEnfin, des études ont été menées pour comprendre l’influence de l’incorporation de principes actifs (API) sur le procédé. Ainsi, il a été montré que l’ajout de caféine, chloroxylénol, quercétine et tricloasan dans la formulation n’altérait pas la morphologie des JNP contrairement à l’érythromycine et à la dioxybenzone dans une moindre mesure.L’ensemble de ces résultats a montré que les nanoparticules compartimentées Janus sont des systèmes prometteurs de transport et de protection de principes actifs. / The use of Janus nanoparticles (JNPs) as constituent of drug delivery formulations has been a topic of considerable interest for the past several years. However, the formation of vesicles and nanoparticle-associated drug/active are still unclear.The aim of the present study was a physicochemical characterization of lipid nanodispersions based on polyoxylglycerides, especially focused on lipid-based JNPs. The experiments should lead to a better understanding of structure and behavior of the very interesting carrier system on Helicobacter pylori (the abbreviation is H. pylori).The multicompartment lipid-based JNPs were produced easily at small (10 to 50 ml/batch) and large scale (1 liter/batch) by hot high pressure homogenization method. Samples were very well long-time stable for at least over 12 months with respect to particle size, DSC, XRD, and special particle morphology characteristics. Especially for particles containing 20% of lipid phase (Labrafil® M1944CS or Labrafil® M2125CS) and surfactant mixture of Gelucire® 50/13 – Phospholipon® 90G (2:1), strong adhesion could be observed in the studies by cryo-TEM technique. By changing the formulation components and process parameters, data showed that the formation of the multicompartment lipid-based JNPs depended on the using of suitable oil phase with the surfactant mixture and the method to produce the vesicles under the identified conditions.We also successfully prepared the stable nanodispersions to protect a labile antibiotic, erythromycin. The mean diameter of the ERY-loaded nanodispersions was found approximately 150 nm, and the size distribution was unimodal. The system was physically stable at room temperature for over six months. The test of antimicrobial activity in vitro on H. pylori showed that not only the preparation process did not reduce the antimicrobial activity of erythromycin, but also the stability of erythromycin was also improved in acidic environment.Furthermore, the properties of APIs loaded into the blank vesicles also affected their particle morphologies. We achieved the nanoparticles like JNPs when loading caffeine, chloroxylenol, quercetin, and triclosan into the vesicles. These results demonstrated that the multicompartment lipid-based JNPs are a promising carrier to protect unstable APIs and enhance their stability and solubility, despite the changes in the structure of the JNPs when incorporating with erythromycin or dioxybenzone.
354

Molecular interaction of flagellar export chaperone FliS and its interacting partner HP1076 in Helicobacter pylori. / CUHK electronic theses & dissertations collection

January 2010 (has links)
A HP1076 null mutant has been constructed to provide a better understanding of the biological significance of HP1076 in H. pylori . The DeltaHP1076 mutant displays impaired motility and resistance to the antibiotic drug metronidazole. Using a proteomic study, an overall of 40 differentially expressing proteins involved in metabolism and pH homeostasis for bacterial survival, adhesion for colonization, virulence factor to gastric epithelial cells and antigenic proteins have been identified. The virulence factor, Cag pathogenicity island protein (Cag 26) and urease UreA and UreB are confirmed to have enhanced and reduced expression in null mutants. These findings may provide new insight into the infection of H. pylori. / FliS is an export chaperone that binds to flagellin molecules in cytosol in order to prevent pre-mature polymerization. Disruption of FliS would result in formation of shorter flagella and impaired adhesion ability to epithelial cells. Previous yeast two-hybrid study has identified various FliS associated proteins in H. pylori, but with no known implications. Here, we have demonstrated the interaction of FliS and a hypothetical protein HP1076 by biochemical and biophysical methods. Moreover, HP1076 possesses anti-aggregation ability on insoluble FliS-mutants and chaperone activity. Thus, HP1076 is proposed to be a co-chaperone that promotes the folding and chaperone activity of FliS. FliS is demonstrated to have a broad range of substrate specificity that binds to flagellin and flagellar related proteins which may play a key role in flagellar export system different from other flagellated bacteria. / Helicobacter pylori is a pathogenic bacterium and adheres to the gastric mucosal cells. Chronic infection would lead to gastritis or peptic ulceration and is one of the leading causes of gastric cancer. Formation of functional flagella is essential for infection, that it aids in motility of bacteria and colonization on gastric epithelial cells. The process is complex and involves more than 50 proteins in assembly of structural proteins, regulatory proteins, an export apparatus, a motor and a sensory system. Cytosolic chaperones are required to bind to exported proteins in order to facilitate the export or prevent the aggregation of proteins in cytosol. Divergence is found in flagellar system H. pylori that may account for survival inside gastric environment. / The crystal structures of FliS, HP1076 fragment and FliS/HP1076 complex are determined at 2.7A, 1.8A and 2.7A resolution respectively to provide better understanding of their molecular interactions. FliS consists of four helices and HP1076 consists of helical rich bundle structure with three helices and three beta strands that share similar fold to that of a flagellin homologue, hook-associated protein and FliS, suggesting HP1076 is involved in flagellar system. The FliS/HP1076 complex reveals an extensive electrostatic and hydrophobic binding interface which is distinct from the flagellin binding pocket on FliS. HP1076 stabilizes two alpha helices of FliS and therefore the overall bundle structure. Our findings provide new insights into the flagellar export chaperones and other secretion chaperones in Type III secretion system. / Lam, Wai Ling. / Adviser: An Wing-Ngor. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 223-243). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.
355

Prevalência de infecção pelo Helicobacter pylori associada às afecções diagnosticadas por endoscopia digestiva alta: análise retrospectiva de 1478 casos / Prevalence of H. pylori infection associated with clinical disorders diagnosed by upper gastrointestinal endoscopies, retrospective analysis of 1478 cases

Marques, Sérgio Barbosa 23 September 2009 (has links)
INTRODUÇÃO: A prevalência da úlcera péptica e outras afecções esofagogastroduodenais associadas à infecção pelo H. pylori foram alteradas em decorrência da erradicação desta infecção e uso de inibidores de secreção gástrica ácida. OBJETIVO: Determinar a prevalência da infecção pelo Helicobacter pylori associada às afecções diagnosticadas pela endoscopia digestiva alta e analisar fatores de risco. MÉTODOS: Foram analisados dados de 1478 pacientes, e as informações dos achados endoscópicos foram correlacionadas com resultado de teste de urease, faixa etária e gênero. Os pacientes com exame endoscópico normal foram considerados como grupo controle para análise estatística dos fatores de risco, perfazendo um total de 272 indivíduos. RESULTADOS: A prevalência da infecção por H. pylori foi de 53% (n=786), e maior na faixa etária entre 31 e 40 anos. Os achados endoscópicos mais frequentes foram gastrites (n=810; 54,8%), úlceras pépticas duodenais e gástricas (n=494; 33,4%), duodenites (n=287; 19,4%) e esofagites (n=217; 14,7%). Apenas a gastrite nodular e úlcera péptica foram associadas com infecção por H. pylori (p<0,05). Gastrite erosiva no antro (n=644, 78,5%) predominou em relação à pangastrite (n=166; 20,2%) e aquelas no corpo (n=19; 2,3%). Entre os casos de úlcera péptica, 103 (7%) foram gástricas, 343 (23,2%) foram duodenais e 48 (3,2%) foram gástrica e duodenal. A esofagite geralmente foi leve (grau A; 63,1%), 23,5% foram moderada (grau B) e 13,3% foram intensa (graus C e D). Infecção por H. pylori aumentou o risco de úlceras gástrica e duodenal em 1,9 e 1,6 vezes, respectivamente. Gênero masculino e maior idade foram riscos de todas as outras afecções. CONCLUSÃO: Infecção pelo H. pylori associada com maior idade e gênero masculino foram determinantes importantes para evolução de afecções gastrintestinais / Introduction: Peptic ulcer prevalence and other esophageal and gastroduodenal disorders associated with H. pylori infection changed as a consequence of its eradication and the use of gastric acid secretor inhibitors. Purpose: To establish H. pylori infection prevalence associated with clinical disorders diagnosed by upper gastrointestinal endoscopy, and determine the risk factors. Methods: Data from 1478 patients were analyzed, and the endoscopic findings were correlated with the urease test results, age and gender. Patients with normal endoscopy were considered control group for statistical analysis of the risk factors, comprising a total of 272 individuals. Results: The overall prevalence of H. pylori infection was 53% (n=786), being higher between 31 and 40 years old. The most frequent endoscopic findings were gastritis (n=810, 54.8%), peptic ulcer (n=494, 33.4%), duodenitis (n=287, 19.4%) and esophagitis (n=217, 14.7%). Only nodular gastritis and peptic ulcer were associated with H. pylori infection (p<0.05). Erosive gastritis (70%) in the antrum (n=644; 78.5%) predominated in relation to pangastritis (n=166, 20.2%) and the ones in the corpus (n=19, 2.3%). Among peptic ulcer cases, 103 (7%) were gastric, 343 (23.2%) were duodenal and 48 (3.2%) were gastric and duodenal. Esophagitis usually was mild (grade A in 63.1%), 23.5% were moderate (grade B) and 13.3% were intense (grades C and D). H. pylori infection increased the risk of gastric and duodenal ulcers by 1.9 and 1.6-fold, respectively. Male gender and being older were risks of all the other conditions. Conclusion: H. pylori infection associated with older age and male gender were important determinants to gastrointestinal diseases outcome
356

Assoziation zwischen der Besiedlung mit Helicobacter pylori im Kindesalter und dem Body-Mass-Index

Reichel, Anne 04 March 2014 (has links) (PDF)
Diese Dissertation befasst sich mit den möglichen Folgen einer Kolonisation mit Helicobacter pylori (H. pylori) im Kindesalter. Von besonderem Interesse ist dabei die Entwicklung des Body-Mass-Index (BMI). Dazu werden die Daten einer populationsbezogenen Querschnittsstudie, welche 1998 und 2006 unter Leipziger Schulanfängern bzw. Achtklässlern durchgeführt wurde, analysiert. Insgesamt konnten 1349 bzw. 1161 Kinder, deren H. pylori-Status mittels 13C‑Harnstoff-Atemtest untersucht wurde, in die Untersuchung inkludiert werden. Dabei bestätigte sich, dass die Besiedlung mit H. pylori u.a. signifikant mit einem geringeren sozialen Status und einer geringeren Körpergröße der Kinder assoziiert ist. Der BMI der untersuchten Kinder unterscheidet sich jedoch nicht signifikant in Abhängigkeit von einer Kolonisation mit H. pylori. Auf diesen Ergebnissen basierend werden zwei Hypothesen diskutiert. Zum einen wird analysiert, inwieweit ein Einfluss einer Infektion mit dem Erreger auf den BMI der Kinder nicht sicher auszuschließen ist und dieser eventuell aufgrund der Komplexität der Gewichtsentwicklung in den Ergebnissen dieser Untersuchung nicht erkennbar ist. Zum anderen wird die geringere Körpergröße H. pylori‑besiedelter Kinder nicht auf mit der Infektion in Verbindung stehende Ernährungsstörungen in Zusammenhang gebracht, da sonst vor einer entscheidenden Größenminderung das Gewicht bzw. der BMI der Studienteilnehmer zurück bleiben müsste.
357

Bedeutung der Helicobacter-pylori-Infektion für die Pathogenese und Therapie von MALT-Lymphomen des Magens / The Role of Helicobacter pylori Infection for the Development and Treatment of Gastric MALT Lymphomas

Morgner, Andrea, Bayerdörffer, Ekkehard, Thiede, Christian, Alpen, Birgit, Wündisch, Thomas, Neubauer, Andreas, Stolte, Manfred 17 February 2014 (has links) (PDF)
Seit 1983 ist das Konzept des Mukosa-assoziierten lymphatischen Gewebes (MALT) im Magen auf dem Boden einer chronischen Helicobacter(H.)-pylori-Infektion bekannt. Viele epidemiologische, biologische und molekulargenetische Studien haben die Rolle von H. pylori in der Lymphomgenese unterstützt. Bis heute wurden weltweit mehr als 650 Patienten mit gastralem MALT-Lymphom und H.-pylori-Infektion antibiotisch behandelt. Bei etwa 75% der Fälle kann mit Hilfe dieser Therapie eine komplette Lymphomremission induziert werden. Klinische prädiktive Faktoren helfen dabei, Patienten bezüglich ihres Risikos besser zu stratifizieren und damit die Probabilität des Ansprechens zu verbessern. Neue zytogenetische Erkenntnisse haben zudem dazu beigetragen, ein besseres Verständnis der Lymphomgenese zu erlangen. Mit der kürzlich beschrieben Translokation t(11;18) (q21;q21) könnte in Zukunft ein prädiktiver genetischer Faktor verfügbar sein. / The Role of Helicobacter pylori Infection for the Development and Treatment of Gastric MALT Lymphomas Since 1983, it is well known that mucosa-associated lymphoid tissue (MALT)-type lymphoma of the stomach is due to chronic Helicobacter pylori (H. pylori) infection. Many epidemiological, biological, and moleculargenetic studies have implicated the role of H. pylori in lymphomagenesis. Nowadays, more than 650 patients with gastric MALT lymphoma worldwide have been treated with antibiotics for H. pylori infection, achieving a complete remission in about 75% of cases. Clinical predictive factors help to stratify patients into risk groups, and help to predict the probability of lymphoma remission. New insights into cytogenetics have also contributed to the understanding of lymphomagenesis, and with the newly identified translocation t(11;18)(q21;q21) we might have also a genetic factor at hand to predict treatment response. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
358

Studies of immune responses to cell surface proteins of Helicobacter pylori and Borrelia burgdorferi by enzyme imunoassay and immunoblotting

Nilsson, Ingrid. January 1998 (has links)
Thesis (doctoral)--Lund University, 1998. / Added t.p. with thesis statement inserted. Includes bibliographical references.
359

Étude biochimique et structurale de composants essentiels à la biogenèse du pilus du système de sécrétion de type IV de la bactérie Helicobacter pylori / Biochemical and structural study of essential pilus proteins of the Helicobacter pylori type IV secretion system

Bergé, Célia 13 December 2017 (has links)
Helicobacter pylori est une bactérie qui colonise les cellules épithéliales gastriques humaines. Une des conséquences de cette infection est l'induction de cancers de l'estomac dans 1 à 3 % des cas, via l'injection d'une cytotoxine appelée CagA qui dérégule les voies de signalisation des cellules cibles. Cette injection, dont le mécanisme est encore inconnu, se fait grâce à un système de sécrétion de type IV (T4SS). Le pilus du cagT4SS est encore mal caractérisé. Les protéines CagI, CagL et CagH sont essentielles à la fonctionnalité du cagT4SS et à la biogenèse du pilus. De plus les trois protéines forment un sous-complexe dont les détails moléculaires n'ont pas encore été élucidés. Par conséquent mes études se sont focalisées sur ces trois protéines, leurs interactions et leur relation structure/fonction. J'ai mis en évidence que CagL interagissait directement avec CagI et CagH avec une affinité de l'ordre du micromolaire et que CagI et CagH n'interagissaient pas entre elles. La caractérisation de ces interactions a permis notamment d'identifier un complexe CagL-CagI. Afin de comprendre les détails structuraux de ce complexe, j'ai entrepris deux études structurales. La première consiste à déterminer les résidus de CagL impliqués dans l'interface d'interaction avec CagI par RMN. La seconde étude se focalise sur la détermination de la structure 3D du complexe CagI-CagL par microscopie électronique. Pour cela j'ai purifié le complexe CagI-CagL, monodisperse et stable en solution. Nous avons collecté des images du complexe par cryoEM et généré des classes 2D. Cette étude a permis pour la première fois de caractériser les interactions entre CagL-CagI-CagH et d'obtenir des informations structurales du complexe CagI-CagL / Helicobacter pylori is a bacterium that colonizes the human stomach in half of the world population. It is estimated that 20% and 3% of patients develop peptic ulcer and gastric cancer, respectively. For these reasons, H. pylori was identified as a group 1 carcinogen by the World Health Organization (WHO) in 1994. The most virulent strains of H. pylori carry a type IV secretion system (Cag-T4SS) responsible for the injection of the oncoprotein CagA into gastric epithelial cells. One remarkable feature of the cagT4SS is its external pilus which composition is not clear. CagL, CagH and CagI proteins are critical components of the Cag-T4SS because these proteins are necessary for CagA translocation and are involved in pilus formation. Moreover CagL forms a sub-assembly with CagI and CagH but the molecular details of the complex are still to be discovered. Our objective is to better understand the molecular basis of CagLIH complex by interaction and structural study. CagL interacts with CagI and CagH with a with Kds of 5 µM. CagI does not interact with CagH. The structural study of CagL/CagI complex has been investigated by a two-pronged approach. First I have purified the CagL/CagI complex and collected cyo-EM micrographs. In parallel I have collected NMR spectra of CagL in the presence of CagI and identify the changes in the spectra to determine the residues involved in the interaction. In this study we have, for the first time, characterize the CagL-CagI-CagH interactions and obtained structural informations of the CagI-CagL complex
360

Freqüência e distribuição de Helicobacter ssp. na mucosa gástrica de cães / Frequency and distribution of the Helicobacter ssp. in gastric mucosa of the dogs

Vieira, Fernanda de Toledo 30 January 2004 (has links)
Made available in DSpace on 2015-03-26T13:46:44Z (GMT). No. of bitstreams: 1 texto completo.pdf: 854857 bytes, checksum: 0da19cfc06d4ca09fceb926374e1228d (MD5) Previous issue date: 2004-01-30 / The discovery of Helicobacter pylori in human beings and its relation with gastritis, peptic ulcer and gastric neoplasia, has renewed the interest on the establishment of the incidence and on the clinical meaning of this bacteria in pets, specifically in dogs. There are several researches that indicate the presence of Helicobacter ssp in dogs, even though the relation of these bacteria with gastric alterations in dogs has not been clarified yet. The aim of this dissertation was to evaluate the presence of Helicobacter ssp in dogs, to analyse the macro and microscopic findings, determine the correlation between the presence of the bacteria with alterations in the gastric mucosa, and of these with the dogs age, and additionally to investigate the correlation of the positiveness of the urease test with the presence of the bacteria. During the necropsy of 60 dogs, samples from cardia, fundus, body, and pylorus regions were collected from the dogs stomach for conducting the urease test and histopathologic examination. The urease test was positive in 95,12% of the animals. The histopathologic examination using Carbol-Fucsina coloration revealed Helicobacter ssp in 96,66% of the animals. The most frequent observed alteration in preparations colored by HE were infiltrated with inflammatory cells, predominantly mononuclear, lymphoid nodules hyperplasia and hiperemy. Correlation between the urease test and the histopathology for the diagnostic of Helicobacter ssp in dogs was found. Age was not found correlated with infection by Helicobacter ssp. It was not found any correlation between inflamatory alterations, in the presence of the bacteria, with the age of the animals. The fundus and body stomach regions presented more positive results in the urease test and the body and pylorus regions presented more positive results in the histopathologic examination. There was correlation between the number of Helicobacter ssp, the number of inflamatory cells and lymphoid nodules in those regions. The high percentage of dogs infected by Helicobacter ssp and the variation in the patogenicity among the species indicate the necessity of further investigation for the identification of species more pathogenic and mechanisms of patogenicity in dogs. Besides, due to the zoonotic potential, further research should be done on the helicobacterias. / A descoberta do Helicobacter pylori em seres humanos e a sua relação com gastrite, úlcera péptica e neoplasia gástrica, tem levado à renovação do interesse no estabelecimento da incidência e do significado clínico da bactéria em animais domésticos, especificamente cães. Existem vários relatos da presença de Helicobacter ssp em cães, mas a relação dessas bactérias com as alterações gástricas em cães ainda não está esclarecida. Os objetivos desse trabalho foram avaliar a presença de Helicobacter ssp em cães, analisar os achados macro e microscópicos, determinar a correlação entre a presença da bactéria e as alterações da mucosa gástrica, e destas com a idade, além de correlacionar a positividade do teste da urease à presença da bactéria. Durante as necropsias de 60 cães, foram coletadas amostras das regiões cárdica, fúndica, do corpo e pilórica dos estômagos para a realização do teste da urease e exame histopatológico. O teste da urease foi positivo em 95,12% dos animais. O exame histopatológico usando a coloração de Carbol- Fucsina revelou Helicobacter ssp em 96,66% dos animais. As alterações mais freqüentemente observadas em preparações coradas por HE foram infiltrados de células inflamatórias, predominantemente mononucleares, hiperplasia de nódulos linfóides e hiperemia. Houve correlação entre o teste da urease e a histopatologia para o diagnóstico de Helicobacter ssp em cães. Não houve correlação da infecção por Helicobacter ssp com a idade. Também não foi demonstrada correlação entre alterações inflamatórias, na presença da bactéria, com a idade dos animais. As regiões fúndica e do corpo do estômago apresentaram maior número de resultados positivos no teste da urease e as regiões do corpo e pilórica apresentaram maior número de resultados positivos à histopatologia. Houve correlação entre o número de Helicobacter ssp, o número de células inflamatórias e nódulos linfóides nestas regiões. O alto percentual de cães infectados por Helicobacter ssp e a variação na patogenicidade entre as espécies indicam a necessidade de estudos mais profundados para identificação de espécies mais patogênicas e de mecanismos de patogenicidade em cães. Além disto, devido ao potencial zoonótico, grande atenção deve ser dada às helicobactérias.

Page generated in 0.3811 seconds