Inaug.-diss.--München. / At head of title: Aus der II. Medizinischen klinik der Universität München ... Lebenslauf. "Literaturangabe": p. 25.

Inaug.-Diss.--Rostock. / At head of title: Aus der Rostocker Chirurgischen universitätsklinik. Lebenslauf. "Literatur": p. 17.

This thesis describes my study of inhibition of brain regeneration in planaria. The flatworm (Dugesia tigrina) possesses a remarkable ability to regenerate lost parts, including the head. The primary objective of my study was to determine the extent to which an inhibiting substance, located in the head, would prevent regeneration of the brain. A secondary objective was to study whether DMSO (Dimethyl Sulfoxide) would facilitate the action of the inhibitor.

It is known that nerves are particularly critical during the early or dedifferentiative phase of limb regeneration. During this period in the innervated limb, cells just proximal to the amputation surface dedifferentiate, migrate to the limb tip, and undergo mitosis. These processes give rise to a population of undifferentiated mesenchymatous cells capable of redifferentiating into the missing components of the newly forming regenerate. The consequences of denervation stand in stark contrast to the normal events occurring in the innervated limb, because neither a blastema nor a regenerate forms. Results from this study indicate that during the early portion of the dedifferentiative phase in regenerates less than 2 3/4, days old the nerve apparently has little or no effect on the internal stump tissues. Of considerable interest in this regard is this study's documentation of a lack of neural influence on DNA synthesis and thus the cell cycle during the early dedifferentiative phase. Subsequently, during a transition period represented by 2 3/4 to 5 1/2 days regenerates there is some evidence for a neural influence on DNA synthesis in cells of the limb stump. Finally, on days 6 through 8, DNA synthesis is clearly nerve dependent. Since DNA synthesis is a prerequisite for mitosis, the depressed synthesis in a denervated limb precludes mitotic activity during the nerve-dependent, later portion of the dedifferentiative phase. Therefore, this research supports the idea that during the late dedifferentiative phase, including mound and early cone blastemal stages, there is a neural influence on the G1 or S phases of the cell cycle. This conclusion thereby makes progress toward explaining earlier observations of depressed mitotic activity during this period.

No description available.

Bioelectric fields are involved in patterning during embryonic development and play roles in regenerative growth and wound healing. Planaria are flatworms capable of regenerating whole new intact organisms from tiny portions of tissue, owing to a widespread population of adult somatic stem cells known as neoblasts. Previous research has suggested that an endogenous bioelectric field may contribute to the control of axial polarity and regenerative fate during planarian regeneration. By establishing novel techniques, we further investigated this hypothesis in experimentally relevant planarian species Dugesia japonica and Schmidtea mediterranea. Techniques were developed to measure transepithelial potential (TEP), record epithelial ion transport and apply exogenous electric fields to test the hypothesis that an endogenous electrical gradient contributes to axial regenerative polarity in planaria. We found that in the mesenchymal spaces of Dugesia japonica and Schmidtea mediterranea, a voltage gradient exists such that the head region is more negative than the tail. Importantly, this voltage gradient is maintained in regenerating amputated tissue fragments. Disrupting this endogenous electric field by means of exogenous DC electric field application induced regenerative anomalies affecting the anteroposterior axis. Reversal of the TEP gradient and regenerative polarity was achieved by application of an electric field that opposed the direction of the worm's natural electrical polarity, suggesting that the natural electrical gradient contributes to the control of polarity establishment during planarian regeneration.

Lung disease is the third leading cause of death worldwide. The shortage of transplantable donor organs has profound consequences, especially for patients with end-stage lung disease, where transplantation remains the only definitive treatment. Donor organ demand far exceeds supply; and currently four out of five donor lungs are deemed unacceptable for transplantation at the time of donation, making lung the least utilized solid organ. To address the donor organ shortage, the recovery of lungs unacceptable for transplantation and the development of lung substitutes or biologic constructs capable of long-term gas exchange are under investigation. However, significant challenges remain due to a limited understanding of lung development, stem cell biology, and the mechanisms of lung injury and repair. Accordingly, novel biomaterials capable of elucidating underlying mechanisms of lung regeneration as well as facilitating strategies in lung tissue engineering, regenerative medicine, and therapeutic cell delivery would have great utility. Furthermore, robust biosystems capable of prolonged whole organ support would enable extended organ recovery times, advanced therapeutic interventions, and recipient-specific organ manipulation. The integration of new mechanistic insights into lung regeneration, novel biomaterial therapeutics, and a platform for prolonged extracorporeal organ support will enable the functional recovery and use of donor lungs initially unacceptable for transplantation. Herein is described the development and validation of (i) tissue-specific extracellular matrix biomaterials as biomedical research tools, (ii) ex vivo lung perfusion systems in small and large animal models, and (iii) a clinical-scale organ support and recovery system with novel strategies for the delivery of pulmonary therapeutics.

Thesis (Ph.D.) -- James Cook University, 1998. / Typescript (photocopy) Bibliography: leaves 110-118.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references. Also available in print.

Thesis (Ph. D.)--Oregon State University, 2008. / Printout. Includes bibliographical references. Also available on the World Wide Web.