Citations

Abstract The c-jun-NH2-kinases (JNK) play a critical role in tumor promoter–induced cell transformation and apoptosis. Here, we showed that the nuclear factor of activated T3 (NFAT3) is phosphorylated by JNK1 or JNK2 at Ser213 and Ser217, which are located in the conserved SP motif. The transactivation domain of NFAT3 is found between amino acids (aa) 113 and 260 and includes the phosphorylation targets of JNK1 and JNK2. NFAT3 transactivation activity was suppressed in JNK1−/− or JNK2−/− mouse embryonic fibroblast (MEF) cells compared with wild-type MEF cells. Moreover, a 3xNFAT-luc reporter gene assay indicated that NFAT3 transcriptional activity was increased in a dose-dependent manner by JNK1 or JNK2. Double mutations at Ser213 and Ser217 suppressed NFAT3 transactivation activity; and SP600125, a JNK inhibitor, suppressed NFAT3-induced 3xNFAT-luciferase activity. Knockdown of JNK1 or JNK2 suppressed foci formation in NIH3T3 cells. Importantly, ectopic expression of NFAT3 inhibited AP-1 activity and suppressed foci formation. Furthermore, knockdown of NFAT3 enhanced Ras-JNK1 or JNK2-induced foci formation in NIH3T3 cells. Taken together, these results provided direct evidence for the anti-oncogenic potential of the NFAT3 transcription factor. [Cancer Res 2007;67(18):8725–35]

Barriers to early identification of children with developmental delays include time constraints during well-child visits and lack of easily administered, quantitative measures that can be used by pediatricians. This study assesses the ease of administration of the Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) during well-child visits from 2 to 36 months of age. During a single visit 177 children were assessed by either a developmental pediatrician (n = 121) or a third-year pediatric resident (n = 56). The mean time required to complete the CAT/CLAMS for all subjects was 6 minutes and 10 seconds (SD 2 minutes 44 seconds); less than 10 minutes was required in 92% of children assessed. There were no significant differences in the time required by the 2 examiners at any age level. Its ease of administration and psychometric properties make the CAT/CLAMS an excellent choice for the assessment of early development by primary care pediatricians.

Although asthmatic children spend a significant amount of time in child care programs, little is known about child care program directors' knowledge about asthma and what factors influence directors' level of knowledge about asthma. A telephone interview was conducted with directors of a randomly selected sample of all licensed child care centers and group day care homes in Connecticut. Directors of most child care programs were willing to admit asthmatic children to their programs, but their knowledge about asthma needs to be improved. Directors who have served for long periods of time may be a target group for additional education about asthma.

AbstractPurpose: Colorectal carcinoma (CRC) can be divided into two nonoverlapping groups: those that are chromosomally unstable but microsatellite stable (MSS CIN+) and those that are chromosomally stable but microsatellite unstable (MSI CIN−). However, a third group with neither chromosome nor microsatellite instability (MSS CIN−) makes a substantial contribution to the total CRC burden. The clinicopathologic features of MSS CIN− CRC are not well delineated. We assessed the relationship between age and chromosomal instability (CIN) status as measured by ploidy and allelic imbalance in a series of MSS tumors.Experimental Design: We studied a prospectively collected series of CRC patients at Mayo Clinic Rochester. A total of 84 samples of MSS CRC in patients ≤50 years old were identified between 1994 and 1997. A consecutive series of 90 MSS CRC in patients ≥65 years old served as a comparison group. CIN status was assessed using two techniques: ploidy analysis by flow cytometry and small chromosome changes as measured by genomewide fractional allelic imbalance.Results: CRC in the young-onset group was more likely to involve the rectum and to be high stage. MSS tumors in the young-onset group were more often diploid (46%) than those in older patients (26%; P = 0.006). This difference was maintained in the subset of MSS CRC that were high stage (42% versus 18%; P = 0.02) and in rectal cancers (50% versus 23%; P = 0.04).Conclusion: A greater proportion of young patients with MSS CRC has diploid tumors than patients who develop MSS CRC over age 65.

A sample of 31 boys sexually assaulted in the previous 18 months was compared on the Child Behavior Checklist with 33 boys who had a diagnosis of oppositional or conduct disorder. The boys ranged in age from 3 to 8 years old. The conduct-disordered boys were being seen in outpatient therapy with their parents. The two groups did differ significantly, with the sexually abused group being less externalizing and more sexualized than the conduct disorder group.