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  • 1
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    Online Resource
    Adhesion Molecule Behavior during Rejection and Infection Episodes after Heart Transplantation
    Walter de Gruyter GmbH ; 2000
    In:  cclm Vol. 38, No. 5 ( 2000-05-21), p. 403-408
    Details
    In: cclm, Walter de Gruyter GmbH, Vol. 38, No. 5 ( 2000-05-21), p. 403-408
    Abstract: In cardiac transplant recipients the release of soluble cellular adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-Selectin into serum is pronounced during immune activation. It is uncertain whether there is a specific pattern of release during infection or cardiac allograft rejection. In a prospective study, 30 consecutive cardiac allograft recipients were followed for a median period of 11.4 months (range 1–34). Soluble ICAM-1 (sICAM-1), soluble VCAM-1 (sVCAM-1) and soluble E-Selectin (sE-Selectin) were measured in addition to acute phase proteins (C-reactive protein, α 1 -antitrypsin), complement factors (C3, C4) and β 2 -microglobulin. The measured serum levels were correlated with the clinical status of the transplant recipient: 1) uneventful clinical status; 2) asymptomatic infection; 3) symptomatic infection and 4) rejection. Forty age-matched healthy subjects served as controls. Six days before biopsy-proven cardiac allograft rejection sICAM-1-release started to increase (p 〈 0.05) as compared to uneventful clinical status. The peak concentration of sICAM-1 was measured three days before rejection. On the day of rejection, serum concentrations of sICAM-1 (p 〈 0.001) and sVCAM-1 (p 〈 0.05) were increased, whereas sE-Selectin was not markedly elevated. In symptomatic infections, the serum concentrations of sICAM-1 (p 〈 0.001) and sVCAM-1 (p 〈 0.05) were elevated at the day of diagnosis and both parameters reached peak levels three days after onset of chemotherapy. In multivariate analysis soluble adhesion molecules only weakly discriminated between rejection and infection (sensitivity: 13%, specificity: 95%). Although, in combination with routine blood parameters the discriminatory power could be improved (sensitivity: 85%, specificity: 85%) the clinical utility of these markers in non-invasive monitoring is limited.
    Type of Medium: Online Resource
    ISSN: 1434-6621
    URL: Article
    DOI: 10.1515/CCLM.2000.058
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2000
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  • 2
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    A Simple HPLC Method for Monitoring Mycophenolic Acid and Its Glucuronidated Metabolite in Transplant Recipients
    Walter de Gruyter GmbH ; 1999
    In:  cclm Vol. 37, No. 4 ( 1999-04-01), p. 409-415
    Details
    In: cclm, Walter de Gruyter GmbH, Vol. 37, No. 4 ( 1999-04-01), p. 409-415
    Abstract: Mycophenolic acid (MPA) is nowadays in broad clinical use as a substitute for azathioprine. An immunoassay for MPA recently received approval for clinical applications. The high performance liquid chromatography (HPLC) assay for measuring MPA and its glucuronide conjugate (MPAG) we describe here is not only rapid and simple but also extremely sensitive at plasma levels obtained during standard immunosuppressive regimens. The determination of MPAG is possible without any change of the chromatographic conditions (detection wavelength of 214 nm, mobile phase: acetonitrile and 50 mmol/l o-phosphoric acid (50:50, V/V), run time: 15 min). The required equipment is a standard HPLC system including a simple UV-detector. Sample volume of 400 μl is required for both determinations. Detection limit is 0.25 μmol/l for MPA and 5 μmol/l for MPAG. Linearity is excellent for serial dilutions (0.5–25 μmol/l for MPA, 25–500 μmol/l for MPAG) and high accuracies favour the method described. More than 2000 plasma samples tested for MPA in patients after heart transplantation within one year and more than 500 samples for MPAG underline the clinical applicability of this assay.
    Type of Medium: Online Resource
    ISSN: 1434-6621
    URL: Article
    DOI: 10.1515/CCLM.1999.067
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 1999
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  • 3
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    Mycophenolic Acid Influences T Helper 2 (Th2) Cytokine Induced Expression of Intercellular Cell Adhesion Molecule -1 (ICAM-1) on Human Endothelial Cells
    Walter de Gruyter GmbH ; 1999
    In:  cclm Vol. 37, No. 3 ( 1999-03-01), p. 253-257
    Details
    In: cclm, Walter de Gruyter GmbH, Vol. 37, No. 3 ( 1999-03-01), p. 253-257
    Abstract: A possible synergistic effect of mycophenolic acid (MPA) and the immunosuppressive cytokines IL-4, IL-10 and IL-13 was investigated in human umbilical vein endothelial cells (HUVEC). These cytokines, which are produced by Th2-lymphocytes, were shown to induce the expression of vascular cell adhesion molecule-1 (VCAM-1) and production of IL-6 in endothelial cells. In this study we found IL-4 to induce both intercellular cell adhesion molecule-1 (ICAM-1) and VCAM-1 expression, whereas IL-13 induced VCAM-1 only. The surface expression of E-selectin was not influenced by any of the cytokines tested. MPA on its own led to statistically significant ICAM-1 expression on HUVEC. The combination of MPA with IL-4 led to a significant ICAM-1 expression in an additive manner compared to the cytokine alone. In contrast, MPA neither induced VCAM-1 nor did it influence the effects of IL-4 and IL-13 on VCAM-1 expression. A clinically relevant concentration of mycophenolic acid (10 μmol/l) decreased intracellular guanosine-5′-triphosphate (GTP) levels significantly. Since intracellular nucleotides are responsible for the glycosylation of proteins, a disturbance of the endothelial nucleotide balance could be responsible for the effects of MPA on ICAM-1. Guanine and guanosine prevented and partially reversed the actions of MPA, on both intracellular GTP and ICAM-1 expression, which strongly implies that MPA by interfering with nucleotide metabolism, affects the adhesive properties of endothelial cells, and by acting synergistically with IL-4 probably influences Th2 cytokine effects.
    Type of Medium: Online Resource
    ISSN: 1434-6621
    URL: Article
    DOI: 10.1515/CCLM.1999.044
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 1999
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  • 4
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    Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests
    Walter de Gruyter GmbH ; 2012
    In:  Clinical Chemistry and Laboratory Medicine (CCLM) Vol. 50, No. 9 ( 2012-09-1)
    Details
    In: Clinical Chemistry and Laboratory Medicine (CCLM), Walter de Gruyter GmbH, Vol. 50, No. 9 ( 2012-09-1)
    Abstract: Dabigatran etexilate is a new oral anticoagulant for the therapy and prophylaxis of venous thromboembolism and stroke prevention in patients with atrial fibrillation. To investigate the extent of interactions of this new anticoagulant with frequently used coagulation assays, we completed a multicenter in vitro trial with Conformité Européenne(CE)-labeled dabigatran-spiked plasma samples. Lyophilized plasma samples with dabigatran concentrations ranging from 0.00 to 0.48 μg/mL were sent to the coagulation laboratories of six major Austrian hospitals for evaluation. Coagulation assays were performed under routine conditions using standard reagents and analyzer. Dabigatran led to a dose-dependent prolongation of the clotting times in coagulometric tests and influenced the majority of the parameters measured. Statistically significant interference could be observed with the prothrombin time (PT), activated partial thromboplastin time (aPTT) and PT/aPTT-based assays (extrinsic/intrinsic factors, APC-resistance test) as well as lupus anticoagulant testing. Even non-clotting tests, such as the colorimetric factor XIII activity assay and to a minor extent the amidolytic antithrombin activity assay (via factor IIa) were affected. This multicenter trial confirms and also adds to existing data, demonstrating that laboratories should expect to observe strong interferences of coagulation tests with increasing concentrations of dabigatran. This finding might become particularly important in the elderly and in patients with renal impairment as well as patients whose blood is drawn at peak levels of dabigatran.
    Type of Medium: Online Resource
    ISSN: 1437-4331 , 1434-6621
    URL: Article
    DOI: 10.1515/cclm-2011-0888
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2012
    detail.hit.zdb_id: 1492732-9
    SSG: 15,3
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  • 5
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    Alterations of Endothelial Nucleotide Levels by Mycophenolic Acid Result in Changes of Membrane Glycosylation and E-Selectin Expression
    Walter de Gruyter GmbH ; 1999
    In:  cclm Vol. 37, No. 3 ( 1999-03-01), p. 259-264
    Details
    In: cclm, Walter de Gruyter GmbH, Vol. 37, No. 3 ( 1999-03-01), p. 259-264
    Abstract: The effect of the inhibitor of inosine-5′-monophosphate dehydrogenase (IMPDH), mycophenolic acid, on intracellular nucleotides and the synthesis of cellular glycoproteins was evaluated in human umbilical vein endothelial cells. A clinically attainable concentration (10 μmol/l) of mycophenolic acid decreased guanosine-5′-triphosphate (GTP) levels significantly and led to a strong elevation of uridine-5′-triphosphate (UTP), whereas intracellular adenosine-5′-triphosphate (ATP) pools remained unaffected. The staining of the endothelial cell membranes with lectins specific for fucose and mannose ( Ulex europaeus- and Galanthus nivalis agglutinin, respectively) was reduced, reflecting an inhibition of fucose and mannose incorporation into endothelial glycoproteins. The surface expression of E-selectin, an important determinant for leuko-endothelial interactions decreased significantly. Guanine and guanosine prevented the actions of mycophenolic acid and reversed the drug-induced decrease in GTP and its associated effects. The findings that mycophenolic acid produces alterations in the formation of glycoproteins and in the membrane architecture are indicative of metabolic lesions induced by an agent that depresses guanine nucleotide synthesis through inhibtion of IMPDH. The pronounced reduction of E-selectin surface expression on endothelial cells accompanied by changes of endothelial cell fucosylation, a prerequisite for the contact with lymphocytic L-selectin, indicates an inhibitory effect of mycophenolic acid in the rolling phase of leukocyte recruitment and strongly implies a new and additional immunosuppressive mechanism of this agent.
    Type of Medium: Online Resource
    ISSN: 1434-6621
    URL: Article
    DOI: 10.1515/CCLM.1999.045
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 1999
    detail.hit.zdb_id: 1492732-9
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