Objective. To identify a cartilage-derived autoantigen that is relevant to the rheumatoid arthritis (RA) disease process.Methods. A DR4 (DRBl"0401) peptide binding motif was used for the selection of potential self reactive peptides within human cartilage glycoprotein-39 (HC gp-39), a protein that is differentially expressed at the site of chronic inflammation. Synthetic peptides accommodating the motif were tested for binding the RAassociated DR4 (DRBl"0401) molecules. High-affinity binders were then tested for their capacity to stimulate peripheral blood mononuclear cell responses in RA patients or healthy donors. To assess the arthritogenic nature of native HC gp-39, the protein was injected into BALB/c mice.Results. HC gp-39-derived motif-based peptides were selectively recognized by peripheral blood T cells from RA patients. Injection of the intact protein into BALB/c mice resulted in immunity to HC gp-39, which was found to be associated with the development of a chronic, relapsing arthritis. Moreover, inhalation of the protein led to tolerization of antigen-specific T cells and to suppression of HC gp-39-induced arthritis.Conclusion. These data indicate that HC gp-39 is a target of the immune response in RA. Consequently, HC gp-39 is a candidate for antigen-specific immunotherapy.
In general, nurses tended to be wary of the use of complementary and alternative medicine. Nurses were also not satisfied with their relationships with their physicians. Those of middle age were more likely to use complementary and alternative medicine but no other demographic characteristics were associated with knowledge or attitudes towards complementary and alternative medicine. Nurses had higher levels of internal health locus of control which was associated with more positive attitudes and knowledge levels of complementary and alternative medicine.
In the present study, we examined the mechanisms involved in the activation of the adrenocortical axis following surgical stress. Adult male rats underwent surgical laparotomy or craniotomy under ether anesthesia while control rats were only ether-anesthetized. Four hours following laparotomy or craniotomy, serum adrenocorticotropin (ACTH) and corticosterone (CS) were significantly increased and returned to almost basal levels after 24 h. Laparotomy also caused a significant depletion of corticotropin-releasing hormone (CRH-41) in the median eminence (ME). Pretreatment with dexamethasone 50 μg/kg completely abolished the pituitary-adrenal response while pretreatment with type II corticosteroid receptor antagonist caused a significant hypersecretion of both ACTH and CS and inhibited the effect of dexamethasone. The response to laparotomy was markedly attenuated in rats injected with 6-hydroxydopamine into the paraventricular nucleus (PVN) which significantly depletes norepinephrine (NE) PVN content. Intracerebroventricular injection of interleukin-1 receptor antagonist (IL-1ra) also inhibited the pituitary-adrenal response to laparotomy. The results suggest that (1) surgical stress activates the hypothalamo-pituitary-adrenal (HPA) axis via a mechanism which involves the release of CRH from the ME and NE input to the PVN; (2) the adrenocortical response is sensitive to the negative feedback of glucocorticoids via the mediation of type II glucocorticoid receptors, and (3) central IL-1 may be a mediator in the HPA axis response to surgical stress.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.