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Biomedical subjects

G Wakabayashi

Publications and source records attributed to G Wakabayashi.

57 records · Page 4Linked to original sources

Involvement of soluble adhesion molecules in acute pancreatitis.

The relationship between inflammatory cytokines and adhesion molecules in cases of acute pancreatitis was studied. Twenty-five patients were divided into three groups based on the severity of their disease as rated by the Ranson score. They were also divided into two groups according to the presence or absence of the complications of the multiorgan dysfunction syndrome (MODS) and the prognosis. As the severity of acute pancreatitis increased, the plasma levels of TNF-alpha, slCAM-1, sE-selectin, and sVCAM-1 also increased. The levels of all of these soluble adhesion molecules were significantly higher in the MODS-complicated group than in the non-MODS-complicated group. The levels of TNF-alpha, slCAM-1, and sVCAM-1 were significantly higher in patients who eventually died than in patients who survived. Significant correlations were observed between the levels of TNF-alpha and slCAM-1, between those of TNF-alpha and sVCAM-1, and between the levels of slCAM-1 and sVCAM-1. These results suggest that inflammatory cytokines stimulate the expression of adhesion molecules on the vascular endothelium and that mediators, including these adhesion molecules, are closely involved in the pathogenesis of acute pancreatitis. The plasma levels of these soluble adhesion molecules reliably reflected the severity of the disease.

Acute Disease↗

Picogram concentrations of endotoxin stimulate synthesis of IL-1 beta and TNF alpha by human peripheral blood mononuclear cells exposed to recombinant human C5a.

Endotoxemia, complement activation, and the generation of C5a occur in the course of sepsis, trauma, and the adult respiratory distress syndrome, clinical situations in which TNF and IL-1 are thought to play an important role. In the present studies, we examined the effect of picogram concentrations of endotoxin (LPS) on the synthesis of IL-1 beta and TNF alpha by human PBMC exposed to recombinant human C5a (rhuC5a). rhuC5a induced the synthesis of IL-1 beta by PBMC made in response to otherwise substimulatory levels of LPS. In the presence of rhuC5a, LPS concentrations from 10 pg to 1000 pg/ml substantially amplified IL-1 beta synthesis by PBMC compared to LPS alone. Since rhuC5a can induce transcription of IL-1 beta with minimal translation to cytokine protein, these studies support the concept that fM concentrations of LPS can combine with rhuC5a to provide the "second signal" for optimal translation of IL-1 beta mRNA.

Complement C5a↗

Levels of soluble adhesion molecules and cytokines in patients with septic multiple organ failure.

Multiple organ failure (MOF) is a common complication of sepsis or septic shock. In this condition, it is believed that activated neutrophils adhere to the vascular endothelium and induce various mediators and tissue damage, leading to organ damage. We investigated the plasma levels of inflammatory cytokine activating neutrophils, soluble adhesive molecules, and endotoxin in 8 patients with septic MOF, 15 patients with sepsis but without MOF, and in 5 patients with MOF unrelated infection. The soluble intercellular adhesion molecule-1 (sICAM-1) concentration in sepsis-complicated groups was significantly higher than that in the multiple organ failure (MOF) group without infection. Of sepsis-complicated groups, the sICAM-1 value in the MOF group was significantly higher than that in the sepsis group without MOF. In sepsis-complicated groups, both soluble endothelial-leukocyte adhesion molecule-1 (sELAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) concentrations were significantly higher than those in the MOF group without infection. However, there was no significant difference between the septic MOF group and the sepsis group without MOF. In patients showing high levels of soluble adhesion molecule, prognosis was poor, and the concentration of soluble adhesion molecules rapidly decreased during recovery from MOF. It is speculated that endotoxin and inflammatory cytokines damage vascular endothelium as well as various other cells and produce, a large number of adhesion molecule, especially in patients with septic MOF, causing leakage of adhesion molecules into blood.

Adult↗