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Lyle L Moldawer

Publications and source records attributed to Lyle L Moldawer.

74 records · Page 5Linked to original sources

Varying blood monocyte and dendritic cell responses after laparoscopic versus open gastric bypass surgery.

BACKGROUND: Laparoscopy may activate innate immunity less than conventional open surgery. This may be important in obese patients who have pre-existing low-grade inflammation. This study examined phenotypic changes in blood monocytes (Mcs) and dendritic cells (DCs) from patients undergoing laparoscopic (L) or open (O) Roux-en-Y gastric bypass (RYGBP) surgery. METHODS: 8 patients (3 male) had blood drawn before and after RYGBP, and on postoperative day (POD) 1, 3, and 28. Mc and DC quantity, phenotype, and activation status were determined by flow cytometry. RESULTS: Mean BMI was 53 +/- 4 and 46 +/- 1, and length of stay was 6.3 +/- 3.2 and 3.5 +/- 0.6 days, in the O (n=4) versus L (n=4) groups, respectively. Postoperative WBC count was 16 +/- 1 x 10(3)/mm3 after O and 10 +/- 1 x 10(3)/mm3 after LRYGBP (P<0.001). This was due to a greater rise in neutrophils and decline in lymphocytes after ORYGBP (P<0.001). Total Mcs increased in both groups at POD 1, but the number of CD18+ Mcs was reduced after ORYGBP (P=0.04). Mc human leukocyte antigen (HLA)-DR expression was lower in CD16+ Mcs after ORYGBP, suggesting decreased capacity to present antigen (P=0.002). Postoperatively, total DCs decreased in both groups, but recovered (P=0.04). The proportion and activation of the tolerogenic DC2 phenotype was lower, whereas the percentage of the ldDC phenotype was higher, in the O group (P=0.006). CONCLUSION: RYGBP changes the quantity and phenotype of circulating blood Mcs and DCs. Although there were overall similarities in the overall response to gastric surgery between open and laparoscopic, there were some notable differences, including a greater reduction in HLA-DR expression and increased number of immature DCs in the ORYGBP group. The findings suggest that RYGBP may have varying immunologic consequences depending upon the surgical procedure employed.

Adult↗

Structural basis for the proinflammatory cytokine activity of high mobility group box 1.

High mobility group box 1 (HMGB), a ubiquitous DNA-binding protein, has been implicated as a proinflammatory cytokine and late mediator of lethal endotoxemia. HMGB1 is released by activated macrophages. It amplifies and extends the inflammatory response by inducing cytokine release and mediating acute lung injury, anorexia, and the inflammatory response to tissue necrosis. The kinetics of HMGB1 release provide a wide therapeutic window for endotoxemia because extracellular levels of HMGB1 begin to increase 12 to 24 h after exposure to inflammatory stimuli. Here, we demonstrate that a DNA-binding domain of HMGB1, the B box, recapitulates the cytokine activity of full length HMGB1 and efficiently activates macrophages to release tumor necrosis factor (TNF) and other proinflammatory cytokines. Truncation of the B box revealed that the TNF-stimulating activity localizes to 20 amino acids (HMGB1 amino acids 89 to 108). Passive immunization of mice with antibodies raised against B box conferred significant protection against lethal endotoxemia or sepsis, induced by cecal perforation. These results indicate that a proinflammatory domain of HMGB1 maps to the highly conserved DNA-binding B box, making this primary sequence a suitable target in the design of therapeutics.

Animals↗