| peroxiredoxin 1 stimulates secretion of proinflammatory cytokines by binding to tlr4. | peroxiredoxin 1 (prx1) is an antioxidant and molecular chaperone that can be secreted from tumor cells. prx1 is overexpressed in many cancers, and elevation of prx1 is associated with poor clinical outcome. in the current study, we demonstrate that incubation of prx1 with thioglycollate-elicited murine macrophages or immature bone marrow-derived dendritic cells resulted in tlr4-dependent secretion of tnf-alpha and il-6 and dendritic cell maturation. optimal secretion of cytokines in response to ... | 2009 | 20018613 |
| application of nanotechnologies for improved immune response against infectious diseases in the developing world. | there is an urgent need for new strategies to combat infectious diseases in developing countries. many pathogens have evolved to elude immunity and this has limited the utility of current therapies. additionally, the emergence of co-infections and drug resistant pathogens has increased the need for advanced therapeutic and diagnostic strategies. these challenges can be addressed with therapies that boost the quality and magnitude of an immune response in a predictable, designable fashion that ca ... | 2009 | 19922750 |
| application of nanotechnologies for improved immune response against infectious diseases in the developing world. | there is an urgent need for new strategies to combat infectious diseases in developing countries. many pathogens have evolved to elude immunity and this has limited the utility of current therapies. additionally, the emergence of co-infections and drug resistant pathogens has increased the need for advanced therapeutic and diagnostic strategies. these challenges can be addressed with therapies that boost the quality and magnitude of an immune response in a predictable, designable fashion that ca ... | 2009 | 19922750 |
| dyspnea and wheezing after adenosine injection in a patient with eosinophilic bronchitis. | a 58-year-old nonsmoker female was referred for evaluation of chronic cough of 13 months duration. after an initial work-up, the patient was diagnosed to have chronic cough due to eosinophilic bronchitis. the diagnostic work-up for eosinophilic bronchitis and bronchial biopsy is discussed. eosinophilic bronchitis is differentiated from asthma. in addition, the patient developed dyspnea, flushing, and wheezing after the administration of adenosine during a cardiac stress test in spite of a negati ... | 2009 | 19902011 |
| genetic view on the phenomenon of combined diseases in man. | in clinical medicine, the phenomenon of polypathy, as a particular object of investigation, was first put forth by french clinicians at the end of the 19th century through the "arthritismus" doctrine. in the first half of the 20th century, german paediatricians singled out "syntropias," which are combinations of diseases with common pathophysiological mechanisms, and "dystropias," which are diseases that rarely co-occur in one individual. in the present paper, syntropy/dystropy is defined as a n ... | 2009 | 22649614 |
| emerging evidence for the importance of phosphorylation in the regulation of nadph oxidases. | the nadph oxidase (nox) enzyme family generates reactive oxygen species (ros) that contribute to cell signaling, innate immune responses, proliferation, and transcription. the signaling mechanisms that regulate this important enzyme family are only beginning to be understood. evidence is emerging which suggests that phosphorylation of nox and/or their regulatory components may be important means of modulating their activity. we describe here the evidence for nox regulation through the action of ... | 2009 | 19358632 |
| cd14 and toll-like receptors 2 and 4 are required for fibrillar a{beta}-stimulated microglial activation. | microglia are the brain's tissue macrophages and are found in an activated state surrounding beta-amyloid plaques in the alzheimer's disease brain. microglia interact with fibrillar beta-amyloid (fabeta) through an ensemble of surface receptors composed of the alpha(6)beta(1) integrin, cd36, cd47, and the class a scavenger receptor. these receptors act in concert to initiate intracellular signaling cascades and phenotypic activation of these cells. however, it is unclear how engagement of this r ... | 2009 | 19776284 |
| fc-receptors and immunity to malaria: from models to vaccines. | the complexity and number of antigens (ags) seen during an immune response has hampered the development of malaria vaccines. antibodies (abs) play an important role in immunity to malaria and their passive administration is effective at controlling the disease. abs represent approximately 25% of all proteins undergoing clinical trials, and these 'smart biologicals' have undergone a major revival with the realization that abs lie at the interface between innate and adaptive immunity. at least 18 ... | 2009 | 19691552 |
| routine immunization of adults in canada: review of the epidemiology of vaccine-preventable diseases and current recommendations for primary prevention. | vaccination is one of the greatest achievements in public health of the 20th century. however, the success of vaccine uptake and adherence to immunization guidelines seen in pediatric populations has not been observed among adult canadians. as a result of the disparity in susceptibility to vaccine-preventable disease, there has been an increasing shift of vaccine-preventable childhood diseases into adult populations. accordingly, morbidity and mortality due to vaccine-preventable illnesses now o ... | 2009 | 20808459 |
| reproducibility of quantitative rt-pcr array in mirna expression profiling and comparison with microarray analysis. | micrornas (mirnas) have critical functions in various biological processes. mirna profiling is an important tool for the identification of differentially expressed mirnas in normal cellular and disease processes. a technical challenge remains for high-throughput mirna expression analysis as the number of mirnas continues to increase with in silico prediction and experimental verification. our study critically evaluated the performance of a novel mirna expression profiling approach, quantitative ... | 2009 | 19715577 |
| cd47 regulates collagen i-induced cyclooxygenase-2 expression and intestinal epithelial cell migration. | increased epithelial cell expression of the cyclooxygenase-2 (cox-2) enzyme is a characteristic event of both inflammatory bowel disease and colon cancer. we here report the novel findings that collagen i-induced de novo synthesis of cox-2 in intestinal epithelial cells is inhibited by pertussis toxin (ptx) and by an inhibitory peptide selective for the heterotrimeric g alpha(i3)-protein. these findings could be explained by a regulatory involvement of the g-protein-dependent integrin-associated ... | 2009 | 19636412 |
| differential micro rna expression in pbmc from multiple sclerosis patients. | differences in gene expression patterns have been documented not only in multiple sclerosis patients versus healthy controls but also in the relapse of the disease. recently a new gene expression modulator has been identified: the microrna or mirna. the aim of this work is to analyze the possible role of mirnas in multiple sclerosis, focusing on the relapse stage. we have analyzed the expression patterns of 364 mirnas in pbmc obtained from multiple sclerosis patients in relapse status, in remiss ... | 2009 | 19617918 |
| adult vaccination strategies for the control of pertussis in the united states: an economic evaluation including the dynamic population effects. | prior economic evaluations of adult and adolescent vaccination strategies against pertussis have reached disparate conclusions. using static approaches only, previous studies failed to analytically include the indirect benefits derived from herd immunity as well as the impact of vaccination on the evolution of disease incidence over time. | 2009 | 19606227 |
| differential inhibition of various adenylyl cyclase isoforms and soluble guanylyl cyclase by 2',3'-o-(2,4,6-trinitrophenyl)-substituted nucleoside 5'-triphosphates. | adenylyl cyclases (acs) catalyze the conversion of atp into the second messenger camp and play a key role in signal transduction. in a recent study (mol pharmacol 70:878-886, 2006), we reported that 2',3'-o-(2,4,6-trinitrophenyl)-substituted nucleoside 5'-triphosphates (tnp-ntps) are potent inhibitors (k(i) values in the 10 nm range) of the purified catalytic subunits vc1 and iic2 of membranous ac (mac). the crystal structure of vc1:iic2 in complex with tnp-atp revealed that the nucleotide binds ... | 2009 | 19494187 |
| seroprevalence of immunoglobulin g antibodies against pertussis toxin among asymptomatic medical students in the west of iran: a cross sectional study. | pertussis is a highly communicable, vaccine-preventable respiratory infection. immune response against this disease can be induced by infection or vaccination. protection after childhood vaccination is minimal after ten years. our aim was to assess pertussis immunity state in a population of healthy young medical students. | 2009 | 19426546 |
| current advances in research and clinical applications of plga-based nanotechnology. | co-polymer poly(lactic-co-glycolic acid) (plga) nanotechnology has been developed for many years and has been approved by the us fda for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. this article presents the more recent successes of applying plga-based nanotechnologies and tools in these medicine-related applications. it focuses on the possible mechanisms, diagnosis a ... | 2009 | 19435455 |
| regulation of th17 cells in the mucosal surfaces. | the mucosal surfaces represent the main intersection between jawed vertebrates and the environment. the mucosal surface of the intestine alone forms the largest surface that is exposed to exogenous antigens as well as the largest collection of lymphoid tissue in the body. therefore, a protective immune activity must coexist with efficient regulatory mechanisms to maintain a health status of these organisms. the discovery of a new lineage of t(h) cells that produce il-17 has provided valuable new ... | 2009 | 19362732 |
| lightcycler technology in molecular diagnostics. | lightcycler technology combines rapid-cycle polymerase chain reaction with real-time fluorescent monitoring and melting curve analysis. since its introduction in 1997, it is now used in many areas of molecular pathology, including oncology (solid tumors and hematopathology), inherited disease, and infectious disease. by monitoring product accumulation during rapid amplification, quantitative polymerase chain reaction in a closed-tube system is possible in 15 to 30 minutes. furthermore, melting c ... | 2009 | 19196999 |
| the epidemiology of pertussis in germany: past and present. | current and past pertussis epidemiology in the two parts of germany is compared in the context of different histories of vaccination recommendations and coverage to better understand patterns of disease transmission. | 2009 | 19243604 |
| endoplasmic reticulum stress in the intestinal epithelium and inflammatory bowel disease. | the unfolded protein response as a consequence of endoplasmic reticulum (er) stress has recently been implicated as a novel mechanism that may lead to inflammatory bowel disease (ibd). impairment of proper er stress resolution in highly secretory paneth and, to a lesser extent, goblet cells within the epithelium can primarily lead to intestinal inflammation. an inability to manage er stress may not only be a primary originator of intestinal inflammation as exemplified by genetic polymorphisms in ... | 2009 | 19237300 |
| protex technology for the generation of novel therapeutic cancer vaccines. | therapeutic vaccines present an attractive alternative to conventional treatments for cancer. however, tumors have evolved various immune evasion mechanisms to modulate innate, adaptive, and regulatory immunity for survival. therefore, successful vaccine formulations may require a non-toxic immunomodulator or adjuvant that not only induces/stimulates innate and adaptive tumor-specific immune responses, but also overcomes immune evasion mechanisms. given the paramount role costimulation plays in ... | 2009 | 19454266 |
| selection of pneumococci. | | 2009 | 19564975 |
| preclinical assessment of stem cell therapies for neurological diseases. | stem cells, as subjects of study for use in treating neurological diseases, are envisioned as a replacement for lost neurons and glia, a means of trophic support, a therapeutic vehicle, and, more recently, a tool for in vitro modeling to understand disease and to screen and personalize treatments. in this review we analyze the requirements of stem cell-based therapy for clinical translation, advances in stem cell research toward clinical application for neurological disorders, and different anim ... | 2009 | 20075496 |
| review series on helminths, immune modulation and the hygiene hypothesis: how might infection modulate the onset of type 1 diabetes? | the development of type 1 diabetes is influenced by both genetic and environmental factors. the current rise in the incidence of diabetes is occurring more rapidly than can be accounted for by genetic change, highlighting the influence of environmental modifiers. considerable effort has been expended to identify infectious agents that might be responsible for this rise in incidence, but no single infectious agent has been linked to this dramatic increase in type 1 diabetes. there has been increa ... | 2009 | 19120494 |
| pathogenic bacteria as vaccine vectors: teaching old bugs new tricks. | as our scientific knowledge of bacteria grows, so does our ability to manipulate these bacteria to protect rather than infect mammalian hosts from a diverse group of diseases. the old axiom that the best way to protect from a disease is to get infected in the first place is not feasible in the face of the diverse group of pathogens that infect humans. therefore, reprogramming bacteria to protect against diverse bacterial, viral, and parasitic diseases as well as cancer is a new reality in the fi ... | 2010 | 21165341 |
| reducing uncertainty in managing respiratory tract infections in primary care. | respiratory tract infections (rtis) remain the commonest reason for acute consultations in primary care in resource-rich countries. their spectrum and severity has changed from the time that antibiotics were discovered, largely from improvements in the socioeconomic determinants of health as well as vaccination. the benefits from antibiotic treatment for common rtis have been shown to be largely overstated. nevertheless, serious infections do occur. currently, no clinical features or diagnostic ... | 2010 | 21144191 |
| identification of a family of effectors secreted by the type iii secretion system that are conserved in pathogenic chlamydiae. | chlamydiae are gram-negative, obligate intracellular pathogens that replicate within a membrane-bounded compartment termed an inclusion. throughout their development, they actively modify the eukaryotic environment. the type iii secretion (tts) system is the main process by which the bacteria translocate effector proteins into the inclusion membrane and the host cell cytoplasm. here we describe a family of type iii secreted effectors that are present in all pathogenic chlamydiae and absent in th ... | 2010 | 21078856 |
| identification of a family of effectors secreted by the type iii secretion system that are conserved in pathogenic chlamydiae. | chlamydiae are gram-negative, obligate intracellular pathogens that replicate within a membrane-bounded compartment termed an inclusion. throughout their development, they actively modify the eukaryotic environment. the type iii secretion (tts) system is the main process by which the bacteria translocate effector proteins into the inclusion membrane and the host cell cytoplasm. here we describe a family of type iii secreted effectors that are present in all pathogenic chlamydiae and absent in th ... | 2010 | 21078856 |
| induction of polyclonal cd8+ t cell activation and effector function by pertussis toxin. | pertussis toxin (ptx) has pronounced adjuvant activity and strongly enhances innate and adaptive immune responses, including increased antibody production and th1/th2 cytokine production. adjuvant effects of ptx on th1 and th2 cells are primarily mediated via cd80/86 costimulation via enhanced expression of these molecules by apcs. however, it has remained unresolved whether ptx modulates the expression of costimulatory and inhibitory molecules on cd4+ and cd8+ t cells. to address this question, ... | 2010 | 21130421 |
| induction of polyclonal cd8+ t cell activation and effector function by pertussis toxin. | pertussis toxin (ptx) has pronounced adjuvant activity and strongly enhances innate and adaptive immune responses, including increased antibody production and th1/th2 cytokine production. adjuvant effects of ptx on th1 and th2 cells are primarily mediated via cd80/86 costimulation via enhanced expression of these molecules by apcs. however, it has remained unresolved whether ptx modulates the expression of costimulatory and inhibitory molecules on cd4+ and cd8+ t cells. to address this question, ... | 2010 | 21130421 |
| epinome - a novel workbench for epidemic investigation and analysis of search strategies in public health practice. | we present a novel user-centric visual analytics system that supports investigation of simulated disease outbreak and the study of decision-making. we developed epinome as part of our research on decision making in public health and in particular, on the evaluation of information search strategies in public health practice. epinome is a highly dynamic web-based system that provides a platform to track and study subjects' decision making and information search strategies, under controlled and rep ... | 2010 | 21347058 |
| identification and modulation of voltage-gated ca2+ currents in zebrafish rohon-beard neurons. | electrically excitable cells have voltage-dependent ion channels on the plasma membrane that regulate membrane permeability to specific ions. voltage-gated ca(2+) channels (vgccs) are especially important as ca(2+) serves as both a charge carrier and second messenger. zebrafish (danio rerio) are an important model vertebrate for studies of neuronal excitability, circuits, and behavior. however, electrophysiological properties of zebrafish vgccs remain largely unexplored because a suitable prepar ... | 2010 | 20962070 |
| identification and modulation of voltage-gated ca2+ currents in zebrafish rohon-beard neurons. | electrically excitable cells have voltage-dependent ion channels on the plasma membrane that regulate membrane permeability to specific ions. voltage-gated ca(2+) channels (vgccs) are especially important as ca(2+) serves as both a charge carrier and second messenger. zebrafish (danio rerio) are an important model vertebrate for studies of neuronal excitability, circuits, and behavior. however, electrophysiological properties of zebrafish vgccs remain largely unexplored because a suitable prepar ... | 2010 | 20962070 |
| in vivo efficacy of a chitosan/il-12 adjuvant system for protein-based vaccines. | vaccines based on recombinant proteins require adjuvant systems in order to generate th1-type immune responses. we have developed a vaccine adjuvant system using a viscous chitosan solution and interleukin (il)-12, a th1-inducing cytokine. the chitosan solution is designed to create a depot of antigen and il-12 at a subcutaneous injection site. we measured the in vivo immune response of a vaccine containing 0.25, 1, or 4 μg murine il-12 and 75 μg ovalbumin (ova), formulated in a 1.5% chitosan gl ... | 2010 | 20965561 |
| in vivo efficacy of a chitosan/il-12 adjuvant system for protein-based vaccines. | vaccines based on recombinant proteins require adjuvant systems in order to generate th1-type immune responses. we have developed a vaccine adjuvant system using a viscous chitosan solution and interleukin (il)-12, a th1-inducing cytokine. the chitosan solution is designed to create a depot of antigen and il-12 at a subcutaneous injection site. we measured the in vivo immune response of a vaccine containing 0.25, 1, or 4 μg murine il-12 and 75 μg ovalbumin (ova), formulated in a 1.5% chitosan gl ... | 2010 | 20965561 |
| tonb-dependent transporters: regulation, structure, and function. | tonb-dependent transporters (tbdts) are bacterial outer membrane proteins that bind and transport ferric chelates, called siderophores, as well as vitamin b(12), nickel complexes, and carbohydrates. the transport process requires energy in the form of proton motive force and a complex of three inner membrane proteins, tonb-exbb-exbd, to transduce this energy to the outer membrane. the siderophore substrates range in complexity from simple small molecules such as citrate to large proteins such as ... | 2010 | 20420522 |
| a new paradigm for aptamer therapeutic as1411 action: uptake by macropinocytosis and its stimulation by a nucleolin-dependent mechanism. | as1411 is a first-in-class anticancer agent, currently in phase ii clinical trials. it is a quadruplex-forming oligodeoxynucleotide that binds to nucleolin as an aptamer, but its mechanism of action is not completely understood. mechanistic insights could lead to clinically useful markers for as1411 response and to novel targeted therapies. previously, we proposed a model where cell surface nucleolin serves as the receptor for as1411, leading to selective uptake in cancer cells. here, we compare ... | 2010 | 20861190 |
| swabbing for respiratory viral infections in older patients: a comparison of rayon and nylon flocked swabs. | the purpose of this study was to compare the sampling efficacy of rayon swabs and nylon flocked swabs, and of oropharyngeal and nasopharyngeal specimens for the detection of respiratory viruses in elderly patients. samples were obtained from patients 60 years of age or above who were newly admitted to sorlandet hospital arendal, norway. the patients were interviewed for current symptoms of a respiratory tract infection. using rayon swabs and nylon flocked swabs, comparable sets of mucosal sample ... | 2010 | 20853014 |
| swabbing for respiratory viral infections in older patients: a comparison of rayon and nylon flocked swabs. | the purpose of this study was to compare the sampling efficacy of rayon swabs and nylon flocked swabs, and of oropharyngeal and nasopharyngeal specimens for the detection of respiratory viruses in elderly patients. samples were obtained from patients 60 years of age or above who were newly admitted to sorlandet hospital arendal, norway. the patients were interviewed for current symptoms of a respiratory tract infection. using rayon swabs and nylon flocked swabs, comparable sets of mucosal sample ... | 2010 | 20853014 |
| experimental autoimmune encephalomyelitis as a testing paradigm for adjuvants and vaccines. | experimental autoimmune encephalomyelitis (eae) is an experimental model for multiple sclerosis. eae can be induced by inoculation with central nervous system (cns) proteins or peptides emulsified in complete freund's adjuvant. protection from eae, enhancement of eae or subclinical priming for eae can occur as a result of either live viral infection or dna immunization with molecular mimics of cns proteins or peptides. here we review the published data describing modulation of eae through admini ... | 2010 | 20850537 |
| experimental autoimmune encephalomyelitis as a testing paradigm for adjuvants and vaccines. | experimental autoimmune encephalomyelitis (eae) is an experimental model for multiple sclerosis. eae can be induced by inoculation with central nervous system (cns) proteins or peptides emulsified in complete freund's adjuvant. protection from eae, enhancement of eae or subclinical priming for eae can occur as a result of either live viral infection or dna immunization with molecular mimics of cns proteins or peptides. here we review the published data describing modulation of eae through admini ... | 2010 | 20850537 |
| fragile privileges: autoimmunity in brain and eye. | brain and eye tissues are subject to a reduced version of immune surveillance, which has evolved to protect the particularly sensitive tissues from accidental bystander damage created by regular inflammatory responses. yet, there are autoimmune diseases in both organs. this review discusses the nature of immune reactivity in the healthy eye and brain tissues, and mechanisms that can overcome the protective barriers to create tissue specific disease. | 2010 | 20818330 |
| postinfluenza bacterial pneumonia: host defenses gone awry. | influenza is a common respiratory pathogen causing both seasonal and pandemic disease. influenza infection predisposes the host to secondary bacterial infection of the respiratory tract, which is a major cause of both morbidity and mortality in flu-related disease. in this review, we will discuss innate and adaptive antiviral responses during influenza infection, and review how these responses modulate protective immunity against secondary bacterial pathogens of the lung. specific emphasis will ... | 2010 | 20726789 |
| pertussis in florida, 2000-2006: trends in a historically low-incidence state. | florida, the fourth most populous state in the nation, has had historically low incidence rates of pertussis, the only vaccine-preventable disease with increasing numbers of reported cases. we compared the epidemiology and incidence rates of pertussis in florida with other states and the united states. | 2010 | 20873289 |
| pearl kendrick, grace eldering, and the pertussis vaccine. | in light of the reemergence of pertussis (whooping cough), the pioneering research of pearl kendrick and grace eldering is worth revisiting. in the 1930s, working in the michigan department of health laboratory in grand rapids, michigan, usa, they began researching a pertussis vaccine. their research offers an instructive case study of the creative public health research performed in state health department laboratories during the interwar years. state department of health laboratory directors a ... | 2010 | 20678322 |
| identification and characterization of the carbohydrate ligands recognized by pertussis toxin via a glycan microarray and surface plasmon resonance. | binding of pertussis toxin (ptx) was examined by a glycan microarray; 53 positive hits fell into four general groups. one group represents sialylated biantennary compounds with an n-glycan core terminating in alpha2-6-linked sialic acid. the second group consists of multiantennary compounds with a canonical n-glycan core, but lacking terminal sialic acids, which represents a departure from the previous understanding of ptx binding to n-glycans. the third group consists of neu5acalpha2-3(lactose ... | 2010 | 20515023 |
| a comparative approach linking molecular dynamics of altered peptide ligands and mhc with in vivo immune responses. | the recognition of peptide in the context of mhc by t lymphocytes is a critical step in the initiation of an adaptive immune response. however, the molecular nature of the interaction between peptide and mhc and how it influences t cell responsiveness is not fully understood. | 2010 | 20657836 |
| ab toxins: a paradigm switch from deadly to desirable. | to ensure their survival, a number of bacterial and plant species have evolved a common strategy to capture energy from other biological systems. being imperfect pathogens, organisms synthesizing multi-subunit ab toxins are responsible for the mortality of millions of people and animals annually. vaccination against these organisms and their toxins has proved rather ineffective in providing long-term protection from disease. in response to the debilitating effects of ab toxins on epithelial cell ... | 2010 | 22069653 |
| role of mapk p38 in the cellular responses to pore-forming toxins. | understanding the mechanism of action of pore-forming toxins (pfts) produced by different bacteria, as well as the host responses to toxin action, would provide ways to deal with these pathogenic bacteria. pfts affect the permeability of target cells by forming pores in their plasma membrane. target organisms may overcome these effects by triggering intracellular responses that have evolved as defense mechanisms to pft. among them it is well documented that stress-activated protein kinases, and ... | 2010 | 20599578 |
| role of mapk p38 in the cellular responses to pore-forming toxins. | understanding the mechanism of action of pore-forming toxins (pfts) produced by different bacteria, as well as the host responses to toxin action, would provide ways to deal with these pathogenic bacteria. pfts affect the permeability of target cells by forming pores in their plasma membrane. target organisms may overcome these effects by triggering intracellular responses that have evolved as defense mechanisms to pft. among them it is well documented that stress-activated protein kinases, and ... | 2010 | 20599578 |
| mlt-10 defines a family of duf644 and proline-rich repeat proteins involved in the molting cycle of caenorhabditis elegans. | the molting cycle of nematodes involves the periodic synthesis and removal of a collagen-rich exoskeleton, but the underlying molecular mechanisms are not well understood. here, we describe the mlt-10 gene of caenorhabditis elegans, which emerged from a genetic screen for molting-defective mutants sensitized by low cholesterol. mlt-10 defines a large family of nematode-specific proteins comprised of duf644 and tandem p-x(2)-l-(s/t)-p repeats. conserved nuclear hormone receptors promote expressio ... | 2010 | 20335506 |
| mutation bias favors protein folding stability in the evolution of small populations. | mutation bias in prokaryotes varies from extreme adenine and thymine (at) in obligatory endosymbiotic or parasitic bacteria to extreme guanine and cytosine (gc), for instance in actinobacteria. gc mutation bias deeply influences the folding stability of proteins, making proteins on the average less hydrophobic and therefore less stable with respect to unfolding but also less susceptible to misfolding and aggregation. we study a model where proteins evolve subject to selection for folding stabili ... | 2010 | 20463869 |
| interleukin-17 and its expanding biological functions. | interleukin-17 (il-17) and il-17-producing cells have been shown to play important roles in inflammation and the immune response. il-17 is believed to be mainly produced by t helper 17 (th17) cells, a unique helper t-cell subset different from th1 and th2 cells. other subsets of t cells such as gammadeltat and natural killer t (nkt) cells have also been found to produce il-17 in response to innate stimuli. il-17 acts as a proinflammatory cytokine that can induce the release of certain chemokines ... | 2010 | 20383173 |
| cytochrome c biogenesis: the ccm system. | cytochromes of c-type contain covalently attached hemes that are formed via thioether bonds between the vinyls of heme b and cysteines within c(1)xxc(2)h motifs of apocytochromes. in diverse organisms this post-translational modification relies on membrane-associated specific biogenesis proteins, referred to as cytochrome c maturation (ccm) systems. a highly complex version of these systems, ccm or system i, is found in gram-negative bacteria, archaea and plant mitochondria. we describe emerging ... | 2010 | 20382024 |
| design and utilization of epitope-based databases and predictive tools. | in the last decade, significant progress has been made in expanding the scope and depth of publicly available immunological databases and online analysis resources, which have become an integral part of the repertoire of tools available to the scientific community for basic and applied research. herein, we present a general overview of different resources and databases currently available. because of our association with the immune epitope database and analysis resource, this resource is reviewe ... | 2010 | 20213141 |
| characterizing the dynamics of cd4+ t cell priming within a lymph node. | generating adaptive immunity postinfection or immunization requires physical interaction within a lymph node t zone between ag-bearing dendritic cells (dcs) and rare cognate t cells. many fundamental questions remain regarding the dynamics of dc-cd4+ t cell interactions leading to priming. for example, it is not known how the production of primed cd4+ t cells relates to the numbers of cognate t cells, ag-bearing dcs, or peptide-mhcii level on the dc. to address these questions, we developed an a ... | 2010 | 20154206 |
| role of basophils in the initiation of th2 responses. | long appreciated for their role as type-2 effector cells, basophils have recently come into the spotlight for their role in the initiation of type-2 immunity. via an assortment of different activation pathways, basophils produce cytokines such as il-4 that promote th2 differentiation. furthermore, recent studies using different experimental systems have shown that basophils can act as antigen presenting cells both in vitro and in vivo. in addition, basophils shape the type-2 immune response by g ... | 2010 | 20144855 |
| immunity against helminths: interactions with the host and the intercurrent infections. | helminth parasites are of considerable medical and economic importance. studies of the immune response against helminths are of great interest in understanding interactions between the host immune system and parasites. effector immune mechanisms against tissue-dwelling helminths and helminths localized in the lumen of organs, and their regulation, are reviewed. helminth infections are characterized by an association of th2-like and treg responses. worms are able to persist in the host and are ma ... | 2010 | 20150967 |
| th17 cytokines and vaccine-induced immunity. | t helper type 17 (th17) cells are a distinct lineage of t cells that produce the effector molecules il-17, il-17f, il-21, and il-22. although the role of th17 cells in primary immune responses against infections is well documented, there is growing evidence that the th17 lineage maybe critical for vaccine-induced memory immune responses against infectious diseases. here, we summarize recent progress in our understanding of the role of il-17 in vaccine-induced immunity. | 2010 | 20112107 |
| neglected infections of poverty among the indigenous peoples of the arctic. | | 2010 | 20126272 |
| a review of adjuvants for leishmania vaccine candidates. | over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now licensed products or in late stage clinical development. the success of adjuvants in enhancing the immune response to antigens has led many researchers to re-focus their vaccine development programs. although several vaccine candidates have been tested against leishmaniasis, there is yet no effective vaccine against this parasitic disease. recent research has documented that e ... | 2010 | 23554607 |
| how tolerogenic dendritic cells induce regulatory t cells. | since their discovery by steinman and cohn in 1973, dendritic cells (dcs) have become increasingly recognized for their crucial role as regulators of innate and adaptive immunity. dcs are exquisitely adept at acquiring, processing, and presenting antigens to t cells. they also adjust the context (and hence the outcome) of antigen presentation in response to a plethora of environmental inputs that signal the occurrence of pathogens or tissue damage. such signals generally boost dc maturation, whi ... | 2010 | 21056730 |
| use of population health data to refine diagnostic decision-making for pertussis. | to improve identification of pertussis cases by developing a decision model that incorporates recent, local, population-level disease incidence. | 2010 | 20064807 |
| pathogenesis of allergic airway inflammation. | advances have been made in defining the mechanisms for the control of allergic airway inflammation in response to inhaled antigens. several genes, including adam33, dpp10, phf11, gpra, tim-1, pde4d, opn3, and ormdl3, have been implicated in the pathogenesis and susceptibility to atopy and asthma. growing evidence associates asthma with a systemic propensity for allergic t-helper type 2 cytokines. disordered coagulation and fibrinolysis also exacerbate asthma symptoms. balance among functionally ... | 2010 | 20425513 |
| the role of local public health laboratories. | local public health laboratories (phls) serve many of the same roles as state phls and often perform many or portions of the 11 core functions and capabilities of state public health laboratories; however, they differ in several important ways. first, many local laboratories provide testing at the site of patient care (e.g., sexually transmitted infection clinics) or address local environmental issues (e.g., water quality). second, local phls support the missions of local public health departmen ... | 2010 | 20518453 |
| atp-independent control of autotransporter virulence protein transport via the folding properties of the secreted protein. | autotransporter (at) proteins are the largest class of extracellular virulence proteins secreted from gram-negative bacteria. the mechanism by which at proteins cross the bacterial outer membrane (om), in the absence of atp or another external energy source, is unknown. here we demonstrate a linear correlation between localized regions of stability (δg(folding)) in the mature virulence protein (the at "passenger") and om secretion efficiency. destabilizing the c-terminal β-helical domain of a pa ... | 2011 | 22209629 |
| atp-independent control of autotransporter virulence protein transport via the folding properties of the secreted protein. | autotransporter (at) proteins are the largest class of extracellular virulence proteins secreted from gram-negative bacteria. the mechanism by which at proteins cross the bacterial outer membrane (om), in the absence of atp or another external energy source, is unknown. here we demonstrate a linear correlation between localized regions of stability (δg(folding)) in the mature virulence protein (the at "passenger") and om secretion efficiency. destabilizing the c-terminal β-helical domain of a pa ... | 2011 | 22209629 |
| increased risk of pertussis in patients with asthma. | the recent pertussis outbreak in california highlights the effect of pertussis on public health. in 2004, a pertussis outbreak occurred in olmsted county, minnesota, despite a high vaccine uptake. this outbreak provided a natural experiment to assess the relationship between asthma and pertussis. | 2011 | 22206778 |
| increased risk of pertussis in patients with asthma. | the recent pertussis outbreak in california highlights the effect of pertussis on public health. in 2004, a pertussis outbreak occurred in olmsted county, minnesota, despite a high vaccine uptake. this outbreak provided a natural experiment to assess the relationship between asthma and pertussis. | 2011 | 22206778 |
| galline ex-fabp is an antibacterial siderocalin and a lysophosphatidic acid sensor functioning through dual ligand specificities. | galline ex-fabp was identified as another candidate antibacterial, catecholate siderophore binding lipocalin (siderocalin) based on structural parallels with the family archetype, mammalian siderocalin. binding assays show that ex-fabp retains iron in a siderophore-dependent manner in both hypertrophic and dedifferentiated chondrocytes, where ex-fabp expression is induced after treatment with proinflammatory agents, and specifically binds ferric complexes of enterobactin, parabactin, bacillibact ... | 2011 | 22153502 |
| clostridial binary toxins: iota and c2 family portraits. | there are many pathogenic clostridium species with diverse virulence factors that include protein toxins. some of these bacteria, such as c. botulinum, c. difficile, c. perfringens, and c. spiroforme, cause enteric problems in animals as well as humans. these often fatal diseases can partly be attributed to binary protein toxins that follow a classic ab paradigm. within a targeted cell, all clostridial binary toxins destroy filamentous actin via mono-adp-ribosylation of globular actin by the a c ... | 2011 | 22919577 |
| modelling the impact of extended vaccination strategies on the epidemiology of pertussis. | the aim of this study was to investigate the optimal pertussis booster vaccination strategy for the netherlands. a realistic age-structured deterministic model was designed. assuming a steady-state situation and correcting for underreporting, the model was calibrated using notification data from the period 1996-2000. several sensitivity analyses were performed to explore the impact of different assumptions for parameters surrounded by uncertainty (e.g. duration of protection after natural infect ... | 2011 | 22115361 |
| modelling the impact of extended vaccination strategies on the epidemiology of pertussis. | the aim of this study was to investigate the optimal pertussis booster vaccination strategy for the netherlands. a realistic age-structured deterministic model was designed. assuming a steady-state situation and correcting for underreporting, the model was calibrated using notification data from the period 1996-2000. several sensitivity analyses were performed to explore the impact of different assumptions for parameters surrounded by uncertainty (e.g. duration of protection after natural infect ... | 2011 | 22115361 |
| nci, nhlbi/pbmtc first international conference on late effects after pediatric hematopoietic cell transplantation: persistent immune deficiency in pediatric transplant survivors. | defective immune reconstitution is a major barrier to successful hematopoietic cell transplantation (hct), and has important implications in the pediatric population. there are many factors that affect immune recovery, including stem cell source and graft-versus-host disease (gvhd). complete assessment of immune recovery, including t and b lymphocyte evaluation, innate immunity, and response to neoantigens, may provide insight as to infection risk and optimal time for immunizations. the increasi ... | 2011 | 22100979 |
| nci, nhlbi/pbmtc first international conference on late effects after pediatric hematopoietic cell transplantation: persistent immune deficiency in pediatric transplant survivors. | defective immune reconstitution is a major barrier to successful hematopoietic cell transplantation (hct), and has important implications in the pediatric population. there are many factors that affect immune recovery, including stem cell source and graft-versus-host disease (gvhd). complete assessment of immune recovery, including t and b lymphocyte evaluation, innate immunity, and response to neoantigens, may provide insight as to infection risk and optimal time for immunizations. the increasi ... | 2011 | 22100979 |
| the myriad roles of cyclic amp in microbial pathogens: from signal to sword. | all organisms must sense and respond to their external environments, and this signal transduction often involves second messengers such as cyclic nucleotides. one such nucleotide is cyclic amp, a universal second messenger that is used by diverse forms of life, including mammals, fungi, protozoa and bacteria. in this review, we discuss the many roles of camp in bacterial, fungal and protozoan pathogens and its contributions to microbial pathogenesis. these roles include the coordination of intra ... | 2011 | 22080930 |
| induction of tolerance via the sublingual route: mechanisms and applications. | the clinical efficacy of sublingual immunotherapy (slit) with natural allergen extracts has been established in ige-dependent respiratory allergies to grass or tree pollens, as well as house dust mites. sublingual vaccines have an excellent safety record, documented with approximately 2 billion doses administered, as of today, in humans. the oral immune system comprises various antigen-presenting cells, including langerhans cells, as well as myeloid and plasmacytoid dendritic cells (dcs) with a ... | 2011 | 22110534 |
| induction of tolerance via the sublingual route: mechanisms and applications. | the clinical efficacy of sublingual immunotherapy (slit) with natural allergen extracts has been established in ige-dependent respiratory allergies to grass or tree pollens, as well as house dust mites. sublingual vaccines have an excellent safety record, documented with approximately 2 billion doses administered, as of today, in humans. the oral immune system comprises various antigen-presenting cells, including langerhans cells, as well as myeloid and plasmacytoid dendritic cells (dcs) with a ... | 2011 | 22110534 |
| plasticity in mast cell responses during bacterial infections. | mast cells (mcs) have been implicated in orchestrating the host's early innate immune and adaptive immune responses in several models of acute bacterial infections. most of this activity results in early clearance of the bacteria and timely resolution of infection. however, during chronic infections because of the prolonged nature of mc-bacterial interactions, the role of the mc in determining the fate of infection is markedly more complex. depending on the nature of the pathogen, severity of in ... | 2011 | 22055570 |
| plasticity in mast cell responses during bacterial infections. | mast cells (mcs) have been implicated in orchestrating the host's early innate immune and adaptive immune responses in several models of acute bacterial infections. most of this activity results in early clearance of the bacteria and timely resolution of infection. however, during chronic infections because of the prolonged nature of mc-bacterial interactions, the role of the mc in determining the fate of infection is markedly more complex. depending on the nature of the pathogen, severity of in ... | 2011 | 22055570 |
| filmarray, an automated nested multiplex pcr system for multi-pathogen detection: development and application to respiratory tract infection. | the ideal clinical diagnostic system should deliver rapid, sensitive, specific and reproducible results while minimizing the requirements for specialized laboratory facilities and skilled technicians. we describe an integrated diagnostic platform, the "filmarray", which fully automates the detection and identification of multiple organisms from a single sample in about one hour. an unprocessed biologic/clinical sample is subjected to nucleic acid purification, reverse transcription, a high-order ... | 2011 | 22039434 |
| neuroprotective effect of combination therapy of glatiramer acetate and epigallocatechin-3-gallate in neuroinflammation. | multiple sclerosis (ms) is an inflammatory autoimmune disease of the central nervous system. however, studies of ms and the animal model, experimental autoimmune encephalomyelitis (eae), indicate that neuronal pathology is the principle cause of clinical disability. thus, there is need to develop new therapeutic strategies that not only address immunomodulation but also neuroprotection. here we show that the combination therapy of glatiramer acetate (ga), an immunomodulatory ms therapeutic, and ... | 2011 | 22022398 |
| fabrication principles and their contribution to the superior in vivo therapeutic efficacy of nano-liposomes remote loaded with glucocorticoids. | we report here the design, development and performance of a novel formulation of liposome- encapsulated glucocorticoids (gcs). a highly efficient (>90%) and stable gc encapsulation was obtained based on a transmembrane calcium acetate gradient driving the active accumulation of an amphipathic weak acid gc pro-drug into the intraliposome aqueous compartment, where it forms a gc-calcium precipitate. we demonstrate fabrication principles that derive from the physicochemical properties of the gc and ... | 2011 | 21998684 |
| a review on mucoadhesive polymer used in nasal drug delivery system. | this update review is on mucoadhesive polymers used in nasal dosage forms. the nasal mucosa provides a potentially good route for systemic drug delivery. one of the most important features of the nasal route is that it avoids first-pass hepatic metabolism, thereby reducing metabolism. the application of mucoadhesive polymers in nasal drug delivery systems has gained to promote dosage form residence time in the nasal cavity as well as improving intimacy of contact with absorptive membranes of the ... | 2011 | 22247888 |
| array comparative genomic hybridizations: assessing the ability to recapture evolutionary relationships using an in silico approach. | comparative genomic hybridization (cgh) with dna microarrays has many biological applications including surveys of copy number changes in tumorogenesis, species detection and identification, and functional genomics studies among related organisms. array cgh has also been used to infer phylogenetic relatedness among species or strains. although the use of the entire genome can be seen as a considerable advantage for use in phylogenetic analysis, few such studies have questioned the reliability of ... | 2011 | 21936922 |
| microarrays for pathogen detection and analysis. | dna microarrays have emerged as a viable platform for detection of pathogenic organisms in clinical and environmental samples. these microbial detection arrays occupy a middle ground between low cost, narrowly focused assays such as multiplex pcr and more expensive, broad-spectrum technologies like high-throughput sequencing. while pathogen detection arrays have been used primarily in a research context, several groups are aggressively working to develop arrays for clinical diagnostics, food saf ... | 2011 | 21930658 |
| pertussis resurgence in toronto, canada: a population-based study including test-incidence feedback modeling. | pertussis continues to challenge medical professionals; recently described increases in incidence may be due to age-cohort effects, vaccine effectiveness, or changes in testing patterns. toronto, canada has recently experienced increases in pertussis incidence, and provides an ideal jurisdiction for evaluating pertussis epidemiology due to centralized testing. we evaluated pertussis trends in toronto using all available specimen data, which allowed us to control for changing testing patterns and ... | 2011 | 21899765 |
| microbial genomics and infectious diseases. | | 2011 | 21793746 |
| profile-statistical periodicity of dna coding regions. | novel methods for identifying a new type of dna latent periodicity, called latent profile periodicity or latent profility, are used to search for periodic structures in genes. these methods reveal two distinct levels of organization of genetic information encoding. it is shown that latent profility in genes may correlate with specific structural features of their encoded proteins. | 2011 | 21788253 |
| g(i/o) protein-dependent and -independent actions of pertussis toxin (ptx). | pertussis toxin (ptx) is a typical a-b toxin. the a-protomer (s1 subunit) exhibits adp-ribosyltransferase activity. the b-oligomer consists of four subunits (s2 to s5) and binds extracellular molecules that allow the toxin to enter the cells. the a-protomer adp-ribosylates the α subunits of heterotrimeric g(i/o) proteins, resulting in the receptors being uncoupled from the g(i/o) proteins. the b-oligomer binds proteins expressed on the cell surface, such as toll-like receptor 4, and activates an ... | 2011 | 22069745 |
| structural basis for the high-affinity inhibition of mammalian membranous adenylyl cyclase by 2',3'-o-(n-methylanthraniloyl)-inosine 5'-triphosphate. | 2',3'-o-(n-methylanthraniloyl)-itp (mant-itp) is the most potent inhibitor of mammalian membranous adenylyl cyclase (mac) 5 (ac5, k(i), 1 nm) yet discovered and surpasses the potency of mant-gtp by 55-fold (j pharmacol exp ther 329:1156-1165, 2009). ac5 inhibitors may be valuable drugs for treatment of heart failure. the aim of this study was to elucidate the structural basis for the high-affinity inhibition of mac by mant-itp. mant-itp was a considerably more potent inhibitor of the purified ca ... | 2011 | 21498658 |
| advances in microfluidic pcr for point-of-care infectious disease diagnostics. | global burdens from existing or emerging infectious diseases emphasize the need for point-of-care (poc) diagnostics to enhance timely recognition and intervention. molecular approaches based on pcr methods have made significant inroads by improving detection time and accuracy but are still largely hampered by resource-intensive processing in centralized laboratories, thereby precluding their routine bedside- or field-use. microfluidic technologies have enabled miniaturization of pcr processes on ... | 2011 | 21741465 |
| effectiveness of anti-inflammatory treatment versus antibiotic therapy and placebo for patients with non-complicated acute bronchitis with purulent sputum. the baap study protocol. | acute bronchitis is one of the most prevalent respiratory infections in primary care, and in more than 90% of the cases antibiotics are prescribed, mainly when purulent expectoration is present. however, this process is usually viral in origin and the benefits of antibiotic treatment are marginal. on the other hand, in recent years bronchitis has been considered more as an inflammatory than an infectious process. thus, the aim of this study is to evaluate the clinical effectiveness of a schedule ... | 2011 | 21693045 |
| a review of tandem mass spectrometry characterization of adenosine diphosphate-ribosylated peptides. | the use of tandem mass spectrometry to identify and characterize sites of protein adenosine diphosphate (adp) ribosylation will be reviewed. specifically, we will focus on data acquisition schemes and fragmentation techniques that provide peptide sequence and modification site information. also discussed are uses of synthetic standards to aid characterization, and an enzymatic method that converts adp-ribosylated peptides into ribosyl mono phosphorylated peptides making identification amenable t ... | 2011 | 22563295 |
| a review of tandem mass spectrometry characterization of adenosine diphosphate-ribosylated peptides. | the use of tandem mass spectrometry to identify and characterize sites of protein adenosine diphosphate (adp) ribosylation will be reviewed. specifically, we will focus on data acquisition schemes and fragmentation techniques that provide peptide sequence and modification site information. also discussed are uses of synthetic standards to aid characterization, and an enzymatic method that converts adp-ribosylated peptides into ribosyl mono phosphorylated peptides making identification amenable t ... | 2011 | 22563295 |
| structure-activity relationships for the interactions of 2'- and 3'-(o)-(n-methyl)anthraniloyl-substituted purine and pyrimidine nucleotides with mammalian adenylyl cyclases. | membranous adenylyl cyclases (acs) play a key role in signal transduction and are promising drug targets. in previous studies we showed that 2',3'-(o)-(n-methylanthraniloyl) (mant)-substituted nucleotides are potent ac inhibitors. the aim of this study was to provide systematic structure-activity relationships for 21 (m)ant-substituted nucleotides at the purified catalytic ac subunit heterodimer vc1:iic2, the vc1:vc1 homodimer and recombinant acs 1, 2 and 5. (m)ant-nucleotides inhibited fully ac ... | 2011 | 21620805 |
| nitric oxide/cgmp pathway signaling actively down-regulates α4β1-integrin affinity: an unexpected mechanism for inducing cell de-adhesion. | integrin activation in response to inside-out signaling serves as the basis for rapid leukocyte arrest on endothelium, migration, and mobilization of immune cells. integrin-dependent adhesion is controlled by the conformational state of the molecule, which is regulated by seven-transmembrane guanine nucleotide binding protein-coupled receptors (gpcrs). α4β1-integrin (cd49d/cd29, very late antigen-4, vla-4) is expressed on leukocytes, hematopoietic progenitors, stem cells, hematopoietic cancer ce ... | 2011 | 21586157 |
| solid-state nmr studies of amyloid fibril structure. | current interest in amyloid fibrils stems from their involvement in neurodegenerative and other diseases and from their role as an alternative structural state for many peptides and proteins. solid-state nuclear magnetic resonance (nmr) methods have the unique capability of providing detailed structural constraints for amyloid fibrils, sufficient for the development of full molecular models. in this article, recent progress in the application of solid-state nmr to fibrils associated with alzheim ... | 2011 | 21219138 |
| more than one way to control hair growth: regulatory mechanisms in enterobacteria that affect fimbriae assembled by the chaperone/usher pathway. | many gram-negative enterobacteria produce surface-associated fimbriae that facilitate attachment and adherence to eucaryotic cells and tissues. these organelles are believed to play an important role during infection by enabling bacteria to colonize specific niches within their hosts. one class of these fimbriae is assembled using a periplasmic chaperone and membrane-associated scaffolding protein that has been referred to as an usher because of its function in fimbrial biogenesis. the presence ... | 2011 | 21398554 |
| cough: an unmet clinical need. | cough is among the most common complaints for which patients worldwide seek medical attention. thus, the evaluation and treatment of cough result in tremendous financial expenditure and consumption of health care resources. yet, despite the clinical significance of cough, research efforts aimed at improving diagnostic capabilities and developing more effective therapeutic agents have been, to date, disappointing in their limited scope and outcomes. acute cough due to the common cold represents t ... | 2011 | 21198555 |