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

To: Robert S. who wrote (6682)	7/14/1998 5:22:00 PM
From: aknahow	Respond to of 17367

Robert S., I guess you are missing the importance of a big dose of enotoxin vs a smaller dose due to much of it being bound up. Again I am no expert and your question was directed, this time to Tharos, but I thought the body was equipped to deal with some endotoxin every day. Thought it was the overload that caused problems. Bob if you have any information that indicates that even a small amount of endotoxin is a critical problem please post it here. If you just want to post that any amount of endotoxin and bacteria not bound up by BPI is going to be a problem, you can check in at the Yahoo boards and post away! <g>

To: Robert S. who wrote (6682)	7/14/1998 6:17:00 PM
From: Tharos	Respond to of 17367

Infect. Immun., Aug 1994, 3564-3567, Vol 62, No. 8 Copyright c 1994, American Society for Microbiology Recombinant human bactericidal/permeability-increasing protein (rBPI23) is a universal lipopolysaccharide-binding ligand BJ Appelmelk, YQ An, BG Thijs, DM MacLaren and J de Graaff Department of Medical Microbiology, Vrije Universiteit, Amsterdam, The Netherlands. A recombinant 23-kDa protein (rBPI23) derived from human bactericidal/permeability-increasing protein (BPI) possesses potent endotoxin-neutralizing abilities in vitro and in vivo. Binding of rBPI23 to those endotoxins (lipopolysaccharides [LPSs]) encountered clinically would be a prerequisite for efficacy in decreasing mortality among patients suffering from gram-negative sepsis and shock, a disease state in which an etiological role for LPS has been implicated. rBPI23 binds well to lipid A (n = 7), to rough-mutant O-chain-deficient LPS (n = 18, Re to Ra chemotypes), to lipid A-core covalently linked to the O chain, to LPSs from clinically relevant serotypes (n = 100), and to bacterial cells (n = 88) of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, the species most often implicated in clinical gram-negative sepsis and shock. Significant binding of rBPI23 to these antigens took place at rBPI23 concentrations of 1 to 500 ng/ml (median, 16 to 32 ng/ml). Binding did not involve 3-deoxy-D-manno- octulosonate of the inner core. Determining the exact epitope recognized by rBPI23 would require further studies with synthetic lipid A substructures. The demonstrated ability of rBPI23 to universally bind LPS provides a sound basis for further testing of its endotoxin- neutralizing abilities, including clinical trials. iai.asm.org --------------------------------------------------- More recent studies have demonstrated a least four types of lipid proteins that BPI binds to and have not found a lipid protein it does not bind to. The possibility exists, and George more cautiously admits, for BPI not to bind to all gram-negative bacteria. I certainly welcome you, Robert S., to add to the debate by carefully explaining the make-up of each gram-negative bacteria in the type of lipid protein it uses in its cell wall. This may help determine which gram-negative bacteria BPI will most likely have a theraputic effect for. Anxiously awaiting your detailed breakdown of the structure of all gram-negative bacteria. Tharos

To: Robert S. who wrote (6682)	7/15/1998 2:37:00 AM
From: Tharos	Read Replies (2) \| Respond to of 17367

>>What am I missing?<< ----------------------------------------------------- In your enthusiasm to find an inconsistency in George's and my statements, how about you seem to be ignoring what I wrote. So, just for you, I broke out my crayon set to recompose: Some bacteria are composed of lipopolysaccharide. As long as the bacteria are composed of lipopolysaccharide, BPI will bind to the bacteria's lipopolysaccharide, and even if BPI does not kill the bacteria that are composed of lipopolysaccharide, it will neutralize the lipopolysaccharide endotoxins caused by the bacteria's death, that is to say, the bacteria made of lipopolysaccharide that die and give off lipopolysaccharide endotoxins. Not all bacteria are composed of lipopolysaccharide, Not all endotoxins are composed of lipopolysaccharide, not all endotoxins come from bacteria, so George is correct that BPI does not bind up all endotoxin. I'm looking forward to your post with detailed analysis of all gram-negative bacteria and their genetic make-up.