| antibiotic treatment attenuates behavioral and neurochemical changes induced by exposure of rats to group a streptococcal antigen. | post-streptococcal a (gas) sequelae including movement and neuropsychiatric disorders have been associated with improvement in response to antibiotic therapy. besides eradication of infection, the underlying basis of attenuation of neuropsychiatric symptoms following antibiotic treatment is not known. the aim of the present study was to test the efficacy of antibiotic treatment in a rat model of gas-related neuropsychiatric disorders. in the model, rats were not infected but were exposed to gas- ... | 2014 | 24979049 |
| live attenuated b. pertussis bpze1 rescues the immune functions of respiratory syncytial virus infected human dendritic cells by promoting th1/th17 responses. | respiratory syncytial virus (rsv) is the leading cause of acute lower respiratory tract viral infection in young children and a major cause of winter hospitalization. bordetella pertussis is a common cause of bacterial lung disease, affecting a similar age group. although vaccines are available for b. pertussis infection, disease rates have recently increased in many countries. we have therefore developed a novel live attenuated b. pertussis strain (bpze1), which has recently undergone a success ... | 2014 | 24967823 |
| exoy from pseudomonas aeruginosa is a nucleotidyl cyclase with preference for cgmp and cump formation. | in addition to the well known second messengers camp and cgmp, mammalian cells contain the cyclic pyrimidine nucleotides ccmp and cump. soluble guanylyl cyclase and soluble adenylyl cyclase produce all four cnmps. several bacterial toxins exploit mammalian cyclic nucleotide signaling. the type iii secretion protein exoy from pseudomonas aeruginosa induces severe lung damage and effectively produces cgmp. here, we show that transfection of mammalian cells with exoy or infection with exoy-expressi ... | 2014 | 24971548 |
| constitutive gαi coupling activity of very large g protein-coupled receptor 1 (vlgr1) and its regulation by pdzd7 protein. | the very large g protein-coupled receptor 1 (vlgr1) is a core component in inner ear hair cell development. mutations in the vlgr1 gene cause usher syndrome, the symptoms of which include congenital hearing loss and progressive retinitis pigmentosa. however, the mechanism of vlgr1-regulated intracellular signaling and its role in usher syndrome remain elusive. here, we show that vlgr1 is processed into two fragments after autocleavage at the g protein-coupled receptor proteolytic site. the cleav ... | 2014 | 24962568 |
| monitoring the effects of dexamethasone treatment by mri using in vivo iron oxide nanoparticle-labeled macrophages. | rheumatoid arthritis (ra) is a chronic disease causing recurring inflammatory joint attacks. these attacks are characterized by macrophage infiltration contributing to joint destruction. studies have shown that ra treatment efficacy is correlated to synovial macrophage number. the aim of this study was to experimentally validate the use of in vivo superparamagnetic iron oxide nanoparticle (spion) labeled macrophages to evaluate ra treatment by mri. | 2014 | 24957862 |
| in-utero exposure to maternal hiv infection alters t-cell immune responses to vaccination in hiv-uninfected infants. | in sub-saharan africa, hiv-exposed uninfected (heu) infants have higher morbidity and mortality than hiv-unexposed infants. to evaluate whether immune dysfunction contributes to this vulnerability of heu infants, we conducted a longitudinal, observational cohort study to assess t-cell immune responses to infant vaccines (mycobacterium bovis bcg and acellular pertussis) and staphylococcal enterotoxin b (seb). in total, 46 heu and 46 hiv-unexposed infants were recruited from khayelitsha, cape town ... | 2014 | 24785950 |
| haemorrhage, hyponatraemia and more than just a hack. | a 43-year-old previously healthy solicitor presented with a 9-day history of cough productive of yellow sputum with a prodrome of sore throat and myalgia. the cough was paroxysmal in nature and severe enough to cause extensive bilateral subconjunctival haemorrhages and cough syncopes multiple times a day, with one bout of associated haematemesis on the day of admission. he was isolated, treated for a presumed atypical chest infection with tazocin and clarithromycin, and monitored carefully until ... | 2014 | 24943139 |
| therapeutic vaccine strategies against human papillomavirus. | high-risk types of human papillomavirus (hpv) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. the transforming potential of hpvs is mediated by viral oncoproteins. these are essential for the induction and maintenance of the malignant phenotype. thus, hpv-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. therapeutic hpv vaccination is therefore an ideal scenario for proof-of-concept studies of canc ... | 2014 | 26344626 |
| role of il-17a and il-10 in the antigen induced inflammation model by mycoplasma pneumoniae. | mycoplasma pneumoniae is one of the causative organisms of community-acquired pneumonia which is found commonly in younger patients. extrapulmonary complications similar to autoimmune disease are caused by m. pneumoniae following the initial infection. the mechanism and pathology of onset is not clear, but it is considered that excessive host immunoreactions play a part in the onset of mycoplasmal pneumonia and its extrapulmonary complications. in this study, we investigated the participation of ... | 2014 | 24928272 |
| the human antibody response to the surface of mycobacterium tuberculosis. | vaccine-induced human antibodies to surface components of haemophilus influenzae and streptococcus pneumonia are correlated with protection. monoclonal antibodies to surface components of mycobacterium tuberculosis are also protective in animal models. we have characterized human antibodies that bind to the surface of live m. tuberculosis. | 2014 | 24918450 |
| post-tussive carotid artery dissection: could it be whooping cough? | | 2014 | 24914229 |
| allosteric activation of bordetella pertussis adenylyl cyclase by calmodulin: molecular dynamics and mutagenesis studies. | adenylyl cyclase (ac) toxin is an essential toxin that allows bordetella pertussis to invade eukaryotic cells, where it is activated after binding to calmodulin (cam). based on the crystal structure of the ac catalytic domain in complex with the c-terminal half of cam (c-cam), our previous molecular dynamics simulations (selwa, e., laine, e., and malliavin, t. (2012) differential role of calmodulin and calcium ions in the stabilization of the catalytic domain of adenyl cyclase cyaa from bordetel ... | 2014 | 24907274 |
| analysis of mreb interactors in chlamydia reveals a rodz homolog but fails to detect an interaction with mray. | chlamydia is an obligate intracellular bacterial pathogen that has significantly reduced its genome in adapting to the intracellular environment. one class of genes for which the bacterium has few annotated examples is cell division, and chlamydia lacks ftsz, a central coordinator of the division apparatus. we have previously implicated mreb as a potential substitute for ftsz in chlamydia (ouellette et al., 2012). thus, to identify new chlamydial cell division components, we searched for protein ... | 2014 | 24936201 |
| intra-articular injection of mesenchymal stem cells leads to reduced inflammation and cartilage damage in murine antigen-induced arthritis. | rheumatoid arthritis (ra) is a debilitating and painful disease leading to increased morbidity and mortality and novel therapeutic approaches are needed. the purpose of this study was to elucidate if mesenchymal stem cells (mscs) injected in the joints of mice with arthritis are therapeutic, reducing joint swelling and cartilage destruction. | 2014 | 24893776 |
| the first macrolide-resistant bordetella pertussis strains isolated from iranian patients. | whooping cough was considered as one of the major causes of childhood morbidity and mortality worldwide. resistant isolates of bordetella pertussis to macrolides in some countries have been recently reported. | 2014 | 25371806 |
| oral fluid testing for pertussis, england and wales, june 2007-august 2009. | existing pertussis surveillance systems tend to underidentify less severe cases among older children and adults. for routine follow-up of notified, nonconfirmed, clinically diagnosed pertussis cases, use of an oral fluid test was pilot tested in england and wales during june 2007-august 2009. during that period, 1,852 cases of pertussis were confirmed by established laboratory methods and another 591 by oral fluid testing only. although introduction of serologic testing in 2002 led to the greate ... | 2014 | 24856627 |
| sialic acid residues are essential for cell lysis mediated by leukotoxin from aggregatibacter actinomycetemcomitans. | leukotoxin (ltxa) from aggregatibacter actinomycetemcomitans is known to target and lyse β2-integrin-expressing cells such as polymorphonuclear leukocytes and macrophages. ltxa is an important virulence factor that facilitates chronic inflammation and is strongly associated with a fast-progressing form of periodontitis caused by the jp2 clone of the bacterium. here, we show that sialic acid residues are important for ltxa-induced cell lysis, regardless of whether the cell express β2-integrin or ... | 2014 | 24643533 |
| identification of a novel nutrient-sensing histidine kinase/response regulator network in escherichia coli. | when carbon sources become limiting for growth, bacteria must choose which of the remaining nutrients should be used first. we have identified a nutrient-sensing signaling network in escherichia coli that is activated at the transition to stationary phase. the network is composed of the two histidine kinase/response regulator systems yehu/yeht and ypda/ypdb and their target proteins, yjiy and yhjx (both of which are membrane-integrated transporters). the peptide/amino acid-responsive yehu/yeht s ... | 2014 | 24659770 |
| three cases of presumed pneumocystis pneumonia in patients receiving bortezomib therapy for multiple myeloma. | this paper presents three probable cases of pneumocystis pneumonia in patients receiving bortezomib therapy for multiple myeloma. | 2014 | 26955521 |
| iral is an rssb anti-adaptor that stabilizes rpos during logarithmic phase growth in escherichia coli and shigella. | rpos (σ(s)), the general stress response sigma factor, directs the expression of genes under a variety of stressful conditions. control of the cellular σ(s) concentration is critical for appropriately scaled σ(s)-dependent gene expression. one way to maintain appropriate levels of σ(s) is to regulate its stability. indeed, σ(s) degradation is catalyzed by the clpxp protease and the recognition of σ(s) by clpxp depends on the adaptor protein rssb. three anti-adaptors (irad, iram, and irap) exist ... | 2014 | 24865554 |
| transmembrane recognition of the semaphorin co-receptors neuropilin 1 and plexin a1: coarse-grained simulations. | the cancer associated class 3 semaphorins require direct binding to neuropilins and association to plexins to trigger cell signaling. here, we address the role of the transmembrane domains of neuropilin 1 and plexin a1 for the dimerization of the two receptors by characterizing the assembly in lipid bilayers using coarse-grained molecular dynamics simulations. from experimental evidence using a two-hybrid system showing the biochemical association of the two receptors transmembrane domains, we p ... | 2014 | 24858828 |
| involvement of the wbp pathway in the biosynthesis of porphyromonas gingivalis lipopolysaccharide with anionic polysaccharide. | the periodontal pathogen porphyromonas gingivalis has two different lipopolysaccharide (lps) molecules, o-lps and a-lps. we have recently shown that p. gingivalis strain hg66 lacks a-lps. here, we found that introduction of a wild-type wbpb gene into strain hg66 restored formation of a-lps. sequencing of the wbpb gene from strain hg66 revealed the presence of a nonsense mutation in the gene. the wbpb gene product is a member of the wbp pathway, which plays a role in the synthesis of udp-mannac(3 ... | 2014 | 24852504 |
| novel epigenetic target therapy for prostate cancer: a preclinical study. | epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. classic demethylating agents, such as 5-aza-2'-deoxycytidine (decitabine), hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. on the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. appropriate delivery sy ... | 2014 | 24851905 |
| fhac takes a bow to fha in the two-partner do-si-do. | fhac is an outer membrane transporter from bordetella pertussis belonging to the two-partner secretion (tps) pathway with its primary role being the secretion of the virulence factor filamentous haemagglutinin (fha). fhac serves as a model transporter of the tps pathway and significant work has been done to characterize the role of fhac in fha secretion. recent studies characterized interactions between fha and the potra domains of fhac, suggesting that secretion may involve a successive translo ... | 2014 | 24798489 |
| immunization with the recombinant cholera toxin b fused to fimbria 2 protein protects against bordetella pertussis infection. | this study examined the immunogenic properties of the fusion protein fimbria 2 of bordetella pertussis (fim2)-cholera toxin b subunit (ctb) in the intranasal murine model of infection. to this end b. pertussis fim2 coding sequence was cloned downstream of the cholera toxin b subunit coding sequence. the expression and assembly of the fusion protein into pentameric structures (ctb-fim2) were evaluated by sds-page and monosialotetrahexosylgaglioside (gm1-ganglioside) enzyme-linked immunosorbent as ... | 2014 | 24982881 |
| selective targeting of toll-like receptors and ox40 inhibit regulatory t-cell function in follicular lymphoma. | immunotherapeutic strategies are promising approaches for the treatment of follicular lymphoma (fl). however, their efficacy may be limited by immunosuppressive elements in the immune system and tumor microenvironment. therefore, strategies to reverse the effects of the immunosuppressive elements are needed. we observed that regulatory t cells (tregs) were increased in the peripheral blood at diagnosis and persisted in high numbers after induction of clinical remission with a cyclophosphamide an ... | 2014 | 24771328 |
| diffusion basis spectrum imaging detects and distinguishes coexisting subclinical inflammation, demyelination and axonal injury in experimental autoimmune encephalomyelitis mice. | clinicopathological paradox has hampered significantly the effective assessment of the efficacy of therapeutic intervention for multiple sclerosis. neuroimaging biomarkers of tissue injury could guide more effective treatment by accurately reflecting the underlying subclinical pathologies. diffusion tensor imaging-derived directional diffusivity and anisotropy indices have been applied to characterize white matter disorders. however, these biomarkers are sometimes confounded by the complex patho ... | 2014 | 24816651 |
| efficient neutrophil extracellular trap induction requires mobilization of both intracellular and extracellular calcium pools and is modulated by cyclosporine a. | excessive or aberrant generation of neutrophil extracellular traps (nets) has recently become implicated in the underlying aetiology of a number of human pathologies including preeclampsia, systemic lupus erythromatosus, rheumatoid arthritis, auto-antibody induced small vessel vasculitis, coagulopathies such as deep vein thrombosis or pulmonary complications. these results imply that effective pharmacological therapeutic strategies will need to be developed to counter overt netosis in these and ... | 2014 | 24819773 |
| de novo synthesis of a bacterial toxin/antitoxin system. | the prevalence of toxin/antitoxin (ta) systems in almost all genomes suggests they evolve rapidly. here we show that an antitoxin from a type v system (ghos, an endoribonuclease specific for the mrna of the toxin ghot) can be converted into a novel toxin (art) simply by adding two mutations. in contrast to ghos, which increases growth, the new toxin art decreases growth dramatically in escherichia coli. transmission electron microscopy analysis revealed that the nucleoid in art-producing cells i ... | 2014 | 24797297 |
| estimating the prevalence of coinfection with influenza virus and the atypical bacteria bordetella pertussis, chlamydophila pneumoniae, and mycoplasma pneumoniae. | coinfections with common bacterial respiratory pathogens and influenza viruses are well-known causes of disease, often via synergistic interactions between the influenza virus, the bacteria, and the human host. however, relatively little is known about interactions between atypical bacteria and influenza viruses. a recent report by reinton et al. explored this issue by analyzing data from 3,661 patients seeking medical assistance for the presence of mycoplasma pneumoniae, chlamydophila pneumonia ... | 2014 | 24789653 |
| differential effects of the gβ5-rgs7 complex on muscarinic m3 receptor-induced ca2+ influx and release. | the g protein β subunit gβ5 uniquely forms heterodimers with r7 family regulators of g protein signaling (rgs) proteins (rgs6, rgs7, rgs9, and rgs11) instead of gγ. although the gβ5-rgs7 complex attenuates ca(2+) signaling mediated by the muscarinic m3 receptor (m3r), the route of ca(2+) entry (i.e., release from intracellular stores and/or influx across the plasma membrane) is unknown. here, we show that, in addition to suppressing carbachol-stimulated ca(2+) release, gβ5-rgs7 enhanced ca(2+) i ... | 2014 | 24586057 |
| picornavirus infection leading to immunosuppression. | viruses, such as hiv, hepatitis a, poliovirus, coxsackievirus b3 and foot-and-mouth disease virus, use a variety of mechanisms to suppress the human immune system in order to evade clearance by the host. therefore, investigating how a few changes in the viral genome of a nonlethal virus can lead to an alteration in disease, from survivable to immunosuppression and death, would provide valuable information into viral pathogenesis. in addition, we propose that gaining a better insight into how the ... | 2014 | 25214881 |
| the real-life effectiveness of palivizumab for reducing hospital admissions for respiratory syncytial virus in infants residing in nunavut. | background⁄ | 2014 | 24367792 |
| serodiagnosis as adjunct assay for pertussis infection in são paulo, brazil. | pertussis remains an important public health problem in many countries despite extensive immunization. cultures and real-time pcr (rt-pcr) assays are the recommended pertussis diagnostic tests, but they lack sensitivity at the later stage of the disease. this study introduces the igg anti-pertussis toxin enzyme-linked immunosorbent assay (pt elisa) in our routine diagnosis to improve disease burden estimation. serum samples and nasopharyngeal swabs (n = 503) were collected at the same time from ... | 2014 | 24599531 |
| bordetella pertussis proteins dominating the major histocompatibility complex class ii-presented epitope repertoire in human monocyte-derived dendritic cells. | knowledge of naturally processed bordetella pertussis-specific t cell epitopes may help to increase our understanding of the basis of cell-mediated immune mechanisms to control this reemerging pathogen. here, we elucidate for the first time the dominant major histocompatibility complex (mhc) class ii-presented b. pertussis cd4(+) t cell epitopes, expressed on human monocyte-derived dendritic cells (mddc) after the processing of whole bacterial cells by use of a platform of immunoproteomics techn ... | 2014 | 24599530 |
| toll-like receptor 2-dependent protection against pneumococcal carriage by immunization with lipidated pneumococcal proteins. | infections with streptococcus pneumoniae cause substantial morbidity and mortality, particularly in children in developing nations. polysaccharide-conjugate vaccines provide protection against both invasive disease and colonization, but their use in developing countries is limited by restricted serotype coverage and expense of manufacture. using proteomic screens, we recently identified several antigens that protected mice from pneumococcal colonization in a cd4(+) t cell- and interleukin-17a (i ... | 2014 | 24614661 |
| helminth-induced interleukin-4 abrogates invariant natural killer t cell activation-associated clearance of bacterial infection. | helminth infections affect 1 billion people worldwide and render these individuals susceptible to bacterial coinfection through incompletely understood mechanisms. this includes urinary tract coinfection by bacteria and schistosoma haematobium worms, the etiologic agent of urogenital schistosomiasis. to study the mechanisms of s. haematobium-bacterial urinary tract coinfections, we combined the first tractable model of urogenital schistosomiasis with an established mouse model of bacterial urina ... | 2014 | 24643536 |
| vibrio vulnificus biotype 3 multifunctional autoprocessing rtx toxin is an adenylate cyclase toxin essential for virulence in mice. | vibrio vulnificus is an environmental organism that causes both food-borne and wound infections with high morbidity and mortality in humans. the annual incidence and global distribution of infections associated with this pathogen are increasing with climate change. in the late 1990s, an outbreak of tilapia-associated wound infections in israel was linked to a previously unrecognized variant of v. vulnificus designated biotype 3. the sudden emergence and clonality of the outbreak suggest that thi ... | 2014 | 24614656 |
| the phou protein from escherichia coli interacts with phor, pstb, and metals to form a phosphate-signaling complex at the membrane. | robust growth in many bacteria is dependent upon proper regulation of the adaptive response to phosphate (pi) limitation. this response enables cells to acquire pi with high affinity and utilize alternate phosphorous sources. the molecular mechanisms of pi signal transduction are not completely understood. phou, along with the high-affinity, pi-specific atp-binding cassette transporter pstscab and the two-component proteins phor and phob, is absolutely required for pi signaling in escherichia co ... | 2014 | 24563032 |
| mannan-binding lectin in cardiovascular disease. | cardiovascular disease remains the leading cause of mortality and morbidity worldwide so research continues into underlying mechanisms. since innate immunity and its potent component mannan-binding lectin have been proven to play an important role in the inflammatory response during infection and ischaemia-reperfusion injury, attention has been paid to its role in the development of cardiovascular complications as well. this review provides a general outline of the structure and genetic polymorp ... | 2014 | 24877121 |
| regulatory lymphocytes are key factors in mhc-independent resistance to eae. | resistant and susceptible mouse strains to experimental autoimmune encephalomyelitis (eae), an inducible demyelinating experimental disease serving as animal model for multiple sclerosis, have been described. we aimed to explore mhc-independent mechanisms inducing resistance to eae. | 2014 | 24868560 |
| development of inhibitors of heterotrimeric gαi subunits. | heterotrimeric g-proteins are the immediate downstream effectors of g-protein coupled receptors (gpcrs). endogenous protein guanine nucleotide dissociation inhibitors (gdis) like ags3/4 and rgs12/14 function through gpr/goloco gdi domains. extensive characterization of gpr domain peptides indicate they function as selective gdis for gαi by competing for the gpcr and gβγ and preventing gdp release. we modified a gpr consensus peptide by testing fgf and tat leader sequences to make the peptide cel ... | 2014 | 24818958 |
| pertussis seroprevalence in korean adolescents and adults using anti-pertussis toxin immunoglobulin g. | this study was conducted to evaluate age-specific seroprevalence of pertussis in korea and to formulate a strategy to prevent and reduce the incidence of pertussis. residual serum samples of healthy adolescents and adults 11 yr of age or older were collected between july 2012 and december 2012, and anti-pertussis toxin (pt) igg titers were measured using a commercial elisa kit. we compared the mean anti-pt igg titers and seroprevalence of pertussis of the six age groups: 11-20, 21-30, 31-40, 41- ... | 2014 | 24851020 |
| role of calmodulin-calmodulin kinase ii, camp/protein kinase a and erk 1/2 on aeromonas hydrophila-induced apoptosis of head kidney macrophages. | the role of calcium (ca2+) and its dependent protease calpain in aeromonas hydrophila-induced head kidney macrophage (hkm) apoptosis has been reported. here, we report the pro-apoptotic involvement of calmodulin (cam) and calmodulin kinase ii gamma (camkiig) in the process. we observed significant increase in cam levels in a. hydrophila-infected hkm and the inhibitory role of bapta/am, egta, nifedipine and verapamil suggested cam elevation to be ca2+-dependent. our studies with cam-specific sirn ... | 2014 | 24763432 |
| dysregulated microrna expression in serum of non-vaccinated children with varicella. | circulating micrornas (mirnas) may play an important role in pathogen-host interactions and can serve as molecular markers for the detection of infectious diseases. to date, the relationship between circulating mirnas and varicella-zoster virus (vzv) caused varicella has not been reported. using taqman low-density array (tlda) analysis, expression levels of mirnas in serum samples from 29 patients with varicella and 60 patients with bordetella pertussis (bp), measles virus (mev) and enterovirus ... | 2014 | 24759212 |
| transport proteins promoting escherichia coli pathogenesis. | escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. we examined seven well-characterized e. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. their transport proteins were identified and compared with each other and a non-pathogenic e. coli k12 strain to identify transport proteins related to pathogenesis. each pathogen possesses a unique set of protein secretion systems for export ... | 2014 | 24747185 |
| interleukin-35 induces regulatory b cells that suppress autoimmune disease. | interleukin-10 (il-10)-producing regulatory b (breg) cells suppress autoimmune disease, and increased numbers of breg cells prevent host defense to infection and promote tumor growth and metastasis by converting resting cd4(+) t cells to regulatory t (treg) cells. the mechanisms mediating the induction and development of breg cells remain unclear. here we show that il-35 induces breg cells and promotes their conversion to a breg subset that produces il-35 as well as il-10. treatment of mice with ... | 2014 | 24743305 |
| vaccine potentiation by combination adjuvants. | adjuvants are crucial components of vaccines. they significantly improve vaccine efficacy by modulating, enhancing, or extending the immune response and at the same time reducing the amount of antigen needed. in contrast to previously licensed adjuvants, current successful adjuvant formulations often consist of several molecules, that when combined, act synergistically by activating a variety of immune mechanisms. these "combination adjuvants" are already registered with several vaccines, both i ... | 2014 | 26344621 |
| infection prevention in the emergency department. | infection prevention remains a major challenge in emergency care. acutely ill and injured patients seeking evaluation and treatment in the emergency department (ed) not only have the potential to spread communicable infectious diseases to health care personnel and other patients, but are vulnerable to acquiring new infections associated with the care they receive. this article will evaluate these risks and review the existing literature for infection prevention practices in the ed, ranging from ... | 2014 | 24721718 |
| a comparative study of experimental mouse models of central nervous system demyelination. | several mouse models of multiple sclerosis (ms) are now available. we have established a mouse model, in which ocular infection with a recombinant hsv-1 that expresses murine interleukin (il)-2 constitutively (hsv-il-2) causes central nervous system demyelination in different strains of mice. this model differs from most other models, in which it represents a mixture of viral and immune triggers. in the present study, we directly compared mog35-55, mbp35-47 and plp190-209 models of experimental ... | 2014 | 24718267 |
| plasmacytoid dendritic cells mediate anti-inflammatory responses to a gut commensal molecule via both innate and adaptive mechanisms. | polysaccharide a (psa), the archetypical immunomodulatory molecule of the gut commensal bacteroides fragilis, induces regulatory t cells to secrete the anti-inflammatory cytokine interleukin-10 (il-10). the cellular mediators of psa's immunomodulatory properties are incompletely understood. in a mouse model of colitis, we find that psa requires both innate and adaptive immune mechanisms to generate protection. plasmacytoid dcs (pdcs) exposed to psa do not produce proinflammatory cytokines, but i ... | 2014 | 24721570 |
| targeting insulin-like growth factor 1 leads to amelioration of inflammatory demyelinating disease. | in patients with multiple sclerosis (ms) and in mice with experimental autoimmune encephalomyelitis (eae), proliferating autoreactive t cells play an important role in the pathogenesis of the disease. due to the importance of these myelin-specific t cells, these cells have been therapeutic targets in a variety of treatments. previously we found that lenaldekar (ldk), a novel small molecule, could inhibit exacerbations in a preclinical model of ms when given at the start of an eae exacerbation. i ... | 2014 | 24718491 |
| bhba suppresses lps-induced inflammation in bv-2 cells by inhibiting nf-κb activation. | β-hydroxybutyric acid (bhba) has neuroprotective effects, but the underlying molecular mechanisms are unclear. microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. the current study investigates the potential mechanisms whereby bhba affects the expression of potentially proinflammatory proteins by cultured murine microglial bv-2 cells stimulated with lipopolysaccharide (lps). the results showed tha ... | 2014 | 24803746 |
| how advances in immunology provide insight into improving vaccine efficacy. | vaccines represent one of the most compelling examples of how biomedical research has improved society by saving lives and dramatically reducing the burden of infectious disease. despite the importance of vaccinology, we are still in the early stages of understanding how the best vaccines work and how we can achieve better protective efficacy through improved vaccine design. most successful vaccines have been developed empirically, but recent advances in immunology are beginning to shed new ligh ... | 2014 | 24709587 |
| the pseudomonas aeruginosa exoenzyme y impairs endothelial cell proliferation and vascular repair following lung injury. | exoenzyme y (exoy) is a pseudomonas aeruginosa toxin that is introduced into host cells through the type 3 secretion system (t3ss). once inside the host cell cytoplasm, exoy generates cyclic nucleotides that cause tau phosphorylation and microtubule breakdown. microtubule breakdown causes interendothelial cell gap formation and tissue edema. although exoy transiently induces interendothelial cell gap formation, it remains unclear whether exoy prevents repair of the endothelial cell barrier. here ... | 2014 | 24705722 |
| dynamics of high-risk nonvaccine human papillomavirus types after actual vaccination scheme. | human papillomavirus (hpv) has been identified as the main etiological factor in the developing of cervical cancer (cc). this finding has propitiated the development of vaccines that help to prevent the hpvs 16 and 18 infection. both genotypes are associated with 70% of cc worldwide. in the present study, we aimed to determine the emergence of high-risk nonvaccine hpv after actual vaccination scheme to estimate the impact of the current hpv vaccines. a sir-type model was used to study the hpv dy ... | 2014 | 24803952 |
| trends in hospital admission rates for whooping cough in england across five decades: database studies. | our aim was to report on trends in hospitalisation rates for pertussis in england from the 1960s to 2011; and to provide context for the recent unexpected activity of bordetella pertussis in the uk. | 2014 | 24526463 |
| nonhuman primate and human challenge models of pertussis. | despite pertussis vaccination rates in excess of 95%, pertussis rates in the united states have been rising over the last 30 years, with increasingly larger outbreaks in 2004, 2010, and 2012. the reasons for this resurgence of pertussis are not clearly understood. the recent development of a baboon model of pertussis, along with the future development of a human challenge model of pertussis, has the potential to provide a path forward for answering critical questions about pertussis pathogenesis ... | 2014 | 24626867 |
| enhanced interaction of vibrio cholerae virulence regulators tcpp and toxr under oxygen-limiting conditions. | vibrio cholerae is the causative agent of the diarrheal disease cholera. the ability of v. cholerae to colonize and cause disease requires the intricately regulated expression of a number of virulence factors during infection. one of the signals sensed by v. cholerae is the presence of oxygen-limiting conditions in the gut. it has been shown that the virulence activator aphb plays a key role in sensing low oxygen concentrations and inducing the transcription of another key virulence activator, t ... | 2014 | 24491579 |
| the protein tyrosine kinases epsb and ptka differentially affect biofilm formation in bacillus subtilis. | the gram-positive soil bacterium bacillus subtilis is able to choose between motile and sessile lifestyles. the sessile way of life, also referred to as biofilm, depends on the formation of an extracellular polysaccharide matrix and some extracellular proteins. moreover, a significant proportion of cells in a biofilm form spores. the first two genes of the 15-gene operon for extracellular polysaccharide synthesis, epsa and epsb, encode a putative transmembrane modulator protein and a putative pr ... | 2014 | 24493247 |
| pertussis vaccine trials in the 1990s. | the significant burden of disease due to pertussis, which predominantly affects newborns during their first few months of life, was substantially decreased following the introduction of inactivated whole-bacterial-cell vaccines in the middle of the 20th century. although these vaccines were effective in reducing the incidence of pertussis in the countries that implemented their widespread use, increasing concerns about pertussis vaccine-associated adverse events led the development of acellular ... | 2014 | 24626871 |
| rapid increase in pertactin-deficient bordetella pertussis isolates, australia. | acellular vaccines against bordetella pertussis were introduced in australia in 1997. by 2000, these vaccines had replaced whole-cell vaccines. during 2008-2012, a large outbreak of pertussis occurred. during this period, 30% (96/320) of b. pertussis isolates did not express the vaccine antigen pertactin (prn). multiple mechanisms of prn inactivation were documented, including is481 and is1002 disruptions, a variation within a homopolymeric tract, and deletion of the prn gene. the mechanism of l ... | 2014 | 24655754 |
| histamine h₂ receptor signaling × environment interactions determine susceptibility to experimental allergic encephalomyelitis. | histamine and its receptors are important in both multiple sclerosis and experimental allergic encephalomyelitis (eae). c57bl/6j (b6) mice deficient for the histamine h2 receptor (h2rko) are less susceptible to eae and exhibit blunted th1 responses. however, whether decreased antigen-specific t-cell effector responses in h2rko mice were due to a lack of h2r signaling in cd4(+) t cells or antigen-presenting cells has remained unclear. we generated transgenic mice expressing h2r specifically in t ... | 2014 | 24371118 |
| pertussis pathogenesis--what we know and what we don't know. | pertussis is a worldwide public health threat. bordetella pertussis produces multiple virulence factors that have been studied individually, and many have recently been found to have additional biological activities. nevertheless, how they interact to cause the disease pertussis remains unknown. new animal models, particularly the infection of infant baboons with b. pertussis, are enabling longstanding questions about pertussis pathogenesis to be answered and new ones to be asked. enhancing our ... | 2014 | 24626533 |
| proteomic analysis of vibrio cholerae outer membrane vesicles. | outer membrane vesicles (omvs) produced by gram-negative bacteria provide an interesting research material for defining cell-envelope proteins without experimental cell disruption. omvs are also promising immunogenic platforms and may play important roles in bacterial survival and pathogenesis. we used in-solution trypsin digestion coupled to mass spectrometry to identify 90 proteins present in omvs of vibrio cholerae when grown under conditions that activate the tcp pilus virulence regulatory p ... | 2014 | 24706774 |
| distinct docking and stabilization steps of the pseudopilus conformational transition path suggest rotational assembly of type iv pilus-like fibers. | the closely related bacterial type ii secretion (t2s) and type iv pilus (t4p) systems are sophisticated machines that assemble dynamic fibers promoting protein transport, motility, or adhesion. despite their essential role in virulence, the molecular mechanisms underlying helical fiber assembly remain unknown. here, we use electron microscopy and flexible modeling to study conformational changes of pulg pili assembled by the klebsiella oxytoca t2ss. neural network analysis of 3,900 pilus models ... | 2014 | 24685147 |
| parent-of-origin effects implicate epigenetic regulation of experimental autoimmune encephalomyelitis and identify imprinted dlk1 as a novel risk gene. | parent-of-origin effects comprise a range of genetic and epigenetic mechanisms of inheritance. recently, detection of such effects implicated epigenetic mechanisms in the etiology of multiple sclerosis (ms), a chronic inflammatory disease of the central nervous system. we here sought to dissect the magnitude and the type of parent-of-origin effects in the pathogenesis of experimental neuroinflammation under controlled environmental conditions. we investigated inheritance of an ms-like disease in ... | 2014 | 24676147 |
| immunologic treatments for precancerous lesions and uterine cervical cancer. | development of hpv-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. in this way, hpv-related tumors usually present mhc class i down-regulation, impaired antigen-processing ability, avoidance of t-cell mediated killing, increased immunosuppression due to treg infiltration and secrete immunosuppressive cytoki ... | 2014 | 24667138 |
| comparison of microglia and infiltrating cd11c⁺ cells as antigen presenting cells for t cell proliferation and cytokine response. | tissue-resident antigen-presenting cells (apc) exert a major influence on the local immune environment. microglia are resident myeloid cells in the central nervous system (cns), deriving from early post-embryonic precursors, distinct from adult hematopoietic lineages. dendritic cells (dc) and macrophages infiltrate the cns during experimental autoimmune encephalomyelitis (eae). microglia are not considered to be as effective apc as dc or macrophages. | 2014 | 24666681 |
| geographical differences in whooping cough in catalonia, spain, from 1990 to 2010. | whooping cough is a communicable disease whose incidence has increased in recent years in some countries with vaccination. since 1981, in catalonia (spain), cases must be reported to the public health department. in 1997, surveillance changed from aggregated counts to individual report and the surveillance system was improved after 2002. catalan public health is universal with equal coverage geographically. the aim of this study was to determine whether there are differences in whooping cough in ... | 2014 | 24649975 |
| escherichia coli heat-labile detoxified enterotoxin modulates dendritic cell function and attenuates allergic airway inflammation. | various mutant forms of escherichia coli heat-labile enterotoxin (lt) have been used as a mucosal adjuvant for vaccines, as it enhances immune responses to specific antigens including antigen-specific iga antibodies when administrated intranasally or orally. we hypothesized that a detoxified mutant form of lt, lts61k, could modulate dendritic cell (dc) function and alleviate allergen-induced airway inflammation. two protocols, preventative and therapeutic, were used to evaluate the effects of lt ... | 2014 | 24637787 |
| promising potential of new generation translocator protein tracers providing enhanced contrast of arthritis imaging by positron emission tomography in a rat model of arthritis. | early diagnosis of and subsequent monitoring of therapy for rheumatoid arthritis (ra) could benefit from detection of (sub)clinical synovitis. imaging of (sub)clinical arthritis by targeting the translocator protein (tspo) on activated macrophages is feasible using (r)-[¹¹c] pk11195-based positron emission tomography (pet), but clinical applications are limited by background uptake in peri-articular bone/bone marrow. the purpose of the present study was to evaluate two other tspo ligands with po ... | 2014 | 24625077 |
| staphylococcus aureus infection of mice expands a population of memory γδ t cells that are protective against subsequent infection. | the development of vaccines against staphylococcus aureus has consistently failed in clinical trials, likely due to inefficient induction of cellular immunity. t cell-derived il-17 is one of the few known correlates of antistaphylococcoal immunity, conferring protection against s. aureus infections through its ability to promote phagocytic cell effector functions. a comprehensive understanding of the discrete t cell subsets critical for site-specific il-17-mediated bacterial clearance will there ... | 2014 | 24623128 |
| variable virulence factors in burkholderia pseudomallei (melioidosis) associated with human disease. | burkholderia pseudomallei is a gram-negative environmental bacterium that causes melioidosis, a potentially life-threatening infectious disease affecting mammals, including humans. melioidosis symptoms are both protean and diverse, ranging from mild, localized skin infections to more severe and often fatal presentations including pneumonia, septic shock with multiple internal abscesses and occasionally neurological involvement. several ubiquitous virulence determinants in b. pseudomallei have al ... | 2014 | 24618705 |
| imidazol-1-ylethylindazole voltage-gated sodium channel ligands are neuroprotective during optic neuritis in a mouse model of multiple sclerosis. | a series of imidazol-1-ylethylindazole sodium channel ligands were developed and optimized for sodium channel inhibition and in vitro neuroprotective activity. the molecules exhibited displacement of a radiolabeled sodium channel ligand and selectivity for blockade of the inactivated state of cloned neuronal nav channels. metabolically stable analogue 6 was able to protect retinal ganglion cells during optic neuritis in a mouse model of multiple sclerosis. | 2014 | 24601592 |
| skewed b cell differentiation affects lymphoid organogenesis but not t cell-mediated autoimmunity. | b cell receptor (bcr) signalling determines b cell differentiation and may potentially alter t cell-mediated immune responses. in this study we used two transgenic strains of bcr-deficient mice expressing epstein-barr virus latent membrane protein (lmp)2a in b cells, where either follicular and marginal zone differentiation (d(h)lmp2a mice) or b-1 cell development (v(h)lmp2a mice) were supported, and evaluated the effects of skewed b lymphocyte differentiation on lymphoid organogenesis and t cel ... | 2014 | 24325711 |
| tlr agonists for cancer immunotherapy: tipping the balance between the immune stimulatory and inhibitory effects. | | 2014 | 24624132 |
| invasion-inhibitory antibodies elicited by immunization with plasmodium vivax apical membrane antigen-1 expressed in pichia pastoris yeast. | in a recent vaccine trial performed with african children, immunization with a recombinant protein based on plasmodium falciparum apical membrane antigen 1 (ama-1) conferred a significant degree of strain-specific resistance against malaria. to contribute to the efforts of generating a vaccine against plasmodium vivax malaria, we expressed the ectodomain of p. vivax ama-1 (pvama-1) as a secreted soluble protein in the methylotrophic yeast pichia pastoris. recognized by a high percentage of sera ... | 2014 | 24379279 |
| fatal subacute myocarditis associated with human bocavirus 2 in a 13-month-old child. | human bocavirus has rarely been incriminated in fatal or life-threatening respiratory infections. we report a case of fatal disseminated infection with subacute lymphocytic myocarditis in a 13-month-old child. the human bocavirus 2 genome was detected by pcr analysis in nasal swab, plasma, urine, ascitic fluid, and mesenteric node, skeletal muscle, and lung tissue specimens. | 2014 | 24371238 |
| the sensor kinase dcts forms a tripartite sensor unit with dctb and dcta for sensing c4-dicarboxylates in bacillus subtilis. | the dctsr two-component system of bacillus subtilis controls the expression of the aerobic c4-dicarboxylate transporter dcta. deletion of dcta leads to an increased dcta expression. the inactivation of dctb, an extracellular binding protein, is known to inhibit the expression of dcta. here, interaction between the sensor kinase dcts and the transporter dcta as well as the binding protein dctb was demonstrated in vivo using streptavidin (strep) or his protein interaction experiments (mspine or mh ... | 2014 | 24375102 |
| recent trends of antigenic variation in bordetella pertussis isolates in korea. | pertussis is a representative vaccine-preventable disease. however, there have been recent outbreaks in countries where even higher vaccination against the disease. one reason is the emergence of antigenic variants, which are different to vaccine type. in korea, reported cases have rapidly increased since 2009. therefore, we analyzed genotype of strains isolated in 2011-2012 by multilocus sequence typing method. as expected, the genotype profiles of tested genes dramatically changed. the major s ... | 2014 | 24616579 |
| sensor domain of histidine kinase kinb of pseudomonas: a helix-swapped dimer. | the overproduction of polysaccharide alginate is responsible for the formation of mucus in the lungs of cystic fibrosis patients. histidine kinase kinb of the kinb-algb two-component system in pseudomonas aeruginosa acts as a negative regulator of alginate biosynthesis. the modular architecture of kinb is similar to other histidine kinases. however, its periplasmic signal sensor domain is unique and is found only in the pseudomonas genus. here, we present the first crystal structures of the kinb ... | 2014 | 24573685 |
| behavioral and neural effects of intra-striatal infusion of anti-streptococcal antibodies in rats. | group a β-hemolytic streptococcal (gas) infection is associated with a spectrum of neuropsychiatric disorders. the leading hypothesis regarding this association proposes that a gas infection induces the production of auto-antibodies, which cross-react with neuronal determinants in the brain through the process of molecular mimicry. we have recently shown that exposure of rats to gas antigen leads to the production of anti-neuronal antibodies concomitant with the development of behavioral alterat ... | 2014 | 24561489 |
| toward a mechanism-based in vitro safety test for pertussis toxin. | pertussis vaccines are routinely administered to infants to protect them from whooping cough. still, an adequate safety test for pertussis toxin (pt), one of the main antigens in these vaccines, is not available. the histamine sensitization test is currently the only assay accepted by regulatory authorities to test for the absence of active pt in vaccines. this is however, a lethal animal test with poor reproducibility. in addition, it is not clear whether the assumed underlying mechanism, i.e., ... | 2014 | 24553455 |
| diagnosis of whooping cough in switzerland: differentiating bordetella pertussis from bordetella holmesii by polymerase chain reaction. | bordetella holmesii, an emerging pathogen, can be misidentified as bordetella pertussis by routine polymerase chain reaction (pcr). in some reports, up to 29% of the patients diagnosed with pertussis have in fact b. holmesii infection and invasive, non-respiratory b. holmesii infections have been reported worldwide. this misdiagnosis undermines the knowledge of pertussis' epidemiology, and may lead to misconceptions on pertussis vaccine's efficacy. recently, the number of whooping cough cases ha ... | 2014 | 24586447 |
| lack of association between mannose binding lectin and antibody responses after acellular pertussis vaccinations. | mannose-binding lectin (mbl) is one of the key molecules in innate immunity and its role in human vaccine responses is poorly known. this study aimed to investigate the possible association of mbl polymorphisms with antibody production after primary and booster vaccinations with acellular pertussis vaccines in infants and adolescents. | 2014 | 24558451 |
| the bordetella pertussis bps polysaccharide enhances lung colonization by conferring protection from complement-mediated killing. | bordetella pertussis is a human-restricted gram-negative bacterial pathogen that causes whooping cough or pertussis. pertussis is the leading vaccine preventable disease that is resurging in the usa and other parts of the developed world. there is an incomplete understanding of the mechanisms by which b. pertussis evades killing and clearance by the complement system, a first line of host innate immune defence. the present study examined the role of the bps polysaccharide to resist complement ac ... | 2014 | 24438122 |
| g(i)α proteins exhibit functional differences in the activation of erk1/2, akt and mtorc1 by growth factors in normal and breast cancer cells. | in a classic model, g(i)α proteins including g(i1)α, g(i2)α and g(i3)α are important for transducing signals from g(i)α protein-coupled receptors (g(i)αpcrs) to their downstream cascades in response to hormones and neurotransmitters. our previous study has suggested that g(i1)α, g(i2)α and g(i3)α are also important for the activation of the pi3k/akt/mtorc1 pathway by epidermal growth factor (egf) and its family members. however, a genetic role of these g(i)α proteins in the activation of extrace ... | 2014 | 24521094 |
| substantial gaps in knowledge of bordetella pertussis antibody and t cell epitopes relevant for natural immunity and vaccine efficacy. | the recent increase in whooping cough in vaccinated populations has been attributed to waning immunity associated with the acellular vaccine. the immune epitope database (iedb) is a repository of immune epitope data from the published literature and includes t cell and antibody epitopes for human pathogens. the iedb conducted a review of the epitope literature, which revealed 300 bordetella pertussis-related epitopes from 39 references. epitope data are currently available for six virulence fact ... | 2014 | 24530743 |
| maternal and neonatal vaccination protects newborn baboons from pertussis infection. | the united states is experiencing a pertussis resurgence that resulted in a 60-year high of 48 000 cases in 2012. the majority of hospitalizations and deaths occur in infants too young to be vaccinated. neonatal and maternal vaccination have been proposed to protect newborns until the first vaccination, currently recommended at 2 months of age. these interventions result in elevated anti-bordetella pertussis titers, but there have been no studies demonstrating that these measures confer protecti ... | 2014 | 24526741 |
| the gβγ-src signaling pathway regulates tnf-induced necroptosis via control of necrosome translocation. | formation of multi-component signaling complex necrosomes is essential for tumor necrosis factor α (tnf)-induced programmed necrosis (also called necroptosis). however, the mechanisms of necroptosis are still largely unknown. we isolated a tnf-resistant l929 mutant cell line generated by retrovirus insertion and identified that disruption of the guanine nucleotide-binding protein γ 10 (gγ10) gene is responsible for this phenotype. we further show that gγ10 is involved in tnf-induced necroptosis ... | 2014 | 24513853 |
| il-15 regulates memory cd8+ t cell o-glycan synthesis and affects trafficking. | memory and naive cd8+ t cells exhibit distinct trafficking patterns. specifically, memory but not naive cd8+ t cells are recruited to inflamed tissues in an antigen-independent manner. however, the molecular mechanisms that regulate memory cd8+ t cell trafficking are largely unknown. here, using murine models of infection and t cell transfer, we found that memory but not naive cd8+ t cells dynamically regulate expression of core 2 o-glycans, which interact with p- and e-selectins to modulate tra ... | 2014 | 24509081 |
| reply to domenech de cellès et al.: infection and transmission of pertussis in the baboon model. | | 2014 | 24693544 |
| comparative genomic hybridization identifies virulence differences in streptococcus suis. | streptococcus suis is an important zoonotic pathogen. however, identification of virulent s. suis strains is complicated because of the high diversity of the species. here we evaluated the genetic difference among s. suis strains using comparative genomic hybridization (cgh) and virulence variation in vivo and in vitro. we showed that different clades differed in their ability to activate tlr2/6 in vitro and their capacity to induce cytokine production in vivo as well as their resistance to phag ... | 2014 | 24503649 |
| protecting infants from pertussis. | with the increased rate of pertussis in children, several families have asked me about ways to protect their young infants from pertussis infection. what should i recommend to these families? | 2014 | 24522676 |
| g proteins gαi1/3 are critical targets for bordetella pertussis toxin-induced vasoactive amine sensitization. | pertussis toxin (ptx) is an ab5-type exotoxin produced by the bacterium bordetella pertussis, the causative agent of whooping cough. in vivo intoxication with ptx elicits a variety of immunologic and inflammatory responses, including vasoactive amine sensitization (vaas) to histamine (ha), serotonin (5-ht), and bradykinin (bdk). previously, by using a forward genetic approach, we identified the ha h1 receptor (hrh1/h1r) as the gene in mice that controls differential susceptibility to b. pertussi ... | 2014 | 24478091 |
| prevalence and molecular characterization of pertactin-deficient bordetella pertussis in the united states. | pertussis has shown a striking resurgence in the united states, with a return to record numbers of reported cases as last observed in the 1950s. bordetella pertussis isolates lacking pertactin, a key antigen component of the acellular pertussis vaccine, have been observed, suggesting that b. pertussis is losing pertactin in response to vaccine immunity. screening of 1,300 isolates from outbreak and surveillance studies (historical isolates collected from 1935 up to 2009, isolates from the 2010 c ... | 2014 | 24256623 |
| antibody responses to bordetella pertussis fim2 or fim3 following immunization with a whole-cell, two-component, or five-component acellular pertussis vaccine and following pertussis disease in children in sweden in 1997 and 2007. | bordetella pertussis fimbriae (fim2 and fim3) are components of a five-component acellular pertussis vaccine (diphtheria-tetanus-acellular pertussis vaccine [dtap5]), and antibody responses to fimbriae have been associated with protection. we analyzed the igg responses to individual fim2 and fim3 in sera remaining from a swedish placebo-controlled efficacy trial that compared a whole-cell vaccine (diphtheria-tetanus-whole-cell pertussis vaccine [dtwp]), a two-component acellular pertussis vaccin ... | 2014 | 24307240 |
| amidate prodrugs of 9-[2-(phosphonomethoxy)ethyl]adenine as inhibitors of adenylate cyclase toxin from bordetella pertussis. | adenylate cyclase toxin (act) is the key virulence factor of bordetella pertussis that facilitates its invasion into the mammalian body. 9-[2-(phosphonomethoxy)ethyl]adenine diphosphate (pmeapp), the active metabolite of the antiviral drug bis(pom)pmea (adefovir dipivoxil), has been shown to inhibit act. the objective of this study was to evaluate six novel amidate prodrugs of pmea, both phenyloxy phosphonamidates and phosphonodiamidates, for their ability to inhibit act activity in the j774a.1 ... | 2014 | 24145524 |
| bordetella pertussis in sporadic and outbreak settings in alberta, canada, july 2004-december 2012. | provlab alberta provides all laboratory testing for bordetella pertussis including sporadic cases and outbreak investigations through collaborations with provincial public health partners. we describe b. pertussis activity in alberta from july 2004 to december 2012. | 2014 | 24476570 |