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      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        PloS one
      6. Products :
      7. Volume :
        2
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Adhesins, Bacterial; Animals; Antigens, CD46; Bacteremia; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Translocation; Bioware; Blood-Brain Barrier; Central Nervous System; Disease Progression; Female; Luminescent Measurements; Luminescent Proteins; Male; Meningitis, Meningococcal; Meningococcal Infections; Mice; Mice, Transgenic; Nasal Cavity; pXen-13; Recombinant Fusion Proteins; Respiratory System; Sepsis; Thyroid Gland
      12. Abstract :
        Neisseria meningitidis is a human pathogen that causes septicemia and meningitis with high mortality. The disease progression is rapid and much remains unknown about the disease process. The understanding of disease development is crucial for development of novel therapeutic strategies and vaccines against meningococcal disease. The use of bioluminescent imaging combined with a mouse disease model allowed us to investigate the progression of meningococcal sepsis over time. Injection of bacteria in blood demonstrated waves of bacterial clearance and growth, which selected for Opa-expressing bacteria, indicating the importance of this bacterial protein. Further, N. meningitidis accumulated in the thyroid gland, while thyroid hormone T4 levels decreased. Bacteria reached the mucosal surfaces of the upper respiratory tract, which required expression of the meningococcal PilC1 adhesin. Surprisingly, PilC1 was dispensable for meningococcal growth in blood and for crossing of the blood-brain barrier, indicating that the major role of PilC1 is to interact with mucosal surfaces. This in vivo study reveals disease dynamics and organ targeting during meningococcal disease and presents a potent tool for further investigations of meningococcal pathogenesis and vaccines in vivo. This might lead to development of new strategies to improve the outcome of meningococcal disease in human patients.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17311106
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9032
      1. Author :
        Yipp, B. G.; Petri, B.; Salina, D.; Jenne, C. N.; Scott, B. N.; Zbytnuik, L. D.; Pittman, K.; Asaduzzaman, M.; Wu, K.; Meijndert, H. C.; Malawista, S. E.; de Boisfleury Chevance, A.; Zhang, K.; Conly, J.; Kubes, P.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Med
      6. Products :
      7. Volume :
        18
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen8.1, Xen 8.1, S. aureus, IVIS, bioluminescence imaging, Analysis of Variance; Animals; Extracellular Space/*metabolism; Genetic Vectors/genetics; Green Fluorescent Proteins/metabolism; Humans; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Movement/*physiology; Neutrophils/*immunology/metabolism/physiology; Opsonin Proteins/metabolism; Skin Diseases, Bacterial/*immunology/metabolism; Toll-Like Receptor 2/metabolism
      12. Abstract :
        Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live polymorphonuclear cells (PMNs) in vivo rapidly releasing NETs, which prevented systemic bacterial dissemination. NETosis occurred during crawling, thereby casting large areas of NETs. NET-releasing PMNs developed diffuse decondensed nuclei, ultimately becoming devoid of DNA. Cells with abnormal nuclei showed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release. Additionally, live human PMNs injected into mouse skin developed decondensed nuclei and formed NETS in vivo, and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22922410
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10565
      1. Author :
        Heit, Bryan; Robbins, Stephen M; Downey, Charlene M; Guan, Zhiwen; Colarusso, Pina; Miller, B Joan; Jirik, Frank R; Kubes, Paul
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Nature immunology
      6. Products :
      7. Volume :
        9
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Arthritis, Experimental; Bioware; Chemotaxis, Leukocyte; Humans; Inflammation; Mice; Mice, Transgenic; Neutrophils; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Phosphatidylinositol Phosphates; Protein Transport; PTEN Phosphohydrolase; Xen29
      12. Abstract :
        Neutrophils encounter and 'prioritize' many chemoattractants in their pursuit of bacteria. Here we tested the possibility that the phosphatase PTEN is responsible for the prioritization of chemoattractants. Neutrophils induced chemotaxis by two separate pathways, the phosphatidylinositol-3-OH kinase (PI(3)K) phosphatase and tensin homolog (PTEN) pathway, and the p38 mitogen-activated protein kinase pathway, with the p38 pathway dominating over the PI(3)K pathway. Pten(-/-) neutrophils could not prioritize chemoattractants and were 'distracted' by chemokines when moving toward bacterial chemoattractants. In opposing gradients, PTEN became distributed throughout the cell circumference, which inhibited all PI(3)K activity, thus permitting 'preferential' migration toward bacterial products via phospholipase A(2) and p38. Such prioritization was defective in Pten(-/-) neutrophils, which resulted in defective bacterial clearance in vivo. Our data identify a PTEN-dependent mechanism in neutrophils to prioritize, 'triage' and integrate responses to multiple chemotactic cues.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18536720
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9048
      1. Author :
        Marcella A. Calfon, Claudio Vinegoni, Vasilis Ntziachristos and Farouc A. Jaffer
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Journal of Biomedical Optics
      6. Products :
      7. Volume :
        15
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        in vivo imaging; Cat K FAST; Cat B FAST; MMPSense
      12. Abstract :
        New imaging methods are urgently needed to identify high-risk atherosclerotic lesions prior to the onset of myocardial infarction, stroke, and ischemic limbs. Molecular imaging offers a new approach to visualize key biological features that characterize high-risk plaques associated with cardiovascular events. While substantial progress has been realized in clinical molecular imaging of plaques in larger arterial vessels (carotid, aorta, iliac), there remains a compelling, unmet need to develop molecular imaging strategies targeted to high-risk plaques in human coronary arteries. We present recent developments in intravascular near-IR fluorescence catheter-based strategies for in vivo detection of plaque inflammation in coronary-sized arteries. In particular, the biological, light transmission, imaging agent, and engineering principles that underlie a new intravascular near-IR fluorescence sensing method are discussed. Intravascular near-IR fluorescence catheters appear highly translatable to the cardiac catheterization laboratory, and thus may offer a new in vivo method to detect high-risk coronary plaques and to assess novel atherosclerosis biologics.
      13. URL :
        http://spiedl.aip.org/getabs/servlet/GetabsServlet?prog=normal&id=JBOPFO000015000001011107000001&idtype=cvips&gifs=yes&ref=no
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4556
      1. Author :
        Jadert, C.; Petersson, J.; Massena, S.; Ahl, D.; Grapensparr, L.; Holm, L.; Lundberg, J. O.; Phillipson, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Free Radic Biol Med
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xen29, Xen 29, Staphylococcus aureus Xen29
      12. Abstract :
        Nitric oxide (NO) generated by vascular NO synthases can exert anti-inflammatory effects, partly through its ability to decrease leukocyte recruitment. Inorganic nitrate and nitrite, from endogenous or dietary sources, have emerged as alternative substrates for NO formation in mammals. Bioactivation of nitrate is believed to require initial reduction to nitrite by oral commensal bacteria. Here we investigated the effects of inorganic nitrate and nitrite on leukocyte recruitment in microvascular inflammation and in NSAID-induced small-intestinal injury. We show that leukocyte emigration in response to the proinflammatory chemokine MIP-2 is reduced by 70% after 7days of dietary nitrate supplementation as well as by acute intravenous nitrite administration. Nitrite also reduced leukocyte adhesion to a similar extent and this effect was inhibited by the soluble guanylyl cyclase inhibitor ODQ, whereas the effect on emigrated leukocytes was not altered by this treatment. Further studies in TNF-alpha-stimulated endothelial cells revealed that nitrite dose-dependently reduced the expression of ICAM-1. In rats and mice subjected to a challenge with diclofenac, dietary nitrate prevented the increase in myeloperoxidase and P-selectin levels in small-intestinal tissue. Antiseptic mouthwash, which eliminates oral nitrate reduction, markedly blunted the protective effect of dietary nitrate on P-selectin levels. Despite attenuation of the acute immune response, the overall ability to clear an infection with Staphylococcus aureus was not suppressed by dietary nitrate as revealed by noninvasive IVIS imaging. We conclude that dietary nitrate markedly reduces leukocyte recruitment to inflammation in a process involving attenuation of P-selectin and ICAM-1 upregulation. Bioactivation of dietary nitrate requires intermediate formation of nitrite by oral nitrate-reducing bacteria and then probably further reduction to NO and other bioactive nitrogen oxides in the tissues.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22178413
      14. Call Number :
        PKI @ kd.modi @ 18
      15. Serial :
        10452
      1. Author :
        Vandamme, M.; Robert, E.; Lerondel, S.; Sarron, V.; Ries, D.; Dozias, S.; Sobilo, J.; Gosset, D.; Kieda, C.; Legrain, B.; Pouvesle, J. M.; Pape, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Int J Cancer
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        U87-MG-luc2, U-87-MG-luc2, U87MG-luc2, Bioluminescence, Glioma, IVIS
      12. Abstract :
        Non-thermal plasma (NTP) is generated by ionizing neutral gas molecules/atoms leading to a highly reactive gas at ambient temperature containing excited molecules, reactive species and generating transient electric fields. Given its potential to interact with tissue or cells without a significant temperature increase, NTP appears as a promising approach for the treatment of various diseases including cancer. The aim of our study was to evaluate the interest of NTP both in vitro and in vivo. To this end, we evaluated the antitumor activity of NTP in vitro on two human cancer cell lines (glioblastoma U87MG and colorectal carcinoma HCT-116). Our data showed that NTP generated a large amount of reactive oxygen species (ROS), leading to the formation of DNA damages. This resulted in a multiphase cell cycle arrest and a subsequent apoptosis induction. In addition, in vivo experiments on U87MG bearing mice showed that NTP induced a reduction of bioluminescence and tumor volume as compared to nontreated mice. An induction of apoptosis was also observed together with an accumulation of cells in S phase of the cell cycle suggesting an arrest of tumor proliferation. In conclusion, we demonstrated here that the potential of NTP to generate ROS renders this strategy particularly promising in the context of tumor treatment.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21702038
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10424
      1. Author :
        Vandamme, M.; Robert, E.; Lerondel, S.; Sarron, V.; Ries, D.; Dozias, S.; Sobilo, J.; Gosset, D.; Kieda, C.; Legrain, B.; Pouvesle, J. M.; Pape, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Int J Cancer
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        HCT-116-luc2, IVIS, Bioware, HCT116-luc2
      12. Abstract :
        Non-thermal plasma (NTP) is generated by ionizing neutral gas molecules/atoms leading to a highly reactive gas at ambient temperature containing excited molecules, reactive species and generating transient electric fields. Given its potential to interact with tissue or cells without a significant temperature increase, NTP appears as a promising approach for the treatment of various diseases including cancer. The aim of our study was to evaluate the interest of NTP both in vitro and in vivo. To this end, we evaluated the antitumor activity of NTP in vitro on two human cancer cell lines (glioblastoma U87MG and colorectal carcinoma HCT-116). Our data showed that NTP generated a large amount of reactive oxygen species (ROS), leading to the formation of DNA damages. This resulted in a multiphase cell cycle arrest and a subsequent apoptosis induction. In addition, in vivo experiments on U87MG bearing mice showed that NTP induced a reduction of bioluminescence and tumor volume as compared to nontreated mice. An induction of apoptosis was also observed together with an accumulation of cells in S phase of the cell cycle suggesting an arrest of tumor proliferation. In conclusion, we demonstrated here that the potential of NTP to generate ROS renders this strategy particularly promising in the context of tumor treatment.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21702038
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10498
      1. Author :
        Kadurugamuwa, J. L.; Modi, K.; Yu, J.; Francis, K. P.; Orihuela, C.; Tuomanen, E.; Purchio, A. F.; Contag, P. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        Mol Imaging
      6. Products :
      7. Volume :
        4
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals, Diagnostic Imaging, Disease Models, Animal, Female, Luminescent Measurements/methods, Meningitis, Pneumococcal/drug therapy/microbiology/ radiography, Mice, Mice, Inbred BALB C, Streptococcus pneumoniae/drug effects IVIS, Xenogen, Xen10
      12. Abstract :
        Noninvasive real-time in vivo bioluminescent imaging was used to assess the spread of Streptococcus pneumoniae throughout the spinal cord and brain during the acute stages of bacterial meningitis. A mouse model was established by lumbar (LP) or intracisternal (IC) injection of bioluminescent S. pneumoniae into the subarachnoid space. Bacteria replicated initially at the site of inoculation and spread progressively from the spinal cord to the brain or from the brain down to the cervical part of the spinal column and to the lower vertebral levels. After 24 hr, animals showed strong bioluminescent signals throughout the spinal canal, indicating acute meningitis of the intracranial and intraspinal meninges. A decline in bacterial cell viability, as judged by a reduction in the bioluminescent signal, was observed over time in animals treated with ceftriaxone, but not in untreated groups. Mice treated with the antibiotic survived infection, whereas all mice in untreated groups became moribund, first in the IC group then in the LP group. No untreated animal survived beyond 48 hr after induction of infection. Colony counts of infected cerebrospinal fluid (CSF) correlated positively with bioluminescent signals. This methodology is especially appealing because it allows detecting infected mice as early as 3 hr after inoculation, provide temporal, sequential, and spatial distribution of bacteria within the brain and spinal cord throughout the entire disease process and the rapid monitoring of treatment efficacy in a nondestructive manner. Moreover, it avoids the need to sacrifice the animals for CSF sampling and the potential manipulative damage that can occur with other conventional methods.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16105511
      14. Call Number :
        139330
      15. Serial :
        7143
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