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Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms. IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4Ralpha and either gammac or IL-13Ralpha1) and IL-13 operates through IL-13R (a heterodimer of IL-4Ralpha and IL-13Ralpha1) to promote IgE(More)
The reasons for differences in vulnerability or resilience to the development of posttraumatic stress disorder (PTSD) are unclear. Here we review key genetic diatheses and molecular targets especially signaling pathways that mediate responses to trauma and severe stress and their potential contribution to the etiology of PTSD. Sensitization of(More)
Integrating vector systems used in clinical gene therapy have proven their therapeutic potential in the long-term correction of immunodeficiencies. The integration loci of such vectors in the cellular genome represent a molecular marker unique for each transduced cell and its clonal progeny. To gain insight into the physiology of gene-modified hematopoietic(More)
Protein levels within signal transduction pathways vary strongly from cell to cell. Here, we analysed how signalling pathways can still process information quantitatively despite strong heterogeneity in protein levels. We systematically perturbed the protein levels of Erk, the terminal kinase in the MAPK signalling pathway in a panel of human cell lines. We(More)
Since the incidence of the metabolic syndrome is on the rise in the western world, its coherence to cancer is becoming more apparent. In this review we discuss the different potential factors involved in the increase of cancer in the metabolic syndrome including obesity, dyslipidemia and Type 2 Diabetes Mellitus (T2DM) as well as inflammation and hypoxia.(More)
Protein kinase C (PKC)-mediated desensitization of the corticotropin releasing factor type 1 (CRF1) receptor was investigated in human retinoblastoma Y79 and transfected COS-7 cells. Because stimulation of Y79 cells with CRF resulted in large ( approximately 30-fold) increases in intracellular cAMP accumulation without changing inositol phosphate levels,(More)
The EC(50) values for concentration-dependent stimulation of cAMP accumulation by CRF (1.3nM) and urocortin (1.0nM) were equivalent in human retinoblastoma Y79 cells. The time course and magnitude of CRF- and urocortin-induced CRF(1) receptor desensitization were similar. A significant 3-fold increase in GRK3, but not GRK2, mRNA levels accompanied the(More)
BACKGROUND Although IL-4 and IL-13 share the IL-13 receptor, IL-13 exhibits unique functions. To elicit the cellular basis of these differences, signal transduction processes have been compared. Additionally, the role of the IL-4 receptor alpha (IL-4Ralpha) variant Q551R was investigated. METHODS Peripheral blood mononuclear cells from donors were(More)
The primary goal was to determine agonist-specific regulation of CRF2(a) receptor function. Exposure of human retinoblastoma Y79 cells to selective (UCN2, UCN3 or stresscopins) and non-selective (UCN1 or sauvagine) agonists prominently desensitized CRF2(a) receptors in a rapid, concentration-dependent manner. A considerably slower rate and smaller magnitude(More)
Background: Valve replacement has been the treatment of choice for patients with valvular complications of infectious endocarditis (IE). However, excellent results with valve repair allowed it to become a new therapeutic alternative for these patients. Aim: To evaluate the results of valve repair in patients with valvular complications of IE. Patients and(More)