Publications

[heterogeneity of bacillus anthracis strains in terms of their adhesive capacity].	the homogeneity of colonies of two b. anthracis vaccine strains in r- and rs- forms (100 colonies of each strain) in terms of their adhesive capacity was studied. b. anthracis strain 228/8 showed more heterogeneous composition than b. anthracis strain 71/12, moderately and highly adhesive colonies prevailing in both forms and nonadhesive colonies being absent. the prevalence of highly adhesive clones was established in the rs- form of b. anthracis strain 72/12 in comparison with r- form. by the ...	2004	15346957
phylogenetic discovery bias in bacillus anthracis using single-nucleotide polymorphisms from whole-genome sequencing.	phylogenetic reconstruction using molecular data is often subject to homoplasy, leading to inaccurate conclusions about phylogenetic relationships among operational taxonomic units. compared with other molecular markers, single-nucleotide polymorphisms (snps) exhibit extremely low mutation rates, making them rare in recently emerged pathogens, but they are less prone to homoplasy and thus extremely valuable for phylogenetic analyses. despite their phylogenetic potential, ascertainment bias occur ...	2004	15347815
tem8 interacts with the cleaved c5 domain of collagen alpha 3(vi).	tumor endothelial marker (tem)8 was uncovered as a gene expressed predominantly in tumor endothelium, and its protein product was recently identified as the receptor for anthrax toxin. here, we demonstrate that tem8 protein is preferentially expressed in endothelial cells of neoplastic tissue. we used the extracellular domain of tem8 to search for ligands and identified the alpha 3 subunit of collagen vi as an interacting partner. the tem8-interacting region on collagen alpha 3(vi) was mapped to ...	2004	14871805
prediction of proprotein convertase cleavage sites.	many secretory proteins and peptides are synthesized as inactive precursors that in addition to signal peptide cleavage undergo post-translational processing to become biologically active polypeptides. precursors are usually cleaved at sites composed of single or paired basic amino acid residues by members of the subtilisin/kexin-like proprotein convertase (pc) family. in mammals, seven members have been identified, with furin being the one first discovered and best characterized. recently, the ...	2004	14985543
preparation of a positive control dna for molecular diagnosis of bacillus anthracis.	bacillus anthracis is considered to be one of the most potent biological weapons because of its highly pathogenic nature and efficiency of transmission. routinely, a presumptive diagnosis of anthrax is achieved if the bands with predicted sizes are detected after the pcr targeted to the pag and cap genes residing on pxo1 and pxo2 plasmids, respectively. a positive control dna prepared from the standard strains of b. anthracis (pai and paii) is usually included in the pcr tests. the handling of l ...	2004	14985634
is it influenza or anthrax? a decision analytic approach to the treatment of patients with influenza-like illnesses.	we analyze the risks and benefits of alternative treatment strategies for non-septic-appearing febrile patients with influenza-like illnesses and possible exposure to anthrax.	2004	14985657
chinese curses, anthrax, and the risk of bioterrorism.		2004	14985658
two distinct types of rrna operons in the bacillus cereus group.	the bacillus cereus group includes insecticidal bacteria (b. thuringiensis), food-borne pathogens (b. cereus and b. weihenstephanensis) and b. anthracis, the causative agent of anthrax. the precise number of rrna operons in 12 strains of the b. cereus group was determined. most of the tested strains possess 13 operons and the tested psychrotolerant strains contain 14 operons, the highest number ever found in bacteria. the separate clustering of the tested psychrotolerant strains was confirmed by ...	2004	14993309
identification of chromosomally encoded membranal polypeptides of bacillus anthracis by a proteomic analysis: prevalence of proteins containing s-layer homology domains.	bacillus anthracis is the causative agent of anthrax disease. improvement of existing anthrax vaccines, which are currently based on the administration of protective antigen (the highly immunogenic nontoxic subunit of the bacterial toxin) may entail other bacterial immunogenic elements, part of which are predicted to reside on the surface of bacterial cells. in the present study, membranal proteins extracted from a stationary-phase culture of a nonvirulent b. anthracis strain, devoid of the nati ...	2004	14997491
immune system paralysis by anthrax lethal toxin: the roles of innate and adaptive immunity.	since the deliberate use of anthrax as a bioweapon in the usa in 2001, an enormous amount of attention has been focused on the biology of bacillus anthracis, the causative bacterium of anthrax. fatal systemic anthrax involves massive bacteraemia and toxaemia with non-descript early symptoms until the onset of shock and sudden death. the outbreak of fatal symptoms after the incubation period of b anthracis suggests an impairment of the host immune system against this pathogen. thus, it is likely ...	2004	14998502
in vitro post-antibiotic effect of fluoroquinolones, macrolides, beta-lactams, tetracyclines, vancomycin, clindamycin, linezolid, chloramphenicol, quinupristin/dalfopristin and rifampicin on bacillus anthracis.	the aim of this study was to investigate in vitro the post-antibiotic effect (pae) of 19 antibacterial agents against two strains of bacillus anthracis (st-1 and sterne strains).	2004	14998982
modification of clastogenesis and carcinogenesis in rats and mice by means of anthrax live vaccine.	possible micronuclei (mn) inducing activity of anthrax live vaccine (alv; produced in armenia and used for immunization of animals) was studied on rats and mice. it has been shown that alv did not induce mn in rodents' bone marrow erythrocytes. for the first time it has been shown that immunization of rats and mice with alv led to decrease of micronuclei number induced by cyclophosphamide and 7,12-dimethylbenz(a)anthracene in bone marrow cells. immunized rats were also resistant to carcinogenic ...	2004	15004654
pathogen-specific recombinant human polyclonal antibodies: biodefence applications.	the potential use of biological agents such as viruses, bacteria or bacterial toxins as weapons of mass destruction has fuelled significant national and international research and development in novel prophylactic or therapeutic countermeasures. such measures need to be fast-acting and broadly specific, a hallmark of target-specific polyclonal antibodies (pabs). as reviewed here, pathogen-specific antibodies in the form of human or animal serum have long been recognised as effective therapies in ...	2004	15006732
lethal toxin of bacillus anthracis inhibits tissue factor expression in vascular cells.		2004	15009481
anthrax lethal toxin rapidly activates caspase-1/ice and induces extracellular release of interleukin (il)-1beta and il-18.	anthrax lethal toxin (lt), a critical virulence factor for bacillus anthracis, has been demonstrated to cleave and to inactivate mitogen-activated protein kinase kinases (mapkks) that propagate prosurvival signals in macrophages (1-5). whether this action of anthrax lt leads to the production of proinflammatory cytokines by macrophages has been more controversial (6, 7). we now report that anthrax lt treatment leads to the specific extracellular release of interleukin (il)-1beta and il-18 by the ...	2004	15010463
proliferation of biological weapons: challenges and responses.	the threat posed by the proliferation of biological weapons (bw) confronts all strata of our society, from the individual, the nation, or the region to the truly international. the history of state-run offensive bw programmes and the attacks in the united states with powdered anthrax demonstrate that existing measures fall short of addressing this threat. this article examines the current regime and the concerns that confront it in order to suggest possible responses across the social strata tha ...	2004	15015544
evaluation of the washington state national pharmaceutical stockpile dispensing exercise, part ii--dispensary site worker findings.	on january 24, 2002, the washington state department of health, in collaboration with local and federal agencies, conducted an exercise of the centers for disease control and prevention's national pharmaceutical stockpile dispensing portion of the washington state plan. this exercise included predrill planning, training, and the orchestration of services of more than 40 dispensary site workers. these workers provided education and post-exposure prophylaxis for over 230 patient volunteers in the ...	2004	15018345
anthrax vaccination and self-reported symptoms, functional status, and medical conditions in the national health survey of gulf war era veterans and their families.	to evaluate the health status of gulf war veterans who reported receipt of anthrax vaccination and a small group of gulf war veterans for whom documentation of anthrax vaccination exists.	2004	15018879
comparative proteomics of the mycobacterium leprae binding protein myelin p0: its implication in leprosy and other neurodegenerative diseases.	mycobacterium leprae, the causative agent of leprosy invades schwann cells of the peripheral nerves leading to nerve damage and disfigurement, which is the hallmark of the disease. wet experiments have shown that m. leprae binds to a major peripheral nerve protein, the myelin p zero (p0). this protein is specific to peripheral nerve and may be important in the initial step of m. leprae binding and invasion of schwann cells which is the feature of leprosy. though the receptors on schawann cells, ...	2004	15019586
the osmoprotectants glycine and its methyl derivatives prevent the thermal inactivation of protective antigen of bacillus anthracis.	protective antigen (pa) is the main immunogenic constituent of all vaccines against anthrax. it is known to lose its biological activity even at 37 degrees c. its thermolabile nature has, thus, remained a cause of concern as even transient exposure of the vaccine to higher temperature could compromise its efficacy. various types of cosolvent excipients have been used to stabilize a number of proteins with variable success. however, no comprehensive and systematic study to stabilize anthrax pa mo ...	2004	15020254
chemical, biological, radiological and nuclear terrorism: an introduction for occupational physicians.	chemical, biological, radiological and nuclear terrorism poses considerable threat throughout the world.	2004	15020728
[effect of hydrogen peroxide on the virulent properties of anthrax pathogen spores].	the impact exerted by hydrogen peroxide on the virulent properties of anthrax pathogen spores was experimentally evaluated. even a short-term exposure of them to a disinfect was shown to cause impairments of the functional nature in the spores' vital structures, e.g. suppression of multiplication. at the same time, the biological monitoring of disinfection efficiency does not always rule out the presence of viable pathogen spores in the disinfected objects.	2004	15022549
validation of the anthrax lethal toxin neutralization assay.	a validation of the performance characteristics of a toxin neutralization assay is presented. this in vitro assay measures the functional ability of antisera, containing antibodies to anthrax lethal toxin, to specifically protect j774a.1 cells against bacillus anthracis lethal toxin cytotoxicity. this colormetric assay is based upon the reduction of mtt by living cells. human and rabbit antisera produced against anthrax vaccine absorbed (ava) were used to validate the assay. results showed a hig ...	2004	15026022
identification of bacillus anthracis specific chromosomal sequences by suppressive subtractive hybridization.	bacillus anthracis, bacillus thuringiensis and bacillus cereus are closely related members of the b. cereus-group of bacilli. suppressive subtractive hybridization (ssh) was used to identify specific chromosomal sequences unique to b. anthracis.	2004	15028116
"the history of anthrax", by sternbach g.		2004	15028341
bacillus anthracis and bacillus cereus pcra helicases can support dna unwinding and in vitro rolling-circle replication of plasmid pt181 of staphylococcus aureus.	replication of rolling-circle replicating (rcr) plasmids in gram-positive bacteria requires the unwinding of initiator protein-nicked plasmid dna by the pcra helicase. in this report, we demonstrate that heterologous pcra helicases from bacillus anthracis and bacillus cereus are capable of unwinding staphylococcus aureus plasmid pt181 from the initiator-generated nick and promoting in vitro replication of the plasmid. these helicases also physically interact with the repc initiator protein of pt ...	2004	15028705
the protein kinase pkr is required for macrophage apoptosis after activation of toll-like receptor 4.	macrophages are pivotal constituents of the innate immune system, vital for recognition and elimination of microbial pathogens. macrophages use toll-like receptors (tlrs) to detect pathogen-associated molecular patterns--including bacterial cell wall components, such as lipopolysaccharide or lipoteichoic acid, and viral nucleic acids, such as double-stranded (ds)rna--and in turn activate effector functions, including anti-apoptotic signalling pathways. certain pathogens, however, such as salmone ...	2004	15029200
potent inhibitors of anthrax lethal factor from green tea.	the anthrax lethal factor (lf) has a major role in the development of anthrax. lf is delivered by the protective antigen (pa) inside the cell, where it exerts its metalloprotease activity on the n-terminus of mapk-kinases. pa+lf are cytotoxic to macrophages in culture and kill the fischer 344 rat when injected intravenously. we describe here the properties of some polyphenols contained in green tea as powerful inhibitors of lf metalloproteolytic activity, and how the main catechin of green tea, ...	2004	15031715
time-lapse confocal imaging of development of bacillus anthracis in macrophages.	macrophages attempt to battle infection with bacillus anthracis spores by phagocytosis of the spores. however, it is believed that b. anthracis spores may survive phagocytosis and may actually use the macrophages that ingest them as a means of transport to lymph nodes. thus far, the events that occur after spores undergo phagocytosis have remained unclear. to elucidate the fate of spores internalized by macrophages, we have used time-lapse confocal microscopy to follow individual fluorescent spo ...	2004	15031802
vaccines and immunotherapies for the prevention of infectious diseases having cutaneous manifestations.	although the development of antimicrobial drugs has advanced rapidly in the past several years, such agents act against only certain groups of microbes and are associated with increasing rates of resistance. these limitations of treatment force physicians to continue to rely on prevention, which is more effective and cost-effective than therapy. from the use of the smallpox vaccine by jenner in the 1700s to the current concerns about biologic warfare, the technology for vaccine development has s ...	2004	15034501
molecular koch's postulates applied to bacterial pathogenicity--a personal recollection 15 years later.	koch's postulates were derived from robert koch's work on infectious diseases, such as anthrax and tuberculosis, which still engage us to this day. these guidelines were an attempt to establish a standard for identifying the specific causation of an infectious disease and to convince sceptics that microorganisms could cause disease. they were also established to encourage an increasing number of novice microbiologists to use more rigorous criteria before claiming a causal relationship between a ...	2004	15035010
rapid dipicolinic acid extraction from bacillus spores detected by surface-enhanced raman spectroscopy.		2004	15035719
the roles of anthrax toxin in pathogenesis.	anthrax lethal toxin is a multi-functional virulence factor that has evolved to target multiple host functions to allow for optimal establishment of bacillus anthracis infection. the toxin appears to play a role in all stages of infection, from germination to the induction of vascular collapse leading to host death. early in infection, at sublethal doses, it acts to suppress immune cell and cytokine responses, thereby promoting bacterial outgrowth. later in the disease, lethal levels of toxin in ...	2004	15036135
differentiating inhalational anthrax from other influenza-like illnesses in the setting of a national or regional anthrax outbreak.	the workup of a febrile patient who presents with an influenza-like illness in the setting of a national or regional anthrax outbreak presents a unique challenge to the physicians who initially evaluate this patient, and the diagnostic challenge can be even more profound during the influenza season. based on information gathered from the recent inhalational anthrax cases, we have developed an algorithm to be used by physicians in the emergency department to evaluate patients with influenza-like ...	2004	15037498
induction of opsonic antibodies to the gamma-d-glutamic acid capsule of bacillus anthracis by immunization with a synthetic peptide-carrier protein conjugate.	the capsule of bacillus anthracis, a polymer of gamma-d-glutamic acid, functions as a virulence determinant and is a poor immunogen. in this study we show that antibodies reactive with the b. anthracis capsule can be elicited in mice by immunization with a conjugate consisting of a synthetic gamma-d-glutamic acid nonamer peptide (gamma-d-glu9) covalently coupled to keyhole limpet hemocyanin. the serum response to gamma-d-glu9 was comprised primarily of igg antibodies that recognized an epitope r ...	2004	15039099
anthrax in america 2001-2003.	anthrax caused by bacillus anthracis in humans is rare. two recent outbreaks that were intentionally caused occurred among postal employees, politicians, and journalists in the united states. this has caused tremendous fear, and our experience with these "anthrax incidents" has changed our views on the natural history of this disease in people. in this paper, we review the lifecycle and biology of this micro-organism. anthrax that occurs from a weaponized form of this micro-organism has a specif ...	2004	15040516
[microchips based on three dimensional gel cells: history and perspective].	the review describes the history of creation and development of the microchip technology and its role in the human genome project in russia. the emphasis is placed on the three-dimensional gel-based microchips developed at the center of biological microchips headed by a.d. mirzabekov since 1988. the gel-based chips of the last generation, image chips (immobilized micro array of gel elements), have a number of advantages over the previous versions. the microchips are manufactured by photo-initiat ...	2004	15042831
current therapy and the development of therapeutic options for the treatment of diseases due to bacterial agents of potential biowarfare and bioterrorism.	an important part of biodefense is the optimization of current therapy and the development of new therapeutic options for the treatment of the diseases most likely encountered in the form of biological weapons. guidelines for the prevention and treatment of anthrax, plague, tularemia and botulinum toxin intoxication are reviewed. the strategies in development for the prevention of anthrax focus primarily on active and passive immunization against protective antigen, because of its central role a ...	2004	15043386
protecting america's secrets while maintaining academic freedom.	the terrorist attacks of september 11, 2001, and the subsequent anthrax mail attacks, have had a profound impact on americans' personal and professional lives and have sparked an active debate regarding the delicate balance between the need for national security and the pursuit of academic freedom. although academic freedom can be defined in many ways, there are four primary tenets of freedom in an academic environment: freedom to research, freedom to publish, freedom to teach, and freedom to sp ...	2004	15044166
binding stoichiometry and kinetics of the interaction of a human anthrax toxin receptor, cmg2, with protective antigen.	the protective antigen (pa) moiety of anthrax toxin binds to cellular receptors and mediates entry of the two enzymatic moieties of the toxin into the cytosol. two pa receptors, anthrax toxin receptor (atr)/tumor endothelial marker 8 (tem8) and capillary morphogenesis protein 2 (cmg2), have been identified. we expressed and purified the von willebrand a (vwa) domain of cmg2 and examined its interactions with monomeric and heptameric forms of pa. monomeric pa bound a stoichiometric equivalent of ...	2004	15044490
fate of bioterrorism-relevant viruses and bacteria, including spores, aerosolized into an indoor air environment.	an aerosol physics test facility was used in a series of eight experiments to gather an integrated comprehensive broad base of data on the fate of surrogates of microorganisms that cause smallpox, plague, glanders, anthrax, and viral hemorrhagic fevers. the results are directly relevant to the public health issue of how to protect the occupants of buildings against bioterrorism. the test conditions were directly relevant to the indoor air environment situation, and the results can be generalized ...	2004	15044718
western blot analysis of the exotoxin components from bacillus anthracis separated by isoelectric focusing gel electrophoresis.	the components of the bacillus anthracis exotoxins, protective antigen (pa), lethal factor (lf), and edema factor (ef), from 24 isolates were separated by isoelectric focusing gel electrophoresis and detected by western blot with monoclonal antibodies. only two isoforms each were observed for pa and ef. four isoforms were identified for lf. the biological activities of both lethal toxin and edema toxin were measured by using in vitro cell-based assays. this study provides another method of chara ...	2004	15047182
mabs to bacillus anthracis capsular antigen for immunoprotection in anthrax and detection of antigenemia.	bacillus anthracis is surrounded by an antiphagocytic polypeptide capsule composed of poly gamma-d-glutamic acid (gammadpga). gammadpga has been identified recently as a potential target for vaccine development. studies of the role of gammadpga in disease have been hampered by the poor ab response to this antigen and the lack of immunochemical reagents. as a consequence, neither the extent of gammadpga production during anthrax nor the protective activity of gammadpga abs in inhalation anthrax a ...	2004	15051894
nerd: a dna processing-related domain present in the anthrax virulence plasmid, pxo1.	we have identified a new domain in a broad range of bacterial, as well as single archaeal and plant proteins. its presence in the virulence-related pxo1 plasmid of bacillus anthracis as well as in several other pathogens makes it a possible drug target. we term the new domain nuclease-related domain (nerd) because of its distant similarity to endonucleases.	2004	15055202
bioterrorism and emerging infectious disease - antimicrobials, therapeutics and immune-modulators. sars coronavirus.	the purpose of this meeting was to provide a forum for expert presentations and discussion about the threats of bioterrorism and emerging infectious diseases, and to address the issues relating to epidemics, prevention of infection and treatment of some of these emerging infectious diseases classified as potential agents of bioterror. included in the talks were state-of-the-art presentations about infectious clone technology and recombinant viruses, pathogen and receptor interactions at the cell ...	2004	15057645
characterization of a major bacillus anthracis spore coat protein and its role in spore inactivation.	a major bacillus anthracis spore coat protein of 13.4 kda, designated cot alpha, was found only in the bacillus cereus group. a stable ca. 30-kda dimer of this protein was also present in spore coat extracts. cot alpha, which is encoded by a monocistronic gene, was first detected late in sporulation, consistent with a sigma(k)-regulated gene. on the basis of immunogold labeling, the protein is in the outer spore coat and absent from the exosporium. in addition, disruption of the gene encoding co ...	2004	15060044
the 26 nudix hydrolases of bacillus cereus, a close relative of bacillus anthracis.	the genome of bacillus cereus contains 26 nudix hydrolase genes, second only to its closest relative, bacillus anthracis which has 30. all 26 genes have been cloned, 25 have been expressed, and 21 produced soluble proteins suitable for analysis. substrates for 16 of the enzymes were identified; these included adp-ribose, diadenosine polyphosphates, sugar nucleotides, and deoxynucleoside triphosphates. one of the enzymes was a cdp-choline pyrophosphatase, the first nudix hydrolase active on this ...	2004	15060060
inhalational anthrax.	anthrax remains a real threat. in a spore form, it is highly infectious and dispersible. the initial symptoms are similar to those of influenza, and the early stage of inhalational anthrax may not be recognized. early antibiotic treatment is important to achieving a good outcome. contrary to historical experience. many patients with even advanced anthrax can be saved with aggressive medical care. prevention of anthrax infections requires vigilant infection control methods as well as a rational p ...	2004	15062228
vaccines against biologic agents: uses and developments.	although the geneva protocol that prohibits the use of chemical and biologic weapons was ratified in 1925, many countries failed to accept this protocol: others stipulated retaliation, and some, like the united states, did not ratify the protocol for decades. this delay allowed the continued development of chemical and biologic agents. members of the health care community are responsible for determining the best way to protect society from the potentially devastating effects of these biologic ag ...	2004	15062232
up-regulation of bradykinin receptors in a murine in-vitro model of chronic airway inflammation.	tumour necrosis factor-alpha (tnf-alpha) is a mediator with a likely role in chronic airway inflammation and airway hyperresponsiveness. in the present study, mouse tracheal segments were cultured for 1, 4 or 8 days in the absence and presence of tnf-alpha. contractile response of cultured segments to des-arg9-bradykinin and bradykinin was assessed in myographs and mrna for bradykinin b1 and b2 receptors was quantified by real-time polymerase chain reaction. both contraction to des-arg9-bradykin ...	2004	15063163
structure of anthrax edema factor-calmodulin-adenosine 5'-(alpha,beta-methylene)-triphosphate complex reveals an alternative mode of atp binding to the catalytic site.	anthrax edema factor (ef) is a key virulence factor secreted by bacillus anthracis. here, we report a structure, at 3.0 a resolution, of the catalytic domain of ef (ef3) in complex with calmodulin (cam) and adenosine 5'-(alpha,beta-methylene)-triphosphate (ampcpp). although the binding of the triphosphate of ampcpp to ef3 can be superimposed on that of previously determined 3'deoxy-atp (3'datp) and 2'deoxy 3' anthraniloyl-atp (2'd3' ant-atp) in ef3-cam, the ribose and the adenine rings of ampcpp ...	2004	15063758
using light scattering to determine the stoichiometry of protein complexes.	the stoichiometry of a protein complex can be calculated from an accurate measurement of the complex's molecular weight. multiangle laser light scattering in combination with size-exclusion chromatography and interferometric refractometry provides a powerful means for determining the molecular weights of proteins and protein complexes. in contrast to conventional size-exclusion chromatography and analytical centrifugation, measurements do not rely on the use of molecular weight standards and are ...	2004	15064452
use of phage display and polyvalency to design inhibitors of protein-protein interactions.	we describe the synthesis of an inhibitor that interferes with critical protein-protein interactions occurring during the assembly of anthrax toxin. using a phage display selection strategy, we isolated a peptide directed against the cell binding moiety of the toxin that was able to interfere with binding of the enzymatic moieties. because the cell binding moiety of the toxin is a heptamer, the peptide can potentially bind up to seven equivalent sites. we synthesized a polyvalent molecule displa ...	2004	15064461
genetic immunization against anthrax.	the objective of this study was to determine whether a dna prime-protein boost immunization against the bacillus anthracis protective antigen (pa) and lethal factor (lf) antigens could induce a protective immune response against significant aerosol challenge in the rabbit model. rabbits were vaccinated with different regimens of dna vaccines (table 1) and aerosol challenged with b. anthracis spores, ames strain, with an average dose of 50 ld(50s) with a range from 18 to 169 ld(50s.) of the five ...	2004	15068841
gyrb as a phylogenetic discriminator for members of the bacillus anthracis-cereus-thuringiensis group.	bacillus anthracis, the causative agent of the human disease anthrax, bacillus cereus, a food-borne pathogen capable of causing human illness, and bacillus thuringiensis, a well-characterized insecticidal toxin producer, all cluster together within a very tight clade (b. cereus group) phylogenetically and are indistinguishable from one another via 16s rdna sequence analysis. as new pathogens are continually emerging, it is imperative to devise a system capable of rapidly and accurately different ...	2004	14967230
british society for immunology-annual conference 2003.		2004	14968818
exogenous gamma and alpha/beta interferon rescues human macrophages from cell death induced by bacillus anthracis.	during the recent bioterrorism-related outbreaks, inhalational anthrax had a 45% mortality in spite of appropriate antimicrobial therapy, underscoring the need for better adjuvant therapies. the variable latency between exposure and development of disease suggests an important role for the host's innate immune response. alveolar macrophages are likely the first immune cells exposed to inhalational anthrax, and the interferon (ifn) response of these cells comprises an important arm of the host in ...	2004	14977930
selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis b virus infection.	edema factor (ef), a key virulence factor in anthrax pathogenesis, has calmodulin (cam)-activated adenylyl cyclase activity. we have found that adefovir dipivoxil, a drug approved to treat chronic infection of hepatitis b virus, effectively inhibits ef-induced camp accumulation and changes in cytokine production in mouse primary macrophages. adefovir diphosphate (pmeapp), the active cellular metabolite of adefovir dipivoxil, inhibits the adenylyl cyclase activity of ef in vitro with high affinit ...	2004	14978283
the genome sequence of bacillus cereus atcc 10987 reveals metabolic adaptations and a large plasmid related to bacillus anthracis pxo1.	we sequenced the complete genome of bacillus cereus atcc 10987, a non-lethal dairy isolate in the same genetic subgroup as bacillus anthracis. comparison of the chromosomes demonstrated that b.cereus atcc 10987 was more similar to b.anthracis ames than b.cereus atcc 14579, while containing a number of unique metabolic capabilities such as urease and xylose utilization and lacking the ability to utilize nitrate and nitrite. additionally, genetic mechanisms for variation of capsule carbohydrate an ...	2004	14960714
a universal nucleic acid sequence biosensor with nanomolar detection limits.	a quantitative universal biosensor was developed on the basis of olignucleotide sandwich hybridization for the rapid (30 min total assay time) and highly sensitive (1 nm) detection of specific nucleic acid sequences. the biosensor consists of a universal membrane and a universal dye-entrapping liposomal nanovesicle. two oligonucleotides, a reporter and a capture probe that can hybridize specifically with the target nucleic acid sequence, can be coupled to the universal biosensor components withi ...	2004	14961717
differential inhibition of adenylyl cyclase isoforms and soluble guanylyl cyclase by purine and pyrimidine nucleotides.	mammals express nine membranous adenylyl cyclase isoforms (acs 1-9), a structurally related soluble guanylyl cyclase (sgc) and a soluble ac (sac). moreover, bacillus anthracis and bacillus pertussis produce the ac toxins, edema factor (ef), and adenylyl cyclase toxin (act), respectively. 2'(3')-o-(n-methylanthraniloyl)-guanosine 5'-[gamma-thio]triphosphate is a potent competitive inhibitor of ac in s49 lymphoma cell membranes. these data prompted us to study systematically the effects of 24 nucl ...	2004	14981084
an unusual inhalational exposure to bacillus anthracis in a research laboratory.		2004	15076646
bacillus anthracis contamination and inhalational anthrax in a mail processing and distribution center.	four inhalational anthrax cases occurred in a large mail processing and distribution center in washington, dc, after envelopes containing bacillus anthracis spores were processed. this report describes the results of sampling for b. anthracis spores during investigations conducted in october and december 2001.	2004	15078521
crystal structure of the von willebrand factor a domain of human capillary morphogenesis protein 2: an anthrax toxin receptor.	anthrax toxin is released from bacillus anthracis as three monomeric proteins, which assemble into toxic complexes at the surface of receptor-bearing host cells. one of the proteins, protective antigen (pa), binds to receptors and orchestrates the delivery of the other two (the lethal and edema factors) into the cytosol. pa has been shown to bind to two cellular receptors: anthrax toxin receptor/tumor endothelial marker 8 and capillary morphogenesis protein 2 (cmg2). both are type 1 membrane pro ...	2004	15079089
the sniper and the public's mental health.		2004	15079941
inhibition of the proteolytic activity of anthrax lethal factor by aminoglycosides.	the anthrax lethal factor (lf), a zn-dependent endopeptidase, is considered the dominant virulence factor of anthrax. because pharmacological inhibition of the catalytic activity of lf is considered a plausible mechanism for preventing the lethality of anthrax, a high-throughput screening experiment based on lf-catalyzed cleavage of a fluorescent substrate was performed to identify novel inhibitors of lf. the rna-targeting antibiotics, neomycin b and some synthetic dimeric aminoglycosides, were ...	2004	15080670
the plague under marcus aurelius and the decline and fall of the roman empire.	the roman empire of the second century was a superpower that, in relative terms, dominated its world as much as the united states does today. in 166 ad, a plague broke out od pandemic proportions. the pandemic ravaged the entire extent of the roman empire, from its eastern frontiers in iraq to its western frontiers on the rhine river and gaul, modern france, and western germany. the disease is identified most often as smallpox, but it may have been anthrax. the study of bacterial dna may enable ...	2004	15081505
atypical pathogens and challenges in community-acquired pneumonia.	atypical organisms such as mycoplasma pneumoniae, chlamydia pneumoniae, and legionella pneumophila are implicated in up to 40 percent of cases of community-acquired pneumonia. antibiotic treatment is empiric and includes coverage for both typical and atypical organisms. doxycycline, a fluoroquinolone with enhanced activity against streptococcus pneumoniae, or a macrolide is appropriate for outpatient treatment of immunocompetent adult patients. hospitalized adults should be treated with cefotaxi ...	2004	15086042
detection of antibodies to squalene: iii. naturally occurring antibodies to squalene in humans and mice.	an elisa-based assay is described for the measurement of antibodies to squalene (sqe) in human serum and plasma. the assay was adapted from the previously described assay for murine antibodies to sqe (j. immunol. methods 267 (2002) 119). like the murine sqe antibody assay, the human antibody assay used sterile cell culture 96-well plates coated with sqe (20 nmol/well). phosphate-buffered saline (pbs)-0.5% casein was used as both a blocking agent and dilution buffer. the assay has a high through- ...	2004	15087221
tracking human antigen-specific memory b cells: a sensitive and generalized elispot system.	in the interest of better understanding the role of human memory b cells in protection against disease, we developed an assay to quantitate antigen-specific memory b cells in human blood. this assay utilizes a 6-day polyclonal stimulation of pbmc followed by an antigen-specific elispot for the detection of memory b cells that have differentiated into antibody secreting cells (asc) in vitro. we have used this assay to demonstrate that the anthrax vaccine (ava; biothrax) elicits a substantial popu ...	2004	15087226
anthrax versus the flu.	as state governments in the united states slash their public health budgets, federal money is pouring in for bioterror preparedness.	2004	15088680
isolation of a minireplicon of the virulence plasmid pxo2 of bacillus anthracis and characterization of the plasmid-encoded reps replication protein.	a minireplicon of plasmid pxo2 of bacillus anthracis was isolated by molecular cloning in escherichia coli and shown to replicate in b. anthracis, bacillus cereus, and bacillus subtilis. the pxo2 replicon included (i) an open reading frame encoding the putative reps replication initiation protein and (ii) the putative origin of replication. the reps protein was expressed as a fusion with the maltose binding protein (mbp) at its amino-terminal end and purified by affinity chromatography. electrop ...	2004	15090513
principles of 3' splice site selection and alternative splicing for an unusual group ii intron from bacillus anthracis.	we investigated the self-splicing properties of two introns from the bacterium bacillus anthracis. one intron (b.a.i1) splices poorly in vitro despite having typical structural motifs, while the second (b.a.i2) splices well while having apparently degenerated features. the spliced exons of b.a.i2 were sequenced, and splicing was found to occur at a 3' site shifted one nucleotide from the expected position, thus restoring missing gamma-gamma' and ibs3-ebs3 pairings, but leaving the two conserved ...	2004	15100440
the kindest cuts of all: crystal structures of kex2 and furin reveal secrets of precursor processing.	pro-hormone or pro-protein convertases are a conserved family of eukaryotic serine proteases found in the secretory pathway. these endoproteases mature precursors for peptides and proteins that perform a wide range of physiologically important and clinically relevant functions. the first member of this family to be identified was kex2 in the yeast saccharomyces cerevisiae. one mammalian member of this family - furin - is responsible for processing substrates that include insulin pro-receptor, hu ...	2004	15102434
macrophages release tumor necrosis factor alpha and interleukin-12 in response to intracellular bacillus anthracis spores.	herein we report that infection of a murine macrophage cell line with bacillus anthracis results in the production of tumor necrosis factor alpha and interleukin-12 (il-12). when infected with b. anthracis spores in combination with lipopolysaccharide, macrophages release increased amounts of il-12. we found no evidence of inhibition of cytokine responses in macrophages infected with b. anthracis spores.	2004	15102824
the internet as a vehicle to communicate health information during a public health emergency: a survey analysis involving the anthrax scare of 2001.	the recent public health risks arising from bioterrorist threats and outbreaks of infectious diseases like sars (severe acute respiratory syndrome) highlight the challenges of effectively communicating accurate health information to an alarmed public.	2004	15111274
bacillus anthracis incident, kameido, tokyo, 1993.		2004	15112666
evaluation of bacillus anthracis extractable antigen for testing anthrax immunity.	three extractable bacillus anthracis cell-wall-associated antigens were evaluated for potential use as skin testing agents, and as possible candidates for in-vitro diagnosis of anthrax immunity. anthraxin and a partially purified extractable antigen (eap) were produced from avirulent b. anthracis strain 34f2 (sterne). the thermoextractable antigen used for the ascoli reaction was obtained commercially. guinea-pigs were immunised and boosted several times subcutaneously with the sterne live veter ...	2004	15113319
one-year health assessment of adult survivors of bacillus anthracis infection.	little is known about potential long-term health effects of bioterrorism-related bacillus anthracis infection.	2004	15113818
anthrax toxin: can a little be a good thing?		2004	15116717
treatments for patients exposed to bioterrorism agents.		2004	15117009
visual diagnosis: an infant who has a red papule on a swollen, tender arm.		2004	15121911
an extracytoplasmic-function sigma factor is involved in a pathway controlling beta-exotoxin i production in bacillus thuringiensis subsp. thuringiensis strain 407-1.	beta-exotoxin i is an insecticidal nucleotide analogue secreted by various bacillus thuringiensis strains. in this report, we describe the characterization and transcriptional analysis of a gene cluster, designated sigw-ecfx-ecfy, that is essential for beta-exotoxin i production in b. thuringiensis subsp. thuringiensis strain 407-1. in this strain, the disruption of the sigw cluster resulted in nontoxic culture supernatants. sigw encodes a protein of 177 residues that is 97 and 94% identical to ...	2004	15126472
low-level detection of a bacillus anthracis simulant using love-wave biosensors on 36 degrees yx litao3.	we present an acoustic love-wave biosensor for detection of the bacillus anthracis simulant, bacillus thuringiensis at or below inhalational infectious levels. the present work is an experimental study of 36 degrees yx cut litao3 based love-wave devices for detection of pathogenic spores in aqueous conditions. given that the detection limit (d1) of love-wave-based sensors is a strong function of the overlying waveguide, two waveguide materials have been investigated, which are polyimide and poly ...	2004	15128104
bioshield defence programme set to fund anthrax vaccine.		2004	15129240
gastrointestinal adverse reactions following anthrax vaccination: an analysis of the vaccine adverse events reporting system (vaers) database.	the institute of medicine (iom) of the united states academy of sciences in 2000 encouraged the evaluation of active long-term monitoring studies of large populations to further evaluate the relative safety of anthrax vaccine. anthrax is a deadly bacterial infectious disease that currently has been engineered as a biological warfare agent. the vaccine produced against anthrax is a cell-free crude culture of the various toxin components of the natural disease. the u.s. military current goal is to ...	2004	15143911
chemical screening by mass spectrometry to identify inhibitors of anthrax lethal factor.	mass spectrometry (ms) analysis is applicable to a broad range of biological analytes and has the important advantage that it does not require analytes to be labeled. a drawback of ms methods, however, is the need for chromatographic steps to prepare the analyte, precluding ms from being used in chemical screening and rapid analysis. here, we report that surfaces that are chemically tailored for characterization by matrix-assisted laser-desorption ionization time-of-flight ms eliminate the need ...	2004	15146199
anthrax protective antigen: efficiency of translocation is independent of the number of ligands bound to the prepore.	heptameric anthrax protective antigen (termed prepore), which assembles at the mammalian cell surface, competitively binds edema factor (ef) and/or lethal factor (lf). it then transports them to an acidic intracellular compartment and mediates their translocation across the membrane to the cytosol. steric constraints limit to three the number of molecules of ef and/or lf that can bind simultaneously to prepore. to determine whether the number of ligand molecules bound per heptamer affects the ef ...	2004	15147218
in vivo bacillus anthracis gene expression requires pagr as an intermediate effector of the atxa signalling cascade.	transcription of the major bacillus anthracis virulence genes is triggered by co2, a signal mimicking the host environment. a 182-kb plasmid, pxo1, carries the anthrax toxin genes and the genes responsible for their regulation of transcription, namely atxa and, pagr, the second gene of the pag operon. atxa has major effects on the physiology of b. anthracis. it coordinates the transcription activation of the toxin genes with that of the capsule biosynthetic enzyme operon, located on the second v ...	2004	15149039
specificity of an immunochromatographic test for anthrax.	to evaluate the specificity of an immunochromatographic test (ict) for anthrax in cattle.	2004	15149073
distinct mutations in plcr explain why some strains of the bacillus cereus group are nonhemolytic.	bacillus thuringiensis, bacillus cereus, and bacillus anthracis are closely related species belonging to the bacillus cereus group. b. thuringiensis and b. cereus generally produce extracellular proteins, including phospholipases and hemolysins. transcription of the genes encoding these factors is controlled by the pleiotropic regulator plcr. disruption of plcr in b. cereus and b. thuringiensis drastically reduces the hemolytic, lecithinase, and cytotoxic properties of these organisms. b. anthra ...	2004	15150241
novel oligosaccharide side chains of the collagen-like region of bcla, the major glycoprotein of the bacillus anthracis exosporium.	spores of bacillus anthracis, the causative agent of anthrax, are enclosed by a prominent loose fitting layer called the exosporium. the exosporium consists of a basal layer and an external hairlike nap. the filaments of the nap are composed of a highly immunogenic glycoprotein called bcla, which has a long, central collagen-like region with multiple xxg repeats. most of the triplet repeats are ptg, and nearly all of the triplet repeats contain a threonine residue, providing multiple potential s ...	2004	15152001
structural and kinetic analyses of the interaction of anthrax adenylyl cyclase toxin with reaction products camp and pyrophosphate.	anthrax edema factor (ef) raises host intracellular camp to pathological levels through a calcium-calmodulin (cam)-dependent adenylyl cyclase activity. here we report the structure of ef.cam in complex with its reaction products, camp and pp(i). mutational analysis confirmed the interaction of ef with camp and pp(i) as depicted in the structural model. while both camp and pp(i) have access to solvent channels to exit independently, pp(i) is likely released first. ef can synthesize atp from camp ...	2004	15131111
regionalization of bioterrorism preparedness and response.		2004	15133889
bioterrorism: the need to be prepared.	postal distribution of anthrax spores in october 2001 in the usa resulted in cases of pulmonary anthrax. in consequence, interest and concern about terrorist attacks on civilian populations using biological weapons have increased, particularly when one recent authoritative assessment suggested that an attack using some form of unconventional weapon on a western city was 'inevitable'. this article reviews the steps necessary to minimise the probability of a successful attack. despite best endeavo ...	2004	15139737
human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed.	background: potent anthrax toxin neutralizing human monoclonal antibodies were generated from peripheral blood lymphocytes obtained from anthrax vaccine adsorbed (ava) immune donors. the anti-anthrax toxin human monoclonal antibodies were evaluated for neutralization of anthrax lethal toxin in vivo in the fisher 344 rat bolus toxin challenge model. methods: human peripheral blood lymphocytes from ava immunized donors were engrafted into severe combined immunodeficient (scid) mice. vaccination wi ...	2004	15140257
a second-generation anthrax "smoke detector".		2004	15154269
enhancement of anthrax lethal toxin cytotoxicity: a subset of monoclonal antibodies against protective antigen increases lethal toxin-mediated killing of murine macrophages.	we investigated the ability of using monoclonal antibodies (mabs) against anthrax protective antigen (pa), an anthrax exotoxin component, to modulate exotoxin cytotoxic activity on target macrophage cell lines. anthrax pa plays a critical role in the pathogenesis of bacillus anthracis infection. pa is the cell-binding component of the two anthrax exotoxins: lethal toxin (letx) and edema toxin. several mabs that bind the pa component of letx are known to neutralize letx-mediated killing of target ...	2004	15155630
contribution of immunological memory to protective immunity conferred by a bacillus anthracis protective antigen-based vaccine.	protective antigen (pa)-based vaccination is an effective countermeasure to anthrax infection. while neutralizing anti-pa antibody titers elicited by this vaccine serve as good correlates for protection against anthrax (s. reuveny, m. d. white, y. y. adar, y. kafri, z. altboum, y. gozes, d. kobiler, a. shafferman, and b. velan, infect. immun. 69:2888-2893, 2001), no data are available on the contribution of the immunological memory for pa itself to protection. we therefore developed a guinea pig ...	2004	15155654
identification of anthrax toxin genes in a bacillus cereus associated with an illness resembling inhalation anthrax.	bacillus anthracis is the etiologic agent of anthrax, an acute fatal disease among mammals. it was thought to differ from bacillus cereus, an opportunistic pathogen and cause of food poisoning, by the presence of plasmids pxo1 and pxo2, which encode the lethal toxin complex and the poly-gamma-d-glutamic acid capsule, respectively. this work describes a non-b. anthracis isolate that possesses the anthrax toxin genes and is capable of causing a severe inhalation anthrax-like illness. although init ...	2004	15155910