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D Bicknell

Publications and source records attributed to D Bicknell.

5 recordsLinked to original sources

Molecular analysis of APC mutations in familial adenomatous polyposis and sporadic colon carcinomas.

Mutations in the APC gene give rise to familial adenomatous polyposis (FAP) and also occur in many, perhaps most, sporadic colon cancers. By screening with single-strand conformation polymorphism analysis we identified several mutations in a small region of the APC gene in both FAP and sporadic cancers. These mutations were either point mutations or small deletions or insertions causing frameshifts, and all generated stop codons. One 5 base-pair deletion was found in a sporadic colon tumour, a colorectal cancer cell line derived from a sporadic colon tumour, and in four unrelated FAP patients. This mutation produces distinctive heteroduplex bands, which can be detected with a simple non-radioactive assay. Our findings suggest that highly localised short sequences, essentially runs that code for adenine and thymine, may account for up to 20% of all observed APC mutations.

Adenomatous Polyposis Coli

Changes in cell surface antigen expression during hemopoietic differentiation.

Human bone marrow cells were separated on a fluorescence activated cell sorter (FACS) according to their binding of a series of monoclonal antibodies; the positive and negative fractions were cloned for erythroid burst and colony-forming units (BFU-E and CFU-E) and myeloid colony-forming units (CFU-GM), and cytocentrifuge slides were prepared for microscopy of maturing precursors. The pattern of antigen expression on hemopoietic progenitor and precursor populations has been established using antibodies defining blood group (A, I/i), HLA-associated (*A, B, C, DR, DC1), lineage specific, and transferrin receptor antigens. Like monomorphic HLA-DR, the antigen defined by monoclonal antibody OKT10 is expressed on the earliest progenitors and lost during differentiation, suggesting a role in interactions regulating the differentiation of these cells. The HLA-linked DC1 determinant, in contrast to HLA-DR, is not expressed at a detectable level on progenitor cells. Although a lineage-specific early antigen has not been identified, the transferrin receptor is expressed on the majority of erythroid progenitors, but only weakly on myeloid progenitors, and may provide an approach to isolating erythroid progenitors. These and earlier studies with monoclonal antibodies against HLA-DR and glycophorin now provide a detailed "map" of antigen expression during hemopoietic differentiation.

ABO Blood-Group System

A monoclonal antibody detecting an antigen shared by neural and granulocytic cells.

A monoclonal antibody, MI/N1, is described that reacts predominantly with fresh neuroblastoma tissue, human neuroblastoma cell lines, and cells of the myeloid lineage. Investigation of the binding of this antibody to four different neuroblastoma cell lines showed CHP 100 bound approximately 4 times more antibody than CHP 126. Only 30% of the cells in the line CHP 100 bound MI/N1 as determined by indirect immunofluorescence. Thus, both quantitative and qualitative differences in the expression of antigen recognised by MI/N1 are detected on human neuroblastoma cell lines. Inasmuch as only five of eight marrow aspirates heavily infiltrated with neuroblasts bound the monoclonal, this also suggests a heterogeneity in antigenic expression on fresh tumour cells. Absorption studies indicate that the antigen recognised by MI/N1 is present on human foetal brain and adult human cerebellum. At a dilution of 1/750, equal volumes of foetal brain and adult cerebellum absorbed out 30 and 60% of the reactivity to the human neuroblastoma cell line CHP 100. No reactivity was found towards murine neuroblastoma cells or rat brain. Expression of antigen on cells in the myeloid lineage appears dependent upon their stage of maturation, increasing as cells mature to neutrophils and eosinophils. It is suggested that the quantitative and qualitative differences seen in the expression of antigen on neuroblastoma cells may relate to their being blocked at different stages of differentiation.

Adult