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J K Scott

Publications and source records attributed to J K Scott.

13 recordsLinked to original sources

A family of concanavalin A-binding peptides from a hexapeptide epitope library.

The lectin concanavalin A (Con A) binds methyl alpha-D-mannopyranoside (Me alpha Man) as well as alpha-D-mannosyl groups at the nonreducing terminus of oligosaccharides. Ligand peptides that mimic the binding of Me alpha Man to Con A were identified from screening an epitope library composed of filamentous phage displaying random hexapeptides. A consensus sequence was identified among affinity-purified phage; Con A binds phage bearing this sequence and is inhibited from doing so by Me alpha Man. When tested for binding against a panel of lectins, phage bearing this sequence bind only weakly to a closely related D-mannose-binding lectin, indicating that binding to Con A is highly selective. A synthetic peptide bearing the consensus sequence blocks the precipitation of Con A by dextran with an inhibition strength equivalent to that of methyl alpha-D-glucopyranoside. These results demonstrate that the specificity of Con A is not limited to carbohydrates and that highly selective sugar-mimics for lectins of plant, animal, or bacterial origin may be identified from epitope libraries.

Amino Acid Sequence

Discovering peptide ligands using epitope libraries.

Epitope libraries are large collections of peptides. Each peptide is displayed on the surface of a bacteriophage particle and is encoded by a randomly mutated region of the phage genome, thus associating each unique peptide with the DNA molecule encoding it. Antibodies and other binding proteins are used to select specifically for rare, phage-bearing peptide ligands; sequencing of the corresponding viral DNA will reveal their amino acid sequences. Relatively high-affinity peptides for a variety of peptide- and non-peptide-binding ligates have been affinity-isolated from epitope libraries. This technology has been used to map epitopes on proteins and to find peptide mimics for non-peptide-binding ligates. The current challenge lies in developing epitope library technology so that tight-binding peptide ligands can be detected for a wider variety of ligates, including those that recognize folded proteins. Should this be accomplished, many powerful applications can be envisioned in the areas of drug design and the development of diagnostic markers and vaccines.

Amino Acid Sequence

Conotoxins.

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Amino Acid Sequence

Searching for peptide ligands with an epitope library.

Tens of millions of short peptides can be easily surveyed for tight binding to an antibody, receptor or other binding protein using an "epitope library." The library is a vast mixture of filamentous phage clones, each displaying one peptide sequence on the virion surface. The survey is accomplished by using the binding protein to affinity-purify phage that display tight-binding peptides and propagating the purified phage in Escherichia coli. The amino acid sequences of the peptides displayed on the phage are then determined by sequencing the corresponding coding region in the viral DNA's. Potential applications of the epitope library include investigation of the specificity of antibodies and discovery of mimetic drug candidates.

Amino Acid Sequence

Diagnostic pneumoperitoneum.

Pneumoperitoneum as a diagnostic procedure has been practised for many years but there is a reluctance to make use of it. The author believes that this is due in some degree to lack of clearly defined indications and partly to lack of confidence in the safety of the procedure. In this paper the technique of diagnostic pneumoperitoneum is described and the risks are examined. Indications for its use are described. Finally, three case histories of special relevance are described and a summary of the results is tabulated with a view of giving an estimate of the diagnostic value which may be expected.

Adult

Mechanical property changes of barium titanate (ceramic) after in vivo and in vitro aging.

Since barium titanate (BaTi03) can be made piezoelectric, it may be used to substitute hard tissues directly. As a first step in testing this concept, a series of in vivo and in vitro aging and biocompatibility studies were performed. The mean compressive strength of samples implanted subcutaneously in the backs of rabbits decreased to 138 MPa after 20 weeks from a control value of 281 MPa. Similar, though less drastic losses of strength were seen when specimens were aged in distilled water (182 MPa at 28 weeks) and Ringer's solution (159 MPa at 28 weeks). The most rapid decrease of strength in all cases was seen prior to 4 weeks. Thereafter, the decrease was much slower. Histological evaluation of the tissue surrounding the implant revealed a thin fibrous capsule and no evidence of tissue inflammation.

Animals

S-carboxymethylcysteine in the fluidification of sputum and treatment of chronic airway obstruction.

The clinical results and changes in sputum found in both a short-term inpatient trial and a subsequent long-term outpatient investigation (three-month double-blind controlled study) of 82 patients with chronic bronchitis treated with a new mucolytic agent, S-carboxymethylcysteine (Mucodyne), are reported. Fluidification of sputum with reduction in certain measurements of the viscosity of morning sputum aliquots, associated with improvement in the ability to cough up bronchial secretions, significant increase in sputum volume output, and improvement in ventilation (as estimated by the forced expiratory volume in one second), were observed in both trials as dose-related responses, with an increase in the ease of expectoration and a reduction in cough frequency and dyspnea. Therapy with S-carboxymethylcysteine was well tolerated, and there were no serious adverse effects, either immediate or delayed. We suggest that the effect of the drug in fluidifying sputum may be due to a mucoregulatory mechanism which reverses the sputum macromolecular disturbances seen in chronic bronchitis.

Administration, Oral

The diagnosis of asbestosis.

Lung biopsy in 16 patients with abnormal lung function and who had been exposed to asbestos revealed asbestosis in 4 with considerable radiological evidence of the disease, in of 4 with minimal radiological changes and in none of 8 with completely clear radiographs. Thus biopsy for the diagnosis of this condition should be avoided if the chest radiograph shows no evidence of it.

Adult