Immunological and biochemical evidence for identity of tartrate-resistant isoenzymes of acid phosphatases from human serum and tissues

We purified acid phosphatase isoenzyme 5b from a human spleen affected by leukemic reticuloendotheliosis and used it to produce a specific antiserum. The antiserum was used to show complete immunological identity among isoenzymes 5a and 5b in human serum, and 5b isolated from a giant-cell bone tumor and from the spleen of a case of Hodgkin's disease. Acid phosphatase 5b in a giant-cell bone tumor was isolated for biochemical characterization. Its pH optimum and substrate specificity were very similar to those of isoenzyme 5b from human spleen.     

Prostaglandins for duodenal ulcer

Studies to date indicate that certain synthetic prostaglandin E derivatives, notably misoprostol and enprostil, possess duodenal ulcer healing efficacy that is equivalent to that of the existing H2-receptor antagonists. Whether healing is achieved by virtue of their antisecretory action alone or in combination with their cytoprotective properties cannot be ascertained. Earlier reports that non-antisecretory prostaglandin E2 was effective for duodenal-ulcer healing suggested that cytoprotective mechanisms may contribute to ulcer healing, but this needs be confirmed. Chronic cigarette smoking adversely affects duodenal ulcer healing despite treatment with potent acid-reducing regimens. Evidence is available that cigarette smoking reduces luminal prostaglandins in the stomach, and that misoprostol, a prostaglandin E1 is able to overcome the adverse effect of smoking on duodenal ulcer healing, further suggesting that cytoprotective mechanisms may contribute to ulcer healing. Furthermore, misoprostol has been shown to be the first therapeutic agent capable of improving active chronic antral gastritis, which has recently been found to be almost invariably associated with active duodenal ulcer.     

Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity

RANK, the receptor activator of NF-kappaB, and its ligand RANKL (initially termed TRANCE, also termed ODF and OPGL), are a TNF superfamily receptor-ligand pair that govern the development and function of osteoclasts, lymphoid tissue, and mammary epithelium. While TNF family cytokines share a common structural scaffold, individual receptor-ligand pairs associate with high specificity. Given the low level of amino acid conservation among members of the TNF superfamily, the means by which these molecules achieve specificity cannot be completely understood without knowledge of their three-dimensional structures. To determine the elements of RANKL that mediate RANK activation, we have crystallized the ectodomain of murine RANKL and solved its structure to a resolution of 2.6 A. RANKL self-associates as a homotrimer with four unique surface loops that distinguish it from other TNF family cytokines. Mutagenesis of selected residues in these loops significantly modulates RANK activation, as evidenced by in vitro osteoclastogenesis, thereby establishing their necessity in mediating the biological activities of RANKL. Such structural determinants of RANKL-RANK specificity may be of relevance in the pharmacologic design of compounds to ameliorate osteopenic disorders of bone.     

Iodination of thyroliberin by use of Iodogen

In this method of labeling thyroliberin for radioimmunoassay, 1,3,4,6-tetrachloro-3 alpha,6 alpha-diphenylglycoluril (Iodogen) is used as oxidant. By cation-exchange chromatography and in response to antibody, thyroliberin so labeled behaved similarly to that produced by the conventional Chloramine-T method. Major advantages of the Iodogen method are its reliability, simplicity, and higher yield of stable RIA label in its most convenient (diiodinated) form.