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

To: Bluegreen who wrote (9565)	4/9/1999 1:55:00 PM
From: aknahow	Read Replies (1) \| Respond to of 17367

Who is (Keynote lecture: Tom. Ganz, Los Angeles: The antimicrobial peptides - an overview )???

To: Bluegreen who wrote (9565)	4/9/1999 1:59:00 PM
From: aknahow	Respond to of 17367

In search for Ganz found program. grc.uri.edu

To: Bluegreen who wrote (9565)	4/9/1999 2:21:00 PM
From: aknahow	Read Replies (1) \| Respond to of 17367

Sutro presentation made at 8:00 a.m. today, friday 9 April. Doyle at XOMA is source.

To: Bluegreen who wrote (9565)	4/10/1999 9:09:00 PM
From: aknahow	Respond to of 17367

Il Ciocco, Barga, Italy about 100 miles from Nice, France. Probably coastal drive.

To: Bluegreen who wrote (9565)	4/10/1999 9:25:00 PM
From: aknahow	Respond to of 17367

Who where? RI Lehrer and T Ganz Antimicrobial polypeptides of human neutrophils Blood Dec 1 1990; 76: 2169-2181. Abstract was not available!

To: Bluegreen who wrote (9565)	4/10/1999 9:44:00 PM
From: aknahow	Respond to of 17367

Ganz is with Will Rogers Pulmonary etc. The pro region of human neutrophil defensin contains a motif that is essential for normal subcellular sorting L Liu and T Ganz Will Rogers Pulmonary Research Laboratory, University of California, Los Angeles School of Medicine 90024-1736. Human defensins (human neutrophil peptides) HNP 1-3 are 29-30 amino acid antibiotic and cytotoxic peptides highly abundant in the cytoplasmic granules of polymorphonuclear leukocytes. The peptides are produced from 94 amino acid (aa) prepropeptides by proteolytic cleavage of the signal sequence and stepwise removal of the 44-45 aa anionic propiece. To study the role of the propiece, we constructed five in- frame deletions in preproHNP-1 cDNA between the signal peptidase site and the amino-terminus of the mature defensin region (aa 21-64). The wild type HNP-1 cDNA and the deletion mutants were ligated into the pBabe-Neo retroviral vector, expressed in GP+E86 packaging derivative of NIH 3T3 cells, then transduced into the 32D cl3 granulocytic cell line. For each construction and both cell lines, we measured the accumulation of the various defensin forms in cells and media by 24- hour labeling or pulse-chase with 35S-cysteine- and immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Deletions in the amino-terminal two-fifths of the propiece, delta 21-28 and delta 21-38, had only minor effects on defensin biosynthesis in both cell lines and did not interfere with the accumulation of mature defensin in the granules of 32D cl3 cells. Deletions in the carboxyterminal three-fifths of the propiece (delta 21- 51 and delta 21-64) diminished net defensin synthesis, blocked constitutive secretion of prodefensin in both cell lines, and interfered with defensin accumulation in cytoplasmic granules of 32D cl3 cells. These effects were reproduced by the smaller deletion delta 40-51, which contains highly conserved secondary structure. The propiece segment 40-51 appears to be essential for the subcellular trafficking and sorting of HNP-1 defensin. Volume 85, Issue 4, pp. 1095-1103, 02/15/1995 Copyright © 1995 by The American Society of Hematology

To: Bluegreen who wrote (9565)	4/10/1999 10:09:00 PM
From: aknahow	Respond to of 17367

Beutler perhaps knows Dr. Giroir??? Bruce A. Beutler, M.D. Professor of Internal Medicine Biochemistry and Molecular Biology Office: 214-648-5006 FAX: 214-648-6395 Email: beutler@howie.swmed.edu Innate immunity is largely dependent upon the actions of macrophages and NK cells, which seem capable of sensing host invasion in a rather non-specific fashion. Unlike lymphocytes, which depend upon a huge array of highly specific receptors, macrophages utilize a much smaller array of molecules that are rather flexible in their ability to detect microbial pathogens. Far less is known about these broadly active receptor systems. However, it is clear that they are able to recognize whole categories of micro-organisms. A case in point is the detection of gram negative bacteria, which are, as a group, united in their ability to synthesize lipopolysaccharide (LPS), or endotoxin. LPS is a highly toxic molecule, prompting massive release of toxic cytokines from macrophages. In large part, is thought to be responsible for the shock syndrome that develops in the course of a serious gram negative infection. While LPS binds to macrophages via CD14, it is not known how the the LPS signal traverses the cell membrane. In mice, a single codominant mutation (Lpsd) can abolish all responses to LPS. Mice homozygous for the Lpsd allele are highly resistant to the lethal effect of LPS; however, they are very susceptible to gram negative infection. Our laboratory is attempting to clone the Lps gene through a positional approach. The location of the mutation has been narrowed to an interval well beneath 1 megabase in size, and a number of candidate genes are being closely examined for evidence of a genetic lesion. It is believed that isolation of the Lps gene will permit far more detailed understanding of the mechanisms of LPS signal transduction. Conceivably, the protein encoded by Lps will itself be a target for the design of drugs that block endotoxin signaling. Further, it is likely that variability in human susceptibility to endotoxic shock may be determined by polymorphism at this locus. ------------------------------- Kruys V, Thompson P and Beutler B (1993) Extinction of the TNF locus, and of genes encoding the LPS signaling pathway. J Exp Med 177:1383-1390 Beutler B and Brown T (1993) Polymorphism of the mouse TNFa locus: sequence studies of the 3'UTR and first intron. Gene 129:279-283 Kolls J, Peppel K, Silva M and Beutler B (1994) Prolonged and effective blockade of TNF activity through adenovirus-mediated gene transfer. Proc Natl Acad Sci 91:215-219 Bazzoni F, Kruys V, Shakhov A, Jongeneel CV and Beutler B (1994) Analysis of TNF promoter responses to ultraviolet light. J Clin Invest 93:56-62 Geppert TD, Whitehurst CE, Thompson P, and Beutler B (1994) LPS signals activation of TNF biosynthesis through the RAS/RAF-1/MEK/MAPK pathway. Mol Med 1:93-103 Bazzoni F, Alejos E, and Beutler B (1995) Chimeric TNF receptors with constitutive signalling activity. Proc Natl Acad Sci 92:5376-5380 Bazzoni F and Beutler B (1996) The tumor necrosis factor ligand and receptor families. N Engl J Med 334:1717-1725 [Back to Faculty Research Interests Search] [Back to UT Southwestern Home Page] Page maintained by Carolyn Paulk UT Southwestern Medical Center Last Updated: September 13, 1997

To: Bluegreen who wrote (9565)	4/12/1999 1:23:00 PM
From: aknahow	Respond to of 17367

Barga meeting on 25 th. April. Guess I would prefer that Dr. Scannon say something in London. I do believe that biotech companies wait for so called scientific meetings to announce certain types of news. Even though XOMA apparently is not going to be present at the Barga meeting, Elsbach and Beutler will be there. Amazed that XOMA does not plan a press release until all details of the GNE agreement are final. More amazed that details supposedly are not final. This is based on a conversation with J. Doyle.