Members of the TNFR family play critical roles in the regulation of the immune system. One member of the family critical for efficient activation of T-dependent humoral immune responses is CD40, a cell surface protein expressed by B cells and other APC. The cytoplasmic domain of CD40 interacts with several members of the TNFR-associated factor (TRAF) family, which link CD40 to intracellular signaling pathways. TRAF2 and 6 appear to play particularly important roles in CD40 signaling. Previous studies suggest that the two molecules have certain overlapping roles in signaling, but that unique roles for each molecule also exist. To better define the roles of TRAF2 and TRAF6 in CD40 signaling, we used somatic cell gene targeting to generate TRAF-deficient mouse B cell lines. A20.2J cells deficient in TRAF6 exhibit marked defects in CD40-mediated JNK activation and the up-regulation of CD80. Our previous experiments with TRAF2-deficient B cell lines suggest that TRAF6 and TRAF2 may have redundant roles in CD40-mediated NF-κB activation. Consistent with this hypothesis, we found CD40-mediated activation of NF-κB intact in TRAF6-deficient cells and defective in cells lacking both TRAF2 and TRAF6. Interestingly, we found that TRAF6 mutants defective in CD40 binding were able to restore CD40-mediated JNK activation and CD80 up-regulation in TRAF6-deficient cells, indicating that TRAF6 may be able to contribute to certain CD40 signals without directly binding CD40.

The histologic diagnosis of LE is associated with pediatric CD and was found in 28% of CD patients. If LE is identified in pediatric CD, it is likely a manifestation of UGI-CD rather than esophagitis due to other etiologies or a variant of normal.

Skeletal muscle tissue was obtained by open biopsy from the vastus lateralis and peroneus brevis muscles from 12 and 16 healthy paid volunteers, respectively. Frozen sections were examined with standard histochemical methods. Central nuclei, small and large angular fibers, and small round fibers were the most common "abnormalities" present. The number of fibers of these types were quantified, along with other more rare deviations from normal morphology. Several of the abnormalities were more common in the peroneus brevis than in the vastus lateralis.

An 18-year-old male with profound developmental delay was evaluated for recurrent vomiting. Acid suppression therapy did not alleviate his symptoms. An upper endoscopy showed 5 polypoid lesions in the mid-and upper esophagus (Fig. 1). Cold biopsies showed stratified squamous epithelium with submucosal bland spindled cell proliferation (Fig. 2). Smooth muscle myosin staining was positive (Fig. 3). These findings were diagnostic of esophageal leiomoymas.Leiomyomas are the most common benign esophageal tumors usually affecting the distal two thirds of the esophagus. In 5% of patients, they can be multiple (1). This should be differentiated from leiomyomatosis, which is characterized by diffuse hypertrophy of the muscular layer (2). Although a leiomyoma is the most likely etiology of an esophageal polypoid lesion in a child, other diagnoses are possible that rarely include malignancy, so histological evaluation is often recommended (3,4).Esophageal leiomyomas are rarely symptomatic when small (<5 cm in diameter). Large tumors can present with dysphagia, chest pain, obstruction, regurgitation, and, rarely, bleeding. Histologically, leiomyomas are composed of bundles of interlacing smooth muscle cells with a connective tissue capsule covered by mucosa (5).Asymptomatic or small lesions can be followed periodically as they have a slow growth rate and negligible risk of malignant transformation. Surgical excision is recommended for symptomatic leiomyomas and those >5 cm (1).

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