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      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 :
        Nguyen, V. H.; Kim, H. S.; Ha, J. M.; Hong, Y.; Choy, H. E.; Min, J. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer Res
      6. Products :
      7. Volume :
        70
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen26, Xen 26, Salmonella typhumurium, Animals; Blotting, Western; Cell Line, Tumor; Diagnostic Imaging/methods; Gene Therapy/*methods; Genetic Engineering/*methods; Genetic Vectors/*therapeutic use; Humans; Male; Mice; Mice, Inbred BALB C; Neoplasms/*therapy; Perforin/*genetics/therapeutic use; Promoter Regions, Genetic; Salmonella typhimurium/*genetics; bcl-Associated Death Protein/genetics
      12. Abstract :
        Tumor-targeting bacteria have been studied in terms of their ability to visualize the infection pathway (through imaging probes) or to carry therapeutic molecules to tumors. To integrate these monitoring and therapeutic functions, we engineered attenuated Salmonella typhimurium defective in guanosine 5'-diphosphate-3'-diphosphate synthesis to carry cytotoxic proteins (cytolysin A) and express reporter genes. We successfully visualized the therapeutic process with these engineered bacteria in mice and found that they often mediated complete tumor (CT-26) eradication on cytotoxic gene induction. Furthermore, treatment with the engineered bacteria markedly suppressed metastatic tumor growth.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20028866
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10560
      1. Author :
        Yun, M.; Pan, S.; Jiang, S. N.; Nguyen, V. H.; Park, S. H.; Jung, C. H.; Kim, H. S.; Min, J. J.; Choy, H. E.; Hong, Y.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Microbiol
      6. Products :
      7. Volume :
        50
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen26, Xen 26, Salmonella typhumurium, Animals; Biological Therapy/*methods; Colonic Neoplasms/chemistry/*therapy; Disease Models, Animal; Electrophoresis, Gel, Two-Dimensional; Male; Mass Spectrometry; Mice; Mice, Inbred BALB C; Proteome/analysis; Salmonella typhimurium/*growth & development/*pathogenicity
      12. Abstract :
        The use of bacteria has contributed to recent advances in targeted cancer therapy especially for its tumor-specific accumulation and proliferation. In this study, we investigated the molecular events following bacterial therapy using an attenuated Salmonella Typhimurium defective in ppGpp synthesis (DeltappGpp), by analyzing those proteins differentially expressed in tumor tissues from treated and untreated mice. CT26 murine colon cancer cells were implanted in BALB/c mice and allowed to form tumors. The tumor-bearing mice were treated with the attenuated Salmonella Typhimurium. Tumor tissues were analyzed by 2D-PAGE. Fourteen differentially expressed proteins were identified by mass spectrometry. The analysis revealed that cytoskeletal components, including vimentin, drebrin-like protein, and tropomyosin-alpha 3, were decreased while serum proteins related to heme or iron metabolism, including transferrin, hemopexin, and haptoglobin were increased. Subsequent studies revealed that the decrease in cytoskeletal components occurred at the transcriptional level and that the increase in heme and iron metabolism proteins occurred in liver. Most interestingly, the same pattern of increased expression of transferrin, hemopexin, and haptoglobin was observed following radiotherapy at the dosage of 14 Gy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22752915
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10561
      1. Author :
        Hamrahi, V.; Hamblin, M. R.; Jung, W.; Benjamin, J. B.; Paul, K. W.; Fischman, A. J.; Tompkins, R. G.; Carter, E. A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Interdiscip Perspect Infect Dis
      6. Products :
      7. Volume :
        2012
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen44, Xen 44, Proteus mirabilis, bioluminescence imaging
      12. Abstract :
        Sepsis remains the major cause of death in patients with major burn injuries. In the present investigation we evaluated the interaction between burn injuries of varying severity and preexisting distant infection. We used Gram-negative bacteria (Pseudomonas aeruginosa and Proteus mirabilis) that were genetically engineered to be bioluminescent, which allowed for noninvasive, sequential optical imaging of the extent and severity of the infection. The bioluminescent bacteria migrated from subcutaneous abscesses in the leg to distant burn wounds on the back depending on the severity of the burn injury, and this migration led to increased mortality of the mice. Treatment with ciprofloxacin, injected either in the leg with the bacterial infection or into the burn eschar, prevented this colonization of the wound and decreased mortality. The present data suggest that burn wounds can readily become colonized by infections distant from the wound itself.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22899912
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10562
      1. Author :
        Lu, Z.; Dai, T.; Huang, L.; Kurup, D. B.; Tegos, G. P.; Jahnke, A.; Wharton, T.; Hamblin, M. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Nanomedicine (Lond)
      6. Products :
      7. Volume :
        5
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen44, Xen 44, Proteus mirabilis, bioluminescence imaging, Animals; Fullerenes/*chemistry; Male; Mice; Mice, Inbred BALB C; Photochemotherapy/*methods; Photosensitizing Agents/*chemistry; Pseudomonas Infections/*drug therapy; Pseudomonas aeruginosa/drug effects; Wound Infection/*drug therapy
      12. Abstract :
        AIMS: Fullerenes are under intensive study for potential biomedical applications. We have previously reported that a C60 fullerene functionalized with three dimethylpyrrolidinium groups (BF6) is a highly active broad-spectrum antimicrobial photosensitizer in vitro when combined with white-light illumination. We asked whether this high degree of in vitro activity would translate into an in vivo therapeutic effect in two potentially lethal mouse models of infected wounds. MATERIALS & METHODS: We used stable bioluminescent bacteria and a low light imaging system to follow the progress of the infection noninvasively in real time. An excisional wound on the mouse back was contaminated with one of two bioluminescent Gram-negative species, Proteus mirabilis (2.5 x 10(7) cells) and Pseudomonas aeruginosa (5 x 10(6) cells). A solution of BF6 was placed into the wound followed by delivery of up to 180 J/cm(2) of broadband white light (400-700 nm). RESULTS: In both cases there was a light-dose-dependent reduction of bioluminescence from the wound not observed in control groups (light alone or BF6 alone). Fullerene-mediated photodynamic therapy of mice infected with P. mirabilis led to 82% survival compared with 8% survival without treatment (p < 0.001). Photodynamic therapy of mice infected with highly virulent P. aeruginosa did not lead to survival, but when photodynamic therapy was combined with a suboptimal dose of the antibiotic tobramycin (6 mg/kg for 1 day) there was a synergistic therapeutic effect with a survival of 60% compared with a survival of 20% with tobramycin alone (p < 0.01). CONCLUSION: These data suggest that cationic fullerenes have clinical potential as an antimicrobial photosensitizer for superficial infections where red light is not needed to penetrate tissue.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21143031
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10563
      1. Author :
        Lorentzen, D.; Durairaj, L.; Pezzulo, A. A.; Nakano, Y.; Launspach, J.; Stoltz, D. A.; Zamba, G.; McCray, P. B., Jr.; Zabner, J.; Welsh, M. J.; Nauseef, W. M.; Banfi, B.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Free Radic Biol Med
      6. Products :
      7. Volume :
        50
      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
      12. Abstract :
        A recently discovered enzyme system produces antibacterial hypothiocyanite (OSCN(-)) in the airway lumen by oxidizing the secreted precursor thiocyanate (SCN(-)). Airway epithelial cultures have been shown to secrete SCN(-) in a CFTR-dependent manner. Thus, reduced SCN(-) availability in the airway might contribute to the pathogenesis of cystic fibrosis (CF), a disease caused by mutations in the CFTR gene and characterized by an airway host defense defect. We tested this hypothesis by analyzing the SCN(-) concentration in the nasal airway surface liquid (ASL) of CF patients and non-CF subjects and in the tracheobronchial ASL of CFTR-DeltaF508 homozygous pigs and control littermates. In the nasal ASL, the SCN(-) concentration was ~30-fold higher than in serum independent of the CFTR mutation status of the human subject. In the tracheobronchial ASL of CF pigs, the SCN(-) concentration was somewhat reduced. Among human subjects, SCN(-) concentrations in the ASL varied from person to person independent of CFTR expression, and CF patients with high SCN(-) levels had better lung function than those with low SCN(-) levels. Thus, although CFTR can contribute to SCN(-) transport, it is not indispensable for the high SCN(-) concentration in ASL. The correlation between lung function and SCN(-) concentration in CF patients may reflect a beneficial role for SCN(-).
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21334431
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10564
      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 :
        Goldberg, M. S.; Xing, D.; Ren, Y.; Orsulic, S.; Bhatia, S. N.; Sharp, P. A.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Proc Natl Acad Sci U S A
      6. Products :
      7. Volume :
        108
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VivoTag, IVIS, Vivotag, Animals; BRCA1 Protein/*genetics; Drug Carriers; Drug Delivery Systems; Female; Humans; Mice; Nanoparticles/*chemistry; Nanotechnology/methods; Neoplasm Transplantation; Ovarian Neoplasms/*genetics/*therapy; Poly(ADP-ribose) Polymerases/*genetics; RNA Interference; RNA, Small Interfering/*metabolism; Treatment Outcome
      12. Abstract :
        Inhibition of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) with small molecules has been shown to be an effective treatment for ovarian cancer with BRCA mutations. Here, we report the in vivo administration of siRNA to Parp1 in mouse models of ovarian cancer. A unique member of the lipid-like materials known as lipidoids is shown to deliver siRNA to disseminated murine ovarian carcinoma allograft tumors following intraperitoneal (i.p.) injection. siParp1 inhibits cell growth, primarily by induction of apoptosis, in Brca1-deficient cells both in vitro and in vivo. Additionally, the treatment extends the survival of mice bearing tumors derived from Brca1-deficient ovarian cancer cells but not from Brca1 wild-type cells, confirming the proposed mechanism of synthetic lethality. Because there are 17 members of the Parp family, the inherent complementarity of RNA affords a high level of specificity for therapeutically addressing Parp1 in the context of impaired homologous recombination.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/21187397
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10566
      1. Author :
        Kwong, G. A.; von Maltzahn, G.; Murugappan, G.; Abudayyeh, O.; Mo, S.; Papayannopoulos, I. A.; Sverdlov, D. Y.; Liu, S. B.; Warren, A. D.; Popov, Y.; Schuppan, D.; Bhatia, S. N.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Nat Biotechnol
      6. Products :
      7. Volume :
        31
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VivoTag, IVIS, Vivotag
      12. Abstract :
        Biomarkers are becoming increasingly important in the clinical management of complex diseases, yet our ability to discover new biomarkers remains limited by our dependence on endogenous molecules. Here we describe the development of exogenously administered 'synthetic biomarkers' composed of mass-encoded peptides conjugated to nanoparticles that leverage intrinsic features of human disease and physiology for noninvasive urinary monitoring. These protease-sensitive agents perform three functions in vivo: they target sites of disease, sample dysregulated protease activities and emit mass-encoded reporters into host urine for multiplexed detection by mass spectrometry. Using mouse models of liver fibrosis and cancer, we show that these agents can noninvasively monitor liver fibrosis and resolution without the need for invasive core biopsies and substantially improve early detection of cancer compared with current clinically used blood biomarkers. This approach of engineering synthetic biomarkers for multiplexed urinary monitoring should be broadly amenable to additional pathophysiological processes and point-of-care diagnostics.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23242163
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10567
      1. Author :
        Tafreshi, N. K.; Bui, M. M.; Bishop, K.; Lloyd, M. C.; Enkemann, S. A.; Lopez, A. S.; Abrahams, D.; Carter, B. W.; Vagner, J.; Grobmyer, S. R.; Gillies, R. J.; Morse, D. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Clin Cancer Res
      6. Products :
      7. Volume :
        18
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        VivoTag, IVIS, Vivotag, Animals; Antibodies, Monoclonal/*diagnostic use/immunology/pharmacokinetics; Antigens, Neoplasm/*metabolism; Blotting, Western; Breast/immunology/metabolism/pathology; Breast Neoplasms/*diagnosis/immunology/metabolism; Carbonic Anhydrases/*metabolism; Carcinoma, Ductal, Breast/*diagnosis/immunology/metabolism; Carcinoma, Intraductal, Noninfiltrating/*diagnosis/immunology/metabolism; *Diagnostic Imaging; Female; Fluorescent Antibody Technique; Gene Expression Profiling; Humans; Luciferases/metabolism; Luminescent Measurements; Lymphatic Metastasis; Mice; Mice, Nude; Neoplasm Invasiveness; Oligonucleotide Array Sequence Analysis; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction; Tissue Array Analysis; Tissue Distribution; Tumor Cells, Cultured; Tumor Markers, Biological/genetics/metabolism
      12. Abstract :
        PURPOSE: To develop targeted molecular imaging probes for the noninvasive detection of breast cancer lymph node metastasis. EXPERIMENTAL DESIGN: Six cell surface or secreted markers were identified by expression profiling and from the literature as being highly expressed in breast cancer lymph node metastases. Two of these markers were cell surface carbonic anhydrase isozymes (CAIX and/or CAXII) and were validated for protein expression by immunohistochemistry of patient tissue samples on a breast cancer tissue microarray containing 47 normal breast tissue samples, 42 ductal carcinoma in situ, 43 invasive ductal carcinomas without metastasis, 46 invasive ductal carcinomas with metastasis, and 49 lymph node macrometastases of breast carcinoma. Targeted probes were developed by conjugation of CAIX- and CAXII-specific monoclonal antibodies to a near-infrared fluorescent dye. RESULTS: Together, these two markers were expressed in 100% of the lymph node metastases surveyed. Selectivity of the imaging probes were confirmed by intravenous injection into nude mice-bearing mammary fat pad tumors of marker-expressing cells and nonexpressing cells or by preinjection of unlabeled antibody. Imaging of lymph node metastases showed that peritumorally injected probes detected nodes harboring metastatic tumor cells. As few as 1,000 cells were detected, as determined by implanting, under ultrasound guidance, a range in number of CAIX- and CAXII-expressing cells into the axillary lymph nodes. CONCLUSION: These imaging probes have potential for noninvasive staging of breast cancer in the clinic and elimination of unneeded surgery, which is costly and associated with morbidities.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22016510
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10568
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