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R Mead

Publications and source records attributed to R Mead.

15 recordsLinked to original sources

Molecular cloning, expression and characterization of the rat analogue of human membrane cofactor protein (MCP/CD46).

In humans, host cells are protected from homologous complement by membrane proteins encoded in the regulators of complement activation (RCA) gene cluster. These include complement receptor 1 (CR1), decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46). In mouse and rat a single membrane inhibitor, Crry, appeared to perform the functions of both DAF and MCP and was proposed to be the functional analogue of both. Recently, however, murine homologues of DAF and MCP have been identified, prompting a search for the rat counterparts. We have described the identification of rat DAF and here describe the cloning of rat MCP from cDNA and genomic libraries, using a probe based on the mouse MCP cDNA sequence. The domain structure for rat MCP was identical to that of mouse MCP with four short consensus repeats (SCRs) followed by a STP domain, transmembrane segment and cytoplasmic tail. Overall identity of rat and mouse MCP was 77% at the amino acid level and 88% at the nucleotide level. Northern blot analysis from a range of tissues indicated that high-level expression was limited to the testis, although expression in other tissues was detected using reverse transcription-polymerase chain reaction. Rat MCP mRNA localized to Sertoli cells and spermatogonia in seminiferous tubules by in situ hybridization, but was absent in mature sperm. In cofactor assays utilizing human factor I, a recombinant soluble form of rat MCP catalysed cleavage of human C3ma.

Amino Acid Sequence↗

On the clonal origin of tumours--lessons from studies of intestinal epithelium.

Clonal studies of adult chimaeric mouse epithelium have demonstrated the monoclonal composition of crypts of Lieberkühn. In neonatal life, however, polyclonal crypts have been found, indicating that crypts are of polyclonal origin. We here relate these findings to studies of mosaic tissues which have addressed the question whether solid tumours are of monoclonal or polyclonal origin. The issues has so far remained unresolved because the expected frequencies of polyclonal tumours, given polyclonal origins, have not previously been estimated. A general approach for the calculation of such expected values is suggested. The consistent reports of tumours with polyclonal components suggest that autocrine or paracrine mechanisms play an important role during tumorigenesis.

Animals↗

Calculating numbers of tissue progenitor cells using chimaeric animals.

Experimental chimaeras have been used to estimate the number of tissue progenitors from the variation in the proportions of cells of each genotype that can be found in a given tissue. However, because of a failure to appreciate the importance of assessing the extent of agreement required between the predictions made by a specific mathematical model and the actual data, we believe that the statistical procedures were inappropriate and have led to unjustified conclusions. We illustrate our argument by reference to published data on the number of progenitor cells in the facial nerve nucleus of the mouse (K. Herrup, T. Diglio, A. Letsou, (1984). Dev. Biol. 103, 329-336).

Animals↗