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Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells.

Das R, Hammamieh R, Neill R, Ludwig GV, Eker S, Lincoln P, Ramamoorthy P, Dhokalia A, Mani S, Mendis C, Cummings C, Kearney B, Royaee A, Huang XZ, Paranavitana C, Smith L, Peel S, Kanesa-Thasan N, Hoover D, Lindler LE, Yang D, Henchal E, Jett M - BMC Infect. Dis. (2008)

Bottom Line: We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness.Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared.Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Pathology, Walter Reed Army Institute of Research, Silver Spring, MD, USA. dasr2@nhlbi.nih.gov

ABSTRACT

Background: Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.

Methods: To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.

Results: We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin.

Conclusion: Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.

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Related in: MedlinePlus

Confirmation of selected gene changes by RT-PCR with in vitro and in vivo samples for IL-6 (a) and Transducin beta-1 subunit, GNB1, (b).
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Figure 6: Confirmation of selected gene changes by RT-PCR with in vitro and in vivo samples for IL-6 (a) and Transducin beta-1 subunit, GNB1, (b).

Mentions: A few genes were selected that showed changes induced by B. anthracis exposure were confirmed by RT-PCR, and the level of expression was compared both in vitro and in vivo after anthrax exposure. The in vivo/in vitro trends were very similar for many genes including IL-6 (Fig. 6a) and Transducin beta-1 subunit (GNB1) (Fig. 6b). Altered regulation of that G-protein was not seen with the other pathogenic agents. In an experiment of SEB exposure to NHP (Fig. 7), IL-6 and guanylate binding protein GBP-2 were up regulated (6- and 65-fold, respectively) by 30 min post-exposure and the increased expression persisted through 24 h (the last time point tested, data not shown). Among all the pathogens studied so far, SEB was found to be the only pathogen to dramatically alter GBP-2.


Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells.

Das R, Hammamieh R, Neill R, Ludwig GV, Eker S, Lincoln P, Ramamoorthy P, Dhokalia A, Mani S, Mendis C, Cummings C, Kearney B, Royaee A, Huang XZ, Paranavitana C, Smith L, Peel S, Kanesa-Thasan N, Hoover D, Lindler LE, Yang D, Henchal E, Jett M - BMC Infect. Dis. (2008)

Confirmation of selected gene changes by RT-PCR with in vitro and in vivo samples for IL-6 (a) and Transducin beta-1 subunit, GNB1, (b).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2542375&req=5

Figure 6: Confirmation of selected gene changes by RT-PCR with in vitro and in vivo samples for IL-6 (a) and Transducin beta-1 subunit, GNB1, (b).
Mentions: A few genes were selected that showed changes induced by B. anthracis exposure were confirmed by RT-PCR, and the level of expression was compared both in vitro and in vivo after anthrax exposure. The in vivo/in vitro trends were very similar for many genes including IL-6 (Fig. 6a) and Transducin beta-1 subunit (GNB1) (Fig. 6b). Altered regulation of that G-protein was not seen with the other pathogenic agents. In an experiment of SEB exposure to NHP (Fig. 7), IL-6 and guanylate binding protein GBP-2 were up regulated (6- and 65-fold, respectively) by 30 min post-exposure and the increased expression persisted through 24 h (the last time point tested, data not shown). Among all the pathogens studied so far, SEB was found to be the only pathogen to dramatically alter GBP-2.

Bottom Line: We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness.Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared.Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Pathology, Walter Reed Army Institute of Research, Silver Spring, MD, USA. dasr2@nhlbi.nih.gov

ABSTRACT

Background: Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs.

Methods: To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays.

Results: We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin.

Conclusion: Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.

Show MeSH
Related in: MedlinePlus