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      1. Author :
        Smith, B. R.; Kempen, P.; Bouley, D.; Xu, A.; Liu, Z.; Melosh, N.; Dai, H.; Sinclair, R.; Gambhir, S. S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nano Lett
      6. Products :
      7. Volume :
        12
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; *Disease Models, Animal; Ear Neoplasms/*blood supply/pathology; Humans; Mice; Microscopy, Fluorescence; Nanoparticles/*chemistry; *Nanotechnology; Nanotubes, Carbon/chemistry; Neoplasms, Experimental/*blood supply/pathology; Particle Size; Quantum Dots; Surface Properties
      12. Abstract :
        Delivery is one of the most critical obstacles confronting nanoparticle use in cancer diagnosis and therapy. For most oncological applications, nanoparticles must extravasate in order to reach tumor cells and perform their designated task. However, little understanding exists regarding the effect of nanoparticle shape on extravasation. Herein we use real-time intravital microscopic imaging to meticulously examine how two different nanoparticles behave across three different murine tumor models. The study quantitatively demonstrates that high-aspect ratio single-walled carbon nanotubes (SWNTs) display extravasational behavior surprisingly different from, and counterintuitive to, spherical nanoparticles although the nanoparticles have similar surface coatings, area, and charge. This work quantitatively indicates that nanoscale extravasational competence is highly dependent on nanoparticle geometry and is heterogeneous.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22650417
      14. Call Number :
        PKI @ kd.modi @ 9
      15. Serial :
        10439
      1. Author :
        Kirby, A. C.; Beattie, L.; Maroof, A.; Rooijen, N. van; Kaye, P. M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        American Journal of Pathology
      6. Products :
      7. Volume :
        175
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, Xen10
      12. Abstract :
        Marginal zone macrophages in the murine spleen play an important role in the capture of blood-borne pathogens and are viewed as an essential component of host defense against the development of pneumococcal sepsis. However, we and others have previously described the loss of marginal zone macrophages associated with the splenomegaly that follows a variety of viral and protozoal infections; this finding raises the question of whether these infected mice would become more susceptible to secondary pneumococcal infection. Contrary to expectations, we found that mice lacking marginal zone macrophages resulting from Leishmania donovani infection have increased resistance to Streptococcus pneumoniae type 3 and do not develop sepsis. Using biophotonic imaging, we observed that pneumococci are rapidly trapped in the spleens of L. donovani-infected mice. By selective depletion studies using clodronate liposomes, depleting monoclonal antibodies specific for Ly6C/G and Ly6G, and CD11c-DTR mice, we show that the enhanced early resistance in L. donovani-infected mice is entirely due to the activity of SIGNR1? red pulp macrophages. Our data demonstrate, therefore, that the normal requirement for SIGNR1+ marginal zone macrophages to protect against a primary pneumococcal infection can, under conditions of splenomegaly, be readily compensated for by activated red pulp macrophages.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19644016
      14. Call Number :
        139699
      15. Serial :
        7610
      1. Author :
        Marttila-Ichihara, Fumiko; Castermans, Karolien; Auvinen, Kaisa; Oude Egbrink, Mirjam G A; Jalkanen, Sirpa; Griffioen, Arjan W; Salmi, Marko
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Journal of immunology (Baltimore, Md.: 1950)
      6. Products :
      7. Volume :
        184
      8. Issue :
        6
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Adjuvants, Immunologic; Allylamine; Amine Oxidase (Copper-Containing); Animals; Antibodies, Blocking; Antibodies, Monoclonal; B16-F10-luc-G5 cells; Bioware; Cell Adhesion Molecules; Cell Line, Tumor; Cell Migration Inhibition; Enzyme Inhibitors; Female; Growth Inhibitors; Lymphoma, T-Cell; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Myeloid Cells; Semicarbazides
      12. Abstract :
        Vascular adhesion protein-1 (VAP-1) is an endothelial, cell surface-expressed oxidase involved in leukocyte traffic. The adhesive function of VAP-1 can be blocked by anti-VAP-1 Abs and small-molecule inhibitors. However, the effects of VAP-1 blockade on antitumor immunity and tumor progression are unknown. In this paper, we used anti-VAP-1 mAbs and small-molecule inhibitors of VAP-1 in B16 melanoma and EL-4 lymphoma tumor models in C57BL/6 mice. Leukocyte accumulation into tumors and neoangiogenesis were evaluated by immunohistochemistry, flow cytometry, and intravital videomicroscopy. We found that both anti-VAP-1 Abs and VAP-1 inhibitors reduced the number of leukocytes in the tumors, but they targeted partially different leukocyte subpopulations. Anti-VAP-1 Abs selectively inhibited infiltration of CD8-positive lymphocytes into tumors and had no effect on accumulation of myeloid cells into tumors. In contrast, the VAP-1 inhibitors significantly reduced only the number of proangiogenic Gr-1(+)CD11b(+) myeloid cells in melanomas and lymphomas. Blocking of VAP-1 by either means left tumor homing of regulatory T cells and type 2 immune-suppressing monocytes/macrophages intact. Notably, VAP-1 inhibitors, but not anti-VAP-1 Abs, retarded the growth of melanomas and lymphomas and reduced tumor neoangiogenesis. The VAP-1 inhibitors also reduced the binding of Gr-1(+) myeloid cells to the tumor vasculature. We conclude that tumors use the catalytic activity of VAP-1 to recruit myeloid cells into tumors and to support tumor progression. Small-molecule VAP-1 inhibitors therefore might be a potential new tool for immunotherapy of tumors.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20154208
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8996
      1. Author :
        Sharma, Prashant K; Engels, Eefje; Van Oeveren, Wim; Ploeg, Rutger J; van Henny der Mei, C; Busscher, Henk J; Van Dam, Gooitzen M; Rakhorst, Gerhard
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Surgery
      6. Products :
      7. Volume :
        147
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bacteroides fragilis; Diagnostic Imaging; Disease Progression; Escherichia coli; Luciferases, Bacterial; Luminescent Agents; Male; Peritoneal Lavage; Peritonitis; Rats; Rats, Wistar; Xen14
      12. Abstract :
        BACKGROUND Bacterial peritonitis is a life-threatening abdominal infection associated with high morbidity and mortality. The rat is a popular animal model for studying peritonitis and its treatment, but longitudinal monitoring of the progression of peritonitis in live animals has been impossible until now and thus required a large number of animals. Our objective was to develop a noninvasive in vivo imaging technique to monitor the spatiotemporal spread of bacterial peritonitis. METHODS Peritonitis was induced in 8 immunocompetent male Wistar rats by placing fibrin clots containing 5x10(8) cells of both Bacteroides fragilis (American Type Tissue Culture [ATCC)] 25,285 and bioluminescent Escherichia coli Xen14. After 1 or 2 days, infected clots were removed and open abdomen lavage was performed. In vivo bioluminescent imaging was used to monitor the spread of peritonitis. RESULTS Bioluminescent in vivo imaging showed an increase in the area of spread, and the number of E. coli tripled into the rat's abdominal cavity on day 1 after clot insertion; however, on day 2, encapsulation of the clot confined bacterial spread. Bioluminescent E. coli respread over the peritoneal cavity after lavage; within 10 days, however, in vivo imaging showed a decrease of 3-4 orders of magnitude in bacterial load. CONCLUSION Bioluminescent in vivo imaging can be effectively used to monitor the spatiotemporal behavior of the peritonitis during 3 different stages of the disease process: initiation, treatment, and follow-up. Imaging allows researchers to repeatedly image the same animal, thereby reducing variability and providing greater confidence in determining treatment efficacies for therapeutic interventions using a small number of animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19733882
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        10005
      1. Author :
        Sharma, P. K.; Engels, E.; Van Oeveren, W.; Ploeg, R. J.; van Henny der Mei, C.; Busscher, H. J.; Van Dam, G. M.; Rakhorst, G.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Surgery
      6. Products :
      7. Volume :
        147
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen14, Xen 14, E. coli Xen14, IVIS, Animals; Bacteroides fragilis/*isolation & purification; Diagnostic Imaging/methods; Disease Progression; Escherichia coli/*isolation & purification; Luciferases, Bacterial/*diagnostic use; Luminescent Agents/*diagnostic use; Male; Peritoneal Lavage; Peritonitis/*microbiology/pathology/therapy; Rats; Rats, Wistar
      12. Abstract :
        BACKGROUND: Bacterial peritonitis is a life-threatening abdominal infection associated with high morbidity and mortality. The rat is a popular animal model for studying peritonitis and its treatment, but longitudinal monitoring of the progression of peritonitis in live animals has been impossible until now and thus required a large number of animals. Our objective was to develop a noninvasive in vivo imaging technique to monitor the spatiotemporal spread of bacterial peritonitis. METHODS: Peritonitis was induced in 8 immunocompetent male Wistar rats by placing fibrin clots containing 5x10(8) cells of both Bacteroides fragilis (American Type Tissue Culture [ATCC)] 25,285 and bioluminescent Escherichia coli Xen14. After 1 or 2 days, infected clots were removed and open abdomen lavage was performed. In vivo bioluminescent imaging was used to monitor the spread of peritonitis. RESULTS: Bioluminescent in vivo imaging showed an increase in the area of spread, and the number of E. coli tripled into the rat's abdominal cavity on day 1 after clot insertion; however, on day 2, encapsulation of the clot confined bacterial spread. Bioluminescent E. coli respread over the peritoneal cavity after lavage; within 10 days, however, in vivo imaging showed a decrease of 3-4 orders of magnitude in bacterial load. CONCLUSION: Bioluminescent in vivo imaging can be effectively used to monitor the spatiotemporal behavior of the peritonitis during 3 different stages of the disease process: initiation, treatment, and follow-up. Imaging allows researchers to repeatedly image the same animal, thereby reducing variability and providing greater confidence in determining treatment efficacies for therapeutic interventions using a small number of animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19733882
      14. Call Number :
        PKI @ kd.modi @ 7
      15. Serial :
        10396
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        International Journal of Cardiovascular Imaging
      6. Products :
      7. Volume :
        26
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        Cardiovascular disease; Atherosclerosis; Vulnerable plaque; Spectroscopy; Intravascular; in vivo imaging; MMPSense
      12. Abstract :
        Many apparent healthy persons die from cardiovascular disease, despite major advances in prevention and treatment of cardiovascular disease. Traditional cardiovascular risk factors are able to predict cardiovascular events in the long run, but fail to assess current disease activity or nearby cardiovascular events. There is a clear relation between the occurrence of cardiovascular events and the presence of so-called vulnerable plaques. These vulnerable plaques are characterized by active inflammation, a thin cap and a large lipid pool. Spectroscopy is an optical imaging technique which depicts the interaction between light and tissues, and thereby shows the biochemical composition of tissues. In recent years, impressive advances have been made in spectroscopy technology and intravascular spectroscopy is able to assess the composition of plaques of interest and thereby to identify and actually quantify plaque vulnerability. This review summarizes the current evidence for spectroscopy as a measure of plaque vulnerability and discusses the potential role of intravascular spectroscopic imaging techniques.
      13. URL :
        http://www.springerlink.com/content/kx38073782g98666/
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4552
      1. Author :
        Strasky, Zbynek; Zemankova, Lenka; Nemeckova, Ivana; Rathouska, Jana; Wong, Ronald J; Muchova, Lucie; Subhanova, Iva; Vanikova, Jana; Vanova, Katerina; Vitek, Libor
      2. Title :
        Spirulina platensis and phycocyanobilin activate atheroprotective heme oxygenase-1: A possible implication for atherogenesis
      3. Type :
        Journal Article
      4. Year :
        2013
      5. Publication :
        Food Funct.
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS Imaging
      12. Abstract :
        Spirulina platensis, a water blue-green alga, has been associated with potent biological effects, which might have important relevance in atheroprotection. We investigated whether S. platensis or phycocyanobilin (PCB), its tetrapyrrolic chromophore, can activate atheroprotective heme oxygenase-1 (Hmox1), a key enzyme in the heme catabolic pathway responsible for generation of a potent antioxidant bilirubin, in endothelial cells and in a mouse model of atherosclerosis. In vitro experiments were performed on EA.hy926 endothelial cells exposed to extracts of S. platensis or PCB. In vivo studies were performed on ApoE-deficient mice fed a cholesterol diet and S. platensis. The effect of these treatments on Hmox1, as well as other markers of oxidative stress and endothelial dysfunction, was then investigated. Both S. platensis and PCB markedly upregulated Hmox1 in vitro, and a substantial overexpression of Hmox1 was found in aortic atherosclerotic lesions of ApoE-deficient mice fed S. platensis. In addition, S. platensis treatment led to a significant increase in Hmox1 promoter activity in the spleens of Hmox-luc transgenic mice. Furthermore, both S. platensis and PCB were able to modulate important markers of oxidative stress and endothelial dysfunction, such as eNOS, p22 NADPH oxidase subunit, and/or VCAM-1. Both S. platensis and PCB activate atheroprotective HMOX1 in endothelial cells and S. platensis increased the expression of Hmox1 in aortic atherosclerotic lesions in ApoE-deficient mice, and also in Hmox-luc transgenic mice beyond the lipid lowering effect. Therefore, activation of HMOX1 and the heme catabolic pathway may represent an important mechanism of this food supplement for the reduction of atherosclerotic disease.
      13. URL :
        N/A
      14. Call Number :
        PKI @ catherine.lautenschlager @ 6049
      15. Serial :
        14630
      1. Author :
        Thurlow, L. R.; Hanke, M. L.; Fritz, T.; Angle, A.; Aldrich, A.; Williams, S. H.; Engebretsen, I. L.; Bayles, K. W.; Horswill, A. R.; Kielian, T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Immunol
      6. Products :
      7. Volume :
        186
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29, Animals; *Biofilms; Catheter-Related Infections/immunology/metabolism/microbiology; Cytokines/immunology/metabolism; Green Fluorescent Proteins/genetics/metabolism; Host-Pathogen Interactions/immunology; Immune Evasion/immunology; Inflammation/*immunology/metabolism; Macrophages/*immunology/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Confocal; Microscopy, Electron, Scanning; Models, Immunological; Phagocytosis/*immunology; Staphylococcal Infections/*immunology/metabolism/microbiology; Staphylococcus aureus/*immunology/physiology/ultrastructure; Toll-Like Receptor 2/genetics/immunology; Toll-Like Receptor 9/genetics/immunology
      12. Abstract :
        Biofilms are complex communities of bacteria encased in a matrix composed primarily of polysaccharides, extracellular DNA, and protein. Staphylococcus aureus can form biofilm infections, which are often debilitating due to their chronicity and recalcitrance to antibiotic therapy. Currently, the immune mechanisms elicited during biofilm growth and their impact on bacterial clearance remain to be defined. We used a mouse model of catheter-associated biofilm infection to assess the functional importance of TLR2 and TLR9 in the host immune response during biofilm formation, because ligands for both receptors are present within the biofilm. Interestingly, neither TLR2 nor TLR9 impacted bacterial density or inflammatory mediator secretion during biofilm growth in vivo, suggesting that S. aureus biofilms circumvent these traditional bacterial recognition pathways. Several potential mechanisms were identified to account for biofilm evasion of innate immunity, including significant reductions in IL-1beta, TNF-alpha, CXCL2, and CCL2 expression during biofilm infection compared with the wound healing response elicited by sterile catheters, limited macrophage invasion into biofilms in vivo, and a skewing of the immune response away from a microbicidal phenotype as evidenced by decreases in inducible NO synthase expression concomitant with robust arginase-1 induction. Coculture studies of macrophages with S. aureus biofilms in vitro revealed that macrophages successful at biofilm invasion displayed limited phagocytosis and gene expression patterns reminiscent of alternatively activated M2 macrophages. Collectively, these findings demonstrate that S. aureus biofilms are capable of attenuating traditional host proinflammatory responses, which may explain why biofilm infections persist in an immunocompetent host.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21525381
      14. Call Number :
        PKI @ kd.modi @ 19
      15. Serial :
        10457
      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
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