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Biomedical subjects

M R Price

Publications and source records attributed to M R Price.

205 records · Page 12Linked to original sources

Analysis of monoclonal antibodies for identification of antigens associated with tumours of the gastrointestinal tract.

The reactivity of a new anti-human gastric carcinoma antibody, GL-013 with gastrointestinal tissue sections, with subcellular membranes (both from normal and malignant specimens), and with a variety of purified tumour antigens, has been evaluated and compared with that of a panel of monoclonal antibodies. These include antibodies against carcinoembryonic antigen (CEA), normal cross reacting antigen (NCA) and the Y-hapten. The reactivity of GL-013 antibody was distinct from, but not superior to that of the existing reagents. Of these, the antibody against the Y hapten was the most discriminatory with respect to its preferential reactivity with tumours, and the target tetrasaccharide comprising the Y hapten determinant was identified upon a variety of cellular macromolecules, including glycoproteins, glycolipids and on epidermal growth factor receptors. This is in accord with its frequent association with tumours.

Antibodies, Monoclonal↗

Sequential order of T and B cell epitopes affects immunogenicity but not antibody recognition of the B cell epitope.

Synthetic peptide constructs, co-linearly linking a MUC1 mucin B cell epitope peptide to a known murine T cell epitope, both in T-B and B-T orientations, show that induction of high murine anti-MUC1 antibody titers is dependent on the presence and orientation of the T cell determinant. However, the sequential order of the epitopes does not affect binding of anti-B cell epitope antibodies to the constructs. Haplotype mismatching leads to a significant lowering of the anti-MUC1 antibody responses, implicating a central role for the T cell epitope in eliciting anti-B cell epitope responses. Secondary structure analysis by circular dichroism spectroscopy reveals the T-B construct to be partially ordered, while the B-T peptide adopts a highly ordered conformation in trifluoroethanol. These studies suggest that the sequential order of epitopes may significantly alter the immunogenicity of the peptide but may not necessarily affect its antigenicity. Immunogenicity of the peptide constructs may be governed by subtle differences in secondary structure, leading to variation in the way peptides are presented or processed within cells governing immune responses. These findings have relevance for the construction of peptides to be utilized as potential synthetic vaccines and for the design of peptide immunogens.

Amino Acid Sequence↗

Evaluation of the IMMULITE BR-MA and CEA assays and comparison with immunoradiometric assays for CA15-3 and CEA in breast cancer.

This study was designed to evaluate the performance of a new automated assay system, the IMMULITE Automated Immunoassay Analyzer in comparison with more commonly used IRMA assays for measuring circulating tumour marker levels in breast cancer patients. The assays investigated measure the MUC1 mucin (CA15-3 antigen) or CEA. Serum samples from breast cancer patients with various stages of disease and from a group of normal individuals were analysed. Significant correlations were found between tumour marker levels measured using the IMMULITE BR-MA and the CA15-3 assays and between levels measured using the two CEA assay formats. Levels of IMMULITE BR-MA and CEA correlated with stage of disease suggesting that both are markers of tumour burden Levels in Stage III breast cancer patients were found to be significantly higher than those of normals using the IMMULITE system but not the IRMA assays. This would suggest a role for the automated system in the monitoring of breast cancer at an earlier stage than that at which tumour markers are routinely used. Elevated marker levels did not correspond to any particular site of metastasis however, a greater proportion of patients with multiple sites of metastasis had elevated levels compared with those with secondary disease at a single site. We conclude that the IMMULITE Automated Immunoassay Analyzer is of value in the routine surveillance of tumour marker levels.

Automation↗

Expression of tumour associated antigens in normal, benign and malignant human mammary epithelial tissue: a comparative immunohistochemical study.

Breast carcinoma cells may express a variety of clinically relevant epitopes, some of which are associated with aberrant glycosylation of MUC1 mucin molecules, as well as determinants which are commonly expressed on their normal molecular counterparts. The present investigation is primarily an immunochemical analysis of MUC1 epitopes and other tumour associated antigenic determinants, as defined by their reaction with monoclonal antibodies and expressed in normal, benign and malignant epithelia. It was determined that malignant tissues of the breast expressed MUC1 mucin, as well as the Le(y) hapten and CEA, at different intensities, cellular distribution and patterns and percentages of positively stained cells. Conversely, benign tissues expressed a low intensity of MUC1 which was restricted to apical cell surface membranes and lumen debris; a similar pattern was found in some normal breast sections. It was concluded that MUC1 mucin exhibits heterogeneous antigenicity (as defined by its reactivity with a panel of related anti-MUC1 monoclonal antibodies) which is predominantly related to the progression of malignant disease. Le(y) is a marker of breast neoplasia, while CEA was found on only a small proportion of tumours. These immunohistochemical findings are considered in the context of improving breast cancer diagnosis and therapy.

Antibodies, Monoclonal↗

A pharmacology review for private duty nurses using computers and self learning concepts.

Computers, rather than instructors, patiently tutored the nurses, providing them with as much practice as necessary to master calculation skills. Instruction was consistent and readily available. Traditional printed material also was used because of its portability and accessibility. It was reassuring for the nurses to have something tangible to review. Program evaluations were positive. Comments such as the following were not uncommon: "The computer is a patient tutor; it never criticizes or tires"; "It was better than attending a workshop or lecture. I really learned the material because I was responsible for my learning." Currently, this group of nurses is using computer-assisted instructional programs for professional development. With the help and guidance of the PENZANCE staff, they overcame their fear of the technology and are now requesting that more programs be made available. It was a good experience for all.

Computer-Assisted Instruction↗

Evaluation of Pepscan analyses for epitope mapping of anti-MUC1 monoclonal antibodies--a comparative study and review of five antibodies.

Many murine monoclonal antibodies against MUC1 mucin have been analysed for reactivity against short overlapping peptides with sequences based upon that of the 20 amino acid tandem repeat of the MUC1 protein core, in order to identify the minimum binding units or epitopes. This report summarises the findings using a set of overlapping heptamers to identify the epitopes of 5 established anti-MUC1 antibodies. The results are evaluated and reviewed in comparison to those obtained using other length peptides and other assay formats for epitope mapping using the Pepscan technique.

Amino Acid Sequence↗