Publications

[use of variable-number tandem repeats to examine genetic diversity of bacillus anthracis].	to study the genotyping of bacillus anthracis based on multiple-locus variable-number tandem repeats(vntr) in the b. anthracis genome.	2006	17172115
data vs conclusions in the optic neuritis vaccination investigation.		2006	17172627
a fully integrated microfluidic genetic analysis system with sample-in-answer-out capability.	we describe a microfluidic genetic analysis system that represents a previously undescribed integrated microfluidic device capable of accepting whole blood as a crude biological sample with the endpoint generation of a genetic profile. upon loading the sample, the glass microfluidic genetic analysis system device carries out on-chip dna purification and pcr-based amplification, followed by separation and detection in a manner that allows for microliter samples to be screened for infectious patho ...	2006	17159153
synthesis and antigenic analysis of the bcla glycoprotein oligosaccharide from the bacillus anthracis exosporium.	the glycoprotein bcla is an important constituent of the exosporium of bacillus anthracis spores. this glycoprotein is substituted with an oligosaccharide composed of a beta-l-rhamnoside substituted with the previously unknown terminal saccharide, 2-o-methyl-4-(3-hydroxy-3-methylbutanamido)-4,6-dideoxy-d-glucopyranose, also referred to as anthrose. anthrose has not been found in spores of b. cereus and b. thuringiensis, making it a potential species-specific marker for b. anthracis. in order to ...	2006	17133642
ecopathological approach in tropical countries: a challenge in intensified production systems.	from the 1960s, in developed countries, epidemiological approach widened in veterinary sciences in order to understand and analyze the emergence of "production diseases" in "modern farms" where animal management was compared to industrial process. this approach was linked to "productivism" in livestock farming system. in france, this approach included formerly the understanding of farmers' practices and considered the health disorders as an output of farming system. this theory was known as "eco ...	2006	17135503
cpg oligonucleotides improve the protective immune response induced by the licensed anthrax vaccine.	synthetic oligodeoxynucleotides (odn) containing unmethylated cpg motifs act as immune adjuvants, improving the response elicited by a coadministered vaccine. combining cpg odn with anthrax vaccine adsorbed (ava, the licensed human vaccine) increases the speed, magnitude, and avidity of the resultant antibody response. igg abs against anthrax protective antigen (pa) protect mice, guinuea pigs, and rhesus macaques from infection.	2006	17145935
evaluation of bacillus anthracis thymidine kinase as a potential target for the development of antibacterial nucleoside analogs.	bacillus anthracis, which causes anthrax, has attracted attention because of its potential use as a biological weapon. the risk of multidrug resistance against b. anthracis increases the need for antibiotics with new molecular targets. nucleoside analogs are well-known antiviral and anticancer prodrugs, and thymidine kinase catalyzes the rate-limiting step in the activation of pyrimidine nucleoside analogs used in chemotherapy. the thymidine kinase gene from b. anthracis sterne strain (34f2) (ba ...	2006	17132103
anthrax pathogen evades the mammalian immune system through stealth siderophore production.	systemic anthrax, caused by inhalation or ingestion of bacillus anthracis spores, is characterized by rapid microbial growth stages that require iron. tightly bound and highly regulated in a mammalian host, iron is scarce during an infection. to scavenge iron from its environment, b. anthracis synthesizes by independent pathways two small molecules, the siderophores bacillibactin (bb) and petrobactin (pb). despite the great efficiency of bb at chelating iron, pb may be the only siderophore neces ...	2006	17132740
anthrax, but not bacillus anthracis?		2006	17121463
[wedding and anthrax].		2006	17117209
inhalational anthrax.	inhalational anthrax is a lethal infection acquired from the inhalation of bacillus anthracis, a pathogen classified as a category a bioterrorist agent by the centers for disease control and prevention. the recent 2001 attack in which weaponized spores were delivered by mail to several us cities exposed our vulnerability to bioterrorism, and taught us important lessons in the timely diagnosis of this devastating disease. it is clear that patient mortality is significantly decreased by early reco ...	2006	17110848
anthrax: a disease in waiting?	anthrax was a relatively unknown disease in the western world until 2001, when spores were maliciously mailed in the us, causing five deaths. the mortality of the disease, the stability of its spores and the subsequent lack of person-to-person spread make anthrax an attractive biological weapon for terrorists with a desire for targeted mass destruction.	2006	17099096
sentencing. enhanced sentence for hiv-positive inmate affirmed.		2006	17099962
complement and the multifaceted functions of vwa and integrin i domains.	the recent crystal structure of complement protein component c2a reveals an interface between its vwa and serine protease domains that could not exist in the zymogen c2. the implied change in vwa domain conformation between c2 and c2a differs from that described for other vwa domains, including the i domains in integrins. here, the remarkable diversity in both conformational regulation and ligand binding among vwa domains that function in complement, hemostasis, cell adhesion, anthrax toxin bind ...	2006	17098186
lysine methylation as a routine rescue strategy for protein crystallization.	crystallization remains a critical step in x-ray structure determination. because it is not generally possible to rationally predict crystallization conditions, commercial screens have been developed which sample a wide range of crystallization space. while this approach has proved successful in many cases, a significant number of proteins fail to crystallize despite being soluble and monodispersed. it is established that chemical modification can facilitate the crystallization of otherwise intr ...	2006	17098187
assessing surveillance using sensitivity, specificity and timeliness.	monitoring ongoing processes of illness to detect sudden changes is an important aspect of practical epidemiology and medicine more generally. most commonly, the monitoring has been restricted to a unidimensional stream of data over time. in such situations, analytic results from the industrial process monitoring have suggested optimal approaches to monitor the data streams. data streams including spatial location as well as temporal sequence are becoming available. monitoring methods that incor ...	2006	17089948
targeting proteins to the cell wall of sporulating bacillus anthracis.	dormant spores of bacillus anthracis germinate during host infection and their vegetative growth and dissemination precipitate anthrax disease. upon host death, bacilli engage a developmental programme to generate infectious spores within carcasses. hallmark of sporulation in bacillus spp. is the formation of an asymmetric division septum between mother cell and forespore compartments. we show here that sortase c (srtc) cleaves the lpnta sorting signal of bash and basi, thereby targeting both po ...	2006	17074072
cell entry and camp imaging of anthrax edema toxin.	the entry and enzymatic activity of the anthrax edema factor (ef) in different cell types was studied by monitoring ef-induced changes in intracellular camp with biochemical and microscopic methods. camp was imaged in live cells, transfected with a fluorescence resonance energy transfer biosensor based on the protein kinase a regulatory and catalytic subunits fused to cfp and yfp, respectively. the camp biosensor was located either in the cytosol or was membrane-bound owing to the addition of a ...	2006	17082768
evaluation of the ability of n-terminal fragment of lethal factor of bacillus anthracis for delivery of mycobacterium t cell antigen esat-6 into cytosol of antigen presenting cells to elicit effective cytotoxic t lymphocyte response.	we report the ability of n-terminal fragment of lethal factor of bacillus anthracis to deliver genetically fused esat-6 (early secretory antigen target), a potent t cell antigen of mycobacterium tuberculosis, into cytosol to elicit cytotoxic t lymphocyte (ctl) response. in vitro th1 cytokines data and ctl assay proved that efficient delivery of lfn.esat-6 occurs in cytosol, in the presence of protective antigen (pa), and leads to generation of effective ctl response. since ctl response is essent ...	2006	17084814
analogies and surprising differences between recombinant nitric oxide synthase-like proteins from staphylococcus aureus and bacillus anthracis in their interactions with l-arginine analogs and iron ligands.	genome sequencing has recently shown the presence of genes coding for no-synthase (nos)-like proteins in bacteria. the roles of these proteins remain unclear. the interactions of a series of l-arginine (l-arg) analogs and iron ligands with two recombinant nos-like proteins from staphylococcus aureus (sanos) and bacillus anthracis (banos) have been studied by uv-visible spectroscopy. sanos and banos in their ferric native state, as well as their complexes with l-arg analogs and with various ligan ...	2006	17084900
pharmacokinetic considerations and efficacy of levofloxacin in an inhalational anthrax (postexposure) rhesus monkey model.	because the treatment of inhalational anthrax cannot be studied in human clinical trials, it is necessary to conduct efficacy studies using a rhesus monkey model. however, the half-life of levofloxacin was approximately three times shorter in rhesus monkeys than in humans. computer simulations to match plasma concentration profile, area under the concentration-time curve (auc), and time above mic for a human oral dose of 500 mg levofloxacin once a day identified a dosing regimen in rhesus monkey ...	2006	17065619
anthrax in south africa: economics, experiment and the mass vaccination of animals, c. 1910-1945.		2006	17066129
inhibition of bacillus anthracis and potential surrogate bacilli growth from spore inocula by nisin and other antimicrobial peptides.	the ability of nisin, synthetic temporin analogs, magainins, defensins, and cecropins to inhibit bacillus anthracis, bacillus cereus, bacillus thuringiensis, bacillus mycoides, and bacillus subtilis growth from spore inocula was determined using well diffusion assays. nisin, magainin ii amide, and defensins were inhibitory in screening against b. anthracis sterne or b. cereus atcc 7004, but only nisin inhibited virulent b. anthracis strains. the mics of nisin against the 10 bacillus strains exam ...	2006	17066940
united states biodefense, international law, and the problem of intent.	since the anthrax attacks of 2001 in the united states, annual u.s. government spending on biodefense programs has increased enormously. u.s. biodefense was once exclusively the domain of military agencies and was aimed principally at protecting battlefield troops against the products of state-run biological warfare programs. today, it is engaged in and promoted by a variety of government agencies contemplating "bioterrorism," and it is aimed principally at protecting the american civilian popul ...	2006	17059319
a urokinase-activated recombinant anthrax toxin is selectively cytotoxic to many human tumor cell types.	urokinase plasminogen activator (upa) is a tumor-specific protease highly expressed in several types of solid tumors and rarely present on normal cells under physiologic conditions. due to its high expression on metastatic tumors, several different strategies have been used to target the urokinase system. these have mostly led to tumor growth inhibition rather than tumor regression. a different approach was adopted by replacing the furin activation site on a recombinant anthrax toxin with a urok ...	2006	17041100
systemic hyalinosis: a distinctive early childhood-onset disorder characterized by mutations in the anthrax toxin receptor 2 gene (antrx2).	we sought to further characterize the phenotype and facilitate clinical recognition of systemic hyalinosis in children who present with chronic pain and progressive contractures in early childhood.	2006	17043134
a linguistic model for the rational design of antimicrobial peptides.	antimicrobial peptides (amps) are small proteins that are used by the innate immune system to combat bacterial infection in multicellular eukaryotes. there is mounting evidence that these peptides are less susceptible to bacterial resistance than traditional antibiotics and could form the basis for a new class of therapeutic agents. here we report the rational design of new amps that show limited homology to naturally occurring proteins but have strong bacteriostatic activity against several spe ...	2006	17051220
development of methods to measure humoral immune responses against selected antigens in the common marmoset (callithrix jacchus) and the effect of pyridostigmine bromide administration.	this methodological study was carried out in preparation for a major long term study, also reported in this volume, which was designed to investigate whether the combination of vaccines and pyridostigmine bromide (pb) could have been responsible for adverse signs and symptoms reported by a number of veterans of the 1990/1991 gulf conflict. in this context, the marmoset has been used to model aspects of the human immune system. the purposes of this methodological study were to select appropriate ...	2006	17052666
multiple vaccine and pyridostigmine bromide interactions in the common marmoset callithrix jacchus: immunological and endocrinological effects.	following active service during the 1990/1991 gulf conflict, a number of uk and us veterans presented with a diverse range of symptoms, collectively known as gulf veterans illnesses (gvi). the administration of vaccines and/or the pretreatment against possible nerve agent poisoning, pyridostigmine bromide (pb), given to armed forces personnel during the gulf conflict has been implicated as a possible factor in the aetiology of these illnesses. the possibility that adverse health effects may resu ...	2006	17052667
anthrax toxin receptor 2-dependent lethal toxin killing in vivo.	anthrax toxin receptors 1 and 2 (antxr1 and antxr2) have a related integrin-like inserted (i) domain which interacts with a metal cation that is coordinated by residue d683 of the protective antigen (pa) subunit of anthrax toxin. the receptor-bound metal ion and pa residue d683 are critical for antxr1-pa binding. since pa can bind to antxr2 with reduced affinity in the absence of metal ions, we reasoned that d683 mutant forms of pa might specifically interact with antxr2. we show here that this ...	2006	17054395
application of paramagnetic beads for purifying bacillus anthracis protective antigen.	paramagnetic beads coated with protein g and tosylactivated-280 dynabeads have been used to purify bacillus anthracis protective antigen from a liquid culture. the obtained protein was used in the enzyme-linked immunosorbent assay test to detect b. anthracis protective antigen antibodies in human sera collected from immunized individuals. the purification method using paramagnetic beads is very effective. it is fast, easy and may be carried out practically in any laboratory.	2006	17010044
surface protein isdc and sortase b are required for heme-iron scavenging of bacillus anthracis.	bacillus anthracis, the spore-forming agent of anthrax, requires iron for growth and is capable of scavenging heme-iron during infection. we show here that the b. anthracis iron-regulated surface determinants (isd) locus encompasses isdc, specifying a heme-iron binding surface protein. anchoring of isdc to the cell wall envelopes of vegetative bacilli requires srtb, which encodes sortase b. purified sortase b cleaves isdc between the threonine and the glycine of its npktg motif sorting signal. b ...	2006	17012401
destruction of spores on building decontamination residue in a commercial autoclave.	the u.s. environmental protection agency conducted an experiment to evaluate the effectiveness of a commercial autoclave for treating simulated building decontamination residue (bdr). the bdr was intended to simulate porous materials removed from a building deliberately contaminated with biological agents such as bacillus anthracis (anthrax) in a terrorist attack. the purpose of the tests was to assess whether the standard operating procedure for a commercial autoclave provided sufficiently robu ...	2006	17012597
military hospitalizations among deployed us service members following anthrax vaccination, 1998-2001.	safety concerns have confronted the department of defense anthrax vaccine immunization program since inception in 1998. to determine if anthrax vaccination was associated with an increased risk of hospitalization, a historical cohort study utilizing pre- and post-anthrax-vaccination hospitalizations was undertaken and analyzed with cox proportional hazards models. the study population consisted of 170,723 active duty us service members who were anthrax-vaccinated and deployed during the time per ...	2006	17012889
generalized cutaneous reactions to the anthrax vaccine: preliminary results of anthrax vaccine-specific cell mediated immunity and cytokine profiles.	over two years, the vaccine adverse event reporting system reported that 0.042% of all anthrax vaccine (biothrax, bioport corporation) doses administered were associated with cutaneous reactions, half of which were eczematous. this case series attempts to immunologically detail this eczematous reaction in four patients by measuring anthrax vaccine-specific cell mediated immunity (ascmi), profiling th1 and th2 cytokine response to the anthrax vaccine in vitro, and analyzing of skin biopsy specime ...	2006	17012907
evaluation of promed-mail as an electronic early warning system for emerging animal diseases: 1996 to 2004.	to identify emerging animal and zoonotic diseases and associated geographic distribution, disease agents, animal hosts, and seasonality of reporting in the program for monitoring emerging diseases (promed)-mail electronic early warning system.	2006	17014355
hypersensitivity reactions to quinolones.	quinolones are one of the most important classes of antimicrobial agents discovered in the recent years and one of the most widely used classes of antibiotics in clinical medicine. their broad spectrum of activity and pharmacokinetic properties make them ideal agents for treating a variety of infections. their clinical importance is further demonstrated by their activity against a wide range of diseases of public health importance such as anthrax, tuberculosis, bacterial pneumonia, and sexually ...	2006	17017926
structure and action of the binary c2 toxin from clostridium botulinum.	c2 toxin from clostridium botulinum is composed of the enzyme component c2-i, which adp-ribosylates actin, and the binding and translocation component c2-ii, responsible for the interaction with eukaryotic cell receptors and the following endocytosis. three c2-i crystal structures at resolutions of up to 1.75 a are presented together with a crystal structure of c2-ii at an appreciably lower resolution and a model of the prepore formed by fragment c2-iia. the c2-i structure was determined at ph 3 ...	2006	17027031
microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine.	the recombinant protective antigen (rpa) of bacillus anthracis is a promising anthrax vaccine. we compared serum immunoglobulin g levels and toxin-neutralizing antibody titers in rabbits following delivery of various doses of vaccine by microneedle-based intradermal (i.d.) delivery or intramuscular (i.m.) injection using conventional needles. intradermal delivery required less antigen to induce levels of antibody similar to those produced via i.m. injection during the first 2 weeks following pri ...	2006	17030580
flow cytometry sorting protocol of bacillus spore using ultraviolet laser and autofluorescence as main sorting criterion.	the ultraviolet (uv) fluorescent aerodynamic particle sizer (flaps), a flow cytometer-like apparatus was developed by the canadian department of national defence for real-time detection of autofluorescence of biological aerosol particles such as bacterial spores. the direct relation between autofluorescence intensity and viability has recently been reported and viable spore are more autofluorescent in uv (laflamme, frontiers in bioscience). the goal of this manuscript is to describe a flow cytom ...	2006	17031569
unique aggregation of anthrax (bacillus anthracis) spores by sugar-coated single-walled carbon nanotubes.	there has been significant interest in the binding of anthrax spores by molecular species, but with only limited success. proteins and more recently peptides were used. however, despite the known presence of carbohydrates on the spore surface, carbohydrate-carbohydrate interactions have hardly been explored likely because of the lack of required specific platform for synthetic carbohydrates. we report the successful use of single-walled carbon nanotubes as a truly unique scaffold for displaying ...	2006	17031942
a preliminary assessment of bacillus anthracis spore inactivation using an electrochemically activated solution (ecasol).	to evaluate the efficacy of electrochemically activated solution (ecasol) in decontaminating bacillus anthracis ames and vollum 1b spores, with and without changing the source water hardness and final ecasol ph.	2006	17032220
reducing mortality from anthrax bioterrorism: strategies for stockpiling and dispensing medical and pharmaceutical supplies.	a critical question in planning a response to bioterrorism is how antibiotics and medical supplies should be stockpiled and dispensed. the objective of this work was to evaluate the costs and benefits of alternative strategies for maintaining and dispensing local and regional inventories of antibiotics and medical supplies for responses to anthrax bioterrorism. we modeled the regional and local supply chain for antibiotics and medical supplies as well as local dispensing capacity. we found that ...	2006	16999586
use of the internet to enhance infectious disease surveillance and outbreak investigation.	modernization of electronic communication systems to facilitate infectious disease surveillance and outbreak investigation became a priority after the 2001 anthrax attacks. however, the extent to which communicable disease investigators are using web-based information resources, e-mail notifications, or secure information exchange systems to facilitate surveillance is unknown. to address this question, we conducted a survey in 2004 of state and local communicable disease investigators responsibl ...	2006	16999590
the crystal structure of the e. coli stress protein ycif.	ycif is a protein that is up-regulated when bacteria experience stress conditions, and is highly conserved in a range of bacterial species. ycif has no known structure or biochemical function. to learn more about its potential molecular function and its role in the bacterial stress response, we solved the crystal structure of ycif at 2.0 angstrom resolution by the multiple wavelength anomalous diffraction (mad) technique. ycif is a dimer in solution, and forms a homodimer in the crystal asymmetr ...	2006	17001035
structural characterization of spo0e-like protein-aspartic acid phosphatases that regulate sporulation in bacilli.	spore formation is an extreme response of many bacterial species to starvation. in the case of pathogenic species of bacillus and clostridium, it is also a component of disease transmission. entry into the pathway of sporulation in bacillus subtilis and its relatives is controlled by an expanded two-component system in which starvation signals lead to the activation of sensor kinases and phosphorylation of the master sporulation response regulator spo0a. accumulation of threshold concentrations ...	2006	17001075
application of high-throughput technologies to a structural proteomics-type analysis of bacillus anthracis.	a collaborative project between two structural proteomics in europe (spine) partner laboratories, york and oxford, aimed at high-throughput (htp) structure determination of proteins from bacillus anthracis, the aetiological agent of anthrax and a biomedically important target, is described. based upon a target-selection strategy combining ;low-hanging fruit' and more challenging targets, this work has contributed to the body of knowledge of b. anthracis, established and developed htp cloning and ...	2006	17001104
production of biopharmaceuticals and vaccines in plants via the chloroplast genome.	transgenic plants offer many advantages, including low cost of production (by elimination of fermenters), storage and transportation; heat stability; and absence of human pathogens. when therapeutic proteins are orally delivered, plant cells protect antigens in the stomach through bioencapsulation and eliminate the need for expensive purification and sterile injections, in addition to development of both systemic and mucosal immunity. chloroplast genetic engineering offers several advantages, in ...	2006	17004305
characterization of cidr-mediated regulation in bacillus anthracis reveals a previously undetected role of s-layer proteins as murein hydrolases.	recent studies have shown that the staphylococcus aureus cidabc and lrgab operons are involved in the regulation of cell death and lysis. the transcription of cidabc and lrgab was shown to be induced by acetic acid and was dependent on the cidr gene encoding a new member of the lysr-type transcription regulator (lttr) family of proteins. in the study presented here, we examined the phenotypic and regulatory effects of disrupting a cidr homologue in bacillus anthracis. as in s. aureus, the cidr m ...	2006	17005012
structure-activity relationships of bacillus cereus and bacillus anthracis dihydrofolate reductase: toward the identification of new potent drug leads.	new and improved therapeutics are needed for bacillus anthracis, the etiological agent of anthrax. to date, antimicrobial agents have not been developed against the well-validated target dihydrofolate reductase (dhfr). in order to address whether dhfr inhibitors could have potential use as clinical agents against bacillus, 27 compounds were screened against this enzyme from bacillus cereus, which is identical to the enzyme from b. anthracis at the active site. several 2,4-diamino-5-deazapteridin ...	2006	17005826
comparative analysis of two-component signal transduction systems of bacillus cereus, bacillus thuringiensis and bacillus anthracis.	members of the bacillus cereus group are ubiquitously present in the environment and can adapt to a wide range of environmental fluctuations. in bacteria, these adaptive responses are generally mediated by two-component signal transduction systems (tcss), which consist of a histidine kinase (hk) and its cognate response regulator (rr). with the use of in silico techniques, a complete set of hks and rrs was recovered from eight completely sequenced b. cereus group genomes. by applying a bidirecti ...	2006	17005984
significant passive protective effect against anthrax by antibody to bacillus anthracis inactivated spores that lack two virulence plasmids.	the protective-antigen (pa)-based cell-free vaccine is the only vaccine licensed for use against bacillus anthracis infection in humans. although the pa shows strong immunogenicity, the capsule or spore-associated somatic antigens may be important as additional vaccine targets for full protection against anthrax. in this study, the protective effect of spore-associated antigens against b. anthracis infection was determined. rabbits were immunized with formalin-fixed spores of a non-toxigenic une ...	2006	17005989
detection and phylogenic analysis of one anthrax virulence plasmid pxo1 conservative open reading frame ubiquitous presented within bacillus cereus group strains.	the presence of one of the anthrax virulence plasmid pxo1 conserved fragments was analyzed in 24 bacillus cereus and b. thuringiensis strains, including 6 b. thuringiensis subspecies, by polymerase chain reactions. twelve out of 24 strains showed pcr-positive for an orf101 homologous sequence. two pxo1-orf101-like fragments from a b. cereus b-4ac and a commercial b. thuringiensis kurstaki hd1 were cloned, sequenced and expressed in escherichia coli. toxicity assays revealed that the product enco ...	2006	16978581
plcr papr-independent expression of anthrolysin o by bacillus anthracis.	cholesterol-dependent cytolysins (cdcs) are secreted, pore-forming toxins that are associated with pathogenesis in a variety of gram-positive bacteria. bacillus anthracis produces anthrolysin o (alo), a cdc that is largely responsible for the hemolytic activity of culture supernates when the bacterium is cultured in appropriate conditions. b. cereus and b. thuringiensis, species closely related to b. anthracis, produce cdcs with significant amino acid sequence homology to alo. transcription of t ...	2006	16980467
bacteriophage t4 capsid: a unique platform for efficient surface assembly of macromolecular complexes.	we report the first description of a macromolecular complex display system using bacteriophage t4. decorated with two dispensable outer capsid proteins, hoc (155 copies) and soc (810 copies), the 120 nm x 86 nm t4 capsid particle offers a unique binding site-rich platform for surface assembly of hetero-oligomeric complexes. to display the 710 kda anthrax toxin complex, two bipartite functional fusion proteins, lf-hoc and lfn-soc, were constructed. using a defined in vitro binding system, sequent ...	2006	16982068
search for cyclodextrin-based inhibitors of anthrax toxins: synthesis, structural features, and relative activities.	recently, using structure-inspired drug design, we demonstrated that aminoalkyl derivatives of beta-cyclodextrin inhibited anthrax lethal toxin action by blocking the transmembrane pore formed by the protective antigen (pa) subunit of the toxin. in the present study, we evaluate a series of new beta-cyclodextrin derivatives with the goal of identifying potent inhibitors of anthrax toxins. newly synthesized hepta-6-thioaminoalkyl and hepta-6-thioguanidinoalkyl derivatives of beta-cyclodextrin wit ...	2006	16982795
synthesis of potent inhibitors of anthrax toxin based on poly-l-glutamic acid.	we report the synthesis of biodegradable polyvalent inhibitors of anthrax toxin based on poly-l-glutamic acid (plga). these biocompatible polyvalent inhibitors are at least 4 orders of magnitude more potent than the corresponding monovalent peptides in vitro and are comparable in potency to polyacrylamide-based inhibitors of anthrax toxin assembly. we have elucidated the influence of peptide density on inhibitory potency and demonstrated that these inhibitory potencies are limited by kinetics, w ...	2006	16984137
inactivation of bacillus anthracis spores in murine primary macrophages.	the current model for pathogenesis of inhalation anthrax indicates that the uptake and fate of bacillus anthracis spores in alveolar macrophages are critical to the infection process. we have employed primary macrophages, which are more efficient for spore uptake than the macrophage-like cell line raw264.7, to investigate spore uptake and survival. we found that at a multiplicity of infection (moi) of 5, greater than 80% of the spores of the sterne strain containing only the pxo1 plasmid were in ...	2006	16984418
phylogenetic analysis of bacillus cereus isolates from severe systemic infections using multilocus sequence typing scheme.	bacillus cereus strains from cases of severe or lethal systemic infections, including respiratory symptoms cases, were analyzed using multilocus sequence typing scheme of b. cereus mlst database. the isolates were evenly distributed between the two main clades, and 60% of them had allele profiles new to the database. half of the collection's strains clustered in a lineage neighboring bacillus anthracis phylogenetic origin. strains from lethal cases with respiratory symptoms were allocated in bot ...	2006	16985296
prophylaxis and therapy of inhalational anthrax by a novel monoclonal antibody to protective antigen that mimics vaccine-induced immunity.	the neutralizing antibody response to the protective antigen (pa) component of anthrax toxin elicited by approved anthrax vaccines is an accepted correlate for vaccine-mediated protection against anthrax. we reasoned that a human anti-pa monoclonal antibody (mab) selected on the basis of superior toxin neutralization activity might provide potent protection against anthrax. the fully human mab (also referred to as mdx-1303 or valortim) was chosen from a large panel of anti-pa human mabs generate ...	2006	16988263
protective antigen as a correlative marker for anthrax in animal models.	the most aggressive form of anthrax results from inhalation of airborne spores of bacillus anthracis and usually progresses unnoticed in the early stages because of unspecific symptoms. the only reliable marker of anthrax is development of bacteremia, which increases with disease progress. rapid diagnosis of anthrax is imperative for efficient treatment and cure. herein we demonstrate that the presence and level of a bacterial antigen, the protective antigen (pa), a component of b. anthracis tox ...	2006	16988266
mass vaccination: solutions in the skin.	the skin is populated with langerhans cells, thought to be efficient, potent antigen-presenting cells, that are capable of inducing protective immunity by targeting antigen delivery to the skin. delivery to the skin may be accomplished by active delivery such as intradermal injection, use of patches or a combination of a universal adjuvant patch with injections. the robust immunity induced by skin targeting can lead to dose sparing, novel vaccines and immune enhancement in populations with poorl ...	2006	16989274
recombinant protective antigen 102 (rpa102): profile of a second-generation anthrax vaccine.	recent terrorist attacks involving the use of bacillus anthracis spores have stimulated interest in the development of new vaccines for anthrax prevention. studies of the pathogenesis of anthrax and of the immune responses following infection and immunization underscore the pivotal role that antibodies to the protective antigen play in protection. the most promising vaccine candidates contain purified recombinant protective antigen. clinical trials of one of these, recombinant protective antigen ...	2006	16989623
intra-endosomal membrane traffic.	following endocytosis, ubiquitinated signaling receptors are incorporated within intraluminal vesicles of forming multivesicular endosomes. these vesicles then follow the pathway from early to late endosomes, remaining within the endosomal lumen, and are eventually delivered to lysosomes, where they are degraded together with their protein cargo. however, intraluminal vesicles do not always end up in lysosomes for degradation; they can also fuse back with the limiting membrane of late endosomes. ...	2006	16949287
immunohistochemical evidence of clostridium sp, staphylococcus aureus, and group a streptococcus in severe soft tissue infections related to injection drug use.	severe soft tissue infections are caused by either single or multiple microorganisms. we performed a retrospective immunohistochemical (ihc) study on formalin-fixed, paraffin-embedded soft tissue samples from 20 injection drug users who were part of a cluster of severe illness and death after skin and soft tissue infections in scotland and ireland in 2000. the ihc assays used antibodies against clostridium sp, staphylococcus aureus, group a streptococci, and bacillus anthracis. intact bacilli an ...	2006	16949918
proteomic analyses of murine macrophages treated with bacillus anthracis lethal toxin.	bacillus anthracis is the etiological agent of anthrax and the bacterium produces a tripartite anthrax toxin composed of protective antigen (pa), lethal factor (lf) and edema factor (ef). pa represents the binding domain of the toxin and acts in concert with either lf, a metalloprotease, or ef, an adenylate cyclase, to form lethal toxin (letx) or edema toxin (edtx), respectively. we analyzed the proteomics response of two murine macrophage cell lines (j774.1a and raw264.7) following b. anthracis ...	2006	16950595
the use of systemic fluoroquinolones.	the only indications for which a fluoroquinolone (ie, ciprofloxacin) is licensed by the us food and drug administration for use in patients younger than 18 years are complicated urinary tract infections, pyelonephritis, and postexposure treatment for inhalation anthrax. nonetheless, approximately 520,000 prescriptions for fluoroquinolones were written in the united states for patients younger than 18 years in 2002; 13,800 were written for infants and children 2 to 6 years of age, and 2750 were w ...	2006	16951028
lessons learned from clinical anthrax drills: evaluation of knowledge and preparedness for a bioterrorist threat in israeli emergency departments.	emergency department (ed) physicians and nurses are considered critical sentinels of a bioterrorist attack. we designed a special hospital drill to test eds' response to inhalational anthrax and assess the level of preparedness for anthrax bioterrorism. we hypothesized that the occurrence of such a drill in an ed would improve the knowledge of its physicians, even those who had not actually participated in the drill.	2006	16953532
anthrax edema factor, voltage-dependent binding to the protective antigen ion channel and comparison to lf binding.	anthrax toxin complex consists of three different molecules, the binding component protective antigen (pa, 83 kda), and the enzymatic components lethal factor (lf, 90 kda) and edema factor (ef, 89 kda). the 63-kda n-terminal part of pa, pa(63), forms a heptameric channel that inserts at low ph in endosomal membranes and that is necessary to translocate ef and lf in the cytosol of the target cells. ef is an intracellular active enzyme, which is a calmodulin-dependent adenylate cyclase (89 kda) th ...	2006	16954207
the actin cross-linking domain of the vibrio cholerae rtx toxin directly catalyzes the covalent cross-linking of actin.	vibrio cholerae is a gram-negative bacterial pathogen that exports enterotoxins to alter host cells and to elicit diarrheal disease. among the secreted toxins is the multifunctional rtx toxin, which causes cell rounding and actin depolymerization by covalently cross-linking actin monomers into dimers, trimers, and higher multimers. the region of the toxin responsible for cross-linking activity is the actin cross-linking domain (acd). in this study, we further investigated the role of the acd in ...	2006	16954226
characterization of bacillus cereus isolates associated with fatal pneumonias: strains are closely related to bacillus anthracis and harbor b. anthracis virulence genes.	bacillus cereus is ubiquitous in nature, and while most isolates appear to be harmless, some are associated with food-borne illnesses, periodontal diseases, and other more serious infections. in one such infection, b. cereus g9241 was identified as the causative agent of a severe pneumonia in a louisiana welder in 1994. this isolate was found to harbor most of the b. anthracis virulence plasmid pxo1 (13). here we report the characterization of two clinical and one environmental b. cereus isolate ...	2006	16954272
antibiotic susceptibility and molecular diversity of bacillus anthracis strains in chad: detection of a new phylogenetic subgroup.	we genotyped 15 bacillus anthracis isolates from chad, africa, using multiple-locus variable-number tandem repeat analysis and three additional direct-repeat markers. we identified two unique genotypes that represent a novel genetic lineage in the a cluster. chadian isolates were susceptible to 11 antibiotics and free of 94 antibiotic resistance genes.	2006	16954291
mycobacterium tuberculosis possesses a functional enzyme for the synthesis of vitamin c, l-gulono-1,4-lactone dehydrogenase.	the last step of the biosynthesis of l-ascorbic acid (vitamin c) in plants and animals is catalyzed by l-gulono-1,4-lactone oxidoreductases, which use both l-gulono-1,4-lactone and l-galactono-1,4-lactone as substrates. l-gulono-1,4-lactone oxidase is missing in scurvy-prone, vitamin c-deficient animals, such as humans and guinea pigs, which are also highly susceptible to tuberculosis. a blast search using the rat l-gulono-1,4-lactone oxidase sequence revealed the presence of closely related ort ...	2006	16956367
proteomic profiling and identification of immunodominant spore antigens of bacillus anthracis, bacillus cereus, and bacillus thuringiensis.	differentially expressed and immunogenic spore proteins of the bacillus cereus group of bacteria, which includes bacillus anthracis, bacillus cereus, and bacillus thuringiensis, were identified. comparative proteomic profiling of their spore proteins distinguished the three species from each other as well as the virulent from the avirulent strains. a total of 458 proteins encoded by 232 open reading frames were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectro ...	2006	16957262
chloroquine prevents t lymphocyte suppression induced by anthrax lethal toxin.	lysosomal processing of lethal toxin (ltx) is a key event in the pathogenesis of anthrax. this study investigated the ability of chloroquine (cq) to interfere with this processing and thereby to reduce suppression of t lymphocytes. t lymphocytes isolated from blood were activated, by cross-linking of cd3, in both the absence and presence of ltx and cq and then were assayed by flow cytometry and immunoblotting. ltx was found to disrupt intracellular signaling, and it down-regulated t lymphocyte f ...	2006	16960789
anthrax vaccines: pasteur to the present.	anthrax has been a major cause of death in grazing animals and an occasional cause of death in humans for thousands of years. since the late 1800s there has been an exceptional international history of anthrax vaccine development. due to animal vaccinations, the rate of infection has dropped dramatically. anthrax vaccines have progressed from uncharacterized whole-cell vaccines in 1881, to pxo2-negative spores in the 1930s, to culture filtrates absorbed to aluminum hydroxide in 1970, and likely ...	2006	16964578
development of a matrix to evaluate the threat of biological agents used for bioterrorism.	adequate public health preparedness for bioterrorism includes the elaboration of an agreed list of biological and chemical agents that might be used in an attack or as threats of deliberate release. in the absence of counterterrorism intelligence information, public health authorities can also base their preparedness on the agents for which the national health structures would be most vulnerable. this article aims to describe a logical method and the characteristics of the variables to be brough ...	2006	16964580
bioterrorism: management of major biological agents.	bioterrorism is defined by the intentional or threatened of microorganisms or toxins derived from living organisms to cause death or diseases in humans, animals or plants on which we depend. the other major point is to generate fear in the population. more than 180 pathogens have been reported to be potential agents for bioterrorism. the following is an overview of several agents that could be involved in a biological attack.	2006	16964582
order out of chaos: the self-organization of communication following the anthrax attacks.	this article describes 5 communication challenges faced by the author as she managed the communication response by the centers for disease control and prevention to the anthrax attacks of 2001: communicating uncertainty, selecting credible spokespersons, collaborating with other organizations, satisfying a competitive 24/7 media, and speed. the lessons learned in responding to these challenges led to profound changes in the way communication was organized in the agency. these changes are describ ...	2006	16965251
probable human anthrax death in scotland.		2006	16966782
differential identification of bacillus anthracis from environmental bacillus species using microarray analysis.	to determine whether microarray analysis could be employed for the differential identification of a range of environmental bacillus sp. from four strains of bacillus anthracis.	2006	16968287
concentration of bacillus spores by using silica magnetic particles.	silica particles are mainly used for the concentration of nucleic acid for diagnostic purposes. this is usually done under acidic or chaotropic conditions that will demolish most of the living organisms and prevent the application of other diagnostic tests. here we describe the development of a method for the capturing and concentration of bacillus spores using silica magnetic particles to enable fast and sensitive detection. we have shown that capturing various bacilli spores via silica magneti ...	2006	16970351
development of a risk-priority score for category a bioterrorism agents as an aid for public health policy.	in developing public health policy and planning for a bioterrorist attack or vaccination of military personnel, the most common method for assigning priority is using the probability of attack with a particular agent as the single criterion. using this approach, smallpox is often dismissed as an unlikely threat. we aimed to develop an evidence-based, systematic, multifactorial method for prioritizing the level of risk of each category a bioterrorism agent. using 10 criterion, anthrax scored the ...	2006	16895121
anthrax in western and central african great apes.	during the period of december 2004 to january 2005, bacillus anthracis killed three wild chimpanzees (pan troglodytes troglodytes) and one gorilla (gorilla gorilla gorilla) in a tropical forest in cameroon. while this is the second anthrax outbreak in wild chimpanzees, this is the first case of anthrax in gorillas ever reported. the number of great apes in central africa is dramatically declining and the populations are seriously threatened by diseases, mainly ebola. nevertheless, a considerable ...	2006	16900500
evaluation and binding-mode prediction of thiopyrone-based inhibitors of anthrax lethal factor.		2006	16902919
meningoencephalitis due to anthrax: ct and mr findings.	anthrax is primarily a disease of herbivores, but it also causes cutaneous, respiratory and gastrointestinal infections in humans. bacillus anthracis is an uncommon cause of meningitis and generally produces a haemorrhagic meningoencephalitis. we present the ct and mr findings of anthrax meningoencephalitis due to the cutaneous form of anthrax in a 12-year-old boy. they showed focal intracerebral haemorrhage with leptomeningeal enhancement.	2006	16906391
past, imminent and future human medical countermeasures for anthrax.	anthrax is caused by the bacterium bacillus anthracis. although primarily a disease of animals, it can also infect man, sometimes with fatal consequences. as a result of concerns over the illicit use of this organism, considerable effort is focussed on the development of therapies capable of conferring protection against anthrax. this brief review will describe the efforts being made to address these issues.	2006	16907809
examining the cdcynergy event assessment tool: an investigation of the anthrax crisis in boca raton, florida.	this paper examines the dependability of the event assessment tool over time. the latter is part of a cd-rom--emergency risk communication cdcynergy--distributed primarily to public information officers in the united states by the centers for disease control and prevention. the event assessment tool is designed to aid emergency professionals in identifying the magnitude of a crisis event and to suggest appropriate actions to confront such a situation. applied twice during the 2001 anthrax bioter ...	2006	16911433
emission wavelength dependence of fluorescence lifetimes of bacteriological spores and pollens.	concern about biological terrorism has greatly increased in the 21st century, and correspondingly, so has the need for accurate detection and identification of biological hazards, such as bacillus anthracis. optical techniques have been shown to be useful for this purpose. use of fluorescence lifetimes as a function of emission wavelength for different materials using point- detection methods appears to be an additional viable option. although the lifetimes range only between 2 and 6 ns, most bi ...	2006	16912807
novel small-molecule inhibitors of anthrax lethal factor identified by high-throughput screening.	anthrax lethal factor (lf) is a key virulence factor of anthrax lethal toxin. we screened a chemolibrary of 10,000 drug-like molecules for their ability to inhibit lf and identified 18 novel small molecules with potent lf inhibitory activity. three additional lf inhibitors were identified through further structure-activity relationship (sar) analysis. all 21 compounds inhibited lf with an ic50 range of 0.8 to 11 mum, utilizing mixed-mode competitive inhibition. an evaluation of inhibitory activi ...	2006	16913712
anti-carbohydrate antibodies for the detection of anthrax spores.		2006	16917815
cpg 7909: pf 3512676, pf-3512676.	cpg 7909 [pf-3512676] is an immunomodulating synthetic oligonucleotide designed to specifically agonise the toll-like receptor 9 (tlr9). it is being developed for the treatment of cancer [promune] as a monotherapy and in combination with chemotherapeutic agents, and it is also under development as an adjuvant [vaximmune] for vaccines against cancer and infectious diseases. cpg 7909, acting through the tlr9 receptor present in b cells and plasmacytoid dendritic cells, stimulates human b-cell prol ...	2006	16922592
toxin-deficient mutants of bacillus anthracis are lethal in a murine model for pulmonary anthrax.	bacillus anthracis, the etiologic agent of anthrax, produces at least three primary virulence factors: lethal toxin, edema toxin, and a capsule. the capsule is absolutely required for dissemination and lethality in a murine model of inhalation anthrax, yet the roles for the toxins during infection are ill-defined. we show in a murine model that when spores of specific toxin-null mutants are introduced into the lung, dissemination and lethality are comparable to those of the parent strain. mutant ...	2006	16923785
transcriptional profiling of the bacillus anthracis life cycle in vitro and an implied model for regulation of spore formation.	the life cycle of bacillus anthracis includes both vegetative and endospore morphologies which alternate based on nutrient availability, and there is considerable evidence indicating that the ability of this organism to cause anthrax depends on its ability to progress through this life cycle in a regulated manner. here we report the use of a custom b. anthracis genechip in defining the gene expression patterns that occur throughout the entire life cycle in vitro. nearly 5,000 genes were expresse ...	2006	16923876
sensor domains encoded in bacillus anthracis virulence plasmids prevent sporulation by hijacking a sporulation sensor histidine kinase.	anthrax toxin and capsule, determinants for successful infection by bacillus anthracis, are encoded on the virulence plasmids pxo1 and pxo2, respectively. each of these plasmids also encodes proteins that are highly homologous to the signal sensor domain of a chromosomally encoded major sporulation sensor histidine kinase (ba2291) in this organism. b. anthracis sterne overexpressing the plasmid pxo2-61-encoded signal sensor domain exhibited a significant decrease in sporulation that was suppress ...	2006	16923903
factors influencing laboratory workers' decisions to accept or decline anthrax vaccine adsorbed (ava): results of a decision-making study in cdc's anthrax vaccination program.	laboratory technicians, laboratory supervisors, decontamination/remediation workers, and environmental investigators are at increased risk for repeated occupational exposure to bacillus anthracis. in 2002, the advisory committee on immunization practices (acip) recommended pre-exposure vaccination for these occupational groups.	2006	16924600
a selective chromogenic agar that distinguishes bacillus anthracis from bacillus cereus and bacillus thuringiensis.	a selective and differential plating medium, r & f anthracis chromogenic agar (aca), has been developed for isolating and identifying presumptive colonies of bacillus anthracis. aca contains the chromogenic substrate 5-bromo-4-chloro-3-indoxyl-choline phosphate that upon hydrolysis yields teal (blue green) colonies indicating the presence of phosphatidylcholine-specific phospholipase c (pc-plc) activity. among seven bacillus species tested on aca, only members of the bacillus cereus group (b. an ...	2006	16924932
development of size-selective sampling of bacillus anthracis surrogate spores from simulated building air intake mixtures for analysis via laser-induced breakdown spectroscopy.	size-selective sampling of bacillus anthracis surrogate spores from realistic, common aerosol mixtures was developed for analysis by laser-induced breakdown spectroscopy (libs). a two-stage impactor was found to be the preferential sampling technique for libs analysis because it was able to concentrate the spores in the mixtures while decreasing the collection of potentially interfering aerosols. three common spore/aerosol scenarios were evaluated, diesel truck exhaust (to simulate a truck runni ...	2006	16925921
secreted neutral metalloproteases of bacillus anthracis as candidate pathogenic factors.	to evaluate the pathogenic potential of bacillus anthracis-secreted proteases distinct from lethal toxin, two neutral zinc metalloproteases were purified to apparent homogeneity from the culture supernatant of a non-virulent delta ames strain (pxo1-, pxo2-). the first (designated npr599) is a thermolysin-like enzyme highly homologous to bacillolysins from other bacillus species. the second (designated inha) is a homolog of the bacillus thuringiensis immune inhibitor a. these proteases belong to ...	2006	16926147
anthrax lethal toxin impairs innate immune functions of alveolar macrophages and facilitates bacillus anthracis survival.	alveolar macrophages (am) are very important for pulmonary innate immune responses against invading inhaled pathogens because they directly kill the organisms and initiate a cascade of innate and adaptive immune responses. although several factors contribute to inhalational anthrax, we hypothesized that unimpeded infection of bacillus anthracis is directly linked to disabling the innate immune functions contributed by am. here, we investigated the effects of lethal toxin (lt), one of the binary ...	2006	16926394