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


To: aknahow who wrote (5004)12/5/1997 10:24:00 AM
From: Robert K.  Respond to of 17367
 
Just out. Journal of immunology. Underscores role of bpi......................

Ralf R. Schumann, Norbert Lamping, and Adolf Hoess

Host defense against microorganisms involves proteins that bind specifically to bacterial endotoxins (LPS), causing different cellular effects. Although LPS-binding protein (LBP) can enhance LPS activities, while bactericidal/permeability-increasing protein (BPI) and Limulus anti-LPS factor (LALF) neutralize LPS, it has been proposed that their LPS-binding domains possess a similar structure. Here, we provide evidence that the LBP/LPS-binding domain is, as in the LALF structure, solvent exposed and therefore available for LPS binding. Our investigations into the activity of LPS-binding domains of different LPS-binding proteins, in the context of LBP, provide the first functional analysis of these domains in a whole protein. We constructed domain exchange hybrid proteins by substituting 12 amino acids of the LBP/LPS-binding domain with those of BPI and LALF and expressed them in Chinese hamster ovary cells. Although discrete point mutations within the LPS-binding domain of LBP disrupted its specific functions, the hybrid proteins were still able to bind LPS and, in addition, retained the wild-type LBP activity of enhancing LPS priming for FMLP-induced oxygen radical production by neutrophils and transferring LPS aggregates to CD14. Although BPI and LALF display opposite activities to LBP, and LALF does not share any sequence homology with LBP, our data provide strong evidence that LBP, BPI, and LALF possess a solvent-exposed, interchangeable LPS binding motif that is functionally independent of LPS transport or neutralization.



To: aknahow who wrote (5004)12/5/1997 12:16:00 PM
From: Eric Klein  Read Replies (1) | Respond to of 17367
 
I subscribe to Michael Murphy's Calif. Tech Stock Newsletter. He's a big promoter of XOMA.

I think that infectious diseases are (unfortunately) making a big comeback as a public health problem. TB, for example, is ISPO (In Some People's Opinion, WOW I coined a new I**O abbreviation, I wonder if it will catch on?) a bigger public health problem than AIDS. Some of the numbers going around are horribly frightening.

Could BPI be effective in treating TB? Why or why not?