Malignant salivary gland tumors can arise from a t(11;19) translocation that fuses 42 residues from Mect1/Torc1, a cyclic AMP (cAMP)/cAMP-responsive element binding protein (CREB)-dependent transcriptional coactivator, with 982 residues from Maml2, a NOTCH receptor coactivator. To determine if the Mect1-Maml2 fusion oncogene mediates tumorigenicity by disrupting cAMP/CREB signaling, we have generated in-frame deletions within the CREB-binding domain of Mect1/Torc1 for testing transformation activity and have also developed a doxycycline-regulated Mect1-Maml2 mammalian expression vector for global gene expression profiling. We observed that small deletions within the CREB-binding domain completely abolished transforming activity in RK3E epithelial cells. Further, we have shown that the ectopic induction of Mect1-Maml2 in HeLa cells strongly activated the expression of a group of known cAMP/CREBregulated genes. In addition, we detected candidate cAMPresponsive element sites within 100 nucleotides of the transcriptional start sites of other genes activated by Mect1-Maml2 expression. In contrast, we did not observe alterations of known Notch-regulated target genes in these expression array profile experiments. We validated the results by reverse transcription-PCR in transfected HeLa, RK3E, and H2009 lung tumor cells and in mucoepidermoid cancer cells that endogenously express the fusion oncopeptide. Whereas overexpression of components of the cAMP pathway has been associated with a subset of human carcinomas, these data provide a direct genetic link between deregulation of cAMP/ CREB pathways and epithelial tumorigenesis and suggest future therapeutic strategies for this group of salivary gland tumors. (Cancer Res 2005; 65(16): 7137-44)

A management approach using clinical presentation to determine the need for antibiotics in chorioamnionitis-exposed infants was successful in reducing antibiotic exposure and was not associated with any clinically relevant delays in care or adverse outcomes.

The majority of pediatric cryptococcosis occurred in non-HIV-infected patients. However, most patients had other immunocompromising medical conditions. Patients with CM usually received therapy in accordance with the Infectious Disease Society of America guidelines for adults, but patients with non-CM were more likely to receive therapies not supported by these guidelines.

Repeated, thorough clinical examination and carefully selected laboratory examinations proved useful in the diagnosis of FUO. Serology (e.g. enteric fever) and bone marrow examination (e.g. leishmaniasis, malignancy) were the most useful diagnostic tests.

BACKGROUND: Antibiotic use in well-appearing late preterm and term chorioamnionitis-exposed (CE) infants was reduced by 88% after the adoption of a care approach that was focused on clinical monitoring in the intensive care nursery to determine the need for antibiotics. However, this approach continued to separate mothers and infants. We aimed to reduce maternal-infant separation while continuing to use a clinical examination-based approach to identify early-onset sepsis (EOS) in CE infants. METHODS: Within a quality improvement framework, well-appearing CE infants $35 weeks' gestation were monitored clinically while in couplet care in the postpartum unit without laboratory testing or empirical antibiotics. Clinical monitoring included physician examination at birth and nurse examinations every 30 minutes for 2 hours and then every 4 hours until 24 hours of life. Infants who developed clinical signs of illness were further evaluated and/or treated with antibiotics. Antibiotic use, laboratory testing, and clinical outcomes were collected. RESULTS: Among 319 initially well-appearing CE infants, 15 (4.7%) received antibiotics, 23 (7.2%) underwent laboratory testing, and 295 (92.5%) remained with their mothers in couplet care throughout the birth hospitalization. One infant had group B Streptococcus EOS identified and treated at 24 hours of age based on new-onset tachypnea and had an uncomplicated course. CONCLUSIONS: Management of well-appearing CE infants by using a clinical examination-based approach during couplet care in the postpartum unit maintained low rates of laboratory testing and antibiotic use and markedly reduced mother-infant separation without adverse events. A framework for repeated clinical assessments is an essential component of identifying infants with EOS.

A randomized, double-blinded, placebo-controlled 2 Â 2 factorial chemoprevention trial was conducted in Linxian, China to assess the effects of selenomethionine and celecoxib on the natural history of esophageal squamous dysplasia. Results from this study indicated that asymptomatic adults with mild dysplasia were more likely to show an improvement when treated with selenomethionine compared with placebo (P = 0.02). Prompted by this finding, we examined the molecular profiles associated with regression and progression of dysplastic lesions in normal mucosa from 29 individuals, a subset of the Linxian cohort, using the Affymetrix U133A chip. Twenty differentially expressed genes were associated with regression and 129 were associated with progression when we compared the change in gene expression over time. Genes associated with immune response (n = 15), cell cycle (n = 15), metabolism (n = 15), calcium transport or calcium ion activity (n = 10

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The ability to accurately and non-invasively characterize breast lesions and their vasculature would greatly limit the number of unneeded biopsies performed annually. Subharmonic ultrasound imaging (SHI) allows exclusive imaging of vasculature in real time, while completely suppressing tissue signals. Previously, cumulative maximum intensity (CMI) projections of SHI data were shown to be useful for characterization, but lacked means of quantification. In this study we investigate three potential thinning algorithms for defining breast lesion architecture. Sequential thinning, parallel thinning, and distance transformation algorithms were compared using 40 in vitro test images. Sequential thinning was selected due to superior connectivity, minimal rotational variance, and sufficient data reduction. This algorithm was then applied to 16 CMI SHI images of breast lesions, out of which 13 were successfully skeletonized. Average bifurcations were 9.8 ± 8.18 and 6.9 ± 6.50 in malignant and benign lesions, respectively (p > 0.60). Average vessel-chain length was 88.9 ± 79.10 pixels versus 63.2 ± 45.65 pixels in malignant versus benign lesions (p > 0.40). While the sequential thinning algorithm was promising for quantifying breast vasculature, its ability to significantly differentiate between malignant and benign lesions in this study was limited by a high degree of variability and limited sample size.