The caspases are cysteine proteases that have been implicated in the execution of programmed cell death in organisms ranging from nematodes to humans.

Rta, encoded by Epstein-Barr virus (EBV), is a potent activator of transcription via enhancer sequences located upstream of several viral genes. To identify the domains of Rta that facilitate transcription by interacting with cellular transcription factors, different segments of Rta were linked to the DNA binding domain of yeast transactivator GAL4 (residues 1 to 147). These GALA-Rta fusion proteins were tested in transfected cells for their ability to activate the adeno Elb promoter with an upstream GALA DNA binding site. The acidic C-terminal domain of Rta (amino acids 520 to 605) was a potent activator but behaved differently from VP16 in dose-response and competition experiments. A subterminal domain of Rta (amino acids 416 to 519) linked to GALA had weak activation activity. Deletion of these domains from native Rta showed that the C-terminal domain was required for transactivation, but the subterminal domain was required only in B cells. The C-terminal activation domain of Rta contains a pattern of positionally conserved hydrophobic residues shared with VP16 and other transactivators. Substitution of several conserved hydrophobic amino acids in Rta severely impaired transactivation. The importance of hydrophobic residues was further substantiated by comparing EBV Rta with that of herpesvirus saimiri, which revealed little sequence similarity except for a few acidic residues and the positionally conserved hydrophobic amino acids. The C-terminal domain of EBV Rta contains three partially overlapping copies of this hydrophobic motif. Mutational analysis indicated that all three copies were required for full activity. However, two of the three copies appeared to be sufficient to produce full activity on a target promoter with multiple binding sites, suggesting that these motifs are

Here we demonstrate that open reading frame 16 (ORF16) of the oncogenic herpesvirus saimiri protects cells from heterologous virus-induced apoptosis. The BH1 and BH2 homology domains are highly conserved in ORF16, and ORF16 heterodimerizes with Bcl-2 family members Bax and Bak. However, ORF16 lacks the core sequence of the conserved BH3 homology domain, suggesting that this region is not essential for anti-apoptotic activity. Conservation of a functional bcl-2 homolog among gammaherpesviruses suggests that inhibition of programmed cell death is important in the biology of these viruses.

The Roux-en-Y gastric bypass procedure (RYGBP) is an effective treatment for morbid obesity. Anastomotic strictures are a common complication after RYGBP. This study examines the frequency of post-RYGBP gastrojejunal strictures (GJS), methods of evaluation, and the outcome of endoscopic intervention. Medical records of patients who had RYGBP for morbid obesity at our institution during four consecutive years were reviewed for patient demographics, medical comorbidities, surgical technique, and outcomes. Radiographic and endoscopic findings of those patients suspected to have GJS were noted. The impact of patient-related variables and surgical technique on risk of GJS, time to diagnosis of GJS, and treatment outcomes for GJS was determined. Of 888 patients, 503 had open RYGBP (57%) and 385 laparoscopic RYGBP (43%). Ninety-four patients (10.6%) underwent esophagogastroduodenoscopy (EGD) for possible GJS and 58 (6.5%) were found to have anastomotic stricture. Laparoscopic RYGBP was associated with increased incidence of GJS (43/385, 11.1%) compared with open RYGBP (15/503 or 2.9%, P = 0.0003). A total of 125 dilations were performed with an average of 2.2 dilations per patient. None of the strictures needed surgical revision. There were four perforations (3.2%) related to EGD. Mean time to diagnosis of GJS was 66.2 days. Eighty-seven of 94 patients underwent radiologic upper gastrointestinal (UGI) evaluation prior to EGD. UGI evaluation demonstrated a positive predictive value (PPV) of only 66% [95% confidence interval (CI) 52-77], and negative predictive value (NPV) of 83% (95% CI 65-93). Laparoscopic GBP is associated with increased risk of GJS. Endoscopic dilation of GJS is an effective treatment with minimal risk. Radiographic studies appear to have poor specificity for diagnosis of GJS and have a low positive predictive value. EGD should be performed in all suspected cases of GJS.