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      1. Author :
        Sottnik, Joseph L; U'Ren, Lance W; Thamm, Douglas H; Withrow, Stephen J; Dow, Steven W
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Cancer immunology, immunotherapy: CII
      6. Products :
      7. Volume :
        59
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Chronic Disease; Disease Models, Animal; Immunity, Innate; Killer Cells, Natural; Macrophages; Mice; Mice, Inbred C3H; Mice, Inbred Strains; Monocytes; Neoplasms; Neovascularization, Pathologic; Osteomyelitis; Osteosarcoma; Staphylococcal Infections; Xen36
      12. Abstract :
        Clinical studies over the past several years have reported that metastasis-free survival times in humans and dogs with osteosarcoma are significantly increased in patients that develop chronic bacterial osteomyelitis at their surgical site. However, the immunological mechanism by which osteomyelitis may suppress tumor growth has not been investigated. Therefore, we used a mouse model of osteomyelitis to assess the effects of bone infection on innate immunity and tumor growth. A chronic Staphylococcal osteomyelitis model was established in C3H mice and the effects of infection on tumor growth of syngeneic DLM8 osteosarcoma were assessed. The effects of infection on tumor angiogenesis and innate immunity, including NK cell and monocyte responses, were assessed. We found that osteomyelitis significantly inhibited the growth of tumors in mice, and that the effect was independent of the infecting bacterial type, tumor type, or mouse strain. Depletion of NK cells or monocytes reversed the antitumor activity elicited by infection. Moreover, infected mice had a significant increase in circulating monocytes and numbers of tumor associated macrophages. Infection suppressed tumor angiogenesis but did not affect the numbers of circulating endothelial cells. Therefore, we concluded that chronic localized bacterial infection could elicit significant systemic antitumor activity dependent on NK cells and macrophages.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19701748
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9980
      1. Author :
        Burkatovskaya, Marina; Castano, Ana P; Demidova-Rice, Tatiana N; Tegos, George P; Hamblin, Michael R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2008
      5. Publication :
        Wound repair and regeneration: official publication of the Wound Healing Society [and] the European Tissue Repair Society
      6. Products :
      7. Volume :
        16
      8. Issue :
        3
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Infective Agents; Bandages; Biocompatible Materials; Bioware; Chitosan; Cyclophosphamide; Male; Mice; Mice, Inbred BALB C; Staphylococcal Skin Infections; Staphylococcus aureus; Wound Healing; Wound Infection; Xen8.1
      12. Abstract :
        HemCon bandage is an engineered chitosan acetate preparation designed as a hemostatic dressing, and is under investigation as a topical antimicrobial dressing. We studied its effects on healing of excisional wounds that were or were not infected with Staphylococcus aureus, in normal mice or mice previously pretreated with cyclophosphamide (CY). CY significantly suppressed wound healing in both the early and later stages, while S. aureus alone significantly stimulated wound healing in the early stages by preventing the initial wound expansion. CY plus S. aureus showed an advantage in early stages by preventing expansion, but a significant slowing of wound healing in later stages. In order to study the conflicting clamping and stimulating effects of chitosan acetate bandage on normal wounds, we removed the bandage from wounds at times after application ranging from 1 hour to 9 days. Three days application gave the earliest wound closure, and all application times gave a faster healing slope after removal compared with control wounds. Chitosan acetate bandage reduced the number of inflammatory cells in the wound at days 2 and 4, and had an overall beneficial effect on wound healing especially during the early period where its antimicrobial effect is most important.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/18471261
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9986
      1. Author :
        Burkatovskaya, Marina; Tegos, George P; Swietlik, Emilia; Demidova, Tatiana N; P Castano, Ana; Hamblin, Michael R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Biomaterials
      6. Products :
      7. Volume :
        27
      8. Issue :
        22
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Acetates; Alginates; Animals; Anti-Infective Agents; Bandages; Bioware; Chitosan; Glucuronic Acid; Hexuronic Acids; Male; Mice; Mice, Inbred BALB C; Occlusive Dressings; Proteus mirabilis; Pseudomonas aeruginosa; Silver Sulfadiazine; Staphylococcus aureus; Wound Healing; Wound Infection; Xen8.1, Xen5, Xen44
      12. Abstract :
        HemCon bandage is an engineered chitosan acetate preparation used as a hemostatic control dressing, and its chemical structure suggests that it should also be antimicrobial. We tested its ability to rapidly kill bacteria in vitro and in mouse models of infected wounds. We used the Gram-negative species Pseudomonas aeruginosa and Proteus mirabilis and the Gram-positive Staphylococcus aureus that had all been stably transduced with the entire bacterial lux operon to allow in vivo bioluminescence imaging. An excisional wound in Balb/c mice was inoculated with 50-250 million cells followed after 30 min by application of HemCon bandage, alginate sponge bandage, silver sulfadiazine cream or no treatment. HemCon was more adhesive to the wound and conformed well to the injury compared to alginate. Animal survival was followed over 15 days with observations of bioluminescence emission and animal activity daily. Chitosan acetate treated mice infected with P. aeruginosa and P. mirabilis all survived while those receiving no treatment, alginate and silver sulfadiazine demonstrated 25-100% mortality. Chitosan acetate was much more effective than other treatments in rapidly reducing bioluminescence in the wound consistent with its rapid bactericidal activity in vitro as well as its light-scattering properties. S. aureus formed only non-lethal localized infections after temporary immunosuppression of the mice but HemCon was again more effective in reducing bioluminescence. The data suggest that chitosan acetate rapidly kills bacteria in the wound before systemic invasion can take place, and is superior to alginate bandage and silver sulfadiazine that may both encourage bacterial growth in the short term.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16616364
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9987
      1. Author :
        Georgel, Philippe; Crozat, Karine; Lauth, Xavier; Makrantonaki, Evgenia; Seltmann, Holger; Sovath, Sosathya; Hoebe, Kasper; Du, Xin; Rutschmann, Sophie; Jiang, Zhengfan; Bigby, Timothy; Nizet, Victor; Zouboulis, Christos C; Beutler, Bruce
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        Infection and immunity
      6. Products :
      7. Volume :
        73
      8. Issue :
        8
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Bioware; Chromosome Mapping; Eye Diseases; Fatty Acids, Monounsaturated; Likelihood Functions; Lod Score; Mice; Mice, Inbred C57BL; Oleic Acid; Receptors, Immunologic; Sequence Analysis, DNA; Skin; Staphylococcal Skin Infections; Stearoyl-CoA Desaturase; Streptococcus pyogenes; Time Factors; Toll-Like Receptor 2; Xen8.1, Xen20, Xen14
      12. Abstract :
        flake (flk), an N-ethyl-N-nitrosourea-induced recessive germ line mutation of C57BL/6 mice, impairs the clearance of skin infections by Streptococcus pyogenes and Staphylococcus aureus, gram-positive pathogens that elicit innate immune responses by activating Toll-like receptor 2 (TLR2). Positional cloning and sequencing revealed that flk is a novel allele of the stearoyl coenzyme A desaturase 1 gene (Scd1). flake homozygotes show reduced sebum production and are unable to synthesize the monounsaturated fatty acids (MUFA) palmitoleate (C(16:1)) and oleate (C(18:1)), both of which are bactericidal against gram-positive (but not gram-negative) organisms in vitro. However, intradermal MUFA administration to S. aureus-infected mice partially rescues the flake phenotype, which indicates that an additional component of the sebum may be required to improve bacterial clearance. In normal mice, transcription of Scd1-a gene with numerous NF-kappaB elements in its promoter--is strongly and specifically induced by TLR2 signaling. Similarly, the SCD1 gene is induced by TLR2 signaling in a human sebocyte cell line. These observations reveal the existence of a regulated, lipid-based antimicrobial effector pathway in mammals and suggest new approaches to the treatment or prevention of infections with gram-positive bacteria.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16040962
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9990
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        Nature
      6. Products :
      7. Volume :
        433
      8. Issue :
        7025
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Aging; Animals; Antigens, CD36; Cell Line; Dimerization; Ethylnitrosourea; Gene Deletion; Glycerides; Homozygote; Humans; Immunologic Deficiency Syndromes; Lipopeptides; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutagenesis; Mutation; Oligopeptides; Peptidoglycan; Phenotype; Receptors, Cell Surface; Signal Transduction; Staphylococcal Infections; Staphylococcus aureus; Toll-Like Receptor 2; Toll-Like Receptors; Tumor Necrosis Factor-alpha; Zymosan
      12. Abstract :
        Toll-like receptor 2 (TLR2) is required for the recognition of numerous molecular components of bacteria, fungi and protozoa. The breadth of the ligand repertoire seems unusual, even if one considers that TLR2 may form heteromers with TLRs 1 and 6 (ref. 12), and it is likely that additional proteins serve as adapters for TLR2 activation. Here we show that an N-ethyl-N-nitrosourea-induced nonsense mutation of Cd36 (oblivious) causes a recessive immunodeficiency phenotype in which macrophages are insensitive to the R-enantiomer of MALP-2 (a diacylated bacterial lipopeptide) and to lipoteichoic acid. Homozygous mice are hypersusceptible to Staphylococcus aureus infection. Cd36(obl) macrophages readily detect S-MALP-2, PAM(2)CSK(4), PAM(3)CSK(4) and zymosan, revealing that some--but not all--TLR2 ligands are dependent on CD36. Already known as a receptor for endogenous molecules, CD36 is also a selective and nonredundant sensor of microbial diacylglycerides that signal via the TLR2/6 heterodimer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/15690042
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9991
      1. Author :
        Kuklin, Nelly A; Clark, Desmond J; Secore, Susan; Cook, James; Cope, Leslie D; McNeely, Tessie; Noble, Liliane; Brown, Martha J; Zorman, Julie K; Wang, Xin Min; Pancari, Gregory; Fan, Hongxia; Isett, Kevin; Burgess, Bruce; Bryan, Janine; Brownlow, Michelle; George, Hugh; Meinz, Maria; Liddell, Mary E; Kelly, Rosemarie; Schultz, Loren; Montgomery, Donna; Onishi, Janet; Losada, Maria; Martin, Melissa; Ebert, Timothy; Tan, Charles Y; Schofield, Timothy L; Nagy, Eszter; Meineke, Andreas; Joyce, Joseph G; Kurtz, Myra B; Caulfield, Michael J; Jansen, Kathrin U; McClements, William; Anderson, Annaliesa S
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Infection and immunity
      6. Products :
      7. Volume :
        74
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antibodies, Bacterial; Antigens, Bacterial; Bioware; Cation Transport Proteins; Disease Models, Animal; Female; Humans; Macaca mulatta; Mice; Mice, Inbred BALB C; Mice, Inbred ICR; Sepsis; Sequence Homology, Amino Acid; Staphylococcal Infections; Staphylococcal Vaccines; Staphylococcus aureus; Survival Rate; Xen8.1
      12. Abstract :
        Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the rate of resistance to clinically relevant antibiotics, such as methicillin, is increasing; furthermore, there has been an increase in the number of methicillin-resistant S. aureus community-acquired infections. Effective treatment and prevention strategies are urgently needed. We investigated the potential of the S. aureus surface protein iron surface determinant B (IsdB) as a prophylactic vaccine against S. aureus infection. IsdB is an iron-sequestering protein that is conserved in diverse S. aureus clinical isolates, both methicillin resistant and methicillin sensitive, and it is expressed on the surface of all isolates tested. The vaccine was highly immunogenic in mice when it was formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant, and the resulting antibody responses were associated with reproducible and significant protection in animal models of infection. The specificity of the protective immune responses in mice was demonstrated by using an S. aureus strain deficient for IsdB and HarA, a protein with a high level of identity to IsdB. We also demonstrated that IsdB is highly immunogenic in rhesus macaques, inducing a more-than-fivefold increase in antibody titers after a single immunization. Based on the data presented here, IsdB has excellent prospects for use as a vaccine against S. aureus disease in humans.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16552052
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9989
      1. Author :
        Kuklin, Nelly A; Pancari, Gregory D; Tobery, Timothy W; Cope, Leslie; Jackson, Jesse; Gill, Charles; Overbye, Karen; Francis, Kevin P; Yu, Jun; Montgomery, Donna; Anderson, Annaliesa S; McClements, William; Jansen, Kathrin U
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2003
      5. Publication :
        Antimicrobial agents and chemotherapy
      6. Products :
      7. Volume :
        47
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Abscess; Acetamides; Animals; Anti-Bacterial Agents; Bioware; Catheterization; Colony Count, Microbial; Dose-Response Relationship, Drug; Female; Foreign Bodies; Luminescent Measurements; Mice; Mice, Inbred BALB C; Muscle, Skeletal; Oxazolidinones; Staphylococcal Infections; Staphylococcus aureus; Thigh; Time Factors; Wound Infection; Xen8.1
      12. Abstract :
        Staphylococcal infections associated with catheter and prosthetic implants are difficult to eradicate and often lead to chronic infections. Development of novel antibacterial therapies requires simple, reliable, and relevant models for infection. Using bioluminescent Staphylococcus aureus, we have adapted the existing foreign-body and deep-wound mouse models of staphylococcal infection to allow real-time monitoring of the bacterial colonization of catheters or tissues. This approach also enables kinetic measurements of bacterial growth and clearance in each infected animal. Persistence of infection was observed throughout the course of the study until termination of the experiment at day 16 in a deep-wound model and day 21 in the foreign-body model, providing sufficient time to test the effects of antibacterial compounds. The usefulness of both animal models was assessed by using linezolid as a test compound and comparing bioluminescent measurements to bacterial counts. In the foreign-body model, a three-dose antibiotic regimen (2, 5, and 24 h after infection) resulted in a decrease in both luminescence and bacterial counts recovered from the implant compared to those of the mock-treated infected mice. In addition, linezolid treatment prevented the formation of subcutaneous abscesses, although it did not completely resolve the infection. In the thigh model, the same treatment regimen resulted in complete resolution of the luminescent signal, which correlated with clearance of the bacteria from the thighs.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/12936968
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9992
      1. Author :
        Lambrechts, Saskia A G; Demidova, Tatiana N; Aalders, Maurice C G; Hasan, Tayyaba; Hamblin, Michael R
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2005
      5. Publication :
        Photochemical & photobiological sciences: Official journal of the European Photochemistry Association and the European Society for Photobiology
      6. Products :
      7. Volume :
        4
      8. Issue :
        7
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Burns; Mice; Photochemotherapy; Staphylococcal Infections; Staphylococcus aureus; Xen8.1
      12. Abstract :
        The rise of multiply antibiotic resistant bacteria has led to searches for novel antimicrobial therapies to treat infections. Photodynamic therapy (PDT) is a potential candidate; it uses the combination of a photosensitizer with visible light to produce reactive oxygen species that lead to cell death. We used PDT mediated by meso-mono-phenyl-tri(N-methyl-4-pyridyl)-porphyrin (PTMPP) to treat burn wounds in mice with established Staphylococcus aureus infections The third degree burn wounds were infected with bioluminescent S. aureus. PDT was applied after one day of bacterial growth by adding a 25% DMSO/500 microM PTMPP solution to the wound followed by illumination with red light and periodic imaging of the mice using a sensitive camera to detect the bioluminescence. More than 98% of the bacteria were eradicated after a light dose of 210 J cm(-2) in the presence of PTMPP. However, bacterial re-growth was observed. Light alone or PDT both delayed the wound healing. These data suggest that PDT has the potential to rapidly reduce the bacterial load in infected burns. The treatment needs to be optimized to reduce wound damage and prevent recurrence.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/15986057
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9993
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        American journal of respiratory and critical care medicine
      6. Products :
      7. Volume :
        175
      8. Issue :
        2
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Cattle; Cells, Cultured; Cystic Fibrosis; Flavoproteins; Humans; Hydrogen peroxide; Immunity, Innate; Immunity, Mucosal; Lactoperoxidase; Lung Diseases; Pseudomonas aeruginosa; Rats; Reactive Oxygen Species; Respiratory Mucosa; RNA, Small Interfering; Staphylococcus aureus; Thiocyanates; Trachea; Xen8.1
      12. Abstract :
        RATIONALE The respiratory tract is constantly exposed to airborne microorganisms. Nevertheless, normal airways remain sterile without recruiting phagocytes. This innate immune activity has been attributed to mucociliary clearance and antimicrobial polypeptides of airway surface liquid. Defective airway immunity characterizes cystic fibrosis (CF), a disease caused by mutations in the CF transmembrane conductance regulator, a chloride channel. The pathophysiology of defective immunity in CF remains to be elucidated. OBJECTIVE We investigated the ability of non-CF and CF airway epithelia to kill bacteria through the generation of reactive oxygen species (ROS). METHODS ROS production and ROS-mediated bactericidal activity were determined on the apical surfaces of human and rat airway epithelia and on cow tracheal explants. MEASUREMENTS AND MAIN RESULTS Dual oxidase enzyme of airway epithelial cells generated sufficient H(2)O(2) to support production of bactericidal hypothiocyanite (OSCN(-)) in the presence of airway surface liquid components lactoperoxidase and thiocyanate (SCN(-)). This OSCN(-) formation eliminated Staphylococcus aureus and Pseudomonas aeruginosa on airway mucosal surfaces, whereas it was nontoxic to the host. In contrast to normal epithelia, CF epithelia failed to secrete SCN(-), thereby rendering the oxidative antimicrobial system inactive. CONCLUSIONS These data indicate a novel innate defense mechanism of airways that kills bacteria via ROS and suggest a new cellular and molecular basis for defective airway immunity in CF.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17082494
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9988
      1. Author :
        Shi, Lei; Takahashi, Kazue; Dundee, Joseph; Shahroor-Karni, Sarit; Thiel, Steffen; Jensenius, Jens Christian; Gad, Faten; Hamblin, Michael R; Sastry, Kedarnath N; Ezekowitz, R Alan B
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2004
      5. Publication :
        The Journal of experimental medicine
      6. Products :
      7. Volume :
        199
      8. Issue :
        10
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Disease Susceptibility; DNA, Bacterial; Lung; Mannose-Binding Lectin; Mice; Mice, Knockout; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Spleen; Staphylococcal Infections; Xen8.1
      12. Abstract :
        Gram-positive organisms like Staphylococcus aureus are a major cause of morbidity and mortality worldwide. Humoral response molecules together with phagocytes play a role in host responses to S. aureus. The mannose-binding lectin (MBL, also known as mannose-binding protein) is an oligomeric serum molecule that recognizes carbohydrates decorating a broad range of infectious agents including S. aureus. Circumstantial evidence in vitro and in vivo suggests that MBL plays a key role in first line host defense. We tested this contention directly in vivo by generating mice that were devoid of all MBL activity. We found that 100% of MBL-null mice died 48 h after exposure to an intravenous inoculation of S. aureus compared with 45% mortality in wild-type mice. Furthermore, we demonstrated that neutrophils and MBL are required to limit intraperitoneal infection with S. aureus. Our study provides direct evidence that MBL plays a key role in restricting the complications associated with S. aureus infection in mice and raises the idea that the MBL gene may act as a disease susceptibility gene against staphylococci infections in humans.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/15148336
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9994
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