No abstract

Tumor biological factors including favorable tumor grade may be the most important influence on 5 year actual survival in esophageal cancer.

The initiation of programmed cell death at CD95 (Fas, Apo-1) is achieved by forming a death-inducing signaling complex (DISC) at the cytoplasmic membrane surface. Assembly of the DISC has been proposed to occur via homotypic interactions between the death domain (DD) of FADD and the cytoplasmic domain of CD95. Previous analysis of the FADD/CD95 interaction led to the identification of a putative CD95 binding surface within FADD DD formed by ␣ helices 2 and 3. More detailed analysis of the CD95/FADD DD interaction now demonstrates that a bimodal surface exists in the FADD DD for interaction with CD95. An expansive surface on one side of the domain is composed of elements in ␣ helices 1, 2, 3, 5, and 6. This major surface is common to many proteins harboring this motif, whether or not they are associated with programmed cell death. A secondary surface resides on the opposite face of the domain and involves residues in helices 3 and 4. The major surface is topologically similar to the protein interaction surface identified in Drosophila Tube DD and the death effector domain of hamster PEA-15, two physiologically unrelated proteins which interact with structurally unrelated binding partners. These results demonstrate the presence of a structurally conserved surface within the DD which can mediate protein recognition with homoand heterotypic binding partners, whereas a second surface may be responsible for stabilizing the higher order complex in the DISC. The subgroup of tumor necrosis factor receptor (TNFR)1 superfamily members that contain a death domain (DD) within their cytoplasmic region have been termed "death receptors" (1). The receptor DD is the nucleus of an intracellular deathinducing cellular signaling complex (DISC), which forms in response to ligand binding by the receptor. The DISC of CD95 (Fas, Apo-1), one of six TNFRs that initiate cell death, is composed of the activated receptor (2, 3), the adaptor protein FADD (4, 5), and the initiator caspases, caspase-8 (6 -8) and caspase-10 (9, 10). A key molecule in this assembly is FADD, which links the death receptor to the caspases, a function attributed to FADD at nearly all death receptors identified to date (1). FADD contains two ϳ90-amino acid protein interaction modules, an N-terminal death effector domain (DED), and a C-terminal DD, each of which adopts a structurally similar six ␣-helical bundle (11-13). It has been suggested that the two domains of FADD function independently of each other (4, 5), with the DD responsible for interaction with CD95 and the DED responsible for the subsequent recruitment of caspases into the DISC (11-13).Despite knowledge of the three-dimensional structures of the DD (12-17) and DED (11, 18) motifs from a variety of proteins, the mechanism of protein recognition by these structurally homologous motifs has not been clearly defined. The crystal structure of Drosophila Tube DD bound to the DD from the serine/threonine kinase Pelle demonstrated that the DD motif possessed two distinct and opposing protein interaction surfac...

Background: Uric acid has been reported to be a risk factor for the development of chronic kidney disease; however, no study has examined whether uric acid may confer a risk for acute kidney injury. Methods: We investigated the relation between serum uric acid and the incidence of postoperative acute kidney injury in patients undergoing high-risk cardiovascular surgery (cardiac valve and aneurysm surgery). Results: Following cardiovascular surgery, 18 of 58 patients (31%) developed acute kidney injury, with 11 of 24 (45.8%) in the elevated uric acid group (defined as >6 mg/dl) and 7 of 34 (20.5%) in the normal uric acid group (p = 0.05). After controlling for baseline renal function, left ventricular ejection fraction, use of nesiritide, type of surgery, and history of previous surgery, an elevated preoperative uric acid conferred a 4-fold risk for acute kidney injury (OR: 3.98, CI: 1.10–14.33, p = 0.035) and longer hospital stay (36.35 vs. 24.66 days, p = 0.009). Conclusion: This preliminary study suggests that uric acid may be a novel risk factor for acute kidney injury in patients undergoing high-risk cardiovascular surgery.