The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in human breast carcinomas. The functional role of DF3 is unknown. The present studies demonstrate that DF3 associates with ␤-catenin. Similar findings have been obtained for ␥-catenin but not ␣-catenin. DF3, like E-cadherin and the adenomatous polyposis coli gene product, contains an SXXXXXSSL site that is responsible for direct binding to ␤-catenin. The results further demonstrate that interaction of DF3 and ␤-catenin is dependent on cell adhesion. These findings and the role of ␤-catenin in cell signaling support a role for DF3 in the adhesion of epithelial cells.The human DF3 (MUC1, episialin, PEM) gene encodes a high molecular mass membrane-associated glycoprotein with a mucin-like external domain. The DF3 glycoprotein is expressed on the apical borders of secretory mammary epithelial cells and aberrantly expressed over the entire surface of carcinoma cells (1). The ectodomain consists of varying numbers of 20-amino acid tandem repeats that are subject to O-glycosylation and that contribute to the expression of a polymorphic protein (2-4). The N-terminal region contains hydrophobic signal sequences that vary as a consequence of alternate splicing (5-7). The C-terminal region includes a transmembrane domain and a 72-amino acid cytoplasmic tail that contains tyrosine phosphorylation sites (8, 9). The function of DF3 is unclear. However, high levels found on carcinoma cells reduce cell-cell and cell-extracellular matrix adhesion in a nonspecific manner (10 -12). These studies have suggested that DF3 interferes with cellular adhesion by steric hindrance from the rigid ectodomain (11).Cadherin cell adhesion molecules form complexes with the cytoplasmic ␣-, ␤-, and ␥-catenin proteins (13). ␣-Catenin is required for cadherin-mediated cell adhesion and links cadherins to the actin cytoskeleton (14, 15). ␤-Catenin links ␣-catenin to the cadherins and is highly related to plakoglobin (␥-catenin) (16 -18). ␤-Catenin is homologous to the Drosophila segment polarity gene product Armadillo (19) that acts downstream of Wingless (20). Armadillo forms complexes with Drosophila E-cadherin and ␣-catenin (21, 22). These findings have supported a role for ␤-catenin in morphogenetic signals. Other studies have demonstrated that ␤-catenin binds directly to the adenomatous polyposis coli (APC) 1 gene product (23-25). The APC protein and E-cadherin form independent complexes with ␤-catenin (25). ␥-Catenin mediates similar interactions among APC, ␣-catenin, and the cytoskeleton (16).The present results demonstrate that DF3 interacts directly with ␤-catenin. An SXXXXXSSL motif in the DF3 cytoplasmic domain is responsible for binding to ␤-catenin. We also demonstrate that cell adhesion induces the interaction between DF3 and ␤-catenin. MATERIALS AND METHODSCell Culture-Human ZR-75-1 breast carcinoma cells were grown in RPMI 1640 medium containing 10% heat-inactivated fetal bovine serum, 100 g/ml streptomycin, 100 units/ml penicillin, and 2 mM Lglutamine. Cells were grown...

Objectives To report early experience with treatment of intrauterine cytomegalovirus (CMV) infection using maternal oral administration of valaciclovir (VACV).Design Observational study of fetuses infected with CMV with or without treatment with valaciclovir.Population Pregnancies with confirmed fetal CMV infection were treated with oral VACV (8 g/day).Main outcome measures Fetal viral load and drug concentration were monitored in amniotic fluid and in fetal blood. Data on the course and outcome of a group of untreated symptomatic fetuses infected with CMV are also reported.Results Therapeutic concentrations were achieved in maternal and fetal bloods. The viral load in the fetal blood (VLFB) decreased significantly after 1-12 weeks of treatment (Wilcoxon paired test P = 0.02). Twenty pregnancies including 21 fetuses were treated at 28 weeks (median, range: 22-34) for 7 weeks (median, range: 1-12). Ten infants were developing normally at between 1 and 5 years of age. Two infants (both aged 2 years) had severe isolated unilateral deafness. One neonate presented with microcephaly and severe deafness but was also diagnosed with incontinentia pigmenti. Six out of seven cases that eventually required termination of pregnancy (TOP) had evidence of in utero progression of the disease with worsening cerebral lesions. One fetus died in utero. The outcome of 14/24 (58.3%) untreated symptomatic infected fetuses was poor with either TOP, intrauterine fetal demise or severe congenital infection disease of the neonate; the remaining ten infants were healthy at follow up.Conclusion Maternal oral administration of VACV leads to therapeutic concentrations in the maternal and fetal compartments, with a decrease in VLFB. Our results suggest that in cases where TOP is declined, a randomised controlled trial to study this treatment option further is indicated.

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We examined the difference between Escherichia coli O157 and non-pathogenic E. coli in their tolerance to spices. Various spices (5 g each) were homogenized at 25 degrees C for 10 min with 5 ml of 70% ethyl alcohol, and the supernatant solutions obtained by centrifugation were used as spice extracts. When the E. coli strains were incubated with each spice extract at concentrations of 0.01% and 0.1%, a noteworthy difference was observed between the O157 and non-pathogenic strains in their tolerance to nutmeg. The populations of the non-pathogenic strains could not be reduced, but those of the O157 strains were remarkably reduced. Antibacterial activity by the nutmeg extract was also found against the enteropathogenic E. coli O111, but not against enterotoxigenic (O6 and O148) and enteroinvasive (O29 and O124) E. coli. When we examined the antibacterial effect of volatile oils in nutmeg on the O157 and non-pathogenic E. coli strains, all O157 strains tested were found to be more sensitive to beta-pinene than non-pathogenic E. coli strains.