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Berlin Brandenburg

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  • 1
    Language: English
    In: Western Folklore, 1 July 2011, Vol.70(3/4), pp.287-309
    Description: The authors describe three projects—the Greenbush Cultural Tour, the Neighborhood Games Design Project, and a workshop for folklorists on Augmented Reality Interactive Storytelling—that demonstrate the importance of place-based education and promote learning outside formal classrooms with mobile devices and local games. These projects share a concern with creating deeper appreciation of local places, increasing civic engagement, and involving students and adults as digital producers as well as consumers.
    Keywords: Behavioral sciences -- Sociology -- Human societies ; Business -- Industry -- Industrial sectors ; Behavioral sciences -- Anthropology -- Applied anthropology ; Education -- Educational resources -- Educational technology ; Behavioral sciences -- Leisure studies -- Recreation ; Education -- Specialized education -- Community education ; Arts -- Applied arts -- Design ; Social sciences -- Human geography -- Social geography ; Behavioral sciences -- Sociology -- Human societies ; Arts -- Applied arts -- Architecture
    ISSN: 0043373X
    E-ISSN: 2325811X
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  • 2
    Language: English
    In: PLoS ONE, 2011, Vol.6(10), p.e26734
    Description: A new hypervirulent (hypermucoviscous) clinical variant of Klebsiella pneumoniae (hvKP) has emerged over the last decade. Our goal is to identify new mechanisms, which increase the virulence hvKP compared to “classic” K. pneumoniae (cKP). ; Various growth assays were performed in human ascites, human serum, and laboratory medium with the hvKP strain hvKP1 (wt), randomly chosen blood isolates of cKP strains (cKP1-4), and mutant constructs deficient in the secretion of selected compounds. An in vivo mouse model that mimics infection due to hvKP and a quantitative siderophore assay were also used. It was established that a molecule(s)/factor(s) was secreted by hvKP1 significantly enhanced its growth and/or survival in human ascites. This molecule(s)/factor(s) also increased the growth and/or survival of hvKP1 in serum ex vivo and in an in vivo mouse model that measures metastatic spread after subcutaneous challenge, thereby further establishing biologic significance. Although features such as a size of 〈3kD, heat stability, and growth characteristics in ascites suggested this molecule(s) was a quorum-sensing compound, data presented demonstrates that this molecule(s)/factor(s) is involved in iron uptake and is likely a siderophore(s) or another iron-acquisition molecule. Although it is known that iron acquisition is critical for virulence, a novel aspect of this observation is that hvKP1 produces quantitatively more siderophores that appear to be biologically more active (increased affinity for iron or more resistant to host factors) than those produced by cKP strains. ; The data presented delineates a new mechanism by which hvKP increases its pathogenic potential compared to cKP strains. This paradigm may be broadly applicable to other extraintestinal gram-negative bacilli.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Infectious Diseases ; Microbiology ; Gastroenterology And Hepatology
    E-ISSN: 1932-6203
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  • 3
    Language: English
    In: Infection and immunity, October 2017, Vol.85(10)
    Description: Hypervirulent (hvKP) is an emerging pathotype that is capable of causing tissue-invasive and organ- and life-threatening infections in healthy individuals from the community. Knowledge on the virulence factors specific to hvKP is limited. In this report, we describe a new factor (PEG344) that increases the virulence of hvKP strain hvKP1. is present on the hvKP1 virulence plasmid, is broadly prevalent among hvKP strains, and has increased RNA abundance when grown in human ascites. An isogenic derivative of hvKP1 (hvKP1Δ) was constructed and compared with its wild-type parent strain in , , and infection model studies. Both survival and competition experiments with outbred CD1 mice demonstrated that PEG344 was required for full virulence after pulmonary challenge but, interestingly, not after subcutaneous challenge. analysis suggested that PEG344 serves as an inner membrane transporter. Compared to hvKP1, a small but significant decrease in the growth/survival of hvKP1Δ was observed in human ascites, but resistance to the bactericidal activity of complement was similar. These data suggested that PEG344 may transport an unidentified growth factor present in ascites. The data presented are important since they expand our limited knowledge base on virulence factors unique to hvKP, which is needed to lay the groundwork for translational approaches to prevent or treat these devastating infections.
    Keywords: Klebsiella Pneumoniae ; Hypervirulent ; Infection Model ; Pathogenesis ; Reference Gene ; Superbug ; Virulence Factors ; Ascites -- Microbiology ; Bacterial Proteins -- Physiology ; Klebsiella Pneumoniae -- Pathogenicity ; Membrane Transport Proteins -- Pharmacology ; Virulence Factors -- Physiology
    ISSN: 00199567
    E-ISSN: 1098-5522
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  • 4
    Language: English
    In: Infection and immunity, August 2015, Vol.83(8), pp.3325-33
    Description: The siderophore aerobactin is the dominant siderophore produced by hypervirulent Klebsiella pneumoniae (hvKP) and was previously shown to be a major virulence factor in systemic infection. However, strains of hvKP commonly produce the additional siderophores yersiniabactin, salmochelin, and enterobactin. The roles of these siderophores in hvKP infection have not been optimally defined. To that end, site-specific gene disruptions were created in hvKP1 (wild type), resulting in the generation of hvKP1ΔiucA (aerobactin deficient), hvKP1ΔiroB (salmochelin deficient), hvKP1ΔentB (enterobactin and salmochelin deficient), hvKP1Δirp2 (yersiniabactin deficient), and hvKP1ΔentBΔirp2 (enterobactin, salmochelin, and yersiniabactin deficient). The growth/survival of these constructs was compared to that of their wild-type parent hvKP1 ex vivo in human ascites fluid, human serum, and human urine and in vivo in mouse systemic infection and pulmonary challenge models. Interestingly, in contrast to aerobactin, the inability to produce enterobactin, salmochelin, or yersiniabactin individually or in combination did not decrease the ex vivo growth/survival in human ascites or serum or decrease virulence in the in vivo infection models. Surprisingly, none of the siderophores increased growth in human urine. In human ascites fluid supplemented with exogenous siderophores, siderophores increased the growth of hvKP1ΔiucA, with the relative activity being enterobactin 〉 aerobactin 〉 yersiniabactin 〉 salmochelin, suggesting that the contribution of aerobactin to virulence is dependent on both innate biologic activity and quantity produced. Taken together, these data confirm and extend a role for aerobactin as a critical virulence factor for hvKP. Since it appears that aerobactin production is a defining trait of hvKP strains, this factor is a potential antivirulence target.
    Keywords: Enterobactin -- Analogs & Derivatives ; Glucosides -- Metabolism ; Hydroxamic Acids -- Metabolism ; Klebsiella Infections -- Microbiology ; Klebsiella Pneumoniae -- Growth & Development ; Phenols -- Metabolism ; Siderophores -- Metabolism ; Thiazoles -- Metabolism
    ISSN: 00199567
    E-ISSN: 1098-5522
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  • 5
    Article
    Article
    Language: English
    In: JAMA, 02/28/2007, Vol.297(8), p.787
    Keywords: Medicine;
    ISSN: 0098-7484
    E-ISSN: 15383598
    Source: American Medical Association (via CrossRef)
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  • 6
    Language: English
    In: Infection and immunity, December 2017, Vol.85(12)
    Description: has become an important concern for human health due to rapid development and wide spread of antimicrobial-resistant strains and high mortality associated with the infection. Passive immunizations with antisera targeting outer membrane proteins (OMPs) have shown encouraging results in protecting mice from infection, but monoclonal anti-OMP antibodies have not been developed, and their potential therapeutic properties have not been explored. The goal of this report is to evaluate the antibacterial activity of monoclonal antibodies (MAbs) targeting outer membrane protein A (OmpA) of Five anti-OmpA MAbs were developed using hybridoma technology and showed strong binding to strain ATCC 19606. However, low antibody binding was observed when they were tested against six clinical isolates, which included extensively drug-resistant strains. In contrast, high binding to an isogenic K1 capsule-negative mutant (AB307.30) was shown, suggesting that capsular polysaccharide mediated the inhibition of MAb binding to OmpA. Anti-OmpA MAbs increased the macrophage-mediated bactericidal activity of AB307.30 but failed to increase phagocytic killing of capsule-positive strains. Capsular polysaccharide was also protective against complement-mediated bactericidal activity in human ascites in the presence and absence of opsonization. Lastly, passive immunization with anti-OmpA MAbs did not confer protection against challenge with AB307-0294, the encapsulated parent strain of AB307.30, in a mouse sepsis infection model. These results reveal the important role of capsule polysaccharide in shielding OmpA and thereby inhibiting anti-OmpA MAb binding to clinical isolates. This property of capsule hindered the therapeutic utility of anti-OmpA MAbs, and it may apply to other conserved epitopes in .
    Keywords: Acinetobacter Baumannii ; Capsule Polysaccharide ; Monoclonal Antibody ; Outer Membrane Protein A ; Passive Immunization ; Immunization, Passive ; Acinetobacter Infections -- Therapy ; Acinetobacter Baumannii -- Immunology ; Antibodies, Bacterial -- Therapeutic Use ; Antibodies, Monoclonal -- Therapeutic Use ; Bacterial Outer Membrane Proteins -- Immunology ; Polysaccharides, Bacterial -- Metabolism
    ISSN: 00199567
    E-ISSN: 1098-5522
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  • 7
    Language: English
    In: The American Journal of Public Health, Jan, 2010, Vol.100(1), p.9(4)
    Description: Many Medicare recipients do not understand their health care rights. Lumetra, formerly California's Medicare quality improvement organization, developed a multifaceted outreach program to increase beneficiary awareness of its services and of the right to file quality-of-care complaints and discharge appeals. Layered outreach activities to Medicare members and their caregivers in 2 targeted counties consisted of paid media, direct mailings, community outreach, and online marketing. Calls to Lumetra's helpline and visits to its Web site-measures of beneficiary awareness of case review services-increased by 106% and 1214%, respectively, in the targeted counties during the 4-month outreach period. Only small increases occurred in nontargeted counties. Increases in quality-of-care complaints and discharge appeal rates were detected during a longer follow-up period. (Am J Public Health. 2010;100:9-12. doi: 10.2105/AJPH.2008.152264)
    Keywords: Public Health ; Elderly ; Medicare ; Caregivers
    ISSN: 0090-0036
    Source: Cengage Learning, Inc.
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  • 8
    In: Infection and Immunity, 2010, Vol. 78(5), p.2017
    Description: Although Acinetobacter baumannii has emerged as a significant cause of nosocomial infections worldwide, there have been few investigations describing the factors important for A. baumannii persistence and pathogenesis. This paper describes the first reported identification of a glycosyltransferase, LpsB, involved in lipopolysaccharide (LPS) biosynthesis in A. baumannii. Mutational, structural, and complementation analyses indicated that LpsB is a core oligosaccharide glycosyl transferase. Using a genetic approach, lpsB was compared with the lpsB homologues of several A. baumannii strains. These analyses indicated that LpsB is highly conserved among A. baumannii isolates. Furthermore, we developed a monoclonal antibody, monoclonal antibody 13C11, which reacts to an LPS core epitope expressed by approximately one-third of the A. baumannii clinical isolates evaluated to date. Previous studies describing the heterogeneity of A. baumannii LPS were limited primarily to structural analyses; therefore, studies evaluating the correlation between these surface glycolipids and pathogenesis were warranted. Our data from an evaluation of LpsB mutant 307::TN17, which expresses a deeply truncated LPS glycoform consisting of only two 3-deoxy-d-manno-octulosonic acid residues and lipid A, suggest that A. baumannii LPS is important for resistance to normal human serum and confers a competitive advantage for survival in vivo. These results have important implications for the role of LPS in A. baumannii infections.
    Keywords: Acinetobacter Baumannii -- Enzymology ; Bacterial Proteins -- Metabolism ; Glycosyltransferases -- Metabolism ; Lipopolysaccharides -- Biosynthesis;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 9
    In: Infection and Immunity, 2010, Vol. 78(9), p.3993
    Description: Acinetobacter baumannii is a pathogen of increasing medical importance with a propensity to be multidrug resistant, thereby making treatment challenging. Little is known of virulence traits in A. baumannii. To identify virulence factors and potential drug targets, random transposon (Tn) mutants derived from the A. baumannii strain AB307-0294 were screened to identify genes essential for growth in human ascites fluid in vitro, an inflammatory exudative fluid. These studies led to the identification of two genes that were predicted to be required for capsule polymerization and assembly. The first, ptk, encodes a putative protein tyrosine kinase (PTK), and the second, epsA, encodes a putative polysaccharide export outer membrane protein (EpsA). Monoclonal antibodies used in flow cytometric and Western analyses confirmed that these genes are required for a capsule-positive phenotype. A capsule-positive phenotype significantly optimized growth in human ascites fluid, survival in human serum, and survival in a rat soft tissue infection model. Importantly, the clearance of the capsule-minus mutants AB307.30 (ptk mutant, capsule minus) and AB307.45 (epsA mutant, capsule minus) was complete and durable. These data demonstrated that the K1 capsule from AB307-0294 was an important protectin. Further, these data suggested that conserved proteins, which contribute to the capsule-positive phenotype, are potential antivirulence drug targets. Therefore, the results from this study have important biologic and translational implications and, to the best of our knowledge, are the first to address the role of capsule in the pathogenesis of A. baumannii infection.
    Keywords: Translation ; Outer Membrane Proteins ; Data Processing ; Polymerization ; Virulence Factors ; Monoclonal Antibodies ; Animal Models ; Survival ; Medical Importance ; Pathogens ; Infection ; Inflammation ; Flow Cytometry ; Transposons ; Ascites ; Protein-Tyrosine Kinase ; Multidrug Resistance ; Soft Tissues ; Capsular Polysaccharides ; Drugs ; Acinetobacter Baumannii ; Microorganisms & Parasites ; Immunology;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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  • 10
    Language: English
    In: Infection and immunity, March 2013, Vol.81(3), pp.915-22
    Description: The emergence of extremely resistant and panresistant Gram-negative bacilli, such as Acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target. Its structure was determined by a combination of mass spectrometric and nuclear magnetic resonance (NMR) techniques. Molecular mimics that might raise the concern for autoimmune disease were not identified. Immunization of CD1 mice demonstrated that the K1 capsule is immunogenic. The monoclonal antibody (MAb) 13D6, which is directed against the K1 capsule from A. baumannii, was used to determine the seroprevalence of the K1 capsule in a collection of 100 A. baumannii strains. Thirteen percent of the A. baumannii isolates from this collection were seroreactive to MAb 13D6. Opsonization of K1-positive strains, but not K1-negative strains, with MAb 13D6 significantly increased neutrophil-mediated bactericidal activity in vitro (P 〈 0.05). Lastly, treatment with MAb 13D6 3 and 24 h after bacterial challenge in a rat soft tissue infection model resulted in a significant decrease in the growth/survival of a K1-positive strain compared to that of a K1-negative strain or to treatment with a vehicle control (P 〈 0.0001). These data support the proof of principle that the K1 capsule is a potential therapeutic target via passive immunization. Other serotypes require assessment, and pragmatic challenges exist, such as the need to serotype infecting strains and utilize serotype-specific therapy. Nonetheless, this approach may become an important therapeutic option with increasing antimicrobial resistance and a diminishing number of active antimicrobials.
    Keywords: Acinetobacter Infections -- Prevention & Control ; Acinetobacter Baumannii -- Metabolism ; Antibodies, Monoclonal -- Immunology ; Bacterial Capsules -- Metabolism ; Bacterial Vaccines -- Immunology
    ISSN: 00199567
    E-ISSN: 1098-5522
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