Bestandsdichte in Beziehung zu Halmertrag,Assimilation und Standfestigkeit

Theoretical and Applied Genetics -     

Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB beta2 microglobulin-deficient mice

Human gammaherpesvirus infections are associated with development of lymphoproliferative disease. Understanding of the mechanisms of gammaherpesvirus lymphomagenesis during chronic infection in a natural host has been limited by the exquisite species specificity of human gammaherpesviruses and the expense of primates. Murine gammaherpesvirus gammaHV68 is genetically and biologically related to human gammaherpesviruses and herpesvirus saimiri and has been reported to be associated with lymphoproliferative disease in mice (N. P. Sunil-Chandra, J. Arno, J. Fazakerley, and A. A. Nash, Am. J. Pathol. 145:818-826, 1994). We report the development of an animal model of gammaHV68 lymphomagenesis in BALB/c beta2 microglobulin-deficient mice (BALB beta2m-/-). GammaHV68 infection induced two lymphoproliferative lesions: B-cell lymphoma and atypical lymphoid hyperplasia (ALH). ALH lesion histology resembled lesions of Epstein-Barr virus-associated posttransplant lymphoproliferative disease and was characterized by the abnormal infiltration of the white pulp with cells expressing the plasma cell marker CD138. Lymphomas observed in gammaHV68-infected animals were B220+/CD3- large-cell lymphomas. GammaHV68-infected cells were common in ALH lesions as measured by in situ hybridization with a probe specific for viral tRNAs (vtRNAs), but they were scarce in gammaHV68-infected spleens with normal histology. Unlike ALH lesions, gammaHV68 vtRNA-positive cells were rare in lymphomas. GammaHV68 infection of BALB beta2m-/- mice results in lymphoproliferation and lymphoma, providing a valuable tool for identifying viral and host genes involved in gammaherpesvirus-associated malignancies. Our findings suggest that gammaHV68 induces lymphomas via hit-and-run oncogenesis, paracrine effects, or stimulation of chronic inflammation.     

Synthesis and anti-HIV properties of new hydroxyquinoline-polyamine conjugates on cells infected by HIV-1 LAV and HIV-1 BaL viral strains

To find new derivatives that block different virus strains entry in cells bearing specific surface receptors represent an interesting challenge for medicinal chemists. Here, we report the synthesis and the anti-HIV properties of a new series of analogues based on the introduction of quinoline moiety on various polyamine backbones, including polyazamacrocycles. Three compounds 7, 8, and 10 of this series were found active on PBMCs cells infected by HIV-1 LAV or by HIV-1 BaL, in contrast the well-known reference compound 1a (AMD 3100) was found only active on HIV-1 LAV strain.     

Functional lactide monomers: methodology and polymerization

Side-chain-functionalized lactide analogues have been synthesized from commercially available amino acids and polymerized using stannous octoate as a catalyst. The synthetic strategy presented allows for the incorporation of any protected amino acid for the preparation of functionalized diastereomerically pure lactide monomers. The resulting functionalized cyclic monomers can be homopolymerized and copolymerized with lactides and then quantitatively deprotected forming new functional poly(lactide)-based materials. This strategy allows for the introduction of functional groups along a poly(lactide) (PLA) backbone that after deprotection can be viewed as chemical handles for further functionalization of PLA, yielding improved biomaterials for a variety of applications.     

Synthesis and modification of functional poly(lactide) copolymers: toward biofunctional materials

A polylactide copolymer with pendant benzyloxy groups has been synthesized by the copolymerization of a benzyl-ether substituted monomer with lactide. Debenzylation of the polymer to provide pendant hydroxyl groups followed by modification with succinic anhydride affords the corresponding carboxylic acid functionalized copolymer that is amenable to standard carbodiimide coupling conditions to attach amine-containing biological molecules. An amino-substituted biotin derivative was coupled to the carboxyl functional groups of copolymer films as proof-of-concept. In a demonstration of the function of these new materials, an RGD-containing peptide sequence was tethered to copolymer films at various densities and was shown to enhance the adhesion of epithelial cells. This strategy provides the opportunity for the attachment of a variety of ligands, allowing for the fabrication of a versatile class of biodegradable, biocompatible materials.     

A Novel Interleukin Stimulating Free Radical Production by Granulocytes

Polymorphonuclear granulocytes (PMN) are potent producers of free oxygen-derived radicals. Since other granulocyte functions are affected by interleukins, we investigated whether free-radical production can be initiated by a similar mediator. For estimation of free radical production, SOD-inhibitable lucigenin-dependent chemiluminescence and SOD-inhibitable cytochrome C reduction were used. As a source of interleukins, serum-free 24 h culture supernatants of human mononuclear cells (MNC) stimulated with bacterial lipopolysaccharide were prepared. Addition of such supernatants to PMN caused stimulation of sod-inhibitable chemiluminescence and superoxide production. Studies with separated MNC showed that monocytes were the cellular source of the activity. Biochemically, this activity of the supernatants was due to a heat-labile glycoprotein with a MW of approx. 60KDa. This mediator, termed granulocyte chemiluminescence inducer (GCI), appears to be distinct from interleukin 1 (a and j?) and interferon (a and y). In conclusion we describe a novel monokine, granulocyte chemiluminescence inducer (GCI), which initiates granulocyte free radical production. This interaction of monocytes and granulocytes may also in vivo constitute a new and potent pathway leading to stimulation of free oxygen production by granulocytes.