Thermodynamic analysis of the CSL x Notch interaction: distribution of binding energy of the Notch RAM region to the CSL beta-trefoil domain and the mode of competition with the viral transactivator EBNA2.

The Notch signaling pathway is a cell-cell communication network giving rise to cell differentiation during metazoan development. Activation of the pathway releases the intracellular portion of the Notch receptor to translocate to the nucleus, where it is able to interact with the effector transcription factor CSL, converting CSL from a transcriptional repressor to an activator. This conversion is dependent upon the high affinity binding of the RAM region of the Notch receptor to the beta-trefoil domain (BTD) of CSL. Here we probe the energetics of binding to BTD of each conserved residue of RAM through the use of isothermal titration calorimetry and single residue substitution. We find that although the highly conserved PhiW PhiP motif is the largest determinant of binding, energetically significant interactions are contributed by N-terminal residues, including a conserved Arg/Lys-rich region. Additionally, we present a thermodynamic analysis of the interaction between the Epstein-Barr virus protein EBNA2 with BTD and explore the extent to which the EBNA2- and RAM-binding sites on BTD are nonoverlapping, as proposed by Fuchs et al. (Fuchs, K. P., Bommer, G., Dumont, E., Christoph, B., Vidal, M., Kremmer, E., and Kempkes, B. (2001) Eur. J. Biochem. 268, 4639-4646). Combining these results with displacement isothermal titration calorimetry, we propose a mechanism by which the PhiW PhiP motif of RAM and EBNA2 compete with one another for binding at the hydrophobic pocket of BTD using overlapping but specific interactions that are unique to each BTD ligand.

How gastroenterologists inform patients of results after lower endoscopy.

OBJECTIVE: Little is known about how gastroenterologists communicate endoscopic findings and biopsy results to their patients. We sought to determine the factors that may influence this behavior. METHODS: A survey questionnaire was developed and mailed to the 80 members of the Delaware Valley Society for GI Endoscopy. Information was obtained on the demographic characteristics and responses to six case vignettes prepared to examine communication patterns. We determined possible influences of conscious sedation and the benignity or severity of findings on communication practices. RESULTS: Sixty-one surveys (76%) were completed and analyzed. Endoscopists immediately inform patients of normal results. For abnormal results, 92% would immediately inform nonsedated patients versus 79% that would inform sedated patients (p < 0.008). Analysis of responses to the case vignettes indicated that 82% of endoscopists would immediately reassure the patient about a benign appearing (< 1 cm) polyp, but only 70% would do so for a polyp > 2 cm (p < 0.01). In contrast, when presented with a frank malignancy, 94% would inform the patient. Eighty-four percent of endoscopists would telephone results of a benign pathology report, but only 34% would telephone report a dysplastic lesion (p < 0.001). There was no correlation between the response rate and various demographic parameters such as physician age, type of, or length of time in practice. CONCLUSIONS: Gastroenterologists usually report normal findings immediately, but are less likely to do so after use of sedation or encountering abnormal findings. Most of those surveyed would use the telephone to communicate abnormal findings.

Picture archiving communication system does not decrease the number of radiographs needed to evaluate the trauma patient.

BACKGROUND: Picture Archiving Communication System (PACS) is a sophisticated software and hardware package that enables clinicians to retrieve, review, and digitally manipulate radiographs from computer workstations throughout the hospital. PACS was instituted at Brooke Army Medical Center in July 1993. METHODS: Fifty consecutive trauma and 50 consecutive motor vehicle crash (MVC) trauma admissions to an urban trauma center were reviewed before PACS (January 1993) and 18 months after PACS was instituted (January 1995). Patients were compared by the number of radiographs needed during the initial evaluation by type and total. The trauma groups were subdivided by mechanism and also compared. Demographic and physiologic data were collected for each patient. RESULTS: There are no differences in the demographic and physiologic data between groups. For the 50 consecutive trauma admissions, only two areas of statistical difference were found: more chest films were obtained in the MVC PACS group and more pelvis films were obtained in the gunshot wound pre-PACS group. For the 50 consecutive MVC trauma admissions, the PACS group had more chest and total radiographs per patient than the pre-PACS group. More computed tomographic scans of the neck were obtained in the PACS group. CONCLUSION: PACS did not decrease the number of radiographs needed to adequately and fully evaluate the trauma patient.