Publications

During 1988 through 1990, California experienced its worst measles epidemic in more than a decade, with 16,400 reported cases, 3,390 hospital admissions, and 75 deaths. More than half of the patients were younger than 5 years; the highest incidence was among infants younger than 12 months. The epidemic centered in low-income Hispanic communities in southern and central California. The major cause of the epidemic was low immunization levels among preschool-aged children and young adults. Rates of complications, admission to hospital, and death were surprisingly high. Outbreak control efforts met with indeterminate success. Problems with these efforts included insufficient funding early in the epidemic and disappointing public response to community-based immunization campaigns. The cost of medical care and outbreak control for the epidemic is conservatively estimated at $30.9 million. Unless the level of immunization in preschool-aged children is increased, this type of epidemic will probably recur.

NF-kappa B and AP-1 represent distinct mammalian transcription factors that target unique DNA enhancer elements. The heterodimeric NF-kappa B complex is typically composed of two DNA binding subunits, NF-kappa B p50 and NF-kappa B p65, which share structural homology with the c-rel proto-oncogene product. Similarly, the AP-1 transcription factor complex is comprised of dimers of the c-fos and c-jun proto-oncogene products or of closely related proteins. We now demonstrate that the bZIP regions of c-Fos and c-Jun are capable of physically interacting with NF-kappa B p65 through the Rel homology domain. This complex of NF-kappa B p65 and Jun or Fos exhibits enhanced DNA binding and biological function via both the kappa B and AP-1 response elements including synergistic activation of the 5' long terminal repeat of the human immunodeficiency virus type 1. These findings support a combinatorial mechanism of gene regulation involving the unexpected cross-coupling of two different classes of transcription factors to form novel protein complexes exhibiting potentiated biological activity.