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      1. Author :
        Tsunooka, N.; Hirayama, S.; Medin, J. A.; Liles, W. C.; Keshavjee, S.; Waddell, T. K.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Ann Thorac Surg
      6. Products :
      7. Volume :
        91
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29, Animals; Disease Models, Animal; Female; Mice; Mice, Inbred C57BL; Pneumonectomy/*adverse effects; Postoperative Complications/*surgery; Stem Cell Transplantation/*methods; Thoracic Cavity/*surgery; Thoracoplasty/*methods; Tissue Engineering/*methods
      12. Abstract :
        BACKGROUND: Transfer of viable tissue flaps and thoracoplasty are effective against pleural space complications after pneumonectomy but highly disfiguring. The aim of this study was to explore the possibility of engineered tissue to treat space complications after pneumonectomy. METHODS: A left pneumonectomy was performed in mice, and the cavity immediately filled with the cellularized collagen matrices. First, bone marrow derived-mesenchymal stroma cells with luciferase expression were used as donor cells to evaluate cell viability and angiogenesis using bioluminescence imaging. Second, using bone marrow cells from GFP mice, histologic evaluation, immunohistochemistry for von Willebrand Factor, and flow cytometric analysis was performed compared with acellular matrix implants. The effect on bacterial clearance was examined using an empyema model with Staphylococcus aureus expressing luciferase. RESULTS: Embedded cells proliferated within the denatured collagen matrices ex vivo. In vivo, bioluminescent imaging activity could be detected till day 8, and the slope (suggesting rate of perfusion with luciferin) increased with time up to day 6 but decreased after day 7. Although GFP-positive donor cells decreased with time, total cellularity increased. Furthermore, vessels stained by von Willebrand factor were significantly increased. Both cellularized and acellularized matrices showed bacterial clearance in vivo. CONCLUSIONS: Cells within collagen matrices survive in the thoracic cavity at early time points. Cellularized matrices quickly lead to neovascularization and recipient cell infiltration. Both cellularized and acellularized matrices show bacterial clearance in vivo. This study indicates the potential feasibility of a novel tissue engineering approach to problems of the postpneumonectomy space.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21353020
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10458
      1. Author :
        Ryan, P. L.; Christiansen, D. L.; Hopper, R. M.; Walters, F. K.; Moulton, K.; Curbelo, J.; Greene, J. M.; Willard, S. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        J Anim Sci
      6. Products :
      7. Volume :
        89
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen14, Xen 14, E. coli Xen14, IVIS, Horse, bioluminescence
      12. Abstract :
        Uterine and placental infections are the leading cause of abortion, stillbirth, and preterm delivery in the mare. Whereas uterine and placental infections in women have been studied extensively, a comprehensive examination of the pathogenic processes leading to this unsatisfactory pregnancy outcome in the mare has yet to be completed. Most information in the literature relating to late-term pregnancy loss in mares is based on retrospective studies of clinical cases submitted for necropsy. Here we report the development and application of a novel approach, whereby transgenically modified bacteria transformed with lux genes of Xenorhabdus luminescens or Photorhabdus luminescens origin and biophotonic imaging are utilized to better understand pathogen-induced preterm birth in late-term pregnant mares. This technology uses highly sensitive bioluminescence imaging camera systems to localize and monitor pathogen progression during tissue invasion by measuring the bioluminescent signatures emitted by the lux-modified pathogens. This method has an important advantage in that it allows for the potential tracking of pathogens in vivo in real time and over time, which was hitherto impossible. Although the application of this technology in domestic animals is in its infancy, investigators were successful in identifying the fetal lungs, sinuses, nares, urinary, and gastrointestinal systems as primary tissues for pathogen invasion after experimental infection of pregnant mares with lux-modified Escherichia coli. It is important that pathogens were not detected in other vital organs, such as the liver, brain, and cardiac system. Such precision in localizing sites of pathogen invasion provides potential application for this novel approach in the development of more targeted therapeutic interventions for pathogen-related diseases in the equine and other domestic species.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21239661
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10395
      1. Author :
        Engelsman, Anton F; van der Mei, Henny C; Francis, Kevin P; Busscher, Henk J; Ploeg, Rutger J; van Dam, Gooitzen M
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Journal of biomedical materials research. Part B, Applied biomaterials
      6. Products :
      7. Volume :
        88
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Infective Agents; Bacterial Adhesion; Biofilms; Bioware; Chromosomes, Bacterial; Colony Count, Microbial; Disease Models, Animal; Female; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Prostheses and Implants; pXen-5; Soft Tissue Infections; Staphylococcal Infections; Staphylococcus aureus; Xen29
      12. Abstract :
        Infection is the main cause of biomaterials-related failure. A simple technique to test in-vivo new antimicrobial and/or nonadhesive implant coatings is unavailable. Current in vitro methods for studying bacterial adhesion and growth on biomaterial surfaces lack the influence of the host immune system. Most in vivo methods to study biomaterials-related infections routinely involve implant-removal, preventing comprehensive longitudinal monitoring. In vivo imaging circumvents these drawbacks and is based on the use of noninvasive optical imaging of bioluminescent bacteria. Staphylococcus aureus Xen29 is genetically modified to be stably bioluminescent, by the introduction of a modified full lux operon onto its chromosome. Surgical meshes with adhering S. aureus Xen29 were implanted in mice and bacterial growth and spread into the surrounding tissue was monitored longitudinally from bioluminescence with a highly sensitive CCD camera. Distinct spatiotemporal bioluminescence patterns, extending beyond the mesh area into surrounding tissues were observed. After 10 days, the number of living organisms isolated from explanted meshes was found to correlate with bioluminescence prior to sacrifice of the animals. Therefore, it is concluded that in vivo imaging using bioluminescent bacteria is ideally suited to study antimicrobial coatings taking into account the host immune system. In addition, longitudinal monitoring of infection in one animal will significantly reduce the number of experiments and animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18618733
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9020
      1. Author :
        Engelsman, A. F.; Mei, H. C. van der; Francis, K. P.; Busscher, H. J.; Ploeg, R. J.; Dam, G. M. van
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        J Biomed Mater Res B Appl Biomater
      6. Products :
      7. Volume :
        88
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Bioware; IVIS, Xenogen; Xen29
      12. Abstract :
        Infection is the main cause of biomaterials-related failure. A simple technique to test in-vivo new antimicrobial and/or nonadhesive implant coatings is unavailable. Current in vitro methods for studying bacterial adhesion and growth on biomaterial surfaces lack the influence of the host immune system. Most in vivo methods to study biomaterials-related infections routinely involve implant-removal, preventing comprehensive longitudinal monitoring. In vivo imaging circumvents these drawbacks and is based on the use of noninvasive optical imaging of bioluminescent bacteria. Staphylococcus aureus Xen29 is genetically modified to be stably bioluminescent, by the introduction of a modified full lux operon onto its chromosome. Surgical meshes with adhering S. aureus Xen29 were implanted in mice and bacterial growth and spread into the surrounding tissue was monitored longitudinally from bioluminescence with a highly sensitive CCD camera. Distinct spatiotemporal bioluminescence patterns, extending beyond the mesh area into surrounding tissues were observed. After 10 days, the number of living organisms isolated from explanted meshes was found to correlate with bioluminescence prior to sacrifice of the animals. Therefore, it is concluded that in vivo imaging using bioluminescent bacteria is ideally suited to study antimicrobial coatings taking into account the host immune system. In addition, longitudinal monitoring of infection in one animal will significantly reduce the number of experiments and animals.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18618733
      14. Call Number :
        137698
      15. Serial :
        7462
      1. Author :
        Akudugu, J. M.; Azzam, E. I.; Howell, R. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Int J Radiat Biol
      6. Products :
      7. Volume :
        88
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-D3H1, MDA-MB-231-luc-D3H1, IVIS, Bioware, Breast Cancer
      12. Abstract :
        Abstract Purpose: This study uses a three-dimensional cell culture model to investigate lethal bystander effects in human breast cancer cell cultures (MCF-7, MDA-MB-231) treated with (125)I-labeled 5-iodo-2 -deoxyuridine ((125)IdU). These breast cancer cell lines respectively form metastatic xenografts in nude mice in an estrogen-dependent and independent manner. Materials and methods: In the present study, these cells were cultured in loosely-packed three-dimensional architecture in a Cytomatrix carbon scaffold. Cultures were pulse-labeled for 3 h with (125)IdU to selectively irradiate a minor fraction of cells, and simultaneously co-pulse-labeled with 0.04 mM 5-ethynyl-2'-deoxyuridine (EdU) to identify the radiolabeled cells using Click-iT((R)) EdU and flow cytometry. The cultures were then washed and incubated for 48 h. The cells were then harvested, serially diluted, and seeded for colony formation. Aliquots of cells were subjected to flow cytometry to determine the percentage of cells labeled with (125)IdU/EdU. Additional aliquots were used to determine the mean (125)I activity per labeled cell. The percentage of labeled cells was about 15% and 10% for MCF-7 and MDA cells, respectively. This created irradiation conditions wherein the cross-dose to unlabeled cells was small relative to the self-dose to labeled cells. The surviving fraction relative to EdU-treated controls was measured. Results: Survival curves indicated significant lethal bystander effect in MCF-7 cells, however, no significant lethal bystander effect was observed in MDA-MB-231 cells. Conclusions: These studies demonstrate the capacity of (125)IdU to induce lethal bystander effects in human breast cancer cells and suggest that the response depends on phenotype.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22489958
      14. Call Number :
        PKI @ kd.modi @ 6
      15. Serial :
        10514
      1. Author :
        Rosenzweig HL, Jann MM, Glant TT, Martin TM, Planck SR, van Eden W, van Kooten PJ, Flavell RA, Kobayashi KS, Rosenbaum JT and Davey MP
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Journal of Leukocyte Biology
      6. Products :
      7. Volume :
        85
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        Physiology
      11. Keywords :
        ProSense; in vivo imaging; NOD2; mice; inflammatory arthritis; TCR transgenic; knockout
      12. Abstract :
        In addition to its role in innate immunity, nucleotide oligomerization domain 2 (NOD2) has been shown to play a suppressive role in models of colitis. Notably, mutations in NOD2 cause the inherited granulomatous disease of the joints called Blau syndrome, thereby linking NOD2 with joint disease as well. However, the role of NOD2 in joint inflammation has not been clarified. We demonstrate here that NOD2 is functional within the mouse joint and promotes inflammation, as locally or systemically administered muramyl dipeptide (MDP; the NOD2 agonist) resulted in significant joint inflammation that was abolished in NOD2-deficient mice. We then sought to investigate the role of NOD2 in a mouse model of inflammatory arthritis dependent on adaptive immunity using TCR-transgenic mice whose T cells recognized the dominant epitope of proteoglycan (PG). Mice immunized with PG in the presence of MDP developed a more severe inflammatory arthritis and histopathology within the joints. Antigen-specific activation of splenocytes was enhanced by MDP with respect to IFN-gamma production, which would be consistent with the Th1-mediated disease in vivo. Intriguingly, NOD2 deficiency did not alter the PG-induced arthritis, indicating that NOD2 does not play an essential role in this model of joint disease when it is not activated by MDP. In conclusion, we demonstrate that in a model of inflammatory arthritis dependent on T and B cell priming, NOD2 activation potentiates disease. However, the absence of NOD2 does not alter the course of inflammatory arthritis, in contrast to models of intestinal inflammation.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718807/?tool=pubmed
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4535
      1. Author :
        Vintonenko, N.; Jais, J. P.; Kassis, N.; Abdelkarim, M.; Perret, G. Y.; Lecouvey, M.; Crepin, M.; Di Benedetto, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Mol Pharmacol
      6. Products :
      7. Volume :
        82
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-luc-D3H2Ln, D3H2Ln, IVIS, Breast cancer, Bioware
      12. Abstract :
        Statins and bisphosphonates are two distinct classes of isoprenoid pathway inhibitors targeting downstream enzyme to HMG-CoA reductase (upstream enzyme) and farnesyl-pyrophosphate synthase, respectively. Here, we studied fluvastatin (Fluva) and zoledronate (Zol), representative molecules of each class, respectively. In vivo metastatic potentials of both molecules were assessed. For the first time, we observed a significant reduction in progression of established metastases with Fluva treatment. Treatment with both Zol at 100 mug/kg and Fluva at 15 mg/kg inhibited 80% of the metastasis bioluminescence signal and increased survival of mice. The Zol and Fluva transcriptomic profiles of treated MDA-MB-231 cells revealed analogous patterns of affected genes, but each of them reached with different kinetics. The observable changes in gene expression started after 24 h for Fluva IC(50 72 h) and only after 48 h for Zol IC(50 72 h). To obtain early changes in gene expression of Zol-treated cells, a 3 times higher dose of Zol IC(50 72 h) had to be applied. Combining Fluva and Zol in vivo showed no synergy, but a benefit of several days in survival of mice. This study demonstrated that Zol or Fluva is of potential clinical use for the treatment of established metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22723339
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10509
      1. Author :
        Griffin, A. J.; Li, L. X.; Voedisch, S.; Pabst, O.; McSorley, S. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Infect Immun
      6. Products :
      7. Volume :
        79
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen26, Xen 26, Salmonella typhumurium, Animals; Anti-Bacterial Agents/therapeutic use; Cell Separation; Disease Models, Animal; Flow Cytometry; Fluoroquinolones/therapeutic use; Intestine, Small/microbiology; Lymph Nodes/*microbiology; Mesentery/immunology/microbiology; Mice; Mice, Inbred C57BL; Monocytes/immunology/*microbiology; Recurrence; Salmonella Infections, Animal/immunology/*microbiology/pathology; Salmonella typhi/immunology
      12. Abstract :
        Enteric pathogens can cause relapsing infections in a proportion of treated patients, but greater understanding of this phenomenon is hindered by the lack of appropriate animal models. We report here a robust animal model of relapsing primary typhoid that initiates after apparently successful antibiotic treatment of susceptible mice. Four days of enrofloxacin treatment were sufficient to reduce bacterial loads below detectable levels in all major organs, and mice appeared otherwise healthy. However, any interruption of further antibiotic therapy allowed renewed fecal shedding and renewed bacterial growth in systemic tissues to occur, and mice eventually succumbed to relapsing infection. In vivo imaging of luminescent Salmonella identified the mesenteric lymph nodes (MLNs) as a major reservoir of relapsing infection. A magnetic-bead enrichment strategy isolated MLN-resident CD11b(+) Gr-1(-) monocytes associated with low numbers of persistent Salmonella. However, the removal of MLNs increased the severity of typhoid relapse, demonstrating that this organ serves as a protective filter to restrain the dissemination of bacteria during antibiotic therapy. Together, these data describe a robust animal model of typhoid relapse and identify an important intestinal phagocyte subset involved in protection against the systemic spread of enteric infection.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21263018
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10559
      1. Author :
        Daugimont, L.; Vandermeulen, G.; Defresne, F.; Bouzin, C.; Mir, L. M.; Bouquet, C.; Feron, O.; Preat, V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Eur J Pharm Biopharm
      6. Products :
      7. Volume :
        78
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        B16-F10-luc-G5, B16F10-luc-G5, B16-F10-luc, B16F10-luc, IVIS
      12. Abstract :
        BACKGROUND: Despite the discovery of novel inhibitors of tumor angiogenesis, protein-based antiangiogenic cancer therapy suffers some limitations that antiangiogenic gene therapy could overcome. We investigated whether intra-tumoral electrotransfer of three angiogenic plasmids could inhibit tumor growth and metastasis. METHODS: Plasmids encoding recombinant disintegrin domain of ADAM-15 (RDD), thrombospondin 1 (TSP-1), and the soluble isoform of the VEGF receptor 1 (sFlt-1) were injected into B16F10 melanoma-bearing C57BL/6 mice followed by electroporation. Tumor volume was measured daily using a digital caliper. Metastasis was monitored by in vivo bioluminescence after surgical removal of the primary luciferase-encoding B16F10 tumor 5 days after intra-tumoral electrotransfer. Markers of vascularization and cell proliferation were quantified by immunohistochemistry. RESULTS: Intra-tumoral electrotransfer of the antiangiogenic plasmids induced a significant inhibition of tumor growth, doubling of mean survival time and long-term survivors ( approximately 40% vs 0% in control). When the tumor was removed by surgery after intra-tumoral plasmid electrotransfer, a significant decrease in tumor metastasis was observed leading to long-term tumor-free survival especially after treatment with pRDD plasmid (84% vs 0% in control). Unlike pTSP-1 and psFlt-1, pRDD significantly decreased cell proliferation in B16F10 primary tumors which express alphavbeta3 and alpha5beta1 integrins. No effect of antiangiogenic plasmid electrotransfer on normal skin blood flow was detected. CONCLUSION: The intra-tumoral electrotransfer of the three antiangiogenic plasmids is a promising method for the treatment of melanoma. The plasmid encoding RDD seems to be particularly effective due to its direct antitumoral activity combined with angiogenesis suppression, and its marked inhibition of metastasis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21316447
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10353
      1. Author :
        Penna, F. J.; Freilich, D. A.; Alvarenga, C.; Nguyen, H. T.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Urology
      6. Products :
      7. Volume :
        78
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, Animals; Fluorescence; Fluorescent Dyes/*diagnostic use; Guinea Pigs; Lymph Node Excision/*methods; Male; Models, Animal; *Molecular Imaging; Retroperitoneal Space
      12. Abstract :
        OBJECTIVES: To propose that fluorescent molecular imaging has utility in specifically identifying the lymph nodes, thereby enabling more definitive lymph node visualization and dissection. Retroperitoneal lymph node dissection (RPLND) is an invasive procedure with significant morbidity. A minimally invasive approach would be of great clinical benefit but has been limited by the extensive perivascular dissection required to remove all lymphatic tissue. Directed lymph node visualization would allow a limited dissection, making a laparoscopic approach more feasible. METHODS: Ten male Hartley guinea pigs underwent nonsurvival RPLND, 5 with the protease activatable in vivo fluorescent molecular imaging agent, ProSense and 5 without image guidance (control). ProSense was administered 24 hours before surgery and detected 24 hours later using a photodynamic detector. In group 1, RPLND was first performed without molecular imaging followed by image-guided lymph node dissection for residual nodes. In group 2, the near infrared detector was used initially for lymph node excision followed by traditionally unassisted extraction of the residual lymph nodes. The lymph nodes were extracted, counted, and sent for histopathologic analysis. RESULTS: With the assistance of molecular imaging, no additional lymph nodes were identified after complete dissection, and all tissue identified by ProSense was confirmed by histopathologic analysis to be lymph nodes. Without molecular imaging, all lymph nodes were not identified, and in 2 instances, the tissue was incorrectly thought to be lymphatic tissue. CONCLUSIONS: Molecular image-guided RPLND is a promising technique to improve in vivo, live visualization and dissection of lymph nodes and has the potential for application in improving the diagnosis and treatment of other urologic malignancies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21601249
      14. Call Number :
        PKI @ kd.modi @ 13
      15. Serial :
        10474
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