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      1. Author :
        Bethunaickan, R.; Berthier, C.C.; Ramanujam, M.; Sahu, R.; Zhang, W.; Sun, Y.; Bottinger, E.P.; Ivashkiv, L.; Kretzler, M.; Davidson, A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Journal of Immunology (Baltimore, Md.: 1950)
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        In vivo; kidney; mice; MMPSense 680; ProSense 680
      12. Abstract :
        Renal infiltration with mononuclear cells is associated with poor prognosis in systemic lupus erythematosus. A renal macrophage/dendritic cell signature is associated with the onset of nephritis in NZB/W mice, and immune-modulating therapies can reverse this signature and the associated renal damage despite ongoing immune complex deposition. In nephritic NZB/W mice, renal F4/80(hi)/CD11c(int) macrophages are located throughout the interstitium, whereas F4/80(lo)/CD11c(hi) dendritic cells accumulate in perivascular lymphoid aggregates. We show here that F4/80(hi)/CD11c(int) renal macrophages have a Gr1(lo)/Ly6C(lo)/VLA4(lo)/MHCII(hi)/CD43(lo)/CD62L(lo) phenotype different from that described for inflammatory macrophages. At nephritis onset, F4/80(hi)/CD11c(int) cells upregulate cell surface CD11b, acquire cathepsin and matrix metalloproteinase activity, and accumulate large numbers of autophagocytic vacuoles; these changes reverse after the induction of remission. Latex bead labeling of peripheral blood Gr1(lo) monocytes indicates that these are the source of F4/80(hi)/CD11c(int) macrophages. CD11c(hi)/MHCII(lo) dendritic cells are found in the kidneys only after proteinuria onset, turnover rapidly, and disappear rapidly after remission induction. Gene expression profiling of the F4/80(hi)/CD11c(int) population displays increased expression of proinflammatory, regulatory, and tissue repair/degradation-associated genes at nephritis onset that reverses with remission induction. Our findings suggest that mononuclear phagocytes with an aberrant activation profile contribute to tissue damage in lupus nephritis by mediating both local inflammation and excessive tissue remodeling.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21411733
      14. Call Number :
        PKI @ user @ 8549
      15. Serial :
        4801
      1. Author :
        Evans, L.; Williams, A.S.; Hayes, A.J.; Jones, S.A.; Nowell, M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Arthritis and Rheumatism
      6. Products :
      7. Volume :
        N/A
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Apo866; Arthritis; In vivo; Living Image software; MMPSense 750 FAST; Xenogen Caliper IVIS 200
      12. Abstract :
        OBJECTIVE: Using APO866, studies assessed the ability of Pre-B-cell colony-Enhancing Factor (PBEF) to regulate inflammatory and degradative processes in fibroblasts and collagen-induced arthritis. METHODS: ELISAs were used to examine regulation of metalloproteinases and chemokine expression by HFF fibroblasts. PBEF was further examined in the collagen-induced arthritis model using APO866. Disease activity was assessed using radiography, histology, in vivo imaging and quantitative PCR (qPCR). RESULTS: In vitro activation of fibroblasts with PBEF promoted MMP-3, CCL-2 and CXCL-8 expression, an effect inhibited by APO866. Early intervention with APO866 in collagen-induced arthritis inhibited both synovial inflammation, including chemokine-directed leukocyte infiltration, and the systemic marker of inflammation, serum hyaluronic acid. Blockade of degenerative processes by APO866 was further illustrated by the reduced expression of MMP-3 and MMP-13 in joint extracts and reduction of the systemic marker of cartilage erosion, serum cartilage oligomeric matrix protein (COMP). Radiology showed that APO866 protected against bone erosion, whilst qPCR demonstrated inhibition of RANKL expression. APO866 treatment in established disease (clinical score >=5) reduced synovial inflammation, cartilage destruction and halted bone erosion. MMP-3, CCL-2 and RANKL activity, as assessed by in vivo imaging with MMPSense750 and qPCR were reduced in treated animals. qPCR of synovial explants from animals with CIA showed that APO866 inhibited MMP-3, CCL-2 and RANKL production, a result that was reversed with nicotinamide mononucleotide (NMN) CONCLUSIONS: These data confirm PBEF to be an important regulator of inflammation, cartilage catabolism and bone erosion, and highlights APO866 as a promising therapy for targeting PBEF activity in inflammatory arthritis.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21400478
      14. Call Number :
        PKI @ user @ 8551
      15. Serial :
        4800
      1. Author :
        Mathew, B.; Lennon, F.E.; Siegler, J.; Mirzapoiazova, T.; Mambetsariev, N.; Sammani, S.; Gerhold, L.M.; Lariviere, P.J.; Chen, C.-T.; Garcia, J.G.N.; Salgia, R.; Moss, J.; Singleton, P.A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Anesthesia and Analgesia
      6. Products :
      7. Volume :
        112
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Cancer; flank tumor; In vivo; MMPSense 750; ProSense 680; tomography; VisEn FMT
      12. Abstract :
        <AbstractText Label=“BACKGROUND” NlmCategory=“BACKGROUND”>The possibility that μ opioid agonists can influence cancer recurrence is a subject of recent interest. Epidemiologic studies suggested that there were differences in cancer recurrence in breast and prostate cancer contingent on anesthetic regimens. In this study, we identify a possible mechanism for these epidemiologic findings on the basis of μ opioid receptor (MOR) regulation of Lewis lung carcinoma (LLC) tumorigenicity in cell and animal models.</AbstractText> <AbstractText Label=“METHODS” NlmCategory=“METHODS”>We used human lung tissue and human non-small cell lung cancer (NSCLC) cell lines and evaluated MOR expression using immunoblot and immunohistochemical analysis. LLC cells were treated with the peripheral opioid antagonist methylnaltrexone (MNTX) or MOR shRNA and evaluated for proliferation, invasion, and soft agar colony formation in vitro and primary tumor growth and lung metastasis in C57BL/6 and MOR knockout mice using VisEn fluorescence mediated tomography imaging and immunohistochemical analysis.</AbstractText> <AbstractText Label=“RESULTS” NlmCategory=“RESULTS”>We provide several lines of evidence that the MOR may be a potential target for lung cancer, a disease with high mortality and few treatment options. We first observed that there is ~5- to 10-fold increase in MOR expression in lung samples from patients with NSCLC and in several human NSCLC cell lines. The MOR agonists morphine and [d-Ala(2), N-MePhe(4), Gly-ol]-enkephalin (DAMGO) increased in vitro LLC cell growth. Treatment with MNTX or silencing MOR expression inhibited LLC invasion and anchorage-independent growth by 50%-80%. Injection of MOR silenced LLC lead to a ~65% reduction in mouse lung metastasis. In addition, MOR knockout mice do not develop significant tumors when injected with LLC in comparison with wild-type controls. Finally, continuous infusion of the peripheral opioid antagonist MNTX attenuates primary LLC tumor growth and reduces lung metastasis.</AbstractText> <AbstractText Label=“CONCLUSIONS” NlmCategory=“CONCLUSIONS”>Taken together, our data suggest a possible direct effect of opiates on lung cancer progression, and provide a plausible explanation for the epidemiologic findings. Our observations further suggest a possible therapeutic role for opioid antagonists.</AbstractText>
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21156980
      14. Call Number :
        PKI @ user @ 8557
      15. Serial :
        4797
      1. Author :
        Napp, J.; Mathejczyk, J.E.; Alves, F.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Pediatric Radiology
      6. Products :
      7. Volume :
        41
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        AngioSense 680; Cancer; glioblastoma xenograft; mice; tumor vascularization
      12. Abstract :
        To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21221568
      14. Call Number :
        PKI @ user @ 8559
      15. Serial :
        4796
      1. Author :
        David E Sosnovik, Matthias Nahrendorf and Ralph Weissleder
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Nature Reviews Cardiology
      6. Products :
      7. Volume :
        5
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        in vivo imaging; fluorescence imaging, molecular imaging, MRI, myocardium, SPECT; MMPSense
      12. Abstract :
        Molecular imaging agents can be targeted to a specific receptor or protein on the cardiomyocyte surface, or to enzymes released into the interstitial space, such as cathepsins, matrix metalloproteinases and myeloperoxidase. Molecular imaging of the myocardium, however, requires the imaging agent to be small, sensitive (nanomolar levels or better), and able to gain access to the interstitial space. Several novel agents that fulfill these criteria have been used for targeted molecular imaging applications in the myocardium. Magnetic resonance, fluorescence, and single-photon emission CT have been used to image the molecular signals generated by these agents. The use of targeted imaging agents in the myocardium has the potential to provide valuable insights into the pathophysiology of myocardial injury and to facilitate the development of novel therapeutic strategies.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2597275/?tool=pubmed
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4650
      1. Author :
        Wunder A and Klohs J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Basic Research in Cardiology
      6. Products :
      7. Volume :
        103
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        Cardiovascular Research
      11. Keywords :
        In vivo imaging; atherosclerosis; bioluminescence imaging; fluorescence imaging; myocardial infarction; stroke; ProSense
      12. Abstract :
        Pathophysiological processes in the vascular system are the major cause of mortality and disease. Atherosclerosis, an inflammatory process in arterial walls, can lead to formation of plaques, whose rupture can lead to thrombus formation, obstruction of vessels (thrombosis), reduction of the blood flow (ischemia), cell death in the tissue fed by the occluded vessel, and depending on the affected vessel, to myocardial infarction or stroke. Imaging techniques enabling visualization of the biological processes involved in this scenario are therefore highly desirable. In recent years, a number of reporter agents and reporter systems have been developed to visualize these processes using different imaging modalities including nuclear imaging techniques, such as positron emission tomography or single photon emission computed tomography, magnetic resonance imaging, and ultrasound. This article comprises a brief overview of optical imaging techniques, such as fluorescence imaging and bioluminescence imaging for the visualization of vascular pathophysiology.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18324374
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4649
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