Rheumatoid Arthritis: Field J

Alderuccio F, Siatskas C, Chan J, Field J, Murphy K, Nasa Z, Toh BH. · Department of Immunology, Monash University, Commercial Road, Prahran, Victoria 3181, Australia. · Curr Stem Cell Res Ther. · Pubmed #18220873 No free full text.

Abstract: Autoimmune diseases affect approximately 6% of the population and are characterised by a pathogenic immune response that targets self-antigens. Well known diseases of this nature include type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Treatment is often restricted to replacement therapy or immunosuppressive regimes and to date there are no cures. The strategy of utilising autologous or allogeneic haematopoietic stem cell transplantation to treat autoimmunity and induce immunological tolerance has been trailed with various levels of success. A major issue is disease relapse as the autoimmune response is reinitiated. Cells of the immune system originate from bone marrow and have a central role in the induction of immunological tolerance. The ability to isolate and genetically manipulate bone marrow haematopoietic stem cells therefore makes these cells a suitable vehicle for driving ectopic expression of defined autoantigens and induction of immunological tolerance.

Field J. · Consultant Orthopaedic and Hand Surgeon, Cheltenham General Hospital, Gloucestershire Hospitals NHS Foundation Trust UK, Cheltenham, UK. · J Hand Surg Eur Vol. · Pubmed #18332018 No free full text.

Abstract: This paper presents a retrospective series of 20 LPM semi-constrained ceramic coated cobalt chrome proximal interphalangeal joint arthroplasties performed consecutively in 12 patients for arthritis of the proximal interphalangeal joint by a single surgeon between 2000 and 2004. Eleven were performed for osteoarthritis, four for post-traumatic arthritis and five for rheumatoid arthritis. Although 12 joints had an improvement in pain and an increased functional arc of movement, six joints required revision surgery for implant failure at an average of 19 months, with clinical signs of increasing pain, deteriorating motion and radiological signs of implant loosening and subsidence. This rate of revision is higher than in published series for other PIP joint implants and, therefore, close surveillance of all patients with this prosthesis currently in situ is recommended. Use of the prosthesis has ceased in this unit.

Fryer BH, Wang C, Vedantam S, Zhou GL, Jin S, Fletcher L, Simon MC, Field J. · Department of Pharmacology, School of Medicine, Abramson Family Cancer Research Institute, and Howard Hughes Medical Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. · J Biol Chem. · Pubmed #16490784 links to  free full text

Abstract: Endothelial cells are normally non-motile and quiescent; however, endothelial cells will become permeable and invade and proliferate to form new blood vessels (angiogenesis) in response to wounding, cancer, diabetic retinopathy, age-related macular degeneration, or rheumatoid arthritis. p21-activated kinase (Pak), an effector for the Rho GTPases Rac and Cdc42, is required for angiogenesis and regulates endothelial cell permeability and motility. Although Pak is primarily activated by Rac and Cdc42, there are additional proteins that regulate Pak activity and localization, including three AGC protein kinase family members, Akt-1, PDK-1, and cAMP-dependent protein kinase. We describe phosphorylation and regulation of Pak localization by a fourth AGC kinase family member, cGMP-dependent protein kinase (PKG). Using in vitro mapping, a phosphospecific antibody, co-transfection assays, and untransfected bovine aortic endothelial cells we determined that PKG phosphorylates Pak at serine 21. Phosphorylation was accompanied by changes in proteins associated with Pak. The adaptor protein Nck was released, whereas a novel complex with vasodilator-stimulated phosphoprotein was stimulated. Furthermore Ser-21 phosphorylation of Pak appears to be important for regulation of cell morphology. In both human umbilical vein endothelial cells and HeLa cells, activation of PKG in the presence of Pak stimulated tail retraction and cell polarization. However, in cells expressing S21A mutant Pak1, PKG activation or treatment with a peptide that blocks Nck/Pak binding caused aberrant cell morphology, blocked cell retraction, and mislocalized Pak, producing uropod (tail-like) structures. These data suggest that PKG regulates Pak and that the interaction plays a role in tail retraction.