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京都大学 / 新制・課程博士 / 博士(医学) / 甲第23765号 / 医博第4811号 / 新制||医||1056(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 辻川 明孝, 教授 寺田 智祐, 教授 濵﨑 洋子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Folliculogenesis is a complex and dynamic process by which follicles grow and develop with the goal of releasing a fertilizable oocyte upon ovulation. At birth, most females have a large pool of follicles; however, this pool is naturally depleted over time until ovarian senescence occurs and ovulation ceases. Thus, the population of preantral follicles is an appealing target for studies focused on female fertility, with the hopes of extending female reproductive lifespan. The studies within this thesis characterize, for the first time in mares, the population and spatial distribution of preantral follicles within the ovary and provide preliminary results documenting the success of a novel ovarian tissue transplantation site. The results from these studies showed that the population of preantral follicles in the mare ovary is similar to that of other species and that these follicles cluster in the ovary, comparable to mice and women. Furthermore, effects of age were observed, with young mares showing (i) a higher preantral follicle population, (ii) increased preantral follicle density in portions and regions, (iii) increased follicular clustering, specifically in the lateral and dorsal area of the ovary, and (iv) more numbers of neighbors per follicle than old mares. Additionally, interesting effects of spatial distribution in the ovary were also observed, with morphologically abnormal follicles in the intermediary portion being closest to the ovarian geometric center and with a tendency for increased follicular clustering in the ventral region. Furthermore, preantral follicles with neighbors were more likely to be morphologically normal. Moreover, despite having increased odds of lacking neighbors, it was observed that morphologically normal activated follicles had a higher number of neighbors than normal resting follicles. Lastly, the novel subvulvar mucosa was comparable to the established intramuscular location for heterotopic ovarian tissue transplantation, producing similar findings for macroscopic graft appearance, follicular density, and percentages of developing/growing follicles. The findings from these studies provide vital advancements in scientific understanding of preantral folliculogenesis in the mare and build important foundations for continuing to study folliculogenesis and treatments for infertility using the mare as an animal model.

Hemolymph of Tipula trivittata larvae permits freeze tolerance of this insect due to its content of cryoprotectants and ice nucleating proteins. Spontaneous ice nucleation of the dialyzed hemolymph occurs between -5 C and -11 C up to dilutions of 1:1000. The objectives of this study were to evaluate the effects of seeding temperature (-5 C vs -7 C), and the presence of hemolymph at a low (.1% v/v) and a high (10% v/v) level on the survival of frozen-thawed bovine embryos. In Exp. l, survival rates of 6 and 7 day bovine embryos frozen in medium containing .1% hemolymph and seeded at -5 C or -7 C, were compared to evaluate the effect of seeding temperature. The effect of hemolymph was evaluated by including a control without hemolymph seeded at -7 C. In Exp. 2, survival rates of embryos frozen with and without 10% hemolymph were compared. In Exp. 3 the evaluation of the effect of 10% hemolymph was continued. Also included was a control handled identically to embryos frozen in medium with 10% hemolymph regarding pre and post freeze manipulations but which was not frozen. This allowed evaluation of freezing damage per se. For Exps. l, 2, and 3, survival based on mean final development score and time to advance a developmental stage in vitro did not differ for embryos frozen. However, in Exp.· 3, the control which was not frozen had 30% greater survival than embryos undergoing the same manipulations but which were frozen. Thus, neither seeding temperature nor inclusion of .1% or 10% hemolymph in freezing medium had a significant effect on survival of frozen-thawed bovine embryos. / Master of Science

Aim: To analyze differences in patients’ clinical course, we compared two regimes of either preemptive therapy or prophylaxis after liver transplantation. Methods: This retrospective study was reviewed and approved by the institutional review board of the University of Leipzig. Cytomegalovirus (CMV) prophylaxis with valganciclovir hydrochloride for liver transplant recipients was replaced by a preemptive strategy in October 2009. We retrospectively compared liver transplant recipients 2 years before and after October 2009. During the first period, all patients received valganciclovir daily. During the second period all patients included in the analysis were treated following a preemptive strategy. Outcomes included one year survival and therapeutic intervention due to CMV viremia or infection. Results: Between 2007 and 2010 n = 226 patients underwent liver transplantation in our center. n = 55 patients were D+/R- high risk recipients and were excluded from further analysis. A further 43 patients had to be excluded since CMV prophylaxis/preemptive strategy was not followed although there was no clinical reason for the deviation. Of the remaining 128 patients whose data were analyzed, 60 received prophylaxis and 68 were treated following a preemptive strategy. The difference in overall mortality was not significant, nor was it significant for one-year mortality where it was 10% (95%CI: 8%-28%, P = 0.31) higher for the preemptive group. No significant differences in blood count abnormalities or the incidence of sepsis and infections were observed other than CMV. In total, 19 patients (14.7%) received ganciclovir due to CMV viremia and/or infections. Patients who were treated according to the preemptive algorithm had a significantly higher rate risk of therapeutic intervention with ganciclovir [n = 16 (23.5%) vs n = 3 (4.9%), P = 0.003)].

published_or_final_version / abstract / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Psychiatry / Master / Master of Philosophy

published_or_final_version / abstract / Surgery / Doctoral / Doctor of Philosophy

The purpose of this study was to describe the presence of uncertainty experienced by heart transplant recipients at one and two year diagnostic follow-up evaluations. Twelve one year and eleven two year transplant recipients completed the Mishel Uncertainty in Illness Scale (MUIS), prior to and after cardiac catheterization. There was a decrease in uncertainty levels from pre to post-catheterization, for both one and two year recipients, however, findings were not significant. Recipients prior experience with catheterization and the interaction effects of the complete evaluation process or future health status may have affected the subject's uncertainty response. Two year transplant recipients demonstrated significantly higher uncertaintly levels, before and after cardiac catheterization, when compared to one year recipients. These findings lend initial and tentative support to the proposal that uncertainty increases with time post-transplant. The yearly follow-up evaluation may represent an episodic focusing for the transplant recipient on health status.