Search results for "Wester"

Norrie gene product is necessary for regression of hyaloid vessels.

2004

To investigate the nature and origin of the vitreous membranes in mice with knock-out of the Norrie gene product (ND mice).Eighty-two eyes of ND mice of different age groups (postnatal day [P]0-13 months) and 95 age-matched wild-type control mice were investigated. In vitreoretinal wholemounts and in sagittal sections, vessels and free cells were visualized by labeling for lectin. In addition, staining with a marker for macrophages (F4/80) and collagen XVIII/endostatin known to be involved in regression of hyaloid vessels was performed for light and electron microscopic investigations. Endostatin expression was confirmed by Western blot analysis.Wild-type controls showed the typical pattern…

0331 : Pathophysiology of the ubiquitine ligase E3, PDZRN3, in the development of dilated cardiomyopathies

2015

Dilated cardiomyopathy is a major cause of heart failure with a poor prognostic. Molecular mechanisms underlying the transition toward the dilated phenotype are still not known. In heart, individual cardiomyocytes connect some with the others via their extremities by junctional platform (Intercalated Discs, ID) crucial for the mechanical coupling and the anisotropic conduction of the electric signal. In this project, we are interested in an Ubiquitine ligase E3 called PDZRN3, which is expressed and regulated in cardiomyocytes during their maturation. We have previously identified PDZRN3 involvement in the the Wnt Planar Cell Polarity (Wnt/PCP) signaling in vascular morphogenesis. In the hea…

Cigarette smoke alters primary human bronchial epithelial cell (PBEC) differentiation at air-liquid interface (ALI) and induces expression of CD105 a…

2016

Dys-regulation of airway epithelial cell function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD. CD105, a component of TGF-β complex, and CD146, an epithelial-mesenchymal transition inducer, are adhesion molecules involved in cellular proliferation, differentiation, transmigration and tissue remodelling. After validation of an ex vivo ALI culture of PBEC, we assessed the effect of long-term cigarette smoke extract (CSE) exposure on epithelium regeneration and differentiation. Endobronchial biopsy specimens (EBBs) were obtained from 8 controls (C) and 9 COPD. ALI cultures from EBBs of C were exposed to CSE for 7, 14, 21 days. Transepithelial Elect…

A monoclonal Ro-antibody and the serum of a Ro-positive patient with subacute cutaneous lupus erythematosus (SCLE) react with basal layers of human e…

1988

Skin lesions, especially at areas exposed to sunlight, prove to be a major form of manifestation of diseases related to Ro-antibodies and neonatal-, 'ANA-negative-', and cutaneous types of lupus erythe- matosus. A monoclonal Ro-antibody established by our group reacts with a 60 kD polypeptide in extracts from human spleen, whereas in extracts from human epidermis the monoclonal Ro-antibody and a purified Ro-antibody from a monospecific serum of a patient with subacute cutaneous lupus erythematosus reacted with a 60 kD and a 48 kD protein. Performing immunofluorescence microscopy on HEp2-cells both antibodies showed a nuclear speckled staining pattern and a reaction with cytokeratin filament…

Inhibiting proliferation in KB cancer cells by RNA interference-mediated knockdown of nicotinamide N-methyltransferase expression.

2011

The enzyme Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide and other pyridines, playing a pivotal role in the biotransformation and detoxification of many drugs and xenobiotic compounds. Several tumours have been associated with abnormal NNMT expression, however its role in tumour development remains largely unknown. In this study we investigated expression levels of Nicotinamide N-methyltransferase in a cancer cell line and we evaluated the effect of shRNA-mediated silencing of NNMT on cell proliferation. Cancer cells were examined for NNMT expression by semiquantitative RT-PCR and Western blot analysis. A HPLC-based catalytic assay was performed to asses…

Treating cancer in older and oldest old patients.

2015

The so-called “silver tsunami” is a metaphor that the individuals 65 and older represent the most rapidly growing segment of the Western world population. Aging is an ongoing process that leads to the loss of functional reserve of multiple organ systems, increased susceptibility to stress, it is associated with increased prevalence of chronic disease, and functional dependence. Determined by a combination of genetic and environmental factors, this process is highly individualized and poorly reflected in chronologic age. The heterogeneity and the complexity of the older old population represent the main challenge to the treatment of cancer in those patients. We should discern "fit" elderly i…

2015

The pathogenesis of glaucoma, a common neurodegenerative disease, involves an immunologic component. Changes in the natural autoantibody profile of glaucoma patients were detected, showing not only up-regulated but also down-regulated immunoreactivities. In recent studies we were able to demonstrate that the antibody changes have a large influence on protein profiles of neuroretinal cells. Furthermore we could demonstrate neuroprotective potential of one of the down-regulated antibodies (γ-synuclein antibody). Anti-GFAP antibody is another antibody found down-regulated in glaucoma patients. Since GFAP expression is intensified in glaucomatous retina, the aim of this study was to detect the …

Growth hormone protects human lymphocytes from irradiation-induced cell death

2003

1. Undesired effects of cancer radiotherapy mainly affect the hematopoietic system. Growth hormone (GH) participates in both hematopoiesis and modulation of the immune response. We report both r-hGH cell death prevention and restoration of secretory capacities of irradiated human peripheral blood lymphocytes (PBL) in vitro. 2. r-hGH induced cell survival and increased proliferation of irradiated cells. Western blot analysis indicated that these effects of GH were paralleled by increased expression of the antiapoptotic protein Bcl-2. 3. r-hGH restored mitogen-stimulated release of IL-2 by PBL. Preincubation of irradiated lymphocytes with the growth hormone receptor (GHR) antagonists B2036 an…

Regulatory evaluation of Glybera in Europe — two committees, one mission

2013

Representing the first gene therapy to be approved in the Western world, alipogene tiparvovec (Glybera; Uniqure) has recently been said to have had a “substantial impact from a regulatory perspective” (Nature Rev. Drug Discov. 11, 664; 2012) 1 . The therapy was granted marketing authorization in the European Union for the treatment of lipoprotein lipase deficiency, which results in a clinically heterogeneous condition with a risk of potentially life-threatening pancreatitis 2 , at the end of 2012. The decision followed a positive opinion by the European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) 3

Down-regulation of microglial cyclo-oxygenase-2 and inducible nitric oxide synthase expression by lipocortin 1

1999

Activated microglial cells are believed to play an active role in most brain pathologies, during which they can contribute to host defence and repair but also to the establishment of tissue damage. These actions are largely mediated by microglial secretory products, among which are prostaglandins (PGs) and nitric oxide (NO). The anti-inflammatory protein, lipocortin 1 (LC1) was reported to have neuroprotective action and to be induced by glucocorticoids in several brain structures, with a preferential expression in microglia. In this paper we tested whether the neuroprotective effect of LC1 could be explained by an inhibitory effect on microglial activation. We have previously shown that ba…