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Biotech / Medical : Biotransplant(BTRN) -- Ignore unavailable to you. Want to Upgrade?


To: tnsaf who wrote (76)8/30/1998 2:58:00 PM
From: scaram(o)uche  Respond to of 1475
 
Jason:

Thank you, thank you, thank you!

Wow. It wasn't there a couple of days ago. It used to take about three months to get a Medline reference into the database, back in the days of Grateful Med. I have recently noticed stuff showing up at PubMed virtually days after publication. We increasingly have access to very powerful tools.

The work..... good stuff, a very new concept to me. However, we'd still be talking a generalized immunosuppressant. The BTRN concept involves only the elimination of cells that are reacting with antigen at the time of anti-CD2 administration (I am not saying that I've seen sufficient evidence that it will work). Here's something related......

Infect Immun 1994 Sep;62(9):3705-3711

Tryptophan depletion as a mechanism of gamma interferon-mediated
chlamydial persistence.

Beatty WL, Belanger TA, Desai AA, Morrison RP, Byrne GI

Department of Medical Microbiology and Immunology, University of Wisconsin, Madison 53706.

Previous studies have shown that the immune-regulated cytokine gamma interferon (IFN-gamma) activates host cells to restrict
intracellular growth of the bacterial pathogen Chlamydia trachomatis by induction of the tryptophan-catabolizing enzyme
indoleamine 2,3-dioxygenase (IDO). Recently, subinhibitory levels of IFN-gamma were used to generate an in vitro persistent
chlamydial infection characterized by large aberrant, noninfectious reticulate bodies from which infectious progeny could be
recovered following the removal of IFN-gamma. Studies were done to determine if the mechanism functioning to induce
chlamydiae to enter a persistent state in the presence of low levels of IFN-gamma was similar to that reported to inhibit
chlamydial growth. Host cells treated with levels of IFN-gamma required to induce persistence were assessed for IDO activity
by high-performance liquid chromatography analysis of tryptophan and its catabolic products. Substantial tryptophan
catabolism was detected in acid-soluble cellular pools, indicating that the intracellular availability of this essential amino acid was
limited under these conditions. In addition, a mutant cell line responsive to IFN-gamma but deficient in IDO activity was shown
to support C. trachomatis growth, but aberrant organisms were not induced in response to IFN-gamma treatment. Analyses of
infected cells cultured in medium with incremental levels of exogenous tryptophan indicated that persistent growth was induced
by reducing the amount of this essential amino acid. These studies confirmed that nutrient deprivation by IDO-mediated
tryptophan catabolism was the mechanism by which IFN-gamma mediates persistent growth of C. trachomatis.