Publications

protection from anthrax toxin-mediated killing of macrophages by the combined effects of furin inhibitors and chloroquine.	cell surface proteolytic processing of anthrax protective antigen by furin or other furin-related proteases is required for its oligomerization, endocytosis, and function as a translocon for anthrax lethal and edema factors. countering toxin lethality is essential to developing effective chemotherapies for anthrax infections that have proceeded beyond the stage at which antibiotics are effective. the primary target for toxin is the macrophage, which can be killed by lethal factor via both necrot ...	2005	16127065
anthrax vaccines: a development update.	the current human anthrax vaccines licensed in the us and uk consist of aluminum hydroxide-adsorbed or alum-precipitated culture supernatant material from fermentor cultures of toxigenic noncapsulated strains of bacillus anthracis. the threat of b. anthracis being used as a biowarfare agent has led to a wider usage of these vaccines, which has heightened concerns regarding the need for frequent boosters and the occasional local reactogenicity associated with vaccination. these concerns have prov ...	2005	16128606
rational monoclonal antibody development to emerging pathogens, biothreat agents and agents of foreign animal disease: the antigen scale.	many factors influence the choice of methods used to develop antibody to infectious agents. in this paper, we review the current status of the main technologies used to produce monoclonal antibodies (mabs) from the b cells of antigen-sensitized animals. while companies are adopting advanced high-throughput methods, the major technologies used by veterinary and medical research laboratories are classical hybridoma fusion and recombinant library selection techniques. these methods have inherent ad ...	2005	16129340
structural basis for the interaction of bordetella pertussis adenylyl cyclase toxin with calmodulin.	cyaa is crucial for colonization by bordetella pertussis, the etiologic agent of whooping cough. here we report crystal structures of the adenylyl cyclase domain (acd) of cyaa with the c-terminal domain of calmodulin. four discrete regions of cyaa bind calcium-loaded calmodulin with a large buried contact surface. of those, a tryptophan residue (w242) at an alpha-helix of cyaa makes extensive contacts with the calcium-induced, hydrophobic pocket of calmodulin. mutagenic analyses show that all fo ...	2005	16138079
crystal structure of pure (ba0288) from bacillus anthracis at 1.8 a resolution.		2005	16138311
biodefense. microbiologist resigns after pitch for antianthrax product.		2005	16141039
receptor-specific requirements for anthrax toxin delivery into cells.	the three proteins that constitute anthrax toxin self-assemble into toxic complexes after one of these proteins, protective antigen (pa), binds to tumor endothelial marker 8 (tem8) or capillary morphogenesis protein 2 (cmg2) cellular receptors. the toxin receptor complexes are internalized, and acidic endosomal ph triggers pore formation by pa and translocation of the catalytic subunits into the cytosol. in this study we show that the ph threshold for conversion of the pa prepore to the pore and ...	2005	16141341
no evidence of a mild form of inhalational bacillus anthracis infection during a bioterrorism-related inhalational anthrax outbreak in washington, d.c., in 2001.	the mail-related dispersal of bacillus anthracis spores in the washington, d.c., area during october 2001 resulted in 5 confirmed cases of inhalational anthrax. we identified an additional 144 ill persons who were potentially exposed to aerosolized spores and whose symptoms were compatible with early inhalational anthrax but whose clinical course and nonserologic laboratory evaluation revealed no evidence for b. anthracis infection. we hypothesized that early antibiotic use could have decreased ...	2005	16142664
cutaneous anthrax.		2005	16143204
structure of purine nucleoside phosphorylase (deod) from bacillus anthracis.	protein structures from the causative agent of anthrax (bacillus anthracis) are being determined as part of a structural genomics programme. amongst initial candidates for crystallographic analysis are enzymes involved in nucleotide biosynthesis, since these are recognized as potential targets in antibacterial therapy. purine nucleoside phosphorylase is a key enzyme in the purine-salvage pathway. the crystal structure of purine nucleoside phosphorylase (deod) from b. anthracis has been solved by ...	2005	16511068
structures of two superoxide dismutases from bacillus anthracis reveal a novel active centre.	the ba4499 and ba5696 genes of bacillus anthracis encode proteins homologous to manganese superoxide dismutase, suggesting that this organism has an expanded repertoire of antioxidant proteins. differences in metal specificity and quaternary structure between the dismutases of prokaryotes and higher eukaryotes may be exploited in the development of therapeutic antibacterial compounds. here, the crystal structure of two mn superoxide dismutases from b. anthracis solved to high resolution are repo ...	2005	16511113
[toxin-neutralizing monoclonal antibodies to the different domains of anthrax protective antigen].	anthrax toxin from bacillus anthracis is a three-component toxin consisting of lethal factor (lf), edema factor (ef), and protective antigen (pa). pa binds to target cells and transports lf or ef into the cell cytosol where they carry out their enzymatic functions. pa can induce protective immunity to the infection of the bacterium and is the major component in the only anthrax vaccine approved by fda of usa. mouse hybridoma clones specifically secreting anti-pa monoclonal antibodies (mabs) were ...	2005	16496709
[virulotypes of bacillus anthracis strains isolated in poland].	bacillus anthracis--the causative agent of anthrax--possesses several virulence genes located in the chromosome as well as in two b. anthracis virulence plasmids: pxo1 and pxo2. in the presented study, we determined occurrence of six virulence markers located in the virulence plasmids (capa, capb, capc, paga, lef and cya) for capsule and toxin production together with virulence-associated gene gerxa and chromosomal gene sap, which are responsible for germination and s-layer biosynthesis respecti ...	2005	16494203
[application of the multiplex pcr and pcr-rflp method in the identification of the bacillus anthracis].	the aim of this study was to apply the multiplex pcr and pcr-rflp method for the identification of the b. anthracis strains and to distinguish those bacteria from other members of the bacillus cereus group. the multiplex pcr method enables to detect the virulence factors, i.e. the toxin and the capsule in b. anthracis strains. to do that, the authors have used 5 primer pairs specific for the fragments of lef, cya, pag genes which are present in the pxo1 plasmid and encode the toxin, the cap gene ...	2005	16494204
[the discovery of the tubercle bacillus by robert koch: a milestone for 123 years].	the discovery of the tubercle bacillus and its causal relationship to tuberculosis by the general practitioner robert koch (1843-1910) in 1882 was truly a revolutionary discovery by a pioneer. this discovery was very well-documented, making use of optical equipment that had just appeared on the market, and was accomplished in his own home without outside support. in spite of the publication of the discovery in a german medical periodical with only local circulation, the entire scientific world q ...	2005	16402521
surface-enhanced raman spectroscopy biosensors: excitation spectroscopy for optimisation of substrates fabricated by nanosphere lithography.	in the 28 years since its discovery, surface-enhanced raman scattering (sers) has progressed from model system studies of pyridine on a roughened silver electrode to state-of-the-art surface science studies and real-world sensing applications. each year, the number of sers publications increases as nanoscale material design techniques advance and the importance of trace analyte detection increases. to achieve the lowest limits of detection, both the relationship between surface nanostructure and ...	2005	16441180
[bioterrorism agents: getting ready for the unthinkable].	the september 11, 2001 terrorist attacks in the u.s.a. demonstrated our vulnerability to terrorist raids. furthermore, in the same year inhalational anthrax cases in humans caused by the intentional [corrected] release of bacillus anthracis spores via the u.s.a. postal system inflicted a lot of panic and terror over the civilian population. the succeeding terrorist events scattered in several other countries are continuous reminders of our frailness [corrected] and of the risk that terrorists at ...	2005	16419465
cutaneous reactions in nuclear, biological and chemical warfare.	nuclear, biological and chemical warfare have in recent times been responsible for an increasing number of otherwise rare dermatoses. many nations are now maintaining overt and clandestine stockpiles of such arsenal. with increasing terrorist threats, these agents of mass destruction pose a risk to the civilian population. nuclear and chemical attacks manifest immediately while biological attacks manifest later. chemical and biological attacks pose a significant risk to the attending medical per ...	2005	16394378
an outbreak of cutaneous anthrax in a non-endemic district--visakhapatnam in andhra pradesh.	anthrax is a disease of herbivorous animals, and humans incidentally acquire the disease by handling infected dead animals and their products. sporadic cases of human anthrax have been reported from southern india.	2005	16394383
protecting public health in the age of bioterrorism surveillance: is the price right?	millions of dollars have been spent improving the bioterrorism surveillance capabilities of the public health system. yet relatively little attention has been paid to the benefits that such expenditures yield. to assess the impact of an aerosol release of bacillus anthracis, this article collects the available evidence on the potential benefits of environmental detection relative to the costs of a bioterrorist attack like the one in 2001, which occurred in the absence of any such detection. the ...	2005	16392626
petrobactin is the primary siderophore synthesized by bacillus anthracis str. sterne under conditions of iron starvation.	the siderophores of bacillus anthracis are critical for the pathogen's proliferation and may be necessary for its virulence. bacillus anthracis str. sterne cells were cultured in iron free media and the siderophores produced were isolated and purified using a combination of xad-2 resin, reverse-phase fplc, and size exclusion chromatography. a combination of 1h and 13c nmr spectroscopy, uv spectroscopy and esi-ms/ms fragmentation were used to identify the primary siderophore as petrobactin, a cat ...	2005	16388397
evaluation of public health interventions for anthrax: a report to the secretary's council on public health preparedness.	to aid in understanding how best to respond to a bioterror anthrax attack, we analyze a system of differential equations that includes a disease progression model, a set of spatially distributed queues for distributing antibiotics, and vaccination (pre-event and/or post-event). we derive approximate expressions for the number of casualties as a function of key parameters and management levers, including the time at which the attack is detected, the number of days to distribute antibiotics, the a ...	2005	16366844
postexposure management and treatment of anthrax in dogs--executive councils of the american academy of veterinary pharmacology and therapeutics and the american college of veterinary clinical pharmacology.	dogs are generally at low risk of developing disease following exposure to anthrax. when disease does occur, it appears associated with oral exposure to the bacteria leading to massive swelling of the head, neck, and mediastinal regions. death is due to toxemia and shock. for animals at high risk, such as search and rescue dogs with a known exposure, doxycycline at 5 mg/kg orally once daily for 45 to 60 days is suggested as a prophylactic treatment. additional information on the diagnosis, preve ...	2005	16353908
anthrax in eastern turkey, 1992-2004.	we investigated animal and human anthrax cases during a 13-year period in eastern turkey. from 1992 to 2004, a total of 464 animal and 503 human anthrax cases were detected. most cases occurred in summer. anthrax remains a health problem in eastern turkey, and preventive measures should be taken.	2005	16485484
the role of lumbar puncture as a diagnostic tool in 2005.	analysis of cerebrospinal fluid (csf) obtained by lumbar puncture (lp) is fundamental to the management of inflammatory disease of the central nervous system (cns), particularly that due to infection. this review summarises the role of lumbar puncture, anatomy and pathophysiology of csf, techniques of obtaining csf, indications, contraindications and complications of lp, methods of analysis and some of the implications of specific changes in csf. the cns is protected by unique immunological barr ...	2005	16545048
old legacies and new paradigms: confusing "research" and "treatment" and its consequences in responding to emergent health threats.		2005	16538801
plasmid vaccines and therapeutics: from design to applications.	in the late 1980s, vical and collaborators discovered that the injection into tissues of unformulated plasmid encoding various proteins resulted in the uptake of the plasmid by cells and expression of the encoded proteins. after this discovery, a period of technological improvements in plasmid delivery and expression and in pharmaceutical and manufacturing development was quickly followed by a plethora of human clinical trials testing the ability of injected plasmid to provide therapeutic benefi ...	2005	16568888
preventive and therapeutic effects of alpha-acid glycoprotein in mice infected with b. anthracis.	we studied the effects of alpha1-acid glycoprotein preparations on the survival rate of balb/c mice infected with the lethal dose of b. anthracis sti-1. apart from native alpha1-acid glycoprotein from donor blood, we studied 3 glycoforms differing in the affinity for concanavalin a and structure of carbohydrate chains. the protective effect of alpha1-acid glycoprotein preparations did not depend on its dose and was observed 3 months after treatment (0.3 mg per mouse). the protective effect was r ...	2005	16671576
syndromic surveillance in bioterrorist attacks.		2005	16673516
bioterrorism: is it a real threat?	the geneva protocol of 1925 commits the signatory nations to refraining from the use of biological weapons. however, the terrorist assaults of september 2001 and, subsequently, the anthrax-containing letters are cause for great concerns: new threats to the security of nations are expected, as terrorist organizations seem to increasingly explore novel ways of spreading terror. in this context, naturally emerging diseases such as sars, monkeypox or west nile fever assume new importance because it ...	2005	15349775
the effect of anthrax bioterrorism on emergency department presentation.	from september through december 2001, 22 americans were diagnosed with anthrax, prompting widespread national media attention and public concern over bioterrorism. the purpose of this study was to determine the effect of the threat of anthrax bioterrorism on patient presentation to a west coast emergency department (ed).	2005	20847852
towards advanced chemical and biological nanosensors-an overview.	this paper reviews recent developments in the design and application of two types of optical nanosensor, those based on: (1) localized surface plasmon resonance (lspr) spectroscopy and (2) surface-enhanced raman scattering (sers). the performance of these sensors is discussed in the context of biological and chemical sensing. the first section addresses the lspr sensors. arrays of nanotriangles were evaluated and characterized using realistic protein/ligand interactions. isolated, single nanopar ...	2005	18970187
detection of bacillus subtilis spores in water by means of broadband coherent anti-stokes raman spectroscopy.	broadband coherent anti-stokes raman scattering (cars) spectroscopy is used for detection of bacterial spores in aqueous solution. polarization cars spectroscopy is employed to suppress the non-resonant background. cars spectrum recorded in the spectral region from 700 to 1900 cm(-1) exhibits all the characteristic features of spontaneous raman spectrum taken for a solid powder and resembles that one of the dipicolinic acid, which is considered to be the major component of bacterial spores, incl ...	2005	19503156
enhanced optical chromatography in a pdms microfluidic system.	the purely refractive index driven separation of uniformly sized polystyrene, n = 1.59 and poly(methylmethacrylate), n = 1.49 in an optical chromatography system has been enhanced through the incorporation of a custom poly(dimethysiloxane) (pdms) microfluidic system. a customized channel geometry was used to create separate regions with different linear flow velocities tailored to the specific application. these separate flow regions were then used to expose the entities in the separation to dif ...	2005	19503255
the rapidly advancing field of biodefense benefits many other, critical public health concerns.	extract: in 2001, the public was introduced to one of the deadliest of biowarfare agents -- bacillus anthracis -- the bacterium that causes anthrax. at the time, it was unimaginable that one might come into contact with such a deadly pathogen by simply opening the mail. today anthrax is a nearly ubiquitous household word. this single act of bioterrorism had a profound effect in that it clearly demonstrated that even a small-scale attack could incur huge repercussions: the loss of life, the need ...	2005	20704875
avidin/biotin-liposome system injected in the pleural space for drug delivery to mediastinal lymph nodes.	the objective of this study was to develop a more effective liposome-based method for delivering drugs to mediastinal nodes. nodal uptake was determined after intrapleural injection of the avidin/biotin-liposome system in normal rats. the effect of injection sequence (avidin injected 2 h before biotin-liposomes and vice versa), volume injected, and administered dose of the agents is described. pharmacokinetics of the avidin/biotin-liposome system was monitored with scintigraphic imaging by label ...	2004	15349969
the nhea component of the non-hemolytic enterotoxin of bacillus cereus is produced by bacillus anthracis but is not required for virulence.	a non-hemolytic enterotoxin (nhe) is one of the two enterotoxins thought to cause diarrhea produced by bacillus cereus. we identified genes in bacillus anthracis homologous to the b. cereus nheab genes encoding proteins of the nhe complex. the nhea component was detected immunologically in culture supernatants from b. anthracis but not from a nhea(-) mutant, suggesting that b. anthracis produces and secretes the nhea subunit of nhe. a nhea deletion mutant was not attenuated in the guinea pig sug ...	2004	15351038
identification of bacillus anthracis proteins associated with germination and early outgrowth by proteomic profiling of anthrax spores.	the use of anthrax spores as a bioweapon has spurred efforts aimed at identifying key proteins expressed in bacillus anthracis. because spore germination and outgrowth occur prior to and are required for disease manifestations, blocking germination and early outgrowth with novel vaccines or inhibitors targeting critical b. anthracis germination and outgrowth-associated factors is a promising strategy in mitigating bioterror. by screening 587 paired protein spots that were isolated from dormant a ...	2004	15352240
binary bacterial toxins: biochemistry, biology, and applications of common clostridium and bacillus proteins.	certain pathogenic species of bacillus and clostridium have developed unique methods for intoxicating cells that employ the classic enzymatic "a-b" paradigm for protein toxins. the binary toxins produced by b. anthracis, b. cereus, c. botulinum, c. difficile, c. perfringens, and c. spiroforme consist of components not physically associated in solution that are linked to various diseases in humans, animals, or insects. the "b" components are synthesized as precursors that are subsequently activat ...	2004	15353562
[monoclonal antibodies to b.anthracis protective antigen are capable to neutralize and to enhance the anthrax lethal toxin action in vitro].	anthrax belongs to highly dangerous infections of man and animals. no effective treatment methods for pulmonary types of the disease have been yet developed. the existing anthrax vaccines were designed decades ago and need improvement to fit the large-scale vaccination of population. at the same time, the immunological properties of the anthrax vaccine main component, i.e. of the protective agent, have been poorly studied. we obtained, within the present case study, a panel of mouse monoclonal a ...	2004	15354937
stevens-johnson syndrome after immunization with smallpox, anthrax, and tetanus vaccines.	a 19-year-old male military recruit developed erythema multiforme 20 days after receiving a triad of vaccinations: smallpox (vaccinia virus), anthrax, and tetanus. over the course of a few days, the erythema multiforme evolved into stevens-johnson syndrome, associated with widespread bullae, stomatitis, conjunctivitis, and fever. after 7 days of conservative management, the patient's signs and symptoms improved. this case serves as a timely reminder of a severe and potentially life-threatening c ...	2004	15357044
anthrax exposure--stay alert, act swiftly.	initiating appropriate antibiotic therapy as soon as anthrax infection is suspected is not only acceptable but is also justified by the outcomes of the 2001 anthrax cases.	2004	15357168
cross-inhibition between furin and lethal factor inhibitors.	bacillus anthracis synthesizes two toxins composed of the three proteins: protective antigen (pa), lethal factor (lf), and edema factor (ef). the cleavage of pa on the cell surface by the convertase furin leads to the translocation of lf and ef into the cytosol. we have investigated the cross-inhibitory activities of the furin inhibitors hexa-d-arginine amide (d6r) and nona-d-arginine amide (d9r), which block the proteolytic activation of pa; and of the lf inhibitor in-2-lf, a peptide hydroxamat ...	2004	15358148
mass value assignment of total and subclass immunoglobulin g in a human standard anthrax reference serum.	an anti-anthrax vaccine adsorbed (anti-ava) standard human reference serum pool, avr414, has been prepared, and the total and protective antigen (pa)-specific immunoglobulin g (igg) were quantified. avr414 was prepared by plasmapheresis of healthy adults who had received a minimum of four subcutaneous injections of ava. mass values (in milligrams per milliliter) for total igg and igg subclasses 1 to 4 were determined by radial immunodiffusion. anti-pa-specific igg assignment (in micrograms per m ...	2004	15358653
identifying respiratory findings in emergency department reports for biosurveillance using metamap.	clinical conditions described in patients' dictated reports are necessary for automated detection of patients with respiratory illnesses such as inhalational anthrax and pneumonia. we applied metamap to emergency department reports to extract a set of 71 clinical conditions relevant to detection of a lower respiratory outbreak. we indexed umls terms in emergency department reports with metamap, filtered the indexed output with a specialized lexicon of umls terms for the domain, and mapped the cl ...	2004	15360860
the rods open source project: removing a barrier to syndromic surveillance.	the goal of the real-time outbreak and disease surveillance (rods) open source project is to accelerate deployment of computer-based syndromic surveillance. to this end, the project has released the rods software under the gnu general public license and created an organizational structure to catalyze its development. this paper describes the design of the software, requested extensions, and the structure of the development effort.	2004	15361001
characterization of the human immune response to the uk anthrax vaccine.	the anthrax bipartite lethal toxin (protective antigen (pa) and lethal factor (lf))-specific antibody responses of humans receiving the uk licensed anthrax vaccine were determined. the pa-specific igg response peaked two weeks post immunization and fell back to pre-boost levels by week 12. the heterogeneity of the host population modulated the extent of the pa-specific antibody response. significantly lower levels of lf-specific antibodies were also detected. vaccinated individuals recognized th ...	2004	15364114
[use of anthrax as biological weapon].	we describe the epidemiology of anthrax and the several human disease aspect, by spores penetration through the skin or by inhalation or ingestion, and the action of exotoxin secreted by b. anthracis. we detail pulmonary anthrax that could derive from intentional release of endospore as biological weapon. laboratory diagnosis of cereus group with cultural, fda and pcr methods are reported. environment disinfection, vaccination, antibiotic prophylaxis, passive antibody administration and treatmen ...	2004	15366519
antitoxins: novel strategies to target agents of bioterrorism.	never before has there been such a strong possibility that biological agents might be used indiscriminately on civilian populations. this review focuses on the use of antitoxins - antibodies, receptor decoys, dominant-negative inhibitors of translocation, small-molecule inhibitors and substrate analogues - to counteract those biological weapons for which toxins are an important mechanism of disease pathogenesis.	2004	15372082
knock-on effect of anthrax lethal toxin on macrophages potentiates cytotoxicity to endothelial cells.	herein we report the knock-on cytotoxic effect of lethal toxin (letx) on human umbilical vascular endothelial cells (huvecs). huvecs were treated either directly with letx or indirectly with letx conditioned medium (letxcm) prepared from raw264.7 macrophage cells. cytotoxicity assays were done on huvecs and a549 cells using letx. huvecs were more susceptible to letx (61-74% survivals) as compared to a549 cells (83-94% survivals, p < 0.005). however, letxcm from raw264.7 further potentiated killi ...	2004	15374005
protein translocation through anthrax toxin channels formed in planar lipid bilayers.	the 63-kda fragment of the protective antigen (pa) component of anthrax toxin forms a heptameric channel, (pa63)7, in acidic endosomal membranes that leads to the translocation of edema factor (ef) and lethal factor (lf) to the cytosol. it also forms a channel in planar phospholipid bilayer membranes. what role does this channel play in the translocation of ef and lf? we report that after the 263-residue n-terminal piece of lf (lfn) binds to its receptor on the (pa63)7 channel and its n-terminal ...	2004	15377524
a targeted proteomics approach to the rapid identification of bacterial cell mixtures by matrix-assisted laser desorption/ionization mass spectrometry.	a proteomic approach to the rapid identification of bacteria is presented, which relies on the solubilization of a limited number of proteins from intact cells combined with on-probe tryptic digestion. within 20 min, complete cleavage products of a limited set of bacterial proteins with molecular masses of about 4-125 kda were obtained by on-probe digestion with immobilized trypsin. bacterial peptides suitable for unimolecular decomposition analysis were generated within 5 min, and the sequence ...	2004	15378756
mass violence and early mental health intervention: a proposed application of best practice guidelines to chemical, biological, and radiological attacks.	based on past episodes, there will be psychological sequelae to chemical, biological, and radiological attacks. some of the psychological morbidity should be able to be ameliorated through planning and appropriate early intervention. key components of early intervention are illustrated following a hypothetical scenario of a bomb and anthrax threat near the pentagon. many of these components, such as monitoring clear, consistent messages about health risks, are provided by physicians or politicia ...	2004	15379065
pharmacokinetic-pharmacodynamic analysis of fluoroquinolones against bacillus anthracis.	based on the pharmacokinetic-pharmacodynamic (pk-pd) parameters of ciprofloxacin in rhesus monkeys, the efficacies of levofloxacin, sparfloxacin, norfloxacin, and tosufloxacin against anthrax in humans were examined. the optimal pk-pd parameter for the prophylaxis or treatment of infection with bacillus anthracis is not clearly defined. to evaluate the efficacy of fluoroquinolones against anthrax, pk-pd parameters and the protein-binding effect of fluoroquinolones are used. b. anthracis is very ...	2004	15160302
molecular beacons for multiplex detection of four bacterial bioterrorism agents.		2004	15161722
cutaneous anthrax.		2004	15163220
post-exposure prophylaxis of systemic anthrax in mice and treatment with fluoroquinolones.	to compare the fluoroquinolones gatifloxacin and moxifloxacin with ciprofloxacin for post-exposure prophylaxis of systemic anthrax in a balb/c mouse model.	2004	15163650
aids-vaccine firm needled by stock-exchange rules.		2004	15164031
geobacillus stearothermophilus v ubie gene product is involved in the evolution of dimethyl telluride in escherichia coli k-12 cultures amended with potassium tellurate but not with potassium tellurite.	a 3.8-kb fragment of chromosomal dna of geobacillus stearothermophilus v cloned in psp72 (p1vh) confers resistance to potassium tellurite (k(2)teo(3)) and to potassium tellurate (k(2)teo(4)) when the encoded genes are expressed in escherichia coli k-12. the nt sequence of the cloned fragment predicts three orfs of 780, 399, and 600 bp, whose encoded protein products exhibit about 80% similarity with the sumt methyltransferase and the btur protein of bacillus megaterium, and with the ubie methylt ...	2004	15164269
icbs: a database of interactions between protein chains mediated by beta-sheet formation.	interchain beta-sheet (icbs) interactions occur widely in protein quaternary structures, interactions between proteins and protein aggregation. these interactions play a central role in many biological processes and in diseases ranging from aids and cancer to anthrax and alzheimer's.	2004	15166020
message from the editor.		2004	15236393
development of evaluation procedures for local exhaust ventilation for united states postal service mail-processing equipment.	researchers from the national institute for occupational safety and health (niosh) have conducted several evaluations of local exhaust ventilation (lev) systems for the united states postal service (usps) since autumn 2001 when (a) terrorist(s) employed the mail system for acts of bioterrorism. as a part of the usps 2002 emergency preparedness plan, the development and installation of lev onto usps mail-processing equipment can reduce future exposures to operators from potentially hazardous cont ...	2004	15238311
rapid anthrax test approved.		2004	15238576
risk factors for human anthrax among contacts of anthrax-infected livestock in kazakhstan.	a retrospective cohort analysis was conducted in kazakhstan to define modifiable risk factors during seven outbreaks of human anthrax. fifty-three cases and 255 non-ill persons with an epidemiologic link to an infected animal were enrolled. cases were 58% male and had a median age of 35 years (range = 5-71). nearly all cases had cutaneous disease (96%). two patients (4%) were diagnosed with gastrointestinal disease. although all cases had some contact with an infected animal other than consumpti ...	2004	15238688
structures of sortase b from staphylococcus aureus and bacillus anthracis reveal catalytic amino acid triad in the active site.	surface proteins attached by sortases to the cell wall envelope of bacterial pathogens play important roles during infection. sorting and attachment of these proteins is directed by c-terminal signals. sortase b of s. aureus recognizes a motif npqtn, cleaves the polypeptide after the thr residue, and attaches the protein to pentaglycine cross-bridges. sortase b of b. anthracis is thought to recognize the npktg motif, and attaches surface proteins to m-diaminopimelic acid cross-bridges. we have d ...	2004	15242591
crystal structure of a complex between anthrax toxin and its host cell receptor.	anthrax toxin consists of the proteins protective antigen (pa), lethal factor (lf) and oedema factor (ef). the first step of toxin entry into host cells is the recognition by pa of a receptor on the surface of the target cell. subsequent cleavage of receptor-bound pa enables ef and lf to bind and form a heptameric pa63 pre-pore, which triggers endocytosis. upon acidification of the endosome, pa63 forms a pore that inserts into the membrane and translocates ef and lf into the cytosol. two closely ...	2004	15243628
identification of bacillus anthracis by multiprobe microarray hybridization.	we have developed a rapid assay based on microarray analysis of amplified genetic markers for reliable identification of bacillus anthracis and its discrimination from other closely related bacterial species of the bacillus cereus group. by combining polymerase chain reaction (pcr) amplification of six b. anthracis-specific genes (plasmid-associated genes encoding virulence factors (cyaa, paga, lef, and capa, capb, capc) and one chromosomal marker ba-5449) with analysis of amplicons by microarra ...	2004	15246505
development of an in vitro-based potency assay for anthrax vaccine.	the potency assay currently used to evaluate consistency of manufacture for the anthrax vaccine is contingent upon meeting specified parameters after statistical analysis of the percent survival and time to death of vaccinated guinea pigs after challenge with spores of a virulent strain of bacillus anthracis. during the development of a new anthrax vaccine based upon recombinant protective antigen (rpa) adsorbed to aluminum hydroxide gel (alhydrogel), we found that the serological response of fe ...	2004	15246620
cpg oligonucleotides improve the protective immune response induced by the anthrax vaccination of rhesus macaques.	synthetic oligodeoxynucleotides (odn) containing unmethylated cpg motifs act as immune adjuvants, improving the immune response elicited by co-administered vaccines. combining cpg odn with anthrax vaccine adsorbed (ava, the licensed human vaccine) increased the speed, magnitude and avidity of the resultant anti-anthrax response. the protective activity of these abs was established by passive transfer to anthrax-challenged mice. the ability of cpg odn to accelerate and magnify the immune response ...	2004	15246624
terrorism-preparedness training for non-clinical hospital workers: tailoring content and presentation to meet workers' needs.	clinicians have been the primary focus of health care worker training in response to the 2001 terrorist and anthrax attacks. however, many nonclinical hospital workers also are critical in providing medical care during any large-scale emergency. we designed a training program, guided by focus groups, to provide them with information to recognize unusual events and to protect themselves. we compared four different training methods: workbook, video, lecture, and a small-group discussion. one hundr ...	2004	15247806
uncertain benefit: the public policy of approving smallpox vaccine research.	without an accurate assessment of the prospect of bioterrorist attack, it is especially challenging to evaluate the protocols for testing smallpox vaccines in the pediatric population. usual regulatory mechanisms cannot shepherd research protocols with benefits that can only be characterized as "uncertain" in the face of more than minimal risk. when a protocol is placed in a government forum for analysis, the public has a unique opportunity to debate the balancing of research risks and benefits ...	2004	15249295
looking at big brothers for clues.		2004	15250878
industrial radiation processing--working behind the scenes.		2004	15254319
anthrax molecular epidemiology and forensics: using the appropriate marker for different evolutionary scales.	precise identification of bacillus anthracis isolates has aided forensic and epidemiological analyses of natural anthrax cases, bioterrorism acts and industrial scale accidents by state-sponsored bioweapons programs. because there is little molecular variation among b. anthracis isolates, identifying and using rare variation is crucial for precise strain identification. we think that mutation is the primary diversifying force in a clonal, recently emerged pathogen, such as b. anthracis, since mu ...	2004	15450200
characterization and applications of catacleave probe in real-time detection assays.	cycling probe technology (cpt), which utilizes a chimeric dna-rna-dna probe and rnase h, is a rapid, isothermal probe amplification system for the detection of target dna. upon hybridization of the probe to its target dna, rnase h cleaves the rna portion of the dna/rna hybrid. utilizing cpt, we designed a catalytically cleavable fluorescence probe (catacleave probe) containing two internal fluorophores. fluorescence intensity of the probe itself was weak due to förster resonance energy transfer. ...	2004	15450799
the pitfalls of bioterrorism preparedness: the anthrax and smallpox experiences.	bioterrorism preparedness programs have contributed to death, illness, and waste of public health resources without evidence of benefit. several deaths and many serious illnesses have resulted from the smallpox vaccination program; yet there is no clear evidence that a threat of smallpox exposure ever existed. the anthrax spores released in 2001 have been linked to secret us military laboratories-the resultant illnesses and deaths might not have occurred if those laboratories were not in operati ...	2004	15451727
evaluation of an anti-rpa igg elisa for measuring the antibody response in mice.	a recombinant protective antigen (rpa)-based enzyme-linked immunosorbent assay (elisa) was developed to measure the serological response of female a/j mice after inoculation with the new rpa-based anthrax vaccine. several fundamental parameters of the elisa were evaluated: specificity, precision, accuracy, linearity, and stability. experimental results suggested that the quantitative anti-rpa igg elisa could be used to measure antibody levels in female a/j mice and may be useful as a potency ass ...	2004	15454183
respiratory protection against bioaerosols: literature review and research needs.	research on respiratory protection against biologic agents is important to address major concerns such as occupational safety and terrorist attack. this review describes the literature on respiratory protection against bioaerosols and identifies research gaps. respiratory protection is a complex field involving a number of factors, such as the efficiency of respirator filter material; face-piece fitting; and maintenance, storage, and reuse of respirators. several studies used nonpathogenic micro ...	2004	15454893
prevalence of presumptive bacillus anthracis in the human population examined by nasal swabs.	routine cultures may reveal presumptive bacillus anthracis microorganisms in human samples. our study of 1336 individuals showed the probability of encountering presumptively positive cultures using routine microbiologic examination was approximately 0.4% (5 individuals) when nasal swabs were examined for the following characteristics indicative of bacillus anthracis : nonhemolytic ground-glass colonies retaining their shape when manipulated, nonmotile in testing media, and microscopically revea ...	2004	15454894
identification and biochemical characterization of two novel collagen binding mscramms of bacillus anthracis.	cell wall-anchored proteins play critical roles in the pathogenesis of infections caused by gram-positive bacteria. through the analysis of the genome of bacillus anthracis ames strain, we identified two novel putative cell wall-anchored proteins, ba0871 and ba5258, which have sequence homology to cna, a cell wall-anchored collagen adhesin of staphylococcus aureus. the two proteins have similar domain organization to that of cna, with typical signal peptide sequences, a non-repetitive a region f ...	2004	15456768
the use of a model of in vivo macrophage depletion to study the role of macrophages during infection with bacillus anthracis spores.	the pathogenesis of infection by bacillus anthracis has been the subject of many investigations, but remains incompletely understood. it has been shown that b. anthracis spores germinate in macrophages and perhaps require this intracellular niche to germinate in vivo before outgrowth of the vegetative organism. however, it has also been reported that macrophages are sporicidal in vitro. in our in vivo model, macrophages were depleted from mice by either silica treatment or treatment with liposom ...	2004	15458777
stable isotope ratios as a tool in microbial forensics--part 2. isotopic variation among different growth media as a tool for sourcing origins of bacterial cells or spores.	since the anthrax attacks of 2001 the need for methods to trace the origins of microbial agents has become urgent. the stable isotope ratios of bacteria record information from both the nutrients and the water used to make their culture media and could potentially be used to provide information about their growth environment. we present a survey of carbon (c), nitrogen (n), and hydrogen (h) stable isotope ratios in 516 samples of bacteriological culture media. the observed variation was consiste ...	2004	15461096
dna vaccines against anthrax.	dna vaccination is vaccination at its simplest. due to renewed interest in vaccination against anthrax and other biothreat agents, a genetic immunisation approach offers attractive possibilities for rapid, responsive vaccine development. dna vaccination against anthrax is an active area of research showing promising results at present, which in the short-term and in the future could form the basis for new advances in multi-agent vaccine development. the anthrax 'model' constitutes an important e ...	2004	15461577
involvement of domain ii in toxicity of anthrax lethal factor.	anthrax lethal factor (lf) is a zn2+ -metalloprotease that cleaves and inactivates mitogen-activated protein kinase kinases (meks). we have used site-directed mutagenesis to identify a cluster of residues in domain ii of lf that lie outside the active site and are required for cellular proteolytic activity toward meks. alanine substituted for leu293, lys294, leu514, asn516, or arg491 caused a 10-50-fold reduction in lf toxicity. further, whereas pairwise substitution of alanine for leu514 and ei ...	2004	15465830
quorum quenching: enzymatic disruption of n-acylhomoserine lactone-mediated bacterial communication in burkholderia thailandensis.	many species of gram-negative bacteria communicate by synthesizing, secreting, and responding to n-acylhomoserine lactones (ahls), a mechanism termed quorum sensing. several investigations have characterized numerous ahl-degrading enzymes (aiia lactonases) encoded by environmental isolates of bacillus spp. the burkholderia thailandensis quorum system is comprised of at least three ahl synthases (ahss) and five transcriptional regulators belonging to the luxir class of proteins. expression of the ...	2004	15466564
taking the sting out of the anthrax vaccine.		2004	15467819
comparative analysis of the schleicher and schuell isocode stix dna isolation device and the qiagen qiaamp dna mini kit.	efficient, rapid, and reproducible procedures for isolating high-quality dna before pcr gene amplification are essential for the diagnostic and molecular identification of pathogenic bacteria. this study evaluated the qiagen qiaamp dna mini kit and the schleicher and schuell isocode stix dna isolation device for isolating nucleic acid. buffer, serum, and whole-blood samples were spiked with bacillus anthracis sterne vegetative cells and yersinia pestis, while water was spiked with b. anthracis s ...	2004	15472363
three-dimensional model of the pore form of anthrax protective antigen. structure and biological implications.	although pore formation by protective antigen (pa) is critical to cell intoxication by anthrax toxin (at), the structure of the pore form of pa (the pa63 pore) has not been determined. hence, in this study, the pa63 pore was modeled using the x-ray structures of monomeric pa and heptameric alpha-hemolysin (alpha-hl) as templates. the pa63 pore model consists of two weakly associated domains, namely the cap and stem domains. the ring-like cap domain has a length of 80 a and an outside diameter of ...	2004	15473701
characterisation of adsorbed anthrax vaccine by two-dimensional gel electrophoresis.	the current uk anthrax vaccine is an alum precipitate prepared from static culture filtrate of the avirulent, unencapsulated sterne strain of bacillus anthracis. protective antigen (pa) is regarded as the major immunogen in the vaccine and production conditions are intended to maximize the pa content. however, the precise composition of the vaccine is unknown and there are concerns that the observed side effects of vaccination may be caused by residual enzymatically active toxin components. two- ...	2004	15474715
expression of bacillus anthracis protective antigen in transgenic chloroplasts of tobacco, a non-food/feed crop.	the centers for disease control (cdc) lists bacillus anthracis as a category a agent and estimates the cost of an anthrax attack to exceed us$ 26 billion per 100,000 exposed individuals. concerns regarding anthrax vaccine purity, a requirement for multiple injections, and a limited supply of the protective antigen (pa), underscore the urgent need for an improved vaccine. therefore, the 83 kda immunogenic bacillus anthracis protective antigen was expressed in transgenic tobacco chloroplasts. the ...	2004	15474731
using snps to decode anthrax.		2004	15475316
the dxdxdg motif for calcium binding: multiple structural contexts and implications for evolution.	calcium ions regulate many cellular processes and have important structural roles in living organisms. despite the great variety of calcium-binding proteins (cabps), many of them contain the same ca(2+)-binding helix-loop-helix structure, referred to as the ef-hand. in the canonical ef-hand, the loop contains three calcium-binding aspartic acid residues, which form the dxdxdg sequence motif, and is flanked by two alpha-helices. recently, other cabps containing the same motif, but lacking one or ...	2004	15476814
intriguing diversity of bacillus anthracis in eastern poland--the molecular echoes of the past outbreaks.	the multiple locus vntrs analysis (mlva) revealed the presence of five genotypes in a group of 10 bacillus anthracis isolates from epidemiologically unrelated cases of bovine-anthrax in eastern poland. eight tested isolates possessed the paga and capb genes indicating the presence of both virulence plasmids, while two isolates revealed only paga and lacked pxo2. the mlva and dna sequence analysis indicated that seven tested isolates represent four novel genotypes. five tested strains revealed a ...	2004	15476971
production and purification of bacillus anthracis protective antigen from escherichia coli.	anthrax is caused by the gram-positive, spore-forming bacterium, bacillus anthracis. the anthrax toxin consists of three proteins, protective antigen (pa), lethal factor, and edema factor. current vaccines against anthrax use pa as their primary component since it confers protective immunity. in this work, we expressed soluble, recombinant pa in relatively high amounts in the periplasm of e. coli from shake flasks and bioreactors. the pa protein was purified using q-sepharose-hp and hydroxyapati ...	2004	15477093
antibiotics for anthrax: patient requests and physician prescribing practices during the 2001 new york city attacks.	little is known about patient encounters with primary care physicians and prescribing practices during the 2001 us anthrax attacks.	2004	15477436
chloroquine enhances survival in bacillus anthracis intoxication.	the intentional release of anthrax in the united states in 2001 resulted in 11 cases of inhalational disease, with an attendant mortality rate of 45%. current therapeutic options for anthrax are limited; antimicrobials target only replicating organisms, thus allowing bacterial toxins to cause unchecked, devastating physiological derangements in the host. novel approaches that target the cytotoxic effects of anthrax exotoxins are needed. chloroquine (cq), a commonly used antimalarial agent, endow ...	2004	15478072
[changes in fine morphological structures of escherichia coli, staphylococcus aureus and spores of bacillus anthracis vaccine strain sti under the action of the disinfectant "veltolen"].	changes in fine morphological structures of e. coli, s. aureus and spores of b. anthracis vaccine strain sti under the action of the disinfectant "veltolen" manufactured by the closed joint-stock company "velt", were evaluated. when used at concentrations of 0.0025-0.025%, the preparation induced the loosening of the cell wall in all microorganisms under study, the intensive formation of bubbles on the cell wall surface with their subsequent separation from the cell wall and the formation of "ro ...	2004	15481924
the anthrax protective antigen (pa63) bound conformation of a peptide inhibitor of the binding of lethal factor to pa63: as determined by trnoesy nmr and molecular modeling.	anthrax protective antigen (pa) is one of the three proteins produced by the gram positive bacteria bacillus anthracis collectively known as the "anthrax toxin" (ascenzi, p.; visca, p.; ippolito, g.; spallarossa, a.; bolognesi, m.; et al. anthrax toxin: a tripartite lethal combination. febs lett. 2002, 531, 384-388). the role played by pa in anthrax intoxication is to transport the two enzymes lethal factor (lf) and edema factor (ef) into the cell. collier and co-workers (mourez, m.; kane, r. s. ...	2004	15481973
poisoned food, poisoned uniforms, and anthrax: or, how guerillas die in war.	many people believe that rhodesia, struggling to maintain minority rule in africa, used chemical and biological weapons against african guerilla armies in the liberation war. clothes and food were routinely poisoned, and rhodesian agents, perhaps in concert with global forces of reaction, caused the largest single outbreak of anthrax in modern times. oral interviews with traditional healers and rhodesians' confessional memoirs of the war suggest that deaths by poisoning or disease were not so st ...	2004	15484386
bioterrorism: what level is the threat and are vaccines the answer?		2004	15485326