Identification and characterization of canine dendritic cells generated in vivo.

Emerging evidence suggests that host dendritic cells (DC) initiate and regulate graft-versus-host and graft-versus-tumor reactions after allogeneic hematopoietic cell transplantation (HCT). Even though decades of experimentation in the preclinical canine HCT model have substantially improved our understanding of the biology and safety of HCT in human patients, the in vivo phenotype of potent antigen-presenting cells in dogs is poorly defined. Therefore, peripheral blood leukocytes were obtained from dogs treated with recombinant human Flt3-ligand and phenotypically distinct cell populations, including putative DC, were purified by 4-color flow-cytometry and tested for their stimulatory potential in allogeneic mixed lymphocyte cultures (MLC). Cells characterized by surface expression of CD11c and HLA-DR, and absence of expression of CD14 and DM5, a marker of mature granulocytes, were found to be highly potent stimulators in allogeneic MLC. In contrast, all other immunophenotypically different cell populations tested had either weak or absent allostimulatory potential. Transmission electron microscopy of CD11c+/HLA-DR+/CD14-/DM5- cells revealed the morphology similar to that described for DC in humans and ex vivo-generated canine DC, including long cytoplasmic extensions, discrete lysosomes, and an abundant Golgi apparatus and endoplasmatic reticulum. In summary, CD11c+/HLA-DR+/CD14-/DM5- cells obtained from canine peripheral blood have functional and morphologic characteristics similar to those of human myeloid DC.

Tracheal replacements: Part 2.

In this review, we summarize the history of tracheal reconstruction and replacement as well as progress in current tracheal substitutes. In Part 1, we covered the historical highlights of grafts, flaps, tube construction, and tissue transplants and addressed the progress made in tracheal stenting as a means of temporary tracheal support. In Part 2 we analyze solid and porous tracheal prostheses in experimental and clinical trials and provide a summary of efforts aimed at generating a bioengineered trachea. In both parts, we provide an algorithm on the spectrum of options available for tracheal replacement.

Tracheal replacements: part 1.

In this review, we summarize the history of tracheal reconstruction and replacement as well as progress in current tracheal substitutes. In Part 1, we cover the historical highlights of grafts, flaps, tube construction, and tissue transplants and address the progress made in tracheal stenting as a means of temporary tracheal support. This is followed in Part 2 by an analysis of solid and porous tracheal prostheses in experimental and clinical trials. We conclude Part 2 with a summary of recent efforts toward generating a bioengineered trachea. Finally, we provide an algorithm on the spectrum of options available for tracheal replacement.

Nicotinanilides as inhibitors of neutrophil chemotaxis.

A series of 4-fluoronicotinanilides was synthesized and shown to be novel, potent, and selective inhibitors against GRO-alpha-driven human neutrophil chemotaxis. Compounds of this class may be useful for the treatment of inflammatory, autoimmune, and allergic disorders.

Benzobicyclooctanes as novel inhibitors of TNF-alpha signaling.

A novel series of TNF-alpha inhibitors based on a benzobicyclooctane scaffold is reported. The compounds display good potency in inhibiting TNF-alpha induced apoptosis and NF kappa B activation. Additionally, they are selective for TNF-alpha as they do not inhibit apoptosis induced by soluble Fas ligand. The compounds described here can act as leads for future medicinal chemistry efforts and may also be useful tools for elucidating the TNF-alpha signaling pathway.