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Biomedical subjects

P Wyeth

Publications and source records attributed to P Wyeth.

16 recordsLinked to original sources
PubMed1997

Cuticular metals: quantification and mapping by complementary techniques.

Metal-replete cuticle was characterised by back-scattered electron imaging, secondary ion mass spectrometry, proton induced X-ray emission and SEM-X-ray microanalysis. Each technique was found to have singular advantages and limitations for localising and quantifying metal content. Manganese and zinc were found coincident at the mandibular cutting edge of the leaf-cutting ant Atta sexdens; these two metals were found in different zones within jaws of the ragworm, Nereis virens; while only manganese was found in the jaws of the termite C. cumulans. Copyright 1997 Academic Press

Journal Article↗
PubMed1991

The enzyme-inhibitor approach to cell-selective labelling--I. Sulphonamide inhibitors of carbonic anhydrase as carriers for red cell labelling: in vitro uptake of pIBS by human red blood cells.

Red cell carbonic anhydrase is identified as an ideal target in an enzyme-inhibitor approach to radiolabel localisation. Current problems in blood pool labelling could be overcome by using selective sulphonamide inhibitors as carriers. p-Iodobenzenesulphonamide (pIBS) was selected as the choice reagent for red blood cell labelling. Rapid uptake of [125I]-pIBS was found in vitro, consistent with passive diffusion across the cell membrane. The intracellular binding could be attributed to interaction with two specific acceptor sites, with dissociation constants of 4.9 +/- 1.0 and 0.10 +/- 0.05 mumol dm-3, and maximum binding capacities of 166 +/- 5 and 19.9 +/- 1.0 mumol dm-3, respectively under the experimental conditions. These data correlate with the two major carbonic anhydrase isozymes; acceptor assignments were confirmed by gel chromatography of the red cell lysate.

Carbonic Anhydrase Inhibitors↗
PubMed1991

The enzyme-inhibitor approach to cell-selective labelling--II. In vivo studies with pIBS in small animals and man.

p-Iodobenzenesulphonamide (pIBS), a potent red cell carbonic anhydrase inhibitor, was used as a carrier for radioiodine in the enzyme-inhibitor approach to cell-specific blood labelling. Radioactivity distribution was monitored in rats and man following i.v. administration of the radiolabelled carrier or of pre-labelled red cells. Rat blood activity fitted a two compartment model; the half-life for overall elimination was 69 +/- 27 h. At 24 h most activity remained associated with red cells, but there was a significant uptake in the large intestine (10 +/- 6%). In man there was no significant accretion by gut or any other organ over 93 h, and the blood clearance was mono-exponential (t1/2 = 9.8 +/- 1.5 days).

Animals↗
PubMed1991

The enzyme-inhibitor approach to cell-selective labelling. III. Sulphonamide inhibitors of carbonic anhydrase as carriers for red cell labelling.

Selective radiolabelling of red blood cells via an enzyme-inhibitor approach represents a novel method in diagnostic nuclear medicine. Current problems in blood pool labelling could be overcome by using selective sulphonamide inhibitors as carriers. Red cell carbonic anhydrase is identified as an ideal target enzyme for such an approach. A brief review of the target enzyme is presented together with the screening of a series of synthesised sulphonamide inhibitors. p-Iodobenzenesulphonamide, 4-[(4-iodophenyl)thio]benzenesulphonamide and 5-(4-bromophenyl)sulphonyl]thiophene-2-sulphonamide were found to be particularly potent, reversible, lipophilic inhibitors of carbonic anhydrase, characteristics that warrant their further investigation as potential carriers. 4-Iodo-3-(iodoacetamido)benzenesulphonamide was a moderate inhibitor but caused relatively fast irreversible inactivation, making it a candidate for longer term studies.

Animals↗
PubMed1986

Radioiodinated iodobenzylguanidines for diagnosis and therapy.

Radiolabelled meta-iodobenzylguanidine has been one of the most successful of recent radiopharmaceuticals. In the short period of five years it has been shown to have high diagnostic sensitivity and specificity for many tumours of neuroectodermal origin. Furthermore its excellent concentration in many malignant tumours of this type offers a novel alternative treatment to those available at present.

3-Iodobenzylguanidine↗
PubMed1985

Lymphocyte labelling with indium: cytotoxicity studies.

Viability studies on lymphocytes labelled with indium In111 using oxine as a ligand showed impairment as measured by trypan-blue assessment and rosetting ability. In addition, lymphocyte response to phytohaemagglutinin stimulation as measured by tritiated-thymidine uptake was also impaired at levels where adequate cell labelling had taken place. Cadmium toxicity was not noticed, and the use of tropolone as a ligand offered possibilities of reduced cellular toxicity. Such cytotoxicity may not have been important in earlier reported studies on granulocytes where the large numbers available for in vivo work and the short periods of study still allowed useful conclusions to be drawn. However, because of the prolonged lifespan of the human lymphocyte, the cytotoxic effects of the processing might well make the long-term studies which would be of interest much less reliable for clinical assessment.

Cytotoxicity, Immunologic↗
PubMed1984

New approach to the localisation of phaeochromocytoma: imaging with iodine-131-meta-iodobenzylguanidine.

Thirty eight patients with known or suspected phaeochromocytoma were studied by radioisotope imaging after intravenous administration of iodine-131-meta- iodobenzylguanidine (131I- mIBG ), a radiopharmaceutical which has affinity for chromaffin tumours. Seventeen positive results (including one false positive) and 21 negative results (including two false negatives) were obtained. Clinical accuracy was 92%. Urinary noradrenaline concentrations were raised in all patients with confirmed phaeochromocytoma. These findings show that 131I- mIBG is of value in localising and assessing the extent of chromaffin tumours.

3-Iodobenzylguanidine↗
PubMed1982

Disseminated malignant phaeochromocytoma: localisation with iodine-131-labelled meta-iodobenzylguanidine.

Meta-iodobenzylguanidine, a guanethidine analogue, is a newly synthesised substance capable of imaging the adrenal medulla. In a woman in whom phaeochromocytoma has been diagnosed iodine-131-labelled metaiodobenzylguanidine was given intravenously; gamma-camera images showed bilateral adrenal tumours and uptake corresponding to bone and liver metastases. 131I-meta-iodobenzylguanidine is effective in localising phaeochromocytomas, and the technique is safe, specific, and non-invasive.

3-Iodobenzylguanidine↗
PubMed1982

The comparison of 8-hydroxyquinoline, tropolone, and acetylacetone as mediators in the labelling of polymorphonuclear leucocytes with indium-111: a functional study.

Tropolone forms a lipophilic complex with indium-111 which is capable of mediating the labelling of polymorphonuclear leucocytes (PMNs) by this isotope; labelling efficiencies are comparable with the best achieved using 8-hydroxyquinoline and acetylacetone. However, in terms of PMN chemotaxis and phagocytosis, tropolone is significantly less toxic than either of te other ligands. 8-Hydroxyquinoline was found to reduce PMN chemotaxis and phagocytosis to approximately 70% of the control values at a concentration of 20 micro M. Tropolone may prove a superior labelling reagent.

Chemotaxis, Leukocyte↗
PubMed1980

A proton-magnetic-resonance study of N-trifluoroacetyl-L-alanyl-L-phenylalaninal binding to alpha-chymotrypsin.

Cross-saturation NMR studies have shown that the dipeptide aldehyde N-trifluoroacetyl-L-alanyl-L-phenylalaninal forms a hemiacetal complex with alpha-chymotrypsin. The free aldehyde resonance was seen to broaden upon addition of alpha-chymotrypsin and a detailed analysis has identified the enzyme-bound hemiacetal as the species which was in slow exchange with the free aldehyde and so gave rise to the perturbation. The line broadening was found to be dependent on p2H and this behaviour could be adequately described by the ionisation of a single group on the free enzyme (pKa2H7.6) with the alkaline form being required for hemiacetal formation. The pH dependence of alpha-chymotrypsin-induced catalysis around neutral pH correlates well with the observed p2H dependence of hemiacetal formation, indicating that it is an intermediate in the catalytic mechanism.

Binding Sites↗
PubMedDate not supplied

Preparation and properties of FabIgG, a chimeric univalent antibody designed to attack tumour cells.

In order to promote the killing of tumour cells by antibody a derivative has been synthesized in which Fab'gamma from xenogeneic antibody is thioether-bonded to half-cystine on normal IgG of the species to be treated. The resulting entity, FabIgG, is obtained with about a 40% yield of the starting Fab'gamma. Being univalent it evades antigenic modulation. It activates complement efficiently, is minimally immunogenic, and appears to be catabolized at the slow rate characteristic of autologous IgG.

Animals↗