Huntington's Disease (HD) is one of many neurodegenerative diseases that are associated with protein misfolding, aggregation and oxidative stress. While several changes in the redox homeostasis have been shown to occur in HD animal models and HD brains, the formal relationships …
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GPVI activates platelets through an ITAM pathway by activation of Src and Syk kinases leading to activation of PLC\(_y\)2. CLEC-2 has been shown to activate platelets using an ITAM-like sequence in its cytoplasmic tail that is also dependent on Src and Syk kinases, but shows a p…
Raf Kinase Inhibitor Protein (RKIP) was originally described as an inhibitor of the Ras-Raf-MEK-ERK pathway, exerting its action by the physical inhibition of the interaction of Raf with MEK. It has subsequently been shown to play important roles in a number of other signalling …
The origins of respiratory disease, such as asthma in childhood and COPD in later life are unclear. Maternal smoking during pregnancy and low birth weight is associated with increased risk of asthma, poor lung function in adults and COPD in old age. Exposure to oxidative stress …
Serum Amyloid P Component (SAP), a putative molecular chaperone, is a homopentameric plasma protein of 25kDa subunits. It binds to the amyloid fibrils of misfolded proteins, which cause amyloidosis in humans. SAP not only stabilizes amyloid fibrils but also protects them from pr…
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of haematological stem cell malignancies characterised by proliferation of one or more cells of the myeloid lineage. The molecular investigation of MPN was revolutionized in 2005 by the finding that approximately 95% …
Intrinsic protein folding pathways are modulated by molecular chaperones, such as the diverse group of heat shock proteins (Hsps). Among these is the small heat shock protein (sHsp) family which in the mammalian genome consists of 10 low molecular weight (15-30kDa) members. The …
Chronic obstructive pulmonary disease (COPD) is a debilitating disease that as of yet has no cure and therapy is limited to symptomatic relief. A major risk factor for the development of COPD is smoking, although the disease does have some component of genetic predisposition. In…
Smoking is the major risk factor for COPD. Smoking also has systemic effects and is considered as one of the risk factors for metabolic syndrome (MeS). It is unclear whether it is smoking per se or the systemic effects of COPD that cause metabolic syndrome in smokers. Smokers wi…
Autoimmune diseases (AID) are chronic inflammatory diseases (CID) mediated by selfreactive T and B cells and are generally the results of the breakdown of T cell tolerance to self-antigen and failure of peripheral regulatory mechanisms. In this thesis I studied different mechani…
Evidence suggests haematopoietic stem cells (HSCs) can migrate to injured liver and influence tissue repair. However, the molecular adhesive mechanisms governing HSC recruitment to injured hepatic microcirculation are poorly understood. These mechanisms were investigated in vivo…
The aim of this thesis was to determine the diagnostic accuracy of outpatient endometrial evaluation using endometrial biopsy (EB), ultrasound scan (USS) and hysteroscopy (OPH) by conducting systematic quantitative reviews of the published literature. The optimum diagnostic stra…
The Apc gene encodes the Adenomatous polyposis coli tumour suppressor protein, the germ line mutation of which characterizes Familial Adenomatous Polyposis (FAP), an autosomal syndrome characterized by multiple colorectal lesions. Inactivation of the Apc gene is recognized as a …
Breast cancer is the most common female cancer in Scotland, in common with many Western countries. This thesis aimed to analyse changes in the incidence and molecular epidemiology of breast cancer in Scotland. Part 1 concentrated on epidemiological research, with data derived fr…
Abstract Background: Pulmonary hypertension (PH) is a rare condition that can occur as a primary disease process, Idiopathic Pulmonary Hypertension (IPH) or secondary to other disorders. In Familial IPH mutations have been identified in the bone morphogenetic protein receptor II…
Acute tubulointerstitial nephritis (ATIN) is an important cause of renal morbidity. This study showed that it represents up to 8% of acute renal failure where biopsy material was available and accounted for 1% of all renal biopsy material. This study, which is believed to be the…
Fibroblasts are the most abundant cell type of the stroma, producing extracellular matrix components which provide mechanical strength to tissues. Recent work has shown that fibroblasts are not simply passive structural cells but active participants in the immune response. In th…
The physicochemical nature of the infectious agent in prion diseases creates a significant challenge for decontamination services. It has been shown to be both resistant to standard methods of decontamination, used to inactivate viruses and bacteria, and to associate avidly with…
Patients with rheumatoid arthritis (RA) frequently present with pain under their feet. Forefoot bursae can give rise to such symptoms, but are rarely investigated. The aim of this thesis was to use musculoskeletal ultrasound (MSUS) performed by a podiatrist to evaluate the preva…