Publications

Murine lupus in NZB/NZW F1 (B/W) mice can be retarded by sustained administration of CTLA4Ig and by brief treatment early in life with mAb that block CD40/gp39 interactions. We sought to determine whether brief therapy with CTLA4Ig could provide sustained benefit in B/W mice and whether a synergistic effect could be derived by blockade of both the B7/CD28 and the CD40/gp39 pathways. We found that a short course of CTLA4Ig at the onset of disease produced only short-term benefit. However, when CTLA4Ig was combined with anti-gp39, there was long-lasting inhibition of autoantibody production and renal disease. Ten months after the 2-wk course of therapy, 70% of these mice were alive, compared with only 18% and 0% of those that received only anti-gp39 or CTLA4Ig, respectively. These findings demonstrate that brief simultaneous blockade of the B7/CD28 and CD40/gp39 costimulation pathways can produce benefit that lasts long after treatment has been discontinued.

The majority of patients who present with acute upper gastrointestinal hemorrhage are found to be bleeding from acid peptic disease including ulcer, esophagitis and gastritis, and variceal disease. Mallory-Weiss tear, Dieulafoy's lesion, cancer, and other rare lesions account for the bleeding source in the remaining patients. Endoscopic hemostasis may be effective in many of the conditions, but only Mallory-Weiss tear and Dieulafoy's lesion are encountered frequently enough to be clinically significant.