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Biotech / Medical : XOMA. Bull or Bear? -- Ignore unavailable to you. Want to Upgrade?

To: aknahow who wrote (6801)	7/26/1998 9:21:00 AM
From: Robert K.	Respond to of 17367

More on LBP>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> >>PLASMA LEVELS OF LIPOPOLYSACCHARIDE BINDING PROTEIN (LBP) CORRELATE WITH OUTCOME IN SEPSIS AND OTHER PATIENTS Stephen F. Carroll, Russell L. Dedrick and Mark L. White. XOMA Corporation, 2910 Seventh Street, Berkeley, CA 94596, USA. Lipopolysaccharide binding protein (LBP) is a 60 kDa plasma glycoprotein that participates in the host response to bacteria and their endotoxins. We developed an ELISA for human LBP and examined the levels of LBP in plasma samples from healthy adults and patients with various illnesses. Plasma samples from more than 700 patients suffering from 20 different septic, inflammatory and non-inflammatory diseases were studied. Relative to values measured in healthy adults (4.1 æg/mL), significant elevations in the plasma levels of LBP were only identified in patients with inflammatory bowel diseases (17.4 æg/mL), meningococcemia (19.7 æg/mL), presumed gram-negative sepsis (30.6 æg/mL), and complicated abdominal infections (52.1 æg/mL). Also, sepsis patients with high initial levels of LBP had high 28 day mortality, whereas patients with low initial levels of LBP had low mortality. These results prompted us to monitor the plasma levels of LBP in patients enrolled in clinical trials investigating the anti-infective properties of rBPI21, a recombinant modified N-terminal fragment of human bactericidal/ permeability-increasing protein. Data are now available for meningococcemia patients and patients undergoing partial hepatectomy. Both populations exhibited increased levels of LBP, the magnitude, kinetics and duration of which were reflective of clinical outcome. These results suggest that the plasma levels of LBP are significantly elevated only in diseases involving exposure to bacteria and their endotoxins, and that measuring LBP levels may be of clinical value in multiple patient populations.

To: aknahow who wrote (6801)	7/26/1998 9:29:00 AM
From: Robert K.	Respond to of 17367

Bpi neutralizes endotoxin, blocks LBP, Might stop TNF,kills bacteria> >>>>>>>> DDDDDUUUUUUHHHHHHHH>>>>> >The role of bactericidal/permeability-increasing protein as a natural inhibitor of bacterial endotoxin. Marra MN, Wilde CG, Collins MS, Snable JL, Thornton MB, Scott RW Incyte Pharmaceuticals, Palo Alto, CA 94304. Systemic release of endotoxin (LPS) after Gram-negative infection initiates a cascade of host cytokines that are thought to be the direct cause of shock, multisystem organ failure, and death. Endogenous LPS-binding proteins may play a role in regulating LPS toxicity in vivo. The human neutrophil granule protein bactericidal/permeability-increasing protein (BPI) shares sequence homology and immunocrossreactivity with an acute phase lipopolysaccharide binding protein (LBP) which has been shown to bind to LPS and accelerate LPS activation of neutrophils and macrophages. Although structurally similar, LBP and BPI are apparently functionally antagonistic. We previously showed that BPI inhibits LPS-mediated neutrophil activation in vitro. Here we demonstrate that BPI binds to LPS near the lipid A domain, and formation of the LPS-BPI complex abrogates detrimental host responses to LPS. For example, BPI blocks LPS-stimulated TNF release in vitro and in vivo, and LPS complexed to BPI is not pyrogenic in rabbits. Results demonstrating that BPI is released by stimulated human neutrophils further support the idea that BPI functions extracellularly in vivo to neutralize endotoxin. Taken together, these data argue that BPI neutralizes the toxic effects of LPS in vivo, and that BPI may represent a new therapeutic approach to the treatment of endotoxic shock. PMID: 1729370, UI: 92105751