Abdominal and thoracoabdominal aortic aneurysm

Most abdominal aortic aneurysms (AAA) and thoracoabdominal aortic aneurysms (TAAA) are asymptomatic and are found on physical exam or incidentally during radiological studies for other indications. These aneurysms are repaired primarily because their risk of rupture increases geometrically as the size exceeds 5 cm. The potential morbidity of intraoperative visceral and spinal ischemia involved with TAAA repair may be reduced with various adjunctive maneuvers.     

Anti-CD4 activity of normal human immunoglobulin G for therapeutic use. (Intravenous immunoglobulin, IVIg)

The effects of intravenously administered normal immunoglobulin G (IVIg) in autoimmune diseases are dependent on the ability of IVIg to interact with surface molecules of lymphocytes. In the present study, we demonstrate the presence of anti-CD4 activity in IVIg by showing the ability of IVIg to bind to CD4 and to inhibit CD4-dependent cellular functions. Binding of IVIg to recombinant soluble human CD4 was assessed by ELISA, immunoblotting and real time analysis of complex formation. Anti-CD4 antibodies isolated from IVIg by affinity-chromatography bound to human CD4+ T cells. These anti-CD4 antibodies inhibited proliferative responses in MLR and infection of CD4+ human T cells with HIV. These results indicate that IVIg contains antibodies reactive with human CD4 and that these anti-CD4 antibodies exhibit biological functions. The presence of anti-CD4 antibodies in IVIg may be relevant to the immunoregulatory effects of normal polyspecific immunoglobulin G.     

Changes in plasma and colonic mucosa fatty acid profiles in rats with ulcerative colitis induced by trinitrobenzene sulfonic acid

Polyunsaturated fatty acids have a key role in the pathogenesis of inflammatory bowel disease since some of the arachidonic acid-derived eicosanoids have been found to be increased in inflamed intestinal mucosa in the acute phase of human disease. The aim of this study was to prospectively assess plasma and colon mucosa fatty acid patterns in rats with experimental ulcerative colitis. Twenty rats were treated with trinitrobenzene sulfonic acid and 20 with NaCl; two groups were killed after one week and two after two weeks to evaluate colon damage. Plasma was obtained by aortic puncture and colonic mucosa was scraped off and the fatty acid pattern was determined by gas-liquid chromatography. Total, saturated, and monounsaturated plasma fatty acids were significantly higher in both periods of ulcerative colitis as compared to controls. Plasma n-6 fatty acids were increased after treatment, but no significant changes were observed concerning to n-3 fatty acids. With regard to colon mucosa, saturated and monounsaturated fatty acids did not change because of the disease; however, n-6 fatty acids decreased in the first week and increased in the second week and n-3 fatty acids were increased. Changes on the fatty acid distribution in plasma did not parallel to those of colonic mucosa except for 22:6(n-3). We have also found that experimental ulcerative colitis induced by trinitrobenzene sulfonic acid reproduces many of the features related to changes in plasma and colon mucosa fatty acids observed in the human disease.     

Synthesis and in vitro antimalarial activity of sulfone endoperoxides

A series of 4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]+ ++nonanes, carrying a variety of substituents at position-8 (4) were prepared by a short and efficient method from R-(+)-limonene. Key reactions include thiol oxygen cooxidation, and alkylation and acylation of a sterically hindered tertiary alcohol compatible with the endoperoxy functionality. Some of compounds 4, which are structurally related to yingzhaosu A (2), were found to exhibit in vitro antimalarial activity comparable to that of artemisinin (1) and superior to that of arteflene (3).     

Structural and thermodynamic characterization of the interaction of the SH3 domain from Fyn with the proline-rich binding site on the p85 subunit of PI3-kinase

The interaction of the Fyn SH3 domain with the p85 subunit of PI3-kinase is investigated using structural detail and thermodynamic data. The solution structure complex of the SH3 domain with a proline-rich peptide mimic of the binding site on the p85 subunit is described. This indicates that the peptide binds as a poly(L-proline) type II helix. Circular dichroism spectroscopic studies reveal that in the unbound state the peptide exhibits no structure. Thermodynamic data for the binding of this peptide to the SH3 domain suggest that the weak binding (approximately 31 microM) of this interaction is, in part, due to the entropically unfavorable effect of helix formation (delta S0 = -78 J.mol-1.K-1). Binding of the SH3 domain to the intact p85 subunit (minus its own SH3 domain) is tighter, and the entropic and enthalpic contributions are very different from those given by the peptide interaction (delta S0 = +252 J.mol-1.K-1; delta H0 = +44 kJ.mol-1). From these dramatically different thermodynamic measurements we are able to conclude that the interaction of the proline-rich peptide does not effectively mimic the interaction of the intact p85 subunit with the SH3 domain and suggest that other interactions could be important.     

Routine intraoperative laparoscopic cholangiography

BACKGROUND: Whether intraoperative laparoscopic cholangiography should be routine is debatable. METHODS: We reviewed the cholangiography experience in 669 consecutive laparoscopic cholecystectomies. RESULTS: Mean age of the patients was 39 years, 78% were female, and 29% had acute cholecystitis. Cholecystectomy was completed laparoscopically in 606 (91%). Laparoscopic cholangiography was completed in 562 (93%) and 348 (62%) were routine (no preoperative indication). The mean operating time in 1996 was 61 minutes. Out of the 348 routine cholangiograms, 17 demonstrated evidence of unsuspected choledocholithiasis. Five patients had choledocholithiasis documented by laparoscopic common bile duct exploration and/or endoscopic retrograde cholangiopancreatography. Two patients had normal postoperative cholangiopancreatography. One of 10 patients managed expectantly was readmitted postoperatively with obstructive jaundice. In 4 patients, routine cholangiography revealed unexpected anatomy, and in 2, this prevented misidentification and transection of the common bile duct. CONCLUSION: Laparoscopic cholangiography is safe, quick, detects unsuspected choledocholithiasis, and can prevent common bile duct transection. It should be routine.     

Selectivity of recognition of variable (V) regions of autoantibodies by intravenous immunoglobulin (IVIg)

In the present study, we demonstrate that intravenous immunoglobulin (IVIg) is capable of binding to variable (V) regions of anti-endothelial cell antibodies (AECA) of healthy donors and patients with systemic lupus erythematosus (SLE). Among V regions of AECAs, IVIg selectively recognized certain idiotypes expressed by the autoantibodies of a given individual, in the case of both natural and SLE-associated AECAs. These observations provide new and direct evidence that IVIg interacts idiotypically with V regions of autoantibodies and that the efficacy of such interaction depends on individual autoantibody specificity. Our findings may be relevant for the understanding of the mechanisms that control expression of natural autoantibody activity in serum and for that of the differences in response to IVIg therapy that are seen between patients with autoimmune disease.