Adeno-associated viral vector-mediated (AAV-mediated) expression of allogeneic major histocompatibility complex class I (MHC class I) in recipient liver induces donor-specific tolerance in mouse skin transplant models in which a class I allele (H-2Kb or H-2Kd) is mismatched between donor and recipient. Tolerance can be induced in mice primed by prior rejection of a donor-strain skin graft, as well as in naive recipients. Allogeneic MHC class I may be recognized by recipient T cells as an intact molecule (direct recognition) or may be processed and presented as an allogeneic peptide in the context of self-MHC (indirect recognition). The relative contributions of direct and indirect allorecognition to tolerance induction in this setting are unknown. Using hepatocyte-specific AAV vectors encoding WT allogeneic MHC class I molecules, or class I molecules containing a point mutation (D227K) that impedes direct recognition of intact allogeneic MHC class I by CD8+ T cells without hampering the presentation of processed peptides derived from allogeneic MHC class I, we show here that tolerance induction depends upon recognition of intact MHC class I. Indirect recognition alone yielded a modest prolongation of subsequent skin graft survival, attributable to the generation of CD4+ Tregs, but it was not sufficient to induce tolerance.

Our study confirms the increasing number of patients being seen with idiopathic AA amyloidosis. More research is needed to determine if these patients have an underlying genetic susceptibility encoded in pyrin or other genes. Our study also confirms the dominance of renal disease in this population. The elevated levels of interleukin-6, in comparison with other cytokines, could represent a therapeutic target.

Entheses are complex structures which act to reduce stress concentrations between tendon and skeleton tissues. Understanding the development and function of the enthesis organ has implications for surgical repair, particularly in regards to healing and the regulation of tendon to bone engraftment. In this paper we review the development and function of entheses as well as the enthesis organ concept. Next we examine the process of tendon to bone healing and how this can be regulated, before addressing implications for surgical repair and post-operative care.

Pedunculated lipomas arising from the peritoneal wall are a rare finding during abdominal surgery. These benign tumours of mesenchymal origin can arise anywhere in the body and are usually asymptomatic. We present a case of a torted, pedunculated parietal wall lipoma in the right iliac fossa that gave rise to a clinical diagnosis of appendicitis. To our knowledge, such a case has never been reported in the literature previously. We suggest that torsion of a pedunculated parietal lipoma is a rare differential of acute abdominal pain.

SummaryEntheses are complex structures which act to reduce stress concentrations between tendon and skeleton tissues. Understanding the development and function of the enthesis organ has implications for surgical repair, particularly in regards to healing and the regulation of tendon to bone engraftment. In this paper we review the development and function of entheses as well as the enthesis organ concept. Next we examine the process of tendon to bone healing and how this can be regulated, before addressing implications for surgical repair and post-operative care.