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Title: Human epidermal dendritic cells : an ultrastructural study of human epidermal dendritic cells under physical stress and after malignant change
Author: Hunter, J. A. A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1977
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This thesis describes ultrastructural observations on normal dendritic cells (melanocytes and Langerhans cells) of human epidermis, and changes in their fine structure after various forms of physical stress and malignant transformation. The historical background and previous research on the structure and function of the melanocyte and Langerhans cell are reviewed. During a holiday in Madeira the grave of Paul Langerhans was found neglected and overgrown, but arrangements made with a chance acquaintance should ensure that it is looked after in perpetuo. The unique fragility of melanocyte mitochondria was the only new finding noted in studies of normal skin. Ultrastructural dopa and tyrosine studies were made on skin exposed to ultraviolet radiation. They highlight the central role of the Golgi apparatus and surrounding system of smooth endoplasmic reticulum (GERL) in the transport of tyrosinase from ribosome to melanosome, and indicate that Stage I melanosomas arise from all parts of the Golgi apparatus as well as from GERL. The concept that the fine structure with periodicity in early melanosomes is the supporting structure of tyrosines was not confirmed. After a single exposure to ultraviolet radiation (6 X minimal erythome done), reaction product was not noted in melanocytes until twenty four hours after irradiation. It was then seen within the Golgi apparatus and neighbouring GERL; seventy two hours after irradiation it was seen mainly in peripheral cytoplasmic vesicles. Langerhans and mast cells were consistently dopa negative. Suction and friction stress to the epidermis have a profound effect on keratinocytes but cause minimal damage to dendritic cells, probably due to their lack of attachment with surrounding cells. Suction experiments indicate that, in contrast to keratinocytes, there is no communication between the extracellular space and system of smooth endoplasmic reticulum in dendritic cells. Subcellular observations on a single case of histiocytosis X were similar to those of others, and support the view that this condition is due to reactive proliferation of the epidermal Langerhans cell. Ultrastructural studies were carried out on forty specimens of invasive malignant melanoma. The findings support the concept that the fine structure of lentigo maligna melanoma is usually characteristic, and differs from that of superficial spreading and nodular malignant melanoma. The melanosomes in lentigo maligns melanoma are usually ellipsoidal and resemble those of normal melanocytes, whereas the melanocomes in superficial spreading and nodular melanoma are most often spheroidal and abnormal in appearance. Superficial spreading and nodular melanomas cannot be reliably distinguished by their ultrastructure, though vascular melanosomes are more common in superficial spreading melanoma. There was no support for the hypothesis that superficial spreading melanomas and nodular melanomas develop from pre-existing naevi. Ultrastructural dope reactions carried out on ten malignant melanoma specimens indicated that malignant transformation effects the structural protein of the EB/U melanosome rather than the distribution and passage of tyrosinase. Vacuolar melanosomes seem to represent an arrest in the development of Stage I melanosomes. A single case of a breast carcinoma invading the overlying epidermis and causing gross proliferation and activity of the melanocytes is described. Hyperactive melanocytes, which had migrated from the epidermis, were seen surrounding dermal tumour cell, but little evidence of phagocytosis, either by the melanocytes or tumour cells, was noted. This curiosity illustrates the close relationship which exists between melanocytes and cells of epithelial origin.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available