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    Identification and characterisation of mucin abnormalities in the ganglionic bowel in Hirschsprung's disease 
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    • Identification and characterisation of mucin abnormalities in the ganglionic bowel in Hirschsprung's disease
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    • Identification and characterisation of mucin abnormalities in the ganglionic bowel in Hirschsprung's disease
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    Identification and characterisation of mucin abnormalities in the ganglionic bowel in Hirschsprung's disease

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    SPEAREIdentification2010.pdf (4.673Mb)
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    Queen Mary University of London
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    Abstract
    Hirschsprung’s disease (HD) is a congenital abnormality of unknown origin, characterised by a lack of ganglion cells in the distal colon which results in functional colonic obstruction. The major cause of morbidity and mortality in these children results from an inflammatory condition called enterocolitis. Mucins are large glycoproteins produced by intestinal cells which are a vital part of the colonic defensive barrier to infection. Previous work has found that this barrier is deficient in children with HD in the aganglionic colon and in the immediately adjacent ganglionic colon and that this is related to the risk of developing enterocolitis. This study aimed to further investigate the mucin defensive barrier in a greater region of the ganglionic colon in HD, to establish the extent of any mucin deficiencies and whether these were confined to a limited region close to the aganglionic colon. Mucosal biopsies were collected at intervals along the colon at the time of corrective surgery or colostomy closure in the controls. Organ culture with radioactive mucin precursors was performed and the mucin produced was purified and analysed, results quantified by DNA content in the sample. Lectin binding studies were also carried out. Patients were found to produce lower levels of new mucins most distally, but much higher levels five centimetres proximal when compared to controls. The rest of the colon studied also showed changes in mucin production, with a lack of production of gel-forming mucins and sulphated secreted mucins in Hirschsprung’s disease higher up the colon. Lectin binding studies, which indicate the presence of existing mucins as well as those produced during organ culture, demonstrated greater levels of binding in patients compared to controls for wheat germ agglutinin and Maackia amurensis agglutinin.
    Authors
    Speare, Ruth Marian
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    https://qmro.qmul.ac.uk/xmlui/handle/123456789/424
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    The copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author
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