No description available.

Thesis (doctoral)--Münster in Westfalen, 1933.

Thesis (doctoral)--Münster in Westfalen, 1933.

published_or_final_version / Dentistry / Master / Master of Dental Surgery

No description available.

No description available.

21-hydroxylase deficiency is the commonest enzyme defect in congenital adrenal hyperplasia resulting in low circulating cortisol and, in severe cases, low aldosterone which may lead to cardiac arrest in the neonate. As the low levels of coitisol· lead to raised levels of adrenocorticotrophic hormone large concentrations of androgens are formed in utero which may lead to cliteromegaly and consequent confusion of the sexes at birth. High concentrations of the androgens give rise to rapid growth in early childhood and early fusion of the epiphyses results in short stature of the adult. 17-alphahydroxyprogesterone (170HP) is raised in the blood and saliva of children with 21-hydroxylase deficiency. 170HP is commonly measured by radioimmunoassay which limits the assay to being performed by laboratories equipped with beta or gamma counters. The aim of this project was to develop an enzymeimmunoassay which could be carried out using the minimum amount of equipment. Horseradish peroxidase was conjugated to 170HP-O-carboxymethyloxime using a mixed anhydride reaction. Separation of free and bound label was achieved using a second antibody linked to magnetisable particle solid phase. Measurement of the bound enzyme activity yielded colours which could be compared by eye, with known standards, to give a semi-quantitative assay. Alternatively the absorbance could be measured using a spectrophotometer for full quantitative results. The developed assays were evaluated, comparing the results with radioimmunoassay, and then used for measuring 170HP in blood and saliva in various clinical situations.

The burden of osteoarthritis continuous to increase. While joint replacement surgery provides a cost effective and efficacious treatment for end stage osteoarthritis, no treatment exists to prevent or slow the progression of the disease. Understanding the cellular and molecular changes in the synovium following trauma and in early osteoarthritis could facilitate the identification of novel therapeutic targets. Previous studies identified synovial hyperplasia following intra-articular fractures, cartilage injury and in osteoarthritis. In mice, proliferation of synovial mesenchymal stromal/stem cells (MSCs) leads to synovial hyperplasia following joint surface injury. The driver for this expansion of MSCs in the synovium is unknown. Recently, YAP, a key downstream effector of the Hippo pathway, has been shown to causes tissue overgrowth due to modulation of MSC proliferation. The joint surface injury model of osteoarthritis was used to investigate whether YAP may play a role in synovial hyperplasia following joint surface injury. This work shows that synovial hyperplasia is common to both healer and non-healer mouse strains after joint injury and that Yap expression is up regulated on a protein and mRNA level. Using the same injury model in a mouse with a conditional knockout of Yap in Gdf5 lineage cells, showed that a Yap knockout in Gdf5 progeny cells prevented hyperplasia of synovial lining after joint surface injury, suggesting that YAP is required for MSCs in the synovium to proliferate. In patient synovial samples, YAP expression was up regulated in activated synovium, including a subset of CD55 positive fibroblast-like synoviocytes in the synovial lining. Proliferating cells were positive for active YAP. This suggests that findings in our mouse model are clinically relevant. Furthermore, modulation of YAP and synovial MSC proliferation after JSI provides a means to study the role of synovial hyperplasia after trauma. This could lead to a potential novel therapeutic target for the treatment of posttraumatic osteoarthritis.

Thesis (M.D.S.)--University of Hong Kong, 2000. / Includes bibliographical references (leaves 121-140) Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 166-207).