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784 results on '"Marynen, P"'

2. Silicone adhesive multilayer foam dressings to prevent hospital-acquired sacrum pressure ulcers: An economic evaluation based on a publicly funded pragmatic randomized controlled trial linked with real-world data.

Author

Neyt, Mattias, De Meester, Christophe, Devriese, Stephan, Marynen, Elisabeth, and Beeckman, Dimitri

Abstract

To estimate the cost-effectiveness of sacrum multilayer silicone foam dressings as an adjuvant prophylactic therapy compared to standard pressure ulcer prevention in a hospital population at high risk for pressure ulcer development. An economic evaluation is performed from a healthcare payer's perspective. This evaluation is based on a Belgian publicly funded pragmatic randomized controlled trial (RCT), linked with real-world data from administrative claims database and a Belgian cost analysis. A cost-consequences analysis with a one-year time horizon is performed. The RCT has shown that the risk of developing a new pressure ulcer on the sacrum was statistically significantly reduced by 41 % in the treatment group (RR = 0.59, 95 % CI 0.35–0.98, p = 0.04). The absolute risk reduction of 2.0 % (95 % CI -0.1–4.1 %) coincides with a number needed to treat of 50.0 to prevent one new pressure ulcer of category II or worse. The evolution of quality of life is on average negative for patients who developed a pressure ulcer before day 3, while it is positive for patients without pressure ulcers. In a scenario with conservative assumptions, i.e. without inclusion of price discounts for the multilayer silicone foam dressings and only including costs during the hospitalization, pressure ulcer prevention with dressings on the sacrum was already cost-neutral. The preventive use of silicone adhesive multilayer foam dressings on the sacrum for a population similar to the pragmatic trial population can be supported both from a clinical and economic point of view. • Silicone multilayer foam dressings on the sacrum avoid pressure ulcers (pragmatic RCT-based evidence). • This economic evaluation links RCT information with real-world administrative claims data. • This approach retains the advantage of randomization in combination with real-world data. • The use of the studied dressings is supported from both a clinical and economic point of view. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Transformation of hematopoietic cell lines to growth-factor independence and induction of a fatal myelo- and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion genes.

Author

Schwaller, J, Frantsve, J, Aster, J, Williams, I R, Tomasson, M H, Ross, T S, Peeters, P, Van Rompaey, L, Van Etten, R A, Ilaria, R, Jr, Marynen, P, and Gilliland, D G

Subjects
Animals, Bone Marrow Transplantation, Cell Division, Cell Line, Transformed, DNA: metabolism, DNA, Recombinant, DNA, Viral: analysis, DNA-Binding Proteins: metabolism, Hematopoietic Stem Cells: cytology, Humans, Interleukin-3: physiology, Lymphoproliferative Disorders: genetics, Mice, Mice, Transgenic, Milk Proteins, Myeloproliferative Disorders: genetics, pathology, Oncogene Proteins, Fusion: genetics, physiology, Retroviridae: genetics, STAT5 Transcription Factor, Trans-Activators: metabolism, Transformation, Genetic, Virus Integration
Abstract

Recent reports have demonstrated fusion of the TEL gene on 12p13 to the JAK2 gene on 9p24 in human leukemias. Three variants have been identified that fuse the TEL pointed (PNT) domain to (i) the JAK2 JH1-kinase domain, (ii) part of and (iii) all of the JH2 pseudokinase domain. We report that all of the human TEL/JAK2 variants, and a human/mouse chimeric hTEL/mJAK2(JH1) fusion gene, transform the interleukin-3 (IL-3)-dependent murine hematopoietic cell line Ba/F3 to IL-3-independent growth. Transformation requires both the TEL PNT domain and JAK2 kinase activity. Furthermore, all TEL/JAK2 variants strongly activated STAT 5 by phosphotyrosine Western blots and by electrophoretic mobility shift assays (EMSA). Mice (n = 40) transplanted with bone marrow infected with the MSCV retrovirus containing either the hTEL/mJAK2(JH1) fusion or its human counterpart developed a fatal mixed myeloproliferative and T-cell lymphoproliferative disorder with a latency of 2-10 weeks. In contrast, mice transplanted with a TEL/JAK2 mutant lacking the TEL PNT domain (n = 10) or a kinase-inactive TEL/JAK2(JH1) mutant (n = 10) did not develop the disease. We conclude that all human TEL/JAK2 fusion variants are oncoproteins in vitro that strongly activate STAT 5, and cause lethal myelo- and lymphoproliferative syndromes in murine bone marrow transplant models of leukemia.

Published
1998

7. The mitochondrial solute carrier SLC25A5 at Xq24 is a novel candidate gene for non-syndromic intellectual disability

Author

Vandewalle, Joke, Bauters, Marijke, Van Esch, Hilde, Belet, Stefanie, Verbeeck, Jelle, Fieremans, Nathalie, Holvoet, Maureen, Vento, Jodie, Spreiz, Ana, Kotzot, Dieter, Haberlandt, Edda, Rosenfeld, Jill, Andrieux, Joris, Delobel, Bruno, Dehouck, Marie-Bertille, Devriendt, Koen, Fryns, Jean-Pierre, Marynen, Peter, Goldstein, Amy, and Froyen, Guy

Published
2013
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46. Malt1 self-cleavage is critical for regulatory T cell homeostasis and anti-tumor immunity in mice

Author

Baens, M, Stirparo, R, Lampi, Y, Verbeke, D, Vandepoel, R, Cools, J, Marynen, P, de Bock, CE, Bornschein, S, Baens, M, Stirparo, R, Lampi, Y, Verbeke, D, Vandepoel, R, Cools, J, Marynen, P, de Bock, CE, and Bornschein, S

Abstract

Mucosa-associated lymphoid tissue 1 (Malt1) regulates immune cell function by mediating the activation of nuclear factor κB (NF-κB) signaling through both its adaptor and proteolytic function. Malt1 is also a target of its own protease activity and this self-cleavage further contributes to NF-κB activity. Until now, the functional distinction between Malt1 self-cleavage and its general protease function in regulating NF-κB signaling and immune activation remained unclear. Here we demonstrate, using a new mouse model, the importance of Malt1 self-cleavage in regulating expression of NF-κB target genes and subsequent T cell activation. Significantly, we further establish that Treg homeostasis is critically linked to Malt1 function via a Treg intrinsic and extrinsic mechanism. TCR-mediated Malt1 proteolytic activity and self-cleavage was found to drive Il2 expression in conventional CD4 + T cells, thereby regulating Il2 availability for Treg homeostasis. Remarkably, the loss of Malt1-mediated self-cleavage alone was sufficient to cause a significant Treg deficit resulting in increased anti-tumor immune reactivity without associated autoimmunity complications. These results establish for the first time that inhibition of MALT1 proteolytic activity could be a viable therapeutic strategy to augment anti-tumor immunity.

Published
2018

48. Identification of Intellectual Disability Genes in Female Patients with a Skewed X-Inactivation Pattern

Author

Fieremans N, Van Esch H, Holvoet M, Van Goethem G, Devriendt K, Rosello M, Mayo S, Martinez F, Jhangiani S, Muzny DM, Gibbs RA, Lupski JR, Vermeesch JR, Marynen P, and Froyen G

Subjects
escape genes, skewing of X-inactivation, intellectual disability, exome sequencing
Abstract

Intellectual disability (ID) is a heterogeneous disorder with an unknown molecular etiology in many cases. Previously, X-linked ID (XLID) studies focused on males because of the hemizygous state of their X chromosome. Carrier females are generally unaffected because of the presence of a second normal allele, or inactivation of the mutant X chromosome in most of their cells (skewing). However, in female ID patients, we hypothesized that the presence of skewing of X-inactivation would be an indicator for an X chromosomal ID cause. We analyzed the X-inactivation patterns of 288 females with ID, and found that 22 (7.6%) had extreme skewing (>90%), which is significantly higher than observed in the general population (3.6%; P=0.029). Whole-exome sequencing of 19 females with extreme skewing revealed causal variants in six females in the XLID genes DDX3X, NHS, WDR45, MECP2, and SMC1A. Interestingly, variants in genes escaping X-inactivation presumably cause both XLID and skewing of X-inactivation in three of these patients. Moreover, variants likely accounting for skewing only were detected in MED12, HDAC8, and TAF9B. All tested candidate causative variants were de novo events. Hence, extreme skewing is a good indicator for the presence of X-linked variants in female patients.

Published
2016

49. Small chromosomal regions position themselves autonomously according to their chromatin class

Author

Werken, H.J.G. (Harmen) van de, Haan, J.C. (Josien C.), Feodorova, Y. (Yana), Bijos, D. (Dominika), Weuts, A. (An), Theunis, K. (Koen), Holwerda, S.J.B. (Sjoerd J.), Meuleman, W. (Wouter), Pagie, L. (Ludo), Thanisch, K. (Katharina), Kumar, P. (Parveen), Leonhardt, H. (Heinrich), Marynen, P. (Peter), Steensel, B. (Bas) van, Voet, T. (Thierry), Laat, W.L. (Wouter) de, Solovei, I. (Irina), Joffe, B. (Boris), Werken, H.J.G. (Harmen) van de, Haan, J.C. (Josien C.), Feodorova, Y. (Yana), Bijos, D. (Dominika), Weuts, A. (An), Theunis, K. (Koen), Holwerda, S.J.B. (Sjoerd J.), Meuleman, W. (Wouter), Pagie, L. (Ludo), Thanisch, K. (Katharina), Kumar, P. (Parveen), Leonhardt, H. (Heinrich), Marynen, P. (Peter), Steensel, B. (Bas) van, Voet, T. (Thierry), Laat, W.L. (Wouter) de, Solovei, I. (Irina), and Joffe, B. (Boris)

Abstract

The spatial arrangement of chromatin is linked to the regulation of nuclear processes. One striking aspect of nuclear organization is the spatial segregation of heterochromatic and euchromatic domains. The mechanisms of this chromatin segregation are still poorly understood. In this work, we investigated the link between the primary genomic sequence and chromatin domains. We analyzed the spatial intranuclear arrangement of a human artificial chromosome (HAC) in a xenospecific mouse background in comparison to an orthologous region of native mouse chromosome. The two orthologous regions include segments that can be assigned to three major chromatin classes according to their gene abundance and repeat repertoire: (1) gene-rich and SINE-rich euchromatin; (2) gene-poor and LINE/LTR-rich heterochromatin; and (3) genedepleted and satellite DNA-containing constitutive heterochromatin. We show, using fluorescence in situ hybridization (FISH) and 4C-seq technologies, that chromatin segments ranging from 0.6 to 3 Mb cluster with segments of the same chromatin class. As a consequence, the chromatin segments acquire corresponding positions in the nucleus irrespective of their chromosomal context, thereby strongly suggesting that this is their autonomous property. Interactions with the nuclear lamina, although largely retained in the HAC, reveal less autonomy. Taken together, our results suggest that building of a functional nucleus is largely a self-organizing process based on mutual recognition of chromosome segments belonging to the major chromatin classes.

Published
2017
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50. Small chromosomal regions position themselves autonomously according to their chromatin class

Author

van de Werken, Harmen, Haan, JC, Feodorova, Y, Bijos, D, Weuts, A, Theunis, K, Holwerda, SJB, Meuleman, W, Pagie, L, Thanisch, K, Kumar, P, Leonhardt, H, Marynen, P, van Steensel, B, Voet, T, de Laat, WL, Solovei, I, Joffe, B, van de Werken, Harmen, Haan, JC, Feodorova, Y, Bijos, D, Weuts, A, Theunis, K, Holwerda, SJB, Meuleman, W, Pagie, L, Thanisch, K, Kumar, P, Leonhardt, H, Marynen, P, van Steensel, B, Voet, T, de Laat, WL, Solovei, I, and Joffe, B

Published
2017

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