This is the first report to quantify volumetric changes in the upper airway in obese children with OSAS after adenotonsillectomy showing significant residual adenoid tissue and an increase in the volume of the tongue and soft palate. These findings could explain the low success rate of AT reported in obese children with OSAS and are important considerations for clinicians treating these children.

Wnt signaling regulates cell fate determination, proliferation, and survival, among other processes. Certain Wnt ligands stabilize the ␤-catenin protein, leading to the ability of ␤-catenin to activate T cell factor-regulated genes. In the absence of Wnts, ␤-catenin is phosphorylated at defined serine and threonine residues in its amino (N) terminus. The phosphorylated ␤-catenin is recognized by a ␤-transducin repeat-containing protein (␤TrCP) and associated ubiquitin ligase components. The serine/threonine residues and ␤TrCP-binding site in the N-terminal region of ␤-catenin constitute a key regulatory motif targeted by somatic mutations in human cancers, resulting in constitutive stabilization of the mutant ␤-catenin proteins. Structural studies have implicated ␤-catenin lysine 19 as the major target for ␤TrCP-dependent ubiquitination, but Lys-19 mutations in cancer have not been reported. We studied the consequences of single amino acid substitutions of the only 2 lysine residues in the N-terminal 130 amino acids of ␤-catenin. Mutation of Lys-19 minimally affected ␤-catenin levels and functional activity, and mutation of Lys-49 led to reduced ␤-catenin levels and function. In contrast, ␤-catenin proteins with substitutions at both Lys-19 and Lys-49 positions were present at elevated levels and had the ability to potently activate T cell factor-dependent transcription and promote neoplastic transformation. We furthermore demonstrate that the K19/K49 double mutant forms of ␤-catenin are stabilized as a result of reduced ␤TrCP-dependent ubiquitination. Our findings suggest that Lys-19 is a primary in vivo site of ␤TrCP-dependent ubiquitination and Lys-49 may be a secondary or cryptic site. Moreover, our results inform understanding of why single amino acid substitutions at lysine 19 or 49 have not been reported in human cancer.Wnts are a family of secreted proteins with critical roles in embryonic development and adult tissues, including functions in regulating cell fate specification, proliferation, survival, and motility (1-5). The "canonical" Wnt pathway is the best characterized Wnt-dependent signaling pathway, and mutations altering essential factors in this pathway have been most clearly implicated in cancer. In the canonical pathway, the ␤-catenin protein is a key downstream mediator, with certain Wnts (e.g. Wnt-1) acting to stabilize ␤-catenin. In the absence of activating Wnt signals, glycogen synthase kinase 3␤ functions in concert with the Axin and adenomatous polyposis coli tumor suppressor proteins and other factors, such as casein kinase I␣, to phosphorylate ␤-catenin at defined serine and threonine residues in its N-terminal domain. The phosphorylated ␤-catenin is recognized and ubiquitinated by a complex containing a ␤-transducin repeat-containing protein (␤TrCP), 2 , and ␤-catenin is then degraded by the proteasome (6 -11). Wnt binding to the Frizzled low density lipoprotein-related protein-5/6 co-receptor complex on the cell surface leads to inhibition of the AXIN/ glycogen synthase kinase 3␤ c...

BACKGROUND: Pertussis is a highly communicable, vaccine-preventable respiratory disease. Although the largest number of reported cases is among young infants, the most rapidly increasing incidence in the USA is in adolescents and young adults. Importantly, adult family members are the likely major reservoir, infecting susceptible infants before completion of childhood vaccination. We studied maternal-neonatal paired blood samples for the presence of pertussis-related antibodies to assess level of immunity and passive transplacental antibody passage. METHODS. Unselected maternal-neonatal cord blood samples were collected from 101 term deliveries in a single urban uninsured/underinsured hospital setting. Sera were analyzed for anti-pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) IgG antibodies by enzyme-linked immunosorbent assay (ELISA). Antibody titers were calculated using reference line methodology. Antibody values were log-transformed to establish geometric mean titers (GMT) for analysis. Student's t-test, Mann-Whitney, Pearson correlation and chi square were used for statistical comparisons as appropriate. RESULTS. Mean (SD) maternal age, gestational age and birth weight were 26.8 (6.8) years, 38.9 (1.4) weeks and 3239 (501) g, respectively. Detectable maternal levels of anti-PT, FHA and PRN were found in 34.7%, 95.0% and 80.2%, respectively. Maternal GMT (SD) for PT, FHA and PRN were 4.4 (2.6), 26.6 (3.1) and 12.3 (2.9), respectively. There was no significant relationship between PT, FHA or PRN detection or antibody GMT and maternal age. Maternal anti-PT, FHA and PRN were highly correlated with neonatal cord blood values. CONCLUSION: Despite previous childhood immunization, a large number of parous women have low or undetectable pertussis-related antibody levels, suggesting susceptibility to infection. Even with efficient transplacental passage of these antibodies, neonates similarly have limited measurable protection as detected by cord blood sampling. These data support the need for adolescent or adult vaccination against Bordetella pertussis. Healthcare providers and their clients should be aware of the risk for infant infection via family member transmission.

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