This thesis examined molecular changes in the quinolone-resistance determining regions (QRDRs) of the topoisomerase genes, gyrA and parC of Neisseria gonorrhoeae and Neisseria meningitidis and their contribution to fluoroquinolone resistance (FQR). Initially models of FQR emergence were developed from analysis of resistant mutants generated in vitro. The effects of the nature and order of sequential changes in GyrA and ParC on FQR were explored by correlating QRDR changes with ciprofloxacin minimum inhibitory concentration (MIC) determinations. The in vitro models were validated by comparisons of QRDR changes and MICs in two populations of wild-type FQR N. gonorrhoeae over a wide MIC range (0.09 to 24??g/mL), and in a wild type FQR meningococcus. The in vitro activities of three newer quinolones with differential activity on GyrA and ParC were compared with that of ciprofloxacin. Key findings were that the initial QRDR changes always occurred in gyrA and were the predominant influence on phenotypic expression of FQR. QRDR alterations were acquired sequentially and two GyrA and two ParC changes represented the full complement of changes observed in gonococci and two GyrA and one ParC change those in meningococci. GyrA alterations at Ser-91 in gonococci and Thr???91 in meningococci were pivotal for the development of further resistance. ParC changes required the presence of two GyrA alterations for any major impact on FQR. ParC substitutions, Ser-87???Arg and Glu-91???Gly in gonococci and Cys- 85???Asp and Glu-91???Lys in meningococci led to the expression of the highest FQR levels. Examination of FQR in wild-type meningococci was necessarily restricted, but analyses using the broader MIC range available in in-vitro-derived FQR meningococci (0.09 to 16??g/mL) revealed the first ParC changes in N. meningitidis. The study also redefined QRDR boundaries and described novel mutations within them. The nature of sequence changes in GyrA and ParC in FQR Neisseria also affected the relative activities of the three newer quinolones. Trovafloxacin was the most active quinolone in vitro but MIC differences with ciprofloxacin were mutation-dependent. Grepafloxacin and moxifloxacin were only slightly more active than ciprofloxacin in the presence of multiple QRDR changes. This thesis provides a comprehensive analysis of the relationship between QRDR alterations and FQR in N. gonorrhoeae and offers insights into the potential for FQR development in N. meningitidis.

Kyoto University (京都大学) / 0048 / 新制・論文博士 / 博士(薬学) / 乙第12194号 / 論薬博第742号 / 新制||薬||222(附属図書館) / UT51-2008-C964 / (主査)教授 藤井 信孝, 教授 掛谷 秀昭, 教授 竹島 浩 / 学位規則第4条第2項該当

Proefschrift--Amsterdam. / "Literatuuroverzicht": p. 303-315.

Proefschrift--Amsterdam. / "Literatuuroverzicht": p. 303-315.

No description available.

Th.--Méd.--Paris, 1840. / Voyez tome 10, page N ° 344. Paris 1840.

Th.--Méd.--Paris, 1840. / Voyez tome 4, page, N ° 264. Paris, 1840.

Th.--Méd.--Paris, 1841. / Voyez tome 5, page N ° 160. Paris, 1841.

Th.--Méd.--Montpellier, 1840. / Voyez tome 3 N ° 46 Montpellier 1840.

Ancrée dans une pratique personnelle de la gravure s’associant à la photographie, la vidéo et l’installation, cette thèse en arts plastiques explore l’hybridation entre arts et sciences. Elle commence par une recherche des spécificités de la gravure pour construire un point de vue singulier sur les œuvres d’artistes travaillant entre arts et sciences quels que soient leurs médiums. La première partie questionne l’hybridation de la gravure et du numérique comme voie d’accès à la contemporanéité définie par Giorgio Agamben comme «en déphasage» avec son temps. Dans une deuxième partie, l’imagerie médicale et la photographie questionnent l’altérité animale. La recherche se poursuit par l’analyse d’œuvres de Nagi Noda, Wanda Wulz et Xavier Lucchesi qui amènent la question de la référence aux mythes dans le travail personnel. Enfin dans une troisième partie, la recherche théorique et le travail plastique achèvent leur hybridation. Les mythes de Méduse, Orphée ou Épiméthée deviennent le point de départ de créations entre arts et sciences où le processus de la gravure actualise les mythes par l’empreinte qu’elle laisse dans les photographies, les vidéos ou les installations qui mettent en scène des images médicales. Notre thèse est que la gravure constitue, à l’image des archées – organismes récemment découverts par les biologistes – une pratique vivante qui se retrouve là où on ne l’attend pas. L’hybridation dans notre pratique artistique rapproche les archées de l’archè, qui signifie proche de l’origine. / Rooted in my personal practice of engraving combined with photography, video and installation art, this plastic arts thesis explores the hybridisation of arts and science; starting with research into the specificities of engraving to then construct a singular point of view on the works of artists whose practice falls between arts and science, whatever the medium. The first part questions the hybridisation of engraving and digital techniques as an access route to a contemporaneity described by Giogio Agamben as “out of phase” with its time. In the second part, medical imagery and photography question animal alterity. Then the research will be furthered through the analysis of works by Nagi Noda, Wanda Wulz, and Xavier Lucchesi which bring us to the matter of references to myths in personal work. Lastly, in a third part, theoretical research and physical art practice complete their hybridisations. The myths of Medusa, Orpheus and Epimetheus become the starting point of works between art and science where the process of engraving actualises the myths by the imprints it leaves in photographs, videos or installations which show medical imagery. Our thesis is that engraving is, like the archaea – recently discovered microorganisms –, a living practise that can sometimes be found where one least expects it. The hybridisation of our practise bring archaea closer to the arche, and thus closer to the origin.