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isdg and isdi, heme-degrading enzymes in the cytoplasm of staphylococcus aureus.staphylococcus aureus requires iron for growth and utilizes heme as a source of iron during infection. staphylococcal surface proteins capture hemoglobin, release heme from hemoglobin and transport this compound across the cell wall envelope and plasma membrane into the bacterial cytoplasm. here we show that staphylococcus aureus isdg and isdi encode cytoplasmic proteins with heme binding properties. isdg and isdi cleave the tetrapyrrol ring structure of heme in the presence of nadph cytochrome ...200414570922
acylation of sc4 dodecapeptide increases bactericidal potency against gram-positive bacteria, including drug-resistant strains.we have conjugated dodecyl and octadecyl fatty acids to the n-terminus of sc4, a potently bactericidal, helix-forming peptide 12-mer (klfkrhlkwkii), and examined the bactericidal activities of the resultant sc4 'peptide-amphiphile' molecules. sc4 peptide-amphiphiles showed up to a 30-fold increase in bactericidal activity against gram-positive strains (staphylococcus aureus, streptococcus pyogenes and bacillus anthracis), including s. aureus strains resistant to conventional antibiotics, but lit ...200414609430
anthrax lethal factor-cleavage products of mapk (mitogen-activated protein kinase) kinases exhibit reduced binding to their cognate mapks.anthrax lethal toxin is the major cause of death in systemic anthrax. lethal toxin consists of two proteins: protective antigen and lf (lethal factor). protective antigen binds to a cell-surface receptor and transports lf into the cytosol. lf is a metalloprotease that targets mkks [mapk (mitogen-activated protein kinase) kinases]/meks [mapk/erk (extracellular-signal-regulated kinase) kinases], cleaving them to remove a small n-terminal stretch but leaving the bulk of the protein, including the p ...200414616089
defining a serological correlate of protection in rabbits for a recombinant anthrax vaccine.in these studies, a serological correlate of protection against anthrax was identified in new zealand white (nzw) rabbits that had been given one or two injections of various amounts of recombinant protective antigen (rpa) combined with aluminum hydroxide adjuvant (alhydrogel). rabbits were subsequently challenged by the aerosol route with spores of the ames isolate of bacillus anthracis. results suggested that the antibody response, as determined by the quantitative anti-rpa igg elisa and toxin ...200414670324
implication of ph in the catalytic properties of anthrax lethal factor.the anthrax lethal factor (lf) is a zn(2+)-endopeptidase specific for mitogen-activated protein kinase kinases (mapkks), which are cleaved within their n-terminal region. much line of effort was carried out to elucidate the catalytic activity of lf for designing the inhibitor and to understand the cellular mechanism of its cytotoxicity. current assay methods to analyze the lf activity have been based on a synthetic peptide, consisting of 15-20 residues around being cleaved. however, there are ac ...200414672720
tumor endothelial markers: new targets for cancer therapy.targeting the endothelial cells that line tumor infiltrating blood vessels is a new anticancer strategy that has gained widespread support from biologists and clinicians. here we highlight different approaches currently being used to target tumor endothelium and discuss new avenues for intervention that have been opened through the recent identification of tumor endothelial markers (tems).200414685092
in vitro susceptibility of bacillus anthracis to various antibacterial agents and their time-kill activity.to investigate the in vitro acquisition of resistance to antibiotics by bacillus anthracis.200414688054
anthrax lethal toxin induces human endothelial cell apoptosis.because of its ease of dispersal and high lethality, bacillus anthracis is one of the most feared biowarfare agents. a better understanding of anthrax pathogenesis is urgently needed to develop new therapies for systemic disease that is relatively unresponsive to antibiotics. although experimental evidence has implicated a role for macrophages in anthrax pathogenesis, clinical and pathological observations suggest that a direct insult to the host vasculature may also be important. two bacterial ...200414688124
protection against anthrax toxemia by hexa-d-arginine in vitro and in vivo.the anthrax toxin protective antigen precursor is activated by proteolytic cleavage by furin or a furin-like protease. we present here data demonstrating that the small stable furin inhibitor hexa-d-arginine amide delays anthrax toxin-induced toxemia both in cells and in live animals, suggesting that furin inhibition may represent a reasonable avenue for therapeutic intervention in anthrax.200414688144
formation and composition of the bacillus anthracis endospore.the endospores of bacillus anthracis are the infectious particles of anthrax. spores are dormant bacterial morphotypes able to withstand harsh environments for decades, which contributes to their ability to be formulated and dispersed as a biological weapon. we monitored gene expression in b. anthracis during growth and sporulation using full genome dna microarrays and matched the results against a comprehensive analysis of the mature anthrax spore proteome. a large portion (approximately 36%) o ...200414679236
tyrosine-728 and glutamic acid-735 are essential for the metalloproteolytic activity of the lethal factor of bacillus anthracis.the lethal factor (lf) of bacillus anthracis is a zn2+-endopeptidase specific for the mapk-kinase family of proteins. the catalytic zinc atom is coordinated by a first shell of residues including the two histidines and the glutamate of the zinc-binding motif hexxh and by glu-735. a characteristic feature of lf is the presence, within the second shell of residues, of a tyrosine (tyr-728) in close proximity (3.3 a) to the zinc atom. to investigate the role of tyr-728 and glu-735, lf mutants with o ...200414697216
evaluation of penicillin-based inhibitors of the class a and b beta-lactamases from bacillus anthracis.bacillus anthracis contains a class a (bla1) and class b (bla2) beta-lactamase, which confer resistance to beta-lactam antibiotics when expressed in escherichia coli. in an effort to find new beta-lactamase inhibitors, several penicillin derivatives have been evaluated including experimental compounds incorporating a 6-mercaptomethyl group or a 6-pyridylmethylidene group, along with clavulanate and tazobactam, as inhibitors against bla1 and bla2. the 6-mercaptomethyl-substituted penicillins show ...200414697223
oral pemphigus vulgaris after anthrax vaccine administration: association or coincidence?pemphigus vulgaris is an autoimmune blistering disorder of the skin and mucous membranes. numerous medications, ultraviolet light, and radiation have all been implicated in the etiology of the disease. we present a patient with pemphigus vulgaris whose disease developed after administration of anthrax vaccine. the histologic and immunofluorescence findings were characteristic of pemphigus vulgaris. adverse systemic events associated with the anthrax vaccine consist primarily of flu-like symptoms ...200414699385
atxa controls bacillus anthracis capsule synthesis via acpa and a newly discovered regulator, acpb.two regulatory genes, acpa and atxa, have been reported to control expression of the bacillus anthracis capsule biosynthesis operon capbcad. the atxa gene is located on the virulence plasmid pxo1, while pxo2 carries acpa and the cap genes. acpa has been viewed as the major regulator of the cap operon because it is essential for capsule gene expression in a pxo1(-) pxo2(+) strain. atxa is essential for toxin gene transcription but has also been implicated in control of the cap genes. the molecula ...200414702298
surface layer protein ea1 is not a component of bacillus anthracis spores but is a persistent contaminant in spore preparations.ea1 is an abundant, highly antigenic, surface layer protein of bacillus anthracis vegetative cells. recent studies indicate that ea1 is also a component of b. anthracis spores and a potential marker for spore detection. we show here that ea1 is not a spore component but a persistent contaminant in spore preparations.200414702325
combined effects of high hydrostatic pressure and temperature for inactivation of bacillus anthracis spores.spores of bacillus anthracis are known to be extremely resistant to heat treatment, irradiation, desiccation, and disinfectants. to determine inactivation kinetics of spores by high pressure, b. anthracis spores of a sterne strain-derived mutant deficient in the production of the toxin components (strain rp42) were exposed to pressures ranging from 280 to 500 mpa for 10 min to 6 h, combined with temperatures ranging from 20 to 75 degrees c. the combination of heat and pressure resulted in comple ...200414711702
lethality during continuous anthrax lethal toxin infusion is associated with circulatory shock but not inflammatory cytokine or nitric oxide release in rats.although circulatory shock related to lethal toxin (letx) may play a primary role in lethality due to bacillus anthracis infection, its mechanisms are unclear. we investigated whether letx-induced shock is associated with inflammatory cytokine and nitric oxide (no) release. sprague-dawley rats with central venous and arterial catheters received 24-h infusions of letx (lethal factor 100 microg/kg; protective antigen 200 microg/kg) that produced death beginning at 9 h and a 7-day mortality rate of ...200414715494
comparison of a multiplexed fluorescent covalent microsphere immunoassay and an enzyme-linked immunosorbent assay for measurement of human immunoglobulin g antibodies to anthrax toxins.recently, the centers for disease control and prevention reported an accurate, sensitive, specific, reproducible, and quantitative enzyme-linked immunosorbent assay (elisa) for immunoglobulin g (igg) antibodies to bacillus anthracis protective antigen (pa) in human serum (c. p. quinn, v. a. semenova, c. m. elie et al., emerg. infect. dis. 8:1103-1110, 2002). the elisa had a minimum detectable concentration (mdc) of 0.06 microgram/ml, which, when dilution adjusted, yielded a whole-serum mdc of 3. ...200414715544
detection of the bacillus anthracis gyra gene by using a minor groove binder probe.identification of chromosomal markers for rapid detection of bacillus anthracis is difficult because significant chromosomal homology exists among b. anthracis, bacillus cereus, and bacillus thuringiensis. we evaluated the bacterial gyra gene as a potential chromosomal marker for b. anthracis. a real-time pcr assay was developed for the detection of b. anthracis. after analysis of the unique nucleotide sequence of the b. anthracis gyra gene, a fluorescent 3' minor groove binding probe was tested ...200414715750
cutting edge: anthrax lethal toxin inhibits activation of ifn-regulatory factor 3 by lipopolysaccharide.ifn-regulatory factor 3 (irf3) is known to participate in the transcriptional induction of chemokines and cytokines, including ifns, as a result of viral or bacterial infection. in this study, we demonstrate that the lps-mediated activation of irf3 and subsequent induction of chemokine genes or irf3-responsive reporter constructs are inhibited after exposure of human or murine macrophages to the bacillus anthracis toxin lethal factor. the inhibitory effect is caused by interference with the acti ...200414707042
hierarchical scaffolding with bambus.the output of a genome assembler generally comprises a collection of contiguous dna sequences (contigs) whose relative placement along the genome is not defined. a procedure called scaffolding is commonly used to order and orient these contigs using paired read information. this ordering of contigs is an essential step when finishing and analyzing the data from a whole-genome shotgun project. most recent assemblers include a scaffolding module; however, users have little control over the scaffol ...200414707177
a genomics-based approach to biodefence preparedness. 200414708013
the structural basis for substrate and inhibitor selectivity of the anthrax lethal factor.recent events have created an urgent need for new therapeutic strategies to treat anthrax. we have applied a mixture-based peptide library approach to rapidly determine the optimal peptide substrate for the anthrax lethal factor (lf), a metalloproteinase with an important role in the pathogenesis of the disease. using this approach we have identified peptide analogs that inhibit the enzyme in vitro and that protect cultured macrophages from lf-mediated cytolysis. the crystal structures of lf bou ...200414718924
identification of small molecule inhibitors of anthrax lethal factor.the virulent spore-forming bacterium bacillus anthracis secretes anthrax toxin composed of protective antigen (pa), lethal factor (lf) and edema factor (ef). lf is a zn-dependent metalloprotease that inactivates key signaling molecules, such as mitogen-activated protein kinase kinases (mapkk), to ultimately cause cell death. we report here the identification of small molecule (nonpeptidic) inhibitors of lf. using a two-stage screening assay, we determined the lf inhibitory properties of 19 compo ...200414718925
[bioterrorism and the lungs]. 200414724783
anthrax and the etiology of the english sweating sickness.in 2001, spores of bacillus anthracis were deliberately sent through the united states postal system, resulting in five deaths from inhalational anthrax. rarely observed clinical symptoms associated with these cases led to a hypothesis about the etiology of the english sweating sickness. the disease appeared sporadically in england between 1485 and 1551. numerous viruses have been proposed as possible causes of the "english sweat". anthrax has not previously been considered because, documented c ...200414729023
treatment of anthrax infection with combination of ciprofloxacin and antibodies to protective antigen of bacillus anthracis.currently there is no effective treatment for inhalational anthrax beyond administration of antibiotics shortly after exposure. there is need for new, safe and effective treatments to supplement traditional antibiotic therapy. our study was based on the premise that simultaneous inhibition of lethal toxin action with antibodies and blocking of bacterial growth by antibiotics will be beneficial for the treatment of anthrax. in this study, we tested the effects of a combination treatment using pur ...200414734189
one hundred years of anthrax. 200414739373
the dissemination of anthrax from imported wool: kidderminster 1900-14.a century ago anthrax was a continuing health risk in the town of kidderminster. the distribution of cases in people and in animals provides an indication of the routes by which spores were disseminated. the response to these cases provides an insight into attitudes to an occupational and environmental risk at the time and can be compared with responses in more recent times.200414739375
a generalized linear mixed models approach for detecting incident clusters of disease in small areas, with an application to biological terrorism.since the intentional dissemination of anthrax through the us postal system in the fall of 2001, there has been increased interest in surveillance for detection of biological terrorism. more generally, this could be described as the detection of incident disease clusters. in addition, the advent of affordable and quick geocoding allows for surveillance on a finer spatial scale than has been possible in the past. surveillance for incident clusters of disease in both time and space is a relatively ...200414742279
needle-free skin patch vaccination method for anthrax.three immunizations of mice with recombinant protective antigen (rpa) by transcutaneous immunization (tci) induced long-term neutralizing antibody titers that were superior to those obtained with aluminum-adsorbed rpa. in addition, rpa alone exhibited adjuvant activity for tci. forty-six weeks after completion of tci, 100% protection was observed against lethal anthrax challenge.200414742571
a microtiter fluorometric assay to detect the germination of bacillus anthracis spores and the germination inhibitory effects of antibodies.bacillus anthracis spore germination is usually detected in vitro by alterations in spore refractility, heat resistance, and stainability. we developed a more quantitative, sensitive, and semi-automated procedure for detecting germination by using a microtiter kinetic reader for fluorescence spectrophotometry. the procedure was based on the increase in fluorescence of spores with time during their incubation in germination medium containing a fluorescent nucleic acid-binding dye which stained ge ...200414744454
communicating health information to an alarmed public facing a threat such as a bioterrorist attack.considerable literature exists on the communication of risk to the public through channels such as television, radio, and newspapers. however, little has been written on the communication of risk through less traditional communication forms, such as the internet. the purpose of this study was to investigate the role of the internet as an additional source of health information to that provided by the traditional news media in managing the public's response to an emerging health risk such as a bi ...200414761834
insight into the activation mechanism of bordetella pertussis adenylate cyclase by calmodulin using fluorescence spectroscopy.the interaction of the adenylate cyclase catalytic domain (ac) of the bordetella pertussis major exotoxin with its activator calmodulin (cam) was studied by time-resolved fluorescence spectroscopy using three fluorescent groups located in different regions of ac: tryptophan residues (w69 and w242), a nucleotide analogue (3'-anthraniloyl-2'-deoxyadenosine 5'-triphosphate, ant-datp) and a cysteine-specific probe (acrylodan). cam binding elicited large changes in the dynamics of w242, which dominat ...200414764099
systemic cytokine response in murine anthrax.systemic pro-inflammatory cytokine release has been previously implicated as a major death-causing factor in anthrax, however, direct data have been absent. we determined the levels of il-1 beta, il-6 and tnf-alpha in serum of mice challenged with virulent (ames) or attenuated (sterne) strains of bacillus anthracis. more than 10-fold increase in the il-1beta levels was detected in ames-challenged balb/c mice, in contrast to more susceptible c57bl/6 mice, which showed no il-1beta response. balb/c ...200414764106
effect of extracellular products of pseudoalteromonas atlantica on the edible crab cancer pagurus.previous studies have shown that injection of extracellular products (ecp) of pseudoalteromononas atlantica isolated from shell disease-infected edible crabs (cancer pagurus) into healthy crabs causes rapid death. in this study we examined the nature of the active lethal factor(s) in ecp. injection of ecp into crabs caused a rapid decline in the total number of circulating hemocytes (blood cells), and the crabs died within 60 to 90 min. the individuals that died showed eyestalk retraction, limb ...200414766548
fluorescent amplified fragment length polymorphism analysis of bacillus anthracis, bacillus cereus, and bacillus thuringiensis isolates.dna from over 300 bacillus thuringiensis, bacillus cereus, and bacillus anthracis isolates was analyzed by fluorescent amplified fragment length polymorphism (aflp). b. thuringiensis and b. cereus isolates were from diverse sources and locations, including soil, clinical isolates and food products causing diarrheal and emetic outbreaks, and type strains from the american type culture collection, and over 200 b. thuringiensis isolates representing 36 serovars or subspecies were from the u.s. depa ...200414766590
identification of proteins in the exosporium of bacillus anthracis.spores of bacillus anthracis, the causative agent of anthrax, possess an exosporium. as the outer surface layer of these mature spores, the exosporium represents the primary contact surface between the spore and environment/host and is a site of spore antigens. the exosporium was isolated from the endospores of the b. anthracis wild-type ames strain, from a derivative of the ames strain cured of plasmid pxo2(-), and from a previously isolated pxo1(-), pxo2(-) doubly cured strain, b. anthracis um ...200414766913
[current epidemiology of selected bacterial zoonoses].the present epidemiology of selected bacterial zoonoses brucellosis, anthrax, tularemia, q fever, chlamydia infections, tuberculosis, respectively mycobacteriosis and ehec infections, is discussed.200414770334
[bioterrorism - a challenge for public health services].within the range of highly contagious diseases there are well-known diseases, and those caused by newly detected infectious agents (i. e. sars) or, in the worst case, bioterror agents. public health services as well as clinicians and practitioners will be confronted with a new paradigm of infectious disease control: not only the infectious agent itself, the constitution of the host or the environment will influence the spread of a disease, but also globalization, mobile societies and new communi ...200414770339
making sense of an alphabet soup: the use of a new bioinformatics tool for identification of novel gene islands. focus on "identification of genomic islands in the genome of bacillus cereus by comparative analysis with bacillus anthracis". 200414726601
bacillus anthracis requires siderophore biosynthesis for growth in macrophages and mouse virulence.systemic anthrax infections can be characterized as proceeding in stages, beginning with an early intracellular establishment stage within phagocytes that is followed by extracelluar stages involving massive bacteraemia, sepsis and death. because most bacteria require iron, and the host limits iron availability through homeostatic mechanisms, we hypothesized that b. anthracis requires a high-affinity mechanism of iron acquisition during its growth stages. two putative types of siderophore synthe ...200414756782
us soldiers refuse to fall in line with anthrax vaccination scheme. 200414760404
an outbreak of human anthrax in mysore (india).anthrax is a zoonotic disease caused by bacillus anthracis. intestinal anthrax though a rare entity mostly ends with fatal outcome. very few cases of intestinal anthrax are reported. present outbreak of intestinal anthrax is unique in itself that four cases succumbed to the illness within a span of 48-72 hours in a small hamlet of mysore district of karnataka, after consuming diseased deer meat. confirmation of the diagnosis was carried out at nicd, delhi by bacteriological culture isolation, bi ...200416509258
daily emergency department surveillance system --- bergen county, new jersey.the purpose of the daily emergency department surveillance system (dedss) is to provide consistent, timely, and robust data that can be used to guide public health activities in bergen county, new jersey. dedss collects data on all emergency department visits in four hospitals in bergen county and analyzes them for aberrant patterns of disease or single instances of certain diseases or syndromes. the system monitors for clusters of patients with syndromes consistent with the prodrome of a terror ...200415714627
hospital admissions syndromic surveillance--connecticut, september 200-november 2003.on september 11, 2001, the connecticut department of public health (cdph) initiated daily, statewide syndromic surveillance based on unscheduled hospital admissions (hass). the system's objectives were to monitor for outbreaks caused by category a biologic agents and evaluate limits in space and time of identified outbreaks. thirty-two acute-care hospitals were required to report their previous day's unscheduled admissions for 11 syndromes (pneumonia, hemoptysis, respiratory distress, acute neur ...200415714628
evaluation of syndromic surveillance systems--design of an epidemic simulation model.the paucity of outbreak data from biologic terrorism and emerging infectious diseases limits the evaluation of syndromic surveillance systems. evaluation using naturally occurring outbreaks of proxy disease (e.g., influenza) is one alternative but does not allow for rigorous evaluation. another approach is to inject simulated outbreaks into real background data, but existing simulation models generally do not account for such factors as spatial mobility and do not explicitly incorporate knowledg ...200415714643
pakistan's experience of a bioterrorism-related anthrax scare.from november 2001 to march 2002, the national institute of health, islamabad, pakistan, received 230 samples from 194 different sources for analysis for anthrax spores. these samples were taken from letters/packages suspected of containing anthrax and from individuals exposed to them. when cultured on sheep blood agar, 141 samples yielded growth suggestive of bacillus species. on the basis of growth characteristics, absence of beta-haemolysis, absent or doubtful motility and morphological chara ...200416201705
anthrax: pathological aspects in autopsy cases in shiraz, islamic republic of iran, 1960-2001.anthrax, like tuberculosis, shows a new epidemic spread in industrialized countries, revealing some ambiguous aspects to the disease and providing new challenges to medicine. shiraz university of medical sciences has records of 7130 autopsies performed in the past 40 years, 33 of which are anthrax cases. we reviewed all the pathology slides of these cases and classified the organs involved in a search for unrecognized microscopic findings. the most common cause of death was sepsis, caused by org ...200416201706
[the explicative power of the rules: the case of the koch's postulates].this article traces the emergence of the standard for evidence of causation in infectious diseases, from the scientific discoveries on contagion by agostino bassi, in the first half of the nineteenth century. however, only after the work of robert koch on anthrax and tuberculosis, a set of practical guidelines (koch's postulates) were acknowledged, to establish rigorous criteria before a microbiologist could claim a strictly causal relationship between microbes and infectious diseases. the metho ...200416222849
[carl adolph von basedow on the on the occasion of the 150th anniversary of the day he died].in 2004 we commemorate the 150th day of death of carl adolph von basedow, who takes a lasting place in the history of medicine for his description of the merseburg triad (exophthalmos, goitre, tachycardia) with hyperthyroidism. there has been a long-lasting dispute over who first described these diagnostic features. in germany, the dermatologically-relevant features of hyperthyroidism are known as basedow disease. in the anglo-american literature the name "graves' disease" is predominately used, ...200416281617
using protein-dna chimeras to detect and count small numbers of molecules.we describe general methods to detect and quantify small numbers of specific molecules. we redirected self-splicing protein inteins to create 'tadpoles', chimeric molecules comprised of a protein head covalently coupled to an oligonucleotide tail. we made different classes of tadpoles that bind specific targets, including bacillus anthracis protective antigen and the enzyme cofactor biotin. we measured the amount of bound target by quantifying dna tails by t7 rna polymerase runoff transcription ...200415782158
[bioterrorism and respiratory manifestations]. 200415767948
[amendment to the infectious disease control law].the law concerning the prevention of infectious diseases and medical care for patients of infections (the infectious diseases control law) enacted on april 1, 1999, accompanies an additional rule for reconsideration in five years after putting the law in operation and for taking necessary steps when needed. the responses against bioterrorism involving anthrax and smallpox after the terrorist attacks on september 11, 2001, in the united states of america (a notice on october 11, 2001 by the tuber ...200415745164
latent cytokines: development of novel cleavage sites and kinetic analysis of their differential sensitivity to mmp-1 and mmp-3.we have engineered a latent mouse interferon beta (mifnbeta) using the latency associated peptide (lap) of transforming growth factor beta1 (tgf-beta1) to protect the cytokine and avoid its interaction with its receptors. this approach improves the pharmacokinetic properties and reduces the pleiotropic effects limiting the current therapeutic use of cytokines. ifnbeta was fused to the lap using two flexible linkers flanking a matrix metalloproteinase (mmp) cleavage site for the specific release ...200415708865
contamination and compensation: gruinard as a 'menace to the mainland'.the decades-long contamination of gruinard island by anthrax is now a well-known part of the history of biological weapons (bw) development, as well as that of military encroachments in the scottish highlands and islands (and the authorities' rather less persistent efforts at damage limitation). some accounts have included the related episode, reportedly well-remembered by local people, of anthrax contamination on the mainland close to gruinard. this occurred in 1942--43, when bw experiments wer ...200415688884
managing emerging infectious diseases: is a federal system an impediment to effective laws?in the 1980's and 1990's hiv/aids was the emerging infectious disease. in 2003-2004 we saw the emergence of sars, avian influenza and anthrax in a man made form used for bioterrorism. emergency powers legislation in australia is a patchwork of commonwealth quarantine laws and state and territory based emergency powers in public health legislation. it is time for a review of such legislation and time for consideration of the efficacy of such legislation from a country wide perspective in an age w ...200415679928
a multiplexed pcr-coupled liquid bead array for the simultaneous detection of four biothreat agents.we have developed a 10-plexed pcr assay coupled to a 12-plexed liquid bead array to rapidly screen environmental samples for b. anthracis, y. pestis, f. tularensis, and b. melitensis. highly validated species-specific primer sets were used to simultaneously amplify multiple diagnostic regions unique to each individual pathogen. resolution of the mix of amplified products was achieved by pcr product hybridization to corresponding probe sequences, attached to unique sets of fluorescent beads. the ...200415680215
pathogen survival in the external environment and the evolution of virulence.recent studies have provided evolutionary explanations for much of the variation in mortality among human infectious diseases. one gap in this knowledge concerns respiratory tract pathogens transmitted from person to person by direct contact or through environmental contamination. the sit-and-wait hypothesis predicts that virulence should be positively correlated with durability in the external environment because high durability reduces the dependence of transmission on host mobility. reviewing ...200415682873
project bioshield: protecting americans from terrorism. 200415675025
[anthrax]. 200415676233
bichat guidelines for the clinical management of anthrax and bioterrorism-related anthrax.the spore-forming bacillus anthracis must be considered as one of the most serious potential biological weapons. the recent cases of anthrax caused by a deliberate release reported in 2001 in the united states point to the necessity of early recognition of this disease. infection in humans most often involves the skin, and more rarely the lungs and the gastrointestinal tract. inhalational anthrax is of particular interest for possible deliberate release: it is a life-threatening disease and earl ...200415677848
human monoclonal antibodies that neutralize anthrax toxin by inhibiting heptamer assembly.a panel of human anti-anthrax protective antigen igg1 monoclonal antibodies were evaluated to determine the mechanism of toxin neutralization. avp-22g12, avp-1c6 and avp-21d9 bound to the protective antigen with picomolar affinities to distinct non-overlapping linear epitopes. two of the antibodies neutralized the anthrax toxin by completely inhibiting the protective antigen oligomer assembly process in vitro.200415671576
mouse model characterisation for anthrax vaccine development: comparison of one inbred and one outbred mouse strain.in order to evaluate the immunogenicity and protective efficacy of anthrax vaccine candidates a suitable small animal model is required. the inbred a/j strain of mouse has been selected as a potential model, and its immune response to immunisation with recombinant protective antigen (rpa) vaccine characterised, by assessment of rpa specific antibody production, and protection against injected challenge, with the unencapsulated sti strain of bacillus anthracis. studies were conducted to determine ...200415652293
religion and perceived stress among undergraduates during fall 2001 final examinations.to examine the relationship of religion and perceived stress, 97 undergraduate college students responded to the perceived stress scale, the spiritual well-being scale, and the intrinsic/extrinsic-revised scale during a period of extreme national stressors during fall 2001, namely, the september 11th terrorist attacks, anthrax scare, and war in afghanistan, in addition to the local stressor of pending final college examinations. scores on the perceived stress scale were negatively correlated to ...200415666946
interview with marcelle c. layton, md assistant commissioner, bureau of communicable disease new york city department of health and mental hygiene. interview by madeline drexler. 200415650434
risk of occupationally acquired illnesses from biological threat agents in unvaccinated laboratory workers.many vaccines for bioterrorism agents are investigational and therefore not available (outside of research protocol use) to all at-risk laboratory workers who have begun working with these agents as a result of increased interest in biodefense research. illness surveillance data archived from the u.s. offensive biological warfare program (from 1943 to 1969) were reviewed to assess the impact of safety measures on disease prevention (including biosafety cabinets [bscs]) before and after vaccine a ...200415650438
some pharmacological properties of extracts of terminalia sericea roots.terminalia sericea burch. ex. dc (combretaceae) extracts are used to treat bacterial infections, diarrhea, and diabetes. intermediate and polar extracts of the roots exhibited antibacterial activity against staphylococcus aureus, escherichia coli, bacillus anthracis, and pseudomonas aeruginosa, while the petroleum ether extract was inactive. the extracts were mildly active against bacillus anthracis and pseudomonas aeruginosa but exhibited the highest activity against staphylococcus aureus. they ...200415652273
microarray-based resequencing of multiple bacillus anthracis isolates.we used custom-designed resequencing arrays to generate 3.1 mb of genomic sequence from a panel of 56 bacillus anthracis strains. sequence quality was shown to be very high by replication (discrepancy rate of 7.4 x 10(-7)) and by comparison to independently generated shotgun sequence (discrepancy rate < 2.5 x 10(-6)). population genomics studies of microbial pathogens using rapid resequencing technologies such as resequencing arrays are critical for recognizing newly emerging or genetically engi ...200415642093
damage of office supply, personal use items, and over-the-counter medical devices after sterilization by ethylene oxide gas, electron beam, and gamma radiation.after letters containing bacillus anthracis spores entered the u.s. mail in 2001, a problem emerged regarding how to decontaminate the letters, packages, and personal items in offices that received these letters. the effects of three sterilization methods (i.e. ethylene oxide gas [eo], electron beam [e-beam] radiation, and gamma radiation) were evaluated for a variety of office supply and equipment, personal use items, and over-the-counter medical devices. no single sterilization method was suit ...200415635999
late treatment with a protective antigen-directed monoclonal antibody improves hemodynamic function and survival in a lethal toxin-infused rat model of anthrax sepsis.in animal models, treatment with 5h3, a fully human protective antigen-directed monoclonal antibody (pa-mab), improved survival when administered close to the time of bacillus anthracis lethal toxin (letx) bolus or live bacterial challenge. however, treatment with pa-mab would be most valuable clinically if it were beneficial even when administered after the onset of shock and lethality due to letx.200415633102
flow cytometry analysis of germinating bacillus spores, using membrane potential dye.germination of bacillus anthracis spores is necessary for the transcription of plasmidic genes essential to the infection. assessing germination potential is crucial to predict the risk associated with pathogenic bacillus exposure. the aim of this study was to set up a viability assay based on membrane potential in order to predict the earliest germination event of spores. b. cereus and two strains of b. subtilis were used. the spores were isolated with a sodium bromide gradient. approximately 1 ...200415611861
capsule synthesis by bacillus anthracis is required for dissemination in murine inhalation anthrax.bacillus anthracis, the agent of anthrax, produces a poly-d-glutamic acid capsule that has been implicated in virulence. many strains missing pxo2 (96 kb), which harbors the capsule biosynthetic operon capbcad, but carrying pxo1 (182 kb) that harbors the anthrax toxin genes, are attenuated in animal models. also, noncapsulated strains are readily phagocytosed by macrophage cell lines, whereas capsulated strains are resistant to phagocytosis. we show that a strain carrying both virulence plasmids ...200415616593
novel chromosomally encoded multidrug efflux transporter mdea in staphylococcus aureus.antibiotic efflux is an important mechanism of resistance in pathogenic bacteria. here we describe the identification and characterization of a novel chromosomally encoded multidrug resistance efflux protein in staphylococcus aureus, mdea (multidrug efflux a). mdea was identified from screening an s. aureus open reading frame expression library for resistance to antibiotic compounds. when overexpressed, mdea confers resistance on s. aureus to a range of quaternary ammonium compounds and antibiot ...200414982783
diagnosing smallpox: would you know it if you saw it?the intentional release of anthrax in the united states in 2001 and other recent acts of terrorism have highlighted the possibility of intentional release of smallpox by terrorists. little is known about physicians' ability to diagnose smallpox, especially in the critical first days, when the potential for rapid control of transmission is greatest. during december 2002 and january 2003, primary care and emergency physicians at a large urban academic medical center were surveyed regarding the dia ...200415588053
a bitter pill to swallow: nonadherence with prophylactic antibiotics during the anthrax attacks and the role of private physicians.to generate recommendations for improving adherence to public health advice during public health crises, we conducted semi-structured interviews with employees at the brentwood road postal facility and on capitol hill to identify key themes associated with decisions to adhere to recommended antibiotic prophylaxis during the 2001 anthrax attacks. factors used in deciding to adhere to recommended prophylactic antibiotics and concerns about the official response were similar in brentwood and capito ...200415588055
rabbit and nonhuman primate models of toxin-targeting human anthrax vaccines.the intentional use of bacillus anthracis, the etiological agent of anthrax, as a bioterrorist weapon in late 2001 made our society acutely aware of the importance of developing, testing, and stockpiling adequate countermeasures against biological attacks. biodefense vaccines are an important component of our arsenal to be used during a biological attack. however, most of the agents considered significant threats either have been eradicated or rarely infect humans alive today. as such, vaccine e ...200415590776
new anthrax test. 200415595132
anthrax toxin protective antigen: inhibition of channel function by chloroquine and related compounds and study of binding kinetics using the current noise analysis.protective antigen (pa) of the tripartite anthrax toxin binds to a cell surface receptor and mediates the transport of two enzymatic components, edema factor and lethal factor, into the cytosol of host cells. here recombinant pa(63) from bacillus anthracis was reconstituted into artificial lipid bilayer membranes and formed ion permeable channels. the heptameric pa(63)-channel contains a binding site for 4-aminoquinolones, which block ion transport through pa in vitro. this result allowed a deta ...200415596516
theoretical perspectives on public communication preparedness for terrorist attacks.the experience of federal health authorities in responding to the mailed anthrax attacks in the fall of 2001 sheds light on the challenges of public information dissemination in emergencies. lessons learned from the fall of 2001 have guided more recent efforts related to crisis communication and preparedness goals. this article applies theories and evidence from the field of communication to provide an orientation to how public health communication can best contribute to the preparedness effort. ...200415596970
interscience conference on antimicrobial agents and chemotherapy--44th annual meeting. drug highlights i. 30 october-2 november 2004, washington dc, usa. 200415599792
activation of liver x receptors and retinoid x receptors prevents bacterial-induced macrophage apoptosis.microbe-macrophage interactions play a central role in the pathogenesis of many infections. the ability of some bacterial pathogens to induce macrophage apoptosis has been suggested to contribute to their ability to elude innate immune responses and successfully colonize the host. here, we provide evidence that activation of liver x receptors (lxrs) and retinoid x receptors (rxrs) inhibits apoptotic responses of macrophages to macrophage colony-stimulating factor (m-csf) withdrawal and several i ...200415601766
what is the true number of victims of the postal anthrax attack of 2001? 200415602039
disability among u.s. army personnel vaccinated against anthrax.this study was conducted to examine whether u.s. army personnel receiving > or =1 dose of anthrax vaccine adsorbed (ava) between march 1998 and february 2002 were at higher risk of disability than unvaccinated personnel. we studied a historical cohort study of 716,833 active-duty soldiers (154,456 vaccinated) followed for 4.25 years to determine rates of evaluation for disability discharge. cox proportional hazards models compared estimated risk of evaluation for disability, accounting for occup ...200415602181
public health vaccination policies for containing an anthrax outbreak.concern about biological weapons has raised questions about the most effective public health policies to contain an anthrax outbreak. we developed a probability model to predict the impact of different anthrax antibiotic and vaccination policies. an anthrax outbreak can be significantly contained by minimizing the delay until initiation of antibiotic prophylaxis. however, even if mass distribution of antibiotics is completed within six days of the initial exposure, then at most about 70% of case ...200415602561
mid-ultraviolet light-emitting diode detects dipicolinic acid.dipicolinic acid (dpa, 2,6-pyridinedicarboxylic acid) is a substance uniquely present in bacterial spores such as that from anthrax (b. anthracis). it is known that dpa can be detected by the long-lived fluorescence of its terbium chelate; the best limit of detection (lod) reported thus far using a large benchtop gated fluorescence instrument using a pulsed xe lamp is 2 nm. we use a novel algan light-emitting diode (led) fabricated on a sapphire substrate that has peak emission at 291 nm. althou ...200415606942
protective immunization against inhalational anthrax: a comparison of minimally invasive delivery platforms.a new anthrax vaccine under clinical investigation is based on recombinant bacillus anthracis protective antigen (rpa). here, we investigated microneedle-based cutaneous and nasal mucosal delivery of rpa in mice and rabbits. in mice, intradermal (id) delivery achieved up to 90% seroconversion after a single dose, compared with 20% after intramuscular (im) injection. intranasal (inl) delivery of a liquid formulation required 3 doses to achieve responses that were comparable with those achieved vi ...200415609239
anthrolysin o and other gram-positive cytolysins are toll-like receptor 4 agonists.exposure of bone marrow-derived macrophages (bmdms) to low concentrations of bacillus anthracis lethal toxin (lt), whose catalytic subunit is lethal factor (lf), results in induction of a robust apoptotic response dependent on activation of toll-like receptor (tlr)4. a similar tlr4-dependent apoptotic response is observed when bmdms are infected with live b. anthracis (sterne strain). however, tlr4 is considered to be a specific signaling receptor for lipopolysaccharide (lps), a typical product ...200415611291
a spontaneous translational fusion of bacillus cereus plcr and papr activates transcription of plcr-dependent genes in bacillus anthracis via binding with a specific palindromic sequence.transformation of bacillus anthracis with plasmid pute29-plcr-papr carrying the native bacillus cereus plcr-papr gene cluster did not activate expression of b. anthracis hemolysin genes, even though these are expected to be responsive to activation by the global regulator plcr. to further characterize the action of plcr, we examined approximately 3,000 b. anthracis transformants containing pute29-plcr-papr and found a single hemolytic colony. the hemolytic strain contained a plasmid having a spo ...200415385482
safety of anthrax vaccine: an expanded review and evaluation of adverse events reported to the vaccine adverse event reporting system (vaers).to assess the safety of a licensed anthrax vaccine (ava) given to more than 500,000 us military personnel, through review and medical evaluation of adverse events (aes) reported to the vaccine adverse event reporting system (vaers).200415386719
case reports of aplastic anemia after vaccine administration. 200415389916
cutaneous anthrax on eyelids.ophthalmologists should be aware of the signs and symptoms of anthrax, although it is a rare disease in humans. we report our successful treatment of three patients with cutaneous lesions in the periorbital area.200415175920
ruthenium red staining for ultrastructural visualization of a glycoprotein layer surrounding the spore of bacillus anthracis and bacillus subtilis.ruthenium red is a polycationic stain used to visualize acid polysaccharides on the outer surface of cells. ruthenium red staining followed by electron microscopic analysis was used to demonstrate the presence of an external glycoprotein layer surrounding the spore of both bacillus anthracis and bacillus subtilis. this layer is less apparent with traditional staining methods used for electron microscopy. renografin gradients were used to purify b. subtilis spores. these purified spores displayed ...200415177900
responding to detection of aerosolized bacillus anthracis by autonomous detection systems in the workplace.autonomous detection systems (adss) are under development to detect agents of biologic and chemical terror in the environment. these systems will eventually be able to detect biologic and chemical hazards reliably and provide approximate real-time alerts that an agent is present. one type of ads that tests specifically for bacillus anthracis is being deployed in hundreds of postal distribution centers across the united states. identification of aerosolized b. anthracis spores in an air sample ca ...200415179360
applications of single-molecule detection to the analysis of pathogenic dna.we have devised a new technique based on single fluorescent molecule detection for the analysis of specific sequences of dna. the method consists of synthesizing a fluorescent reporter molecule using a polymerase extension reaction and labeled nucleotides. the fluorescent reporter products are analyzed in a laser-based single-molecule detection system. we have applied this method to the detection of puc19 and bacillus anthracis dna targets. we expect that this method will have applications in ra ...200415180549
media influence on poison center call volume after 11 september 2001. 200415506257
rapid assessment of agents of biological terrorism: defining the differential diagnosis of inhalational anthrax using electronic communication in a practice-based research network.early detection of bioterrorism requires assessment of diagnoses assigned to cases of rare diseases with which clinicians have little experience. in this study, we evaluated the process of defining the differential diagnosis for inhalational anthrax using electronic communication within a practice-based research network (pbrn) and compared the results with those obtained from a nationwide random sample of family physicians with a mailed instrument.200415506577
the primary care differential diagnosis of inhalational anthrax.inhalational anthrax is an extremely rare infectious disease with nonspecific initial symptoms, thus making diagnosis on clinical grounds difficult. after a covert release of anthrax spores, primary care physicians will be among the first to evaluate cases. this study defines the primary care differential diagnosis of inhalational anthrax.200415506578
effects of dynamin inactivation on pathways of anthrax toxin uptake.internalization and traffic to acidic endosomes of anthrax lethal factor (lf) and protective antigen (pa), bound to the anthrax toxin receptor (atr), is required for lf translocation into the cytosol, where it can elicit its toxic effects. dynamin is required for clathrin-mediated endocytosis, and long-term disruption of dynamin function blocks internalization of pa. we have used lfn-dta, a surrogate of lf consisting of the n-terminal domain of lf fused to the catalytic subunit of diphtheria tox ...200415511085
the m'fadyean reaction: a stain for anthrax bacilli. 200415513713
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