A. Stanley Tyms

Ultrastructural changes and immunocytochemical analysis of human placental trophoblast during short-term culture

Trophoblastic cells, of at least 95 per cent purity by immunofluorescence and morphological criteria, were obtained from human term placenta by a simple trypsinisation method without the additional purification steps or complex culture conditions used by others. The differentiation of these cells was followed over four days in culture by fluorescence immunocytochemistry, by scanning and transmission electron microscopy and by light microscopy. The results support the idea that the isolated cells are cytotrophoblast and that these differentiate during this time into cells with characteristics of villous syncytiotrophoblast. This process involved first the formation of a multicellular layer of mononucleated cells, then the development of a syncytium of multinucleated cells and, not necessarily concurrently, functional differentiation. This may be a useful model for the study of syncytiotrophoblast function.

Synthesis and antiviral activity of rigid acyclonucleotide analogs

The synthesis, anti-HIV-1 and anti-herpesvirus activities of new rigid acyclonucleotide analogs are described. 9-[2-methylidene-3-(phosphonomethoxy)propyl]guanine 1a exhibits in vitro anti-HIV-1 activity similar to that of the antiviral agent 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). Compound 1a is 9-fold less toxic to human T-lymphoid cells MT-4 than PMEA.

The inhibitory activity of a peptide derivative against the growth of simian immunodeficiency virus in C8166 cells

The peptide derivative Ro 31-8959 is a potent and selective inhibitor of the aspartic proteinases encoded by HIV-1 and HIV-2 and it arrests the growth of both viruses in cell culture. We have demonstrated similar effects against the simian immunodeficiency virus SIVmac251 in the human T-cell line, C8166 (ED50 = 6nM) with a therapeutic index of 4,500. The antiviral activity of Ro 31-8959 was 250 and 22 times greater than that of ddI and ddC, respectively. The mode of action was confirmed by accumulation of the polyprotein p55 with concomitant reduction of the cleavage product, p27, and by the production of immature virions.

SYNTHESIS, ENZYMATIC PHOSPHORYLATION AND ANTIVIRAL ACTIVITY OF ACYCLIC DIENYL PHOSPHONATE DERIVATIVES OF GUANINE

The synthesis, phosphorylation by guanylate kinase, anti HIV-1 and anti-herpesvirus activity of two acyclic dienyl phosphonate derivatives of guanine are described. (E)-9-(5-phosphono-3-methylene-4-pentenyl)guanine (4) was identified as an excellent substrate of guanylate kinase and a significant inhibitor of HIV-1 replication.

Molecular biology in viral diagnosis: restriction enzyme analysis of viruses from recurrent genital herpes infections

Recurrent genital herpes simplex infections are important causes of sexually transmitted disease (STD). Sub-typing of herpes simplex viruses into type 1 and type 2 has long been possible but restriction enzyme analysis of the viral genome now provides a more versatile tool in the diagnosis and investigation of these virus infections. Isolates were obtained from the genital tract and the electrophoretic profiles of restriction enzyme digests were used for typing and for investigating strain epidemiological patterns in sexual partners. Analysis of deoxyribonucleic acid (DNA) of repeated isolates from discrete sites in individuals may be important in the study of latent infections.