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  1. Article: Prevention of acute lung injury in swine: depletion of pulmonary intravascular macrophages using liposomal clodronate.

    Gaca, Jeffrey G / Palestrant, Daniel / Lukes, Daniel J / Olausson, Michael / Parker, William / Davis, R Duane

    The Journal of surgical research

    2003  Volume 112, Issue 1, Page(s) 19–25

    Abstract: Background: Swine contain large numbers of pulmonary intravascular macrophages (PIMs) that mediate the physiological response observed in acute lung injury (ALI). As the hyperacute dysfunction observed in pulmonary xenotransplantation is similar to ... ...

    Abstract Background: Swine contain large numbers of pulmonary intravascular macrophages (PIMs) that mediate the physiological response observed in acute lung injury (ALI). As the hyperacute dysfunction observed in pulmonary xenotransplantation is similar to endotoxin-induced ALI, PIMs may play a critical role in pulmonary xenograft dysfunction. We used liposomal clodronate to eliminate the PIM population in a model of acute swine lung injury.
    Materials and methods: Experimental swine (n = 6) received liposomal clodronate (1.25 g/10 kg) and control swine (n = 5) received saline containing liposomes before infusion of lipopolysaccharide (450 ng/kg).
    Results: Control swine demonstrated higher peak pulmonary artery pressures (41.8 +/- 2.2 versus 16.8 +/- 1.2 mm Hg; P < 0.0001) and higher peak pulmonary vascular resistances (1405 +/- 209 versus 353 +/- 81 dynes. s. cm(-5); P = 0.0016) in response to lipopolysaccharide infusion. Clodronate treated swine also had significantly lower serum levels of tumor necrosis factor-alpha, interleukin-6, and thrombin.
    Conclusions: Liposomal clodronate effectively attenuates acute swine lung injury induced by endotoxin. This method of depletion of the PIM population presents a promising new treatment of swine lungs before xenotransplantation.
    MeSH term(s) Acute Disease ; Animals ; Animals, Genetically Modified ; Antigens, CD/genetics ; Antimetabolites/pharmacology ; Clodronic Acid/pharmacology ; Cytokines/metabolism ; Graft Survival/drug effects ; Graft Survival/immunology ; Humans ; Lipopolysaccharides/pharmacology ; Liposomes ; Lung Diseases/immunology ; Lung Diseases/prevention & control ; Lung Diseases/surgery ; Lung Transplantation/immunology ; Macrophages, Alveolar/cytology ; Macrophages, Alveolar/drug effects ; Macrophages, Alveolar/metabolism ; Membrane Cofactor Protein ; Membrane Glycoproteins/genetics ; Pulmonary Wedge Pressure ; Swine ; Thrombin/metabolism ; Transplantation, Heterologous ; Vascular Resistance
    Chemical Substances Antigens, CD ; Antimetabolites ; CD46 protein, human ; Cytokines ; Lipopolysaccharides ; Liposomes ; Membrane Cofactor Protein ; Membrane Glycoproteins ; Clodronic Acid (0813BZ6866) ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2003-06-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80170-7
    ISSN 1095-8673 ; 0022-4804
    ISSN (online) 1095-8673
    ISSN 0022-4804
    DOI 10.1016/s0022-4804(03)00142-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 178: Show issues Location:
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  2. Book ; Online: William T. Vollmann

    Coffman, Christopher K / Bauer, Georg / Bolte, Carla / Chandler, Aaron / Corcoran, Heather / Cox, John K / Elliott, Okla / Franco, James / Franzen, Jonathan / Glawogger, Michael / Gusev, Mariya / Jensen, Joshua / Juvelis, Priscilla / Liebtag, Miles / Lukes, Daniel / McCaffery, Larry / Palleau-Papin, Françoise / Petro, Melissa / Rothacker, Jordan A /
    Santin, Bryan / Smith, Geoffrey D / Speaker, Mary Austin / Walonen, Michael K / Wisner, Buell

    A Critical Companion

    2014  

    Abstract: ... This book is the first collection of essays on the works of William T. Vollmann. It offers a comprehensive overview of his writings through scholarly essays and nonscholarly reflections that assess his oeuvre ...

    Abstract This book is the first collection of essays on the works of William T. Vollmann. It offers a comprehensive overview of his writings through scholarly essays and nonscholarly reflections that assess his oeuvre in terms of four conceptual categories: social, historical, political, and methodological. Taken together, these pieces place Vollmann among his peers in contemporary North American literature and open up new avenues for readers to negotiate the many challenges and rewards his texts present.
    Language English
    Size Online-Ressource (384 p)
    Publisher University of Delaware
    Publishing place Lanham
    Document type Book ; Online
    Note Description based upon print version of record
    ISBN 9781611495102 ; 1611495105
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  3. Article: Depletion of pulmonary intravascular macrophages prevents hyperacute pulmonary xenograft dysfunction.

    Cantu, Edward / Gaca, Jeffrey G / Palestrant, Daniel / Baig, Kamran / Lukes, Daniel J / Gibson, Sarah E / Gonzalez-Stawinski, Gonzalo V / Olausson, Michael / Parker, William / Davis, R Duane

    Transplantation

    2006  Volume 81, Issue 8, Page(s) 1157–1164

    Abstract: Background: Recent years have brought dramatic progress in the field of xenotransplantation, with the development of transgenic swine and various other means of overcoming the rejection mediated by xenoreactive antibodies. Although progress has been ... ...

    Abstract Background: Recent years have brought dramatic progress in the field of xenotransplantation, with the development of transgenic swine and various other means of overcoming the rejection mediated by xenoreactive antibodies. Although progress has been rapid with kidney and heart xenografts, progress with pulmonary xenografts has lagged behind. Recent findings have suggested that donor pulmonary intravascular macrophages may play a critical role in the hyperacute dysfunction of pulmonary xenografts.
    Methods: The function of pulmonary xenografts from pigs depleted of pulmonary intravascular macrophages was compared with the function of xenografts from normal pigs.
    Results: Pulmonary xenografts from pigs from which pulmonary intravascular macrophages were depleted survived (23.5+/-0.9 hours) about five times longer than normal (macrophage sufficient) xenografts (4.4+/-1.41 hours) (P< 0.0001). At 21 hours post-reperfusion, the left pulmonary arterial flow was 225.0+/-34 ml/min in lungs depleted of pulmonary intravascular macrophages, whereas all normal xenografts had failed.
    Conclusions: These findings indicate that donor macrophages play a critical role in pulmonary xenograft dysfunction. This finding has broad implications for xenotransplantation, suggesting that porcine macrophages might pose a barrier to the engraftment and function of a variety of porcine organ xenografts.
    MeSH term(s) Animals ; Blood Pressure ; Complement C5a/physiology ; Endothelium, Vascular/physiology ; Graft Survival ; Heart Rate ; Lung/blood supply ; Lung/pathology ; Lung Transplantation/adverse effects ; Macrophages/physiology ; Papio ; Pulmonary Circulation ; Swine ; Transplantation, Heterologous/adverse effects ; Vascular Resistance
    Chemical Substances Complement C5a (80295-54-1)
    Language English
    Publishing date 2006-04-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 208424-7
    ISSN 1534-6080 ; 0041-1337
    ISSN (online) 1534-6080
    ISSN 0041-1337
    DOI 10.1097/01.tp.0000169758.57679.2a
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 488: Show issues Location:
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    Zs.MO 509: Show issues

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  4. Article: Early onset of rejection in concordant hamster xeno hearts display signs of necrosis, but not apoptosis, correlating to the phosphocreatine concentration.

    Lukes, Daniel J / Tivesten, Asa / Wilton, Jakob / Lundgren, Andreas / Rakotonirainy, Olivier / Kjellström, Christer / Isgaard, Jörgen / Karlsson-Parra, Alex / Soussi, Bassam / Olausson, Michael

    Transplant immunology

    2003  Volume 12, Issue 1, Page(s) 29–40

    Abstract: Background: The importance of apoptosis contra necrosis for ischemia/reperfusion (RP) and acute rejection in concordant rodent xenotransplantation is largely unknown. We explored this question by comparing rodent allo and concordant xenotransplants with ...

    Abstract Background: The importance of apoptosis contra necrosis for ischemia/reperfusion (RP) and acute rejection in concordant rodent xenotransplantation is largely unknown. We explored this question by comparing rodent allo and concordant xenotransplants with different morphological methods to detect apoptosis and biochemical data on the levels of high-energy phosphates obtained with in vitro 31Phosphorous Magnetic Resonance Spectroscopy (31P MRS). More specifically, we applied a hitherto unused method in transplantation research, apoptosis specific biotin labeled oligonucleotides designed with a 10 base pair stem region and a 20 nucleotides large loop that form a hairpin like shape. The results obtained with this method were compared to results obtained with the more widely used in situ 3'-end labeling of DNA (TUNEL) assay and extraction and gel electrophoresis of labeled DNA (DNA laddering).
    Methods: Cervical heart transplantations were performed between inbred Lewis (L) (RT1l) to L, L to DA (RT1a) rats, hamster (H) to H and H to L (X) (n=5 for all groups except for X, n=9). All hearts were subjected to 30 min of cold ischemia (+4 degrees C) and 6 h of RP before explantation. In vitro 31P MRS was used to determine the phosphocreatine (PCr), beta-adenosine triphosphate (beta-ATP) concentrations and the PCr/beta-ATP ratio of the transplants. We correlated the biochemical data to haematoxylin and eosin (H & E) stained tissue slides scored for rejection, infiltration of antibodies and complement depositions, DNA extraction and gel electrophoresis of labeled DNA (DNA laddering), in situ 3'-end labeling of DNA (TUNEL) and the apoptosis specific hairpin probe assays scoring.
    Results: The rejection score of the xeno grafts differed significantly compared to their syngeneic hamster to hamster controls (2.40 +/- 0.25 vs. 1.20 +/- 0.20; P=0.005) and they had a significantly higher TUNEL score, 228 +/- 15 vs. 2.44 +/- 0.32 (P=0.009), that correlated to changes in PCr concentration (P<0.001) and to the PCr/beta-ATP ratio (P=0.01). The uptake was mainly (90-95%) located to 1-2 microm large extra cellular 'granule'. A picture resembling early necrosis was seen on the H & E stainings and reflected in the Billingham rejection score above.
    Conclusions: After 6 h of RP the onset of acute rejection in the concordant hamster xeno hearts displayed features of early, possibly mitochondrial, necrosis, but not apoptosis, which correlated to changes in the PCr concentration and the PCr/beta-ATP ratio. The mechanism for the early rejection observed is unclear and might be caused by other factors in the sera apart from cellular components, antibodies and complement factors. Identification of the underlying mechanisms could enable us to design rational therapies that prevent activation of the recipient's innate immune response.
    MeSH term(s) Adenosine Triphosphate/analysis ; Animals ; Antibodies/analysis ; Apoptosis/immunology ; Complement C3a/analysis ; Cricetinae ; DNA Fragmentation ; Data Interpretation, Statistical ; Graft Rejection/immunology ; Heart Transplantation/immunology ; Immunohistochemistry/methods ; In Situ Nick-End Labeling ; Magnetic Resonance Spectroscopy ; Male ; Mesocricetus ; Myocardium/chemistry ; Myocardium/pathology ; Necrosis ; Oligonucleotide Probes/chemistry ; Phosphocreatine/analysis ; Phosphocreatine/metabolism ; Rats ; Rats, Inbred Lew ; Time Factors ; Transplantation, Heterologous ; Transplantation, Homologous ; Transplantation, Isogeneic
    Chemical Substances Antibodies ; Oligonucleotide Probes ; Phosphocreatine (020IUV4N33) ; Complement C3a (80295-42-7) ; Adenosine Triphosphate (8L70Q75FXE)
    Language English
    Publishing date 2003-10
    Publishing country Netherlands
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1160846-8
    ISSN 1878-5492 ; 0966-3274
    ISSN (online) 1878-5492
    ISSN 0966-3274
    DOI 10.1016/S0966-3274(03)00018-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3784: Show issues Location:
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