Female sex hormones and lysosomal stability in gingival polymorphonuclear leucocytes

Summary In a group of 5 women taking oral contraceptives, the concentration of polymorphonuclear leucocytes along the gingival margin and the activities of cathepsin D, -glucuronidase and elastase were found to increase significantly during the intermenstrual phases.Supported by grant 3.604.075 of the Swiss National Fund for scientific Research. The authors thank Dr M. Baggiolini and Prof. A. Linder for the helpful advices.     

Human peripheral blood monuclear cells transfected with messenger RNA stimulate antigen-specific cytotoxic T-lymphocytes in vitro

The efficiency of test vaccines needs to be evaluated by quantification of the triggered cellular immune response. Usually, for these assays, autologous target cells expressing the vaccine antigen are required. In the context of messenger RNA (mRNA)-based vaccinations, the target cells used for the read-out are mRNA-transfected monocyte-derived dendritic cells (Mo-DCs). Their production typically requires samples of 100 ml blood from the patients, and limits the number of assays that can be performed. We show here that fresh peripheral blood mononuclear cells (PBMCs) can be transfected with mRNA by electroporation. Such cells are as efficient as mRNA-transfected Mo-DCs for their ability to activate memory T cells in vitro. Thus, mRNA-transfected PBMCs are a convenient replacement of mRNA-transfected Mo-DCs for the in vitro monitoring of natural or vaccine-induced immune responses.Received 17 February 2005; received after revision 1 May 2005; accepted 7 Juni 2005     

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005     

Marrow mesenchymal stem cells transduced with TPO/FL genes as support for ex vivo expansion of hematopoietic stem/progenitor cells

A new marrow-derived mesenchymal stem cell (hMSC) line that could support expansion of hematopoietic stem/progenitor cells (HSPCs) was developed. Primary hMSCs were infected with retrovirus containing Flt-3 ligand and thrombopoietin genes. CD34+ cells from cord blood were expanded with primary hMSCs or transduced hMSCs. The expansion of total nucleated cells, CD34+ cells and mixed colonies containing erythroid and myeloid cells and megakaryocytes for 2 weeks coculture with transduced hMSCs was remarkably increased. The outputs of long-term culture-initiating cells for 2 and 4 weeks coculture with transduced hMSCs were also largely increased. The expansion rates of HSPCs with transduced hMSCs were unchanged for 6 weeks. In contrast, the expansion rates of HSPCs with primary hMSCs declined drastically through 6 weeks. SCID-repopulating cell expansion with transduced hMSCs for 4 weeks was significantly higher than that of uncultured CD34+ cells and HSPCs expanded with primary hMSCs. Received 21 June 2005; received after revision 30 July 2005; accepted 24 August 2005     

Is chlamydial heat shock protein 60 a risk factor for oncogenesis?

Heat shock protein 60 (HSP60) plays an important role in the protein folding of prokaryotic and eukaryotic cells. Most of the papers published on chlamydial HSP60 concern its role in immune response during infection. In the last decade, exposure to Chlamydia trachomatis has been consistently associated with the development of cervical and ovarian cancer. Moreover, it has been suggested that chlamydial HSP60 may have an anti-apoptotic effect during persistent infection. We hypothesize that the accumulation of exogenous chlamydial HSP60 in the cytoplasm of actively replicating eukaryotic cells may interfere with the regulation of the apoptotic pathway. The concomitant expression of viral oncoproteins and/or the presence of mutations may lead to the ability to survive apoptotic stimuli, loss of replicative senescence, uncontrolled proliferation and, finally neoplastic transformation.Received 15 August 2004; received after revision 1 October 2004; accepted 7 October 2004     

Far-infrared Absorption Spectra and Properties of SnO2 Nanorods

Nanostructured materials have drawn considerable attention because they are promising candidates for nextgeneration electronic and photonic devices with low power consumption[1-5]. A number of methods, such as laser ablation[6], template-induced growth[7], arc discharge [8], vapor transport [9], and molecular-beam epitaxy[10] have been developed to synthesize Si, Ge, MgO,SnO2, GaN, and Ga2O3 nanowires or nanorods[11-15].