Thesis (Ph. D.)--University of Hong Kong, 1997. / Includes bibliographical references (leaf 165-188).

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

Psychology uses theory supported by empirical evidence to accumulate generalisable knowledge and learn from various contexts. Two commonly used theories are the Theory of Planned Behaviour (TPB) and Common-Sense Self Regulation Model (CS-SRM). Possible limitations in previous studies using these theories have been identified: (1) TPB studies focus upon one specified behaviour and ignore behavioural alternatives; (2) the CS-SRM is routinely not fully operationalised. This research aimed to develop an ‘extended TPB’ assessing ‘intention choice’ (where participants report their intended course of action regarding one or more specified behavioural alternatives) and to operationalise the CS-SRM more fully than is usually reported. The context was people with urological cancer. Methods: Three studies were conducted: (1) CS-SRM-based longitudinal study of people with urological cancer (n=172) to predict anxiety and depression; (2) Extended-TPB-based prospective study of men with localised prostate cancer (n=35) using both between- and within-person approaches to explore intention choice with respect to treatment; (3) Extended-TPB-based before-after study of medical students (n=93) to evaluate the effects of teaching on simulated communication behaviour. Results: (1) Anxiety and depression at Time 2 were predicted by number of information sources reported at Time 1 after controlling for baseline anxiety and depression; (2) TPB constructs were consistent with intention choice and intention choice was consistent with actual treatment. Within-persons, the model could not identify men who later reported poor outcomes; (3) All TPB-related cognitions changed between Time 1 and Time 2 but simulated behaviour scores did not change. Discussion: Relationships between the TPB constructs both between- and within-persons were consistent with actual treatment. The extended TPB measures were sensitive to change when behavioural alternatives were assessed. The CS-SRM was operationalised beyond illness representations. Conclusions: It was feasible to apply both the extended TPB (between- and within-persons) and CS-SRM in this context.

The urothelium is a stratified epithelium that serves as a barrier between the urinary tract and blood. It consists of terminally differentiated umbrella cells, which are specialized for synthesizing and assembling uroplakins into a tough apical plaque and responsible for the barrier function; intermediate cells which are few in number but serve as umbrella cell progenitors; and unipotent basal cells, which populate the majority of the urothelium. The urothelium is one of the most quiescent epithelia in the body but can rapidly regenerate in response to damage. The urothelium is also a source of cells that give rise to bladder cancer. Patients with chronic inflammation caused by indwelling catheters or repeated urinary tract infections have a higher risk of developing bladder cancer. Bladder cancers with squamous histological features are considered to be more aggressive with poor prognosis and the majority are categorized as basal subtype. The expression of Peroxisome Proliferator-Activated Receptor-gamma (PPARG) is strongly down regulated in the basal subtype of bladder cancer, suggesting that its removal might be essential in tumorigenesis. PPARG is a nuclear hormone receptor that was originally described as a master regulator of adipogenesis but could also promote cellular differentiation in a number of epithelium. PPARG also serves as an important regulator in anti-inflammatory activity after a variety of injuries, acting in part by antagonizing the NF-B pathway. In urothelial cells, it has been shown that PPARG promotes urothelial differentiation in vitro, but its function in vivo remains unexplored. To determine the role of PPARG in vivo, we used Cre-Lox recombination to conditionally delete the Pparg gene in the mouse urothelium using the ShhCre driver, which drives recombination in basal and intermediate cells, and their respective daughters. Interestingly, ShhCre;Ppargfl/fl mutants lack umbrella and intermediate cells which normally populate the luminal and sub-luminal layers, and are instead populated with an abnormal cell population negative for classical urothelial markers. The basal compartment, which in wild type mice is largely populated by P63+ KRT5+ basal cells with a small sub-population expressing KRT14; has an increased number of KRT14-expressing cells in the mutants and exhibits squamous features that are not present in the normal urothelium. In wild type animals, urinary tract infection (UTI) with uropathogenic E.coli results in a transient innate immune response, followed by proliferation and repair, which is largely complete within 2 weeks. When ShhCre;Ppargfl/fl mutants were challenged with urinary tract infection, the innate immune response was not resolved even after several weeks, as characterized by persistent NF-B activity, excessive influx of neutrophils and macrophages, and massive granulation tissue in the stroma. In addition, the Pparg-knockout urothelium exhibited squamous metaplasia. The Krt14+ basal cell population, which is considered to be the cells of origin of bladder cancer, greatly expanded in the Pparg-deleted urothelium after infection, and some lesions progressed to acquire invasive features. Together these findings suggest that PPARG is essential for the normal differentiation of the urothelium and is a potent regulator of the inflammatory response after UTI. Understanding the link between the loss of PPARG, chronic inflammation and tumorigenesis in the urothelium could shed light on the urothelial differentiation network and pave the way for the development of therapeutic approaches to various urinary diseases.

No description available.

The effect that organic urinary macromolecules have on the crystallization of calcium oxalate from a synthetic urine-like solution was studied in a mixed suspension-mixed product removal (MSMPR) continuous crystallizer. Precipitation of calcium oxalate crystals occurs during the continuous passage of urine through the renal system (kidney, bladder and tubules). While in normal circumstances these crystals remain small in size and exit the system unimpeded, in the pathologic condition calcium oxalate crystals are observed to aggregate and grow beyond a critical size where there is a significant probability of being trapped inside the renal system, e.g., on the kidney wall or in the tubules. Once trapped, the crystals become a nidus for further solute deposition and aggregation, giving origin to a renal calculus or stone. It is shown that this process is significantly affected by the presence or absence of organic macromolecules that act as modifiers of crystal growth, nucleation, and aggregation. An ultrafiltration technique was used to fractionate urine specimens from normal (N) and stone-forming (SF) persons into organic compounds of different molecular weight. These compounds were then added to the MSMPR system to test their effect on calcium oxalate crystallization. Significant differences were found to exist between N and SF urines in the composition, molecular weight distribution, and total quantity of these organic macromolecular compounds. The fraction of macromolecules responsible for the major effects on calcium oxalate crystallization was isolated, and its effect on crystal growth and nucleation rates was quantified. The steady state driving force (supersaturation) in the MSMPR system was measured. Striking differences in supersaturation versus residence time behavior between N and SF macromolecules were observed. The experimental conditions under which calcium oxalate crystals agglomerate were identified. Evidence which supports agglomeration as a key mechanism in urinary stone formation is presented.

No description available.

No description available.

Thesis--Rigshospitalet, University of Copenhagen. / Summary in English and Danish. Bibliography: p. 219-[225]

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