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Biomedical subjects

R N Smith

Publications and source records attributed to R N Smith.

At least 91 records · Page 5Linked to original sources
PubMed1984

Ranitidine and cimetidine in prevention of duodenal ulcer relapse. A double-blind, randomised, multicentre, comparative trial.

In a comparative trial of preventive medication for duodenal ulceration with 51 participating centres, 484 patients were recruited for a year's maintenance treatment with the recommended bedtime dose of ranitidine (150 mg; n = 243) or cimetidine (400 mg; n = 241). These outpatients had recently healed duodenal ulcers, confirmed by endoscopy before and after healing, and ulcer relapse was monitored by endoscopy every 4 months. The distribution of factors likely to influence ulcer recurrence was similar in the two treatment groups. A life-table method of analysis showed that the ulcer relapse rate was consistently and significantly lower on ranitidine that on cimetidine (8% v 21%, p = 0.0018 at 4 months; 14% v 34%, p less than 0.0001 at 8 months; and 23% v 37%, p = 0.004 at 12 months). Crude relapse rate calculations, which underestimate the probability of ulcer recurrence, also confirmed the significant superiority of ranitidine 150 mg over cimetidine 400 mg nightly in preventing ulcer recurrence throughout the year.

Adult↗
PubMed1984

Papain hydrolysis of X-phenyl-N-methanesulfonyl glycinates: a quantitative structure-activity relationship and molecular graphics analysis.

The hydrolysis of 32 X-phenyl-N-methanesulfonyl glycinates by papain was investigated. It was found that the variation in the Michaelis constants could be rationalized by the following correlation equation: log 1/Km = 0.61 pi '3 + 0.46 MR4 + 0.55 sigma + 2.00 with a correlation coefficient of 0.945. In this expression, pi '3 is the hydrophobic constant for the more lipophilic of the two possible meta substituents, MR4 is the molar refractivity of 4-substituents, and sigma is the Hammett constant summed for all substituents. Using this equation, we designed, synthesized, and successfully predicted Km for a new congener intended to maximize binding (1/Km). The interactions involved in enzyme-substrate binding, as characterized by the correlation equation, are interpreted using a computer-constructed color three-dimensional-graphics molecular model of the enzyme active site. The nonenzymatic hydrolysis (both acid and basic) of phenyl hippurates yield rate constants which are well correlated by Hammett equations; however, log k for both acid and alkaline hydrolysis are not linearly related to log 1/Km or log kcat/Km.

Binding Sites↗
PubMed1984

Radioimmunoassay of benzoylecgonine in samples of forensic interest.

A simple and economical radioimmunoassay for benzoylecgonine in blood or urine is described. Haemolysis, decomposition, common anticoagulants and sodium fluoride do not affect the results. A commercially available antiserum is used at a dilution of 1:600. The tracer is radioiodinated p-hydroxybenzoylecgonine. It is prepared by reacting p-acetoxybenzoic anhydride with methyl ecgonine followed by mild hydrolysis and radioiodination by the Iodo-gen method. The product is purified on a disposable silica cartridge and has a specific activity of about 30 TBq mmol-1. Polyethylene glycol is used to separate the bound and free fractions in the assay. The range of the dose-response curve is 0-400 ng ml-1 benzoylecgonine. The assay is largely specific for benzoylecgonine. Cocaine, ecgonine, methylecgonine and cinnamoyl cocaine have slight or negligible cross-reactivities. The inter-assay coefficient of variation is 7.5% and the recovery of benzoylecgonine from 'spiked' blood is 103%. The 'cut-off' is 20 ng ml-1 benzoylecgonine for both blood and urine. Radioimmunoassay and high-performance liquid chromatography results agree well.

Chromatography, High Pressure Liquid↗
PubMed1983

Methadone radioimmunoassay: two simple methods.

Two simple and economical radioimmunoassays for methadone in blood or urine are described. Haemolysis, decomposition, common anticoagulants and sodium fluoride do not affect the results. One assay uses commercially-available [1-3H](-)-methadone hydrobromide as the label, while the other uses a radioiodinated conjugate of 4-dimethylamino-2,2-diphenylpentanoic acid and L-tyrosine methyl ester. A commercially-available antiserum is used in both assays. Normethadone and alpha-methadol cross-react to a small extent with the antiserum while methadone metabolites, dextropropoxyphene, dipipanone and phenadoxone have negligible cross-reactivities. The 'cut-offs' of the two assays as described are 30 and 33 ng ml-1 for blood, and 24 and 21 ng ml-1 for urine. The assay using the radioiodinated conjugate can be made more sensitive if required by increasing the specific activity of the label.

Chromatography, High Pressure Liquid↗
PubMed1982

Susceptibility to adjuvant arthritis in DA and F344 rats. A dominant trait controlled by an autosomal gene locus linked to the major histocompatibility complex.

The hereditary of adjuvant-induced arthritis in rats of the DA and Fisher 344 strains was examined. Development of arthritic lesions in response to a single injection of supplemented Freund's complete adjuvant has been found to be controlled by an autosomal, dominant gene locus, Ar. The capacity to respond was present in DA rats and absent in our Fisher rats. Ar has been found to be linked to the major histocompatibility complex genes with which it exhibits a high rate of recombination.

Animals↗
PubMed1982

The alloantibody response in the allogeneically pregnant rat. II. Primary pregnancy-induced anti-RT1Aa alloantibodies are not as cross-reactive as secondary pregnancy-induced or conventionally raised alloantibodies.

We compared the cross-reactive pattern of alloantibodies from conventional anti-DA alloimmunizations with anti-RT1Aa alloantibodies brought about by secondary and primary pregnancy-induced alloimmunizations caused by pregnancies by DA males. As expected, conventional alloimmunization produces alloantibodies that are cross-reactive; secondary pregnancy-induced anti-RT1Aa alloantibodies induced by pregnancies by DA males in females previously immunized against DA were as cross-reactive as conventionally raised antibodies. But primary pregnancy-induced anti-RI1Aa alloantibodies brought about by DA pregnancies in unimmunized females were not as cross-reactive as alloantibodies from conventional or secondary pregnancy-induced alloimmunizations. The cross-reactive pattern of the alloantibodies from primary pregnancy-induced alloimmunizations was distinctive for each of the three responding strains, but the cross-reactive pattern observed for a particular strain was not uniformly seen in all the responding females of that strain. One such pattern between two congenic strains defines an Ir gene between two RT1 phenotypes that are known to be high responders to RT1Aa.

Animals↗
PubMed1982

The alloantibody response in the allogeneically pregnant rat. I. The primary and secondary responses and detection of Ir gene control.

We compared the primary pregnancy-induced alloantibody responses with secondary pregnancy-induced responses and with conventional immunologic responses and found there are profound differences. Conventional and secondary responses produce strong lytic sera and readily detectable immunologic memory. The primary pregnancy-induced responses lack memory and produce alloantisera or widely variable titer. Such sera were rarely directly lytic. Pregnancy-induced primary responses detect MHC Ir gene control, even when the allogeneic difference is a complete HMC haplotype. The kinetics of the primary and secondary pregnancy-induced alloantibody responses against DA were different. We conclude that the primary pregnancy-induced alloantibody response is very different immunologically from conventional and secondary pregnancy-induced alloimmunizations.

Animals↗
PubMed1982

The alloantibody response in the allogeneically pregnant rat. III. The location of the alloantibody-forming cells.

We determined the location of alloantibody formation in the allogeneically pregnant rat. Greater than 95% of the alloantibody-forming cells were found in the spleen. A few were found in the paraaortic, renal, and parathymic lymph nodes. None were found in other lymphomyeloid organs. In addition, in vitro alloantibody synthesis was largely confined to splenic cells. We conclude that the alloantibody response in the allogeneically pregnant rat is largely peripheral to the uterus and to the lymph nodes that drain the uterus. Therefore, the alloantibody response in the allogeneically pregnant rat cannot be considered an example of a local immune response. In addition, we confirmed that the anti-paternal humoral response against RT1Aa caused by pregnancies by DA males differs dramatically from conventional and secondary pregnancy-induced alloimmunizations because the hierarchy of the number of alloplaques that are developed by these four methods of detecting alloplaques is different for primary pregnancy-induced responses as compared with conventional or secondary pregnancy-induced alloimmunizations.

Animals↗
PubMed1981

A simple solid-phase radioimmunoassay for morphine and related opiates using a mixture of labelled morphine and antiserum pre-precipitated by polyethylene glycol.

A novel, solid-phase radioimmunoassay for morphine and related opiates is described in which radiolabelled morphine, antiserum and polyethylene glycol are premixed before being added to the samples or standards. The mixture can be stored at 2 degrees C and used for several months until decay of the 125I label leads to excessively long counting times. The method was developed using the Roche Abuscreen radioimmunoassay for morphine and has the particular advantages of simplicity (only 2 pipetting steps required instead of 5) and economy (800 assay tubes can be prepared from a 100-tube Abuscreen plus a 50% saving in operator time). The procedure can be applied to other assays providing the polyethylene glycol-precipitated antiserum is stable and that the antibody affinity for the labelled compound is not so high as to prevent displacement of the labelled compound from the antibody binding sites by unlabelled drug.

Barbiturates↗
PubMed1980

Radioimmunoassay of diazepam in samples of forensic interest.

The radioimmunoassay of diazepam in biological fluids is described. The method is particularly applicable to samples encountered in forensic toxicology that may be haemolysed, decmposed and of small volume. The antiserum and tritiated diazepam that are used are commercially available. Polyethylene glycol (mol. wt 6000) is used to separate the bound and free fractons, and the free fracion is counted by extracting the tritiated diazepam into a toluene-based scintillant. Blood samples are extracted with ethyl acetate before analysis but urine samples may be assayed directly. The assay is convenient, quick and virtually specific for diazepam. The results correlate well with those obtained by gas chromatography.

Binding Sites↗