Analysis of the genome of Streptomyces aizunensis NRRL B-11277 indicated its potential to produce a compound of novel and highly predictable structure. The structure was predicted with sufficient accuracy to allow straightforward detection of the specific metabolite in HPLC profiles of fermentation extracts and hence to guide the isolation. The spectroscopic work was reduced to a confirmation of structure rather than a first principle determination. The compound, ECO-02301 (1), demonstrated potent antifungal activity. This work exemplifies not only the discovery of novel antibiotics from well-characterized organisms but also the utility of genomics as a further tool, complementary to spectroscopy, to enable rapid determination of complex structures.

The Pidd (p53-induced protein with death domain) gene was shown to be induced by the tumour suppressor p53 and to mediate p53-dependent apoptosis in mouse and human cells, through interactions with components of both the mitochondrial and the death receptor signalling pathways. To study the role of Pidd in clinical tumours, we measured its expression by quantitative reverse transcription-PCR in microdissected oral squamous cell carcinomas (OSCC) with and without p53 mutation. Tumour cell apoptosis was assessed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. Tumour proliferation was assessed by immunohistochemical staining for the Ki-67 antigen. We found a wide range of Pidd expression among OSCC. Statistical analysis revealed an association between Pidd expression and apoptotic index (Mann -Whitney test, Po0.001), consistent with a role of Pidd in apoptosis in this tumour type. Furthermore, we showed a positive correlation between apoptotic index and proliferative index that has not been previously described for OSCC. There was no correlation between Pidd expression and the p53 mutation status of these tumours, suggesting that Pidd expression may be regulated by p53-independent mechanisms. Further characterisation of these molecular defects in the control of proliferation and apoptosis should help in developing treatments that target OSCC according to their biological properties.

Cowden syndrome (CS) is a cancer predisposition syndrome caused by germline mutations in the PTEN tumor suppressor gene. It is associated with an increased risk of thyroid, breast and endometrial cancer but many manifestations can be found in the head and neck region, some of which are pathognomonic. Here we report a 35-year-old male referred by his dentist for evaluation of a lesion located near the retromolar trigone. Comprehensive clinical examination revealed papillomatous skin lesions, macrocephaly and gingival hypertrophy. Histopathological examination of the lesion showed an acinic cell carcinoma (ACC) of minor salivary gland origin. Analysis of the PTEN gene identified a germline R130Q mutation in exon 5, confirming the diagnosis of CS, but no loss of heterozygosity was seen in DNA extracted from tumor tissue. This is to our knowledge the first case describing an association of ACC of the minor salivary gland with a PTEN-gene related disorder. It emphasizes the importance of head and neck examination in these patients.

To investigate whether oral squamous cell carcinomas (OSCCs) from young (Յ40 years) and older (Ն60 years) patients have differential expression levels of GSTP1, FANCA, FANCC, FANCD2, and FANCG. Design: Quantitative real-time reverse transcriptasepolymerase chain reaction and immunohistochemical analysis were used to assess gene and protein expression, respectively. Setting: This study was performed in a research institute within a hospital setting. Patients: Our study group consisted of 104 patients (42 young and 62 older). We collected RNA from 32 OSCC samples (10 young and 22 older patients) for gene expression analysis. Seventy-seven OSCC samples (37 from young and 40 from older patients) were used for protein expression analysis. Five patients were studied in both analyses. Results: Lower expression of GSTP1 (P=.04) and FANCA (P=.01) was observed in the tumors of young compared with older patients. We also detected lower expression of GSTP1 in the tumors of young patients compared with their nondysplastic mucosa (P = .01). FANCA was underexpressed in nondysplastic mucosa of young compared with older patients (P=.01). GSTP1 protein showed negative or low expression in 41% (n=15 of 37) of young vs 5% (n = 2 of 40) of older patient tumors (P = .001). FANCG protein expression was absent or low in 81% (n=30 of 37) of young compared with 36% (n=15 of 40) of older patient tumors (PϽ.001). Conclusions: Differences in expression levels of GSTP1, FANCA, and FANCG in OSCC of young and older patients suggest that different mechanisms may be involved in tumor development through defective carcinogen metabolism and/or DNA repair capabilities. GSTP1 plays a key role in detoxification; therefore, underexpression of this gene in tumors of young patients may cause deficient detoxification that could lead to an increased susceptibility to the development of oral carcinoma.

Brevifoliol is a natural diterpene isolated from Taxus baccata Nutt. A series of brevifoliol 1 derivatives, 2-8 and 10, were prepared for characterization and semisynthesis purposes and included the introduction of acetyl, Troc, and TES groups at C-5 and C-13. Derivatives 16-20 of 5-acetylbrevifoliol 2 were obtained via esterification with cinnamic acid, with both 2S-(-)- and 2R-(+)-3-phenyllactic acid, and with N-benzoyl-(2'R,3'S)-3'-phenylisoserine at C-13. Brevifoliol compounds 12, 13, and 15 with either 2S-(-)-phenyllactate moieties at C-5 and C-13 or an N-benzoyl-(2'R,3'S)-3'-phenylisoserinyl at C-13 were also prepared. An abeo-taxane structure for 1 was clearly defined from the (13)C NMR analysis of the 5-acetyl-13-oxo derivative 8 and from the conversion of 1 into 10, a conformationally restrained compound having a C-13, C-15 oxygen bridge. The biological activity of each of these derivatives is being studied.

No abstract

A 57-year-old female patient was evaluated for an unstable maxillary dental prosthesis. The patient stated that approximately 2 weeks prior to this consultation the prosthesis was relined four times. Despite this, it often had a tendency to shift during meals. On the other hand, she is very satisfied with a complete fixed prosthesis on implants in the mandibular arch. She has been wearing this latter lower prosthesis for the same length of time as the upper prosthesis. She indicated that a similar problem existed with the former upper prosthesis, resulting in her consulting a prosthodontist.

UIUQAC Mise en garde/AdviceAfin de rendre accessible au plus grand nombre le résultat des travaux de recherche menés par ses étudiants gradués et dans l'esprit des règles qui régissent le dépôt et la diffusion des mémoires et thèses produits dans cette Institution, l'Université du Québec à Chicoutimi (UQAC) est fière de rendre accessible une version complète et gratuite de cette oeuvre.Motivated by a desire to make the results of its graduate students' research accessible to all, and in accordance with the rules governing the acceptation and diffusion of dissertations and theses in this Institution, the Université du Québec à Chicoutimi (UQAC) is proud to make a complete version of this work available at no cost to the reader.L'auteur conserve néanmoins la propriété du droit d'auteur qui protège ce mémoire ou cette thèse. Ni le mémoire ou la thèse ni des extraits substantiels de ceux-ci ne peuvent être imprimés ou autrement reproduits sans son autorisation.The author retains ownership of the copyright of this dissertation or thesis. Neither the dissertation or thesis, nor substantial extracts from it, may be printed or otherwise reproduced without the author's permission. SOMMAIREUn sujet de recherche comme «la co-éducation de la foi des jeunes âgés de 16 à 19 ans» n'est pas un sujet comme les autres. En effet, l'éducation à la foi chrétienne de ces jeunes se révèle être un des problèmes les plus criants dans notre système confessionnel d'éducation au Québec. Que ce soit dans le cadre de l'enseignement au Secondaire ou encore dans les milieux de petits groupes restreints d'apostolat laïc, le constat est ineffable: les jeunes âgés de 16 à 19 ans sont rébarbatifs, voire très récalcitrants envers la foi chrétienne: ils la rejettent carrément du revers de la main! Devant un tel constat, que faire en tant qu'enseignant des sciences morales et religieuses au secondaire, en tant qu'animateur de pastorale ou même en tant que chercheur à l'université? Voilà donc la question fondamentale qui m'a conduit progressivement à rédiger un mémoire de maîtrise en théologie pratique.Mon but en effectuant cette recherche de maîtrise est de répondre adéquatement à la question précédente ou, si vous voulez, de savoir s'il est réaliste de penser bâtir une nouvelle méthode (démarche) de «co-éducation à la foi chrétienne» qui puisse rejoindre des jeunes de 16-19 ans dans leurs milieux respectifs...