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      1. Author :
        Matsumoto, K.; Azami, T.; Otsu, A.; Takase, H.; Ishitobi, H.; Tanaka, J.; Miwa, Y.; Takahashi, S.; Ema, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Genesis
      6. Products :
      7. Volume :
        50
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense, Animals; Blood Vessels/embryology/*physiology; Chromosomes, Artificial, Bacterial; Embryo, Mammalian; Endothelial Cells/cytology/metabolism; Endothelium, Vascular/cytology/embryology/metabolism; Female; Founder Effect; Gene Expression Regulation, Developmental; Genes, Reporter; Mice; *Mice, Transgenic; Microscopy, Fluorescence; Morphogenesis/physiology; *Neovascularization, Pathologic; *Neovascularization, Physiologic; Retina/embryology/*physiology; Vascular Endothelial Growth Factor A/genetics/metabolism; Vascular Endothelial Growth Factor Receptor-1/genetics/*metabolism; Vascular Endothelial Growth Factor Receptor-2/genetics/metabolism
      12. Abstract :
        Blood vessel development and network patterning are controlled by several signaling molecules, including VEGF, FGF, TGF-ss, and Ang-1,2. Among these, the role of VEGF-A signaling in vessel morphogenesis is best understood. The biological activity of VEGF-A depends on its reaction with specific receptors Flt1 and Flk1. Roles of VEGF-A signaling in endothelial cell proliferation, migration, survival, vascular permeability, and induction of tip cell filopodia have been reported. In this study, we have generated Flt1-tdsRed BAC transgenic (Tg) mice to monitor Flt1 gene expression during vascular development. We show that tdsRed fluorescence is observed within blood vessels of adult mice and embryos, indicative of retinal angiogenesis and tumor angiogenesis. Flt1 expression recapitulated by Flt1-tdsRed BAC Tg mice overlapped well with Flk1, while Flt1 was expressed more abundantly in endothelial cells of large blood vessels such as dorsal aorta and presumptive stalk cells in retina, providing a unique model to study blood vessel development.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22489010
      14. Call Number :
        PKI @ kd.modi @ 10
      15. Serial :
        10437
      1. Author :
        Rahul Anil Sheth; Rabi Upadhyay; Lars Stangenberg; Rucha Sheth; Ralph Weissleder; Umar Mahmood
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Gynecologic Oncology
      6. Products :
      7. Volume :
        112
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        Ovarian cancer; Molecular imaging; Intraoperative imaging; Fluorescence imaging
      12. Abstract :
        OBJECTIVES: Cytoreductive surgery is a cornerstone of therapy in metastatic ovarian cancer. While conventional white light (WL) inspection detects many obvious tumor foci, careful histologic comparison has shown considerable miss rates for smaller foci. The goal of this study was to compare tumor detection using WL versus near infrared (NIR) imaging with a protease activatable probe, as well as to evaluate the ability to quantify NIR fluorescence using a novel quantitative optical imaging system.

        METHODS: A murine model for peritoneal carcinomatosis was generated and metastatic foci were imaged using WL and NIR imaging following the i.v. administration of the protease activatable probe ProSense750. The presence of tumor was confirmed by histology. Additionally, the ability to account for variations in fluorescence signal intensity due to changes in distance between the catheter and target lesion during laparoscopic procedures was evaluated.

        RESULTS: NIR imaging with a ProSense750 significantly improved upon the target-to-background ratios (TBRs) of tumor foci in comparison to WL imaging (minimum improvement was approximately 3.5 fold). Based on 52 histologically validated samples, the sensitivity for WL imaging was 69%, while the sensitivity for NIR imaging was 100%. The effects of intraoperative distance changes upon fluorescence intensity were corrected in realtime, resulting in a decrease from 89% to 5% in signal variance during fluorescence laparoscopy.

        CONCLUSIONS: With its molecular specificity, low background autofluorescence, high TBRs, and quantitative signal, optical imaging with NIR protease activatable probes greatly improves upon the intraoperative detection of ovarian cancer metastases.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19135233?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4497
      1. Author :
        Keereweer, S.; Sterenborg, H. J.; Kerrebijn, J. D.; Van Driel, P. B.; de Jong, R. J.; Lowik, C. W.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Head Neck
      6. Products :
      7. Volume :
        34
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IntegriSense
      12. Abstract :
        A key aspect for the postoperative prognosis of patients with head and neck cancer is complete tumor resection. In current practice, the intraoperative assessment of the tumor-free margin is dependent on visual appearance and palpation of the tumor. Optical imaging has the potential of traversing the gap between radiology and surgery by providing real-time visualization of the tumor, thereby allowing for image-guided surgery. The use of the near-infrared light spectrum offers 2 essential advantages: increased tissue penetration of light and an increased signal-to-background ratio of contrast agents. In this review, the current practice and limitations of image-guided surgery by optical imaging using intrinsic fluorescence or contrast agents are described. Furthermore, we provide an overview of the various molecular contrast agents targeting specific hallmarks of cancer that have been used in other fields of oncologic surgery, and we describe perspectives on its future use in head and neck cancer surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21284051
      14. Call Number :
        PKI @ kd.modi @ 31
      15. Serial :
        10369
      1. Author :
        Swirski, F. K.; Nahrendorf, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Immunol Cell Biol
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense
      12. Abstract :
        Macrophages are central regulators of disease progression in both atherosclerosis and myocardial infarction (MI). In atherosclerosis, macrophages are the dominant leukocyte population that influences lesional development. In MI, which is caused by atherosclerosis, macrophages accumulate readily and have important roles in inflammation and healing. Molecular imaging has grown considerably as a field and can reveal biological process at the molecular, cellular and tissue levels. Here, we explore how various imaging modalities, from intravital microscopy in mice to organ-level imaging in patients, are contributing to our understanding of macrophages and their progenitors in cardiovascular disease.Immunology and Cell Biology advance online publication, 4 December 2012; doi:10.1038/icb.2012.72.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23207281
      14. Call Number :
        PKI @ kd.modi @ 12
      15. Serial :
        10441
      1. Author :
        Barman, T. K.; Rao, M.; Bhati, A.; Kishore, K.; Shukla, G.; Kumar, M.; Mathur, T.; Pandya, M.; Upadhyay, D. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Indian J Med Res
      6. Products :
      7. Volume :
        134
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen10, Xen 10, Streptococcus pnuemoniae Xen10, IVIS,
      12. Abstract :
        Background & objectives: In vivo imaging system has contributed significantly to the understanding of bacterial infection and efficacy of drugs in animal model. We report five rapid, reproducible, and non invasive murine pulmonary infection, skin and soft tissue infection, sepsis, and meningitis models using Xenogen bioluminescent strains and specialized in vivo imaging system (IVIS). Methods: The progression of bacterial infection in different target organs was evaluated by the photon intensity and target organ bacterial counts. Genetically engineered bioluminescent bacterial strains viz. Staphylococcus aureus Xen 8.1, 29 and 31; Streptococcus pneumoniae Xen 9 and 10 and Pseudomonas aeruginosa Xen-5 were used to induce different target organs infection and were validated with commercially available antibiotics. Results: The lower limit of detection of colony forming unit (cfu) was 1.7-log10 whereas the lower limit of detection of relative light unit (RLU) was 4.2-log10 . Recovery of live bacteria from different target organs showed that the bioluminescent signal correlated to the live bacterial count. Interpretation & conclusions: This study demonstrated the real time monitoring and non-invasive analysis of progression of infection and pharmacological efficacy of drugs. These models may be useful for pre-clinical discovery of new antibiotics.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22199109
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10399
      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 :
        Francis, K P; Yu, J; Bellinger-Kawahara, C; Joh, D; Hawkinson, M J; Xiao, G; Purchio, T F; Caparon, M G; Lipsitch, M; Contag, P R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2001
      5. Publication :
        Infection and immunity
      6. Products :
      7. Volume :
        69
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Amoxicillin; Animals; Bioware; DNA Transposable Elements; Female; Luminescent Measurements; Lung; Mice; Mice, Inbred BALB C; Nasopharynx; Operon; Promoter Regions, Genetic; pXen-5; Streptococcus pneumoniae; Transformation, Bacterial, Xen10, Xen7
      12. Abstract :
        Animal studies with Streptococcus pneumoniae have provided valuable models for drug development. In order to monitor long-term pneumococcal infections noninvasively in living mice, a novel gram-positive lux transposon cassette, Tn4001 luxABCDE Km(r), that allows random integration of lux genes onto the bacterial chromosome was constructed. The cassette was designed so that the luxABCDE and kanamycin resistance genes were linked to form a single promoterless operon. Bioluminescence and kanamycin resistance only occur in a bacterial cell if this operon has transposed downstream of a promoter on the bacterium's chromosome. S. pneumoniae D39 was transformed with plasmid pAUL-A Tn4001 luxABCDE Km(r), and a number of highly bioluminescent colonies were recovered. Genomic DNA from the brightest D39 strain was used to transform a number of clinical S. pneumoniae isolates, and several of these strains were tested in animal models, including a pneumococcal lung infection model. Strong bioluminescent signals were seen in the lungs of the animals containing these pneumococci, allowing the course and antibiotic treatment of the infections to be readily monitored in real time in the living animals. Recovery of the bacteria from the animals showed that the bioluminescent signal corresponded to the number of CFU and that the lux construct was highly stable even after several days in vivo. We believe that this lux transposon will greatly expand the ability to evaluate drug efficacy against gram-positive bacteria in living animals using bioluminescence.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/11292758
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9027
      1. Author :
        Hardy, Jonathan; Margolis, Jeffrey J; Contag, Christopher H
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Infection and immunity
      6. Products :
      7. Volume :
        74
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bacterial Toxins; Biliary Tract; Bioware; Feces; Food Contamination; Intestines; Listeria monocytogenes; Listeriosis; Mice; Mice, Inbred BALB C; pXen-5
      12. Abstract :
        Listeria monocytogenes is a ubiquitous gram-positive bacterium that can cause systemic and often life-threatening disease in immunocompromised hosts. This organism is largely an intracellular pathogen; however, we have determined that it can also grow extracellularly in animals, in the lumen of the gallbladder. The significance of growth in the gallbladder with respect to the pathogenesis and spread of listeriosis depends on the ability of the bacterium to leave this organ and be disseminated to other tissues and into the environment. Should this process be highly inefficient, growth in the gallbladder would have no impact on pathogenesis or spread, but if it occurs efficiently, bacterial growth in this organ may contribute to listeriosis and dissemination of this organism. Here, we use whole-body imaging to determine the efficacy and kinetics of food- and hormone-induced biliary excretion of L. monocytogenes from the murine gallbladder, demonstrating that transit through the bile duct into the intestine can occur within 5 min of induction of gallbladder contraction by food or cholecystokinin and that movement of bacteria through the intestinal lumen can occur very rapidly in the absence of fecal material. These studies demonstrate that L. monocytogenes bacteria replicating in the gallbladder can be expelled from the organ efficiently and that the released bacteria move into the intestinal tract, where they pass into the environment and may possibly reinfect the animal.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16495556
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9024
      1. Author :
        Schwan, William R; Lehmann, Lynn; McCormick, James
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Infection and immunity
      6. Products :
      7. Volume :
        74
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Amino Acid Transport Systems, Neutral; Animals; Bacterial Proteins; Bioware; Blotting, Northern; Disease Models, Animal; Gene Expression Regulation, Bacterial; Humans; Lac Operon; Mice; Osmolar Concentration; Proline; pXen-5; Recombinant Fusion Proteins; Staphylococcal Infections; Staphylococcus aureus; Symporters; Transcriptional Activation
      12. Abstract :
        Staphylococcus aureus can grow virtually anywhere in the human body but needs to import proline through low- and high-affinity proline transporters to survive. This study examined the regulation of the S. aureus putP gene, which encodes a high-affinity proline permease. putP::lacZ and putP::lux transcriptional fusions were constructed and integrated into the genomes of several S. aureus strains. Enzyme activity was measured after growth in media with various osmolyte concentrations. As osmolarity rose, putP expression increased, with a plateau at 2 M for NaCl in strain LL3-1. Proline concentrations as low as 17.4 muM activated expression of the putP gene. The putP::lux fusion was also integrated into the genomes of S. aureus strains that were either SigB inactive (LL3-1, 8325-4, and SH1003) or SigB active (Newman and SH1000). SigB inactive strains showed increased putP gene expression as NaCl concentrations rose, whereas SigB active strains displayed a dramatic decrease in putP expression, suggesting that the alternative sigma factor B plays a negative role in putP regulation. Mice inoculated with S. aureus strains containing the putP::lux fusion exhibited up to a 715-fold increase in putP expression, although levels in the various murine organs differed. Moreover, urine from human patients infected with S. aureus showed elevated putP levels by use of a PCR procedure, whereas blood and some abscess material had no significant increase. Thus, putP is transcriptionally activated by a low-proline and high osmotic environment both in growth media and in murine or human clinical specimens.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16368996
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9023
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