Tolerance induction using lentiviral gene delivery delays onset and severity of collagen II arthritis.

The treatment of rheumatoid arthritis remains suboptimal; thus there is considerable interest in the development of strategies that mediate tolerance to autoantigens. Using lentiviral gene transfer in vivo, we expressed the immunodominant epitope of collagen type II (CII) on major histocompatibility complex class II molecules (MHC II) in a mouse model of destructive arthritis. A sequence corresponding to amino acids 259-270 of CII was fused into the class II-associated invariant chain peptide (CLIP) position of the invariant chain to achieve efficient binding to MHC II. Transduction of cloned cells and primary antigen-presenting cells (APCs) in vitro demonstrated successful presentation of the peptide on MHC II, and a physiological glycosylation pattern. Compared with controls, mice intravenously injected with lentiviral vectors encoding this epitope displayed significantly less frequent, less severe, and less destructive arthritis, decreased lymphocyte proliferation in response to restimulation with CII, and lower CII-specific antibody levels. This was associated with an increased production of transforming growth factor-beta (TGF-beta) in vitro. We suggest that overexpression of the immunodominant CII epitope on MHC II induces T cell production of TGF-beta and leads to inhibition of arthritis by means of both antigen-specific and bystander mechanisms. Thus, antigen-specific tolerance induction using lentiviral gene delivery can ameliorate arthritis.

Extramedullary hematopoiesis occurring as a nasal polyp in a man with a myeloproliferative disorder.

We describe the case of a patient with a known myeloproliferative disorder who presented with epistaxis and what clinically appeared to be a nasal polyp. The mass was resected and proved to represent a focus of extramedullary hematopoiesis. The patient subsequently developed extramedullary hematopoiesis of the skin and the stomach wall. Following nasal polypectomy, he did well for a time, but he eventually died as a result of other complications of his disease. This unique case serves as a reminder that common rhinologic complaints can be a sign of significant and life-threatening pathology.

Expression of ABO or related antigenic carbohydrates on viral envelopes leads to neutralization in the presence of serum containing specific natural antibodies and complement.

No definitive biologic function has been associated with the human ABO histo-blood group polymorphism, or any other terminal carbohydrate differences within or between closely related species. We have experimentally addressed the question of whether viral particles can become glycosylated as determined by the glycosylation (eg, ABO) status of the producer cell and as a result be affected by human serum containing specific natural antibodies (NAbs). Measles virus was produced in cells transfected with cDNA encoding, either human A-transferase, B-transferase, an inactive "O-transferase," or a pig alpha1-3galactosyltransferase (alpha1-3GT) synthesizing the Galalpha1-3Gal structure. The viruses were shown to carry the same ABO structures as the cells; that is, A but not B if produced in A-type cells, and B but not A if produced in B-type cells. Only O was detected on the virus produced from O-type cells, whereas reduced amounts of O appeared on the A- and B-type viral particles. In addition, the Galalpha1-3Gal structure was transferred onto measles only when grown in human cells expressing this structure. When subjected to human preimmune sera, the A-type, the B-type, and the Galalpha1-3Gal viral particles were partially neutralized in a complement-dependent manner. However, the O-type or the Galalpha1-3Gal-negative viral particles were not neutralized. The neutralization appeared to be mediated by specific NAb, as judged by specific inhibition using synthetic A and Galalpha1-3Gal oligosaccharides. Such viral glycosylation may thus partly explain why the ABO antigens and other similar intraspecies as well as interspecies polymorphic carbohydrates have evolved and been maintained over long evolutionary periods.

Simulation technology: a comparison of experiential and visual learning for undergraduate medical students.

BACKGROUND: The availability of simulator technology at the University of Toronto (Toronto, Ontario, Canada) provided the opportunity to compare the efficacy of video-assisted and simulator-assisted learning. METHODS: After ethics approval from the University of Toronto, all final-year medical students were invited to participate in the current randomized trial comparing video-based to simulator-based education using three scenarios. After an introduction to the simulator environment, a 5-min performance-based pretest was administered in the simulator operating room requiring management of a critical event. A posttest was administered after students had participated in either a faculty-facilitated video or simulator teaching session. Standardized 12-point checklist performance protocols were used for assessment purposes. As well, students answered focused questions related to the educational sessions on a final examination. Student opinions regarding the value of the teaching sessions were obtained. RESULTS: One hundred forty-four medical students participated in the study (scenario 1, n = 43; scenario 2, n = 48; scenario 3, n = 53). There was a significant improvement in posttest scores over pretest scores in all scenarios. There was no statistically significant difference in scores between simulator or video teaching methods. There were no differences in final examination marks when the two educational methods were compared. Student opinions indicated that the experiential simulator sessions were more enjoyable and valuable than the video teaching sessions. CONCLUSIONS: Both simulator and video types of faculty-facilitated education offer a valuable learning experience. Future work is needed that addresses the long-term effects of experiential learning in the retention of knowledge and acquired skills.