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Biomedical subjects

S U Shin

Publications and source records attributed to S U Shin.

23 records · Page 2Linked to original sources

Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells.

We have examined the molecular mechanism and impact of somatic diversification on the T15 heavy chain variable region gene in vivo and in vitro. Somatic point mutation appears to be responsible for the changes we have observed in both hybridomas from early and late in the immune response and in the S107 myeloma cell line in culture. By identifying S107 mutants with decreases in antigen binding, we have shown that a single point mutation can cause the loss of binding to the eliciting antigen and the acquisition of binding to another antigen. Furthermore, in this case a point mutation of the T15 heavy chain variable region gene caused the conversion of an important protective antibody to an autoantibody. While the S107 cell line frequently generates both constant and variable region mutants, hybridomas appear to have relatively stable variable region genes and unstable constant region genes which in some cases result in mutants with increased binding.

Animals↗

The role of monoclonal antibodies and the recombinant DNA technology in studying autoantibody production.

The hybridoma technology has made it possible to sample the B-cell repertoire and to generate monoclonal antibodies which can be analyzed for their specificity and idiotypy. Using the recombinant DNA technology, the structure of the genes which encode those antibodies can be analyzed. The knowledge gained from the application of these techniques has made it possible to pose specific questions about the origins of autoantibodies.

Animals↗

The pharmacokinetics of heroin in patients with chronic pain.

We measured blood concentrations of heroin and its active metabolites, 6-acetylmorphine and morphine, serially in 11 patients with chronic pain (9 of whom had cancer) after intravenous injection, intravenous infusion, intramuscular injection, and an oral dose of heroin hydrochloride. Parenteral heroin provided measureable blood levels of heroin, 6-acetylmorphine, and morphine. Blood levels of heroin and 6-acetylmorphine reached their maximal concentrations within minutes and were cleared rapidly. The mean half-life of heroin (+/- S.D.) after intravenous injection or infusion was only 3.0 +/- 1.3 minutes, and the mean clearance of heroin from the blood at apparent steady state was 30.8 +/- 2.1 ml per kilogram of body weight per minute. Morphine levels rose more gradually, and morphine was cleared much more slowly. Oral administration of heroin resulted in measurable blood levels of morphine but not of heroin or 6-acetylmorphine. The amount of circulating morphine provided by an oral dose of heroin was only 79 per cent of that available from an equal amount of morphine. We conclude that heroin is a pro-drug that serves to determine the distribution of its active metabolites. Parenteral heroin is rapidly converted to 6-acetylmorphine, which contributes to rapid pain relief. Oral heroin is converted to morphine and appears to be an inefficient means of providing morphine to the systemic circulation.

Administration, Oral↗

Determination of heroin and its metabolites by high-performance liquid chromatography.

A method is described for the simultaneous determination of heroin (3,6-diacetylmorphine, DAM) and its two active metabolites 6-acetylmorphine and morphine in blood by high-performance liquid chromatography using a normal-phase column and a UV detector at 218 nm. The compounds are stabilized in blood by rapid freezing and recovered by a multistep liquid--liquid extraction. The mobile phase is acetonitrile--methanol (75:25, v/v) buffered to apparent pH 7 with ammonium hydroxide and acetic acid. Using l-alpha-acetylmethadol as an internal standard, UV detection and a 1-ml biofluid sample, the lower limit of sensitivity is 12.5 ng/ml. Commonly used narcotic analgesics including codeine, propoxyphene, meperidine, methadone and levorphanol do not interfere with the analysis. The method has been applied to blood samples from humans and rats. Extracts of blood from a patient who had received an intravenous dose of 14 mg of DAM contained DAM and both of its active metabolites.

Animals↗