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Biotech / Medical : Rigel Pharmaceuticals, Inc. (RIGL) -- Ignore unavailable to you. Want to Upgrade?

To: tuck who wrote (303)	10/2/2006 12:52:45 PM
From: scaram(o)uche	Read Replies (1) \| Respond to of 566

Preramble..... there's something that I'm missing. So none of what follows actually answers your question. :-) Cool that you ask. I used Shwartzman reactions, a close relative to Arthus, as part of a package to analyze the putative anti-core endotoxin mabs, xoma and cnto. And arthus reactions are a part of any med micro student's first year lab basics. Big believer in these simple, sensitive "animal assays". Know that you'll grimace at that, but this is sorta like getting a smallpox reaction to initial vaccination.... it's not as bad as it sounds. Arthus: You immunize an animal (non-complement-deficient). You LATER come back and inject some antigen INTO the skin (intradermally). At about 24 hours, you begin to see inflammation. This contrasts to IgE-mediated immediate sensitivity and to T cell-mediated delayed hypersensitivity, which show up at about four days. The 24 hour bit is caused by antibody in the immunized animal finding the antigen, localized in the skin. The antigen-antibody (IgG or IgM) complexes fix "complement", and neutrophils and other inflammatory components are attracted to the site. Passive Arthus: Same thing, except the animals are never immunized. Antigen goes into the skin, and you test various IgG and/or IgM preparations -- to see if they are antigen specific -- by passively shooting them intravenously into complement-competent animals. If your intent is to test a complement inhibitor, you use a known positive antibody sample for all animals. Reverse passive Arthus: Antibody goes into the skin, antigen goes systemic. There are now variations on the theme, peritoneal infiltrate instead of skin. So, you get the picture re. "passive" and "reverse". But there's something I'm missing, as they're measuring contributions of Fc receptor binding.... maybe they're using complement deficient animals?? If it gets to be important, let me know and I'll look up the entire paper. Best! Rick

To: tuck who wrote (303)	12/2/2006 12:43:30 PM
From: tuck	Respond to of 566

[R406: Syk is a protooncogene involved in the transformation of lymphocytes, thus making Syk a potential target for the treatment of leukemia.] >>: J Exp Med. 2006 Nov 27; [Epub ahead of print] Deregulated Syk inhibits differentiation and induces growth factor-independent proliferation of pre-B cells. Wossning T, Herzog S, Kohler F, Meixlsperger S, Kulathu Y, Mittler G, Abe A, Fuchs U, Borkhardt A, Jumaa H. Institute of Biology III, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany. The nonreceptor protein spleen tyrosine kinase (Syk) is a key mediator of signal transduction in a variety of cell types, including B lymphocytes. We show that deregulated Syk activity allows growth factor-independent proliferation and transforms bone marrow-derived pre-B cells that are then able to induce leukemia in mice. Syk-transformed pre-B cells show a characteristic pattern of tyrosine phosphorylation, increased c-Myc expression, and defective differentiation. Treatment of Syk-transformed pre-B cells with a novel Syk-specific inhibitor (R406) reduces tyrosine phosphorylation and c-Myc expression. In addition, R406 treatment removes the developmental block and allows the differentiation of the Syk-transformed pre-B cells into immature B cells. Because R406 treatment also prevents the proliferation of c-Myc-transformed pre-B cells, our data indicate that endogenous Syk kinase activity may be required for the survival of pre-B cells transformed by other oncogenes. Collectively, our data suggest that Syk is a protooncogene involved in the transformation of lymphocytes, thus making Syk a potential target for the treatment of leukemia.<< Cheers, Tuck