C. E. Hatton

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BACKGROUND The establishment of donor-derived haemopoiesis in the recipients of allogeneic bone-marrow transplants (BMT) involves extensive proliferation of haemopoietic stem cells. The biological consequences of this replicative stress are ill defined, but any "ageing" effect would carry the risk of an increased frequency of clonal disorders during later(More)
Genomic DNA from 57 unrelated MPS II (Hunter's disease) patients was analysed for mutations of the iduronate sulphatase (IDS) gene. The aim of the study was threefold: to identify the primary genetic lesion in patients, to investigate the correlation between genotype and phenotype, and most importantly, to provide reliable carrier testing for female members(More)
The uptake of recombinant alpha-(L)-iduronidase into glial and neuronal cells, produced by retrovirally transduced NIH3T3 fibroblasts, was studied. We demonstrate that: (1) neuronal and glial cells take up alpha-(L)-iduronidase released into the medium by retrovirally transduced fibroblasts expressing high levels of alpha-(L)-iduronidase; (2) both glial and(More)
DNA from 46 unrelated patients with Gaucher's disease was analysed for 10 known mutations: 84GG(c84 G 85ins), N370S (c1226G), L444P (c1448C), R463C (c1504T), R496H (c1604A), IVS2+1, D409H (c1342C), RecNcil (c1448C-1498C), RecTL (c1342C-1498C), and c1263del (c1264-1318del). Fifty four mutations (90%) were identified in 30 patients with type I disease. These(More)
Marked deficiencies of β-mannosidase activity were demonstrated in plasma, leukocytes, fibroblasts and urine of a patient with β-mannosidosis, similar deficiencies were observed in the proband's sibling. All other lysosomal enzymes measured, including sulphamidase, exhibited normal activity. Both parents showed reduced plasma and leukocyte β-mannosidase(More)
Clinical, pathological and biochemical findings in the mannosidoses are described. Family studies showed granulocyte-rich white cell fractions to be the tissue of choice for carrier detection in beta-mannosidosis. Metabolic labelling studies using [3H] mannose demonstrated accumulation of Man beta 1-4GlcNAc in cultured skin fibroblasts from a patient with(More)
Optimum conditions for assay of human plasma beta-mannosidase activity were determined. Maximum activity was observed at pH 3.0-3.4, the apparent Km was 0.9 mmol L-1 and enzymatic hydrolysis was linear for at least 60 min. Assays were performed on plasma from two siblings with the recently described condition beta-mannosidosis and their parents and(More)
Allogeneic bone marrow transplantation is the most effective treatment for Hurler syndrome but, since this therapy is not available to all patients, we have considered an alternative approach based on transfer and expression of the normal gene in autologous bone marrow. A retroviral vector carrying the full-length cDNA for alpha-L-iduronidase has been(More)
Bone marrow transplantation was performed in a patient with alpha-mannosidosis. To our knowledge this is the first time such treatment has been attempted. The patient died 18 weeks after successful grafting and specimens of tissues were obtained at necropsy. Alpha-mannosidase activity in spleen and liver was just below normal (spleen 102 mumol/g/hour,(More)
Allogeneic bone marrow transplantation is the most effective treatment for Hurler's syndrome. However, due to a lack of matched related donors and unacceptable morbidity of matched unrelated transplants, this therapy is not available to all patients. Therefore we have been developing an alternative approach based on transfer and expression of the normal(More)