NASA Scientific and Technical Aerospace Reports

pathways used by these superantigens; inhibition of cytokine and chemokine production; and inhibition of the downstream
signaling pathways used by proinflammatory cytokines and chemokines. Early blockade of these targets proves to be useful
in vitro and in vivo testing of therapeutics against SEB-induced toxic shock will also be reviewed.
DTIC
Antigens; Chemotherapy; Drugs; Immunity; Staphylococcus
20060001789 Army Medical Research Inst. of Infectious Diseases, Fort Detrick, MD USA
Anthrax Biosensor, Protective Antigen Ion Channel Asymmetric Blockade
Halverson, Kelly M.; Panchal, Rekha G.; Nguyen, Tam L.; Gussio, Rick; Little, Stephen F.; Misakian, Martin; Bavari, Sina;
Kasianowicz, John J.; Oct. 7, 2005; 8 pp.; In English; Original contains color illustrations
Report No.(s): AD-A440215; RPP-05-403; No Copyright; Avail.: Defense Technical Information Center (DTIC)
Bacillus anthracis secretes three proteins (protective antigen, PA; lethal factor, LF; and edema factor, EF) that are the basis
for anthrax infection. We present electrophysiological measurements that demonstrate the effect of full-length LF and EF on
ion channels formed by the proteolytically activated species of PA (PA63) in planar lipid bilayer membranes. LF and EF
convert the heptameric PA63 channel current-voltage relationship from slightly nonlinear to one that is highly rectifying and
diode-like at pH 6.6. This striking effect provides an innovative method for characterizing functional toxin interactions and
can be applied as an anthrax therapeutic biosensor.
DTIC
Antigens; Asymmetry; Bacillus; Bioinstrumentation; Biological Effects; Detection; Infectious Diseases
20060001810 Fox Chase Cancer Center, Philadelphia, PA USA
BRCC36, A Novel Subunit of a BRCA1 E3 Ubiquitin Ligase Complex: Candidates for BRCA3
Chen, Xiaowei; Jun. 1, 2005; 11 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): W81XWH-04-1-0573
Report No.(s): AD-A440291; No Copyright; Avail.: CASI: A03, Hardcopy
Breast cancer is a genetically heterogeneous disease, and multiple genes remain to be identified among non-BRCA1 and
BRCA2 breast cancer-prone families. This statement is supported by the evidences that BRCA1 and BRCA2 mutations are
associated with 20 to 60% of hereditary breast cancer families, which is less than originally estimated, especially in
population-based studies. There is mounting evidence which suggests that there may be additional, less prevalent breast cancer
susceptibility genes; however the identification of these genes remains elusive. Several groups are searching for additional
breast cancer susceptibility genes using whole genome scanning approaches, but the success of many of these approaches
depend on the underlying heterogeneity of the remaining cancer susceptibility loci. The failure to date to identify additional
breast cancer susceptibility genes associated with a high risk of disease suggests that more than one may exist. We have taken
the approach that the next BRCA genes will be those that encode for proteins whose functions are linked to important cell
regulatory pathways. We have recently found one such candidate BRCA3 protein, referred to as BRCC36.
DTIC
Breast; Cancer; Enzymes; Genes; Genetics; Mammary Glands; Proteins
20060001811 Walter Reed Army Inst. of Research, Washington, DC USA
The Medicinal Chemistry of Botulinum, Ricin and Anthrax Toxins
Hicks, Ricky P.; Hartell, Mark G.; Nichols, Daniel A.; Bhattacharjee, Apurba K.; van Hamont, John E.; Skillman, Donald R.;
Jan. 1, 2005; 29 pp.; In English; Original contains color illustrations
Report No.(s): AD-A440292; No Copyright; Avail.: CASI: A03, Hardcopy
The potential use of weapons of mass destruction (nuclear, biological or chemical) by terrorist organizations represents
a major threat to world peace and safety. Only a limited number of vaccines are available to protect the general population
from the medical consequences of these weapons. In addition, there are major health concerns associated with a pre-exposure
mass vaccination of the general population. To reduce or eliminate the impact of these terrible threats, new drugs must be
developed to safely treat individuals exposed to these agents. A review of all therapeutic agents under development for the
treatment of the illnesses and injuries that result from exposure to nuclear, biological or chemical warfare agents is beyond
the scope of any single article. The intent here is to provide a focused review for medicinal and organic chemists of three
widely discussed and easily deployed biological warfare agents, botulinum neurotoxin and ricin toxins and the bacteria
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