The thioether metabolite of sulphinpyrazone is between 8 and 13 times more potent than the parent compound as a competitive inhibitor of human, guinea pig and rabbit platelet aggregation induced by sodium arachidonate. Of the other known metabolites, the sulphone is approximately equipotent and the p-hydroxy compounds are much less potent that sulphinpyrazone itself. Malondialdehyde biosynthesis from sodium arachidonate by washed human platelets and collagen-induced aggregation of all three species is also inhibited by the thioether. It is 10 times more potent than sulphinpyrazone. ADP-induced aggregation is not affected by sulphinpyrazone, its thioether metabolite, nor the other metabolites. After intravenous administration of the thioether metabolite to groups of guinea pigs the inhibitory effect on sodium arachidonate-induced platelet aggregation ex vivo was long lasting (up to 24 h). In view of the recent information about the metabolism of sulphinpyrazone to its thioether in guinea pigs, we conclude that the thioether metabolite is the substance responsible for the prolonged effect of sulphinpyrazone on platelet function in this species and in man.
Five monoclonal antibodies (MAbs) were produced in a mouse hybridoma system against human placental glutathione transferase (GST pi). Four of these monoclonal antibodies, named 461 to 464, were of immunoglobulin G class, whereas the monoclonal antibody 465 was of IgA class. All these MAbs specifically recognized the glutathione transferase from human placenta (class pi) showing no cross reactivity against the basic and the neutral forms of GST from human liver. When each MAb was incubated with the GST pi, no inhibition of enzymatic activity towards 1-chloro-2,4-dinitrobenzene was observed except for MAb 465 which showed a slight inhibition to a serial dilution of 1:128.
The highly polymorphic system of serologically defined genetic markers on human IgG heavy chains (Gm allotypes) is second only to the HLA complex in terms of the large number of determinants, alleles, and haplotypes that can be used for analyses of disease associations and other genetic studies. However, present typing methods are based on the use of antiGm antisera that are derived mainly from fortuitously immunized human donors, often requiring processing before use, and must be used in a hemagglutination-inhibition assay that cannot be used in typing for isoallotypic determinants (currently termed "nonmarkers"). In studies presented here, we describe an allotyping system that utilizes monoclonal antibodies in a "sandwich" modification of the solid-phase radioimmunoassay, which is capable of reliable quantitative typing of allotypic, isoallotypic, and isotypic immunoglobulin determinants. We show that these highly reproducible, easily disseminated, and essentially inexhaustible reagents can be used for rapid, sensitive, and quantitative Gm typing. Using this system we define two previously unrecognized Gm determinants, one of which, found to date only in Caucasians, is different from all known Gm markers and thus defines previously unrecognized alleles and haplotypes. The other determinant cosegregates with the conventional G3m(bl) marker but is distinct from that marker on serological grounds. The successful preparation of mouse monoclonal antibodies that detect human Gm allotypic differences and the development of an assay system capable of typing isoallotypic as well as allotypic determinants opens the way to further dissection and application of this rich genetic system.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.