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Biomedical subjects

R C Foreman

Publications and source records attributed to R C Foreman.

7 recordsLinked to original sources
PubMed1991

The molecular genetics of alpha 1 antitrypsin deficiency.

The human serum protein alpha 1-antitrypsin is the major source of antiprotease activity found in the blood. The protein is synthesised primarily by liver cells but, to a lesser extent, by at least one other cell type. Expression of the gene has provided a paradigm for studies on transcriptional regulation in liver and of tissue-specific promoter activity. The pleiomorphic nature of the gene has given rise to a variety of alpha 1-antitrypsin variants some of which are clinically important. These abnormal variants may be poorly synthesised, rapidly degraded or inefficiently secreted; studies on the molecular mechanisms which underly these events are providing interesting insights into the general processes of protein transport and intracellular protein degradation.

Gene Expression Regulation↗
PubMed1991

Characterisation of a light chain loss variant of the BCL1 lymphoma.

Vaccination of BALB/c mice with idiotypic (id) IgM derived from the murine B cell lymphoma BCL1, protects the animals from challenge with tumour cells. Escape of the tumour cells from immune control is associated with the selection of variant cells which fail to express significant levels of id IgM on their cell surface. We have previously isolated one such variant, SNAG 1, and shown that, while it expresses less than 10% of the levels of surface IgM of the parental BCL1 lymphoma, it continues to synthesise id material which can be detected within the cell. In this report we present a detailed characterisation of this variant and show that the tumour cells no longer synthesise the lambda light chain. This failure to produce the light chain causes the mu heavy chains in SNAG 1 to remain marooned in the endoplasmic reticulum. The mu heavy chains in SNAG 1 have a normal mol. wt and isoelectric point, and so appear not to be mutated. This is unlike the vast majority of light chain loss variants, in which the heavy chains have been shown to contain deletions. Investigation of the mechanisms responsible for the loss of light chain synthesis demonstrated that, while mRNA for the light chain is present, and of a normal size, there was no production of light chain protein in a cell free system. This indicates that the failure to express light chain by SNAG 1 cells is due to an inability to translate the light chain mRNA into the detectable levels of lambda light chain protein.

Animals↗
PubMed1990

The effect of amino acid substitutions at position 342 on the secretion of human alpha 1-antitrypsin from Xenopus oocytes.

A glutamic acid to lysine change in the Z variant of human alpha 1-antitrypsin is associated with a failure to secrete the protein from synthesising cells. The block in export of the protein may be caused either by the loss of an acidic residue or the introduction of a basic one at this point in the polypeptide chain. Site-directed mutagenesis has been used to construct novel alpha 1-antitrypsin mutants which show that the side chain interactions from Glu-342 are not obligatory for protein export and it is rather the introduction of a basic residue at this point which produces the intracellular accumulation of the protein.

Amino Acid Sequence↗
PubMed1990

The complete cDNA and amino acid sequence of bovine fetuin. Its homology with alpha 2HS glycoprotein and relation to other members of the cystatin superfamily.

The cDNA sequence encoding the bovine fetal protein fetuin is reported. The deduced amino acid sequence is identical with that obtained from amino acid sequencing. The protein is a single chain preceded by a signal sequence. The three N-linked glycosylation sites have been determined. The sequence of fetuin shows over 70% similarity to human alpha 2HS glycoprotein. All of the cysteine residues are conserved in both proteins, suggesting that fetuin has the same arrangement of disulfide loops as alpha 2HS glycoprotein and may also be a member of the cystatin family. Southern blot analysis indicates that a single gene codes for fetuin. No evidence for a separate gene for a bovine alpha 2HS glycoprotein was obtained; thus, fetuin in cattle and alpha 2HS glycoprotein in the human are equivalent proteins.

Amino Acid Sequence↗