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Search Results: 1 - 10 of 178161 matches for " Erik B. van den Akker "
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Transcriptional Profiling of Human Familial Longevity Indicates a Role for ASF1A and IL7R
Willemijn M. Passtoors, Judith M. Boer, Jelle J. Goeman, Erik B. van den Akker, Joris Deelen, Bas J. Zwaan, Ann Scarborough, Ruud van der Breggen, Rolf H. A. M. Vossen, Jeanine J. Houwing-Duistermaat, Gert Jan B. van Ommen, Rudi G. J. Westendorp, Diana van Heemst, Anton J. M. de Craen, Andrew J. White, David A. Gunn, Marian Beekman, P. Eline Slagboom
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0027759
Abstract: The Leiden Longevity Study consists of families that express extended survival across generations, decreased morbidity in middle-age, and beneficial metabolic profiles. To identify which pathways drive this complex phenotype of familial longevity and healthy aging, we performed a genome-wide gene expression study within this cohort to screen for mRNAs whose expression changes with age and associates with longevity. We first compared gene expression profiles from whole blood samples between 50 nonagenarians and 50 middle-aged controls, resulting in identification of 2,953 probes that associated with age. Next, we determined which of these probes associated with longevity by comparing the offspring of the nonagenarians (50 subjects) and the middle-aged controls. The expression of 360 probes was found to change differentially with age in members of the long-lived families. In a RT-qPCR replication experiment utilizing 312 controls, 332 offspring and 79 nonagenarians, we confirmed a nonagenarian specific expression profile for 21 genes out of 25 tested. Since only some of the offspring will have inherited the beneficial longevity profile from their long-lived parents, the contrast between offspring and controls is expected to be weak. Despite this dilution of the longevity effects, reduced expression levels of two genes, ASF1A and IL7R, involved in maintenance of chromatin structure and the immune system, associated with familial longevity already in middle-age. The size of this association increased when controls were compared to a subfraction of the offspring that had the highest probability to age healthily and become long-lived according to beneficial metabolic parameters. In conclusion, an “aging-signature” formed of 21 genes was identified, of which reduced expression of ASF1A and IL7R marked familial longevity already in middle-age. This indicates that expression changes of genes involved in metabolism, epigenetic control and immune function occur as a function of age, and some of these, like ASF1A and IL7R, represent early features of familial longevity and healthy ageing.
Hypertension Is Associated with Marked Alterations in Sphingolipid Biology: A Potential Role for Ceramide
Léon J. A. Spijkers, Rob F. P. van den Akker, Ben J. A. Janssen, Jacques J. Debets, Jo G. R. De Mey, Erik S. G. Stroes, Bert-Jan H. van den Born, Dayanjan S. Wijesinghe, Charles E. Chalfant, Luke MacAleese, Gert B. Eijkel, Ron M. A. Heeren, Astrid E. Alewijnse, Stephan L. M. Peters
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0021817
Abstract: Background Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function. Methods and Findings In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4±0.4 and SMase: 2.1±0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0±0.0 and SMase: 0.6±0.1 mN/mm; n = 9, p<0.05). Imaging mass spectrometry and immunohistochemistry indicated that these contractions were most likely mediated by ceramide and dependent on iPLA2, cyclooxygenase-1 and thromboxane synthase. Expression levels of these enzymes were higher in SHR vessels. In concurrence, infusion of dimethylsphingosine caused a marked rise in blood pressure in anesthetized SHR (42±4%; n = 7), but not in WKY (?12±10%; n = 6). Lipidomics analysis by mass spectrometry, revealed elevated levels of ceramide in arterial tissue of SHR compared to WKY (691±42 vs. 419±27 pmol, n = 3–5 respectively, p<0.05). These pronounced alterations in SHR sphingolipid biology are also reflected in increased plasma ceramide levels (513±19 pmol WKY vs. 645±25 pmol SHR, n = 6–12, p<0.05). Interestingly, we observed similar increases in ceramide levels (correlating with hypertension grade) in plasma from humans with essential hypertension (185±8 pmol vs. 252±23 pmol; n = 18 normotensive vs. n = 19 hypertensive patients, p<0.05). Conclusions Hypertension is associated with marked alterations in vascular sphingolipid biology such as elevated ceramide levels and signaling, that contribute to increased vascular tone.
CD4 testing at clinics to assess eligibility for Antiretroviral therapy
R Lumala, T van den Akker, CA Metcalf, E Diggle, B Zamadenga, K Mbewa, A Akkeson
Malawi Medical Journal , 2012,
Abstract: Background In 2011, the Ministry of Health raised the CD4 threshold for antiretroviral therapy (ART) eligibility from <250 cells/μl and <350 cells/μl, but at the same time only 8.8% of facilities in Malawi with HIV services provided CD4 testing. We conducted a record review at 10 rural clinics in Thyolo District to assess the impact of introducing CD4 testing on identifying patients eligible for ART. Methods: We abstracted CD4 counts of all ART-na ve, HIV-infected patients with WHO clinical stages 1 and 2 and an initial CD4 test between May 2008 and June 2009. At four clinics, we also abstracted CD4 counts of patients not initially eligible for ART who were retested before April 2010. Results Of 1,113 patients tested, the initial CD4 was “≤250 cells/μl” and “≤350 cells/μl” in 534 (48.0%). Of 203 patients with follow-up results, the most recent CD4 was ≤250 cells/μl in 34 (24.5%), and ≤350 cells/μl in 64 (46.0%). Conclusions CD4 testing in rural clinics is feasible and identifies many patients eligible for ART who would not be identified without CD4 testing. CD4 testing needs to be scaled-up to identify patients eligible for ART. ART services need to be scaled-up concurrently to meet the resulting increased demand.
A decision analysis approach for optimal groundwater monitoring system design under uncertainty
N. B. Yenigül,A. M. M. Elfeki,C. van den Akker,F. M. Dekking
Hydrology and Earth System Sciences Discussions , 2006,
Abstract: Groundwater contamination is the degradation of the natural quality of groundwater as a result of human activity. Landfills are one of the most common human activities threatening the groundwater quality. The objective of the monitoring systems is to detect the contaminant plumes before reaching the regulatory compliance boundary in order to prevent the severe risk to both society and groundwater quality, and also to enable cost-effective counter measures in case of a failure. The detection monitoring problem typically has a multi-objective nature. A multi-objective decision model (called MONIDAM) which links a classic decision analysis approach with a stochastic simulation model is applied to determine the optimal groundwater monitoring system given uncertainties due to the hydrogeological conditions and contaminant source characteristics. A Monte Carlo approach is used to incorporate uncertainties. Hydraulic conductivity and the leak location are the random inputs of the simulation model. The design objectives considered in the model are: (1) maximizing the detection probability, (2) minimizing the contaminated area and, (3) minimize the total cost of the monitoring system. The results show that the monitoring systems located close to the source are optimal except for the cases with very high unit installation and sampling cost and/or very cheap unit remediation cost.
Response to Ulrich Pfisterer’s review of Paul van den Akker, Looking for Lines. Theories on the Essence of Art and the Problem of Mannerism
Paul van den Akker
Journal of Art Historiography , 2011,
Book received: Paul van den Akker, Looking for Lines: Theories of the Essence of Art and the Problem of Mannerism, Amsterdam: Amsterdam University Press 2010 including preface, contents and introduction.
Paul van den Akker
Journal of Art Historiography , 2010,
Abstract: Paul van den Akker, Looking for Lines: Theories of the Essence of Art and the Problem of Mannerism, Amsterdam: Amsterdam University Press 2010 including preface, contents and introduction.
The role of T cell interleukin-17 in conducting destructive arthritis: lessons from animal models
Erik Lubberts, Marije I Koenders, Wim B van den Berg
Arthritis Research & Therapy , 2004, DOI: 10.1186/ar1478
Abstract: Interleukin-17 (IL-17) is a 17 kDa protein that is secreted as a dimer by a restricted set of cells, predominantly activated human memory T cells or mouse αβTCR+CD4-CD8- thymocytes [1-3]. Rouvier and colleagues have cloned cytotoxic T lymphocyte-associated antigen-8 (rat IL-17) from a T cell subtraction library [4] and mouse IL-17 was cloned from a thymus-derived, activated T cell cDNA library [3]. Subsequently, the human counterpart of mouse IL-17 was cloned by two independent groups [1,2,5]. Human IL-17 has 25% amino acid sequence homology to mouse IL-17, as well as 72% homology to an open-reading frame from the T lymphotropic herpes virus saimiri (HVS13) and 63% homology to CTLA8 [2,4]. In addition to IL-17 (IL-17A) another five members of the IL-17 family have been discovered (IL-17B-F) by large-scale sequencing of the human and other vertebrate genomes (Table 1) [6].The different IL-17 family members seem to have very distinct expression patterns, suggesting distinct biological roles. IL-17B is moderately expressed in several peripheral tissues as well as immune tissues [7,8], and IL-17E is expressed in various peripheral tissues [9]. Interestingly, IL-17F has biological functions similar to those of IL-17(A) and is also produced by activated monocytes [10,11]. This indicates that the IL-17 family might contribute to the pathology of rheumatoid arthritis (RA) and other inflammatory diseases not only through activated T cells but also through activated monocytes/macrophages. Further work will be required to determine the precise mechanism of action of IL-17 and its family members such as IL-17F, IL-17B, and IL-17E in the development of chronic synovitis and tissue destruction during arthritis, especially in relation to other known key cytokines (IL-1, tumor necrosis factor [TNF], and receptor activator of NF-κB ligand [RANKL]).In contrast to the restricted expression of IL-17, the IL-17 receptor (IL-17R) is ubiquitously expressed in virtually all cells and tissu
The Redox State of Transglutaminase 2 Controls Arterial Remodeling
Jeroen van den Akker, Ed VanBavel, Remon van Geel, Hanke L. Matlung, Bilge Guvenc Tuna, George M. C. Janssen, Peter A. van Veelen, Wilbert C. Boelens, Jo G. R. De Mey, Erik N. T. P. Bakker
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023067
Abstract: While inward remodeling of small arteries in response to low blood flow, hypertension, and chronic vasoconstriction depends on type 2 transglutaminase (TG2), the mechanisms of action have remained unresolved. We studied the regulation of TG2 activity, its (sub) cellular localization, substrates, and its specific mode of action during small artery inward remodeling. We found that inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required the presence of a reducing agent. The effect of TG2 depended on its cross-linking activity, as indicated by the lack of effect of mutant TG2. The cell-permeable reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced translocation of endogenous TG2 and high membrane-bound transglutaminase activity. This coincided with inward remodeling, characterized by a stiffening of the artery. The remodeling could be inhibited by a TG2 inhibitor and by the nitric oxide donor, SNAP. Using a pull-down assay and mass spectrometry, 21 proteins were identified as TG2 cross-linking substrates, including fibronectin, collagen and nidogen. Inward remodeling induced by low blood flow was associated with the upregulation of several anti-oxidant proteins, notably glutathione-S-transferase, and selenoprotein P. In conclusion, these results show that a reduced state induces smooth muscle membrane-bound TG2 activity. Inward remodeling results from the cross-linking of vicinal matrix proteins, causing a stiffening of the arterial wall.
Remifentanil patient controlled analgesia versus epidural analgesia in labour. A multicentre randomized controlled trial
Liv M Freeman, Kitty WM Bloemenkamp, Maureen TM Franssen, Dimitri NM Papatsonis, Petra J Hajenius, Marloes E van Huizen, Henk A Bremer, Eline SA van den Akker, Mallory D Woiski, Martina M Porath, Erik van Beek, Nico Schuitemaker, Paulien CM van der Salm, Bianca F Fong, Celine Radder, Caroline J Bax, Marko Sikkema, M van den Akker-van Marle, Jan MM van Lith, Enrico Lopriore, Renske J Uildriks, Michel MRF Struys, Ben Willem J Mol, Albert Dahan, Johanna M Middeldorp
BMC Pregnancy and Childbirth , 2012, DOI: 10.1186/1471-2393-12-63
Abstract: The proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia. We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia.Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief.Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-intensity), mode of delivery and maternal and neonatal side effects.The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared.This study, considering cost effectiveness of remifentanil as first choice analgesia versus epidural analgesia, could strongly improve the care for 180.000 women, giving birth in the Netherlands yearly by giving them access to pain relief during labour, 24 hours a day.Dutch Trial Register NTR2551, http://www.trialregister.nl webciteEpidural analgesia is considered to be the most effective method of pain relief during labour and is recommended as first method of pain relief by the Dutch Societies of Gynecologists and Anesthetists [1,2]. In the Netherlands its uptake by pregnant women in labour of all ethnicities is still limited (11.3% in 2008 but in the last years increasing with 1-2% per year), compared with other western countries, partly as
Socioeconomic factors from midlife predict mobility limitation and depressed mood three decades later findings from the AGES-Reykjavik study
Dani?lle AI Groffen, Annemarie Koster, Hans Bosma, Marjan van den Akker, Thor Aspelund, Kristín Siggeirsdóttir, Gertrudis IJM Kempen, Jacques ThM van Eijk, Gudny Eiriksdottir, Pálmi V Jónsson, Lenore J Launer, Vilmundur Gudnason, Tamara B Harris
BMC Public Health , 2013, DOI: 10.1186/1471-2458-13-101
Abstract: Data were from 4,809 men and women aged 33--65 years who participated in the Reykjavik Study (1967--1992) and who were re-examined in old age in the Age, Gene/Environment Susceptibility (AGES) -Reykjavik Study (2002--2006).Education and occupation predicted mobility limitation and depressed mood. Independently, home and car ownership and the availability of housing features predicted mobility limitation. Shortages of food in childhood and lack of a car in midlife predicted depressed mood.Socioeconomic factors from midlife and from childhood affect mobility limitation and depressed mood in old age. Prevention of health problems in old age should begin as early as midlife. (187)
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