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      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 :
        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 :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Blood
      6. Products :
      7. Volume :
        108
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Adoptive Transfer; Animals; Antigen Presentation; Autoantigens; B16-F10-luc-G5 cells; Bioware; Cancer Vaccines; dendritic cells; Endosomes; Lymphocyte Activation; Lymphoma; Mice; Mice, Knockout; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory; Vaccination
      12. Abstract :
        Lymphoma cells are malignant cells of the T- or B-cell lineage that often express many surface markers inappropriately, yet are not recognized as abnormal by the immune system. We modeled this situation by inoculating ovalbumin-expressing E.G7-OVA lymphoma cells into mice that expressed ovalbumin as a self antigen in pancreatic islets, and investigated the efficacy of dendritic cell (DC) vaccination in these mice. Although vaccination with DC-expressing ovalbumin induced strong cytotoxic T-cell immunity, which led to clearance of E.G7-OVA lymphoma cells in naive C57BL/6 mice, DC vaccination was ineffective in mice expressing ovalbumin as a self antigen. Antigen modification to increase its processing via the endosomal processing pathway dramatically increased CD4 T-cell activation but paradoxically, impaired the protective effect of DC vaccination even in naive mice. Depletion of CD25(+) T cells (regulatory T cells [Tregs]) prior to vaccination restored the efficacy of DC vaccination and allowed eradication of lymphoma also in mice expressing ovalbumin as a self antigen. We conclude that lymphoma cells may be eradicated using DC vaccination if activation of CD25(+) Tregs is simultaneously inhibited, and that intentionally enhanced endosomal antigen processing in DC vaccines may shift the balance from CD4 T-cell help toward stimulation of Tregs.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16621963
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9002
      1. Author :
        Lyons, Scott K; Lim, Ed; Clermont, Anne O; Dusich, Joan; Zhu, Lingyun; Campbell, Kenneth D; Coffee, Richard J; Grass, David S; Hunter, John; Purchio, Tony; Jenkins, Darlene
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Cancer research
      6. Products :
      7. Volume :
        66
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Androgens; Animals; Bioware; Cell Transformation, Neoplastic; Disease Models, Animal; Genes, Reporter; Humans; Image Processing, Computer-Assisted; In Situ Hybridization; Luciferases, Firefly; Luminescent Measurements; Male; Mice; Mice, Transgenic; PC-3M-luc; Promoter Regions, Genetic; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms
      12. Abstract :
        Several transgenic mouse models of prostate cancer have been developed recently that are able to recapitulate many key biological features of the human condition. It would, therefore, be desirable to employ these models to test the efficacy of new therapeutics before clinical trial; however, the variable onset and non-visible nature of prostate tumor development limit their use for such applications. We now report the generation of a transgenic reporter mouse that should obviate these limitations by enabling noninvasive in vivo bioluminescence imaging of normal and spontaneously transformed prostate tissue in the mouse. We used an 11-kb fragment of the human prostate-specific antigen (PSA) promoter to achieve specific and robust expression of firefly luciferase in the prostate glands of transgenic mice. Ex vivo bioluminescence imaging and in situ hybridization analysis confirmed that luciferase expression was restricted to the epithelium in all four lobes of the prostate. We also show that PSA-Luc mice exhibit decreased but readily detectable levels of in vivo bioluminescence over extended time periods following androgen ablation. These results suggest that this reporter should enable in vivo imaging of both androgen-dependent and androgen-independent prostate tumor models. As proof-of-principle, we show that we could noninvasively image SV40 T antigen-induced prostate tumorigenesis in mice with PSA-Luc. Furthermore, we show that our noninvasive imaging strategy can be successfully used to image tumor response to androgen ablation in transgenic mice and, as a result, that we can rapidly identify individual animals capable of sustaining tumor growth in the absence of androgen.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16651422
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8975
      1. Author :
        Beckers, Annelies; Organe, Sophie; Timmermans, Leen; Vanderhoydonc, Frank; Deboel, Ludo; Derua, Rita; Waelkens, Etienne; Brusselmans, Koen; Verhoeven, Guido; Swinnen, Johannes V
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Molecular cancer therapeutics
      6. Products :
      7. Volume :
        5
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Adenosine Triphosphate; Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Bioware; Breast Neoplasms; Carcinoma, Squamous Cell; Cell Line, Tumor; DNA, Neoplasm; Drug Synergism; Enzyme Activation; Humans; Lipids; Methotrexate; Multienzyme Complexes; Nucleotide Deaminases; PC-3M-luc; Phosphoribosylaminoimidazolecarboxamide Formyltransferase; Phosphoribosylglycinamide Formyltransferase; Protein-Serine-Threonine Kinases; Purines; Ribonucleosides; Ribonucleotides; RNA Interference
      12. Abstract :
        Because of its ability to mimic a low energy status of the cell, the cell-permeable nucleoside 5-aminoimidazole-4-carboxamide (AICA) riboside was proposed as an antineoplastic agent switching off major energy-consuming processes associated with the malignant phenotype (lipid production, DNA synthesis, cell proliferation, cell migration, etc.). Key to the antineoplastic action of AICA riboside is its conversion to ZMP, an AMP mimetic that at high concentrations activates the AMP-activated protein kinase (AMPK). Here, in an attempt to increase the efficacy of AICA riboside, we pretreated cancer cells with methotrexate, an antimetabolite blocking the metabolism of ZMP. Methotrexate enhanced the AICA riboside-induced accumulation of ZMP and led to a decrease in the levels of ATP, which functions as an intrasteric inhibitor of AMPK. Consequently, methotrexate markedly sensitized AMPK for activation by AICA riboside and potentiated the inhibitory effects of AICA riboside on tumor-associated processes. As cotreatment elicited antiproliferative effects already at concentrations of compounds that were only marginally effective when used alone, our findings on the cooperation between methotrexate and AICA riboside provide new opportunities both for the application of classic antimetabolic chemotherapeutics, such as methotrexate, and for the exploitation of the energy-sensing machinery as a target for cancer intervention.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/16985054
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8978
      1. Author :
        N/A
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Lasers in surgery and medicine
      6. Products :
      7. Volume :
        39
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Anti-Infective Agents; Biofilms; Dental Pulp Cavity; Dental Pulp Diseases; Endodontics; Humans; Luminescence; Photochemotherapy; Polyethyleneimine; Porphyrins; Proteus Infections; Proteus mirabilis; Pseudomonas aeruginosa; Pseudomonas Infections; Xen5; Xen44
      12. Abstract :
        BACKGROUND AND OBJECTIVE To compare the effectiveness of antimicrobial photodynamic therapy (PDT), standard endodontic treatment and the combined treatment to eliminate bacterial biofilms present in infected root canals. STUDY DESIGN/MATERIALS AND METHODS Ten single-rooted freshly extracted human teeth were inoculated with stable bioluminescent Gram-negative bacteria, Proteus mirabilis and Pseudomonas aeruginosa to form 3-day biofilms in prepared root canals. Bioluminescence imaging was used to serially quantify bacterial burdens. PDT employed a conjugate between polyethylenimine and chlorin(e6) as the photosensitizer (PS) and 660-nm diode laser light delivered into the root canal via a 200-micro fiber, and this was compared and combined with standard endodontic treatment using mechanical debridement and antiseptic irrigation. RESULTS Endodontic therapy alone reduced bacterial bioluminescence by 90% while PDT alone reduced bioluminescence by 95%. The combination reduced bioluminescence by >98%, and importantly the bacterial regrowth observed 24 hours after treatment was much less for the combination (P<0.0005) than for either single treatment. CONCLUSIONS Bioluminescence imaging is an efficient way to monitor endodontic therapy. Antimicrobial PDT may have a role to play in optimized endodontic therapy.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17066481
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9997
      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 :
        Hanai, Koji; Takeshita, Fumitaka; Honma, Kimi; Nagahara, Shunji; Maeda, Miho; Minakuchi, Yoshiko; Sano, Akihiko; Ochiya, Takahiro
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2006
      5. Publication :
        Annals of the New York Academy of Sciences
      6. Products :
      7. Volume :
        1082
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Bone Neoplasms; Collagen; Dermatitis; Disease Models, Animal; Drug Carriers; Gene Therapy; Humans; Hypersensitivity; Mice; Mice, Nude; Nanoparticles; Neoplasm Metastasis; Oligonucleotides; PC-3M-luc; RNA, Small Interfering; Tissue Distribution
      12. Abstract :
        The goal of our research is to provide a practical platform for drug delivery in oligonucleotide therapy. We report here the efficacy of an atelocollagen-mediated oligonucleotide delivery system applied to systemic siRNA and antisense oligonucleotide treatments in animal disease models. Atelocollagen and oligonucleotides formed a complex of nanosized particles, which was highly stable against nucleases. The complex allowed oligonucleotides to be delivered efficiently into several organs and tissues via intravenous administration. In a tumor metastasis model, the complex successfully delivered siRNA to metastasized tumors in bone tissue and inhibited their growth. We also demonstrated that a single intravenous treatment of the antisense oligodeoxynucleotide complex suppressed ear dermatitis in a contact hypersensitivity model. These results indicate the strong potential of the atelocollagen-mediated drug delivery system for practical therapeutic technology.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17145919
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8976
      1. Author :
        Mortin, Lawrence I; Li, Tongchuan; Van Praagh, Andrew D G; Zhang, Shuxin; Zhang, Xi-Xian; Alder, Jeff D
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2007
      5. Publication :
        Antimicrobial agents and chemotherapy
      6. Products :
      7. Volume :
        51
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Acetamides; Animals; Anti-Bacterial Agents; Bioware; Colony Count, Microbial; Daptomycin; Female; Luminescent Measurements; Methicillin Resistance; Mice; Microbial Sensitivity Tests; Neutropenia; Oxazolidinones; Peritonitis; Staphylococcus aureus; Xen29
      12. Abstract :
        The rising rates of antibiotic resistance accentuate the critical need for new antibiotics. Daptomycin is a new antibiotic with a unique mode of action and a rapid in vitro bactericidal effect against gram-positive organisms. This study examined the kinetics of daptomycin's bactericidal action against peritonitis caused by methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in healthy and neutropenic mice and compared this activity with those of other commonly used antibiotics. CD-1 mice were inoculated intraperitoneally with lethal doses of MSSA (Xen-29) or MRSA (Xen-1), laboratory strains transformed with a plasmid containing the lux operon, which confers bioluminescence. One hour later, the animals were given a single dose of daptomycin at 50 mg/kg of body weight subcutaneously (s.c.), nafcillin at 100 mg/kg s.c., vancomycin at 100 mg/kg s.c., linezolid at 100 mg/kg via gavage (orally), or saline (10 ml/kg s.c.). The mice were anesthetized hourly, and photon emissions from living bioluminescent bacteria were imaged and quantified. The luminescence in saline-treated control mice either increased (neutropenic mice) or remained relatively unchanged (healthy mice). In contrast, by 2 to 3 h postdosing, daptomycin effected a 90% reduction of luminescence of MSSA or MRSA in both healthy and neutropenic mice. The activity of daptomycin against both MSSA and MRSA strains was superior to those of nafcillin, vancomycin, and linezolid. Against MSSA peritonitis, daptomycin showed greater and more rapid bactericidal activity than nafcillin or linezolid. Against MRSA peritonitis, daptomycin showed greater and more rapid bactericidal activity than vancomycin or linezolid. The rapid decrease in the luminescent signal in the daptomycin-treated neutropenic mice underscores the potency of this antibiotic against S. aureus in the immune-suppressed host.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/17307984
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9050
      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
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