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      1. Author :
        Li, Min; Rigby, Kevin; Lai, Yuping; Nair, Vinod; Peschel, Andreas; Schittek, Birgit; Otto, Michael
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Antimicrobial agents and chemotherapy
      6. Products :
      7. Volume :
        53
      8. Issue :
        10
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Anti-Bacterial Agents; Bioware; Blotting, Southern; Chromatography, Thin Layer; Computational Biology; Cytochromes c; Genetic Complementation Test; Humans; Microscopy, Electron, Scanning; Microscopy, Immunoelectron; Mutagenesis; Peptides; Phospholipids; Polymerase Chain Reaction; Staphylococcus aureus; Xen36
      12. Abstract :
        Antimicrobial peptides (AMPs) form an important part of the innate host defense. In contrast to most AMPs, human dermcidin has an anionic net charge. To investigate whether bacteria have developed specific mechanisms of resistance to dermcidin, we screened for mutants of the leading human pathogen, Staphylococcus aureus, with altered resistance to dermcidin. To that end, we constructed a plasmid for use in mariner-based transposon mutagenesis and developed a high-throughput cell viability screening method based on luminescence. In a large screen, we did not find mutants with strongly increased susceptibility to dermcidin, indicating that S. aureus has no specific mechanism of resistance to this AMP. Furthermore, we detected a mutation in a gene of unknown function that resulted in significantly increased resistance to dermcidin. The mutant strain had an altered membrane phospholipid pattern and showed decreased binding of dermcidin to the bacterial surface, indicating that dermcidin interacts with membrane phospholipids. The mode of this interaction was direct, as shown by assays of dermcidin binding to phospholipid preparations, and specific, as the resistance to other AMPs was not affected. Our findings indicate that dermcidin has an exceptional value for the human innate host defense and lend support to the idea that it evolved to evade bacterial resistance mechanisms targeted at the cationic character of most AMPs. Moreover, they suggest that the antimicrobial activity of dermcidin is dependent on the interaction with the bacterial membrane and might thus assist with the determination of the yet unknown mode of action of this important human AMP.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19596877
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9983
      1. Author :
        Kuo, Chaincy; Coquoz, Olivier; Troy, Tamara L; Xu, Heng; Rice, Brad W
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Journal of biomedical optics
      6. Products :
      7. Volume :
        12
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Luminescent Proteins; Male; Mice; Microscopy, Fluorescence, Multiphoton; PC-3M-luc; Prostatic Neoplasms; Whole Body Imaging
      12. Abstract :
        A new method is described for obtaining a 3-D reconstruction of a bioluminescent light source distribution inside a living animal subject, from multispectral images of the surface light emission acquired on charge-coupled device (CCD) camera. The method uses the 3-D surface topography of the animal, which is obtained from a structured light illumination technique. The forward model of photon transport is based on the diffusion approximation in homogeneous tissue with a local planar boundary approximation for each mesh element, allowing rapid calculation of the forward Green's function kernel. Absorption and scattering properties of tissue are measured a priori as input to the algorithm. By using multispectral images, 3-D reconstructions of luminescent sources can be derived from images acquired from only a single view. As a demonstration, the reconstruction technique is applied to determine the location and brightness of a source embedded in a homogeneous phantom subject in the shape of a mouse. The technique is then evaluated with real mouse models in which calibrated sources are implanted at known locations within living tissue. Finally, reconstructions are demonstrated in a PC3M-luc (prostate tumor line) metastatic tumor model in nude mice.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17477722
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8968
      1. Author :
        Rice, B W; Cable, M D; Nelson, M B
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2001
      5. Publication :
        Journal of biomedical optics
      6. Products :
      7. Volume :
        6
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Diagnostic Imaging; Fluorescent Dyes; Green Fluorescent Proteins; Luciferases; Luminescent Measurements; Luminescent Proteins; Mice; Mice, Inbred BALB C; Neoplasms; PC-3M-luc; Pneumonia
      12. Abstract :
        In vivo imaging of cells tagged with light-emitting probes, such as firefly luciferase or fluorescent proteins, is a powerful technology that enables a wide range of biological studies in small research animals. Reporters with emission in the red to infrared (>600 nm) are preferred due to the low absorption in tissue at these wavelengths. Modeling of photon diffusion through tissue indicates that bioluminescent cell counts as low as a few hundred can be detected subcutaneously, while approximately 10(6) cells are required to detect signals at approximately 2 cm depth in tissue. Signal-to-noise estimates show that cooled back-thinned integrating charge coupled devices (CCDs) are preferred to image-intensified CCDs for this application, mainly due to their high quantum efficiency (approximately 85%) at wavelengths >600 nm where tissue absorption is low. Instrumentation for in vivo imaging developed at Xenogen is described and several examples of images of mice with bioluminescent cells are presented.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/11728202
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8984
      1. Author :
        Tanaka, M.; Mroz, P.; Dai, T.; Huang, L.; Morimoto, Y.; Kinoshita, M.; Yoshihara, Y.; Shinomiya, N.; Seki, S.; Nemoto, K.; Hamblin, M. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Photochem Photobiol
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen31, Xen 31, MRSA, S. aureus, IVIS, Bioluminescence
      12. Abstract :
        We previously reported that photodynamic therapy (PDT) using intra-articular methylene blue (MB) could be used to treat arthritis in mice caused by bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) either in a therapeutic or in a preventative mode. PDT accumulated neutrophils into the mouse knee via activation of chemoattractants such as inflammatory cytokines or chemokines. In the present study, we asked whether PDT combined with antibiotics used for MRSA could provide added benefit in controlling the infection. We compared MB-PDT alone, systemic administration of either linezolid (LZD) alone or vancomycin (VCM) alone or the combination of PDT with either LZD or VCM. Real-time non-invasive imaging was used to serially follow the progress of the infection. PDT alone was the most effective, while LZD alone was ineffective and VCM alone showed some benefit. Surprisingly the addition of LZD or VCM reduced the therapeutic effect of PDT alone (P<0.05). Considering that PDT in this mouse model stimulates neutrophils to be antibacterial rather than actively killing the bacteria, we propose that LZD and VCM might inhibit the activation of inflammatory cytokines without eradicating the bacteria, and thereby reduce the therapeutic effect of PDT. (c) 2013 Wiley Periodicals, Inc. Photochemistry and Photobiology (c) 2013 The American Society of Photobiology.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23311407
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10558
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Annals of the New York Academy of Sciences
      6. Products :
      7. Volume :
        1192
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Biofilms; Bioware; Bone Density Conservation Agents; Chronic Disease; Cytokines; Drug Evaluation, Preclinical; Humans; Immunity; Incidence; Jaw Diseases; Mice; Neovascularization, Physiologic; Osteoclasts; Osteomyelitis; Osteonecrosis; Staphylococcal Infections; Xen29
      12. Abstract :
        The effects of antiresorptive agents (e.g., alendronate [Aln], osteoprotegerin [OPG]) on bone infection are unknown. Thus, their effects on implant-associated osteomyelitis (OM) were investigated in mice using PBS (placebo), gentamycin, and etanercept (TNFR:Fc) controls. None of the drugs affected humoral immunity, angiogenesis, or chronic infection. However, the significant (P < 0.05 vs. PBS) inhibition of cortical osteolysis and decreased draining lymph node size in Aln- and OPG-treated mice was associated with a significant (P < 0.05) increase in the incidence of high-grade infections during the establishment of OM. In contrast, the high-grade infections in TNFR:Fc-treated mice were associated with immunosuppression, as evidenced by the absence of granulomas and presence of Gram(+) biofilm in the bone marrow. Collectively, these findings indicate that although antiresorptive agents do not exacerbate chronic OM, they can increase the bacterial load during early infection by decreasing lymphatic drainage and preventing the removal of necrotic bone that harbors the bacteria.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20392222
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9034
      1. Author :
        Burkatovskaya, Marina; Castano, Ana P; Demidova-Rice, Tatiana N; Tegos, George P; Hamblin, Michael R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair Society
      6. Products :
      7. Volume :
        16
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Infective Agents; Bandages; Biocompatible Materials; Bioware; Chitosan; Cyclophosphamide; Male; Mice; Mice, Inbred BALB C; Staphylococcal Skin Infections; Staphylococcus aureus; Wound Healing; Wound Infection; Xen8.1
      12. Abstract :
        HemCon bandage is an engineered chitosan acetate preparation designed as a hemostatic dressing, and is under investigation as a topical antimicrobial dressing. We studied its effects on healing of excisional wounds that were or were not infected with Staphylococcus aureus, in normal mice or mice previously pretreated with cyclophosphamide (CY). CY significantly suppressed wound healing in both the early and later stages, while S. aureus alone significantly stimulated wound healing in the early stages by preventing the initial wound expansion. CY plus S. aureus showed an advantage in early stages by preventing expansion, but a significant slowing of wound healing in later stages. In order to study the conflicting clamping and stimulating effects of chitosan acetate bandage on normal wounds, we removed the bandage from wounds at times after application ranging from 1 hour to 9 days. Three days application gave the earliest wound closure, and all application times gave a faster healing slope after removal compared with control wounds. Chitosan acetate bandage reduced the number of inflammatory cells in the wound at days 2 and 4, and had an overall beneficial effect on wound healing especially during the early period where its antimicrobial effect is most important.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18471261
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9986
      1. Author :
        Figg, William D; Li, Haiqing; Sissung, Tristan; Retter, Avi; Wu, Shenhong; Gulley, James L; Arlen, Phil; Wright, John J; Parnes, Howard; Fedenko, Kathy; Latham, Lea; Steinberg, Seth M; Jones, Elizabeth; Chen, Clara; Dahut, William
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        BJU international
      6. Products :
      7. Volume :
        99
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Aged; Androgens; Animals; Antineoplastic Combined Chemotherapy Protocols; Aryl Hydrocarbon Hydroxylases; Bioware; Cytochrome P-450 Enzyme System; Estramustine; Genotype; Humans; Male; Mice; Mice, Nude; Middle Aged; PC-3M-luc; Prostatic Neoplasms; Survival Analysis; Taxoids; Thalidomide; Treatment Outcome
      12. Abstract :
        OBJECTIVE To evaluate the combination of docetaxel plus estramustine (which prolongs survival in patients with androgen-independent prostate cancer, AIPC), and thalidomide (that also adds to docetaxel activity), both pre-clinically and clinically in AIPC. PATIENTS, MATERIALS AND METHODS In the pre-clinical evaluation we injected PC3 cells subcutaneously into severely combined immunodeficient mice and started treatment after the tumour volume reached 50 mm3. We also evaluated the combination using luciferase-labelled PC3M-luc-C6 cells in nude mice. We enrolled 20 patients with metastatic progressive AIPC into a phase II clinical trial to evaluate this combination. Docetaxel (30 mg/m2) was administered every week, for 3 of 4 weeks. The dose of thalidomide was 200 mg/day and estramustine was given three times a day at 1, 2, 3, 8, 9, 10, 15, 16 and 17 days. RESULTS In the mice, thalidomide with docetaxel plus estramustine reduced tumour volume by 88% at 17 days vs the control treatment (p=0.001). The combination of docetaxel, estramustine and thalidomide nearly eradicated the signal from the luciferase-expressing PC3M cells in the metastasis model. Clinically, the progression-free time was 7.2 months with this combination; 18 of 20 patients had a decline of half or more in prostate-specific antigen level and two of 10 patients with soft-tissue lesions had a partial response on computed tomography. There were 24 grade 3 and two grade 4 complications associated with this combination. There was a statistically significant association between overall survival and the CYP1B1*3 genotype (P=0.013). CONCLUSION Docetaxel-based chemotherapy is now regarded as a standard regimen for metastatic AIPC. The combination of estramustine, docetaxel and thalidomide is an advantageous treatment in pre-clinical models of prostate cancer and is a safe, tolerable and active regimen in patients with AIPC.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17437439
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8970
      1. Author :
        van Staden, A. D.; Brand, A. M.; Dicks, L. M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Appl Microbiol
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen36, Xen 36, Staphylococcus aureus Xen36, IVIS
      12. Abstract :
        Aims: To determine if nisin F-loaded self-setting brushite cement could control the growth of Staphylococcus aureus in vivo. Methods and Results: Brushite cement was prepared by mixing equimolar concentrations of beta-tricalcium phosphate and monocalcium phosphate monohydrate. Nisin F was added at 5.0%, 2.5% and 1.0% (w/w) and the cement moulded into cylinders. In vitro antibacterial activity was determined using a delayed agar diffusion assay. Release of nisin F from the cement was determined using BCA protein assays. Based on scanning electron microscopy and X-ray diffraction analysis, nisin F did not cause significant changes in cement structure or chemistry. Cement containing 5.0% (w/w) nisin F yielded the most promising in vitro results. Nisin F-loaded cement was implanted into a subcutaneous pocket on the back of mice and then infected with S. aureus Xen 36. Infection was monitored for 7 days, using an in vivo imaging system. Nisin F prevented S. aureus infection for 7 days and no viable cells were isolated from the implants. Conclusions: Nisin F-loaded brushite cement successfully prevented in vivo growth of S. aureus. Significance and Impact of the Study: Nisin F incorporated into bone cement may be used to control S. aureus infection in vivo. (c) 2012The Authors Journal of Applied Microbiology (c) 2012 The Society for Applied Microbiology.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22268790
      14. Call Number :
        PKI @ kd.modi @ 11
      15. Serial :
        10402
      1. Author :
        Balibar, Carl J; Shen, Xiaoyu; McGuire, Dorothy; Yu, Donghui; McKenney, David; Tao, Jianshi
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Microbiology (Reading, England)
      6. Products :
      7. Volume :
        156
      8. Issue :
        Pt 5
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Bacterial Proteins; Bacteriolysis; Bioware; Cell Wall; Gene Expression Profiling; Gene Knockout Techniques; Genes, Reporter; Lysostaphin; Mice; Microbial Sensitivity Tests; Sepsis; Staphylococcus aureus; Virulence; Xen29
      12. Abstract :
        Transcriptional profiling data accumulated in recent years for the clinically relevant pathogen Staphylococcus aureus have established a cell wall stress stimulon, which comprises a coordinately regulated set of genes that are upregulated in response to blockage of cell wall biogenesis. In particular, the expression of cwrA (SA2343, N315 notation), which encodes a putative 63 amino acid polypeptide of unknown biological function, increases over 100-fold in response to cell wall inhibition. Herein, we seek to understand the biological role that this gene plays in S. aureus. cwrA was found to be robustly induced by all cell wall-targeting antibiotics tested – vancomycin, oxacillin, penicillin G, phosphomycin, imipenem, hymeglusin and bacitracin – but not by antibiotics with other mechanisms of action, including ciprofloxacin, erythromycin, chloramphenicol, triclosan, rifampicin, novobiocin and carbonyl cyanide 3-chlorophenylhydrazone. Although a DeltacwrA S. aureus strain had no appreciable shift in MICs for cell wall-targeting antibiotics, the knockout was shown to have reduced cell wall integrity in a variety of other assays. Additionally, the gene was shown to be important for virulence in a mouse sepsis model of infection.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20167623
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9037
      1. Author :
        Fink, D.; Romanowski, K.; Valuckaite, V.; Babrowski, T.; Kim, M.; Matthews, J. B.; Liu, D.; Zaborina, O.; Alverdy, J. C.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Trauma
      6. Products :
      7. Volume :
        71
      8. Issue :
        N/A
      9. Page Numbers :
        1575-82
      10. Research Area :
        N/A
      11. Keywords :
        Xen41, Xen 41, Pseudomonas aeruginosa Xen41, IVIS
      12. Abstract :
        BACKGROUND: : Experimental models of intestinal ischemia-reperfusion (IIR) injury are invariably performed in mice harboring their normal commensal flora, even though multiple IIR events occur in humans during prolonged intensive care confinement when they are colonized by a highly pathogenic hospital flora. The aims of this study were to determine whether the presence of the human pathogen Pseudomonas aeruginosa in the distal intestine potentiates the lethality of mice exposed to IIR and to determine what role any in vivo virulence activation plays in the observed mortality. METHODS: : Seven- to 9-week-old C57/BL6 mice were exposed to 15 minutes of superior mesenteric artery occlusion (SMAO) followed by direct intestinal inoculation of 1.0 x 10 colony-forming unit of P. aeruginosa PAO1 into the ileum and observed for mortality. Reiterative studies were performed in separate groups of mice to evaluate both the migration/dissemination pattern and in vivo virulence activation of intestinally inoculated strains using live photon camera imaging of both a constitutive bioluminescent P. aeruginosa PAO1 derivative XEN41 and an inducible reporter derivative of PAO1, the PAO1/lecA:luxCDABE that conditionally expresses the quorum sensing-dependent epithelial disrupting virulence protein PA 1 Lectin (PA-IL). RESULTS: : Mice exposed to 15 minutes of SMAO and reperfusion with intestinal inoculation of P. aeruginosa had a significantly increased mortality rate (p < 0.001) of 100% compared with <10% for sham-operated mice intestinally inoculated with P. aeruginosa without SMAO and IIR alone (<50%). Migration/dissemination patterns of P. aeruginosa in mice subjected to IIR demonstrated proximal migration of distally injected strains and translocation to mesenteric lymph nodes, liver, spleen, lung, and kidney. A key role for in vivo virulence expression of the barrier disrupting adhesin PA-IL during IIR was established since its expression was enhanced during IR and mutant strains lacking PA-IL displayed attenuated mortality. CONCLUSIONS: : The presence of intestinal P. aeruginosa potentiates the lethal effect of IIR in mice in part due to in vivo virulence activation of its epithelial barrier disrupting protein PA-IL.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22002612
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10423
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