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respiratory syncytial virus genomic load and disease severity among children hospitalized with bronchiolitis: multicenter cohort studies in the united states and finland.we investigated whether children with a higher respiratory syncytial virus (rsv) genomic load are at a higher risk of more-severe bronchiolitis.201425425699
respiratory syncytial virus genomic load and disease severity among children hospitalized with bronchiolitis: multicenter cohort studies in the united states and finland.we investigated whether children with a higher respiratory syncytial virus (rsv) genomic load are at a higher risk of more-severe bronchiolitis.201425425699
the burden of disease and health care use among pertussis cases in school aged children and adults in england and wales; a patient survey.in 2011-2012 a large pertussis outbreak occurred in england. this provided an opportunity to estimate the disease burden in those aged 5 years and over. as pertussis is likely to be under reported both laboratory-confirmed and non-confirmed cases were included.201425423321
osteopontin expression in the brain triggers localized inflammation and cell death when immune cells are activated by pertussis toxin.upregulation of osteopontin (opn) is a characteristic of central nervous system pathologies. however, the role of opn in inflammation is still controversial, since it can both prevent cell death and induce the migration of potentially damaging inflammatory cells. to understand the role of opn in inflammation and cell survival, we expressed opn, utilizing an adenoviral vector, in the caudoputamen of mice deficient in opn, using beta-galactosidase- (β-gal-) expressing vector as control. the tissue ...201425525298
acthar gel treatment suppresses acute exacerbations in a murine model of relapsing-remitting multiple sclerosis.acthar gel is indicated for the treatment of acute exacerbations of multiple sclerosis (ms) in adults. its effects on immune cells during a relapse are unknown. this study investigated the effects of acthar in an animal model of relapsing-remitting ms, using sjl/j mice sensitized with myelin peptide. all animal studies were reviewed and approved by the university of utah institutional animal care and use committee and conducted in accordance with the guidelines prepared by the committee on care ...201425410153
acthar gel treatment suppresses acute exacerbations in a murine model of relapsing-remitting multiple sclerosis.acthar gel is indicated for the treatment of acute exacerbations of multiple sclerosis (ms) in adults. its effects on immune cells during a relapse are unknown. this study investigated the effects of acthar in an animal model of relapsing-remitting ms, using sjl/j mice sensitized with myelin peptide. all animal studies were reviewed and approved by the university of utah institutional animal care and use committee and conducted in accordance with the guidelines prepared by the committee on care ...201425410153
cutting edge: gpr35/cxcr8 is the receptor of the mucosal chemokine cxcl17.chemokines are chemotactic cytokines that direct the traffic of leukocytes and other cells in the body. chemokines bind to g protein-coupled receptors expressed on target cells to initiate signaling cascades and induce chemotaxis. although the cognate receptors of most chemokines have been identified, the receptor for the mucosal chemokine cxcl17 is undefined. in this article, we show that gpr35 is the receptor of cxcl17. gpr35 is expressed in mucosal tissues, in cxcl17-responsive monocytes, and ...201425411203
cutting edge: gpr35/cxcr8 is the receptor of the mucosal chemokine cxcl17.chemokines are chemotactic cytokines that direct the traffic of leukocytes and other cells in the body. chemokines bind to g protein-coupled receptors expressed on target cells to initiate signaling cascades and induce chemotaxis. although the cognate receptors of most chemokines have been identified, the receptor for the mucosal chemokine cxcl17 is undefined. in this article, we show that gpr35 is the receptor of cxcl17. gpr35 is expressed in mucosal tissues, in cxcl17-responsive monocytes, and ...201425411203
emerging targets in pituitary adenomas: role of the cxcl12/cxcr4-r7 system.chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. in particular, the chemokine cxcl12 and its receptors, cxcr4 and cxcr7, form a functional network that ...201425484899
2- and 3-substituted imidazo[1,2-a]pyrazines as inhibitors of bacterial type iv secretion.a novel series of 8-amino imidazo[1,2-a]pyrazine derivatives has been developed as inhibitors of the virb11 atpase hp0525, a key component of the bacterial type iv secretion system. a flexible synthetic route to both 2- and 3-aryl substituted regioisomers has been developed. the resulting series of imidazo[1,2-a]pyrazines has been used to probe the structure-activity relationships of these inhibitors, which show potential as antibacterial agents.201425438770
p2y₆ receptor inhibition perturbs ccl2-evoked signalling in human monocytic and peripheral blood mononuclear cells.the chemokine ccl2 serves to target circulating monocytes and other leukocytes to tissue during innate immune responses, and modulates the progression of chronic inflammatory disease through activation of the receptor ccr2. here, we show that co-activation of the p2y₆ purinergic receptor (encoded by p2ry₆) occurs when thp-1 cells and human peripheral blood mononuclear cells sense ccl2 through ccr2. furthermore, p2y₆ receptor activation accounts for ∼80% of the intracellular ca²⁺ signal evoked by ...201425271060
antibiotic prescriptions and cycles of mycoplasma pneumoniae infections in norway: can a nationwide prescription register be used for surveillance?mycoplasma pneumoniae outbreaks cause increased use of macrolides and tetracyclines. we aimed to investigate whether drug use data, in addition to laboratory data, could improve understanding of the spread of m. pneumoniae epidemics. number of users of mycoplasma antibiotics (erythromycin, doxycycline, clarithromycin) per week and county of residence in an indicator age group (6-12 years) was retrieved from the norwegian prescription database for the epidemic season 2011-2012 and compared to non ...201425388750
antibiotic prescriptions and cycles of mycoplasma pneumoniae infections in norway: can a nationwide prescription register be used for surveillance?mycoplasma pneumoniae outbreaks cause increased use of macrolides and tetracyclines. we aimed to investigate whether drug use data, in addition to laboratory data, could improve understanding of the spread of m. pneumoniae epidemics. number of users of mycoplasma antibiotics (erythromycin, doxycycline, clarithromycin) per week and county of residence in an indicator age group (6-12 years) was retrieved from the norwegian prescription database for the epidemic season 2011-2012 and compared to non ...201425388750
role of dendritic cells in the pathogenesis of whipple's disease.accumulation of tropheryma whipplei-stuffed macrophages in the duodenum, impaired t. whipplei-specific th1 responses, and weak secretion of interleukin-12 (il-12) are hallmarks of classical whipple's disease (cwd). this study addresses dendritic cell (dc) functionality during cwd. we documented composition, distribution, and functionality of dc ex vivo or after in vitro maturation by fluorescence-activated cell sorting (facs) and by immunohistochemistry in situ. a decrease in peripheral dc of un ...201425385798
role of dendritic cells in the pathogenesis of whipple's disease.accumulation of tropheryma whipplei-stuffed macrophages in the duodenum, impaired t. whipplei-specific th1 responses, and weak secretion of interleukin-12 (il-12) are hallmarks of classical whipple's disease (cwd). this study addresses dendritic cell (dc) functionality during cwd. we documented composition, distribution, and functionality of dc ex vivo or after in vitro maturation by fluorescence-activated cell sorting (facs) and by immunohistochemistry in situ. a decrease in peripheral dc of un ...201425385798
licensed pertussis vaccines in the united states. history and current state.the united states switched from whole cell to acellular pertussis vaccines in the 1990s following global concerns with the safety of the whole cell vaccines. despite high levels of acellular pertussis vaccine coverage, the united states and other countries are experiencing large pertussis outbreaks. the aim of this article is to describe the historical context which led to acellular pertussis vaccine development, focusing on vaccines currently licensed in the us, and to review evidence that wani ...201425483496
da virus mutant h101 has altered cns pathogenesis and causes immunosuppression.viruses use various mechanisms to evade clearance by the host. investigating how a few changes in the genome of a non-lethal virus can lead to altered disease, from survivable to immunosuppression/death, would provide valuable information into viral pathogenesis. the daniels strain of theiler's murine encephalomyelitis virus causes an asymptomatic infection or acute encephalitis followed by viral clearance. a mutant, h101, carries several alterations in the viral genome. h101 infection causes pr ...201425468274
plasmodium berghei circumsporozoite protein encapsulated in oligomannose-coated liposomes confers protection against sporozoite infection in mice.the design and development of an effective malaria vaccine against the pre-erythrocytic and erythrocytic-stages of infection present a great challenge.201425373617
the complementary roles of phase 3 trials and post-licensure surveillance in the evaluation of new vaccines.vaccines have led to significant reductions in morbidity and saved countless lives from many infectious diseases and are one of the most important public health successes of the modern era. both vaccines' effectiveness and safety are keys for the success of immunisation programmes. the role of post-licensure surveillance has become increasingly recognised by regulatory authorities in the overall vaccine development process. safety, purity, and effectiveness of vaccines are carefully assessed bef ...201425444788
the complementary roles of phase 3 trials and post-licensure surveillance in the evaluation of new vaccines.vaccines have led to significant reductions in morbidity and saved countless lives from many infectious diseases and are one of the most important public health successes of the modern era. both vaccines' effectiveness and safety are keys for the success of immunisation programmes. the role of post-licensure surveillance has become increasingly recognised by regulatory authorities in the overall vaccine development process. safety, purity, and effectiveness of vaccines are carefully assessed bef ...201425444788
animal models to investigate the pathogenesis of rheumatic heart disease.rheumatic fever (rf) and rheumatic heart disease (rhd) are sequelae of group a streptococcal (gas) infection. although an autoimmune process has long been considered to be responsible for the initiation of rf/rhd, it is only in the last few decades that the mechanisms involved in the pathogenesis of the inflammatory condition have been unraveled partly due to experimentation on animal models. rf/rhd is a uniquely human condition and modeling this disease in animals is challenging. antibody and t ...201425414841
status of pertussis in iran.pertussis is a respiratory and contagious disease which is mostly caused by bordetella pertussis and b. parapertussis. it usually spreads from person to personduring the incubation or catarrhal phase of the disease. despite of large-scale vaccination, whooping cough is still an endemic disease with several outbreaks.201425774274
clinical and laboratory features of pertussis in hospitalized infants with confirmed versus probable pertussis cases.the clinical presentations of pertussis infection have considerable variation. many infections and illnesses can cause prolonged repetitive paroxysmal cough that could be confused with bordetella pertussis infection.201425506485
monoclonal antibodies against vibrio vulnificus rtxa1 elicit protective immunity through distinct mechanisms.vibrio vulnificus causes rapidly progressing septicemia with an extremely high mortality rate (≥50%), even with aggressive antibiotic treatment. the bacteria secrete multifunctional autoprocessing repeats-in-toxin (martx) toxins, which are involved in the pathogenesis of gram-negative vibrio species. recently, we reported that immunization with the c-terminal region of v. vulnificus rtxa1/martxvv, rtxa1-c, elicits a protective immune response against v. vulnificus through a poorly defined mechan ...201425156730
lipopolysaccharides belonging to different salmonella serovars are differentially capable of activating toll-like receptor 4.salmonella enterica subsp. enterica serovar (serotype) abortusovis is a member of the enterobacteriaceae. this serotype is naturally restricted to ovine species and does not infect humans. limited information is available about the immune response of sheep to s. abortusovis. s. abortusovis, like salmonella enterica subsp. enterica serovar typhi, causes a systemic infection in which, under natural conditions, animals are not able to raise a rapid immune response. failure to induce the appropriate ...201425135686
patterns of expression and translocation of the ubiquitin ligase slrp in salmonella enterica serovar typhimurium.slrp is an e3 ubiquitin ligase that can be translocated into eukaryotic host cells by the two type iii secretion systems that are expressed by salmonella enterica serovar typhimurium and are encoded in salmonella pathogenicity islands 1 (spi1) and 2 (spi2). expression of slrp and translocation of its product were examined using lac, 3×flag, and cyaa' translational fusions. although slrp was expressed in different media, optimal expression was found under conditions that imitate the intravacuolar ...201425182488
constitutive activation of mek1 promotes treg cell instability in vivo.the instability of regulatory t (treg) cells is involved in the pathogenesis of autoimmune diseases and also highlights safety concerns with regard to clinical treg cell therapy. cell-intrinsic molecular events linked to this treg cell instability in vivo cells, which leads to safety concerns regardingare still obscure. here we developed a novel luciferase-based reporter system and performed an unbiased screening for kinases that potentially modulate foxp3 function. we found that the active form ...201425361764
ev71 vaccine, an invaluable gift for children.enterovirus 71 (ev71) is a major pathogen for severe hand, foot and mouth disease (hfmd). development of vaccines against ev71 would be the most effective approach to prevent the ev71 outbreak. research and development (r&d) of ev71 vaccine was carried out in several asian countries. currently three companies in mainland china have completed phase iii clinical trials of inactivated ev71 whole-virus vaccines, whereas the other two companies have completed phase i clinical trials separately in tai ...201425505956
calmodulin-like protein from m. tuberculosis h37rv is required during infection.m. tuberculosis constitutes very sophisticated signaling systems that convert the environment signals into appropriate cellular response and helps the bacilli to overcome the onslaught of host defence mechanisms. although mycobacterial two-component systems and stpks have gained lot of attention as virulence factors, mycobacterial calcium signaling has not been very well studied. calcium signaling has been the primary mechanism in eukaryotes for regulation of kinases, however in prokaryotes auto ...201425359006
cfp-10 from mycobacterium tuberculosis selectively activates human neutrophils through a pertussis toxin-sensitive chemotactic receptor.upon infection with mycobacterium tuberculosis, neutrophils are massively recruited to the lungs, but the role of these cells in combating the infection is poorly understood. through a type vii secretion system, m. tuberculosis releases a heterodimeric protein complex, containing a 6-kda early secreted antigenic target (esat-6) and a 10-kda culture filtrate protein (cfp-10), that is essential for virulence. whereas the esat-6 component possesses multiple virulence-related activities, no direct b ...201425332123
cfp-10 from mycobacterium tuberculosis selectively activates human neutrophils through a pertussis toxin-sensitive chemotactic receptor.upon infection with mycobacterium tuberculosis, neutrophils are massively recruited to the lungs, but the role of these cells in combating the infection is poorly understood. through a type vii secretion system, m. tuberculosis releases a heterodimeric protein complex, containing a 6-kda early secreted antigenic target (esat-6) and a 10-kda culture filtrate protein (cfp-10), that is essential for virulence. whereas the esat-6 component possesses multiple virulence-related activities, no direct b ...201425332123
rpph-dependent pyrophosphohydrolysis of mrnas is regulated by direct interaction with dapf in escherichia coli.similar to decapping of eukaryotic mrnas, the rpph-catalyzed conversion of 5'-terminal triphosphate to monophosphate has recently been identified as the rate-limiting step for the degradation of a subset of mrnas in escherichia coli. however, the regulation of rpph pyrophosphohydrolase activity is not well understood. because the overexpression of rpph alone does not affect the decay rate of most target mrnas, the existence of a mechanism regulating its activity has been suggested. in this study ...201425313159
tc52 amino-terminal-domain dna carried by attenuated salmonella enterica serovar typhimurium induces protection against a trypanosoma cruzi lethal challenge.in this work we immunized mice with dna encoding full-length tc52 or its amino- or carboxy-terminal (n- and c-term, respectively) domain carried by attenuated salmonella as a dna delivery system. as expected, salmonella-mediated dna delivery resulted in low antibody titers and a predominantly th1 response, as shown by the ratio of igg2a/igg1-specific antibodies. despite modest expression of tc52 in trypomastigotes, the antibodies elicited by vaccination were able to mediate lysis of the trypomas ...201425069980
epithelial anion transporter pendrin contributes to inflammatory lung pathology in mouse models of bordetella pertussis infection.pertussis disease, characterized by severe and prolonged coughing episodes, can progress to a critical stage with pulmonary inflammation and death in young infants. however, there are currently no effective treatments for pertussis. we previously studied the role of pertussis toxin (pt), an important bordetella pertussis virulence factor, in lung transcriptional responses to b. pertussis infection in mouse models. one of the genes most highly upregulated in a pt-dependent manner encodes an epith ...201425069981
molecular epidemiology of the pertussis epidemic in washington state in 2012.although pertussis disease is vaccine preventable, washington state experienced a substantial rise in pertussis incidence beginning in 2011. by june 2012, the reported cases reached 2,520 (37.5 cases per 100,000 residents), a 1,300% increase compared with the same period in 2011. we assessed the molecular epidemiology of this statewide epidemic using 240 isolates collected from case patients reported from 19 of 39 washington counties during 2012 to 2013. the typing methods included pulsed-field ...201425031439
bordetella pertussis: an underreported pathogen in pediatric respiratory infections, a prospective cohort study.the incidence of pertussis has been increasing worldwide. in the netherlands, the seroprevalence has risen higher than the reported cases, suggesting that laboratory tests for pertussis are considered infrequently and that even more pertussis cases are missed. the objective of our study was to determine the frequency of pertussis in clinically unsuspect cases compared to suspect cases with the intention of finding clinical predictors.201425267437
regulation of early cartilage destruction in inflammatory arthritis by death receptor 3.to investigate the role of death receptor 3 (dr-3) and its ligand tumor necrosis factor-like molecule 1a (tl1a) in the early stages of inflammatory arthritis.201425044706
the role of multiplex pcr in respiratory tract infections in children.infants, toddlers, and children of primary-school age without any special risk factors generally have three to ten febrile respiratory infections per year. most such infections are of viral origin and self-limiting, but viral infection is often hard to distinguish from bacterial infection. the use of a multiplex polymerase chain reaction (pcr) to detect viruses in respiratory secretions is potentially beneficial, as it might help physicians avoid giving antibiotics unnecessarily.201425316519
inducible polymerization and two-dimensional assembly of the repeats-in-toxin (rtx) domain from the pseudomonas aeruginosa alkaline protease.self-assembling proteins represent potential scaffolds for the organization of enzymatic activities. the alkaline protease repeats-in-toxin (rtx) domain from pseudomonas aeruginosa undergoes multiple structural transitions in the presence and absence of calcium, a native structural cofactor. in the absence of calcium, this domain is capable of spontaneous, ordered polymerization, producing amyloid-like fibrils and large two-dimensional protein sheets. this polymerization occurs under near-physio ...201425232897
calcium, acylation, and molecular confinement favor folding of bordetella pertussis adenylate cyclase cyaa toxin into a monomeric and cytotoxic form.the adenylate cyclase (cyaa) toxin, a multidomain protein of 1706 amino acids, is one of the major virulence factors produced by bordetella pertussis, the causative agent of whooping cough. cyaa is able to invade eukaryotic target cells in which it produces high levels of camp, thus altering the cellular physiology. although cyaa has been extensively studied by various cellular and molecular approaches, the structural and functional states of the toxin remain poorly characterized. indeed, cyaa i ...201425231985
the proton-motive force is required for translocation of cdi toxins across the inner membrane of target bacteria.contact-dependent growth inhibition (cdi) is a mode of bacterial competition orchestrated by the cdib/cdia family of two-partner secretion proteins. the cdia effector extends from the surface of cdi(+) inhibitor cells, binds to receptors on neighbouring bacteria and delivers a toxin domain derived from its c-terminal region (cdia-ct). here, we show that cdia-ct toxin translocation requires the proton-motive force (pmf) within target bacteria. the pmf is also critical for the translocation of col ...201425174572
insulin secretion stimulated by l-arginine and its metabolite l-ornithine depends on gα(i2).bordetella pertussis toxin (ptx), also known as islet-activating protein, induces insulin secretion by adp-ribosylation of inhibitory g proteins. ptx-induced insulin secretion may result either from inactivation of gα(o) proteins or from combined inactivation of gα(o), gα(i1), gα(i2), and gα(i3) isoforms. however, the specific role of gα(i2) in pancreatic β-cells still remains unknown. in global (gα(i2)(-/-)) and β-cell-specific (gα(i2)(βcko)) gene-targeted gα(i2) mouse models, we studied glucos ...201425205820
caspase-1-independent interleukin-1β is required for clearance of bordetella pertussis infections and whole-cell vaccine-mediated immunity.whooping cough remains a significant disease worldwide and its re-emergence in highly vaccinated populations has been attributed to a combination of imperfect vaccines and evolution of the pathogen. the focus of this study was to examine the role of il-1α/β and the inflammasome in generation of the interleukin-1 (il-1) response, which is required for the clearance of bordetella pertussis. we show that il-1β but not il-1α is required for mediating the clearance of b. pertussis from the lungs of m ...201425198773
the chlamydia effector tarp mimics the mammalian leucine-aspartic acid motif of paxillin to subvert the focal adhesion kinase during invasion.host cell signal transduction pathways are often targets of bacterial pathogens, especially during the process of invasion when robust actin remodeling is required. we demonstrate that the host cell focal adhesion kinase (fak) was necessary for the invasion by the obligate intracellular pathogen chlamydia caviae. bacterial adhesion triggered the transient recruitment of fak to the plasma membrane to mediate a cdc42- and arp2/3-dependent actin assembly. fak recruitment was via binding to a domain ...201425193659
clostridium and bacillus binary enterotoxins: bad for the bowels, and eukaryotic being.some pathogenic spore-forming bacilli employ a binary protein mechanism for intoxicating the intestinal tracts of insects, animals, and humans. these gram-positive bacteria and their toxins include clostridium botulinum (c2 toxin), clostridium difficile (c. difficile toxin or cdt), clostridium perfringens (ι-toxin and binary enterotoxin, or bec), clostridium spiroforme (c. spiroforme toxin or cst), as well as bacillus cereus (vegetative insecticidal protein or vip). these gut-acting proteins for ...201425198129
anatomy and neurophysiology of cough: chest guideline and expert panel report.bronchopulmonary c-fibers and a subset of mechanically sensitive, acid-sensitive myelinated sensory nerves play essential roles in regulating cough. these vagal sensory nerves terminate primarily in the larynx, trachea, carina, and large intrapulmonary bronchi. other bronchopulmonary sensory nerves, sensory nerves innervating other viscera, as well as somatosensory nerves innervating the chest wall, diaphragm, and abdominal musculature regulate cough patterning and cough sensitivity. the respons ...201425188530
antioxidant and anti-inflammatory effects of schisandra and paeonia extracts in the treatment of asthma.the aim of the present study was to investigate the antioxidant and anti-inflammatory effects of paeonia and schisandra extracts in asthmatic rats. an ethanol extraction method was used to prepare the schisandra and paeonia extracts, and the levels of hydroxyl radical, total antioxidant activity and total phenolic content were detected. the rats were divided into three groups: treatment (group a), model (group b) and control (group c). the treatment group received traditional chinese antiasthmat ...201425289045
ontogeny of myeloid cells.granulocytes, monocytes, macrophages, and dendritic cells (dcs) represent a subgroup of leukocytes, collectively called myeloid cells. during the embryonic development of mammalians, myelopoiesis occurs in a stepwise fashion that begins in the yolk sac and ends up in the bone marrow (bm). during this process, these early monocyte progenitors colonize various organs such as the brain, liver, skin, and lungs and differentiate into resident macrophages that will self-maintain throughout life. dcs a ...201425232355
microwave & magnetic (m2) proteomics reveals cns-specific protein expression waves that precede clinical symptoms of experimental autoimmune encephalomyelitis.central nervous system-specific proteins (csps), transported across the damaged blood-brain-barrier (bbb) to cerebrospinal fluid (csf) and blood (serum), might be promising diagnostic, prognostic and predictive protein biomarkers of disease in individual multiple sclerosis (ms) patients because they are not expected to be present at appreciable levels in the circulation of healthy subjects. we hypothesized that microwave &magnetic (m(2)) proteomics of csps in brain tissue might be an effective m ...201425182730
schistosome vaccine adjuvants in preclinical and clinical research.there is currently no vaccine available for human use for any parasitic infections, including the helminth disease, schistosomiasis. despite many researchers working towards this goal, one of the focuses has been on identifying new antigenic targets. the bar to achieve protective efficacy in humans was set at a consistent induction of 40% protection or better by the world health organisation (who), and although this is a modest goal, it is yet to be reached with the six most promising schistosom ...201426344751
reconstitution of bacterial autotransporter assembly using purified components.autotransporters are a superfamily of bacterial virulence factors consisting of an n-terminal extracellular ('passenger') domain and a c-terminal β barrel ('β') domain that resides in the outer membrane (om). the mechanism by which the passenger domain is secreted is poorly understood. here we show that a conserved om protein insertase (the bam complex) and a molecular chaperone (sura) are both necessary and sufficient to promote the complete assembly of the escherichia coli o157:h7 autotranspor ...201425182416
epidemiological aspects of pertussis among adults and adolescents in a korean outpatient setting: a multicenter, pcr-based study.epidemiological data of bordetella pertussis infection among adolescents and adults are limited in korea. patients (≥ 11 yr of age) with a bothersome cough for less than 30 days were enrolled during a 1-yr period at 22 hospitals in korea. nasopharyngeal swabs were collected for polymerase chain reaction (pcr) and for bacteriologic culture. in total, 490 patients were finally enrolled, and 34 (6.9%) patients tested positive for b. pertussis; cough duration (14.0 days [7.0-21.0 days]) and age dist ...201425246741
swab sample transfer for point-of-care diagnostics: characterization of swab types and manual agitation methods.the global need for disease detection and control has increased effort to engineer point-of-care (poc) tests that are simple, robust, affordable, and non-instrumented. in many poc tests, sample collection involves swabbing the site (e.g., nose, skin), agitating the swab in a fluid to release the sample, and transferring the fluid to a device for analysis. poor performance in sample transfer can reduce sensitivity and reproducibility.201425181250
rab11-mediated trafficking in host-pathogen interactions.many bacterial and viral pathogens block or subvert host cellular processes to promote successful infection. one host protein that is targeted by invading pathogens is the small gtpase rab11, which functions in vesicular trafficking. rab11 functions in conjunction with a protein complex known as the exocyst to mediate terminal steps in cargo transport via the recycling endosome to cell-cell junctions, phagosomes and cellular protrusions. these processes contribute to host innate immunity by prom ...201425118884
trends in hospitalizations and resource utilization for pediatric pertussis.pertussis is a serious and preventable childhood illness often necessitating hospitalization. the objective was to describe national trends in pediatric pertussis hospitalizations and resource utilization and factors associated with increased length of stay (los).201425318108
immunotherapeutic strategies in autoimmune uveitis.autoimmune uveitis is an organ-specific disorder characterized by irreversible lesions to the eye that predominantly affect people in their most productive years and is among the leading causes of visual deficit and blindness. currently available therapies are effective in the treatment of a wide spectrum of uveitis, but are often associated with severe side effects. here, we review ongoing research with promising immunomodulatory therapeutic strategies, describing their specific features, inter ...201424833504
pertussis-specific memory b-cell and humoral igg responses in adolescents after a fifth consecutive dose of acellular pertussis vaccine.in order to impede the increase in pertussis incidence in the adolescent group, a school-leaving booster dose administered at the age of 14 to 16 years will be introduced in sweden in 2016. preceding this introduction, an open-label, randomized, multicenter, clinical trial without a control group and with blinded analysis was performed, investigating both safety and immunogenicity. reported here are the memory b-cell and serological responses detected in a smaller cohort (n = 34) of the 230 subj ...201425008903
predictors of mortality in mechanically ventilated critical pertussis in a low income country.critical pertussis is characterized by severe respiratory failure, important leukocytosis, pulmonary hypertension, septic shock and encephalopathy.201425237472
alkali metals in addition to acidic ph activate the evgs histidine kinase sensor in escherichia coli.two-component signal transduction systems (tcss) in bacteria perceive environmental stress and transmit the information via phosphorelay to adjust multiple cellular functions for adaptation. the evgs/evga system is a tcs that confers acid resistance to escherichia coli cells. activation of the evgs sensor initiates a cascade of transcription factors, evga, ydeo, and gade, which induce the expression of a large group of acid resistance genes. we searched for signals activating evgs and found that ...201424957621
interleukin-10 regulates the inflammasome-driven augmentation of inflammatory arthritis and joint destruction.activation of the inflammasome has been implicated in the pathology of various autoinflammatory and autoimmune diseases. while the nlrp3 inflammasome has been linked to arthritis progression, little is known about its synovial regulation or contribution to joint histopathology. regulators of inflammation activation, such as interleukin (il)-10, may have the potential to limit the inflammasome-driven arthritic disease course and associated structural damage. hence, we used il-10-deficient (il-10k ...201425175678
aphonia and epiglottitis in neonate with concomitant mrsa skin infection.we report an unusual case of a neonate with aphonia due to epiglottitis with a concomitant methicillin-resistant s taphylococcus aureus (mrsa) infection of the genitalia and associated septic emboli to the groin area and mouth. we postulate that the mrsa infection caused a transient bacteremia that seeded the epiglottis, likely causing the epiglottitis. in the evaluation of a neonate with aphonia, while the two primary differentials to consider are vocal cord paralysis and laryngeal web, among o ...201425473587
a 4-month-old baby presenting with dermal necrotizing granulomatous giant cell reaction at the injection site of 13-valent pneumococcal conjugate vaccine: a case report.adjuvants (for example, aluminum salts) are frequently incorporated in licensed vaccines to enhance the host immune response. such vaccines include the pneumococcal conjugate, combinations of diphtheria-tetanus/acellular pertussis, tetanus- diphtheria/acellular pertussis, hepatitis b, some haemophilus influenzae type b, hepatitis a, and human papillomavirus. these preparations have been associated with complicated local adverse events, especially if administered subcutaneously or intradermally i ...201425152179
the vaccine potential of bordetella pertussis biofilm-derived membrane proteins.pertussis is an infectious respiratory disease of humans caused by the gram-negative pathogen bordetella pertussis. the use of acellular pertussis vaccines (aps) which induce immunity of relative short duration and the emergence of vaccine-adapted strains are thought to have contributed to the recent resurgence of pertussis in industrialized countries despite high vaccination coverage. current pertussis vaccines consist of antigens derived from planktonic bacterial cultures. however, recent stud ...201426038752
phage-host interplay: examples from tailed phages and gram-negative bacterial pathogens.complex interactions between bacteriophages and their bacterial hosts play significant roles in shaping the structure of environmental microbial communities, not only by genetic transduction but also by modification of bacterial gene expression patterns. survival of phages solely depends on their ability to infect their bacterial hosts, most importantly during phage entry. successful dynamic adaptation of bacteriophages when facing selective pressures, such as host adaptation and resistance, dic ...201425191318
annexin a2 mediates mycoplasma pneumoniae community-acquired respiratory distress syndrome toxin binding to eukaryotic cells.mycoplasma pneumoniae synthesizes a novel human surfactant protein a (sp-a)-binding cytotoxin, designated community-acquired respiratory distress syndrome (cards) toxin, that exhibits adp-ribosylating and vacuolating activities in mammalian cells and is directly linked to a range of acute and chronic airway diseases, including asthma. in our attempt to detect additional cards toxin-binding proteins, we subjected the membrane fraction of human a549 airway cells to affinity chromatography using re ...201425139904
molecular signatures of the evolving immune response in mice following a bordetella pertussis infection.worldwide resurgence of pertussis necessitates the need for improvement of pertussis vaccines and vaccination strategies. since natural infections induce a longer-lasting immunity than vaccinations, detailed knowledge of the immune responses following natural infection can provide important clues for such improvement. the purpose was to elucidate the kinetics of the protective immune response evolving after experimental bordetella pertussis (b. pertussis) infection in mice. data were collected f ...201425137043
vaccines, new opportunities for a new society.vaccination is the most effective medical intervention ever introduced and, together with clean water and sanitation, it has eliminated a large part of the infectious diseases that once killed millions of people. a recent study concluded that since 1924 in the united states alone, vaccines have prevented 40 million cases of diphtheria, 35 million cases of measles, and a total of 103 million cases of childhood diseases. a report from the world health organization states that today vaccines preven ...201425136130
proteomics-identified bvg-activated autotransporters protect against bordetella pertussis in a mouse model.pertussis is a highly infectious respiratory disease of humans caused by the bacterium bordetella pertussis. despite high vaccination coverage, pertussis has re-emerged globally. causes for the re-emergence of pertussis include limited duration of protection conferred by acellular pertussis vaccines (ap) and pathogen adaptation. pathogen adaptations involve antigenic divergence with vaccine strains, the emergence of strains which show enhanced in vitro expression of a number of virulence-associa ...201425133400
elucidation of a protein-protein interaction network involved in corynebacterium glutamicum cell wall biosynthesis as determined by bacterial two-hybrid analysis.mycobacterium species have a highly complex and unique cell wall that consists of a large macromolecular structure termed the mycolyl-arabinogalactan-peptidoglycan (magp) complex. this complex is essential for growth, survival and virulence of the human pathogen mycobacterium tuberculosis, and is the target of several anti-tubercular drugs. the closely related species corynebacterium glutamicum has proven useful in the study of orthologous m. tuberculosis genes and proteins involved in magp synt ...201425117516
pertussis.pertussis continues to be an important public-health issue. the high immunization coverage rates achieved, mainly in industrialized countries, have certainly decreased the spread of the pathogen. however, as immunity wanes, adolescents and adults play an important role in the dynamics of the infection. the surveillance system has several limitations and the underestimation of pertussis in adolescents, young adults and adults is mainly related to the atypical clinical characteristics of cases and ...201425483523
pertussis.pertussis continues to be an important public-health issue. the high immunization coverage rates achieved, mainly in industrialized countries, have certainly decreased the spread of the pathogen. however, as immunity wanes, adolescents and adults play an important role in the dynamics of the infection. the surveillance system has several limitations and the underestimation of pertussis in adolescents, young adults and adults is mainly related to the atypical clinical characteristics of cases and ...201425483523
using clinicians' search query data to monitor influenza epidemics.search query information from a clinician's database, uptodate, is shown to predict influenza epidemics in the united states in a timely manner. our results show that digital disease surveillance tools based on experts' databases may be able to provide an alternative, reliable, and stable signal for accurate predictions of influenza outbreaks.201425115873
depletion of regulatory t cells augments a vaccine-induced t effector cell response against the liver-stage of malaria but fails to increase memory.regulatory t cells (t(reg)) have been shown to restrict vaccine-induced t cell responses in different experimental models. in these studies cd4(+)cd25(+) t(reg) were depleted using monoclonal antibodies against cd25, which might also interfere with cd25 on non-regulatory t cell populations and would have no effect on foxp3(+)cd25(-) t(reg). to obtain more insights in the specific function of t(reg) during vaccination we used mice that are transgenic for a bacterial artificial chromosome expressi ...201425115805
the therapeutic effects of msc1 nanocomplex, synthesized by nanochelating technology, on experimental autoimmune encephalomyelitic c57/bl6 mice.currently approved therapies for multiple sclerosis (ms) at best only slow down its progression. therefore, it is necessary to utilize novel technologies in order to synthesize smart multifunctional structures. in the present study, for the first time we evaluated the therapeutic potential of msc1 nanocomplex, which was designed based on novel nanochelating technology.201425143732
the structure and retrotransposition mechanism of ltr-retrotransposons in the asexual yeast candida albicans.retrotransposons constitute a major part of the genome in a number of eukaryotes. long-terminal repeat (ltr) retrotransposons are one type of the retrotransposons. candida albicans have 34 distinct ltr-retrotransposon families. they respectively belong to the ty1/copia and ty3/gypsy groups which have been extensively studied in the model yeast saccharomyces cerevisiae. ltr-retrotransposons carry two ltrs flanking a long internal protein-coding domain, open reading frames. ltr-retrotransposons us ...201425101670
bordetella adenylate cyclase toxin differentially modulates toll-like receptor-stimulated activation, migration and t cell stimulatory capacity of dendritic cells.adenylate cyclase toxin (cyaa) is a key virulence factor of the whooping cough agent bordetella pertussis. the toxin targets cd11b-expressing phagocytes and delivers into their cytosol an adenylyl cyclase (ac) enzyme that subverts cellular signaling by increasing camp levels. in the present study, we analyzed the modulatory effects of cyaa on adhesive, migratory and antigen presenting properties of toll-like receptor (tlr)-activated murine and human dendritic cells (dcs). camp signaling of cyaa ...201425084094
interferon regulatory factor (irf) 3 is critical for the development of experimental autoimmune encephalomyelitis.experimental autoimmune encephalomyelitis (eae) is an animal model of autoimmune inflammatory demyelination that is mediated by th1 and th17 cells. the transcription factor interferon regulatory factor 3 (irf3) is activated by pathogen recognition receptors and induces interferon-β production.201425069698
chitosan oligosaccharides attenuate ocular inflammation in rats with experimental autoimmune anterior uveitis.we investigated the protective effects and mechanisms of chitosan oligosaccharides (cos) on experimental autoimmune anterior uveitis (eaau) in rats. eaau was induced in lewis rats by footpad and intraperitoneal injections of melanin-associated antigen. the rats received intraperitoneal injections of low-dose (5 mg/kg) or high-dose (10 mg/kg) cos or pbs daily after the immunization. the effects of cos were evaluated by determining the clinical scores and the morphology of the iris/ciliary body (i ...201425147441
mucosal vaccines: novel strategies and applications for the control of pathogens and tumors at mucosal sites.the mucosal immune system displays several adaptations reflecting the exposure to the external environment. the efficient induction of mucosal immune responses also requires specific approaches, such as the use of appropriate administration routes and specific adjuvants and/or delivery systems. in contrast to vaccines delivered via parenteral routes, experimental, and clinical evidences demonstrated that mucosal vaccines can efficiently induce local immune responses to pathogens or tumors locate ...201425424921
an intestinal commensal symbiosis factor controls neuroinflammation via tlr2-mediated cd39 signalling.the mammalian immune system constitutively senses vast quantities of commensal bacteria and their products through pattern recognition receptors, yet excessive immune reactivity is prevented under homeostasis. the intestinal microbiome can influence host susceptibility to extra-intestinal autoimmune disorders. here we report that polysaccharide a (psa), a symbiosis factor for the human intestinal commensal bacteroides fragilis, protects against central nervous system demyelination and inflammati ...201425043484
the quest for an hiv-1 vaccine adjuvant: bacterial toxins as new potential platforms.while tremendous efforts are undergoing towards finding an effective hiv-1 vaccine, the search for an hiv-1 vaccine adjuvant lags behind and is understudied. more recently, however, efforts have focused on testing adjuvant formulations that can boost the immune response and generate broadly neutralizing antibodies to hiv-1 env (gp160). despite this, there remain a number of challenges towards achieving this goal. these include safety of adjuvant formulations; stability of the incorporated antige ...201427375924
protecting newborns from pertussis - the challenge of complete cocooning.an increase of pertussis cases, especially in young infants and adolescents, has been noted in various countries. whooping cough is most serious in neonates and young infants in whom it may cause serious complications such as cyanosis, apnoea, pneumonia, encephalopathy and death. to protect newborns and infants too young to be fully immunized, immunization of close contact persons has been proposed ("cocoon strategy") and implemented in several countries, including switzerland in 2011. the goal ...201425037057
moxifloxacin modulates inflammation during murine pneumonia.moxifloxacin is a synthetic antibacterial agent belonging to the fluoroquinolone family. the antimicrobial activity of quinolones against gram-positive and gram-negative bacteria is based on their ability to inhibit topoisomerases. quinolones are described to have immunomodulatory features in addition to their antimicrobial activities. it was the goal of this study to examine whether a short term treatment with moxifloxacin modulates the inflammation during a subsequently induced bacterial infec ...201425034539
protein coated microcrystals formulated with model antigens and modified with calcium phosphate exhibit enhanced phagocytosis and immunogenicity.protein-coated microcrystals (pcmcs) were investigated as potential vaccine formulations for a range of model antigens. presentation of antigens as pcmcs increased the antigen-specific igg responses for all antigens tested, compared to soluble antigens. when compared to conventional aluminium-adjuvanted formulations, pcmcs modified with calcium phosphate (cap) showed enhanced antigen-specific igg responses and a decreased antigen-specific igg1:igg2a ratio, indicating the induction of a more bala ...201424120484
the dichotomy of pathogens and allergens in vaccination approaches.traditional prophylactic vaccination to prevent illness is the primary objective of many research activities worldwide. the golden age of vaccination began with an approach called variolation in ancient china and the evolution of vaccines still continues today with modern developments such as the production of gardasil(tm) against hpv and cervical cancer. the historical aspect of how different forms of vaccination have changed the face of medicine and communities is important as it dictates our ...201425076945
harnessing the helminth secretome for therapeutic immunomodulators.helminths are the largest and most complex pathogens to invade and live within the human body. since they are not able to outpace the immune system by rapid antigen variation or faster cell division or retreat into protective niches not accessible to immune effector mechanisms, their long-term survival depends on influencing and regulating the immune responses away from the mode of action most damaging to them. immunologists have focused on the excretory and secretory products that are released ...201425133189
strong inhibition of fimbrial 3 subunit gene transcription by a novel downstream repressive element in bordetella pertussis.the bvg-regulated promoters for the fimbrial subunit genes fim2 and fim3 of bordetella pertussis behave differently from each other both in vivo and in vitro. in vivo pfim2 is significantly stronger than pfim3 , even though predictions based on the dna sequences of bvga-binding motifs and core promoter elements would indicate the opposite. in vitro pfim3 demonstrated robust bvga∼p-dependent transcriptional activation, while none was seen with pfim2 . this apparent contradiction was investigated ...201424963821
syndecan-3 is selectively pro-inflammatory in the joint and contributes to antigen-induced arthritis in mice.syndecans are heparan sulphate proteoglycans expressed by endothelial cells. syndecan-3 is expressed by synovial endothelial cells of rheumatoid arthritis (ra) patients where it binds chemokines, suggesting a role in leukocyte trafficking. the objective of the current study was to examine the function of syndecan-3 in joint inflammation by genetic deletion in mice and compare with other tissues.201425015005
safety of pertussis vaccination in pregnant women in uk: observational study.to examine the safety of pertussis vaccination in pregnancy.201425015137
functional mapping of community-acquired respiratory distress syndrome (cards) toxin of mycoplasma pneumoniae defines regions with adp-ribosyltransferase, vacuolating and receptor-binding activities.community-acquired respiratory distress syndrome (cards) toxin from mycoplasma pneumoniae is a 591-amino-acid virulence factor with adp-ribosyltransferase (adprt) and vacuolating activities. it is expressed at low levels during in vitro growth and at high levels during colonization of the lung. exposure of experimental animals to purified recombinant cards toxin alone is sufficient to recapitulate the cytopathology and inflammatory responses associated with m. pneumoniae infection in humans and ...201424948331
identification and characterization of the insecticidal toxin "makes caterpillars floppy" in photorhabdus temperata m1021 using a cosmid library.photorhabdus temperata is an entomopathogenic enterobacterium; it is a nematode symbiont that possesses pathogenicity islands involved in insect virulence. herein, we constructed a p. temperata m1021 cosmid library in escherichia coli xl1-blue mrf` and obtained 7.14 × 105 clones. however, only 1020 physiologically active clones were screened for insect virulence factors by injection of each e. coli cosmid clone into galleria mellonella and tenebrio molitor larvae. a single cosmid clone, ptc1015, ...201425014195
effects of inactivated bordetella pertussis on phosphodiesterase in the lung of ovalbumin sensitized and challenged rats.this paper indicated that inactivated bordetella pertussis (ibp) can enhance the lung airway hyperreactivity of the rats sensitized and challenged with ova. the mechanisms were involved in the upregulation of camp-pde activity and pde4a, pde4d, and pde3 gene expression in the lungs. but only pde4 activity was different between the ova and ova+ibp groups, and pde4d expression was significantly increased in ibp rats alone. so, our data suggested that cosensitization with ova and ibp affects lung a ...201425120928
comparative proteomic analysis of the membrane proteins of two haemophilus parasuis strains to identify proteins that may help in habitat adaptation and pathogenesis.haemophilus parasuis is the causative agent of glässer's disease characterized by polyserositis, arthritis, and meningitis in pig, leading to serious economic loss. despite many years of study, virulence factors and the mechanisms of the entire infection process remain largely unclear. so two-dimensional gel electrophoresis and mass spectrometry were used to search for distinctions at the membrane protein expression level between two h. parasuis isolates aimed at uncovering some proteins potenti ...201425057263
genetic profile variation in vaccine strains and clinical isolates of bordetella pertussis recovered from iranian patients.re-emergence of pertussis has been reported in iran despite a high rate of vaccination coverage. low efficacy of the vaccine might be due to the genetic divergence between clinical versus vaccine strains. in the current study, the genetic profiles of clinical isolates and vaccine strains of bordetella pertussis (b. pertussis) were assessed by using pulsed field gel electrophoresis (pfge).201425215182
probing the conformation of fhac with small-angle neutron scattering and molecular modeling.probing the solution structure of membrane proteins represents a formidable challenge, particularly when using small-angle scattering. detergent molecules often present residual scattering contributions even at their match point in small-angle neutron scattering (sans) measurements. here, we studied the conformation of fhac, the outer-membrane, β-barrel transporter of the bordetella pertussis filamentous hemagglutinin adhesin. sans measurements were performed on homogeneous solutions of fhac sol ...201424988353
comparison of rates of positivity for bordetella pertussis by real-time pcr between specimens collected with rayon swabs on aluminum wire shaft in amies gel with charcoal and specimens collected with flocked swabs in universal viral transport medium during an epidemic.a comparison of real-time pcr positivity rates for bordetella pertussis between specimens collected with rayon swabs on an aluminum wire shaft in amies gel with charcoal and those collected with flocked swabs in universal viral transport medium during an epidemic revealed that their performances were comparable.201424789194
pertussis toxin improves immune responses to a combined pneumococcal antigen and leads to enhanced protection against streptococcus pneumoniae.pneumococcal surface protein a (pspa) is a candidate antigen for the composition of protein-based vaccines against streptococcus pneumoniae. while searching for efficient adjuvants for pspa-based vaccines, our group has described the potential of combining pspa with the whole-cell pertussis vaccine (wp). when given to mice through the nasal route, a formulation composed of pspa from clade 5 (pspa5) and wp (pspa5-wp) induced high levels of antibodies and protection against challenges with differe ...201424807055
directing traffic: il-17 and il-22 coordinate pulmonary immune defense.respiratory infections and diseases are among the leading causes of death worldwide, and effective treatments probably require manipulating the inflammatory response to pathogenic microbes or allergens. here, we review mechanisms controlling the production and functions of interleukin-17 (il-17) and il-22, cytokines that direct several aspects of lung immunity. innate lymphocytes (γδ t cells, natural killer cells, innate lymphoid cells) are the major source of il-17 and il-22 during acute infect ...201424942687
reconstruction of mreb expression in staphylococcus aureus via a collection of new integrative plasmids.protein localization has been traditionally explored in unicellular organisms, whose ease of genetic manipulation facilitates molecular characterization. the two rod-shaped bacterial models escherichia coli and bacillus subtilis have been prominently used for this purpose and have displaced other bacteria whose challenges for genetic manipulation have complicated any study of cell biology. among these bacteria is the spherical pathogenic bacterium staphylococcus aureus. in this report, we presen ...201424747904
leukotriene b4 amplifies eosinophil accumulation in response to nematodes.eosinophil accumulation is a defining feature of the immune response to parasitic worm infection. tissue-resident cells, such as epithelial cells, are thought to initiate eosinophil recruitment. however, direct recognition of worms by eosinophils has not been explored as a mechanism for amplifying eosinophil accumulation. here, we report that eosinophils rapidly migrate toward diverse nematode species in three-dimensional culture. these include the mammalian parasite nippostrongylus brasiliensis ...201424889202
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