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Title: Clinical and experimental studies of hereditary and acquired forms of amyloidosis
Author: Tan, S. Y.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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In this thesis, I describe the development of a novel "mini-fibril" extraction technique, allowing the extraction of amyloid fibril proteins from tiny milligram quantities of biopsy tissue. This led directly to the identification of a novel amyloid fibril precursor protein in a case of primary localised orbital amyloidosis and enabled the identification and full characterisations of a novel apolipoprotein AI variant in an Australian family with hereditary renal amyloidosis (HRA). In a large Spanish family with HRA, a novel apolipoprotein AI deletion variant was identified as the precursor protein. In both these families, simple dsDNA sequencing using DNA extracted and amplified from the probands' white blood cells confirmed complete concordance between mutation and the presence of exclusively variant protein sequence in the fibril proteins. Two other families with previously described apolipoprotein AI and fibrinogen α-chain variants, together with an Italian family and a Colombian family with novel transthyretin variants associated with familial amyloid polyneuropathy were also studied. Clinical and scintigraphic studies using radio-labelled serum amyloid P (SAP) component, an in vivo technique for the diagnosis of systemic amyloidosis, was also performed in all these families. Dialysis-related amyloid (DRA) is an invariable complication of long term haemodialysis (HD). The long term outcome of successful renal transplantation and the prevalence of this disease in patients dialysed predominantly by peritoneal dialysis (PD) compared to long term HD populations were studied for the first time using radiolabelled SAP scintigraphy and radiology leading to unique observations demonstrating regression of DRA deposits following a successful renal transplant in contrast to relentless progression of DRA in patients maintained on HD. Although prevalence of the disease appears to be comparable in long term PD populations, clinical expression of the disease may be different, an interesting observation which suggests that dialysis modality may be important in modulating symptoms associated with the deposits.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available