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Biomedical subjects

J R Preston

Publications and source records attributed to J R Preston.

11 recordsLinked to original sources

A RIA combined with SPE for the determination of a dual D2-receptor and beta2-adrenoceptor agonist, AR-C68397XX, in human plasma.

A radioimmunoassay has been developed for the determination of AR-C68397XX, a dual D2-receptor and beta2-adrenoceptor agonist, in human plasma. The method incorporates solid phase sample extraction and is suitable for the determination of the analyte at pg ml(-1) concentrations. The antiserum was raised in Suffolk cross sheep following primary and booster immunisations with an immunogen prepared by conjugating a carboxyphenylmethyl derivative of AR-C68397XX, to bovine serum albumin. The radioligand was prepared by the 125I-labelled iodination of a derivative of AR-C68397XX. The solid phase extraction procedure, using octadecyl sorbent, was introduced to remove matrix interferences in the plasma and to enhance method sensitivity. The calibration range is 20-500 pg ml(-1), using 0.5 ml of undiluted human plasma sample.

Adrenergic beta-2 Receptor Agonists↗

A radioimmunoassay combined with solid-phase extraction for the determination (pg ml-1) of AR-C15849XX) in human plasma.

A radioimmunoassay has been developed for the determination of AR-C15849KF, a CCK-8 analogue, in human plasma. The method incorporates solid-phase sample extraction, is suitable for the determination of the analyte at pg ml-1 concentrations and is based on a method developed and validated for dog plasma. The solid-phase extraction, using ion-exchange aminopropyl and octadecyl sorbents sequentially, was retained for this procedure to remove matrix interferences in the plasma and to enhance method sensitivity. The calibration range is 10-500 pg ml-1, using a 1 ml sample of undiluted human plasma. The method has been successfully used to generate early human pharmacokinetic data during a programme of exploratory development.

Animals↗

A radioimmunoassay combined with solid-phase extraction for the determination of a novel anti-obesity agent, ARL 15849XX, in dog plasma.

A radioimmunoassay has been developed for the determination of ARL 15849XX, a cholecystokinin-8 (CCK-8) analogue, in dog plasma. The method incorporates solid-phase sample extraction and is suitable for the determination of the analyte at picogram per millilitre concentrations. The antiserum was raised in Suffolk-cross sheep following primary and booster immunisations with an immunogen prepared by conjugating ARL 16935XX, an analogue of ARL 15849KF, to bovine serum albumin. The radioligand was prepared by the no-carrier-added 125I iodination of a non-sulphated derivative, ARL 15745XX. The solid-phase extraction procedure, carried out using ion-exchange aminopropyl and octadecyl sorbents sequentially, was introduced to remove matrix interferences in the plasma and to enhance the method sensitivity. The calibration range is 20-1000 pg ml-1, using a 1 ml sample of undiluted dog plasma.

Amino Acid Sequence↗

A radioimmunoassay for the determination of tipredane in human plasma.

A sensitive method for the determination of tipredane in human plasma has been developed. Prior to radioimmunoassay, proteins are removed from plasma by precipitation with acetonitrile. A [125I]iodohistamide derivative of tipredane is used as a heterogeneous radioligand. The primary antiserum is raised in sheep against a tipredane (O-carboxymethyl) oxime-bovine serum albumin conjugate. Donkey anti-sheep IgG antiserum is used as the secondary antiserum in a double antibody separation procedure. The limit of quantification of the method is 1 ng ml-1 for 500 microliters of plasma. There is no significant interference from either established or putative metabolites of tipredane, endogenous steroids or a wide range of other drugs. The assay was used to determine the concentrations of tipredane in plasma samples collected in pilot clinical studies.

Administration, Topical↗

A radioimmunoassay method for the determination of nedocromil sodium in plasma and urine.

A radioimmunoassay method for the determination of nedocromil sodium (FPL 59002 disodium salt) in human plasma and urine is described. The method employs a primary antiserum raised in a sheep, and a mono-tyramide derivative of nedocromil sodium labelled with iodine-125 as a heterogeneous radioligand. Free and bound radioligand are separated using a secondary anti-sheep IgG antiserum. All three reagents are added simultaneously to samples containing nedocromil sodium prior to an overnight incubation. The method has a limit of detection of 0.25 ng ml(-1), when plasma sample volumes of 100 microl are analysed, and is accurate and precise. Inter-assay relative standard deviations (N = 18) of 15.1, 5.0 and 5.6% were found at concentrations in plasma of 0.5, 2.0 and 6.0 ng ml(-1) respectively. The method is specific as indicated by negligible cross-reaction of the anti-nedocromil sodium antiserum with a range of drugs. The method is applicable to the analysis of samples from subjects who have inhaled nedocromil sodium from a pressurised aerosol.

Journal Article↗

Indirect [3H]methyl exchange as a general method for labeling methionine residues: application to calcitonin.

Native porcine calcitonin from Armour is known to contain two components. It is shown that these can be separated by cation-exchange chromatography in 8 M urea. The technique of [3H]methyl exchange on the methionine residue was used to prepare each of these in a tritiated form. The reduced components formed by demethylation were found to readily reoxidize at neutral pH, to regenerate the disulfide bridge. Evidence is provided to show that the two forms were partially interconverted during these steps. The reoxidized 3H-labeled products were found to be indistinguishable in chemical, immunological, and biological properties from the equivalent components in native porcine calcitonin and had specific activities of approximately 20 Ci/mmol. It is concluded that this labeling method can be conveniently applied to peptides containing one or more disulfide bridges, to give products of high specific activity in acceptable yield, provided appropriate conditions are used to ensure correct reoxidation occurs.

Animals↗

Psoriatic spondylitis in a patient with classical rheumatoid arthritis.

A patient exhibiting typical features of classical rheumatoid arthritis and psoriatic spondylitis is described. The patient, a woman, presented at the age of 29 with an inflammatory arthritis. Twenty years later, she developed psoriasis, and after a further 3 years, she was first noted to have rheumatoid nodules and to be strongly seropositive. Now at the age of 60, she has a rigid spine with radiographic changes of spondylitis. Neither rheumatoid arthritis, nor psoriatic spondylitis can account for all the features of her disease and there is evidence to suggest that both conditions combined to damage her peripheral joints.

Adult↗

Radioimmunoassay of sodium cromoglycate in human plasma.

A sensitive radioimmunoassay method for sodium cromoglycate in human plasma is described. The lowest quantifiable concentration of sodium cromoglycate is 0.93 nmol/l when 0.1 ml plasma samples are analysed. Direct analysis of sodium cromoglycate concentrations in plasma samples collected up to several hours after the administration of single therapeutic doses of the compound is possible. An antiserum raised in a sheep, radioligand heterogeneously labelled with iodine-125, and a second antibody technique for the separation of bound and free radioligand are employed. The inter-assay coefficient of variation is less than 14% (n = 23). The range of the method is limited; both 0.01 and 0.1 ml volumes of plasma must be analysed to encompass the concentration range 0.93-139 nmol/l which may be encountered in plasma samples from patients and human volunteers. The method is specific for sodium cromoglycate as indicated by a low cross-reactivity of the anti-cromoglycate antiserum with a number of drugs.

Animals↗

Neonatology.

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Adult↗