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history of a public health emergency. 200515790057
heading-off anthrax at hamilton, new jersey: events of october 2001. 200515790066
genetic diversity among bacillus anthracis, bacillus cereus and bacillus thuringiensis strains using repetitive element polymorphism-pcr.repetitive element polymorphism-pcr (rep-pcr) is one of the tools that has been used to elucidate genetic diversity of related microorganisms. using the mb1 primer, rep-pcr fingerprints from 110 bacillus strains within the "b. cereus group" have identified eighteen distinct categories, while other more distantly related bacterial species fell within six additional categories. all bacillus anthracis strains tested were found to be monomorphic by fluorophore-enhanced rep-pcr (ferp) fingerprinting ...200415790070
the medicinal chemistry of botulinum, ricin and anthrax toxins.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 ...200515790305
anthrax vaccine design: strategies to achieve comprehensive protection against spore, bacillus, and toxin.the successful use of bacillus anthracis as a lethal biological weapon has prompted renewed research interest in the development of more effective vaccines against anthrax. the disease consists of three critical components: spore, bacillus, and toxin, elimination of any of which confers at least partial protection against anthrax. current remedies rely on postexposure antibiotics to eliminate bacilli and pre- and postexposure vaccination to target primarily toxins. vaccines effective against tox ...200515790405
glycerol monolaurate inhibits virulence factor production in bacillus anthracis.anthrax, caused by bacillus anthracis, has been brought to the public's attention because of the 2001 bioterrorism attacks. however, anthrax is a disease that poses agricultural threats in the united states as well as human populations in europe, china, africa, and australia. glycerol monolaurate (gml) is a compound that has been shown to inhibit exotoxin production by staphylococcus aureus and other gram-positive bacteria. here, we study the effects of gml on growth and toxin production in b. a ...200515793101
is in vitro antibiotic combination more effective than single-drug therapy against anthrax?antibiotic combinations are used to enhance antibacterial efficacy and to prevent the development of resistance. we have tested a possible synergistic effect of several antibacterial combinations on bacillus anthracis. the in vitro activities of antibiotic combinations against two strains of b. anthracis, strain sterne and the russian anthrax vaccine strain sti, were tested by the fractional inhibitory concentration (fic) method, derived from the mics of the agents in combination, and by measuri ...200515793105
role of superoxide in the germination of bacillus anthracis endospores.the spore forming gram-positive bacterium bacillus anthracis, the causative agent of anthrax, has achieved notoriety due to its use as a bioterror agent. in the environment, b. anthracis exists as a dormant endospore. germination of endospores during their internalization within the myeloid phagocyte, and the ability of those endospores to survive exposure to antibacterial killing mechanisms such as superoxide (o(2)*-, is a key initial event in the infective process. we report herein that endosp ...200515796976
multilocus sequence typing reveals that bacillus cereus strains isolated from clinical infections have distinct phylogenetic origins.eight strains of bacillus cereus isolated from bacteremia and soft tissue infections were assigned to seven sequence types (sts) by multilocus sequence typing (mlst). two strains from different locations had identical sts. the concatenated sequences of the seven sts were aligned with 65 concatenated sequences from reference sts and a neighbor-joining tree was constructed. two strains were distantly related to all reference sts. three strains were recovered in a clade that included bacillus anthr ...200515796996
antibody microarrays for native toxin detection.we have developed antibody-based microarray techniques for the multiplexed detection of cholera toxin beta-subunit, diphtheria toxin, anthrax lethal factor and protective antigen, staphylococcus aureus enterotoxin b, and tetanus toxin c fragment in spiked samples. two detection schemes were investigated: (i) a direct assay in which fluorescently labeled toxins were captured directly by the antibody array and (ii) a competition assay that employed unlabeled toxins as reporters for the quantificat ...200515797567
inadvertent laboratory exposure to bacillus anthracis--california, 2004.on june 9, 2004, the california department of health services (cdhs) was notified of possible inadvertent exposure to bacillus anthracis spores at children's hospital oakland research institute (chori), where workers were evaluating the immune response of mice to b. anthracis. this report summarizes the subsequent investigation by cdhs and cdc, including assessment of exposures, administration of postexposure chemoprophylaxis, and serologic testing of potentially exposed workers. the findings un ...200515800474
american chemical society meeting. fast, sensitive scan targets anthrax. 200515802583
the evolving field of biodefence: therapeutic developments and diagnostics.the threat of bioterrorism and the potential use of biological weapons against both military and civilian populations has become a major concern for governments around the world. for example, in 2001 anthrax-tainted letters resulted in several deaths, caused widespread public panic and exerted a heavy economic toll. if such a small-scale act of bioterrorism could have such a huge impact, then the effects of a large-scale attack would be catastrophic. this review covers recent progress in develop ...200515803193
genomics of the bacillus cereus group of organisms.members of the bacillus cereus group of organisms include bacillus cereus, bacillus anthracis and bacillus thuringiensis. collectively, these organisms represent microbes of high economic, medical and biodefense importance. given this significance, this group contains the highest number of closely related fully sequenced genomes, giving the unique opportunity for thorough comparative genomic analyses. much of the disease and host specificity of members of this group can be attributed to their pl ...200515808746
annulling a dangerous liaison: vaccination strategies against aids and tuberculosis.human immunodeficiency virus (hiv) and mycobacterium tuberculosis annually cause 3 million and 2 million deaths, respectively. last year, 600,000 individuals, doubly infected with hiv and m. tuberculosis, died. since world war i, approximately 150 million people have succumbed to these two infections--more total deaths than in all wars in the last 2,000 years. although the perceived threats of new infections such as sars, new variant creutzfeldt-jakob disease and anthrax are real, these outbreak ...200515812488
the effect of electron beam irradiation on forensic evidence. 1. latent print recovery on porous and non-porous surfaces.the recent use of the postal system as a means of delivering anthrax spores via several contaminated envelopes has led to the selective irradiation of mail. these as yet unsolved attacks and the u.s. postal service's decision to irradiate certain types of mail has led to some unexpected complications. the high doses of radiation required to destroy biological agents like anthrax are sufficient to induce damage to other materials present in the envelope. there have been reports of damage to many ...200515813540
anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells.bacillus anthracis secretes two critical virulence factors, lethal toxin (lt) and edema toxin (et). in this study, we show that murine bone marrow-derived dendritic cells (dc) infected with b. anthracis strains secreting et exhibit a very different cytokine secretion pattern than dc infected with b. anthracis strains secreting lt, both toxins, or a nontoxinogenic strain. et produced during infection selectively inhibits the production of il-12p70 and tnf-alpha, whereas lt targets il-10 and tnf-a ...200515814721
anthrax lethal toxin blocks mapk kinase-dependent il-2 production in cd4+ t cells.anthrax lethal toxin (lt) is a critical virulence factor that cleaves and inactivates mapk kinases (mapkks) in host cells and has been proposed as a therapeutic target in the treatment of human anthrax infections. despite the potential use of anti-toxin agents in humans, the standard activity assays for anthrax lt are currently based on cytotoxic actions of anthrax lt that are cell-, strain-, and species-specific, which have not been demonstrated to occur in human cells. we now report that t cel ...200515814725
characterization of a bacillus anthracis isolate causing a rare case of fatal anthrax in a 2-year-old boy from hong kong.we used multiple-locus variable-number tandem repeat analysis (mlva) and paga sequencing to genotype a bacillus anthracis isolate from a fatal case of human anthrax in hong kong. the isolate has a unique mlva genotype, is related to the sterne and ames strains, and is consistent with genotypes identified in china.200515815041
use of single nucleotide polymorphisms in the plcr gene for specific identification of bacillus anthracis.a taqman-minor groove binding assay designed around a nonsense mutation in the plcr gene was used to genotype bacillus anthracis, b. cereus, and b. thuringiensis isolates. the assay differentiated b. anthracis from these genetic near-neighbors and determined that the nonsense mutation is ubiquitous across 89 globally and genetically diverse b. anthracis strains.200515815042
infectious disease emergencies: role of the infectious disease specialist.the importance of infections for public health has become obvious during the last decades. examples are emerging infections such as hiv/aids and severe acute respiratory syndrome, deliberate release of microorganisms, such as the anthrax episode in the usa, the increasing problems with organisms resistant to antimicrobial treatment, such as methicillin-resistant staphylococcus aureus, and the threat of a new influenza pandemic with a case fatality rate similar to that in the 1918 outbreak. an ef ...200515816100
bacteria as potential tools in bioterrorism, with an emphasis on bacterial toxins.the threat of bioterrorism remains a reality worldwide and, although of low probability, an attack would be a high-consequence event. microbes are available to individuals with appropriate contacts and even many low-grade bacterial pathogens can severely affect health. toxins provide bacteria with a system of defence that is often detrimental to humans and their versatility makes them potential tools of bioterrorism. it should be remembered that the aim of terrorism is not always to kill but rat ...200515816214
effective antiprotease-antibiotic treatment of experimental anthrax.inhalation anthrax is characterized by a systemic spread of the challenge agent, bacillus anthracis. it causes severe damage, including multiple hemorrhagic lesions, to host tissues and organs. it is widely believed that anthrax lethal toxin secreted by proliferating bacteria is a major cause of death, however, the pathology of intoxication in experimental animals is drastically different from that found during the infectious process. in order to close a gap between our understanding of anthrax ...200515819985
inhalational anthrax with acute respiratory distress syndrome.a 10-year-old boy presented with facial swelling, thick exudates in the nasal cavities with membranes covering the nasopharynx, shock and respiratory distress. x-ray of the paranasal sinuses showed opacification of both maxillary sinuses. nasal diphtheria was suspected but culture of the membranes grew bacillus anthracis. chest x-ray showed mediastinal widening and extensive pulmonary infiltrates compatible with respiratory anthrax.200515822245
viral and bacterial diseases in livestock in mongolia.this review focuses on the status of infectious diseases that are serious for animal health and have adverse economic effects in mongolia. data presented here are limited due to the lack of published or other easily available documents. foot-and-mouth disease continues to cause substantial economic losses as exemplified by the outbreak of infection with serotype o panasia lineage virus. in the case of the 2001 outbreak, a 65% reduction in export revenues was recorded. in order to ascertain the f ...200515822857
veterinarian part of us-russian collaboration on anthrax sensor. 200515825723
hospital preparedness and management of patients affected by viral haemorrhagic fever or smallpox at the lazzaro spallanzani institute, italy.the us cases of anthrax in 2001 and the recent severe acute respiratory syndrome outbreak have heightened the need for preparedness and response to naturally emerging and re-emerging infections or deliberately released biological agents. this report describes the response model of the istituto nazionale per le malattie infettive lazzaro spallanzani (inmi), rome, italy for managing patients suspected of or affected by smallpox or viral haemorrhagic fever (vhf) either in the context of an intentio ...200515827373
emerging infectious diseases: a 10-year perspective from the national institute of allergy and infectious diseases.although optimists once imagined that serious infectious disease threats would by now be conquered, newly emerging (e.g., severe acute respiratory syndrome [sars]), reemerging (e.g., west nile virus), and even deliberately disseminated infectious diseases (e.g., anthrax bioterrorism) continue to appear throughout the world. over the past decade, the global effort to identify and characterize infectious agents, decipher the underlying pathways by which they cause disease, and develop preventive m ...200515829188
an assessment of pasteurization treatment of water, media, and milk with respect to bacillus spores.this study evaluated the ability of spore-forming bacillus spp. to resist milk pasteurization conditions from 72 to 150 degrees c. spores from the avirulent surrogate sterne strain of bacillus anthracis, as well as a representative strain of a common milk contaminant that is also a pathogen, bacillus cereus atcc 9818, were heated at test temperatures for up to 90 min in dh2o, brain heart infusion broth, or skim milk. in skim milk, characteristic log reductions (log cfu per milliliter) for b. ant ...200515830666
ethics and bioterrorism research. 200415832477
wanted, an anthrax vaccine: dead or alive?it has been more than 100 years since the realization that microbes are capable of causing disease. in that time, we have learned a great deal as to how each organism has adapted to the immune system so as to avoid elimination. as well, we have also learned an immense amount since louis pasteur first proposed that the solution to infectious diseases was to culture the microbes and attenuate their virulence, so as to use them as vaccines. from the optimism and promise of the 19th century and immu ...200515836780
efficient gene inactivation in bacillus anthracis.a procedure for high-efficiency gene inactivation in bacillus anthracis has been developed. it is based on a highly temperature-sensitive plasmid vector carrying kanamycin resistance cassette surrounded by dna fragments flanking the desired insertion site. the approach was tested by constructing glutamate racemase e1 (race1), glutamate racemase e2 (race2) and comec knock-out mutants of b. anthracis strain deltaanr. allelic replacements were observed at high frequencies, ranging from approximatel ...200515837388
plasmid-encoded regulator of extracellular proteases in bacillus anthracis.bacillus anthracis sterne cured of the pxo1 plasmid had enhanced secreted protease activity during the postexponential phase but no change in hemolytic or lecithinase activities. a zymogen profile revealed at least six proteases, including serine, metal, and perhaps cysteine types. there were similar amounts of protease secreted by the closely related species bacillus cereus and bacillus thuringiensis, but the patterns differed. among the pxo1 plasmid-encoded proteins, there is a tetratricopepti ...200515838040
summaries for patients. what is the most cost-effective way to protect people in the event of an anthrax terror attack? 200515838060
cost-effectiveness of defending against bioterrorism: a comparison of vaccination and antibiotic prophylaxis against anthrax.weaponized bacillus anthracis is one of the few biological agents that can cause death and disease in sufficient numbers to devastate an urban setting.200515838066
being prepared: modeling the response to an anthrax attack. 200515838074
clostridium botulinum: a bug with beauty and weapon.clostridium botulinum, a gram-positive, anaerobic spore-forming bacteria, is distinguished by its significant clinical applications as well as its potential to be used as bioterror agent. growing cells secrete botulinum neurotoxin (bont), the most poisonous of all known poisons. while bont is the causative agent of deadly neuroparalytic botulism, it also serves as a remarkably effective treatment for involuntary muscle disorders such as blepharospasm, strabismus, hemifacial spasm, certain types ...200515839401
quantitative immunoassay of biotoxins on hydrogel-based protein microchips.three-dimensional gel-based microchips with immobilized proteins were used for quantitative immunoassay of a series of plant (ricin and viscumin) and bacterial (staphylococcal enterotoxin b, tetanus and diphtheria toxins, and lethal factor of anthrax) toxins. it was shown that different types of immunoassays (direct, competitive, and sandwich type) could be carried out on gel microchips. as shown by confocal microscope studies, antigen-antibody interactions involving the formation of tertiary an ...200515840505
cutaneous anthrax: conservative or surgical treatment?this article summarizes the diagnostic features and treatment recommendations for cutaneous anthrax, exemplified by a case report of nontypical cutaneous anthrax. the treatment of choice is medical, with ciprofloxacin or doxycycline the preferred antibiotics. however, surgical biopsy may be used if the clinical setting and microbiologic examination of swabs are not diagnostically conclusive. histopathologic findings explain the clinical observation that most cutaneous anthrax lesions heal withou ...200515840983
evaluation of the vp22 protein for enhancement of a dna vaccine against anthrax.background: previously, antigens expressed from dna vaccines have been fused to the vp22 protein from herpes simplex virus type i in order to improve efficacy. however, the immune enhancing mechanism of vp22 is poorly understood and initial suggestions that vp22 can mediate intercellular spread have been questioned. despite this, fusion of vp22 to antigens expressed from dna vaccines has improved immune responses, particularly to non-secreted antigens. methods: in this study, we fused the gene f ...200515842732
dendritic cells endocytose bacillus anthracis spores: implications for anthrax pathogenesis.phagocytosis of inhaled bacillus anthracis spores and subsequent trafficking to lymph nodes are decisive events in the progression of inhalational anthrax because they initiate germination and dissemination of spores. found in high frequency throughout the respiratory track, dendritic cells (dcs) routinely take up foreign particles and migrate to lymph nodes. however, the participation of dcs in phagocytosis and dissemination of spores has not been investigated previously. we found that human dc ...200515843553
potential applications of conventional and molecular imaging to biodefense research.imaging methods that visualize the structure and function of the living body are widely used in patient care and biomedical research, but their full potential has not yet been applied to the study and treatment of the severe illnesses caused by pathogens of biodefense concern. "conventional" imaging techniques (e.g., radiography, computed tomography, ultrasound, or magnetic resonance imaging) delineate anatomic changes in tissues, whereas "molecular" methods employ magnetic resonance, positron e ...200515844070
cyclopentane-modified pna improves the sensitivity of nanoparticle-based scanometric dna detection.trans-cyclopentane-modified pna has been successfully utilized as a target capture strand to improve the detection limit of a known dna detection assay, and provide high levels of mismatch discrimination.200515846413
[progress on the vaccine for anthrax].bacillus anthracis is the causative organism of the potentially fatal disease anthrax, and the used vaccines have some disadvantages. there are new developments appeared for the bacillus anthracis in recent years, such as anti-pa antibody kills the spore of bacillus anthracis, mucosal immunization induces immune responses in both systemic and secretory immune compartments, poly (gamma-d-pga) protein induce igg antibodies to the vegetative bacteria, new pathogens were found by genomic analysis. t ...200515847185
development of an edema factor-mediated camp-induction bioassay for detecting antibody-mediated neutralization of anthrax protective antigen.intoxication of mammalian cells by bacillus anthracis requires the coordinate activity of three distinct bacterial proteins: protective antigen (pa), edema factor (ef), and lethal factor (lf). among these proteins, pa has become the major focus of work on monoclonal antibodies and vaccines designed to treat or prevent anthrax infection since neither ef nor lf is capable of inducing cellular toxicity in its absence. here, we present the development of a sensitive, precise, and biologically releva ...200515847796
tnxo1, a germination-associated class ii transposon from bacillus anthracis.bacillus anthracis harbours two virulence plasmids, pxo1 (182 kb) and pxo2 (95 kb). whereas pxo2 harbours the cap operon coding for the capsule, pxo1 contains the pag, lef, and cya genes coding for protective antigen, lethal, and oedema factors, respectively, as well as the atxa regulatory gene. these genes are located within a 44.8 kb long pathogenicity island flanked by insertion sequences. here, we describe the presence in the same plasmid region of an 8679 bp genetic element displaying the s ...200515848228
bioterrorism defense: are state mandated compulsory vaccination programs an infringement upon a citizen's constitutional rights? 200215853127
bioterrorism and smallpox: policies, practices, and implications for social work.terrorist acts and the fear of terrorism have become a part of everyday life in the early 21st century. among the threats most feared is bioterrorism, including the intentional release of smallpox. with the invasion of iraq and toppling of the saddam hussein regime, acute bioterrorism fears have abated; however, an ongoing threat remains.this article addresses the need for knowledge and rational policies in dealing with potential bioterrorism attacks. it presents information on four of the most ...200515853189
use of fatty acid profiles to identify food-borne bacterial pathogens and aerobic endospore-forming bacilli.capillary gas chromatography (gc) with flame ionization detection was used to determine the cellular fatty acid profiles of various food-borne microbial pathogens and to compare the fatty acid profiles of spores and vegetative cells of the same endospore-forming bacilli. fifteen bacteria, representing eight genera (staphylococcus, listeria, bacillus, yersinia, salmonella, shigella, escherichia, and vibrio) and 11 species were used to compare the extracted fatty acid methyl esters (fames). endosp ...200515853428
management of anthrax meningitis.meningitis due to infection with bacillus anthracis is considered an infrequent manifestation of the disease but one associated with high mortality. the bioterrorism event in the usa in the autumn of 2001 demonstrated our need for a better understanding of anthrax meningitis, as well as management and antimicrobial therapy. however, human clinical trials are not possible and animal experiments to guide such therapy are limited. an approach to the treatment of anthrax meningitis, based on the pat ...200515854884
prediction of smallpox outbreak and evaluation of control-measure policy in japan, using a mathematical model.since the september 1 terrorist attacks and moreover, since the anthrax exposure events in 2001 in the united states, bioterrorism attacks seem to be a real threat. of course, the public health authorities in japan have started to prepare control measures for such events. we report here our attempts, using a mathematical model, to estimate outbreak size and to examine the most effective measures; comparing ring vaccination (contact tracing, isolation, and vaccination among contacts) and mass vac ...200515856374
a novel semiquantitative fluorescence-based multiplex polymerase chain reaction assay for rapid simultaneous detection of bacterial and parasitic pathogens from blood.a multiplex polymerase chain reaction assay was developed for the rapid simultaneous detection of category a select bacterial agents (bacillus anthracis and yersinia pestis) and parasitic pathogens (leishmania species) in blood using the cepheid smart cycler platform. b. anthracis (sterne) and yersinia. pseudotuberculosis were used in the assay for optimization for b. anthracis and y. pestis, respectively. the specificity of the target amplicons [protective antigen gene of b. anthracis and rrna ...200515858151
anthrax in wabessa village in the dessie zuria district of ethiopia.in 2002 an investigation of sudden death in a goat in wabessa village in the dessie zuria district of ethiopia was undertaken using fresh blood brought to the kombolcha regional veterinary laboratory. the sample was examined using standard bacteriological techniques and animal pathogenicity tests were also performed. the laboratory investigation revealed bacillus anthracis as the cause of sudden death. information gathered from stockowners in the same village revealed other similar recent cases ...200415861891
proteomics reveals that proteins expressed during the early stage of bacillus anthracis infection are potential targets for the development of vaccines and drugs.in this review, we advance a new concept in developing vaccines and/or drugs to target specific proteins expressed during the early stage of bacillus anthracis (anthrax) infection and address existing challenges to this concept. three proteins (immune inhibitor a, gpr-like spore protease, and alanine racemase) initially identified by proteomics in our laboratory were found to have differential expressions during anthrax spore germination and early outgrowth. other studies of different bacillus s ...200415862115
development of high-throughput assay of lethal factor using native substrate.the design of inhibitors for anthrax lethal factor (lf) is currently of interest as an approach for the treatment of anthrax because lf plays a major role in the cytotoxicity of target cells. lf is a zinc-dependent metalloprotease that specifically cleaves the mitogen-activated protein kinase kinase (mkk) family. current assay systems for the screening of lf inhibitor use the optimized synthetic peptide coupled with various kinds of fluorophores, enabling fast, sensitive, and robust assays suite ...200515866525
the application of the haddon matrix to public health readiness and response planning.state and local health departments continue to face unprecedented challenges in preparing for, recognizing, and responding to threats to the public's health. the attacks of 11 september 2001 and the ensuing anthrax mailings of 2001 highlighted the public health readiness and response hurdles posed by intentionally caused injury and illness. at the same time, recent natural disasters have highlighted the need for comparable public health readiness and response capabilities. public health readines ...200515866764
genetic analysis of bacillus anthracis sap s-layer protein crystallization domain.bacillus anthracis, the aetiological agent of anthrax, synthesizes two surface-layer (s-layer) proteins. s-layers are two-dimensional crystalline arrays that completely cover bacteria. in rich medium, the b. anthracis s-layer consists of sap during the exponential growth phase. sap is a modular protein composed of an slh (s-layer homology)-anchoring domain followed by a putative crystallization domain (sap c). a projection map of the two-dimensional sap array has been established on deflated bac ...200515870458
inhibition of bacillus anthracis growth and virulence-gene expression by inhibitors of quorum-sensing.density-dependent gene expression, quorum sensing (qs), involves the synthesis and detection of low-molecular-weight molecules known as autoinducers. inhibitors of bacterial qs systems offer potential treatment of infections with highly virulent or multidrug-resistant agents. we studied the effects on bacillus anthracis growth and the virulence gene (paga, lef, and cya) expression of the qs inhibitor (5z)-4-bromo-5-(bromomethylene)-3-butyl-2(5h)-furanone, which is naturally synthesized by the ma ...200515871122
microarray-based detection of 90 antibiotic resistance genes of gram-positive bacteria.a disposable microarray was developed for detection of up to 90 antibiotic resistance genes in gram-positive bacteria by hybridization. each antibiotic resistance gene is represented by two specific oligonucleotides chosen from consensus sequences of gene families, except for nine genes for which only one specific oligonucleotide could be developed. a total of 137 oligonucleotides (26 to 33 nucleotides in length with similar physicochemical parameters) were spotted onto the microarray. the micro ...200515872258
the effect of filter material on bioaerosol collection of bacillus subtilis spores used as a bacillus anthracis simulant.the objective of this study was to determine filter materials and extraction methods that are appropriate to use for environmental sampling of b. anthracis. four types of filters were tested: mixed cellulose ester (mce) with a pore size of 3 microm, polytetrafluoroethylene (ptfe) with pore sizes of 1 and 3 microm, and gelatin with a pore size of 3 microm. bacillus subtilis var. niger endospores (also known as bacillus globigii[bg]) were used as a surrogate for b. anthracis. endospores were colle ...200515877169
identification of novel anthrax lethal factor inhibitors generated by combinatorial pictet-spengler reaction followed by screening in situ. 200515880659
[characterization of bacillus anthracis typical virulent test strain 81/1].the results of the prolonged and many-sided study of b. anthracis strain 81/1 by different authors are presented. the cultural and morphological, biochemical, antigenic, molecular-genetic characteristics of this strain give grounds for regarding it as a typical test strain to be used for the determination of the vaccines immunogenicity, the effectiveness of antibiotics and immunomodulators.200515881953
occupational physician perceptions of bioterrorism.the rationale for most preparedness training of healthcare professionals is based on the assumption that most persons infected following a biological incident will present first to emergency departments of acute care facilities or to ambulatory settings such as private physician offices, and such incidences would be recognized, appropriately treated, and reported to the local health departments. however, an alternative first point of contact is industry, a location where workers gather and dispe ...200515881986
developmental commitment in a bacterium.we investigated developmental commitment during sporulation in bacillus subtilis. sporulation is initiated by nutrient limitation and involves division of the developing cell into two progeny, the forespore and the mother cell, with different fates. differentiation becomes irreversible following division when neither the forespore nor the mother cell can resume growth when provided with nutrients. we show that commitment is governed by the transcription factors sigma(f) and sigma(e), which are a ...200515882622
degradation of biological weapons agents in the environment: implications for terrorism response.we investigate the impact on effective terrorism response of the viability degradation of biological weapons agents in the environment. we briefly review the scientific understanding and modeling of agent environmental viability degradation. in general, agent susceptibility to viability loss is greatest for vegetative bacteria, intermediate for viruses, and least for bacterial spores. survival is greatest in soil and progressively decreases in the following environments: textiles, water, hard su ...200515884371
us response to anthrax scare "uncoordinated". 200515889475
osler and the infected letter.the spread of infectious agents through the mail has concerned public health officials for 5 centuries. the dissemination of anthrax spores in the us mail in 2001 was a recent example. in 1901, two medical journals reported outbreaks of smallpox presumably introduced by letters contaminated with variola viruses. the stability and infectivity of the smallpox virus are reviewed from both a historical (anecdotal) perspective and modern virologic studies. bubonic plague was the contagious disease th ...200515890120
host-pathogen interactions: a proteomic view.host-pathogen interactions reflect the balance of host defenses and pathogen virulence mechanisms. advances in proteomic technologies now afford opportunities to compare protein content between complex biologic systems ranging from cells to animals and clinical samples. thus, it is now possible to characterize host-pathogen interactions from a global proteomic view. most reports to date focus on cataloging protein content of pathogens and identifying virulence-associated proteins or proteomic al ...200515892564
activation of dendritic cells by microparticles containing bacillus anthracis protective antigen.we have carried out an in vitro investigation into the mechanism by which microencapsulation enhances the immunogenicity of recombinant protective antigen (rpa) from bacillus anthracis. murine bone marrow derived dendritic cells (dc) were cocultured with soluble and microencapsulated rpa and the activation status of the cells monitored using facs. as compared with soluble rpa, it was found that coculture of dc with rpa-loaded microparticles stimulated higher levels of mhc ii, cd54, cd80 and cd86 ...200515893625
intermolecular complementation achieves high-specificity tumor targeting by anthrax toxin.anthrax toxin protective antigen (prag) forms a heptamer in which the binding site for lethal factor (lf) spans two adjacent monomers. this suggested that high cell-type specificity in tumor targeting could be obtained using monomers that generate functional lf-binding sites only through intermolecular complementation. we created prag mutants with mutations affecting different lf-binding subsites and containing either urokinase plasminogen activator (upa) or matrix metalloproteinase (mmp) cleava ...200515895075
inhibition of daptomycin by pulmonary surfactant: in vitro modeling and clinical impact.the lipopeptide daptomycin has been approved for use in skin and skin-structure infections but has failed to meet statistical noninferiority criteria in a clinical trial for severe community-acquired pneumonia. daptomycin exhibited an unusual pattern of activity in pulmonary animal models: efficacy in staphylococcus aureus hematogenous pneumonia and inhalation anthrax but no activity against streptococcus pneumoniae in simple bronchial-alveolar pneumonia. daptomycin was shown to interact in vitr ...200515898002
media exposure to bioterrorism: stress and the anthrax attacks.this study examined media exposure and adjustment to anthrax bioterrorism attacks and the terrorist attacks on 9/11 in a sample of 300 people who lived distant from the attacks. measures of direct and indirect exposure to terrorism, perceived risk of anthrax exposure, psychological distress, and outlook were assessed at 2 to 3 months and at 8 months after the first reported anthrax attack. initial anthrax media exposure was a powerful predictor of distress, whereas subsequent anthrax media expos ...200515899708
an immuno-diffusion assay to assess the protective antigen content of anthrax vaccine.the uk anthrax vaccine uses the culture supernatant of toxigenic non-encapsulated bacillus anthracis as a crude source for protective antigen (pa). the precise amount of pa is not known. we developed a single radial immuno-diffusion (srd) assay and an indirect elisa to measure pa in desorbed anthrax vaccines. based on 23 batches, the pa contents varied from 19.1 to 88.8 microgml(-1), with an average of 39.6 microgml(-1). analysis of four batches by elisa revealed considerably lower levels of pa. ...200515908061
combining anthrax vaccine and therapy: a dominant-negative inhibitor of anthrax toxin is also a potent and safe immunogen for vaccines.anthrax is caused by the unimpeded growth of bacillus anthracis in the host and the secretion of toxins. the currently available vaccine is based on protective antigen (pa), a central component of anthrax toxin. vaccination with pa raises no direct immune response against the bacilli and, being a natural toxin component, pa might be hazardous when used immediately following exposure to b. anthracis. thus, we have sought to develop a vaccine or therapeutic agent that is safe and eliminates both s ...200515908368
comparative secretome analyses of three bacillus anthracis strains with variant plasmid contents.bacillus anthracis, the causative agent of anthrax, secretes numerous proteins into the extracellular environment during infection. a comparative proteomic approach was employed to elucidate the differences among the extracellular proteomes (secretomes) of three isogenic strains of b. anthracis that differed solely in their plasmid contents. the strains utilized were the wild-type virulent b. anthracis ra3 (pxo1(+) pxo2(+)) and its two nonpathogenic derivative strains: the toxigenic, nonencapsul ...200515908394
anthrax, what you should know. 200515909698
anthrax lethal factor inhibition.the primary virulence factor of bacillus anthracis is a secreted zinc-dependent metalloprotease toxin known as lethal factor (lf) that is lethal to the host through disruption of signaling pathways, cell destruction, and circulatory shock. inhibition of this proteolytic-based lf toxemia could be expected to provide therapeutic value in combination with an antibiotic during and immediately after an active anthrax infection. herein is shown the crystal structure of an intimate complex between a hy ...200515911756
sensitivity and specificity of metal surface-immobilized "molecular beacon" biosensors.the separate developments of microarray patterning of dna oligonucleotides, and of dna hairpins as sensitive probes for oligonucleotide identification in solution, have had a tremendous impact on basic biological research and clinical applications. we have combined these two approaches to develop arrayable and label-free biological sensors based on fluorescence unquenching of dna hairpins immobilized on metal surfaces. the thermodynamic and kinetic response of these sensors, and the factors impo ...200515913384
teaching resources. proteases and signaling.this teaching resource provides lecture notes and slides for a class covering proteases and signaling and is part of the course "cell signaling systems: a course for graduate students." the lecture begins with a discussion of protease-activated receptors and the ubiquitin-proteasome system and then proceeds to describe some of the ways that proteolysis can function in signal transduction.200515914727
history of u.s. military contributions to the study of bacterial zoonoses.bacterial zoonoses have afflicted campaigns throughout military history, at times playing an important role in determining their outcomes. in addition, zoonotic bacteria are among the leading biological warfare threats. the u.s. military medical services have been at the forefront of research to define the basic microbiology, ecology, epidemiology, and clinical aspects of these diseases. this historical review discusses the military significance of plague, q fever, anthrax, leptospirosis, barton ...200515916282
anthrax lethal toxin induces endothelial barrier dysfunction.hemorrhage and pleural effusion are prominent pathological features of systemic anthrax infection. we examined the effect of anthrax lethal toxin (lt), a major virulence factor of bacillus anthracis, on the barrier function of primary human lung microvascular endothelial cells. we also examined the distribution patterns of cytoskeletal actin and vascular endothelial-cadherin (ve-cadherin), both of which are involved in barrier function regulation. endothelial monolayers cultured on porous membra ...200515920171
studies toward a conjugate vaccine for anthrax. synthesis and characterization of anthrose [4,6-dideoxy-4-(3-hydroxy-3-methylbutanamido)-2-o-methyl-d-glucopyranose] and its methyl glycosides.the key step in the first chemical synthesis of anthrose (16) and its methyl alpha- (6) and beta-glycoside (22) was inversion of configuration at c-2 in triflates 10, 2, and 18, respectively, obtained from the common intermediate, methyl 4-azido-3-o-benzyl-4,6-dideoxy-alpha-d-mannopyranoside (1). to prepare methyl alpha-anthroside (6), methylation at o-2 of the gluco product 3, obtained from 2, was followed by hydrogenation/hydrogenolysis of the formed 2-methyl ether 4, to simultaneously remove ...200515922317
lessons learned from the cdc's post-exposure prophylaxis program following the anthrax attacks of 2001. 200515924332
the detection of protective antigen (pa) associated with spores of bacillus anthracis and the effects of anti-pa antibodies on spore germination and macrophage interactions.the protective antigen (pa) component of the anthrax toxins is an essential virulence factor of bacillus anthracis and is the major protective immunogen. the kinetics of pa production during growth of b. anthracis, and the roles of anti-pa antibody in host immunity are not clearly defined. production of pa by the vegetative organisms peaks during the shift from exponential to stationary phase of growth. recently, pa was also found to be associated with spores. in our study, pa-specific mrna was ...200515925272
performance of a rapid dermatology referral system during the anthrax outbreak.the bioterrorism-related anthrax outbreak generated unanticipated demand for dermatologic services. in this study we sought to perform rapid, efficient, cost-effective evaluation of patients suspected of having cutaneous anthrax. during the outbreak, we developed an anthrax evaluation system featuring clinical field examination by nondermatologist physicians, followed by rapid referral of selected high-risk patients to a centralized dermatology center. we excluded anthrax in 29 previously screen ...200515928632
generation of mouse polyclonal and human monoclonal antibodies against bacillus anthracis toxin.high titer antisera against the protective antigen (pa) from bacillus anthracis were generated immunizing balb/c mice two times intraperitoneally with pa in combination with lipopeptide adjuvant p3csk4. the sera were able to protect the mouse macrophage cell line j774a.1 from an anthrax toxin challenge. we also tested the blood of anthrax vaccine-immunized persons for pa- and lethal factor (lf)-specific antibodies. an increased titer was found after three immunizations, and the sera were also ab ...200515929604
simultaneous measurement of specific serum igg responses to five select agents.select agents are defined by cdc and the usda animal and plant health inspection service (aphis) as biological agents or toxins deemed a threat to public, animal, or plant health, or to animal or plant products. they are classified on the basis of their ease of dissemination, mortality/morbidity rate, and potential for social disruption. a subset of these agents includes bacillus anthracis, yersinia pestis, francisella tularensis, ricin toxin (rt), and staphylococcal enterotoxin b (seb). infecti ...200515931499
scalable purification of bacillus anthracis protective antigen from escherichia coli.the anthrax toxin consists of three proteins, protective antigen (pa), lethal factor, and edema factor that are produced by the gram-positive bacterium, bacillus anthracis. current vaccines against anthrax use pa as their primary component. in this study, we developed a scalable process to produce and purify multi-gram quantities of highly pure, recombinant pa (rpa) from escherichia coli. the rpa protein was produced in a 50-l fermentor and purified to >99% purity using anion-exchange, hydrophob ...200615935696
particulate delivery systems for biodefense subunit vaccines.expanding identification of potentially protective subunit antigens and correlates of protection has provided a basis for the introduction of safer vaccines. despite encouraging results in animal models, the significant potential of particulate delivery systems in vaccine design has not yet translated into effective vaccines available for use in humans. this review article will focus on the current status of the development of particulate vaccines, mainly liposomes and bio-degradable polymers, a ...200515935873
molecular basis for improved anthrax vaccines.the current vaccine for anthrax has been licensed since 1970 and was developed based on the outcome of human trials conducted in the 1950s. this vaccine, known as anthrax vaccine adsorbed (ava), consists of a culture filtrate from an attenuated strain of bacillus anthracis adsorbed to aluminum salts as an adjuvant. this vaccine is considered safe and effective, but is difficult to produce and is associated with complaints about reactogenicity among users of the vaccine. much of the work in the p ...200515935874
commensal bacteria as a novel delivery system for subunit vaccines directed against agents of bioterrorism.following the anthrax attacks of 2001 and the recent sars outbreak, concerns about emerging and re-emerging infectious diseases have catalyzed a renewed interest in developing new vaccination strategies that provide rapid and flexible response options to future threats. because the probability of encountering one of these exotic agents is unknown, it is essential that new vaccine formulations employ methods that provide effective protection and extremely good safety profiles if they are to be us ...200515935879
a phase 1 study of pamab, a fully human monoclonal antibody against bacillus anthracis protective antigen, in healthy volunteers.inhibition of the binding of bacillus anthracis protective antigen (pa) to its cellular receptor can abrogate the downstream toxin-mediated deleterious effects of the anthrax toxin. a fully human monoclonal antibody against b. anthracis pa, pamab, was previously shown to provide a survival advantage in rabbit and monkey models of inhalational anthrax.200515937757
multiple-locus variable number tandem repeats analysis for genetic fingerprinting of pathogenic bacteria.dna fingerprinting has attracted considerable interest as means for identifying, tracing and preventing the dissemination of infectious agents. various methods have been developed for typing of pathogenic bacteria, which differ in discriminative power, reproducibility and ease of interpretation. during recent years a typing method, which uses the information provided by whole genome sequencing of bacterial species, has gained increased attention. short sequence repeat (ssr) motifs are known to u ...200515937984
protective antigen and toxin neutralization antibody patterns in anthrax vaccinees undergoing serial plasmapheresis.recipients of licensed anthrax vaccine (ava; biothrax) could serve as a source of hyperimmune plasma and immunoglobulin for therapy and prophylaxis. we measured serum antibodies during serial weekly to biweekly plasmapheresis in 38 individuals previously vaccinated with 4 to 27 doses of ava. immunoglobulin g (igg) to protective antigen (pa) and toxin neutralization assay (tna) antibody levels were highly correlated (r = 0.86930 and p < 0.0001 for anti-pa concentration versus tna concentration). ...200515939745
[studies on the germination of bacillus anthracoides spores induced by nutrient germinant].to explore the germination effects of bacillus anthracoides spores germinant to nutrient germinant.200515941512
the dna-binding specificity of the bacillus anthracis abrb protein.the bacillus subtilis abrb protein is a dna-binding global regulator of a plethora of functions that are expressed during the transition from exponential growth to stationary phase and under suboptimal growth conditions. abrb orthologues have been identified in a variety of prokaryotic organisms, notably in all species of bacillus, clostridium and listeria that have been examined. based on amino acid sequence identity in the n-terminal domains of the orthologues from b. subtilis and bacillus ant ...200515941984
functional reconstitution of protein ion channels into planar polymerizable phospholipid membranes.we demonstrate that polymerizable planar membranes permit reconstitution of protein ion channels formed by the bacterial toxins staphylococcus aureus alpha-hemolysin (alphahl) and bacillus anthracis protective antigen 63. the alphahl channel remained functional even after membrane polymerization. surface pressure measurements suggest that the ease of forming membranes depends on membrane surface elasticity estimated from langmuir-blodgett monolayer pressure-area isotherms. the ability to stabili ...200515943465
phosphatidylinositol-specific phospholipase c of bacillus anthracis down-modulates the immune response.phosphatidylinositol-specific phospholipases (pi-plcs) are virulence factors produced by many pathogenic bacteria, including bacillus anthracis and listeria monocytogenes. bacillus pi-plc differs from listeria pi-plc in that it has strong activity for cleaving gpi-anchored proteins. treatment of murine dcs with bacillus, but not listeria, pi-plc inhibited dendritic cell (dc) activation by tlr ligands. infection of mice with listeria expressing b. anthracis pi-plc resulted in a reduced ag-specifi ...200515944308
specific detection of bacillus anthracis using a taqman mismatch amplification mutation assay.single nucleotide polymorphisms (snps) are increasingly recognized as important diagnostic markers for the detection and differentiation of bacillus anthracis. the use of snp markers for identifying b. anthracis dna in environmental samples containing genetically similar bacteria requires the ability to amplify and detect dna with single nucleotide specificity. we designed a taqman mismatch amplification mutation assay (taqmama) around a snp in the plcr gene of b. anthracis. the assay permits sp ...200515945372
multiplexed detection of pathogen dna with dna-based fluorescence nanobarcodes.rapid, multiplexed, sensitive and specific molecular detection is of great demand in gene profiling, drug screening, clinical diagnostics and environmental analysis. one of the major challenges in multiplexed analysis is to identify each specific reaction with a distinct label or 'code'. two encoding strategies are currently used: positional encoding, in which every potential reaction is preassigned a particular position on a solid-phase support such as a dna microarray, and reaction encoding, w ...200515951805
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