Thesis (M.Sc.), Memorial University of Newfoundland, Faculty of Medicine, 1998. / Restricted until June 1999. Bibliography: leaves 123-133.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 97-114).

Proliferative Kidney Disease (PKD) caused by the Malacosporean parasite Tetracapsuloides bryosalmonae, is presently the most economically damaging disease of British rainbow trout farming, costing the industry in excess of £2.5 million per annum in the UK alone. With no vaccine or prophylactic treatment available, and only management techniques currently adopted to minimise the stress and mortality associated with the disease, alternative approaches must now be considered. This document investigates if selective breeding for PKD resistance is possible by assessing the level of additive genetic variation, and calculating the subsequent estimates of heritability, for commercial strains of rainbow trout. During a PKD outbreak on a commercial farm, 1500 communally reared juvenile rainbow trout from two strains (Houghton Spring and Isle of Man) were sampled on a single day, their body weight and fork length measured, and severity of kidney swelling scored according to the scale of Clifton-Hadley et al. (1987). Fish were assigned to individual families using microsatellite parentage assignment. Significant additive genetic variation was observed in the population, and families were ranked according to estimated breeding values. A combined estimate of heritability (h2 = 0.19 ± 0.08) for kidney score suggests the population will respond well to selective breeding for kidney score, which may be deemed a measure of resistance, whilst the favourable genetic correlations between kidney score and the production traits measured suggest simultaneous selection for kidney score and growth traits should also be effective. In order to support the findings of the initial research, controlled challenge experiments were conducted. Using the family EBV information on kidney score from the IoM strain (due to its certification as a disease-free site), four females, two with high and two with low response to PKD, were each crossed with a randomly selected neomale to produce twenty two families for PKD challenge experiments. The PKD experimental challenges showed evidence of additive genetic variation to kidney score over an eleven week period, supporting initial findings. A low score was deemed as evidence of greater resistance to the parasite in this study. Although female EBV was taken into consideration in the statistical model, there was found to be no significant difference in resistance according to family. Immunohistochemistry stained kidney sections from each individual involved in the challenges proved kidney score correlated significantly to the number of parasites in the kidney, suggesting that the scale of Clifton-Hadley et al. (1987) is a sufficient and accurate basis on which to describe the severity of PKD, and infection level in rainbow trout. Having discovered evidence that furunculosis, causative agent Aeromonas salmonicida, plays a major role in the mortality of fish suffering from PKD in the field, the bacterial disease was investigated to assess the resistance of the same families used in the PKD challenges. Twenty one of the families were used to discover that additive genetic variation for resistance to furunculosis is apparent when assessed as both a binary and longitudinal trait, suggesting significant genetic improvement can be made to increase resistance to furunculosis in the IoM stock. No significant correlation was observed between kidney score, EBV, and resistance to this bacterium, but there was a positive phenotypic correlation found between furunculosis resistance and size, suggesting simultaneous selection for performance and resistance is possible within this population.

No description available.

The formation of a continuous tubular network in the mammalian urinary system requires the interconnection of two epithelial populations with distinct cellular origins. The proximal component of the renal network is the nephron--a complex tubule responsible for much of the physiological action of the kidney. Nephrons connect to a collecting duct network to transport urine from the kidney to the bladder, via the ureter. I have used high-resolution image analysis of genetically labeled nephron and collecting duct networks together with apical and luminal markers to characterize the epithelial interconnection process in the developing kidney. Morphological protrusions at the distal end of the nephron precursor, adjacent to the tip of the collecting duct epithelium, precede luminal interconnection at the S-shaped body stage. Distal cells in the nephron precursor do not display clear epithelial junction complexes and show upregulation of phospho-myosin light chain, suggestive of a quasi-mesenchymal cell behavior. The close apposition of this group of cells with the collecting duct epithelium is facilitated by the absence on an intervening basal lamina. Live imaging of explanted kidneys suggests that distal cells break through into the lumen of the collecting duct epithelium and undergo cell death. No interconnection is observed upon Notch-mediated proximalization of distal cell fates. Furthermore, distal factor bone morphogenetic protein 2 (Bmp2) expression is lost in proximalized nephron precursor derivatives. Finally, I demonstrate that mice with specific loss of Bmp2 in nephron precursors and their derivatives results in a fraction of disconnected mature nephrons that later results in nephron atrophy and compromised renal function at juvenile stage compared to control mice. These data support a model in which the establishment of distal identity in nephron precursor cells closest to the nascent collecting duct epithelium leads to an active cell invasion that establishes a patent tubular interconnection between the nephron and collecting duct.

<p>The primary goal of this dissertation was to assess the feasibility of transforming an electromagnetic (EM) shock wave lithotripter with an acoustic lens as its focusing device from the original axisymmetric pressure distribution to a non-axisymmetric steerable acoustic field. This work was motivated by the desire to better match the distribution of effective acoustic pressure and pulse energy with the trajectory and anatomical features around renal and ureteral calculi during clinical shock wave lithotripsy (SWL). The acoustic field transformation was accomplished by the design of a fan-shaped acoustic barrier (mask) placed on top of the lithotripter acoustic lens to selectively reduce the source aperture along the direction of the barrier axis, therefore effectively broadening the beam width (<italic>BW</italic>) of the lithotripter field in this preferred direction. Moreover, the geometry of the original lens (L₁) was modified so that the acoustic focus of the new lens (L₂) at high output voltages (necessitated by the incorporation of the mask) is closely aligned with the lithotripter focus. The mask was further driven by a motor-controlled gear system to rotate around the lithotripter axis, generating a steerable and non-axisymmetric acoustic field. In this dissertation project, a linear acoustic model was first used for parametric studies to assess the effects of mask geometry (opening angle and thickness) on beam elongation and peak pressure reduction. Based on this analysis, two mask geometries (L₂+M₈₀₂₅ and L₂+M₉₀₃₀) were selected for modest and maximum beam elongation within the acceptable output range of the shock wave source. The acoustic and cavitation fields of the new lens with masks, as well as the corresponding field produced by the original lens, were characterized using fiber optical probe hydrophone measurements and stereoscopic high-speed imaging. Different output voltage settings were used for each lens configuration (i.e., 14 kV for L₁, 15.8 kV for L₂+M₈₀₂₅, and 17 kV L₂+M₉₀₃₀) to produce equivalent acoustic pulse energy of 45 mJ in all setups, measured in the lithotripter focal plane. Under this condition, L₂+M₈₀₂₅ and L₂+M₉₀₃₀ generate lower peak pressure (38.2 and 36.8 MPa) with a significantly broadened BW_y (11.4 and 14.3 mm) along the y-axis (head-to-toe direction of the patient), which is aligned with the mask axis, compared to the high peak pressure (44.1 MPa) and moderate <italic>BW</italic> (7.5 mm) of L₁. It is worth noting that L₂+M₈₀₂₅ and L₂+M₉₀₃₀ produce a <italic>BW</italic>_x (7.6 and 7.5 mm) in the orthogonal direction to the mask axis, which is also comparable to L₁. Similarly, the beam width of the cavitation field was broadened from 8.1 to 12.2 mm for L₂+M₈₀₂₅, and from 10.9 to 17.9 mm for L₂+M₉₀₃₀, compared to the range of 8.8 to 9.4 mm measured from L₁. In comparison, L₂+M₈₀₂₅ produces a denser and narrower bubble cloud along the y-axis than L₂+M₉₀₃₀. In vitro stone comminution (<italic>SC</italic>) tests in a tube holder (Diameter = 14 mm) have demonstrated that L₂+M₈₀₂₅ and L₂+M₉₀₃₀ are more effective at off-axis positions and during simulated respiratory motion along the elongated beam direction. The results of <italic>SC</italic> also confirmed the correlation between <italic>SC</italic> and the average peak pressure, p_+(avg), and effective acoustic pulse energy, E_eft, delivered to the stone, as shown in previous studies. Furthermore, a ureter model was developed and used to assess the performance of L₂+M₉₀₃₀, which has the maximally elongated <italic>BW</italic> under various static and simulated respiratory motion conditions. The results suggest that L₂+M₉₀₃₀ can produce significantly better <italic>SC</italic> than L₁ when the elongated beam is effectively aligned with the stone/fragments in the ureter or with their motion trajectory during the course of SWL treatment. Altogether, the results of this dissertation work have demonstrated <italic>in vitro</italic> that a non-axisymmetric and steerable acoustic field can significantly enhance stone comminution under clinically relevant SWL conditions. Future work is warranted to optimize the mask design and steering protocol to maximize the benefit of such an adaptable and versatile design to improve the performance and safety of clinical EM lithotripters.</p> / Dissertation

published_or_final_version / abstract / toc / Medicine / Master / Master of Philosophy

No description available.

No description available.