Major Pathogenic Factor (major + pathogenic_factor)

Distribution by Scientific Domains


Selected Abstracts


Connective tissue growth factor and cardiac fibrosis

ACTA PHYSIOLOGICA, Issue 3 2009
A. Daniels
Abstract Cardiac fibrosis is a major pathogenic factor in a variety of cardiovascular diseases and refers to an excessive deposition of extracellular matrix components in the heart, which leads to cardiac dysfunction and eventually overt heart failure. Evidence is accumulating for a crucial role of connective tissue growth factor (CTGF) in fibrotic processes in several tissues including the heart. CTGF orchestrates the actions of important local factors evoking cardiac fibrosis. The central role of CTGF as a matricellular protein modulating the fibrotic process in cardiac remodelling makes it a possible biomarker for cardiac fibrosis and a potential candidate for therapeutic intervention to mitigate fibrosis in the heart. [source]


Monitoring of cardiac function by serum cardiac troponin T levels, ventricular repolarisation indices, and echocardiography after conditioning with fractionated total body irradiation and high-dose cyclophosphamide

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2002
H.W. Auner
Abstract:Objectives : Highly differing rates of cardiac complications associated with high-dose cyclophosphamide (CY) have been reported, and only one clinical study has been performed on the cardiotoxic effects of CY monotherapy following total body irradiation (TBI). Patients and methods : We prospectively evaluated the potential cardiotoxic effects of conditioning with fractionated total body irradiation and high-dose cyclophosphamide (TBI/CY) by serial measurement of serum cardiac troponin T (cTnT), assessment of systolic and diastolic echocardiographic parameters and analysis of ventricular repolarisation indices (QT-dispersion and corrected QT-dispersion) in 30 adult patients with haematological malignancies undergoing haematopoietic stem cell transplantation. Results: There was no evidence of pretreatment cardiac dysfunction in any patient. Although cTnT was determined serially for a median of 14 d after completion of conditioning, no elevated levels were observed. Echocardiographic parameters did not show any significant change at a median follow-up of 5 months except for one patient with evidence of impaired diastolic filling. No significant differences for mean values before and after high-dose CY were noted for ventricular repolarisation indices. Two patients had a significant increase in corrected QT-dispersion after CY without any other signs of cardiotoxicity. Congestive heart failure or arrythmias were not observed. Conclusions : These data suggest that TBI/CY is safe with respect to cardiotoxicity in patients without pre-existing cardiac dysfunction. Hitherto unknown synergistic cardiotoxic effects of CY with other cytostatic drugs may constitute the major pathogenic factor of myocardial dysfunction after high-dose chemotherapy. [source]


Opsonization of late apoptotic cells by systemic lupus erythematosus autoantibodies inhibits their uptake via an Fc, receptor,dependent mechanism

ARTHRITIS & RHEUMATISM, Issue 10 2007
Esther Reefman
Objective Decreased clearance of apoptotic cells is suggested to be a major pathogenic factor in systemic lupus erythematosus (SLE). The aim of this study was to investigate whether the binding of SLE autoantibodies to apoptotic cells influences the phagocytosis of these cells by macrophages. Methods Apoptosis was induced in a human T cell line (Jurkat) and a keratinocyte cell line (HaCaT) by ultraviolet B irradiation. Binding of purified IgG from 26 SLE patients and 15 healthy controls to apoptotic cells was assessed by flow cytometry and Western blotting. Phagocytosis of IgG-opsonized apoptotic cells by monocyte-derived macrophages was assessed by light microscopy. Similar experiments were performed with a monoclonal antibody against SSA/Ro and IgG fractions from 5 patients with Sjögren's syndrome (SS) and 5 patients with rheumatoid arthritis (RA). Results IgG fractions from all 26 SLE patients bound to late apoptotic, but not early apoptotic, cells. IgG fractions isolated from SLE patients with different autoantibody profiles showed comparable levels of binding. IgG fractions from healthy controls did not bind. Opsonization of apoptotic cells with IgG fractions from SLE patients resulted in a significant inhibition of phagocytosis as compared with healthy control IgG fractions. A monoclonal antibody directed against SSA/Ro and IgG isolated from 5 antinuclear antibody (ANA),positive patients with SS were also able to elicit these effects, whereas IgG from 5 ANA-negative patients with RA did not. The inhibitory effect of patient IgG was abolished by blocking either the Fc, receptors (Fc,R) or the constant region of IgG, using a specific Fc-blocking peptide. Conclusion Autoantibodies from SLE patients are able to opsonize apoptotic cells and inhibit their uptake by macrophages via an Fc,R-dependent mechanism. [source]


FoxO1 , the key for the pathogenesis and therapy of acne?

JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 2 2010
Bodo C. Melnik
Summary Five main factors play a pivotal role in the pathogenesis of acne: androgen dependence, follicular retention hyperkeratosis, increased sebaceous lipogenesis, increased colonization with P. acnes, and inflammatory events. This paper offers a solution for the pathogenesis of acne and explains all major pathogenic factors at the genomic level by a relative deficiency of the nuclear transcription factor FoxO1. Nuclear FoxO1 suppresses androgen receptor, other important nuclear receptors and key genes of cell proliferation, lipid biosynthesis and inflammatory cytokines. Elevated growth factors during puberty and persistent growth factor signals due to Western life style stimulate the export of FoxO1 out of the nucleus into the cytoplasm via activation of the phos-phoinositide-3-kinase (PI3K)/Akt pathway. By this mechanism, genes and nuclear receptors involved in acne are derepressed leading to increased androgen receptor-mediated signal transduction, increased cell proliferation of androgen-dependent cells, induction of sebaceous lipogenesis and upregulation of Toll-like-receptor-2-dependent inflammatory cytokines. All known acne-inducing factors exert their action by reduction of nuclear FoxO1 levels. In contrast, retinoids, antibiotics and dietary intervention will increase the nuclear content of FoxO1, thereby normalizing increased transcription of genes involved in acne. Various receptor-mediated growth factor signals are integrated at the level of PI3K/Akt activation which finally results in nuclear FoxO1 deficiency. [source]