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The Gram-positive bacterium Streptococcus pneumoniae is the leading causative pathogen in community-acquired pneumonia. The ever-increasing frequency of antibiotic-resistant S. pneumoniae strains severely hampers effective treatments. Thus, a better understanding of the mechanisms involved in the pathogenesis of pneumococcal disease is needed; in particular, of the initial interactions that take place between the host and the bacterium. Recognition of pathogens by dendritic cells is one of the most crucial steps in the induction of an immune response. For efficient pathogen recognition, dendritic cells express various kinds of receptors, including the DC-specific C-type lectin DC-SIGN. Pathogens such as Mycobacterium tuberculosis and HIV target DC-SIGN to escape immunity. Here the in vitro binding of DC-SIGN with S. pneumoniae was investigated. DC-SIGN specifically interacts with S. pneumoniae serotype 3 and 14 in contrast to other serotypes such as 19F. While the data described here suggest that DC-SIGN interacts with S. pneumoniae serotype 14 through a ligand expressed by the capsular polysaccharide, the binding to S. pneumoniae serotype 3 appears to depend on an as yet unidentified ligand. Despite the binding capacity of the capsular polysaccharide of S. pneumoniae 14 to DC-SIGN, no immunomodulatory effects on the dendritic cells were observed. The immunological consequences of the serotype-specific capacity to interact with DC-SIGN should be further explored and might result in new insights in the development of new and more potent vaccines. 相似文献
3.
Kenneth Clark Bruce Vendt Kirk Smith John Freymann Justin Kirby Paul Koppel Stephen Moore Stanley Phillips David Maffitt Michael Pringle Lawrence Tarbox Fred Prior 《Journal of digital imaging》2013,26(6):1045-1057
The National Institutes of Health have placed significant emphasis on sharing of research data to support secondary research. Investigators have been encouraged to publish their clinical and imaging data as part of fulfilling their grant obligations. Realizing it was not sufficient to merely ask investigators to publish their collection of imaging and clinical data, the National Cancer Institute (NCI) created the open source National Biomedical Image Archive software package as a mechanism for centralized hosting of cancer related imaging. NCI has contracted with Washington University in Saint Louis to create The Cancer Imaging Archive (TCIA)—an open-source, open-access information resource to support research, development, and educational initiatives utilizing advanced medical imaging of cancer. In its first year of operation, TCIA accumulated 23 collections (3.3 million images). Operating and maintaining a high-availability image archive is a complex challenge involving varied archive-specific resources and driven by the needs of both image submitters and image consumers. Quality archives of any type (traditional library, PubMed, refereed journals) require management and customer service. This paper describes the management tasks and user support model for TCIA. 相似文献
4.
Silliman BR van de Koppel J McCoy MW Diller J Kasozi GN Earl K Adams PN Zimmerman AR 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(28):11234-11239
More than 2 y have passed since the BP-Deepwater Horizon oil spill in the Gulf of Mexico, yet we still have little understanding of its ecological impacts. Examining effects of this oil spill will generate much-needed insight into how shoreline habitats and the valuable ecological services they provide (e.g., shoreline protection) are affected by and recover from large-scale disturbance. Here we report on not only rapid salt-marsh recovery (high resilience) but also permanent marsh area loss after the BP-Deepwater Horizon oil spill. Field observations, experimental manipulations, and wave-propagation modeling reveal that (i) oil coverage was primarily concentrated on the seaward edge of marshes; (ii) there were thresholds of oil coverage that were associated with severity of salt-marsh damage, with heavy oiling leading to plant mortality; (iii) oil-driven plant death on the edges of these marshes more than doubled rates of shoreline erosion, further driving marsh platform loss that is likely to be permanent; and (iv) after 18 mo, marsh grasses have largely recovered into previously oiled, noneroded areas, and the elevated shoreline retreat rates observed at oiled sites have decreased to levels at reference marsh sites. This paper highlights that heavy oil coverage on the shorelines of Louisiana marshes, already experiencing elevated retreat because of intense human activities, induced a geomorphic feedback that amplified this erosion and thereby set limits to the recovery of otherwise resilient vegetation. It thus warns of the enhanced vulnerability of already degraded marshes to heavy oil coverage and provides a clear example of how multiple human-induced stressors can interact to hasten ecosystem decline. 相似文献
5.
Getaw Worku Hassen Mohammed Al-Juboori Barbara Koppel Gokhan Akfirat Hossein Kalantari 《The American journal of emergency medicine》2018,36(4):736.e1-736.e3
Measurement of optic nerve sheath diameter (ONSD) using point of care ultrasound has been used to indirectly assess the intracranial pressure (ICP) particularly in conditions where it is raised. Direct pressure measurements using probes reaching the ventricle system correlated with ONSD using ultrasound. Attempts were made to measure the ONSD pre and post lumbar puncture (LP) after draining cerebrospinal fluid (CSF) as well as post ventricular shunt placement. We report ONSD measurement and demonstrate dynamic changes during LP in a patient with known idiopathic intracranial hypertension (IIH). 相似文献
6.
Cowan AE Olivastro EM Koppel DE Loshon CA Setlow B Setlow P 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(20):7733-7738
Bacterial spores of various Bacillus species are impermeable or exhibit low permeability to many compounds that readily penetrate germinated spores, including methylamine. We now show that a lipid probe in the inner membrane of dormant spores of Bacillus megaterium and Bacillus subtilis is largely immobile, as measured by fluorescence redistribution after photobleaching, but becomes free to diffuse laterally upon spore germination. The lipid immobility in and the slow permeation of methylamine through the inner membrane of dormant spores may be due to a significant (1.3- to 1.6-fold) apparent reduction of the membrane surface area in the dormant spore relative to that in the germinated spore, but is not due to the dormant spore's high levels of dipicolinic acid and divalent cations. 相似文献
7.
A soluble protein is immobile in dormant spores of Bacillus subtilis but is mobile in germinated spores: implications for spore dormancy 下载免费PDF全文
Cowan AE Koppel DE Setlow B Setlow P 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(7):4209-4214
Fluorescence redistribution after photobleaching has been used to show that a cytoplasmic GFP fusion is immobile in dormant spores of Bacillus subtilis but becomes freely mobile in germinated spores in which cytoplasmic water content has increased approximately 2-fold. The GFP immobility in dormant spores is not due to the high levels of dipicolinic acid in the spore cytoplasm, because GFP was also immobile in germinated cwlD spores that had excreted their dipicolinic acid but where cytoplasmic water content had only increased to a level similar to that in dormant spores of several other Bacillus species. The immobility of a normally mobile protein in dormant wild-type spores and germinated cwlD spores is consistent with the lack of metabolism and enzymatic activity in these spores and suggests that protein immobility, presumably due to low water content, is a major reason for the metabolic dormancy of spores of Bacillus species. 相似文献
8.
The need to underpin health and education with a firm evidence base is of increasing significance. Systematic review offers an effective approach to critically assessing research in order to understand its overall impact on practice. Based on 5 years' experience undertaking systematic reviews of interprofessional education, this paper offers guidance for researchers and practitioners about to embark upon systematic review work. 相似文献
9.
Seizures in the critically ill: the role of imipenem 总被引:5,自引:0,他引:5
PURPOSE: To determine the risk of seizures in critically ill patients receiving the antibiotic imipenem, a broad-spectrum antibiotic that has been associated with seizures. Reports generally have not considered other contributing factors such as dose, seizure history, and morbidity index of the underlying illness necessitating the antibiotic. METHODS: Charts of all patients in a 450-bed municipal hospital who received imipenem in a 6-month period, as determined by pharmacy records, were reviewed for dosage and duration of imipenem use, occurrence of seizures. and mortality outcome. Attention was paid to demographic features; pattern of seizure occurrence during, before, and after imipenem use; renal function; and correction for dosage based on size. RESULTS: Seventy-five charts were reviewed. Sixty-three patients had no seizures during the hospitalization, four had seizures while receiving imipenem, and eight had seizures during the hospitalization but before or after imipenem use. The incidence of seizures was 4/1,000 patient-days on, and 3.9/1,000 patient-days off imipenem (not significant). The risk of seizure in both groups was considerably higher in those patients with a history of seizures before hospitalization. The presence of other factors that could contribute to increased concentration of imipenem in the brain, such as renal failure or acute stroke, did not contribute to seizure incidence. Metabolic derangement, anoxia, and phenytoin discontinuation did contribute to seizure incidence. CONCLUSIONS: Seizure incidence is increased in all critically ill patients (16% of patients studied), but with no added risk during the period patients received imipenem. Determining the proper dose based on a patient's body mass, correction of dose in the presence of renal failure, and avoidance of excess of 2 g/day of imipenem removes any added risk for seizures from imipenem. Despite experimental data to suggest action of imipenem on the glutamate/N-methyl-d-aspartate receptor, or interference with binding to the gamma-aminobutyric acid receptor, and early clinical studies that warned against its use because of seizure risk, we found that careful use of this antibiotic is safe. 相似文献
10.