Data from this large series substantiate that autoantibody-associated CHB is not coincident with major structural abnormalities, is most often identified in the late second trimester, carries a substantial mortality in the neonatal period and frequently requires pacing. The recurrence rate of CHB is at least two- to three-fold higher than the rate for a mother with anti-SSA/Ro-SSB/La antibodies who never had an affected child, supporting close echocardiographic monitoring in all subsequent pregnancies, with heightened surveillance between 18 and 24 weeks of gestation.

DNp63 is overexpressed in squamous carcinomas where it is associated with proliferation and is believed to enhance cell growth by blocking p53-mediated transactivation. In normal epithelium, DNp63a protein expression is abundant in basal cells and decreases with differentiation. To explore the biological consequences of DNp63a overexpression in relation to squamous carcinogenesis, we evaluated its effect on normal squamous differentiation and p53 transactivation function in keratinocytes. Forced overexpression of DNp63a in primary murine keratinocytes in vitro inhibits morphological differentiation induced by elevated extracellular [Ca 2 þ ], abrogates Ca 2 þ -induced growth arrest, and blocks expression of maturation-specific proteins keratin 10 and filaggrin. This suggests that DNp63 overexpression in squamous carcinomas may serve to maintain the basal cell phenotype and promote cell survival. DNp63a blocks transactivation of p53 responsive reporter constructs mediated by endogenous or exogenous p53 at 17 h postinfection, as expected. However, at 41 h, when p53-mediated transactivation is diminished, DNp63a enhances transactivation of these reporter constructs by 2.2-12-fold over control. Maximal DNp63a-induced transactivation requires intact p53 responsive elements, but is independent of cellular p53 status. This positive transcriptional function of DNp63a appears to be cell-type specific, as it is not observed in primary dermal fibroblasts or Saos-2 cells. These findings support DNp63a as a master regulator of keratinocyte differentiation, and suggest a novel function of this protein in the maintenance of epithelial homeostasis.

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