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Biomedical subjects

B Eddy

Publications and source records attributed to B Eddy.

8 recordsLinked to original sources
PubMed2003

Reliability of pre-operative biopsies in the histological grading of colorectal adenocarcinomas.

BACKGROUND: Management of colorectal cancer depends on many patient and tumour variables. Decisions are sometimes based on the histological grade of tumour as assessed by initial biopsy. This retrospective study looked at the reliability of grading colorectal cancer from pre-operative biopsies. METHODS: 118 patients with a diagnosis of colorectal cancer, who had adequate pre-operative biopsies, were included in the study. A single consultant histopathologist re-examined all the preoperative biopsy slides, but was blinded to the final grading of the resection specimen. RESULTS: Of the 118 resection specimens, 41 were graded well-differentiated, 52 moderately differentiated and 25 poorly differentiated. When compared with postoperative grading, 37 (31%) initial biopsies were undergraded, 49 (43%) were correctly graded and 32 (26%) were overgraded. CONCLUSIONS: These results suggest that the histological grading of pre-operative specimens is inaccurate and should be used with caution to determine treatment. The difficulty with grading pre-operative biopsies in colorectal cancer may be owing to a lack of specific criteria such as is used in, for example, breast cancer.

Adenocarcinoma↗
PubMed1984

Monoclonal antibodies detect the conservation of muscarinic cholinergic receptor structure from Drosophila to human brain and detect possible structural homology with alpha 1-adrenergic receptors.

Muscarinic cholinergic receptors isolated from Drosophila heads, rat and human brain, dog heart, and monkey ciliary muscle were examined for structural similarities/differences by utilizing isoelectric focusing, sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and monoclonal antibody crossreactivity. Muscarinic receptors were affinity labeled with [3H]propylbenzilylcholine mustard and subjected to isoelectric focusing. Muscarinic receptors from each species focused with an isoelectric point of 5.9. The same proteins all migrated with an apparent molecular mass of 80,000 daltons on sodium dodecyl sulfate gels. Six hybridomas secreting monoclonal antibodies specific for muscarinic receptors were developed by using purified rat brain muscarinic receptors as the antigen. The six different monoclonal antibodies immunoprecipitated muscarinic receptors from all tissues and species tested, including human and Drosophila brains, with equal efficacy. These data indicate that muscarinic receptors are highly conserved over a considerable evolutionary period. One of the six muscarinic receptor monoclonal antibodies also immunoprecipitated rat liver alpha 1-adrenergic receptors. Furthermore, two out of five monoclonal antibodies raised against alpha 1-receptors immunoprecipitated muscarinic receptors. These data suggest that some degree of structural homology exists between muscarinic cholinergic receptors and alpha 1-adrenergic receptors.

Animals↗
PubMed1984

Alpha 1-adrenergic receptor structure.

The structure of the alpha 1-adrenergic receptor was investigated by comparing polypeptides identified by sodium dodecyl sulfate (NaDodSO4)-polyacrylamide gel electrophoresis with the size of the intact receptor in cell membranes as determined by target size analysis. The alpha 1-adrenergic receptor from rat liver membranes affinity-labeled with [3H]phenoxybenzamine, a covalent affinity reagent, appeared as a single polypeptide with a molecular mass of 85,000 daltons (Da) on NaDodSO4-polyacrylamide gels. In the absence of protease inhibitors, smaller peptides of 58-62 kDa and 40-45 kDa, specifically labeled with [3H]phenoxybenzamine, were also apparent on NaDodSO4 gels. In order to determine whether the 85-kDa protein represented all or only a portion of the alpha 1-receptor, radiation inactivation (target size analysis) was undertaken. Radiation-induced receptor inactivation was measured by the loss of specific [3H]phenoxybenzamine and [3H]prazosin binding and by the loss of affinity-labeled alpha 1-adrenergic receptors on NaDodSO4 gels. Target size analysis of rat liver alpha 1-receptors indicated that the intact membrane-bound receptor has an average molecular mass of 160,000 Da. These data suggest that the intact alpha-receptor may exist in the membrane as a dimer of two 85,000-Da subunits. The structure of the alpha 1-receptor was further studied by limited proteolysis of the 85-kDa protein isolated from NaDodSO4 gels. Trypsin, chymotrypsin, and papain produce smaller peptides similar to those produced during membrane isolation in the absence of protease inhibition. Limited proteolysis of the membrane-bound receptor produces water-soluble peptides, the largest of which is 45,000 Da. This peptide contains the ligand-binding domain and protrudes from the membrane into the extracellular space.

Animals↗
PubMed1983

Autoantibodies and monoclonal antibodies in the purification and molecular characterization of neurotransmitter receptors.

The combination of immunological advances with membrane receptor research has promoted rapid progress in the molecular characterization of neurotransmitter receptor molecules. We have to date produced monoclonal antibodies to beta 1-, beta 2-, and alpha 1-adrenergic, D2-dopaminergic, and muscarinic receptors. In addition we have discovered that some allergic respiratory disease patients possess circulating autoantibodies to beta 2-adrenergic receptors. These antireceptor antibodies in conjunction with specific receptor affinity reagents have allowed us to isolate, purify, and begin to characterize alpha- and beta-adrenergic, dopaminergic, and muscarinic receptors. For example, immunoprecipitation of turkey erythrocyte beta 1 receptors with monoclonal antibodies yields a single polypeptide Mr 65--70 K. In contrast, purification of beta 2-adrenergic receptors using either autoantibodies or monoclonal antibodies yields a receptor species with a subunit of Mr 55--59 K. Autoantibodies to beta 2 receptors demonstrate a 50--100% homology among beta 2 receptors from humans to rats, whereas monoclonal antibody FV-104 recognizes a determinant in the ligand binding site of all beta 1 and beta 2 receptors tested to date. These data suggest that beta 1- and beta 2-adrenergic receptors may have evolved from a common ancestor, perhaps by gene duplication.

Animals↗
PubMed1983

Purification and molecular characterization of neurotransmitter receptors.

These data indicate a number of similarities between the neurotransmitter receptors of different pharmacological classes. We are pursuing the hypothesis that the neurotransmitter receptors may have evolved from one another and contain constant regions (eg, adenylate cyclase and calcium channel interaction sites) and variable regions (eg, neurotransmitter- or hormone-binding sites). It is clear that monoclonal antibodies are keys to this end.

Animals↗