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Berlin Brandenburg

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  • 1
    Language: English
    In: Medicinal Research Reviews, May 2005, Vol.25(3), pp.331-342
    Description: Systemically applied agents to modulate the Fas/FasL system, e.g., by stimulation of Fas on activated leukocytes or tumor cells failed as strategies in immune therapy due to severe toxic effects in the host. Recently, a novel strategy has been developed by using immobilized immune active biologicals in a medical device that may allow immune management without expensive systemic therapy. This review reports on the potential role of Fas/FasL in immune therapy and summarizes current experimental and clinical data with the leukocyte inhibition module (LIM), an immobilized anti‐Fas antibody containing device yet used in extracorporeal blood circulation. This proof of principal may stimulate the development of other devices based on the regulation of Fas/FasL or other targets relevant for immune disorders. © 2004 Wiley Periodicals, Inc.
    Keywords: Novel Therapeutic Strategies ; Immune Management ; Apoptosis
    ISSN: 0198-6325
    E-ISSN: 1098-1128
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  • 2
    Language: English
    In: Biochemical and Biophysical Research Communications, 2005, Vol.329(2), pp.616-623
    Description: The adhesion of highly activated neutrophils to cerebral microvascular endothelial cells (MVECs) may contribute to disruption and hyperpermeability of the blood–brain barrier (BBB) after cardiac surgery with prolonged cardiopulmonary bypass (CPB). A correlation between CPB duration and neutrophil-mediated BBB damage has not been investigated on the cellular level yet. Therefore, we studied the effects of neutrophils from cardiac surgery patients with CPB time 〈80 min (group I; = 8) and 〉80 min (group II; = 8) on the integrity of cultured porcine MVEC. Ex vivo, neutrophils of group II but not of group I significantly degraded the molecule β-catenin whereas VE-cadherin and occludin were not modified. The transendothelial electric resistance as a measure for the integrity of the endothelial monolayers was reduced over time in both groups. In conclusion, prolonged CPB time entails neutrophil-mediated decrease in MVEC β-catenin expression, and thus may be an important trigger for BBB disruption.
    Keywords: Blood–Brain Barrier ; Junction Molecule Complexes ; Cardiac Surgery ; Neutrophils ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0006-291X
    E-ISSN: 1090-2104
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  • 3
    In: ASAIO Journal, 2005, Vol.51(2), pp.144-147
    Description: Systemic administration of immune modulating antibodies may play an important role in reducing neutrophil hyperactivity, for example, in patients undergoing cardiac surgery with extracorporeal circulation or in trauma patients. However, this strategy has extremely high costs and is often associated with severe adverse effects. We developed the Leukocyte-Inhibition-Module (LIM), an extracorporeal circulation (ECC) device housing a polyurethane matrix with covalently bound Fas (CD95; APO-1) stimulating antibodies to rapidly prevent neutrophil hyperactivation. A feasibility study with 14 patients undergoing cardiac surgery with the use of immunogenic ECC without (n = 5) and with (n = 9) LIM (venous line) was performed. Our data show that the usually observed ECC associated perioperative increase in neutrophils (control) was prevented by LIM (p = 0.023). Moreover, the increase of the proinflammatory markers tumor necrosis factor (TNF)-α and polymorphonuclear elastase was limited by LIM (p = 0.038 and p = 0.002). In both groups, no significant changes in liver enzymes or in clotting were detected after surgery, and up to 12 months follow up, no unusual complications were reported. This study shows for the first time to our knowledge the feasibility, efficacy, and safety of a new cost effective, immune management strategy in patients with aberrant immune activation by exposing the blood stream to immobilized agonistic anti-Fas antibodies.
    Keywords: Coronary Artery Bypass ; Antibodies -- Therapeutic Use ; Extracorporeal Circulation -- Instrumentation ; Leukocytes -- Drug Effects ; Neutrophil Activation -- Drug Effects ; Fas Receptor -- Immunology;
    ISSN: 1058-2916
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  • 4
    Language: English
    In: Medicinal Research Reviews, March 2005, Vol.25(2), pp.167-185
    Description: It has been known for a long time that cytomegalovirus (CMV) has evolved mechanisms that allow the escape from the host immune surveillance. In the past, many efforts have been done to elucidate the molecular mechanisms underlying this virus‐mediated immune escape and thus virus persistence. However, it is unknown, whether CMV may also impair immune responses directed against tumor cells. This might have severe consequences on tumor progression and may explain the growing evidence for CMV‐mediated oncomodulation. This review summarizes recent work on CMV‐mediated immune escape mechanisms of tumor cells and oncomodulation and proposes novel aspects that may be important for understanding the CMV‐associated tumor progression. © 2004 Wiley Periodicals, Inc.
    Keywords: Human Cytomegalovirus Hcmv ; Oncomodulation ; Tumor ; Dna‐Virus ; Apoptosis ; Angiogenesis
    ISSN: 0198-6325
    E-ISSN: 1098-1128
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