Thèse doctorat : Sciences de la vie et de la santé. Biologie moléculaire et cellulaire : Paris 12 : 2003. / Version électronique uniquement consultable au sein de l'Université Paris 12 (Intranet). Titre provenant de l'écran-titre. Bibliogr. : 220 réf.

Thèse d'exercice : Chirurgie dentaire : Nantes : 2007. / Bibliogr.

Reproduction de : Thèse d'exercice : Médecine. Dermatologie-Vénéréologie : Nantes : 2008. / Bibliogr.

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references. Available also from UMI/Dissertation Abstracts International.

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 102-114). Available also in a digital version from Dissertation Abstracts.

Thesis (M.Sc.(Dietetics))--University of Pretoria, 2009. / Abstract in English. Includes bibliographical references.

Assisted reproduction technology is increasingly used for treatment of couples with subfertility. These women are usually of more advanced maternal age and carry a higher risk of fetal Down syndrome. Results from early publications showed that biochemical markers for screening of fetal Down syndrome in the second trimester were different between pregnancies from in vitro fertilization (IVF) and natural conception. This could potentially increase the false positive rate and result in unnecessary invasive diagnostic procedures. Questions were raised as to whether the alterations were related to ovarian stimulation. This laid the fundamentals of a series of studies presented in this thesis with an aim to address the variations in the concentrations of markers of fetal Down syndrome and the fetal growth profile of pregnancies conceived following different assisted reproduction treatments. Studies were conducted on maternal serum and amniotic fluid alpha fetoprotein (AFP) and human chorionic gonadotrophin (hCG) in the second trimester in pregnancies conceived by assisted reproduction. A reduced level of AFP in maternal serum in pregnancies with fresh embryos together with an elevated level of hCG in both maternal serum and amniotic fluid in pregnancies with frozen thawed embryos were found. This pioneer piece of data showing the raised hCG in frozen thawed embryo pregnancies with unstimulated treatment cycles spoke against the ovarian driven hypothesis, but suggested placental dysfunction be a possible underlying pathophysiology. For markers adopted in the first trimester, the level of pregnancy associated protein A (PAPP-A) was significantly reduced in pregnancies from assisted reproduction. The data on free βhCG was heterogeneous. Apart from biochemical markers, the nuchal translucency was also increased in these singleton pregnancies but not in dichorionic twins. As the direction of deviations of these markers in unaffected pregnancies from assisted reproduction resembled those observed in pregnancies affected by Down syndrome, appropriate adjustment was necessary to reduce the false positive rate for these women. Altered biochemical markers, notably a low PAPP-A level, were also associated with adverse obstetric outcomes. The changes observed in pregnancies from assisted reproduction might be a manifestation of an intrinsic placental insufficiency or fetal developmental delay. A longitudinal study was performed to examine the intrauterine fetal growth profile in these pregnancies. The rate of increment in the mean sac size, which could represent an adaptive compensatory mechanism, was significantly greater in pregnancies from assisted reproduction compared to natural conception. We concluded that pregnancies conceived after assisted reproduction technology were different from pregnancies from natural conception in terms of the concentrations of biochemical and ultrasound markers of Down syndrome. Due to the wide variation in treatment protocols and patients’ background demographics, the exact underlying pathophysiology might be difficult to be explored. Couples undergoing assisted reproduction treatment should be counseled on the increased risk of adverse pregnancy course and perinatal outcome. / published_or_final_version / Medicine / Master / Doctor of Medicine

Drosophila models for human diseases have helped in advancing our knowledge on human diseases and the discovery of potential treatments. Angelman syndrome is a rare neurological disorder that results in severe mental retardation and loss of motor coordination. The disease is caused by loss-of-function mutations in the UBE3A gene encoding a HECT domain ubiquitin protein ligase. Drosophila dube3a is the fly homolog of human UBE3A and their protein products share ~55% similarity in amino acid sequence along the entire length of the proteins. My goal was to develop a Drosophila AS model that will allow us to identify the AS-associated substrate(s) of the Drosophila UBE3A homolog and ultimately, to determine why the lack of UBE3A protein causes Angelman syndrome in humans. Dube3a is present in the embryonic, larval and adult central nervous system, including the adult mushroom bodies, which is the center for learning and memory. I have generated dube3a knock-out flies and they appear normal externally, but display abnormal locomotor behaviors. Flies that overexpress wild-type dube3a in the nervous system also display locomotion defects, and these overexpression phenotypes are dependent on the presence of a conserved cysteine residue essential for HECT domain E3 enzymatic activity. Targeted overexpression of dube3a in the eye, the wing, or ubiquitously causes rough eyes, curly wings and lethality, respectively. These morphological abnormalities in the eye or wing depend on the critical catalytic cysteine of Dube3a. Overexpression of mutant dube3a carrying AS-associated point mutations does not elicit such defects, suggesting they act as loss-of-function mutants. Taken together, dube3a mutants are a candidate fly model for Angelman syndrome, and the flies that overexpress dube3a in the eye or wing are useful for genetic screens to identify the elusive UBE3A substrates relevant to Angelman syndrome.

Toxic shock syndrome is a rare complication of Staphylococcus aureus infection associated with small burn wounds of under 5 % total body surface area; it is predominantly observed in young children. Environmental factors that occur within a burn wound have been suggested to increase the risk of TSS developing, and wound dressings have been implicated to contribute to this risk. This study examined the effects of 11 wound dressings on the production of TSST-1 by two strains of S. aureus (strains T1 and T4). Initially, the effects of the wound dressings on growth and exotoxin production were assessed using a liquid culture medium, as this was used in other studies. The results indicated that growth was not markedly affected using this system, however there were a number of problems associated with the evaluation. TSST-l production was altered (increased or decreased) depending upon the dressing type, the gaseous environment or the strain of S. aureus used. Other exotoxins did not appear to be greatly affected by any of the dressings. When a semi-solid system was developed to minimise disintegration of the dressings and simulate a more appropriate wound model in terms of support and environment, similar results were observed as to those found in a liquid culture system. A l-layered semi-solid agarose system incubated in 6 % (v/v) carbon dioxide supported optimum TSST-1 production by both test strains in the presence and absence of most wound dressings. Actisorb Plus™ and crepe increased TSST-l production. Levels of TSST-l increased over time and Actisorb Plus™ continued to stimulate increased toxin production. Gamgee, and Biobrane ™previously implicated. in TSS, increased TSST-1 production t.. . I between 48-72 hours. Serine, thiol and metalloproteases were produced by both strains of S. aureus and proportions of each were altered by the presence of dressings. This study showed that some wound dressings may potentially increase the risk of a patient developing TSS, but further studies need to be done in vivo.

published_or_final_version / Surgery / Master / Master of Surgery