Publications by authors named "Klappacher G"

Endothelin (ET)-1 is a pro-fibrotic vasoconstrictive peptide causing microvascular dysfunction and cardiac remodelling after acute ST-elevation myocardial infarction (STEMI). It acts via two distinct receptors, ET-A and ET-B, and is involved in inflammation and atherogenesis. Patients with posterior-wall STEMI were randomly assigned to intravenous BQ-123 at 400 nmol/minute (min) or placebo over 60 min, starting immediately prior to primary percutaneous coronary intervention (n=54).

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Monocytes play a critical role in atherogenesis by their inflammatory signals and differentiation into macrophage foam cells through cholesterol accumulation. The seminal finding of high levels of the peroxisome proliferator-activated receptor gamma in macrophage foam cells has opened up the prospect that its ligands, most importantly the thiazolidinedione class of drugs, might directly influence the development of atheromatous lesions. The present review weighs the growing evidence on regulation of both inflammatory responses and cholesterol homeostasis in macrophages by peroxisome proliferator-activated receptor gamma ligands with regard to their overall impact as antiatherogenic agents.

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Defining the molecular mechanisms that coordinately regulate proliferation and differentiation is a central issue in development. Here, we describe a mechanism in which induction of the Ets repressor METS/PE1 links terminal differentiation to cell cycle arrest. Using macrophages as a model, we provide evidence that METS/PE1 blocks Ras-dependent proliferation without inhibiting Ras-dependent expression of cell type-specific genes by selectively replacing Ets activators on the promoters of cell cycle control genes.

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Background: Increased expression of inducible nitric oxide synthase (iNOS) has been described in humans with cardiomyopathies. Most animal models of ischemia-induced heart failure use the surgical ligation of coronary arteries. However, studies of iNOS expression in these models may be confounded by a robust immune response because of the surgical procedure itself leading to iNOS expression in the heart, as well as in other tissues.

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Objective: To evaluate the influence of pentoxifylline (PTX), a phosphodiesterase inhibitor, on cytokines and inflammatory proteins in patients suffering from septic shock.

Design: Prospective study comparing a therapy group to a matched control group.

Setting: Medical intensive care unit at a university hospital.

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Complement-dependent activation of immune cells is regulated by cell surface membrane receptors. In this study, expression of complement receptors (CR) on human blood basophils (n = 11), tissue mast cells (lung, n = 7; skin, n = 10; uterus, n = 4; tonsil, n = 3; heart, n = 10), and on respective human cell lines (basophil line KU-812, mast cell line HMC-1) was analyzed by the use of mAbs and indirect immunofluorescence. Normal blood basophils and KU-812 cells were found to express C5aR (CD88), membrane cofactor protein (CD46), decay-accelerating factor (CD55), and membrane attack complex inhibitory factor (CD59), as well as the previously recognized CR1 (CD35), CR3 alpha (CD11b), CR4 alpha (CD11c), and CR3/4 beta (CD18).

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Circulating levels of extracellular matrix components were measured by radioimmunoassays and tested if they were useful for clinical staging in chronic heart failure. In 41 patients with dilated cardiomyopathy (33 idiopathic and 8 ischemic cases), the serum concentrations of procollagen type III aminoterminal peptide (PIIINP), type I collagen telopeptide (ICTP), and basement membrane laminin were significantly higher than in 30 healthy controls regardless of the underlying etiology. Patients with serum values of PIIINP, ICTP, and laminin > 7 micrograms/L, 7.

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The airway was managed successfully in two cases of difficult intubation using the Combitube, a new device for emergency intubation, which combines the functions of an oesophageal obturator airway and a conventional endotracheal airway. One patient could not be intubated due to lockjaw; in the other patient, the vocal cords could not be seen because of continued vomiting. The cases illustrate the benefit of the Combitube during emergency intubation for different problems and its effectiveness as an alternative to traditional intubation techniques.

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Background: The atrial appendage is a predilection site for thrombus formation. Mast cells (MC) are a rich source of mediators that may be involved in the regulation of thrombus formation. We examined number, distribution, and phenotype of MC in thrombosed versus unaffected auricles to elucidate their possible role in auricular thrombosis (AUTHR).

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We have isolated and characterized the human cardiac mast cell (CMC) and compared this novel mast cell (MC type with MC obtained from uterus, skin, and lung. Heart tissue was obtained from 14 patients with cardiomyopathy (CMP, heart transplantation). CMC were isolated by enzymatic digestion using collagenase, pronase-E, hyaluronidase, and DNAse.

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In a total of 22 failing hearts from human transplant recipients, the expression of major histocompatibility complex (MHC) molecules, the CD phenotype of infiltrating mononuclear cells, and the number of fibroblasts were analyzed by immunohistochemistry. Compared with 10 non-failing control hearts, significantly higher morphometric area fractions of HLA-ABC and HLA-DR with a concomitant increase of CD3-, CD4- and CD8-positive cells were found to be comparable in 12 patients with idiopathic dilated cardiomyopathy and in 10 patients with secondary heart failure. Furthermore, the similarity of T-cell activation in idiopathic and secondary variants of the disease were substantiated by the following observations: (1) the site-specific distribution of MHC molecules and mononuclear cells in the myocardium was comparable in idiopathic and secondary dilated cardiomyopathy; (2) 6 individuals with lymphocytic aggregates in their myocardium in association with the highest levels of HLA-ABC expression were equally distributed among idiopathic and secondary patient subsets; and (3) expression of HLA-ABC and HLA-DR correlated with that of an endothelial cell marker, von Willebrand factor, in failing myocardia of both study groups.

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Serological markers of cell-mediated immunity, i.e., soluble CD4, soluble interleukin-2 (Il-2) receptor and beta 2-microglobulin, were determined in 60 patients with dilated cardiomyopathy.

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Recent data suggest that stem cell factor (SCF or c-kit ligand, KL) is a major regulator of human mast cells (MCs). In the present study, MCs derived from the lung (n = 8), uterus (n = 14) and heart (n = 4) were analyzed for expression of c-kit receptor and for responses to recombinant SCF. MCs of all organs tested were recognized by mAbs to c-kit (YB5.

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Unlabelled: Patient-controlled analgesia (PCA) is a well-proven procedure for individual pain relief in the post-operative period. Despite its superior approach regarding pharmacokinetic and pharmacodynamic considerations, PCA equipment is not available to many in the clinical practice. The goal of this study was to compare the efficacy and safety of PCA with continuous infusion (CI), an easily feasible method, using tramadol (T) as a centrally acting opioid with minor side effects on circulation and ventilation.

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In order to evaluate their divergent effects on binding and lysis of the NCMC, rH IFN-alpha and rH IL-2 were used for the in vitro-preincubation of normal donors' PBL, which were then tested as effector cells against K562 and the long-term cultured melanoma cell line RIMA in the SCCA. Both lymphokines significantly augmented the cytolysis of K562 without relevant influence on the conjugate formation. However, against RIMA IFN-alpha additionally amplified the binding affinity.

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MHC nonrestricted cytotoxic cells play an important role in the killing of tumor cells in vitro and potentially in vivo. The activity of these cells is regulated by several cytokines such as IL-2 and IFN. In the present study we provide first evidence that IL-6 significantly augments the cytotoxic activity of human NK cells.

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In order to evaluate the effect of biological response modifiers on NK- and NK-like activity, interferons were tested in the single cell cytotoxicity assay (SCCA) with various effector/target combinations. alpha Interferon (IFN-alpha) significantly augmented the cytolysis of K 562 in vitro by non-adherent peripheral blood lymphocytes of normal donors without any influence on the binding capacity. Similarly, in vivo, the intraperitoneal administration of gamma Interferon (IFN-gamma) to patients with ovarian carcinomas resulted in a significant increase in the autologous cytotoxicity in the ascitic compartment.

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