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genetic sleuths rush to identify anthrax strains in mail attacks. 200111606978
drugs and vaccines for biological weapons. 200111606896
anthrax toxin.anthrax is primarily a disease of herbivores caused by gram-positive, aerobic, spore-forming bacillus anthracis. humans are accidental hosts through the food of animal origin and animal products. anthrax is prevelant in most parts of the globe, and cases of anthrax have been reported from almost every country. three forms of the disease have been recognized: cutaneous (through skin), gastrointestinal (through alimentary tract), and pulmonary (by inhalation of spores). the major virulence factors ...200111596878
toxins of bacillus anthracis.bacillus anthracis, a gram positive bacterium, is the causative agent of anthrax. this organism is capsulogen and toxinogenic. it secretes two toxins which are composed of three proteins: the protective antigen (pa), the lethal factor (lf) and the edema factor (ef). the lethal toxin (pa+lf) provokes a subit death in animals, the edema toxin (pa+ef) induces edema. the edema and the lethal factors are internalised into the eukaryotic target cells via the protective antigen. ef and lf exert a calmo ...200111595637
kif1c, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor.inbred mouse strains exhibit striking differences in the susceptibility of their macrophages to the effects of anthrax lethal toxin (letx). previous data has shown that this difference in susceptibility lies downstream of toxin entry into macrophages. a locus controlling this phenotype, called ltxs1, has been mapped to chromosome 11, but the responsible gene has not been identified.200111591317
detoxification of a bacterial toxin by the toxin itself. 200111583789
designing a polyvalent inhibitor of anthrax toxin.screening peptide libraries is a proven strategy for identifying inhibitors of protein-ligand interactions. compounds identified in these screens often bind to their targets with low affinities. when the target protein is present at a high density on the surface of cells or other biological surfaces, it is sometimes possible to increase the biological activity of a weakly binding ligand by presenting multiple copies of it on the same molecule. we isolated a peptide from a phage display library t ...200111581662
distribution of s-layers on the surface of bacillus cereus strains: phylogenetic origin and ecological pressure.bacillus anthracis, bacillus cereus and bacillus thuringiensis have been described as members of the bacillus cereus group but are, in fact, one species. b. anthracis is a mammal pathogen, b. thuringiensis an entomopathogen and b. cereus a ubiquitous soil bacterium and an occasional human pathogen. in two clinical isolates of b. cereus, in some b. thuringiensis strains and in b. anthracis, an s-layer has been described. we investigated how the s-layer is distributed in b. cereus, and whether phy ...200111578310
the development of new vaccines against bacillus anthracis. 200111576296
from the centers for disease control and prevention. human anthrax associated with an epizootic among livestock--north dakota, 2000. 200111575325
inhibition of axotomy-induced neuronal apoptosis by extracellular delivery of a bcl-xl fusion protein.bcl-2 and bcl-xl prevent neuronal apoptosis during development, neurodegenerative disease, and trauma. to test a new anti-apoptosis strategy for neuroprotection, we engineered nontoxic components of anthrax toxin into a bcl-xl delivery system. delivery of bcl-xl by this system prevented apoptosis of cultured rat cerebellar granule cells and macrophages, and the prevention depended on both the bcl-xl and the anthrax toxin receptor binding/translocation moieties. furthermore, neuronal death in viv ...200111574549
clinicopathologic aspects of bacterial agents.bacteria were the first organisms recognized for their potential as agents of bioaggression and the possibility of their use by a terrorist or rogue nation is considered a significant threat. five of the more likely agents (anthrax, plague, tularemia, q fever, and brucellosis) are reviewed with emphasis on their epidemiology, clinical presentation, diagnosis, and pathology. particular emphasis is given to the presentation of the diseases as they may appear after use in a biowarfare scenario.200111572140
fluorescent amplified fragment length polymorphism analysis of norwegian bacillus cereus and bacillus thuringiensis soil isolates.we examined 154 norwegian b. cereus and b. thuringiensis soil isolates (collected from five different locations), 8 b. cereus and 2 b. thuringiensis reference strains, and 2 bacillus anthracis strains by using fluorescent amplified fragment length polymorphism (aflp). we employed a novel fragment identification approach based on a hierarchical agglomerative clustering routine that identifies fragments in an automated fashion. no method is free of error, and we identified the major sources so tha ...200111571195
us biological defence research under the spotlight. 200111567711
the cell envelope-bound metalloprotease (camelysin) from bacillus cereus is a possible pathogenic factor.a novel membrane proteinase of the nosocomial important bacteria species bacillus cereus (synonyms: camelysin, ccmp) was purified up to homogeneity as was shown by mass spectrometry in its amphiphilic form. camelysin is a neutral metalloprotease with a molecular mass of 19 kda. its unique n-terminus phe-phe-ser-asp-lys-glu-val-ser-asn-asn-thr-phe-ala-ala-gly-thr-leu-asp-leu-thr-leu-asn-pro-lys-thr-leu-val-asp-(ile-lys-asp)- was not detected in the protein data bases during blast searches, but in ...200111566257
predicting the clinical status of human breast cancer by using gene expression profiles.prognostic and predictive factors are indispensable tools in the treatment of patients with neoplastic disease. for the most part, such factors rely on a few specific cell surface, histological, or gross pathologic features. gene expression assays have the potential to supplement what were previously a few distinct features with many thousands of features. we have developed bayesian regression models that provide predictive capability based on gene expression data derived from dna microarray ana ...200111562467
robust hiv type 2 cellular immune response measured by a modified anthrax toxin-based enzyme-linked immunospot assay.evaluation of immune mechanisms responsible for control of viral replication is critical to understanding hiv-2 attenuated biological characteristics in pathogenesis and transmission. evaluation of the cellular immune response is often based on labor-intensive techniques that limit the scope of most studies performed. a simple and rapid anthrax toxin-based elispot method to assess hiv-2 cellular immune response was developed. the modified anthrax toxin-based antigen presentation process performe ...200111559425
detection of anthrax spores in endemic regions of northern canada.to determine the level of anthrax spore contamination in endemic regions of northern canada between outbreaks.200111556908
a simple and sensitive detection system for bacillus anthracis in meat and tissue.to detect and isolate bacillus anthracis from meat and tissue by rapid and simple procedures.200111556906
detection of anthrax spores from the air by real-time pcr.to detect and isolate bacillus anthracis from the air by a simple and rapid procedure.200111555211
hydrophobic residues phe552, phe554, ile562, leu566, and ile574 are required for oligomerization of anthrax protective antigen.anthrax protective antigen (pa) plays a central role in facilitating the entry of active toxin components, namely, lethal factor and edema factor, into the cells. pa is also the main immunogen of both human and veterinary vaccine against anthrax. during host cell intoxication, protective antigen binds to the receptors on cell surface, gets proteolytically activated, oligomerizes to form a heptamer and binds to lethal factor or edema factor. the complex, formed by binding of lethal factor or edem ...200111554763
purification of anthrax edema factor from escherichia coli and identification of residues required for binding to anthrax protective antigen.the structural gene for anthrax edema factor (ef) was expressed in escherichia coli under the control of a powerful t5 promoter to yield the 89-kda recombinant protein that reacted with anti-ef antibodies. recombinant ef was purified to homogeneity by a two-step procedure involving metal chelate affinity chromatography and cation-exchange chromatography. from 1 liter of culture, 2.5 mg of biologically active ef was easily purified. this is the first report of purification of anthrax ef from e. c ...200111553601
bioterrorism: a threat for which we are ill prepared.of the weapons of mass destruction, the biological ones are the most feared and bioterrorism has become one of the most vicious threats to civilized society in recent times. biological weapons have been sporadically used for centuries. despite international regulations, there has been a global re-emergence of the threat of biological warfare. as many as 17 countries are suspected of either including or developing biological agents in their weapons programmes. in the past decade, a number of terr ...200111547531
anthrax.bacillus anthracis was shown to be the etiological agent of anthrax by r. koch and l. pasteur at the end of the nineteenth century. the concepts on which medical microbiology are based arose from their work on this bacterium. the link between plasmids and major virulence factors of b. anthracis was not discovered until the 1980s. the three toxin components are organized in two a-b type toxins, and the bacilli are covered by an antiphagocytic polyglutamic capsule. structure-function analysis of t ...200111544370
in vitro correlate of immunity in a rabbit model of inhalational anthrax.a serological correlate of vaccine-induced immunity was identified in the rabbit model of inhalational anthrax. animals were inoculated intramuscularly at 0 and 4 weeks with varying doses of anthrax vaccine adsorbed (ava) ranging from a human dose to a 1:256 dilution in phosphate-buffered saline (pbs). at 6 and 10 weeks, both the quantitative anti-protective antigen (pa) igg elisa and the toxin-neutralizing antibody (tna) assays were used to measure antibody levels to pa. rabbits were aerosol-ch ...200111535328
the legacy of robert koch. 200111520262
participation of residue f552 in domain iii of the protective antigen in the biological activity of anthrax lethal toxin.the protective antigen (pa) component of anthrax toxin translocates the catalytic moieties lethal factor (lf) and edema factor (ef) into the cytosol. the proteolytically activated 63 kda form of pa (pa63) has the ability to oligomerize and bind lf/ef. pa has four distinct domains performing specialized functions; whereas the function of domains i, ii and iv has been well characterized, domain iii has no known role in the biological activity of pa. here we report the role of amino acid residues l ...200111501759
ct and mr findings of anthrax meningoencephalitis: report of two cases and review of the literature.anthrax meningoencephalitis is a rare complication of infection with bacillus anthracis and generally produces a hemorrhagic meningoencephalitis. we present the ct and mr imaging findings in two patients demonstrating subarachnoid, intracerebral, and intraventricular hemorrhage with leptomeningeal enhancement.200111498418
[current threat: anthrax]. 200111496783
rapid purification of recombinant anthrax-protective antigen under nondenaturing conditions.anthrax-protective antigen is the central moiety of the anthrax toxin complex that mediates the entry of the other two toxin components, lethal factor and edema factor into the cells. it is also the main immunogen of the cell-free vaccine against anthrax. however, in addition to pa, the vaccine contains trace amounts of other culture-derived proteins that contribute to the side effects of the vaccine like pain, edema, erythrema, etc. thus there is a need to develop high-resolution purification m ...200111485300
passive transfer of protection against bacillus anthracis infection in a murine model.passive transfer of lymphocytes and sera from mice immunised using two different formulations containing recombinant protective antigen (rpa) have been used to further elucidate the mechanism of protection against bacillus anthracis infection. the results demonstrated that an antibody response maybe important in protection against b. anthracis infection, under the conditions tested. the results provide further data for the development of an improved anthrax vaccine.200111483266
susceptibility of irradiated mice to bacillus anthracis sterne by the intratracheal route of infection.the susceptibility of sublethally irradiated mice to pulmonary infection with bacillus anthracis was investigated in a mouse model. female b6d2f1/j mice were challenged intratracheally with 4.3 x 10(6), 3.7 x 10(7) and 4.4 x 10(8) cfu of b. anthracis sterne spores 4 days after 60co gamma-radiation at a dose of 0, 1, 2, 3, 4, 5, 6 or 7 gy. bacterial cultures were obtained from lung, spleen homogenates and heart blood. a biphasic mode of mortality was observed, with a constant response of up to 3 ...200111478674
utilization of the rpob gene as a specific chromosomal marker for real-time pcr detection of bacillus anthracis.the potential use of bacillus anthracis as a weapon of mass destruction poses a threat to humans, domesticated animals, and wildlife and necessitates the need for a rapid and highly specific detection assay. we have developed a real-time pcr-based assay for the specific detection of b. anthracis by taking advantage of the unique nucleotide sequence of the b. anthracis rpob gene. variable region 1 of the rpob gene was sequenced from 36 bacillus strains, including 16 b. anthracis strains and 20 ot ...200111472954
bacillus spore inactivation methods affect detection assays.detection of biological weapons is a primary concern in force protection, treaty verification, and safeguarding civilian populations against domestic terrorism. one great concern is the detection of bacillus anthracis, the causative agent of anthrax. assays for detection in the laboratory often employ inactivated preparations of spores or nonpathogenic simulants. this study uses several common biodetection platforms to detect b. anthracis spores that have been inactivated by two methods and comp ...200111472945
evaluation of spore extraction and purification methods for selective recovery of viable bacillus anthracis spores.to investigate methods of improving anthrax spore detection with plet.200111472515
enhanced expression of the recombinant lethal factor of bacillus anthracis by fed-batch culture.high cell density cultivation has been one of the most effective ways to increase cell as well as the product yields. the structural gene for the 90-kda lethal factor (lf) isolated from bacillus anthracis was expressed as fusion protein with 6x histidine residues under the transcriptional regulation of the t5 promoter in escherichia coli. various strategies were tried to scale up the expression of the recombinant lethal factor by bioprocess optimization using fed batch culture technique in a 14 ...200111467855
anthrax in an infant. 200111463966
detection of anthrax vaccine virulence factors by polymerase chain reaction.in italy, an attenuated bacillus anthracis strain, named 'carbosap', is used for immunization against ovine and bovine anthrax. analysis on 'carbosap', sterne vaccine strain f34 and pasteur vaccine strain ss104, were performed using primers specific for the sequences, encoding the toxic factors, located on plasmids pxo1 and pxo2 and primers specific for the chromosome. the results obtained from polymerase chain reaction (pcr) assay revealed the presence of both plasmids pxo1 and pxo2 in 'carbosa ...200111457547
palbebral anthrax.anthrax is a rare infection transmitted to humans from animals or animal products. in cutaneous anthrax it may produce lesions of the eyelids which can lead to cicatricial ectropion.200111456020
cowpox virus in a 12-year-old boy: rapid identification by an orthopoxvirus-specific polymerase chain reaction.although smallpox was eradicated 20 years ago, other members of the genus orthopoxvirus (opv), such as cowpox virus (cpxv) or monkeypox virus, are still a threat to humans. because human cpxv infection is rare, it is seldom suspected on clinical grounds only. we report a boy who presented with two necrotic ulcers with surrounding erythema. infection with opv was suspected, as antibiotic treatment had not produced improvement and smears were negative for anthrax. an opv was isolated and an opv-sp ...200111453925
cutaneous anthrax in two siblings. 200111450393
use of long-range repetitive element polymorphism-pcr to differentiate bacillus anthracis strains.the genome of bacillus anthracis is extremely monomorphic, and thus individual strains have often proven to be recalcitrant to differentiation at the molecular level. long-range repetitive element polymorphism-pcr (lr rep-pcr) was used to differentiate various b. anthracis strains. a single pcr primer derived from a repetitive dna element was able to amplify variable segments of a bacterial genome as large as 10 kb. we were able to characterize five genetically distinct groups by examining 105 b ...200111425716
anthrax: an overview within the indian subcontinent. 200111422531
cutaneous anthrax in eastern turkey.anthrax, caused by the spore-forming bacterium bacillus anthracis, is rarely seen in industrial nations but is common in developing countries. cutaneous anthrax (ca), the most common form of the disease, accounts for 95% of cases and usually develops on exposed sites. this study reviews the clinical and laboratory findings of 21 patients diagnosed with ca during 2 separate epidemics in the van region of turkey. all patients had a history of direct contact with infected cattle. the patients, aged ...200111419020
application of recovery tests in the validation of immunoassays for assessing the immunogenicity of b. anthracis pa vaccine.in the quantitative assessment of polyclonal serum antibodies, the complex composition and characteristics of the analyte population (serum antibodies) restricts the capability of constructing appropriately defined calibration standards. this fact limits the application of the conservative recovery tests to the validation of immunoassays aimed at determining serum antibody levels. the present report describes a modification of recovery tests that overcomes this impediment. the modified approach ...200111417105
protection against anthrax lethal toxin challenge by genetic immunization with a plasmid encoding the lethal factor protein.the ability of genetic vaccination to protect against a lethal challenge of anthrax toxin was evaluated. balb/c mice were immunized via gene gun inoculation with eucaryotic expression vector plasmids encoding either a fragment of the protective antigen (pa) or a fragment of lethal factor (lf). plasmid pclf4 contains the n-terminal region (amino acids [aa] 10 to 254) of bacillus anthracis lf cloned into the pci expression plasmid. plasmid pcpa contains a biologically active portion (aa 175 to 764 ...200111401993
effect of ph on stability of anthrax lethal factor: correlation between denaturation and activity.anthrax is caused by gram positive bacterium bacillus anthracis. pathogenesis is result of production of three protein components, protective antigen (pa), lethal factor (lf), and edema factor (ef). pa in combination with lf (lethal toxin) is lethal to animals, while pa in combination with ef (edema toxin), causes edema. pa, lf, and ef are very thermolabile. differential scanning calorimetry (dsc) was used to unravel the energetics of lf denaturation as a function of ph ranging from 7.8 to 5.5. ...200111396937
the role of antibodies to bacillus anthracis and anthrax toxin components in inhibiting the early stages of infection by anthrax spores.vaccines which are efficacious against anthrax, such as the human vaccine, anthrax vaccine absorbed (ava), contain the protective antigen (pa) component of the anthrax toxins as the major protective immunogen. although ava protects against inhalational anthrax, the immune responses to and role in protection of pa and possibly other antigens have yet to be fully elucidated. sera from animals immunized with a toxin-producing, unencapsulated live vaccine strain of bacillus anthracis have been repor ...200111390699
a dominant-negative therapy for anthrax. 200111385497
pulmonary manifestations of bioterrorism.along with smallpox, inhalation anthrax and pneumonic plague are among the diseases most likely to be spread by biowarfare, either from a rogue nation or terrorist group. neither anthrax nor plague has been seen by many pulmonary (or any other) physicians in the united states. this article summarizes these two diseases as pulmonary manifestations of bioterrorism and discusses the possibility of avian influenza as a potential respiratory pathogen in biowarfare. it is hoped that phyisicians will n ...200111384555
when anthrax was a delaware valley disease: dr. herman gold's experience with cutaneous anthrax. 200111381482
toxemic shock, hematuria, hypokalemia, and hypoproteinemia in a case of cutaneous anthrax.a 20-year-old woman who had daily contact with domestic herbivores presented with a painless and pruritic lesion in her neck; the lesion ulcerated to a black necrotic eschar from which bacillus anthracis grew. rapidly expanding edema at the site of the ulcer was followed by shock, hematuria, hypokalemia, and hypoproteinemia. the latter symptoms - unusual for cutaneous anthrax - responded to intravenous penicillin therapy.200111373695
role of residues constituting the 2beta1 strand of domain ii in the biological activity of anthrax protective antigen.anthrax toxin consists of three proteins, protective antigen, lethal factor and oedema factor. a proteolytically activated 63-kda fragment of protective antigen binds lethal factor/oedema factor and translocates them into the cytosol. domain ii of protective antigen has been implicated in membrane insertion and channel formation. in the present study, alanine substitutions in 14 consecutive residues of the 2beta1 strand that are highly homologous to the putative membrane interacting segment of c ...200111356563
quantitative pathology of inhalational anthrax i: quantitative microscopic findings.forty-one cases of documented inhalational anthrax from the sverdlovsk epidemic of 1979 traced to release of aerosols of bacillus anthracis at a secret biologic-agent production facility were evaluated by semiquantitative histopathologic analysis of tissue concentrations of organisms, inflammation, hemorrhage, and other lesions in the mediastinum, mediastinal lymph nodes, bronchi, lungs, heart, spleen, liver, intestines, kidneys, adrenal glands, and central nervous system. these data were correl ...200111353060
mowed, a computer program to rapidly deconvolute low resolution electrospray liquid chromatography/mass spectrometry runs to determine component molecular weights.a computer program is described that can rapidly process low-resolution electrospray liquid chromatography/mass spectrometry (lc/ms) for peptides and proteins and assign molecular weights for observed components. the program first analyzes individual scans using a deconvolution algorithm similar to that previously described by zhang and marshall. results for the entire run are then sorted by mass and those values found in adjacent scans are grouped together. the list of found components can also ...200111349958
hospital preparedness for victims of chemical or biological terrorism.this study examined hospital preparedness for incidents involving chemical or biological weapons.200111344876
microbiology. fighting anthrax with a mutant toxin. 200111330322
constitutive expression of protective antigen gene of bacillus anthracis in escherichia coli.the fatal bacterial infection caused by inhalation of the bacillus anthracis spores results from the synthesis of protein toxins-protective antigen (pa), lethal factor (lf), and edema factor (ef)--by the bacterium. pa is the target-cell binding protein and is common to the two effector molecules, lf and ef, which exert their toxic effects once they are translocated to the cytosol by pa. pa is the major component of vaccines against anthrax since it confers protective immunity. the large-scale pr ...200111327699
use of anthrax vaccine in the united states: recommendations of the advisory committee on immunization practices.these recommendations concern the use of aluminum hydroxide adsorbed cell-free anthrax vaccine (anthrax vaccine adsorbed [ava], bioport corporation, lansing, mi) in the united states for protection against disease caused by bacillus anthracis. in addition, information is included regarding the use of chemoprophylaxis against b. anthracis.200111327233
delayed life-threatening reaction to anthrax vaccine.background: anthrax is an acute infectious disease caused by the spore-forming bacterium bacillus anthracis. due to the current world threat of unpredictable biological terrorism, the department of defense has mandated the systematic vaccination of all us military personnel against this warfare agent. many may experience al mild flu-like illness and soreness at the injection site, but systemic reactions are rare. case report: we report a delayed and potentially serious life-threatening adverse r ...200111327232
dominant-negative mutants of a toxin subunit: an approach to therapy of anthrax.the protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes. we identified dominant-negative mutants of protective antigen that co-assemble with the wild-type protein and block its ability to translocate the enzymic moieties across membranes. these mutants strongly inhibited toxin action in cell culture and in an animal intoxication model, suggesting ...200111326092
cutaneous anthrax of the eyelid. 200111324894
a general strategy for identification of s-layer genes in the bacillus cereus group: molecular characterization of such a gene in bacillus thuringiensis subsp. galleriae nrrl 4045.despite its possible role in virulence, there has been little molecular characterization of members of the s-layer protein family of the bacillus cereus group. it is hypothesized that the components of the s-layers are likely to display similar anchoring structures in bacillus thuringiensis and bacillus anthracis. based on inferred sequence similarities, a dna fragment encoding the cell-wall-anchoring domain of an s-layer component of bac: thuringiensis subsp. galleriae nrrl 4045 was isolated. t ...200111320137
genetic, physical, and transcript map of the ltxs1 region of mouse chromosome 11.lethal factor (lf) is a toxin secreted by bacillus anthracis that plays an important role in the pathogenesis of anthrax. intoxication with lf results in a macrophage-specific cytolysis that is not well understood. interestingly, inbred mouse strains exhibit dramatic differences in the susceptibility of their cultured macrophages to killing by lf, and a gene that influences this phenotype, called ltxs1, has been mapped to mouse chromosome 11. here we report a high-resolution genetic map that con ...200111318612
efficacy of a human anthrax vaccine in guinea pigs, rabbits, and rhesus macaques against challenge by bacillus anthracis isolates of diverse geographical origin.the efficacy of a licensed human anthrax vaccine (anthrax vaccine adsorbed (ava)) was tested in guinea pigs, rabbits, and rhesus macaques against spore challenge by bacillus anthracis isolates of diverse geographical origin. initially, groups of hartley guinea pigs were vaccinated at 0 and 4 weeks with ava, then challenged intramuscularly at 10 weeks with spores from 33 isolates of b. anthracis. survival among the vaccinated groups varied from 6 to 100%, although there were no differences in mea ...200111312020
a tandem repeats database for bacterial genomes: application to the genotyping of yersinia pestis and bacillus anthracis.some pathogenic bacteria are genetically very homogeneous, making strain discrimination difficult. in the last few years, tandem repeats have been increasingly recognized as markers of choice for genotyping a number of pathogens. the rapid evolution of these structures appears to contribute to the phenotypic flexibility of pathogens. the availability of whole-genome sequences has opened the way to the systematic evaluation of tandem repeats diversity and application to epidemiological studies.200111299044
bioterrorism. 200111294966
role of furin in delivery of a ctl epitope of an anthrax toxin-fusion protein.anthrax toxin lethal factor (lf) in combination with anthrax toxin protective antigen (pa) was endocytosed and translocated to the cytosol of mammalian cells. residues 1-255 of anthrax toxin lethal factor (lfn) was fused to a cytotoxic t lymphocyte (ctl) epitope of an influenza virus. for processing the toxins, pa must be cleaved into a 63-kda fragment (pa63) by furin, which is a subtilisin-like processing endo-protease expressed by many eukaryotic cells. to test the ability of cells treated wit ...200111293477
search for correlates of protective immunity conferred by anthrax vaccine.vaccination by anthrax protective antigen (pa)-based vaccines requires multiple immunization, underlying the need to develop more efficacious vaccines or alternative vaccination regimens. in spite of the vast use of pa-based vaccines, the definition of a marker for protective immunity is still lacking. here we describe studies designed to help define such markers. to this end we have immunized guinea pigs by different methods and monitored the immune response and the corresponding extent of prot ...200111292703
the science of louis pasteur: a reconsideration. 200111291570
[survival of bacillus anthracis spores in various tannery baths].the influence of tannery baths: liming, deliming, bating, pickling, tanning, retannage on the survival and on the germination dynamism of b. anthracis spores (sterne strain) was investigated. the periods and the conditions of this influence were established according to technological process of cow hide tannage. practically after every bath some part of the spores remained vital. the most effective killing of spores occurred after pickling, liming and deliming. inversely, the most viable spores ...200011286180
anthrax as the cause of preseptal cellulitis and cicatricial ectropion.a 54-year-old female farmer with anthrax infection of the eyelids is presented. she was initially managed with high dose intravenous penicillin g treatment. following complete healing of the eyelid lesions, significant cicatricial ectropion resulted. her right lower eyelid ectropion was corrected by surgical reconstruction using full thickness skin graft after a period of 6 months during which the cicatrization process stabilized. satisfactory cosmetic and functional improvement was achieved. an ...200111284766
targeting of tumor cells by cell surface urokinase plasminogen activator-dependent anthrax toxin.urokinase plasminogen activator receptor (upar) binds pro-urokinase plasminogen activator (pro-upa) and thereby localizes it near plasminogen, causing the generation of active upa and plasmin on the cell surface. upar and upa are overexpressed in a variety of human tumors and tumor cell lines, and expression of upar and upa is highly correlated to tumor invasion and metastasis. to exploit these characteristics in the design of tumor cell-selective cytotoxins, we constructed mutated anthrax toxin ...200111278833
a dominant negative mutant of bacillus anthracis protective antigen inhibits anthrax toxin action in vivo.pa63, a proteolytically activated 63-kda form of anthrax protective antigen (pa), forms heptameric oligomers and has the ability to bind and translocate the catalytic moieties, lethal factor (lf), and edema factor (ef) into the cytosol of mammalian cells. acidic ph triggers oligomerization and membrane insertion by pa63. a disordered amphipathic loop in domain ii of pa (2beta2-2beta3 loop) is involved in membrane insertion by pa63. because conditions required for membrane insertion coincide with ...200111278644
anthrax-toxin-mediated delivery of a 19 kda antigen of mycobacterium tuberculosis into the cytosol of mammalian cells.pa63, the proteolytically activated 63 kda fragment of protective antigen (pa, 83 kda), mediates translocation of lethal factor (lf) and oedema factor into the cytosol. the n-terminal 254 amino acids of lf (lfn) are required for binding to pa63 and mediating translocation of active ligands fused to either the n- or c-terminus. here we report translocation of a 19 kda antigen of mycobacterium tuberculosis into the cytosol of mammalian cells when fused to the c-terminus of lfn (lfn-19kda). the fus ...200111277858
bacillus cereus meningitis complicating cerebrospinal fluid fistula repair and spinal drainage.non-anthrax bacillus species are rare, but serious causes of bacterial meningitis in those either immunocompromised or treated with csf diversion. although resistant to first-line antibiotics, they usually respond to chloramphenicol. we report a case of fulminant bacillus cereus meningitis that complicated lumbar spinal drainage which proved resistant to all first-line antibiotics including chloramphenicol.200011272043
molecular characterization of bacillus anthracis using multiplex pcr, eric-pcr and rapd.to investigate the molecular characterization of bacillus anthracis strains by multiplex pcr, enterobacterial repetitive intergenic consensus-pcr (eric-pcr) and random amplification of polymorphic dna (rapd).200111264741
multiplexing for the detection of multiple biowarfare agents shows promise in the field.standard amplification of nucleic acids, or polymerase chain reaction (pcr), is replacing the more traditional microbiological assays in the detection of biological agents. however, standard pcr is designed as a one program-to-one agent amplification method, and not knowing what agents to test for makes this approach time consuming. during a field training exercise to detect four biowarfare agents using the standard pcr method, we conducted an additional experiment that reduced the diagnostic ti ...200111263027
suppression of ras-mediated transformation and inhibition of tumor growth and angiogenesis by anthrax lethal factor, a proteolytic inhibitor of multiple mek pathways.lethal factor is a protease, one component of bacillus anthracis exotoxin, which cleaves many of the mitogen-activated protein kinase kinases (meks). given the importance of mek signaling in tumorigenesis, we assessed the effects of anthrax lethal toxin (letx) on tumor cells. letx was very effective in inhibiting mitogen-activated protein kinase activation in v12 h-ras-transformed nih 3t3 cells. in vitro, treatment of transformed cells with letx caused them to revert to a nontransformed morpholo ...200111259649
are saudi arabian hospitals prepared for the threat of biological weapons?the use of biological weapons has been recorded repeatedly in history. until recently, biological terrorism had been little discussed or written about. however, events over the past 12 to 18 months have made it clear that likely perpetrators already envisage every possible scenario. nations and dissident groups exist that have both the motivation and access to utilize biological weapons. in april 1994, a russian biological weapons expert presented the conclusions of the russian experts as to the ...200111255601
rapid identification of bacillus cereus based on the detection of a 28.5-kilodalton cell surface antigen.conventional procedures for the identification of suspect bacillus cereus isolated on mannitol-egg yolk-polymyxin (myp) agar may need several days. to facilitate the identification of the bacterium, an enzyme-linked immunosorbent assay (elisa) was developed. the assay was based on the detection of a 28.5-kda cell surface antigen of b. cereus. bacterial colonies grown on myp agar or nutrient agar were suspended in phosphate-buffered saline (ph 7.2) containing 0.1% teepol. the cell suspensions wer ...200111252478
rapid identification of pathogenic bacteria by single-enzyme amplified fragment length polymorphism analysis.despite major progress in their treatment and prevention, bacterial infections remain a significant cause of morbidity and mortality worldwide. in responding to a disease outbreak, rapid and accurate identification of the bacterial species involved is of paramount importance. strain level discrimination is desirable to allow selection of treatment modalities, and in the case of a deliberate release, for identification of the source. single-enzyme amplified fragment length polymorphism (se-aflp) ...200111248519
the malaria vaccine: seventy years of the great immune hope.the cluster of seminal microbiological discoveries at the end of the 19th century through to the first quarter of the 20th century gave rise to the expectation that the control of malaria would be by scientific technology (as opposed to the 'brute force' of bonification/massive engeneering works) and that technology would be immunization by a malaria vaccine. immunology's foundation was in microbiology and the two related disciplines matured concurrently. immunization with dead or inactivated mi ...200011234327
involvement of domain 3 in oligomerization by the protective antigen moiety of anthrax toxin.protective antigen (pa), a component of anthrax toxin, binds receptors on mammalian cells and is activated by a cell surface protease. the resulting active fragment, pa(63), forms ring-shaped heptamers, binds the enzymic moieties of the toxin, and translocates them to the cytosol. of the four crystallographic domains of pa, domain 1 has been implicated in binding the enzymic moieties; domain 2 is involved in membrane insertion and oligomerization; and domain 4 binds receptor. to determine the fu ...200111222612
bioterrorism. 200011219298
citywide pharmaceutical preparation for bioterrorism.one community's efforts to become pharmaceutically prepared for an attack with biological agents is described. in response to recent bioterrorist activities, including a local scare in 1999 involving anthrax, the pharmacy department at deaconess medical center in spokane, washington, was asked to develop a plan for bioterrorism preparedness. a literature search was conducted, and resources, such as the centers for disease control and prevention, were contacted. for each biological agent, informa ...200111217178
early bacillus anthracis-macrophage interactions: intracellular survival survival and escape.this study describes early intracellular events occurring during the establishment phase of bacillus anthracis infections. anthrax infections are initiated by dormant endospores gaining access to the mammalian host and becoming engulfed by regional macrophages (mphi). during systemic anthrax, late stage events include vegetative growth in the blood to very high titres and the synthesis of the anthrax exotoxin complex, which causes disease symptoms and death. experiments focus on the early events ...200011207600
translocation of bacillus anthracis lethal and oedema factors across endosome membranes.the two exotoxins of bacillus anthracis, the causative agent of anthrax, are the oedema toxin (pa-ef) and the lethal toxin (pa-lf). they exert their catalytic activities within the cytosol. the internalization process requires receptor-mediated endocytosis and passage through acidic vesicles. we investigated the translocation of ef and lf enzymatic moieties across the target cell membrane. by selective permeabilization of the plasma membrane with clostridium perfringens delta-toxin, we observed ...200011207582
proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization.immunofluorescence and other methods have been used to probe the self-assembly and internalization of the binary toxin, anthrax lethal toxin (letx), in primary murine macrophages. proteolytic activation of protective antigen (pa; 83 kda, the b moiety of the toxin) by furin was the rate-limiting step in internalization of letx and promoted clearance of pa from the cell surface. a furin-resistant form of pa remained at the cell surface for at least 90 min. oligomerization of receptor-bound pa63, t ...200011207581
emergency: bioterrorism. 200011202782
rapid recovery and identification of anthrax bacteria from the environment.bacillus anthracis has been recognized as a highly likely biological warfare or terrorist agent. we have designed culture techniques to rapidly isolate and identify "live" anthrax from suspected environmental release. a special medium (3at medium) allows for discrimination between closely related bacilli and non-pathogenic strains. nitrate was found to be a primary factor influencing spore formation in bacillus anthracis. nitrate reduction in anthrax is not an adaptation to saprophytic environme ...200011193628
[brief review of the history of zoonoses].by studying the surviving documents describing surveillance and methods of control of zoonoses in the distant past, the history of the fight against these diseases can be retraced. prior to the 20th century, the best known zoonoses were, amongst others, rabies, anthrax, glanders, tuberculosis, plague, yellow fever, influenza, and certain zoonotic parasitic diseases. an analysis of historical events yields a number of lessons as to the positive and negative influences of past theories regarding t ...200011189711
[bioterrorism--a public and health threat].in recent years the fear of bioterrorism, of secret modernization and dissemination of biological weapons is increasing. facts detected recently in iran, japan and the former soviet union provide evidence that there are countries and dissident groups which have access to modern technology of cultivation of dangerous pathogens as well as motivation for their use in acts of terrorism or war. the menace of biological terrorism is nowadays, as compared with the past, much greater. the most feared ca ...200011188765
the bubonic man. lessons from a bioterrorism incident. 200011186485
[study of the virulence of a recombinant strain of bacillus anthracis, obtained as a result of transductive transfer of chromosomal genes from a strain of bacillus cereus].auxotrophic markers of b. anthracis strains differing them from other bacillus representatives have been determined. chromosome genes from prototrophic b. cereus strain were transduced into auxotrophic b. anthracis strain. the properties of transductants were studied in order to establish common transfer of chromosomal determinants responsible for realization of various signs. transduction mating between species resulted in construction of prototroph b. anthracis strains (px01- px02+), whose der ...200011186451
biological consequences of multiple vaccine and pyridostigmine pretreatment in the guinea pig.an investigation of the possible interactions between combinations of vaccines and pyridostigmine bromide (pb) has been undertaken in the guinea pig. this study is part of a research programme funded by the uk government to determine any effects of the pretreatment regimes given to uk forces during the persian gulf conflict of 1990-1991. the study was designed to simulate pb administration and to model multiple vaccination protocols that were experienced by uk forces, modelling a "worst case" si ...200111180281
trp 346 and leu 352 residues in protective antigen are required for the expression of anthrax lethal toxin activity.the three separate proteins that make up anthrax toxin-protective antigen (pa), edema factor (ef) and lethal factor (lf) act in binary combinations to produce two distinct reactions in experimental animals: edema (pa+ef) and death (pa+lf). pa is believed to interact with a membrane receptor and, after proteolytic processing, to mediate endocytosis and subsequent translocation of ef or lf into the cytosol. residues w346, m350, and l352 in loop 3 of domain 2 have been implicated to induce a confor ...200111178978
bacillus anthracis, a bug with attitude!the sequencing of the bacillus anthracis genome and virulence plasmids represents the greatest advance in anthrax research in the past 100 years. the data will provide the foundation of all future work on this organism and will be invaluable to researchers in their battle to understand the basis of the host-microbe interaction.200111173038
risks and prevention of nosocomial transmission of rare zoonotic diseases.americans are increasingly exposed to exotic zoonotic diseases through travel, contact with exotic pets, occupational exposure, and leisure pursuits. appropriate isolation precautions are required to prevent nosocomial transmission of rare zoonotic diseases for which person-to-person transmission has been documented. this minireview provides guidelines for the isolation of patients and management of staff exposed to the following infectious diseases with documented person-to-person transmission: ...200111170953
use of live bacterial vaccine vectors for antigen delivery: potential and limitations.most infectious agents are restricted to the mucosal membranes or their transit through the mucosa constitutes a critical step in the infection process. therefore, the elicitation of an efficient immune response, not only at systemic, but also at mucosal level, after vaccination is highly desirable, representing a significant advantage in order to prevent infection. this goal can be only achieved, when the vaccine formulation is administered by the mucosal route. however, soluble antigens given ...200111166877
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