Prehospital Disaster Med, 2003 Apr-Jun, 18(2), 140 - 7 Terrorism in South Korea; Wang SJ et al.; South Korea has experienced > 30 suspected terrorism-related events since 1958, including attacks against South Korean citizens in foreign countries . The most common types of terrorism used have included bombings, shootings, hijackings, and kidnappings . Prior to 1990, North Korea was responsible for almost all terrorism-related events inside of South Korea, including multiple assassination attempts on its presidents, regular kidnappings of South Korean fisherman, and several high-profile bombings . Since 1990, most of the terrorist attacks against South Korean citizens have occurred abroad and have been related to the emerging worldwide pattern of terrorism by international terrorist organizations or deranged individuals . The 1988 Seoul Olympic Games provided a major stimulus for South Korea to develop a national emergency response system for terrorism-related events based on the participation of multiple ministries . The 11 September 2001 World Trade Center and Pentagon attacks and the 2001 United States of America (US) anthrax letter attacks prompted South Korea to organize a new national system of emergency response for terrorism-related events . The system is based on five divisions for the response to specific types of terrorist events, involving conventional terrorism, bioterrorism, chemical terrorism, radiological terrorism, and cyber-terrorism . No terrorism-related events occurred during the 2002 World Cup and Asian Games held in South Korea . The emergency management of terrorism-related events in South Korea is adapting to the changing risk of terrorism in the new century. Methods Mol Biol, 2004, 261, 213 - 28 Use of phage display and polyvalency to design inhibitors of protein-protein interactions; Mourez M et al.; We describe the synthesis of an inhibitor that interferes with critical protein-protein interactions occurring during the assembly of anthrax toxin . Using a phage display selection strategy, we isolated a peptide directed against the cell binding moiety of the toxin that was able to interfere with binding of the enzymatic moieties . Because the cell binding moiety of the toxin is a heptamer, the peptide can potentially bind up to seven equivalent sites . We synthesized a polyvalent molecule displaying multiple copies of this peptide and showed that it is a much more potent inhibitor than the free peptide . Because little structural knowledge of the interacting proteins was required to synthesize this inhibitor, we believe that this approach may prove useful in the design of inhibitors of protein-protein interactions in other systems. Methods Mol Biol, 2004, 261, 113 - 8 Using light scattering to determine the stoichiometry of protein complexes; Mogridge J; The stoichiometry of a protein complex can be calculated from an accurate measurement of the complex's molecular weight . Multiangle laser light scattering in combination with size-exclusion chromatography and interferometric refractometry provides a powerful means for determining the molecular weights of proteins and protein complexes . In contrast to conventional size-exclusion chromatography and analytical centrifugation, measurements do not rely on the use of molecular weight standards and are not affected by the shape of the proteins . The technique is based on the direct relationship between the amount of light scattered by a protein in solution and the product of its concentration and molecular weight . A typical experimental configuration includes a size-exclusion column to fractionate the sample, a light-scattering detector to measure scattered light, and an interferometric refractometer to measure protein concentration . The determination of the molecular weight of an anthrax toxin complex will be examined to illustrate how multiangle laser light scattering can be used to determine the stoichiometry of protein complexes. Eur J Pharmacol, 2004 Apr 5, 489(1-2), 117 - 26 Up-regulation of bradykinin receptors in a murine in-vitro model of chronic airway inflammation; Zhang Y et al.; Tumour necrosis factor-alpha (TNF-alpha) is a mediator with a likely role in chronic airway inflammation and airway hyperresponsiveness . In the present study, mouse tracheal segments were cultured for 1, 4 or 8 days in the absence and presence of TNF-alpha . Contractile response of cultured segments to des-Arg9-bradykinin and bradykinin was assessed in myographs and mRNA for bradykinin B1 and B2 receptors was quantified by real-time polymerase chain reaction . Both contraction to des-Arg9-bradykinin and bradykinin, mediated via bradykinin B1 and B2 receptors, respectively, and mRNA levels for these receptors were up-regulated following culture . These responses were markedly increased in segments treated with TNF-alpha . Experiments with SP600125 (anthrax(1,9-cd)pyrazol-6(2H)-one) and PD98059 (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) demonstrated that both intracellular c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 pathways were implicated in this process . Thus, TNF-alpha causes an increase of bradykinin contractility in mouse trachea, which at least partly is due to a transcriptional increase of bradykinin receptors. Respir Care Clin N Am, 2004 Mar, 10(1), 123 - 46 Vaccines against biologic agents: uses and developments; Ales NC et al.; Although the Geneva protocol that prohibits the use of chemical and biologic weapons was ratified in 1925, many countries failed to accept this protocol: others stipulated retaliation, and some, like the United States, did not ratify the protocol for decades . This delay allowed the continued development of chemical and biologic agents . Members of the health care community are responsible for determining the best way to protect society from the potentially devastating effects of these biologic agents . Ideally,these diseases would be prevented from ever developing into systemic illnesses . In the past, vaccination has been a successful means of eradicating disease . Vaccines remain a hopeful therapy for the future, but time is short,and there are many obstacles.Information regarding bioterrorism agents and their treatments comes mainly from dated data or from in vitro or animal studies that may not apply to human treatment and disease . Additionally, the current threat of bioterrorism does not allow enough time for accurate, well-designed,controlled studies in humans before the release of investigational vaccines . Furthermore, some human studies would not be safe or ethical . Finally,many members of society suffer from illnesses that would put them at high risk to receive prophylactic vaccination . It is therefore naive to believe that vaccines would be the ultimate protection from these agents . In addition to vaccine development, there must be concurrent investigations into disease management and treatment . Even in instances in which vaccination is known to be an effective means of disease protection . biologic agents may be presented in a manner that renders vaccines ineffective . Virulent strains of organisms may be used, more than one organism may be used in tandem to increase virulence, and strains may be selected for antibiotic and vaccine resistance . Genetically engineered strains may use virulence factors other than those targeted in vaccines, and high concentrations of organisms may overcome vaccine protection . Finally,exposure may not be immediately noted until it is too late to vaccinate, as was the case with anthrax . Even in a case, such as smallpox, in which postexposure vaccination is possible, patients will still develop disease, and the health care system may be overwhelmed.The United States government has been defensively planning and researching the use of vaccines and chemoprophylaxis against any potential biologic agents since at least 1953, and resources are still lacking . There are inadequate stockpiles of vaccine to protect the entire population . The pharmaceutical industry also lacks a means of mass producing vaccines ina short timeframe . There is no policy in place for the use of vaccines that are yet unlicensed and experimental but may be the only therapy in the event ofa terrorist attack . Investigations into these solutions have been instituted only after the September 11, 2001, attacks heightened the awareness of terrorism . Although vaccination is an effective means of prophylaxis and a means of terminating epidemics or treating active disease, there is also resistance from the general public . In some instances there is a lack of acceptance of vaccines, or the risk of side effects is too great . In other cases, a questionable benefit does not justify the expense of mass vaccination . Because of this uncertainty, mass vaccination is deemed an impractical solution to the threat of bioterrorism . Extending vaccination with most vaccines to include all members of society who may be first responders in the event of an attack should be considered . In all instances, the benefit-to-risk must be weighed ratio when deciding how and when to offer preemptive prophylaxis to protect society from a real but unknown threat. Respir Care Clin N Am, 2004 Mar, 10(1), 75 - 82 Inhalational anthrax; Cuneo BM; Anthrax remains a real threat . In a spore form, it is highly infectious and dispersible . The initial symptoms are similar to those of influenza, and the early stage of inhalational anthrax may not be recognized . Early antibiotic treatment is important to achieving a good outcome . Contrary to historical experience . many patients with even advanced anthrax can be saved with aggressive medical care.Prevention of anthrax infections requires vigilant infection control methods as well as a rational prophylactic plan . All health care providers should be familiar with the symptoms and treatment of this disease . It is hoped that future research will clarify tests for early diagnosis, the best methods of prophylaxis, and the most effective treatments . Unfortunately the threat of bioterrorism, and anthrax in particular, is unlikely to go away. Exp Biol Med (Maywood), 2004 Apr, 229(4), 345 - 50 Fate of bioterrorism-relevant viruses and bacteria, including spores, aerosolized into an indoor air environment; Utrup LJ et al.; An aerosol physics test facility was used in a series of eight experiments to gather an integrated comprehensive broad base of data on the fate of surrogates of microorganisms that cause smallpox, plague, glanders, anthrax, and viral hemorrhagic fevers . The results are directly relevant to the public health issue of how to protect the occupants of buildings against bioterrorism . The test conditions were directly relevant to the indoor air environment situation, and the results can be generalized to buildings that are now occupied . The reductions in concentrations of relevant viruses and bacteria--including gram-negative fermenters and nonfermenters, gram-positive cocci and bacilli, and spores--were substantial and statistically robust . The data show that the bioterrorism-relevant aerosolized viruses and bacteria, including spores, respond like small particulates to the primary (electrical) forces that control the distribution of small particulates in a room . Further, these relevant microorganisms respond like small particulates to means designed to control airborne particulates . The results could be used to anticipate the effects of a bioterrorist attack on the public health, provide information on means that can be used to minimize such effects, and used to make decisions on how best to protect occupants of specific buildings at minimal cost and with assurance of success. J Biol Chem, 2004 May 28, 279(22), 23349 - 56 Epub 2004 Mar 24. Binding stoichiometry and kinetics of the interaction of a human anthrax toxin receptor, CMG2, with protective antigen; Wigelsworth DJ et al.; The protective antigen (PA) moiety of anthrax toxin binds to cellular receptors and mediates entry of the two enzymatic moieties of the toxin into the cytosol . Two PA receptors, anthrax toxin receptor (ATR)/tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2), have been identified . We expressed and purified the von Willebrand A (VWA) domain of CMG2 and examined its interactions with monomeric and heptameric forms of PA . Monomeric PA bound a stoichiometric equivalent of CMG2, whereas the heptameric prepore form bound 7 eq . The Kd of the VWA domain-PA interaction is 170 pm when liganded by Mg2+, reflecting a 1000-fold tighter interaction than most VWA domains with their endogenous ligands . The dissociation rate constant is extremely slow, indicating a 30-h lifetime for the CMG2.PA monomer complex . CMG2 metal ion-dependent adhesion site (MIDAS) was studied kinetically and thermodynamically . The association rate constant (approximately 10(5) m(-1) s(-1)) is virtually identical in the presence or absence of Mg2+ or Ca2+ , but the dissociation rate of metal ion liganded complex is up to 4 orders of magnitude slower than metal ion free complex . Residual affinity (Kd approximately 960 nm) in the absence of divalent metal ions allowed the free energy for the contribution of the metal ion to be calculated as 5 kcal mol(-1), demonstrating that the metal ion-dependent adhesion site is directly coordinated by CMG2 and PA in the binding interface . The high affinity of the VWA domain for PA supports its potency in neutralizing anthrax toxin, demonstrating its potential utility as a novel therapeutic for anthrax. Acad Med, 2004 Apr, 79(4), 333 - 42 Protecting America's secrets while maintaining academic freedom; Keel BA; The terrorist attacks of September 11, 2001, and the subsequent anthrax mail attacks, have had a profound impact on Americans' personal and professional lives and have sparked an active debate regarding the delicate balance between the need for national security and the pursuit of academic freedom . Although academic freedom can be defined in many ways, there are four primary tenets of freedom in an academic environment: freedom to research, freedom to publish, freedom to teach, and freedom to speak . Each of these tenets has come under attack in the wake of September 11, 2001 . In this report the author further defines academic freedom and reflects upon recent events that have had a real or perceived impact on this freedom, including (1) attempts to categorize and restrict some research as "sensitive," (2) implementation of export control laws and select agent regulations, (3) limitations on the publication of research findings, (4) prohibition of certain foreign nationals from collaborating with U.S . researchers and receiving education and training in U.S . colleges and universities, and (5) restraint of faculty free speech . The author offers some suggestions as to how academia might achieve a proper balance between protecting our national security while promoting and maintaining academic freedom. Mol Biol (Mosk), 2004 Jan-Feb, 38(1), 5 - 16 {Microchips based on three dimensional gel cells: history and perspective}; Kolchinskii AM et al.; The review describes the history of creation and development of the microchip technology and its role in the human genome project in Russia . The emphasis is placed on the three-dimensional gel-based microchips developed at the Center of Biological Microchips headed by A.D . Mirzabekov since 1988 . The gel-based chips of the last generation, IMAGE chips (Immobilized Micro Array of Gel Elements), have a number of advantages over the previous versions . The microchips are manufactured by photo-initiated copolymerization of gel components and immobilized molecules (DNA, proteins, and ligands) . This ensures an even distribution of the immobilized probe throughout the microchip gel element with a high yield (about 50% for oligonucleotides) . The use of methacrylamide as a main component of the polymerization mixture resulted in a substantial increase of gel porosity without affecting its mechanical strength and stability, which allowed one to work with the DNA fragments of up to 500 nt in length, as well as with rather large protein molecules . At present, the gel-based microchips are widely applied to address different problems . The generic microchips containing a complete set of possible hexanucleotides are used to reveal the DNA motifs binding with different proteins and to study the DNA-protein interactions . The oligonucleotide microchips are a cheap and reliable tool of diagnostics designed for mass application . Biochips have been developed for identification of the tuberculosis pathogen and its antibiotic-resistant forms; for diagnostics of orthopoxviruses, including the smallpox virus; for diagnostics of the anthrax pathogen; and for identification of chromosomal rearrangements in leukemia patients . The protein microchips can be adapted for further use in proteomics . Bacterial and yeast cells were also immobilized in the gel, maintaining their viability, which open a wide potential for creation biosensors on the basis of microchips. Arch Intern Med, 2004 Mar 22, 164(6), 674 - 6 Differentiating inhalational anthrax from other influenza-like illnesses in the setting of a national or regional anthrax outbreak; Cinti SK et al.; The workup of a febrile patient who presents with an influenza-like illness in the setting of a national or regional anthrax outbreak presents a unique challenge to the physicians who initially evaluate this patient, and the diagnostic challenge can be even more profound during the influenza season . Based on information gathered from the recent inhalational anthrax cases, we have developed an algorithm to be used by physicians in the emergency department to evaluate patients with influenza-like illnesses during a national or regional anthrax outbreak . The algorithm necessitates stays no longer than 24 hours in the emergency department or hospital. Nat Rev Microbiol, 2004 Jan, 2(1), 67 - 72 Molecular Koch's postulates applied to bacterial pathogenicity--a personal recollection 15 years later; Falkow S; Koch's postulates were derived from Robert Koch's work on infectious diseases, such as anthrax and tuberculosis, which still engage us to this day . These guidelines were an attempt to establish a standard for identifying the specific causation of an infectious disease and to convince sceptics that microorganisms could cause disease . They were also established to encourage an increasing number of novice microbiologists to use more rigorous criteria before claiming a causal relationship between a microorganism and a disease. EMBO Rep, 2004 Apr, 5(4), 418 - 22 Epub 2004 Mar 12. Potent inhibitors of anthrax lethal factor from green tea; Dell'Aica I et al.; The anthrax lethal factor (LF) has a major role in the development of anthrax . LF is delivered by the protective antigen (PA) inside the cell, where it exerts its metalloprotease activity on the N-terminus of MAPK-kinases . PA+LF are cytotoxic to macrophages in culture and kill the Fischer 344 rat when injected intravenously . We describe here the properties of some polyphenols contained in green tea as powerful inhibitors of LF metalloproteolytic activity, and how the main catechin of green tea, (-)epigallocatechin-3-gallate, prevents the LF-induced death of macrophages and Fischer 344 rats. Vestn Ross Akad Med Nauk, 2004, (1), 21 - 3 {Effect of hydrogen peroxide on the virulent properties of anthrax pathogen spores}; Kanishchev VV et al.; The impact exerted by hydrogen peroxide on the virulent properties of anthrax pathogen spores was experimentally evaluated . Even a short-term exposure of them to a disinfect was shown to cause impairments of the functional nature in the spores' vital structures, e.g . suppression of multiplication . At the same time, the biological monitoring of disinfection efficiency does not always rule out the presence of viable pathogen spores in the disinfected objects. Infect Genet Evol, 2004 Mar, 4(1), 21 - 8 Comparative proteomics of the Mycobacterium leprae binding protein myelin P0: its implication in leprosy and other neurodegenerative diseases; Vardhini D et al.; Mycobacterium leprae, the causative agent of leprosy invades Schwann cells of the peripheral nerves leading to nerve damage and disfigurement, which is the hallmark of the disease . Wet experiments have shown that M . leprae binds to a major peripheral nerve protein, the myelin P zero (P0) . This protein is specific to peripheral nerve and may be important in the initial step of M . leprae binding and invasion of Schwann cells which is the feature of leprosy . Though the receptors on Schawann cells, cytokines, chemokines and antibodies to M . leprae have been identified the molecular mechanism of nerve damage and neurodegeneration is not clearly defined . Recently pathogen and host protein/nucleotide sequence similarities (molecular mimicry) have been implicated in neurodegenerative diseases . The approach of the present study is to utilise bioinformatic tools to understand leprosy nerve damage by carrying out sequence and structural similarity searches of myelin P0 with leproma and other genomic database . Since myelin P0 is unique to peripheral nerve, its sequence and structural similarities in other neuropathogens have also been noted . Comparison of myelin P0 with the M . leprae proteins revealed two characterised proteins, Ferrodoxin NADP reductase and a conserved membrane protein, which showed similarity to the query sequence . Comparison with the entire genomic database by basic local alignment search tool for proteins (BLASTP) and fold classification of structure-structure alignment of proteins (FSSP) searches revealed that myelin P0 had sequence/structural similarities to the poliovirus receptor, coxsackie-adenovirus receptor, anthrax protective antigen, diphtheria toxin, herpes simplex virus, HIV gag-1 peptide, and gp120 among others . These proteins are known to be associated directly or indirectly with neruodegeneration . Sequence and structural similarities to the immunoglobin regions of myelin P0 could have implications in host-pathogen interactions, as it has homophilic adhesive properties . Although these observed similarities are not highly significant in their percentage identity, they could be functionally important in molecular mimicry, receptor binding and cell signaling events involved in neurodegeneration. Ann Epidemiol, 2004 Feb, 14(2), 81 - 8 Anthrax vaccination and self-reported symptoms, functional status, and medical conditions in the National Health Survey of Gulf War Era Veterans and Their Families; Mahan CM et al.; PURPOSE: To evaluate the health status of Gulf War veterans who reported receipt of anthrax vaccination and a small group of Gulf War veterans for whom documentation of anthrax vaccination exists . METHODS: Among the 11,441 Gulf War veterans who completed a health survey, 4601 reported receiving the anthrax vaccine during the war; 2979 veterans reported not receiving it; 3861 were uncertain . Also, 352 of these respondents were documented by the Department of Defense as having received anthrax vaccination . We compared the medical history of these groups of veterans using multivariate analyses . Finally, we analyzed perception of exposure and its relation to reporting bias . RESULTS: There were statistically significant differences in prevalence for almost all outcomes studied between those who reported having received anthrax vaccination and those who did not so report . However, when we compared the veterans for whom vaccination records exist to the group who self-reported that they had not received the vaccine, the significant differences in prevalence for almost all of the outcomes disappeared . CONCLUSIONS: The extent of a reporting bias should be carefully considered when one evaluates the health consequences of anthrax vaccination based on self-reported data. Med Confl Surviv, 2004 Jan-Mar, 20(1), 4 - 18 Proliferation of biological weapons: challenges and responses; Millett PD; The threat posed by the proliferation of biological weapons (BW) confronts all strata of our society, from the individual, the nation, or the region to the truly international . The history of state-run offensive BW programmes and the attacks in the United States with powdered anthrax demonstrate that existing measures fall short of addressing this threat . This article examines the current regime and the concerns that confront it in order to suggest possible responses across the social strata that may mitigate future proliferation of BW. Neoplasma, 2004, 51(1), 21 - 4 Modification of clastogenesis and carcinogenesis in rats and mice by means of anthrax live vaccine; Nersesyan AK; Possible micronuclei (MN) inducing activity of anthrax live vaccine (ALV; produced in Armenia and used for immunization of animals) was studied on rats and mice . It has been shown that ALV did not induce MN in rodents' bone marrow erythrocytes . For the first time it has been shown that immunization of rats and mice with ALV led to decrease of micronuclei number induced by cyclophosphamide and 7,12-dimethylbenz(a)anthracene in bone marrow cells . Immunized rats were also resistant to carcinogenic action of 7,12-dimethylbenz(a)anthracene . Immunization reduced significantly the number of rats with tumor and mean tumor weight, and increase the mean latency period of tumor development . It would be of interest to carry out further investigations of the anticlastogenic/anticarcinogenic effects of ALV used for immunization of humans, if only because anthrax was used and may be used again in future as a biological weapon. Microbiology, 2004 Mar, 150(Pt 3), 601 - 11 Two distinct types of rRNA operons in the Bacillus cereus group; Candelon B et al.; The Bacillus cereus group includes insecticidal bacteria (B . thuringiensis), food-borne pathogens (B . cereus and B . weihenstephanensis) and B . anthracis, the causative agent of anthrax . The precise number of rRNA operons in 12 strains of the B . cereus group was determined . Most of the tested strains possess 13 operons and the tested psychrotolerant strains contain 14 operons, the highest number ever found in bacteria . The separate clustering of the tested psychrotolerant strains was confirmed by partial sequencing of several genes distributed over the chromosomes . Analysis of regions downstream of the 23S rRNA genes in the type strain B . cereus ATCC 14579 indicates that the rRNA operons can be divided into two classes, I and II, consisting respectively of eight and five operons . Class II operons exhibit multiple tRNA genes downstream of the 5S rRNA gene and a putative promoter sequence in the 23S-5S intergenic region, suggesting that 5S rRNA and the downstream tRNA genes can be transcribed independently of the 16S and 23S genes . Similar observations were made in the recently sequenced genome of B . anthracis strain Ames . The existence of these distinct types of rRNA operons suggests an unknown mechanism for regulation of rRNA and tRNA synthesis potentially related to the pool of amino acids available for protein synthesis. Ann Emerg Med, 2004 Mar, 43(3), 318 - 28 Is it influenza or anthrax? A decision analytic approach to the treatment of patients with influenza-like illnesses; Fine AM et al.; STUDY OBJECTIVE: We analyze the risks and benefits of alternative treatment strategies for non-septic-appearing febrile patients with influenza-like illnesses and possible exposure to anthrax . METHODS: We used a decision analytic model to evaluate 6 testing and treatment strategies in an emergency department . Patients were non-septic-appearing and had influenza-like illnesses but low likelihood of exposure to anthrax . The following interventions were used: (1) no empiric antibiotics; (2) blood culture and treatment only if the result was positive; (3) rapid testing for influenza and, for those who tested negative, treatment with 60 days of ciprofloxacin; (4) a two-test strategy in which all patients were first tested for influenza; those who tested negative had a blood culture test and were treated empirically with ciprofloxacin for 3 days while waiting for blood culture results; (5) culture test for all patients and treatment with ciprofloxacin for up to 3 days while waiting for blood culture results; and (6) treatment of all patients with ciprofloxacin empirically for 60 days . Main outcome measures were deaths, complications from anthrax, adverse events from ciprofloxacin, and ciprofloxacin patient-days . RESULTS: For nonzero probabilities of anthrax, patient mortality was always lowest in the strategies in which all patients were treated empirically for anthrax either for 60 days or for 3 days pending blood culture results . These strategies, however, were associated with more morbidity (more ciprofloxacin patient-days and more antibiotic adverse events) than were strategies without empiric treatment . The numbers of adverse events and antibiotic patient-days were reduced substantially with the two-test strategy, in which patients with influenza were identified early and not treated . In general, for probabilities of anthrax equaling or exceeding 2%, treating all patients empirically for 60 days was best, but for probabilities between 0.1% and 2%, the sensitivity of blood culture for anthrax determined the optimal strategy: when the sensitivity exceeded 95%, a short course of empiric ciprofloxacin until blood culture results became available was best, but for sensitivities below 95%, more aggressive empiric antibiotics use was warranted . The proportion of patients with influenza in the community affected the choice of strategy, so that seasonal variation exists . CONCLUSION: During influenza season, our findings support rapid testing for influenza, followed by empiric treatment for anthrax pending blood culture results for those who test negative for influenza . Our results help to highlight the importance of developing rapid and sensitive tests for anthrax and of developing improved surveillance and methods to calculate the previous probability of attacks. Protein Eng Des Sel, 2004 Jan, 17(1), 107 - 12 Prediction of proprotein convertase cleavage sites; Duckert P et al.; Many secretory proteins and peptides are synthesized as inactive precursors that in addition to signal peptide cleavage undergo post-translational processing to become biologically active polypeptides . Precursors are usually cleaved at sites composed of single or paired basic amino acid residues by members of the subtilisin/kexin-like proprotein convertase (PC) family . In mammals, seven members have been identified, with furin being the one first discovered and best characterized . Recently, the involvement of furin in diseases ranging from Alzheimer's disease and cancer to anthrax and Ebola fever has created additional focus on proprotein processing . We have developed a method for prediction of cleavage sites for PCs based on artificial neural networks . Two different types of neural networks have been constructed: a furin-specific network based on experimental results derived from the literature, and a general PC-specific network trained on data from the Swiss-Prot protein database . The method predicts cleavage sites in independent sequences with a sensitivity of 95% for the furin neural network and 62% for the general PC network . The ProP method is made publicly available at http://www.cbs.dtu.dk/services/ProP. Can HIV AIDS Policy Law Rev, 2002 Mar, 6(3), 53 - 4 Canada/US: bioterrorism highlights double standard for access to medicines; Elliott R; In September 2001, shortly after terrorist attacks in the United States, the issue of bioterrorism--and specifically fear about reported cases of anthrax in the US--led the Canadian Minister of Health to be concerned about the available stocks of the drug ciprofloxacin to treat this disease. Proc Natl Acad Sci U S A, 2004 Mar 2, 101(9), 3242 - 7 Epub 2004 Feb 20. Selective inhibition of anthrax edema factor by adefovir, a drug for chronic hepatitis B virus infection; Shen Y et al.; Edema factor (EF), a key virulence factor in anthrax pathogenesis, has calmodulin (CaM)-activated adenylyl cyclase activity . We have found that adefovir dipivoxil, a drug approved to treat chronic infection of hepatitis B virus, effectively inhibits EF-induced cAMP accumulation and changes in cytokine production in mouse primary macrophages . Adefovir diphosphate (PMEApp), the active cellular metabolite of adefovir dipivoxil, inhibits the adenylyl cyclase activity of EF in vitro with high affinity (K(i) = 27 nM) . A crystal structure of EF-CaM-PMEApp reveals that the catalytic site of EF forms better van der Waals contacts and more hydrogen bonds with PMEApp than with its endogenous substrate, ATP, providing an explanation for the approximately 10,000-fold higher affinity EF-CaM has for PMEApp versus ATP . Adefovir dipivoxil is a clinically approved drug that can block the action of an anthrax toxin . It can be used to address the role of EF in anthrax pathogenesis. Cancer Res, 2004 Feb 1, 64(3), 817 - 20 TEM8 interacts with the cleaved C5 domain of collagen alpha 3(VI); Nanda A et al.; Tumor endothelial marker (TEM)8 was uncovered as a gene expressed predominantly in tumor endothelium, and its protein product was recently identified as the receptor for anthrax toxin . Here, we demonstrate that TEM8 protein is preferentially expressed in endothelial cells of neoplastic tissue . We used the extracellular domain of TEM8 to search for ligands and identified the alpha 3 subunit of collagen VI as an interacting partner . The TEM8-interacting region on collagen alpha 3(VI) was mapped to its COOH-terminal C5 domain . Remarkably, collagen alpha 3(VI) is also preferentially expressed in tumor endothelium in a pattern concordant with that of TEM8 . These results suggest that the TEM8/C5 interaction may play an important biological role in tumor angiogenesis. Gesundheitswesen, 2004 Feb, 66 Suppl 1, S26 - 30 {Current epidemiology of selected bacterial zoonoses}; Weber A; The present epidemiology of selected bacterial zoonoses brucellosis, anthrax, tularemia, Q fever, Chlamydia infections, tuberculosis, respectively mycobacteriosis and EHEC infections, is discussed. Eur J Biochem, 2004 Feb, 271(4), 821 - 33 Insight into the activation mechanism of Bordetella pertussis adenylate cyclase by calmodulin using fluorescence spectroscopy; Gallay J et al.; 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 dominates the fluorescence emission of both AC and AC-CaM, similar to that observed for isolated CaM-binding sequences of different lengths {Bouhss, A., Vincent, M., Munier, H., Gilles, A.M., Takahashi, M., Barzu, O., Danchin, A . & Gallay, J . (1996) Eur . J . Biochem.237, 619-628} . In contrast, Ant-dATP remains completely immobile and inaccessible to the solvent in both the AC and AC-CaM nucleotide-binding sites . As AC contains no cysteine residue, a single-Cys mutant at position 75 was constructed which allowed labeling of the catalytic domain with acrylodan . Its environment is strongly apolar and rigid, and only slightly affected by CaM . The protein's hydrodynamic properties were also studied by fluorescence anisotropy decay measurements . The average Brownian rotational correlation times of AC differed significantly according to the probe used (19 ns for W242, 25 ns for Ant-dATP, and 35 ns for acrylodan), suggesting an elongated protein shape (axial ratio of approximately 1.9) . These values increased greatly with the addition of CaM (39 ns for W242, 60-70 ns for Ant-dATP and 56 ns for acrylodan) . This suggests that (a) the orientation of the probes is altered with respect to the protein axes and (b) the protein becomes more elongated with an axial ratio of approximately 2.4 . For comparison, the hydrodynamic properties of the anthrax AC exotoxin were computed by a mathematical approach (hydropro), which uses the 3D structure {Drum, C.L., Yan, S.-Z., Bard, J., Shen, Y.-Q., Lu, D., Soelalman, S., Grabarek, Z., Bohm, A . & Tang, W.-J . (2002) Nature (London)415, 396-402} . A change in axial ratio is also observed on CaM binding, but in the reverse direction from that for AC: from 1.7 to 1.3 . The mechanisms of activation of the two proteins by CaM may therefore be different. J Health Commun, 2004 Jan-Feb, 9(1), 67 - 75 Communicating health information to an alarmed public facing a threat such as a bioterrorist attack; Hobbs J et al.; 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 bioterrorist attack . Despite some of the Internet's advantages over traditional media, including the depth and speed in which information can be conveyed to different audiences, the Internet was underutilized during fall 2001, when it became important to convey information on the risks of anthrax . A number of developments are required if the health care system is to capitalize on the Internet's potential as a risk communication device . These developments include research into public Internet searching behavior and further development in the role of search engines and government agencies in organizing quality health information. Immunol Allergy Clin North Am, 2003 Nov, 23(4), 713 - 30 Anthrax vaccine: a review; Grabenstein JD; Anthrax can be a deadly disease if treatment does not begin early in the course of infection . An effective vaccine has been available in the United States since 1970, although it was not used widely until 1998 . A comprehensive, peer-reviewed evaluation by the National Academy of Sciences affirmed the findings of multiple previous independent panels that found that the US-licensed anthrax vaccine is safe and effective. Infect Immun, 2004 Feb, 72(2), 1181 - 3 Needle-free skin patch vaccination method for anthrax; Matyas GR et al.; 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. Am J Epidemiol, 2004 Feb 1, 159(3), 217 - 24 A generalized linear mixed models approach for detecting incident clusters of disease in small areas, with an application to biological terrorism; Kleinman K et al.; 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 undeveloped arena of statistical methodology . Surveillance for bioterrorism detection, in particular, raises unique issues with methodological relevance . For example, the bioterrorism agents of greatest concern cause initial symptoms that may be difficult to distinguish from those of naturally occurring disease . In this paper, the authors propose a general approach to evaluating whether observed counts in relatively small areas are larger than would be expected on the basis of a history of naturally occurring disease . They implement the approach using generalized linear mixed models . The approach is illustrated using data on health-care visits (1996-1999) from a large Massachusetts managed care organization/multispecialty practice group in the context of syndromic surveillance for anthrax . The authors argue that there is great value in using the geographic data. Occup Environ Med, 2004 Feb, 61(2), 103 - 7 The dissemination of anthrax from imported wool: Kidderminster 1900-14; Carter T; BACKGROUND: 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 . AIMS: To assess the distribution of anthrax cases associated with the use of contaminated wool and to review the response to them . METHODS: The area studied was Kidderminster, Worcestershire, England, from 1900 to 1914 . Data sources were national records of the Factory Inspectorate and local records from the infirmary, Medical Officer of Health and inquest reports, and county agricultural records, supplemented by contemporary and later review articles . Case reports and summary data were analysed, and discussions and actions taken to improve precautions reviewed . RESULTS: There were 36 cases of anthrax, with five deaths, one of which was the sole case of the internal form of the disease . Cases of cutaneous anthrax were most frequently found in those handling raw wool, but they also occurred in workers at later stages of the spinning process and in people with little or no recorded exposure to contaminated wool . Limited precautionary measures were in place at the start of the study period . Some improvements were made, especially in the treatment of infections, but wool with a high risk of anthrax contamination continued to be used and cases continued to arise . Major changes were made to the disposal of waste and to agricultural practice in contaminated areas to curtail outbreaks in farm animals . CONCLUSIONS: The introduction of anthrax as a contaminant of imported wool led not only to cases in the highly exposed groups of workers but also to cases in other members of the population and in farm animals . The measures taken during the study period reduced fatalities from cutaneous anthrax but did not eliminate the disease . Public concern about the cases was muted. AMIA Annu Symp Proc . 2003;:849. Emergency implementation of knowledge management system to support a bioterrorism response; Garrett NY et al.; In a public health emergency, it becomes necessary for public health agencies to provide timely, accurate and useful information to the community . During the anthrax attacks, the Public Health Practice Program Office in the Centers for Disease Control and Prevention implemented a knowledge management (KM) system to respond to an increased number of inquiries from public health officials, first responders, and health care professionals as well as the general public . While it is possible to successfully implement a knowledge management system quickly in a crisis situation, additional challenges to sustainability may result from shortchanging the normal decision-making channels. Emerg Infect Dis, 2003 Dec, 9(12), 1509 - 15 Emerging infectious diseases in Mongolia; Ebright JR et al.; Since 1990, Mongolia's health system has been in transition . Impressive gains have been accomplished through a national immunization program, which was instituted in 1991 . Nevertheless, the country continues to confront four major chronic infections: hepatitis B and C, brucellosis, tuberculosis, and sexually transmitted diseases (STDs) . As of 2001, only two cases of HIV infections had been detected in Mongolia, but concern grows that the rate will increase along with the rising rates of STDs and increase in tourism . Other infectious diseases of importance in Mongolia include echinococcosis, plague, tularemia, anthrax, foot-and-mouth, and rabies. Nat Struct Mol Biol, 2004 Jan, 11(1), 60 - 6 Epub 2003 Dec 29. The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor; Turk BE et al.; 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 bound to an optimized peptide substrate and to peptide-based inhibitors provide a rationale for the observed selectivity and may be exploited in the design of future generations of LF inhibitors. Zh Mikrobiol Epidemiol Immunobiol, 2003 Nov-Dec, (6), 43 - 6 {Epidemiological situation on anthrax in the regions of the Southern Federal District in connection with the flood in June 2002}; Buravtseva NP et al.; Data on the epidemiological situation in anthrax in the regions of the Southern Federal District, situated in the zone of inundation, are presented . In 2002 no epidemic complications in anthrax were noted in the affected territories . The causes contributing to the appearance of anthrax cases among humans and animals are presented . Recommendations on the improvement of anti-epidemic measures are given. Zh Mikrobiol Epidemiol Immunobiol, 2003 Nov-Dec, (6), 29 - 34 {Epidemiologic situation in the quarantine of natural focal infections in the Southern Federal District}; Efremenko VI et al.; Materials on the situation in quarantine natural focal infections (anthrax, plague, tularemia, brucellosis, leptospirosis, etc.) in the Southern Federal District are presented . Experience in the provision of the epidemic safety in the above-mentioned diseases, based on the systematic surveillance on the activity of epizootological factors on the territory of the natural foci of infections, are described . The causes of the possible aggravation of the epidemiological situation in a number of nosological forms in connection with changes in natural and socio-economic factors are given . The results of the realization of regional programs, making it possible to improve the system interaction between the administrative territories, services and departments aimed at ensuring the epidemiological safety of the region, are shown. Med Confl Surviv, 2003 Oct-Dec, 19(4), 326 - 30 Which bio-weapons might be used by terrorists against the United Kingdom? Boulton F. The properties of potential biological weapon agents for bioterrorism include a consistent effect at low dosage and short incubation period in a population of low immunity, being difficult to treat, able to be produced in bulk, stable in storage and readily disseminated . Possible agents include smallpox, haemorrhagic fever viruses, anthrax, tularaemia and plague . The example of Severe Acute Respiratory Syndrome (SARS) demonstrates the possible consequences of an act of bioterrorism, but also the necessary global response . There is scepticism about the practicability of surveillance schemes and the global elimination of biological weapons though the Biological and Toxin Weapons Convention remains urgent. J Am Acad Dermatol, 2004 Jan, 50(1), 136 - 9 Oral pemphigus vulgaris after anthrax vaccine administration: association or coincidence? Muellenhoff M, Cukrowski T, Morgan M, Dorton D. 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 . Previous cases of pemphigus vulgaris associated with anthrax vaccine administration have not been reported . Considering the recent deliberate outbreaks of anthrax and continued threats of bioterrorism, the potential exists for widespread administration of the anthrax vaccine . Accordingly, continued observation and documentation of true adverse events is needed. J Health Commun, 2003, 8 Suppl 1, 130 - 43 Optimistic bias and perceptions of bioterrorism in Michigan corporate spokespersons, fall 2001; Salmon CT et al.; The notion that individuals believe that they are more likely than others to experience positive events and avoid negative ones is a well-documented phenomenon in the combined literatures of social psychology and health communication . The current study focuses on Michigan corporate spokespersons' perceptions of their company's risk and potential for optimistic bias . Beginning on September 10, 2001, and continuing through October 2001, telephone surveys were conducted by a professional survey research firm to assess spokespersons' awareness of and preparedness for a bioterrorism attack at their corporation, as well as to ascertain perceived self-risk relative to that of other, similar corporations . The results offer evidence of a robust optimistic bias, and provide an unusually timely snapshot of levels of corporate awareness of bioterrorism during a critical period of time in which the U.S . experienced its first anthrax attack. J Health Commun, 2003, 8 Suppl 1, 93 - 103; discussion 148-51 Public perceptions of information sources concerning bioterrorism before and after anthrax attacks: an analysis of national survey data; Pollard WE; This study examined data from six national surveys before and after the bioterrorist anthrax attacks in the fall of 2001 . Public perceptions of information sources regarding bioterrorism were examined . The findings highlighted the importance of local television and radio and of cable and network news channels as information sources . The findings also showed the importance of national and local health officials as spokespersons in the event of bioterrorist incidents . Periodic surveys of public attitudes provide important, timely information for understanding audiences in communication planning. J Health Commun, 2003, 8 Suppl 1, 83 - 92; discussion 148-51 Using opinion surveys to track the public's response to a bioterrorist attack; Blendon RJ et al.; To communicate effectively with the public during an emergency, health officials need to find out in real time what Americans know and believe, whom they trust, and what actions they are taking in response to the crisis . Short-duration surveys can provide vital information to guide public officials in their response to events and their communication efforts . Prior research has shown that such surveys, when statistically re-weighted, can offer timely results without unacceptable risk of bias . Using examples from public opinion surveys during the anthrax attacks of 2001, this article examines the role such surveys can play during a public health crisis. J Health Commun, 2003, 8 Suppl 1, 50 - 82; discussion 148-51 Communicating anthrax in 2001: a comparison of CDC information and print media accounts; Mebane F et al.; Information about anthrax released by news media from October 4 to December 3, 2001, was identified, sampled, coded, and compared with information released by CDC during that period using statistical analysis . In addition, communications about two anthrax-related issues were examined in depth . The quantitative analysis showed that, overall, CDC information releases and news coverage tracked fairly closely . When weight was defined as number of mentions, both sources gave the same weight to reports of risk for the population . The news sample gave roughly half the weight as CDC to who was exposed, how people were exposed, and what role antibiotics play in preventing anthrax . The samples were widely divergent (CDC high, news sample low) for public health precautions and other details . The in-depth, qualitative analysis showed that some reporters misinterpreted information provided by CDC, but they responded to requests to clarify the issue . The findings of this study suggest ways to improve future crisis communication efforts and demonstrate how differing methods of analysis can yield substantially different conclusions. J Health Commun, 2003, 8 Suppl 1, 35 - 49; discussion 148-51 Communication monitoring: shaping CDC's emergency risk communication efforts; Prue CE et al.; CDC develops and delivers health messages for a variety of audiences, including the public, health care professionals, public health researchers and practitioners, and policy makers . News media outlets--because of their broad reach and potential to influence knowledge, attitudes, and behaviors--are major channels for disseminating messages to these audiences . CDC has routinely monitored news outlets to identify message/information gaps and opportunities . The 9/11 terrorist attacks and the anthrax incidents that followed required CDC to transform its media monitoring system into a broader communication monitoring system, with both listening and telling functions, to support CDC's public health emergency response. J Health Commun, 2003, 8 Suppl 1, 17 - 34; discussion 148-51 Uncertain science and certain deadlines: CDC responses to the media during the anthrax attacks of 2001; Robinson SJ et al.; This paper presents a study in which communication personnel for the U.S . Centers for Disease Control and Prevention (CDC) provided first-hand accounts of the experience of responding to media inquiries during the 2001 anthrax attacks . In-depth interviews were conducted with 19 communication professionals who worked either at the CDC headquarters in Atlanta or at field locations in the U.S . where persons were exposed to anthrax . The interviews sought CDC staff viewpoints on how the CDC handled a historically unprecedented level of press activity in terms of work locations and equipment, information flow and clearance, and staff roles . Staff reported that the situation led to new work practices, tools for performing the work, and an enhanced understanding of what it takes to be prepared for and to handle communication work during a terrorism-related health crisis . The paper provides a discussion of implications of the findings for CDC and for other public health organizations developing systems for communication response during health-related crises. Infect Immun, 2004 Jan, 72(1), 602 - 5 Protection against anthrax toxemia by hexa-D-arginine in vitro and in vivo; Sarac MS et al.; 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. Curr Opin Oncol, 2004 Jan, 16(1), 44 - 9 Tumor endothelial markers: new targets for cancer therapy; Nanda A et al.; PURPOSE OF REVIEW: 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) . RECENT FINDINGS: The ability of Avastin to prolong survival in a Phase III clinical trial of human colorectal cancer has established the validity of the anti-angiogenic approach . However, realization of the full potential of a vascular targeting strategy may require the exploitation of molecules which are highly restricted in expression to tumor endothelium . Here we explore the potential of TEMs as new targets for cancer therapy . Current knowledge of these markers and their relation to other family members in the context of tumor angiogenesis is discussed . In particular, we highlight those molecules which, by virtue of their structure, cell-surface location and expression pattern, appear to hold promise as targets for future drug development . The identification of TEM8 as the anthrax toxin receptor and the successful targeting of this receptor in preclinical tumor models make this molecule a particularly attractive candidate for future vascular targeting studies . SUMMARY: Technological advances in cellular fractionation and genomics enabled the identification of several markers preferentially expressed on human tumor endothelium . Studies of these TEMs are expected to aid in our understanding of angiogenesis and could lead to the development of new imaging and diagnostic agents for cancer. Mil Med, 2003 Nov, 168(11), 915 - 21 Diagnosis of militarily relevant diseases using oral fluid and saliva antibodies: fluorescence polarization immunoassay; Cullum ME et al.; This laboratory is developing fluorescence polarization (FP) methods as diagnostic tools to assay antibodies in saliva and other oral fluids . FP provides quantitation of molecular interaction, such as antigen-antibody binding, of a single, small-volume sample in real time and without prior separation of components such as blood cells . There is potential for wide-spread use of these homogeneous assays as noninvasive tests, especially as more compact, simplified fluorescence polarimeters become available . FP tests can be designed that are applicable to a wide spectrum of microorganisms and may be used in a clinic or far-forward deployed setting to aid in diagnosis of disease or verification of vaccination . Rapid salivary diagnostics, including FP, have been identified by the Office of Naval Research as requirements for future naval capabilities in basic and applied medical research for warfighter protection in casualty prevention . The applications of FP salivary diagnostics for determination of tuberculosis exposure and of anthrax immunization status are discussed as examples. Arch Dermatol, 2003 Dec, 139(12), 1545 - 52 Increased detection of rickettsialpox in a New York City hospital following the anthrax outbreak of 2001: use of immunohistochemistry for the rapid confirmation of cases in an era of bioterrorism; Koss T et al.; BACKGROUND: Rickettsialpox is a self-limited febrile illness with skin lesions that may be mistaken for signs of potentially more serious diseases, such as cutaneous anthrax or chickenpox . The cluster of cutaneous anthrax cases from bioterrorism in October 2001 likely heightened awareness of and concern for cutaneous eschars . OBJECTIVES: To apply an immunohistochemical technique on paraffin-embedded skin biopsy specimens for diagnosing rickettsialpox, and to compare the reported incidence of rickettsialpox before, during, and after the cluster of cutaneous anthrax cases . DESIGN: Case series . SETTING: Dermatology department in a large tertiary care hospital in New York City . PATIENTS: Eighteen consecutive patients with the clinical diagnosis of rickettsialpox from February 23, 2001, through October 31, 2002 . MAIN OUTCOME MEASURES: Results of immunohistochemical testing of skin biopsy specimens and of serological testing . RESULTS: Immunohistochemical testing revealed spotted fever group rickettsiae in all 16 eschars and in 5 of the 9 papulovesicles tested . A 4-fold or greater increase in IgG antibody titers reactive with Rickettsia akari was observed in all 9 patients for whom acute and convalescent phase samples were available; 6 patients had single titers indicative of rickettsialpox infection (> or =1:64) . Of the 18 patients, 9 (50%) presented in the 5 months following the bioterrorism attacks . CONCLUSIONS: Rickettsialpox remains endemic in New York City, and the bioterrorism attacks of October 2001 may have led to increased awareness and detection of this disease . Because rickettsialpox may be confused with more serious diseases, such as cutaneous anthrax or chickenpox, clinicians should be familiar with its clinical presentation and diagnostic features . Immunohistochemical staining of skin biopsy specimens, particularly from eschars, is a sensitive technique for confirming the clinical diagnosis. Biochem Biophys Res Commun, 2004 Jan 2, 313(1), 217 - 22 Implication of pH in the catalytic properties of anthrax lethal factor; Kim J et al.; 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 accumulating reports that the region distal to cleavage site is required for the LF-mediated proteolysis of substrate . In this study, we demonstrate the catalytic properties of LF, using the full-length native substrate, MEK . We described the catalytic properties of LF focused on the effects of the pH alteration, which was encountered during the endocytosis of lethal toxin, and of the requirement for metal ions . We present the first evidence that additional metal ions are required for the LF catalyzed hydrolysis of native substrate, and that the pH alteration causes a significant change of catalytic properties of LF. Sci Eng Ethics, 2003 Oct, 9(4), 453 - 70 Coding ethical behaviour: the challenges of biological weapons; Rappert B; Since 11 September 2001 and the anthrax attacks that followed in the US, public and policy concerns about the security threats posed by biological weapons have increased significantly . With this has come an expansion of those activities in civil society deemed as potential sites for applying security controls . This paper examines the assumptions and implications of national and international efforts in one such area: how a balance or integration can take place between security and openness in civilian biomedical research through devising professional codes of conduct for scientists . Future attempts to establish such codes must find a way of reconciling or at least addressing dilemmatic and tension-ridden issues about the appropriateness of research; a topic that raises fundamental questions about the position of science within society. Am J Infect Control, 2003 Dec, 31(8), 511 - 4 An innovative approach to training hospital-based clinicians for bioterrorist attacks; Filoromo C et al.; The recent attacks of September 11, 2001, and the subsequent dissemination event of anthrax in the United States demonstrated the necessity for hospitals to initiate bioterrorism education for clinicians . Events such as the release of sarin gas into the Tokyo subway by the Aum Shinrikyo cult provided some insight into how quickly emergency medical personnel may be overwhelmed by causalities of unconventional weapons . Educational interventions to prepare hospital-based practitioners for such disasters must fit among the demands of patient care, administrative duties, and continuing education within specialties . In addition, the priority placed on the topic, confusion about reputable resources to consult, and concerns of funding for preparedness training mandate the need for an authoritative, comprehensive, and easily accessible approach . A pilot project supported in part by the Agency for Healthcare Research and Quality was developed to facilitate streamlining of preparedness efforts through the implementation of interactive screen savers as an alternative to traditional educational modalities . This report presents the successful application of this model, which was quantified with pretests and posttests given to users of the system. J Forensic Sci, 2003 Nov, 48(6), 1302 - 8 Extraction and analysis of human nuclear and mitochondrial DNA from electron beam irradiated envelopes; Withrow AG et al.; The United States Postal Service is considering methods such as electron beam irradiation to neutralize biological agents sent through the mail . While this is proven to reduce/eliminate pathogenic organisms, it may also degrade human genomic DNA and therefore hinder the ability to garner forensically informative genetic profiles . To determine the effects of electron beam irradiation on DNA typing, 16 white, standard letter-sized envelopes were licked . Half of the envelopes served as nonirradiated controls while the other half underwent irradiation at dosages sufficient to kill anthrax spores (29.3 and 51.6 kGy) . Total cellular DNA was extracted from all envelopes; nuclear short tandem repeat loci, as well as the hypervariable region I from mitochondrial DNA, were amplified by means of the polymerase chain reaction . Short tandem repeat profiles and mitochondrial DNA sequence haplotypes were acquired on an ABI Prism 310 Genetic Analyzer platform . Analysis of data from irradiated samples revealed evidence of DNA degradation; however, the ability to construct full genetic profiles from both nuclear and mitochondrial DNA remained largely unaffected . The use of the polymerase chain reaction, coupled with florescent fragment analysis and mitochondrial DNA sequencing, should be considered to profile biological material from evidence enduring irradiation to inactivate infectious agents. Public Health Nurs, 2003 Nov-Dec, 20(6), 422 - 31 The role of an advanced practice public health nurse in bioterrorism preparedness; Mondy C et al.; The 2001 anthrax events have vividly illustrated that terrorism involving the release of a biological agent is a major public health emergency requiring an immediate and well-coordinated response . If healthcare professionals and emergency responders are to be prepared to manage such attacks, unprecedented cooperative efforts at the national, state, and local levels are necessary . To aid such efforts, advanced practice public health nurses (PHNs) must exercise their ability to collaborate with a variety of disciplines and communities . Using the Los Angeles County Public Health Nursing Practice Model, advanced practice PHNs can be trained to deal effectively with acts of bioterrorism . This model defines the practice of public health nursing as working on a population-based level to create conditions under which healthy people can live within healthy communities . This article will discuss the threat of bioterrorism and describe how the Public Health Nursing Practice Model can be applied to assist advanced practice PHNs in the development of a public health plan for preparedness and response to bioterrorism . Six specific interventions that enable advanced practice PHNs to affect populations at the community and systems level will be discussed along with the implications of bioterrorism for advanced practice public health nursing. Proc Natl Acad Sci U S A, 2003 Nov 25, 100(24), 13803 - 8 Epub 2003 Nov 17. Mapping dominant-negative mutations of anthrax protective antigen by scanning mutagenesis; Mourez M et al.; The protective antigen (PA) moiety of anthrax toxin transports edema factor and lethal factor to the cytosol of mammalian cells by a mechanism that depends on its ability to oligomerize and form pores in the endosomal membrane . Previously, some mutated forms of PA, designated dominant negative (DN), were found to coassemble with wild-type PA and generate defective heptameric pore-precursors (prepores) . Prepores containing DN-PA are impaired in pore formation and in translocating edema factor and lethal factor across the endosomal membrane . To create a more comprehensive map of sites within PA where a single amino acid replacement can give a DN phenotype, we used automated systems to generate a Cys-replacement mutation for each of the 568 residues of PA63, the active 63-kDa proteolytic fragment of PA . Thirty-three mutations that reduced PA's ability to mediate toxicity at least 100-fold were identified in all four domains of PA63 . A majority (22) were in domain 2, the pore-forming domain . Seven of the domain-2 mutations, located in or adjacent to the 2beta6 strand, the 2beta7 strand, and the 2beta10-2beta11 loop, gave the DN phenotype . This study demonstrates the feasibility of high-throughput scanning mutagenesis of a moderate sized protein . The results show that DN mutations cluster in a single domain and implicate 2beta6 and 2beta7 strands and the 2beta10-2beta11 loop in the conformational rearrangement of the prepore to the pore . They also add to the repertoire of mutations available for structure-function studies and for designing new antitoxic agents for treatment of anthrax. FEBS Lett, 2003 Nov 20, 554(3), 505 - 10 Conformational fluctuations in anthrax protective antigen: a possible role of calcium in the folding pathway of the protein; Gupta PK et al.; Protective antigen (PA) is the central receptor binding component of anthrax toxin, which translocates catalytic components of the toxin into the cytosol of mammalian cells . Ever since the crystal structure of PA was solved, there have been speculations regarding the possible role of calcium ions present in domain I of the protein . We have carried out a systematic study to elucidate the effect of calcium removal on the structural stability of PA using various optical spectroscopic techniques, limited proteolysis and mutational analysis . Urea denaturation studies clearly suggest that the unfolding pathway of the protein follows a non-two state transition with apo-PA being an intermediate species, whereas the folding pathway shows that calcium ions may be critical for the initial protein assembly. Int J Health Geogr . 2003 Nov 16;2(1):8. Initiating informatics and GIS support for a field investigation of Bioterrorism: The New Jersey anthrax experience; Zubieta JC et al.; BACKGROUND: The investigation of potential exposure to anthrax spores in a Trenton, New Jersey, mail-processing facility required rapid assessment of informatics needs and adaptation of existing informatics tools to new physical and information-processing environments . Because the affected building and its computers were closed down, data to list potentially exposed persons and map building floor plans were unavailable from the primary source . RESULTS: Controlling the effects of anthrax contamination required identification and follow-up of potentially exposed persons . Risk of exposure had to be estimated from the geographic relationship between work history and environmental sample sites within the contaminated facility . To assist in establishing geographic relationships, floor plan maps of the postal facility were constructed in ArcView Geographic Information System (GIS) software and linked to a database of personnel and visitors using Epi Info and Epi Map 2000 . A repository for maintaining the latest versions of various documents was set up using Web page hyperlinks . CONCLUSIONS: During public health emergencies, such as bioterrorist attacks and disease epidemics, computerized information systems for data management, analysis, and communication may be needed within hours of beginning the investigation . Available sources of data and output requirements of the system may be changed frequently during the course of the investigation . Integrating data from a variety of sources may require entering or importing data from a variety of digital and paper formats . Spatial representation of data is particularly valuable for assessing environmental exposure . Written documents, guidelines, and memos important to the epidemic were frequently revised . In this investigation, a database was operational on the second day and the GIS component during the second week of the investigation. Biochem J, 2004 Mar 1, 378(Pt 2), 569 - 77 Anthrax lethal factor-cleavage products of MAPK (mitogen-activated protein kinase) kinases exhibit reduced binding to their cognate MAPKs; Bardwell AJ et al.; 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 protein kinase domain, intact . LF-mediated cleavage of MEK1 and MKK6 has been shown to inhibit signalling through their cognate MAPK pathways . However, the precise mechanism by which this proteolytic cleavage inhibits signal transmission has been unclear . Here we show that the C-terminal LF-cleavage products of MEK1, MEK2, MKK3, MKK4, MKK6 and MKK7 are impaired in their ability to bind to their MAPK substrates, suggesting a common mechanism for the LF-induced inhibition of signalling. J Immune Based Ther Vaccines . 2003 Nov 5;1(1):3. A Canadian national survey of attitudes and knowledge regarding preventive vaccines; Ritvo P et al.; BACKGROUND: Vaccines have virtually eliminated many diseases, but public concerns about their safety could undermine future public health initiatives . OBJECTIVE: To determine Canadians' attitudes and knowledge about vaccines, particularly in view of increasing public concern about bioterrorism and the possible need for emergency immunizations after weaponized anthrax incidents and the events of September 11, 2001 . METHOD: A 20-question survey based on well-researched dimensions of vaccine responsiveness was telephone-administered to a random sample of N = 1330 adult Canadians in January, 2002 . RESULTS: 1057 (79.5%) completed the survey . Respondents perceived vaccines to be highly effective and demonstrated considerable support for further vaccine research . However, results also indicate a lack of knowledge about vaccines and uncertainty regarding the safety . CONCLUSIONS: Support for vaccines is broad but shallow . While Canadians hold generally positive attitudes about vaccines, support could be undermined by widely publicized adverse events . Better public education is required to maintain support for future public health initiatives. Med Sci (Paris), 2003 Oct, 19(10), 967 - 71 {Genomics and bioterrorism}; Boissinot M et al.; The use of biological weapons has been recorded throughout history . However, the anthrax-tainted letters of the fall of 2001 caused shock and panic in several countries . Knowledge of the principal bacteriological weapons allows design of novel rapid DNA-based diagnostic tests that should help defuse the impact of future bioterrorist attacks . Less than one-hour real-time PCR identification of bacteria and their associated antibiotic resistance genes will revolutionize the practice of medicine. Trends Pharmacol Sci, 2003 Nov, 24(11), 558 - 9 Anthrax mounts a nuclear attack on glucocorticoid signaling; Kliewer SA; Anthrax causes profound inflammation and systemic shock . A recent study has shown that anthrax lethal toxin represses the transcriptional activity of the glucocorticoid receptor, which is a crucial component of the body's defenses against inflammation . The study reports evidence that lethal toxin blocks the glucocorticoid receptor by inhibiting the p38 mitogen-activated protein kinase pathway . Thus, these findings suggest that glucocorticoid receptor inactivation contributes to anthrax toxicity and raise the possibility of developing new strategies to combat this deadly disease. J Immunol Methods, 2003 Nov, 282(1-2), 169 - 74 TNF-alpha detection using a flow cytometric assay to determine cellular responses to anthrax vaccine; Shinn AH et al.; This study describes a four-color flow cytometric assay that detects CD4+ T cell responses to the anthrax vaccine . Whole blood from seven volunteers who previously obtained the anthrax vaccine was inoculated in vitro with varying concentrations of the anthrax antigen . TNF-alpha and IFN-gamma production from memory CD4+ T cells were measured and compared to a control group who never received the anthrax vaccine . The optimal antigen concentration for TNF-alpha was determined to be around 7.5 microg/ml and IFN-gamma production was not detected . This assay will be used in future larger prospective studies to further evaluate the cellular immune responses induced by the anthrax vaccine. Alaska Med, 2000 Oct-Dec, 42(4), 101 - 13 Preparedness for a bioterrorism event in Alaska . Part 1: Detection and identification of a biologic event; Funk EA; U.S . military and public health experts are increasingly concerned that the general public is at risk for terrorist attacks . Traditional weapons of mass destruction such as explosive and chemical devices remain the most likely forms of terrorism, however the threat of bioterrorism is also present and may be increasing . An intentional biologic event may be covert and if so, will not become apparent for days or even weeks when many ill people present with an unidentified illness . Health care providers will be the first responders during a biologic attack and will be called upon to diagnose diseases such as anthrax, tularemia or even smallpox . In the first of a two-part article, a hypothetical scenario is presented to illustrate how such an attack might first be discovered and the agent identified . As the scenario unfolds, evidence is collected that suggests the outbreak was intentional . Information about epidemiologic clues, disease syndromes and specific high-risk agents are discussed. EMBO J, 2003 Nov 3, 22(21), 5746 - 56 Xp38gamma/SAPK3 promotes meiotic G(2)/M transition in Xenopus oocytes and activates Cdc25C; Perdiguero E et al.; We have studied the role of p38 mitogen-activated protein kinases (MAPKs) in the meiotic maturation of Xenopus oocytes . Overexpression of a constitutively active mutant of the p38 activator MKK6 accelerates progesterone-induced maturation . Immunoprecipit ation experiments indicate that p38gamma/SAPK3 is the major p38 activated by MKK6 in the oocytes . We have cloned Xenopus p38gamma (Xp38gamma) and show that co-expression of active MKK6 with Xp38gamma induces oocyte maturation in the absence of progesterone . The maturation induced by Xp38gamma requires neither protein synthesis nor activation of the p42 MAPK-p90Rsk pathway, but it is blocked by cAMP-dependent protein kinase . A role for the endogenous Xp38gamma in progesterone-induced maturation is supported by the inhibitory effect of kinase-dead mutants of MKK6 and Xp38gamma . Furthermore, MKK6 can rescue the inhibition of oocyte maturation by anthrax lethal factor, a protease that inactivates MAPK kinases . We also show that Xp38gamma can activate the phosphatase XCdc25C, and we identified Ser205 of XCdc25C as a major phosphorylation site for Xp38gamma . Our results indicate that phosphorylation of XCdc25C by Xp38gamma/SAPK3 is important for the meiotic G(2)/M progression of Xenopus oocytes. MMWR Morb Mortal Wkly Rep, 2003 Oct 31, 52(43), 1051 - 3 Terrorism preparedness in state health departments--United States, 2001-2003; Centers for Disease Control and Prevention (CDC); The anthrax attacks in fall 2001 highlighted the role of infectious disease (ID) epidemiologists in terrorism preparedness and response . Beginning in 2002, state health departments (SHDs) received approximately 1 billion dollars in new federal funding to prepare for and respond to terrorism, infectious disease outbreaks, and other public health threats and emergencies . This funding is being used in part to improve epidemiologic and surveillance capabilities . To determine how states have used a portion of their new funding to increase ID epidemiology capacity, the Iowa Department of Public Health's Center for Acute Disease Epidemiology and the Iowa State University Department of Microbiology conducted two surveys of U.S . state epidemiologists during September 2000-August 2001 and October 2002-June 2003 . This report summarizes the results of these surveys, which determined that although the number of SHD epidemiology workers assigned to ID and terrorism preparedness increased by 132%, concerns remained regarding the ability of SHDs to hire qualified personnel . These findings underscore the need to develop additional and more diverse training venues for current and future ID epidemiologists. J Am Acad Dermatol, 2003 Nov, 49(5), 910 - 1 Milker's nodule in a healthy young woman; Werchniak AE et al.; Milker's nodules (pseudocowpox) are harmless skin lesions most commonly seen in persons whose occupation regularly brings them into close contact with cattle . They are caused by the paravaccinia virus, a member of the poxvirus family . Awareness of their clinical and histopathologic features is important, especially with today's heightened awareness of the threat of biologic warfare, to distinguish them from more worrisome entities such as tularemia and anthrax. Biochem Biophys Res Commun, 2003 Nov 7, 311(1), 229 - 32 Acid induced unfolding of anthrax protective antigen; Gupta PK et al.; Acidic pH plays an important role in the membrane insertion of protective antigen (PA) of anthrax toxin leading to the translocation of the catalytic moieties . The structural transitions occurring in PA as a consequence of change in pH were investigated by fluorescence and circular dichroism measurements . Our studies revealed the presence of two intermediates on-pathway of acid induced unfolding; one at pH 2.0 and other at pH 4-5 . Intrinsic fluorescence measurements of these intermediates showed a red shift in the wavelength of emission maximum with a concomitant decrease in fluorescence intensity, indicative of the exposure of tryptophan residues to the bulk solvent . Furthermore, no significant change was seen in the secondary structure of PA at a pH of 2.0, as indicated by far UV-CD spectra . The low pH intermediate of PA was characterized using the hydrophobic dye, 8-anilino-1-naphthalenesulfonate, and was found to have properties similar to those of a molten globule state. Avian Dis, 2003, 47(3 Suppl), 1063 - 8 Molecular diagnostics in an insecure world; Perdue ML; As of October 2001, the potential for use of infectious agents, such as anthrax, as weapons has been firmly established . It has been suggested that attacks on a nations' agriculture might be a preferred form of terrorism or economic disruption that would not have the attendant stigma of infecting and causing disease in humans . Highly pathogenic avian influenza virus is on every top ten list available for potential agricultural bioweapon agents, generally following foot and mouth disease virus and Newcastle disease virus at or near the top of the list . Rapid detection techniques for bioweapon agents are a critical need for the first-responder community, on a par with vaccine and antiviral development in preventing spread of disease . There are several current approaches for rapid, early responder detection of biological agents including influenza A viruses . There are also several proposed novel approaches in development . The most promising existing approach is real-time fluorescent PCR analysis in a portable format using exquisitely sensitive and specific primers and probes . The potential for reliable and rapid early-responder detection approaches are described, as well as the most promising platforms for using real-time PCR for avian influenza, as well as other potential bioweapon agents. Annu Rev Cell Dev Biol, 2003, 19, 45 - 70 Anthrax toxin; Collier RJ et al.; Anthrax toxin consists of three nontoxic proteins that associate in binary or ternary combinations to form toxic complexes at the surface of mammalian cells . One of these proteins, protective antigen (PA), transports the other two, edema factor (EF) and lethal factor (LF), to the cytosol . LF is a Zn2+-protease that cleaves certain MAP kinase kinases, leading to death of the host via a poorly defined sequence of events . EF, a calmodulin- and Ca2+-dependent adenylate cyclase, is responsible for the edema seen in the disease . Both enzymes are believed to benefit the bacteria by inhibiting cells of the host's innate immune system . Assembly of toxic complexes begins after PA binds to cellular receptors and is cleaved into two fragments by furin proteases . The smaller fragment dissociates, allowing the receptor-bound fragment, PA63 (63 kDa), to self-associate and form a ring-shaped, heptameric pore precursor (prepore) . The prepore binds up to three molecules of EF and/or LF, and the resulting complexes are endocytosed and trafficked to an acidic compartment . There, the prepore converts to a transmembrane pore, mediating translocation of EF and LF to the cytosol . Recent studies have revealed (a) the identity of receptors; (b) crystallographic structures of the three toxin proteins and the heptameric PA63 prepore; and (c) information about toxin assembly, entry, and action within the cytosol . Knowledge of the structure and mode of action of the toxin has unveiled potential applications in medicine, including approaches to treating anthrax infections. Am J Clin Pathol, 2002 Jun, 117 Suppl, S116 - 23 Bioterrorism . Clinical recognition and primary management; Branda JA et al.; The recent anthrax attacks in the United States have demonstrated the reality of bioterrorist threats as well as the need for preparedness and planning to mount a successful response to such events . Medical practitioners have a key role in responding to bioterrorist activity because they can contribute to the timely recognition of an event and to the mitigation of morbidity resulting from a bioterrorist attack . The medical community needs to become familiar with how to recognize and manage diseases produced by the biologic agents that might be used by terrorists . This review summarizes the microbiological and clinical aspects of the agents of anthrax, smallpox, plague, and tularemia, which are all considered likely bioterrorist weapons. Curr Neurol Neurosci Rep, 2003 Nov, 3(6), 476 - 82 Bioterrorism and the nervous system; Han MH et al.; Recent events of war, terrorist attacks, and mail-borne anthrax exposure have produced increasing awareness of potential bioterrorism attacks in the United States and other parts of the world . Physicians and healthcare personnel play a key role in identifying potential bioterrorist attacks . Early recognition and preparedness for bioterrorism-associated illnesses is especially important for neurologists because most bioterrorism agents can directly or indirectly affect the nervous system . This article reviews the neurologic manifestations, diagnosis, and treatments of syndromes caused by potential bioterrorism agents, as well as the potential side effects of vaccines against some of these agents. Infection, 2003 Oct, 31(5), 327 - 30 Cutaneous anthrax in adults: a review of 25 cases in the eastern Anatolian region of Turkey; Demirdag K et al.; BACKGROUND: The clinical features, therapy and outcome of anthrax cases from the Elazig province (the eastern Anatolian region) of Turkey seen in our clinic over an 8-year period were reviewed . PATIENTS AND METHODS: The records of 25 anthrax cases observed in our clinic during the period January 1994 to April 2002 were examined . RESULTS: All cases were cutaneous; 18 (72%) patients exhibited malignant pustules and seven (28%) malignant edema . Three of the patients with a malignant pustule developed anthrax sepsis when admitted to our clinic . All cases were treated with penicillin . One patient who had penicillin allergy was treated with ciprofloxacin . In addition, patients with malignant edema were also treated with systemic corticosteroids (methylprednisolone or dexamethasone) . Two patients died due to anthrax sepsis; one case with anthrax sepsis recovered . The mortality rate was 8% . DISCUSSION: Anthrax is still a reality in Turkey . Cutaneous anthrax should be considered in any patient with a painless ulcer with vesicles, edema and a history of exposure to animals or animal products . In our series, penicillin and ciprofloxacin were effective in treatment of anthrax . Our anthrax sepsis case demonstrates that anthrax sepsis is not always fatal if antibiotic treatment is given early after diagnosis. Nat Biotechnol, 2003 Nov, 21(11), 1305 - 6 Epub 2003 Oct 12. Human antibodies from immunized donors are protective against anthrax toxin in vivo; Wild MA et al.; A panel of Fabs that neutralize anthrax toxin in vitro was selected from libraries generated from human donors vaccinated against anthrax . At least two of these antibodies protect rats from anthrax intoxication in vivo . Fabs 83K7C and 63L1D bind with subnanomolar affinity to protective antigen (PA) 63, and Fab 63L1D neutralizes toxin substoichiometrically, inhibits lethal factor (LF) interaction with PA63 and binds to a conformational epitope formed by PA63. Curr Pharm Des, 2003, 9(25), 2060 - 6 Novel protein targeted therapy of metastatic melanoma; Frankel AE et al.; Metastatic melanoma patients have a dismal prognosis with poor responsiveness to chemotherapy, radiation therapy and current immunotherapy regimens and a median survival of less than six months . Novel therapies directed at melanoma-selective molecular targets are urgently needed . Based on the frequent constitutive activation of the mitogen-activated protein kinase (MAPK) signaling pathway in malignant melanomas and the selective inhibition of MAPK signaling by anthrax lethal factor which proteolytically cleaves MAPK kinases, anthrax lethal toxin may be a useful agent for patients with metastatic melanoma . Anthrax lethal toxin consists of two proteins--protective antigen and lethal factor . These two proteins have been separately produced in good yields and in high purity . The three-dimensional structures of these proteins have been solved, and their molecular mechanisms of cell binding and action determined . Preclinical studies with anthrax lethal toxin show sensitivity of malignant melanoma cell lines in tissue culture and anti-tumor efficacy in melanoma xenograft models . Additional studies to define the maximal tolerated doses and dose-limiting toxicity of anthrax lethal toxin in rodent and primate models should pave the way for phase I studies testing the efficacy of the anthrax lethal toxin in patients with metastatic melanoma. Cell Microbiol, 2003 Nov, 5(11), 755 - 60 Innate immunity and biodefence vaccines; Valiante NM et al.; Host defence in vertebrates is achieved by the integration of two distinct arms of the immune system: the innate and adaptive responses . The innate response acts early after infection (within minutes), detecting and responding to broad cues from invading pathogens . The adaptive response takes time (days to weeks) to become effective, but provides the fine antigenic specificity required for complete elimination of the pathogen and the generation of immunologic memory . Antigen-independent recognition of pathogens by the innate immune system leads to the rapid mobilization of immune effector and regulatory mechanisms that provide the host with three critical advantages: (i) initiating the immune response (both innate and adaptive) and providing the inflammatory and co-stimulatory context for antigen recognition; (ii) mounting a first line of defence, thereby holding the pathogen in check during the maturation of the adaptive response; and (iii) steering the adaptive immune system towards the cellular or humoral responses most effective against the particular infectious agent . The quest for safer and more effective vaccines and immune-based therapies has taken on a sudden urgency with the increased threat of bioterrorism . Only a handful of vaccines covering a small proportion of potential biowarfare agents are available for human use (e.g . anthrax and small pox) and these suffer from poor safety profiles . Therefore, next generation biodefence-related vaccines and therapies with improved safety and the capacity to induce more rapid, more potent and broader protection are needed . To this end, strategies to target both the innate and adaptive immune systems will be required. Clin Leadersh Manag Rev, 2003 Sep-Oct, 17(5), 281 - 2 Detection of the sentinel anthrax case in the United States; Beall A et al.; First-hand knowledge of the detection of the first bioweapon in modern United States history is described in this article . The method by which the presumptive diagnosis of anthrax meningitis was made within 13 hours of the patient presenting to the emergency department is described using pre-analytic, analytic, and post-analytic phases . The lessons learned from this process are briefly presented so that other laboratories may learn from our experience: how to prepare; how to quickly analyze a potential bioweapon; how to communicate with staff and local, regional, and national authorities; and how to deal with disruptive media attention. Annu Rev Phytopathol, 2003, 41, 305 - 24 Advances in molecular-based diagnostics in meeting crop biosecurity and phytosanitary issues; Schaad NW et al.; Awareness of crop biosecurity and phytosanitation has been heightened since 9/11 and the unresolved anthrax releases in October 2001 . Crops are highly vulnerable to accidental or deliberate introductions of crop pathogens from outside U.S . borders . Strategic thinking about protection against deliberate or accidental release of a plant pathogen is an urgent priority . Rapid detection will be the key to success . This review summarizes recent progress in the development of rapid real-time PCR protocols and evaluates their effectiveness in a proposed nationwide network of diagnostic laboratories that will facilitate rapid diagnostics and improved communication. Nurs Stand, 2003 Aug 13-19, 17(48), 33 - 7 Anthrax: forms, symptoms and treatment; Woodrow P; BACKGROUND: This article examines the history of anthrax, the organism, the different forms of human anthrax, its symptoms and treatment . Set against fears of a bioterrorist attack, the article also examines the potential threat of anthrax as a weapon . CONCLUSION: Frontline staff such as nurses can contribute greatly to increasing survival by recognising symptoms, treating patients promptly and helping to allay public concern. Vet Hum Toxicol, 2003 Oct, 45(5), 247 - 8 Calls about anthrax to the Texas Poison Center Network in relation to the anthrax bioterrorism attack in 2001; Forrester MB et al.; Between October 4, 2001 and November 20, 2001, 22 cases of anthrax were identified in a bioterrorism attack on the US . This study examined the patterns of anthrax calls before and after the bioterrorist attack based on calls received by poison centers in Texas, a state that reported no anthrax cases as a result of the attack . During 1998-2002, 553 calls about anthrax were received . The majority of the anthrax calls occurred in 2001 (n = 489, 88.4%) and 2002 (n = 52, 9.4%) . The number of calls increased greatly in the days after October 4, 2001, reaching a peak of 31 anthrax calls in 1 d and then declining sharply in succeeding months . However, by December 2002 the number of calls about anthrax still had not returned to pre-attack levels . This study demonstrated the value of poison centers in documenting public need for information on biological agents used in a terrorist attack, even if the attack did not occur in the area serviced by the poison center . Poison centers may expect to receive calls regarding a bioterrorist attack shortly after the public became aware of the attack and will continue to receive related calls for months afterward . Poison centers need to be prepared with appropriate information prior to such attacks to provide to the public upon request. Am J Hum Genet, 2003 Oct, 73(4), 791 - 800 Epub 2003 Aug 21. Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis; Hanks S et al.; Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are autosomal recessive conditions characterized by multiple subcutaneous skin nodules, gingival hypertrophy, joint contractures, and hyaline deposition . We previously mapped the gene for JHF to chromosome 4q21 . We now report the identification of 15 different mutations in the gene encoding capillary morphogenesis protein 2 (CMG2) in 17 families with JHF or ISH . CMG2 is a transmembrane protein that is induced during capillary morphogenesis and that binds laminin and collagen IV via a von Willebrand factor type A (vWA) domain . Of interest, CMG2 also functions as a cellular receptor for anthrax toxin . Preliminary genotype-phenotype analyses suggest that abrogation of binding by the vWA domain results in severe disease typical of ISH, whereas in-frame mutations affecting a novel, highly conserved cytoplasmic domain result in a milder phenotype . These data (1) demonstrate that JHF and ISH are allelic conditions and (2) implicate perturbation of basement-membrane matrix assembly as the cause of the characteristic perivascular hyaline deposition seen in these conditions. Vaccine, 2003 Oct 1, 21(27-30), 4399 - 409 Using a structured medical note for determining the safety profile of anthrax vaccine for US soldiers in Korea; Hoffman K et al.; Selected military personnel are immunized with an FDA-licensed anthrax vaccine unless there are clinical contraindications . The objective of this analysis is to capture the experience of soldiers receiving anthrax vaccine to assist in better patient-provider communication and clarify the safety profile of the vaccine in this population as a quality-assurance initiative . Between August 1998 and July 1999, 2824 soldiers immunized against anthrax at one military clinic completed a structured medical note that was reviewed by a clinician . Female gender, prior vaccine-associated adverse events, and medication use were significantly related to higher reports of adverse events . All reported immediate consequences resolved. Am Fam Physician, 2003 Sep 1, 68(5), 889 - 96 Smallpox vaccine: contraindications, administration, and adverse reactions; Maurer DM et al.; Since the terrorist attacks of September 11, 2001, and the anthrax exposures in the following weeks, concern that smallpox could be used as a biologic weapon has increased . Public health departments and the U.S . military have begun the process of vaccinating soldiers and civilian first-responders . Smallpox vaccination carries some serious risks: approximately one in 1 million primary vaccinees and one in 4 million revaccinees will die from adverse vaccine reactions . The most serious side effects of smallpox vaccine include progressive vaccinia, postvaccinial central nervous system disease, and eczema vaccinatum . Some of these reactions can be treated with vaccinia immune globulin or cidofovir . Proper patient screening and site care are essential . Family physicians must learn to screen potential vaccinees for contraindications (e.g., immunodeficiency, immunosuppression, certain skin and eye diseases, pregnancy, lactation, allergy to the vaccine or its components, moderate or severe intercurrent illness) and to treat vaccine-associated adverse reactions. Clin Infect Dis, 2003 Oct 1, 37(7), 905 - 11 Epub 2003 Sep 12. Serious adverse events among participants in the Centers for Disease Control and Prevention's Anthrax Vaccine and Antimicrobial Availability Program for persons at risk for bioterrorism-related inhalational anthrax; Tierney BC et al.; On 20 December 2001, the Centers for Disease Control and Prevention (CDC) initiated the Anthrax Vaccine and Antibiotic Availability Program (hereafter, the "Program") under an investigational new drug application with the US Food and Drug Administration . This Program provided options for additional preventive treatment for persons at risk for inhalation anthrax as a result of recent bioterrorism attacks who had concluded or were concluding a 60-day course of antimicrobial prophylaxis . Participants were offered an additional 40 days of antibiotic therapy (with ciprofloxacin, doxycycline, or amoxicillin) or antibiotic therapy plus 3 doses of anthrax vaccine . By 11 February 2002, a total of 5420 persons had received standardized education about the Program and 1727 persons (32%) had enrolled . Twelve participants have been identified as having serious adverse events (SAEs) . One SAE, which occurred in a participant with ciprofloxacin-induced allergic interstitial nephritis, was considered to be probably associated with treatment received in the Program . No SAEs were associated with anthrax vaccine . CDC will continue to monitor Program participants during the next 2 years. Am J Hum Genet, 2003 Oct, 73(4), 957 - 66 Epub 2003 Sep 12. Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis; Dowling O et al.; Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are autosomal recessive syndromes of unknown etiology characterized by multiple, recurring subcutaneous tumors, gingival hypertrophy, joint contractures, osteolysis, and osteoporosis . Both are believed to be allelic disorders; ISH is distinguished from JHF by its more severe phenotype, which includes hyaline deposits in multiple organs, recurrent infections, and death within the first 2 years of life . Using the previously reported chromosome 4q21 JHF disease locus as a guide for candidate-gene identification, we identified and characterized JHF and ISH disease-causing mutations in the capillary morphogenesis factor-2 gene (CMG2) . Although CMG2 encodes a protein upregulated in endothelial cells during capillary formation and was recently shown to function as an anthrax-toxin receptor, its physiologic role is unclear . Two ISH family-specific truncating mutations, E220X and the 1-bp insertion P357insC that results in translation of an out-of-frame stop codon, were generated by site-directed mutagenesis and were shown to delete the CMG-2 transmembrane and/or cytosolic domains, respectively . An ISH compound mutation, I189T, is predicted to create a novel and destabilizing internal cavity within the protein . The JHF family-specific homoallelic missense mutation G105D destabilizes a von Willebrand factor A extracellular domain alpha-helix, whereas the other mutation, L329R, occurs within the transmembrane domain of the protein . Finally, and possibly providing insight into the pathophysiology of these diseases, analysis of fibroblasts derived from patients with JHF or ISH suggests that CMG2 mutations abrogate normal cell interactions with the extracellular matrix. J Vet Med Educ, 2003 Summer, 30(2), 145 - 7 Control and prevention of emerging zoonoses; Chomel BB; Emerging and re-emerging zoonoses are zoonotic diseases caused by either totally new or partially new agents or by microorganisms previously known but now occurring in places or in species where the disease was previously unknown . Zoonotic diseases account for the majority of all emerging infectious diseases . Several factors have led to the emergence of these infections, including human demographics, the industrialization of food production, globalization, international travel and commerce, land use, microbial adaptation, and changes and breakdown in public health measures . Several zoonotic agents are also potential agents that could be used as biological weapons . The recent use of anthrax spores in tainted mall in the US underlines our need for preparedness against bioterrorism . Prevention and control of these emerging zoonotic diseases is based on recognition, investigation, and collaboration, the development of advanced diagnosis and surveillance tools, the use of applied epidemiology and molecular biology methods, as well as education, information, communication, and technology transfer. Ann Intern Med, 2003 Sep 2, 139(5 Pt 1), 337 - 45 Accuracy of screening for inhalational anthrax after a bioterrorist attack; Hupert N et al.; BACKGROUND: Bioterrorism using anthrax claimed five lives in the United States in 2001 and remains a potential public health threat . In the aftermath of a large-scale anthrax attack, mass screening to identify early inhalational anthrax may improve both the management of individual cases and the efficiency of health resource utilization . PURPOSE: To develop the evidence base for outpatient anthrax screening protocols by quantifying differences in clinical presentation between inhalational anthrax and common viral respiratory tract infections . DESIGN: Review, compilation, and data extraction from English-language case reports of inhalational anthrax and epidemiologic studies of influenza and other viral respiratory infections . DATA SOURCES: 13 reports of 28 cases of inhalational anthrax from 1920 to 2001 and 5 studies reporting on the clinical features of 2762 cases of influenza and 1932 cases of noninfluenza viral respiratory disease . DATA SYNTHESIS: Characterization of presenting clinical symptoms in anthrax and viral disease and calculation of likelihood ratios for the presence of selected clinical features . RESULTS: Fever and cough do not reliably discriminate between inhalational anthrax and viral respiratory tract infection . Features suggestive of anthrax include the presence of nonheadache neurologic symptoms (positive likelihood ratio cannot be calculated), dyspnea (positive likelihood ratio, 5.3 {95% CI, 3.7 to 7.4}), nausea or vomiting (positive likelihood ratio, 5.1 {CI, 3.0 to 8.5}), and finding of any abnormality on lung auscultation (positive likelihood ratio, 8.1 {CI, 5.3 to 12.5}) . In contrast, rhinorrhea (positive likelihood ratio, 0.2 {CI, 0.1 to 0.4}) and sore throat (positive likelihood ratio, 0.2 {CI, 0.1 to 0.5}) are more suggestive of viral respiratory tract infection . CONCLUSION: Inhalational anthrax has characteristic clinical features that are distinct from those seen in common viral respiratory tract infections . Screening protocols based on these features may improve rapid identification of patients with presumptive inhalational anthrax in the setting of a large-scale anthrax attack. Proc Natl Acad Sci U S A, 2003 Sep 16, 100(19), 10925 - 30 Epub 2003 Sep 05. A dually active anthrax vaccine that confers protection against both bacilli and toxins; Rhie GE et al.; Systemic anthrax is caused by unimpeded bacillar replication and toxin secretion . We developed a dually active anthrax vaccine (DAAV) that confers simultaneous protection against both bacilli and toxins . DAAV was constructed by conjugating capsular poly-gamma-d-glutamic acid (PGA) to protective antigen (PA), converting the weakly immunogenic PGA to a potent immunogen, and synergistically enhancing the humoral response to PA . PGA-specific antibodies bound to encapsulated bacilli and promoted the killing of bacilli by complement . PA-specific antibodies neutralized toxin activity and protected immunized mice against lethal challenge with anthrax toxin . Thus, DAAV combines both antibacterial and antitoxic components in a single vaccine against anthrax . DAAV introduces a vaccine design that may be widely applicable against infectious diseases and provides additional tools in medicine and biodefense. Appl Occup Environ Hyg, 2003 Oct, 18(10), 780 - 5 Responding to a bioterrorist attack: environmental investigation of anthrax in New Jersey; Valiante DJ et al.; A bioterrorism attack using the United States postal system to deliver a hazardous biological agent to specific targets created mul